Evidence dossier · candidate cand-covid-thrombocytopenia · CICP program · · DRAFT — not a determination
This is a draft research-tracking dossier, not a determination that COVID-19 vaccine causes Thrombocytopenia, and not an incidence or legal finding. All evidence is flagged needs_human_review and must be reviewed before any page is published or cited. Every value is grounded in retrieved citations (PMID + retrieval date); unsourced items read "no evidence found / not assessable". Symmetric search: every supporting query has a mirror/null query, and zeros are shown (negative dossiers report the absence of signal).
Claim matrix (C1–C6, computed)
Claim
Label
Status
Missing nodes
C1
Coherent clinical object exists
supported
C2
Consistent temporal window
supported
C3
Epidemiologic excess risk
supported
C4
Consistency / replication
contested
C5
Specificity (product / dose)
contested
C6
Biological mechanism
supported
Two evidentiary bars apply to the epi nodes/claims (C3, C4): · VICP — preponderance of the evidence. · CICP (off-Table) — compelling, reliable, valid medical and scientific evidence (higher bar).
Bradford Hill assessment (computed)
Each viewpoint is derived from the node statuses below (see the framework crosswalk in compensation-tables-schema.md §8). Hill's viewpoints are aids to judgement, not a scoring checklist that proves causation; temporality is the only strictly necessary criterion.
Viewpoint
What it asks
Status (from evidence)
Temporality(necessary)
cause precedes effect in a plausible window (necessary)
NASEM (formerly IOM), "Adverse Effects of Vaccines: Evidence and Causality" (2011, updated 2024). Independent grading of epidemiologic and mechanistic evidence, synthesized into one of four causal-conclusion categories. This is a computed approximation of that framework, not a NASEM determination. See compensation-tables-schema.md §8bis.
Case-definition standard: ISTH criteria (thrombocytopenia-driven thrombosis per spec §1) — governs the case-certainty scale on A1/A2/A6/A8 below. See compensation-tables-schema.md §8ter.
Evidence matrix (68 nodes by workstream)
68 of 68 nodes evaluated · 136 PubMed queries logged (supporting + mirror, incl. zeros). Statuses are computed from retrieved citations; not hand-set.
Definition & attribution 24/24 evaluated
A1 · Case reportssupports
Measure: New definite object in risk window T Comparator: Pre-vaccination baseline Hit rule: Definite object present, onset in window, competing causes considered
Finding: Multiple case reports describe new-onset immune thrombocytopenia (ITP) with onset within days to weeks after COVID-19 vaccination, after competing causes were considered, supporting the existence of vaccine-associated thrombocytopenia as a rare adverse event.
supporting: COVID-19 vaccine Thrombocytopenia case report OR case series Case reports pubmed · 66504 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia alternative diagnosis OR not vaccine-related pubmed · 4067 hits · run 2026-09-07
19 retrieved record(s)
supports_node 35795543 · Case reports in hematology (2022) — Immune Thrombocytopenia following COVID-19 Vaccine.
supports_node 35449682 · Cureus (2022) — Vaccine-Induced Thrombotic Thrombocytopenia: A Case Report.
supports_node 38883219 · Clinical case reports (2024) — COVID-19-induced immune thrombocytopenia management approach: A case report and literature review.
supports_node 36842342 · Heart & lung : the journal of critical c (2023) — Cardiovascular complications of COVID-19 vaccines: A review of case-report and case-series studies.
supports_node 38979048 · Nigerian medical journal : journal of th (2023) — Hemolytic Uremic Syndrome: A COVID-19 Vaccine Reaction Case Report.
supports_node 38469016 · Cureus (2024) — Immune Thrombocytopenia After COVID-19 Vaccine Requiring Splenectomy: A Case Report and Review of the Literature.
supports_node 38967360 · Immunity, inflammation and disease (2024) — Atypical hemolytic-uremic syndrome after COVID-19 vaccine: A case report.
supports_node 34312301 · Neurology (2021) — Adenovirus-Vectored COVID-19 Vaccine-Induced Immune Thrombosis of Carotid Artery: A Case Report.
A2 · Series with objective confirmationsupports
Measure: Definite object plus objective test Comparator: Reference range / diagnostic criteria Hit rule: Objective confirmation in >=1 case per the working definition
Finding: Three case reports describe immune thrombocytopenia (ITP) after COVID-19 vaccination with objective laboratory confirmation, including platelet counts and, in one case, platelet factor 4 antibody assay. One additional case report describes vaccine-induced thrombotic thrombocytopenia (VITT) with PF4 antibody confirmation.
supporting: COVID-19 vaccine Thrombocytopenia case report OR case series Series with objective confirmation pubmed · 6000 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia alternative diagnosis OR not vaccine-related pubmed · 4067 hits · run 2026-09-07
17 retrieved record(s)
supports_node 35795543 · Case reports in hematology (2022) — Immune Thrombocytopenia following COVID-19 Vaccine.
supports_node 35449682 · Cureus (2022) — Vaccine-Induced Thrombotic Thrombocytopenia: A Case Report.
supports_node 38469016 · Cureus (2024) — Immune Thrombocytopenia After COVID-19 Vaccine Requiring Splenectomy: A Case Report and Review of the Literature.
supports_node 36185940 · Cureus (2022) — COVID-19 Vaccine-Induced Thrombotic Thrombocytopaenia With Venous and Arterial Thrombosis: A Case Report.
supports_node 37376504 · Vaccines (2023) — Vaccine-Induced Immune Thrombotic Thrombocytopenia following BNT162b2 mRNA COVID-19 Booster: A Case Report.
supports_node 38979048 · Nigerian medical journal : journal of th (2023) — Hemolytic Uremic Syndrome: A COVID-19 Vaccine Reaction Case Report.
ambiguous 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
does_not_resolve 36441403 · Current cardiology reports (2022) — COVID-19 Vaccine-Related Myocardial and Pericardial Inflammation.
A3 · Onset histogrammixed
Measure: Distribution of onset times after dose Comparator: Pre-specified risk window Hit rule: Onset clusters inside the pre-specified window (not uniform/flat)
Finding: Case reports describe immune thrombocytopenia (ITP) with onset ranging from two to four weeks after COVID-19 vaccination (e.g., after first dose of Moderna, after third/booster dose of Pfizer-BioNTech), but the onset histogram across these few reports shows variability rather than a tight cluster within a single narrow pre-specified window; moreover, one case of vaccine-induced thrombotic thrombocytopenia (VITT) had onset eight days post-vaccination, adding to temporal heterogeneity.
supporting: COVID-19 vaccine Thrombocytopenia case report OR case series Onset histogram pubmed · 361 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia alternative diagnosis OR not vaccine-related pubmed · 4067 hits · run 2026-09-07
19 retrieved record(s)
supports_node 35795543 · Case reports in hematology (2022) — Immune Thrombocytopenia following COVID-19 Vaccine.
supports_node 35449682 · Cureus (2022) — Vaccine-Induced Thrombotic Thrombocytopenia: A Case Report.
supports_node 38469016 · Cureus (2024) — Immune Thrombocytopenia After COVID-19 Vaccine Requiring Splenectomy: A Case Report and Review of the Literature.
supports_node 38883219 · Clinical case reports (2024) — COVID-19-induced immune thrombocytopenia management approach: A case report and literature review.
ambiguous 38681104 · The Pan African medical journal (2024) — Acute-onset chronic inflammatory demyelinating polyneuropathy following AstraZeneca COVID-19 vaccine: a case report.
supports_node 36842342 · Heart & lung : the journal of critical c (2023) — Cardiovascular complications of COVID-19 vaccines: A review of case-report and case-series studies.
does_not_resolve 37692656 · Cureus (2023) — Takotsubo Cardiomyopathy Following COVID-19 Vaccine Booster Dose: A Case Report.
supports_node 34312301 · Neurology (2021) — Adenovirus-Vectored COVID-19 Vaccine-Induced Immune Thrombosis of Carotid Artery: A Case Report.
A4 · Temporal plausibilitysupports
Measure: Onset latency vs object pathophysiology Comparator: Object's known natural latency Hit rule: Onset latency consistent with the object's pathophysiology
Finding: Several case reports describe immune thrombocytopenia (ITP) and vaccine-induced thrombotic thrombocytopenia (VITT) with onset latency consistent with vaccine pathophysiology: symptoms appearing within 1–4 weeks after COVID-19 vaccination (e.g., 2 weeks after first dose, 4 weeks after booster, or shortly after J&J vaccine), supporting temporal plausibility.
supporting: COVID-19 vaccine Thrombocytopenia case report OR case series Temporal plausibility pubmed · 390 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia alternative diagnosis OR not vaccine-related pubmed · 4067 hits · run 2026-09-07
18 retrieved record(s)
supports_node 35795543 · Case reports in hematology (2022) — Immune Thrombocytopenia following COVID-19 Vaccine.
supports_node 36039236 · Cureus (2022) — A Case of COVID-19 Vaccine-Induced Thrombotic Thrombocytopenia.
supports_node 35449682 · Cureus (2022) — Vaccine-Induced Thrombotic Thrombocytopenia: A Case Report.
supports_node 38469016 · Cureus (2024) — Immune Thrombocytopenia After COVID-19 Vaccine Requiring Splenectomy: A Case Report and Review of the Literature.
supports_node 38883219 · Clinical case reports (2024) — COVID-19-induced immune thrombocytopenia management approach: A case report and literature review.
does_not_resolve 37692656 · Cureus (2023) — Takotsubo Cardiomyopathy Following COVID-19 Vaccine Booster Dose: A Case Report.
ambiguous 37376463 · Vaccines (2023) — Pulmonary Embolism after Vaccination with the COVID-19 Vaccine (Pfizer, BNT162b2): A Case Report.
ambiguous 36842342 · Heart & lung : the journal of critical c (2023) — Cardiovascular complications of COVID-19 vaccines: A review of case-report and case-series studies.
A5 · Onset-interval documentationsupports
Measure: Onset interval documented in source Comparator: Dose date Hit rule: Onset interval is recorded (not imputed) in a primary source
Finding: Two case reports explicitly document the onset interval after vaccination: one notes immune thrombocytopenia manifesting two weeks after the first dose of COVID-19 vaccine [PMID 38469016], and another describes severe refractory ITP beginning 4 weeks after a booster dose [PMID 38883219]. No other retrieved articles provide explicit onset-interval documentation for thrombocytopenia.
supporting: COVID-19 vaccine Thrombocytopenia case report OR case series Onset-interval documentation pubmed · 359 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia alternative diagnosis OR not vaccine-related pubmed · 4067 hits · run 2026-09-07
20 retrieved record(s)
supports_node 35795543 · Case reports in hematology (2022) — Immune Thrombocytopenia following COVID-19 Vaccine.
supports_node 36039236 · Cureus (2022) — A Case of COVID-19 Vaccine-Induced Thrombotic Thrombocytopenia.
supports_node 35449682 · Cureus (2022) — Vaccine-Induced Thrombotic Thrombocytopenia: A Case Report.
supports_node 38469016 · Cureus (2024) — Immune Thrombocytopenia After COVID-19 Vaccine Requiring Splenectomy: A Case Report and Review of the Literature.
ambiguous 38681104 · The Pan African medical journal (2024) — Acute-onset chronic inflammatory demyelinating polyneuropathy following AstraZeneca COVID-19 vaccine: a case report.
supports_node 38883219 · Clinical case reports (2024) — COVID-19-induced immune thrombocytopenia management approach: A case report and literature review.
does_not_resolve 37692656 · Cureus (2023) — Takotsubo Cardiomyopathy Following COVID-19 Vaccine Booster Dose: A Case Report.
supports_node 37376504 · Vaccines (2023) — Vaccine-Induced Immune Thrombotic Thrombocytopenia following BNT162b2 mRNA COVID-19 Booster: A Case Report.
A6 · Differential diagnosis excludedsupports
Measure: Competing causes assessed and excluded Comparator: Likely alternative diagnoses Hit rule: Pre-specified competing causes ruled out per the working definition
Finding: A case report describes a 54-year-old previously healthy female who developed immune thrombocytopenia (ITP) two weeks after the first dose of COVID-19 vaccine, requiring splenectomy, and the report notes that competing causes were assessed as absent (no familial history of autoimmune or hematological disorders).
supporting: COVID-19 vaccine Thrombocytopenia case report OR case series Differential diagnosis excluded pubmed · 786 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia alternative diagnosis OR not vaccine-related pubmed · 4067 hits · run 2026-09-07
13 retrieved record(s)
supports_node 38469016 · Cureus (2024) — Immune Thrombocytopenia After COVID-19 Vaccine Requiring Splenectomy: A Case Report and Review of the Literature.
ambiguous 37376463 · Vaccines (2023) — Pulmonary Embolism after Vaccination with the COVID-19 Vaccine (Pfizer, BNT162b2): A Case Report.
does_not_resolve 41306776 · Frontiers in pharmacology (2025) — HPV vaccine-related thyroid adverse events: temporal patterns and reporting trends.
ambiguous 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
does_not_resolve 36441403 · Current cardiology reports (2022) — COVID-19 Vaccine-Related Myocardial and Pericardial Inflammation.
does_not_resolve 37775180 · Clinical medicine (London, England) (2023) — SARS-CoV-2 vaccines and myocarditis.
ambiguous 40902666 · Journal of the American Academy of Derma (2026) — Drug and vaccine-associated pemphigoid in patients aged 50 years and older: A pharmacovigilance study.
ambiguous 30000765 · (2006) — Human Papillomavirus Vaccines.
A7 · Rechallenge / re-exposureno_data
Measure: Object recurs on a further dose Comparator: First-dose response Hit rule: Object recurs after a subsequent dose (re-exposure)
Finding: The retrieved evidence includes case reports of thrombocytopenia following the first dose of a COVID-19 vaccine and after a booster dose, but does not describe recurrence of thrombocytopenia upon re-exposure (a subsequent dose) in a patient who had already experienced the event after an earlier dose.
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia case report OR case series Rechallenge / re-exposure pubmed · 361 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia alternative diagnosis OR not vaccine-related pubmed · 4067 hits · run 2026-09-07
19 retrieved record(s)
supports_node 35795543 · Case reports in hematology (2022) — Immune Thrombocytopenia following COVID-19 Vaccine.
supports_node 35449682 · Cureus (2022) — Vaccine-Induced Thrombotic Thrombocytopenia: A Case Report.
supports_node 38469016 · Cureus (2024) — Immune Thrombocytopenia After COVID-19 Vaccine Requiring Splenectomy: A Case Report and Review of the Literature.
supports_node 38883219 · Clinical case reports (2024) — COVID-19-induced immune thrombocytopenia management approach: A case report and literature review.
ambiguous 37692656 · Cureus (2023) — Takotsubo Cardiomyopathy Following COVID-19 Vaccine Booster Dose: A Case Report.
ambiguous 37376463 · Vaccines (2023) — Pulmonary Embolism after Vaccination with the COVID-19 Vaccine (Pfizer, BNT162b2): A Case Report.
supports_node 37376504 · Vaccines (2023) — Vaccine-Induced Immune Thrombotic Thrombocytopenia following BNT162b2 mRNA COVID-19 Booster: A Case Report.
ambiguous 36842342 · Heart & lung : the journal of critical c (2023) — Cardiovascular complications of COVID-19 vaccines: A review of case-report and case-series studies.
A8 · Adjudicated by criteria (ISTH criteria)mixed
Measure: Object adjudicated by published criteria Comparator: Published clinical / Brighton criteria Hit rule: Cases adjudicated to 'definite' by a published criterion set
Finding: Multiple case reports describe thrombocytopenia after COVID-19 vaccination, with some cases adjudicated as immune thrombocytopenia (ITP) or vaccine-induced thrombotic thrombocytopenia (VITT) based on published criteria (e.g., positive PF4 ELISA, exclusion of other causes), but none explicitly mention adjudication by a formal published criterion set categorizing cases as 'definite' for thrombocytopenia.
supporting: COVID-19 vaccine Thrombocytopenia case report OR case series Adjudicated by criteria pubmed · 398 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia alternative diagnosis OR not vaccine-related pubmed · 4067 hits · run 2026-09-07
20 retrieved record(s)
supports_node 35795543 · Case reports in hematology (2022) — Immune Thrombocytopenia following COVID-19 Vaccine.
supports_node 36039236 · Cureus (2022) — A Case of COVID-19 Vaccine-Induced Thrombotic Thrombocytopenia.
supports_node 35449682 · Cureus (2022) — Vaccine-Induced Thrombotic Thrombocytopenia: A Case Report.
supports_node 38469016 · Cureus (2024) — Immune Thrombocytopenia After COVID-19 Vaccine Requiring Splenectomy: A Case Report and Review of the Literature.
supports_node 38883219 · Clinical case reports (2024) — COVID-19-induced immune thrombocytopenia management approach: A case report and literature review.
supports_node 37376504 · Vaccines (2023) — Vaccine-Induced Immune Thrombotic Thrombocytopenia following BNT162b2 mRNA COVID-19 Booster: A Case Report.
does_not_resolve 37692656 · Cureus (2023) — Takotsubo Cardiomyopathy Following COVID-19 Vaccine Booster Dose: A Case Report.
ambiguous 36842342 · Heart & lung : the journal of critical c (2023) — Cardiovascular complications of COVID-19 vaccines: A review of case-report and case-series studies.
A9 · Natural-history consistencysupports
Measure: Course matches the object's natural history Comparator: Known natural history of the object Hit rule: Clinical course (onset, peak, recovery) matches the object's natural history
Finding: Multiple case reports describe immune thrombocytopenia (ITP) and vaccine-induced thrombotic thrombocytopenia (VITT) occurring after COVID-19 vaccination, with onset typically within days to weeks post-dose, including after first, second, or booster doses, and clinical courses ranging from recovery to severe complications requiring splenectomy, which is generally consistent with the natural history of acquired thrombocytopenia.
supporting: COVID-19 vaccine Thrombocytopenia case report OR case series Natural-history consistency pubmed · 462 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia alternative diagnosis OR not vaccine-related pubmed · 4067 hits · run 2026-09-07
16 retrieved record(s)
supports_node 35795543 · Case reports in hematology (2022) — Immune Thrombocytopenia following COVID-19 Vaccine.
supports_node 36039236 · Cureus (2022) — A Case of COVID-19 Vaccine-Induced Thrombotic Thrombocytopenia.
supports_node 35449682 · Cureus (2022) — Vaccine-Induced Thrombotic Thrombocytopenia: A Case Report.
supports_node 38469016 · Cureus (2024) — Immune Thrombocytopenia After COVID-19 Vaccine Requiring Splenectomy: A Case Report and Review of the Literature.
supports_node 38883219 · Clinical case reports (2024) — COVID-19-induced immune thrombocytopenia management approach: A case report and literature review.
ambiguous 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
does_not_resolve 41306776 · Frontiers in pharmacology (2025) — HPV vaccine-related thyroid adverse events: temporal patterns and reporting trends.
does_not_resolve 36441403 · Current cardiology reports (2022) — COVID-19 Vaccine-Related Myocardial and Pericardial Inflammation.
A10 · No confounding objectsupports
Measure: Not attributable to a co-occurring condition Comparator: Co-occurring illness that could produce the object Hit rule: Object not better explained by a co-occurring condition (infection, etc.)
Finding: Multiple case reports describe immune thrombocytopenia (ITP) occurring after COVID-19 vaccination, with onset within weeks of vaccination and without a clear alternative cause such as infection. One case (PMID 35795543) reports ITP after Moderna vaccine; another (PMID 38469016) describes severe ITP requiring splenectomy after the first dose; and a third (PMID 38883219) details refractory ITP after a booster dose.
supporting: COVID-19 vaccine Thrombocytopenia case report OR case series No confounding object pubmed · 378 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia alternative diagnosis OR not vaccine-related pubmed · 4067 hits · run 2026-09-07
18 retrieved record(s)
supports_node 35795543 · Case reports in hematology (2022) — Immune Thrombocytopenia following COVID-19 Vaccine.
supports_node 35449682 · Cureus (2022) — Vaccine-Induced Thrombotic Thrombocytopenia: A Case Report.
supports_node 38469016 · Cureus (2024) — Immune Thrombocytopenia After COVID-19 Vaccine Requiring Splenectomy: A Case Report and Review of the Literature.
supports_node 38883219 · Clinical case reports (2024) — COVID-19-induced immune thrombocytopenia management approach: A case report and literature review.
supports_node 37376504 · Vaccines (2023) — Vaccine-Induced Immune Thrombotic Thrombocytopenia following BNT162b2 mRNA COVID-19 Booster: A Case Report.
ambiguous 37692656 · Cureus (2023) — Takotsubo Cardiomyopathy Following COVID-19 Vaccine Booster Dose: A Case Report.
supports_node 36842342 · Heart & lung : the journal of critical c (2023) — Cardiovascular complications of COVID-19 vaccines: A review of case-report and case-series studies.
ambiguous 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
D1 · Predicted site of injuryno_data
Measure: Object at the site the mechanism predicts Comparator: Predicted anatomic site from the mechanism Hit rule: Object localizes to the anatomic site the mechanism predicts
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia anatomic localization Predicted site of injury mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia Predicted site of injury not consistent with mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
D2 · Spared structuresno_data
Measure: Structures the mechanism should spare are spared Comparator: Structures predicted unaffected Hit rule: Structures predicted spared by the mechanism are indeed spared
mirror: COVID-19 vaccine Thrombocytopenia Spared structures not consistent with mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
D3 · Local vs systemic distributionno_data
Measure: Distribution matches mechanism scope Comparator: Local (injection site) vs systemic expectation Hit rule: Observed distribution (local vs systemic) matches the mechanism's predicted scope
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia anatomic localization Local vs systemic distribution mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia Local vs systemic distribution not consistent with mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
D4 · Kinetics classno_data
Measure: Onset/offset kinetics match the mechanism Comparator: Expected kinetic class (acute vs chronic) Hit rule: Onset and offset kinetics are in the class the mechanism predicts
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia anatomic localization Kinetics class mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia Kinetics class not consistent with mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
D5 · Platform-mechanism matchno_data
Measure: Mechanism is consistent with the platform Comparator: Mechanistic expectation for the platform Hit rule: The proposed mechanism is biologically consistent with the vaccine platform
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia anatomic localization Platform-mechanism match mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia Platform-mechanism match not consistent with mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
H3 · Targeted treatment reversesno_data
Measure: A targeted treatment reverses the object in patients Comparator: Treatment-naive / placebo Hit rule: A mechanism-directed treatment reverses the object (vs control treatment)
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia Targeted treatment reverses intervention OR treatment OR reversal pubmed · 15141378 hits · run 2026-09-07
Measure: No node's finding contradicts another Comparator: Internal consistency across nodes Hit rule: No evaluated node directly contradicts another (coherence)
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia No internal contradiction coherence OR latency OR susceptibility pubmed · 870020 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia No internal contradiction inconsistent OR contradicts pubmed · 27612 hits · run 2026-09-07
1 retrieved record(s)
does_not_resolve 25187623 · Reproduction (Cambridge, England) (2014) — Epigenetics and life-long consequences of an adverse nutritional and diabetic intrauterine environment.
I2 · Analogy to a known objectno_data
Measure: Object analogous to a well-established analog Comparator: Established analog's profile Hit rule: The object's profile matches a well-established analog on key features
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia Analogy to a known object coherence OR latency OR susceptibility pubmed · 870020 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia Analogy to a known object inconsistent OR contradicts pubmed · 27612 hits · run 2026-09-07
1 retrieved record(s)
does_not_resolve 25187623 · Reproduction (Cambridge, England) (2014) — Epigenetics and life-long consequences of an adverse nutritional and diabetic intrauterine environment.
I5 · Latency coherenceno_data
Measure: Observed latency matches the mechanism's latency Comparator: Mechanism-predicted latency Hit rule: Observed onset latency is coherent with the mechanism's predicted latency
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia Latency coherence coherence OR latency OR susceptibility pubmed · 870020 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia Latency coherence inconsistent OR contradicts pubmed · 27612 hits · run 2026-09-07
1 retrieved record(s)
does_not_resolve 25187623 · Reproduction (Cambridge, England) (2014) — Epigenetics and life-long consequences of an adverse nutritional and diabetic intrauterine environment.
J1 · Pre-specificationno_data
Measure: Window/hit-rule pre-specified before data Comparator: Pre-specified vs post-hoc Hit rule: The risk window, object, and hit rule were pre-specified before data were seen
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia Pre-specification pre-specified OR adjudicated pubmed · 13548 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia Pre-specification post-hoc OR hypothesis-generating only pubmed · 1698 hits · run 2026-09-07
3 retrieved record(s)
does_not_resolve 39226489 · Journal of clinical oncology : official (2024) — Enhancing Precision in Detecting Severe Immune-Related Adverse Events: Comparative Analysis of Large Language Models and International Classification of Disease
does_not_resolve 42474879 · Biological trace element research (2026) — Cadmium Exposure and Osteoporosis: A Spatially Contextualized Adverse Outcome Pathway Integrating Epidemiology, Toxicogenomics and Transcriptomics.
does_not_resolve 42569385 · Frontiers in medicine (2026) — Antibiotic-associated adverse events in bone and joint infections: a FAERS pharmacovigilance study.
J2 · Contrary-evidence logno_data
Measure: Contrary evidence is logged, not omitted Comparator: Support-only dossier Hit rule: Contrary / null / refuting findings are logged and shown alongside support
Finding: No retrieved studies directly address new Thrombocytopenia attributed to COVID-19 vaccine, with onset within a pre-specified risk window after vaccination, after competing causes are assessed.
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia Contrary-evidence log pre-specified OR adjudicated pubmed · 13548 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia Contrary-evidence log post-hoc OR hypothesis-generating only pubmed · 1698 hits · run 2026-09-07
3 retrieved record(s)
does_not_resolve 39226489 · Journal of clinical oncology : official (2024) — Enhancing Precision in Detecting Severe Immune-Related Adverse Events: Comparative Analysis of Large Language Models and International Classification of Disease
does_not_resolve 38983297 · Radiology case reports (2024) — Identification of perineural invasion at imaging staging as a novel potential risk factor in rectal cancer: A case report.
J3 · No temporality-only claimno_data
Measure: Claim not based on temporality alone Comparator: Sequence-only evidence Hit rule: The claim is not supported by temporal sequence alone (independent evidence exists)
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia No temporality-only claim pre-specified OR adjudicated pubmed · 13549 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia No temporality-only claim post-hoc OR hypothesis-generating only pubmed · 1698 hits · run 2026-09-07
3 retrieved record(s)
does_not_resolve 39226489 · Journal of clinical oncology : official (2024) — Enhancing Precision in Detecting Severe Immune-Related Adverse Events: Comparative Analysis of Large Language Models and International Classification of Disease
does_not_resolve 42474879 · Biological trace element research (2026) — Cadmium Exposure and Osteoporosis: A Spatially Contextualized Adverse Outcome Pathway Integrating Epidemiology, Toxicogenomics and Transcriptomics.
does_not_resolve 42569385 · Frontiers in medicine (2026) — Antibiotic-associated adverse events in bone and joint infections: a FAERS pharmacovigilance study.
J4 · Passive-surveillance roleno_data
Measure: Passive-surveillance findings bounded correctly Comparator: Active-surveillance confirmation Hit rule: Passive-surveillance signals are framed as hypothesis-generating, not confirmatory
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia Passive-surveillance role pre-specified OR adjudicated pubmed · 13548 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia Passive-surveillance role post-hoc OR hypothesis-generating only pubmed · 1698 hits · run 2026-09-07
3 retrieved record(s)
does_not_resolve 39226489 · Journal of clinical oncology : official (2024) — Enhancing Precision in Detecting Severe Immune-Related Adverse Events: Comparative Analysis of Large Language Models and International Classification of Disease
does_not_resolve 42474879 · Biological trace element research (2026) — Cadmium Exposure and Osteoporosis: A Spatially Contextualized Adverse Outcome Pathway Integrating Epidemiology, Toxicogenomics and Transcriptomics.
does_not_resolve 42569385 · Frontiers in medicine (2026) — Antibiotic-associated adverse events in bone and joint infections: a FAERS pharmacovigilance study.
J5 · Dose mappingno_data
Measure: Dose/lot exposure mapped to the object Comparator: Unmapped exposure Hit rule: Dose / lot exposure is mapped to the object where the mechanism predicts it
Finding: The retrieved evidence is about using large language models to identify immune-related adverse events from immune checkpoint inhibitor therapy, not about COVID-19 vaccine-induced thrombocytopenia or dose mapping.
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia Dose mapping pre-specified OR adjudicated pubmed · 13548 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia Dose mapping post-hoc OR hypothesis-generating only pubmed · 1698 hits · run 2026-09-07
1 retrieved record(s)
does_not_resolve 39226489 · Journal of clinical oncology : official (2024) — Enhancing Precision in Detecting Severe Immune-Related Adverse Events: Comparative Analysis of Large Language Models and International Classification of Disease
Epidemiologic chassis 13/13 evaluated
B1 · Excess vs baselineno_data
Measure: RR/IRR vs unexposed or prior window Comparator: Unvaccinated person-time or pre-vaccination window Hit rule: RR/IRR > 1 with CI excluding 1 after pre-specified confounders
Finding: The retrieved evidence includes reviews and case series linking COVID-19 vaccines (particularly adenoviral vector vaccines) to thrombocytopenia, including vaccine-induced immune thrombotic thrombocytopenia (VITT), but no controlled epidemiological studies with RR/IRR > 1 and CI excluding 1 for the specific pair COVID-19 vaccine → Thrombocytopenia were identified among the provided abstracts.
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia Excess vs baseline incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia no association OR null OR no increased risk Excess vs baseline pubmed · 88996 hits · run 2026-09-07
13 retrieved record(s)
does_not_resolve 30172612 · American journal of infection control (2019) — Antibiotic exposure and risk of community-associated Clostridium difficile infection: A self-controlled case series analysis.
does_not_resolve 38089855 · European heart journal open (2023) — Risk of arrhythmias following COVID-19: nationwide self-controlled case series and matched cohort study.
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 38875047 · The International journal of risk & safe (2024) — Self-controlled risk interval study of rotavirus vaccine safety: Findings and implications.
does_not_resolve 40440921 · Vaccine (2025) — Risk of Guillain-Barré syndrome after COVID-19 vaccination or SARS-CoV-2 infection: A multinational self-controlled case series study.
ambiguous 35504917 · Signal transduction and targeted therapy (2022) — COVID-19 vaccine development: milestones, lessons and prospects.
supports_node 36265409 · Thrombosis research (2022) — Vaccine-associated thrombocytopenia.
does_not_resolve 34477808 · JAMA (2021) — Surveillance for Adverse Events After COVID-19 mRNA Vaccination.
B2 · SCCSno_data
Measure: Self-controlled case series risk ratio Comparator: Individuals' own risk intervals (no-event) Hit rule: SCCS risk ratio > 1 in the post-vaccination window, CI excluding 1
Finding: One retrieved SCCS study (PMID 38388239) examined mortality risk after COVID-19 vaccination but did not assess thrombocytopenia; two other SCCS studies (PMID 38089855, 40440921) evaluated arrhythmias and Guillain-Barré syndrome, not thrombocytopenia. No retrieved study reports an SCCS risk ratio for thrombocytopenia following COVID-19 vaccination.
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia SCCS incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia no association OR null OR no increased risk SCCS pubmed · 89099 hits · run 2026-09-07
14 retrieved record(s)
does_not_resolve 30172612 · American journal of infection control (2019) — Antibiotic exposure and risk of community-associated Clostridium difficile infection: A self-controlled case series analysis.
does_not_resolve 38388239 · Vaccine (2024) — Mortality risk after COVID-19 vaccination: A self-controlled case series study.
does_not_resolve 33773635 · The Lancet. Public health (2021) — Periods of altered risk for non-fatal drug overdose: a self-controlled case series.
does_not_resolve 38089855 · European heart journal open (2023) — Risk of arrhythmias following COVID-19: nationwide self-controlled case series and matched cohort study.
does_not_resolve 40818314 · Vaccine (2025) — COVID-19 vaccination and the risk of abnormal uterine bleeding: A nationwide self-controlled case series study.
does_not_resolve 37223097 · Frontiers in immunology (2023) — Safety of COVID-19 vaccine in patients with myasthenia gravis: a self-controlled case series study.
does_not_resolve 40440921 · Vaccine (2025) — Risk of Guillain-Barré syndrome after COVID-19 vaccination or SARS-CoV-2 infection: A multinational self-controlled case series study.
ambiguous 35504917 · Signal transduction and targeted therapy (2022) — COVID-19 vaccine development: milestones, lessons and prospects.
B3 · Cohort / risk-intervalno_data
Measure: Incidence rate ratio in defined window Comparator: Pre-specified risk vs comparison interval Hit rule: IRR > 1 in the pre-specified window, CI excluding 1, stratified by age/sex
Finding: No retrieved study directly reports an IRR for thrombocytopenia following COVID-19 vaccination using a self-controlled design stratified by age/sex; the available studies address other exposures or outcomes (e.g., antibiotic–C. difficile, drug overdose, arrhythmias after COVID-19, abnormal uterine bleeding, rotavirus vaccine, myasthenia gravis exacerbation, and general vaccine safety surveillance) or provide narrative reviews on thrombocytopenia without a cohort-based IRR estimate.
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia Cohort / risk-interval incidence risk cohort OR self-controlled case series pubmed · 946 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia no association OR null OR no increased risk Cohort / risk-interval pubmed · 88604 hits · run 2026-09-07
13 retrieved record(s)
does_not_resolve 30172612 · American journal of infection control (2019) — Antibiotic exposure and risk of community-associated Clostridium difficile infection: A self-controlled case series analysis.
does_not_resolve 33773635 · The Lancet. Public health (2021) — Periods of altered risk for non-fatal drug overdose: a self-controlled case series.
does_not_resolve 38089855 · European heart journal open (2023) — Risk of arrhythmias following COVID-19: nationwide self-controlled case series and matched cohort study.
does_not_resolve 40818314 · Vaccine (2025) — COVID-19 vaccination and the risk of abnormal uterine bleeding: A nationwide self-controlled case series study.
does_not_resolve 38875047 · The International journal of risk & safe (2024) — Self-controlled risk interval study of rotavirus vaccine safety: Findings and implications.
does_not_resolve 37223097 · Frontiers in immunology (2023) — Safety of COVID-19 vaccine in patients with myasthenia gravis: a self-controlled case series study.
ambiguous 35504917 · Signal transduction and targeted therapy (2022) — COVID-19 vaccine development: milestones, lessons and prospects.
supports_node 36265409 · Thrombosis research (2022) — Vaccine-associated thrombocytopenia.
B4 · Meta-analysis / poolingno_data
Measure: Pooled effect across studies Comparator: Pooled estimate with heterogeneity Hit rule: Pooled estimate > 1 (or < 1) with quantified heterogeneity (I2)
Finding: The retrieved evidence includes review articles and case series that describe thrombocytopenia as a rare adverse event following COVID-19 vaccination, particularly vaccine-induced immune thrombotic thrombocytopenia (VITT) associated with adenoviral vector vaccines, but no meta-analysis or pooled estimate with quantified heterogeneity (I²) for the association between COVID-19 vaccination and thrombocytopenia was identified in the provided literature.
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia Meta-analysis / pooling incidence risk cohort OR self-controlled case series pubmed · 948 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia no association OR null OR no increased risk Meta-analysis / pooling pubmed · 112433 hits · run 2026-09-07
15 retrieved record(s)
does_not_resolve 30172612 · American journal of infection control (2019) — Antibiotic exposure and risk of community-associated Clostridium difficile infection: A self-controlled case series analysis.
does_not_resolve 38388239 · Vaccine (2024) — Mortality risk after COVID-19 vaccination: A self-controlled case series study.
does_not_resolve 33773635 · The Lancet. Public health (2021) — Periods of altered risk for non-fatal drug overdose: a self-controlled case series.
does_not_resolve 40818314 · Vaccine (2025) — COVID-19 vaccination and the risk of abnormal uterine bleeding: A nationwide self-controlled case series study.
does_not_resolve 38089855 · European heart journal open (2023) — Risk of arrhythmias following COVID-19: nationwide self-controlled case series and matched cohort study.
ambiguous 37223097 · Frontiers in immunology (2023) — Safety of COVID-19 vaccine in patients with myasthenia gravis: a self-controlled case series study.
does_not_resolve 40440921 · Vaccine (2025) — Risk of Guillain-Barré syndrome after COVID-19 vaccination or SARS-CoV-2 infection: A multinational self-controlled case series study.
ambiguous 35504917 · Signal transduction and targeted therapy (2022) — COVID-19 vaccine development: milestones, lessons and prospects.
B5 · Negative-control outcomesno_data
Measure: No excess for outcomes the vaccine should not cause Comparator: Negative-control outcomes (unaffected by mechanism) Hit rule: Null for negative-control outcomes while target outcome is positive (specificity)
Finding: No retrieved evidence directly evaluates the null association between COVID-19 vaccination and thrombocytopenia as a negative-control outcome. Most retrieved articles discuss thrombocytopenia as a known adverse event (e.g., VITT, ITP) rather than as a negative control.
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia Negative-control outcomes incidence risk cohort OR self-controlled case series pubmed · 946 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia no association OR null OR no increased risk Negative-control outcomes pubmed · 88806 hits · run 2026-09-07
14 retrieved record(s)
does_not_resolve 30172612 · American journal of infection control (2019) — Antibiotic exposure and risk of community-associated Clostridium difficile infection: A self-controlled case series analysis.
does_not_resolve 38388239 · Vaccine (2024) — Mortality risk after COVID-19 vaccination: A self-controlled case series study.
does_not_resolve 33773635 · The Lancet. Public health (2021) — Periods of altered risk for non-fatal drug overdose: a self-controlled case series.
does_not_resolve 38089855 · European heart journal open (2023) — Risk of arrhythmias following COVID-19: nationwide self-controlled case series and matched cohort study.
does_not_resolve 40818314 · Vaccine (2025) — COVID-19 vaccination and the risk of abnormal uterine bleeding: A nationwide self-controlled case series study.
does_not_resolve 37223097 · Frontiers in immunology (2023) — Safety of COVID-19 vaccine in patients with myasthenia gravis: a self-controlled case series study.
does_not_resolve 40440921 · Vaccine (2025) — Risk of Guillain-Barré syndrome after COVID-19 vaccination or SARS-CoV-2 infection: A multinational self-controlled case series study.
ambiguous 35504917 · Signal transduction and targeted therapy (2022) — COVID-19 vaccine development: milestones, lessons and prospects.
B6 · Other-antigen comparisonno_data
Measure: Risk vs a different-antigen comparator Comparator: Comparator product with a different antigen Hit rule: Risk specific to the target antigen, not shared with the comparator antigen
Finding: The retrieved evidence includes a systematic review and narrative reviews reporting thrombocytopenia following COVID-19 vaccination, especially adenoviral vector vaccines, but no study directly compares risk of thrombocytopenia after COVID-19 vaccine versus a different-antigen comparator (as required for Node B6). One review (PMID 36265409) notes that the MMR vaccine is the only vaccine with a demonstrated causal relationship to immune thrombocytopenia, but does not provide a comparative risk estimate against a different-antigen comparator for COVID-19 vaccine.
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia Other-antigen comparison incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia no association OR null OR no increased risk Other-antigen comparison pubmed · 88569 hits · run 2026-09-07
14 retrieved record(s)
does_not_resolve 38388239 · Vaccine (2024) — Mortality risk after COVID-19 vaccination: A self-controlled case series study.
does_not_resolve 38089855 · European heart journal open (2023) — Risk of arrhythmias following COVID-19: nationwide self-controlled case series and matched cohort study.
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 40440921 · Vaccine (2025) — Risk of Guillain-Barré syndrome after COVID-19 vaccination or SARS-CoV-2 infection: A multinational self-controlled case series study.
does_not_resolve 36226469 · Epilepsia (2022) — Association between the risk of seizure and COVID-19 vaccinations: A self-controlled case-series study.
does_not_resolve 40664645 · Nature communications (2025) — Evaluating the safety of XBB.1.5-containing COVID-19 mRNA vaccines using a self-controlled case series study.
does_not_resolve 35489031 · Journal of clinical psychopharmacology (2022) — Prescription Stimulants and the Risk of Psychosis: A Systematic Review of Observational Studies.
supports_node 35504917 · Signal transduction and targeted therapy (2022) — COVID-19 vaccine development: milestones, lessons and prospects.
B7 · Absolute riskno_data
Measure: Per-100k risk in window Comparator: Absolute incidence per 100k Hit rule: Absolute risk reported and stable across the window (not an artifact of rarity)
Finding: The retrieved evidence includes reports of thrombocytopenia following COVID-19 vaccination, primarily in the context of vaccine-induced immune thrombotic thrombocytopenia (VITT) associated with adenoviral vector vaccines, but no retrieved study directly reports a stable per-100k absolute risk estimate for thrombocytopenia attributed to COVID-19 vaccination in a defined risk window after competing causes are assessed.
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia Absolute risk incidence risk cohort OR self-controlled case series pubmed · 946 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia no association OR null OR no increased risk Absolute risk pubmed · 111835 hits · run 2026-09-07
12 retrieved record(s)
does_not_resolve 30172612 · American journal of infection control (2019) — Antibiotic exposure and risk of community-associated Clostridium difficile infection: A self-controlled case series analysis.
does_not_resolve 38388239 · Vaccine (2024) — Mortality risk after COVID-19 vaccination: A self-controlled case series study.
does_not_resolve 38089855 · European heart journal open (2023) — Risk of arrhythmias following COVID-19: nationwide self-controlled case series and matched cohort study.
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 40440921 · Vaccine (2025) — Risk of Guillain-Barré syndrome after COVID-19 vaccination or SARS-CoV-2 infection: A multinational self-controlled case series study.
ambiguous 35504917 · Signal transduction and targeted therapy (2022) — COVID-19 vaccine development: milestones, lessons and prospects.
supports_node 36265409 · Thrombosis research (2022) — Vaccine-associated thrombocytopenia.
refutes_node 34477808 · JAMA (2021) — Surveillance for Adverse Events After COVID-19 mRNA Vaccination.
B8 · Platform splitsupports
Measure: Risk by vaccine platform / product Comparator: Platform (mRNA vs viral vector, etc.) Hit rule: Risk attributable to a specific platform, not to 'a vaccine' generally
Finding: Several retrieved studies (PMID 36265409, 38841785, 36494147, 34774202) indicate that thrombocytopenia following COVID-19 vaccination is primarily associated with adenoviral-vector platforms (e.g., ChAdOx1 nCoV-19, Ad26.COV2.S), manifesting as vaccine-induced immune thrombotic thrombocytopenia (VITT), supporting a platform-specific risk rather than a general vaccine-class effect; however, no retrieved study directly compares risk across all platforms using a self-controlled case series design for this outcome.
supporting: COVID-19 vaccine Thrombocytopenia Platform split incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia no association OR null OR no increased risk Platform split pubmed · 88634 hits · run 2026-09-07
13 retrieved record(s)
does_not_resolve 30172612 · American journal of infection control (2019) — Antibiotic exposure and risk of community-associated Clostridium difficile infection: A self-controlled case series analysis.
does_not_resolve 33773635 · The Lancet. Public health (2021) — Periods of altered risk for non-fatal drug overdose: a self-controlled case series.
does_not_resolve 38089855 · European heart journal open (2023) — Risk of arrhythmias following COVID-19: nationwide self-controlled case series and matched cohort study.
does_not_resolve 40818314 · Vaccine (2025) — COVID-19 vaccination and the risk of abnormal uterine bleeding: A nationwide self-controlled case series study.
does_not_resolve 38875047 · The International journal of risk & safe (2024) — Self-controlled risk interval study of rotavirus vaccine safety: Findings and implications.
does_not_resolve 37223097 · Frontiers in immunology (2023) — Safety of COVID-19 vaccine in patients with myasthenia gravis: a self-controlled case series study.
ambiguous 35504917 · Signal transduction and targeted therapy (2022) — COVID-19 vaccine development: milestones, lessons and prospects.
supports_node 36265409 · Thrombosis research (2022) — Vaccine-associated thrombocytopenia.
B9 · Host-structure stratificationno_data
Measure: Risk by age / sex / host structure Comparator: Unstratified estimate Hit rule: Risk concentrated in a defined host subgroup (e.g. young males), stable across sources
Finding: No retrieved evidence analyzes VITT risk by age, sex, or host structure using a self-controlled case series design or other method that directly examines risk concentration in a defined host subgroup. Multiple PMIDs (36265409, 35339857, 36494147, 34774202) note VITT is often reported in young women after adenoviral vector vaccines, but these are narrative summaries or case series, not structured stratification analyses with stable risk estimates across sources.
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia Host-structure stratification incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia no association OR null OR no increased risk Host-structure stratification pubmed · 88567 hits · run 2026-09-07
14 retrieved record(s)
does_not_resolve 30172612 · American journal of infection control (2019) — Antibiotic exposure and risk of community-associated Clostridium difficile infection: A self-controlled case series analysis.
does_not_resolve 38388239 · Vaccine (2024) — Mortality risk after COVID-19 vaccination: A self-controlled case series study.
does_not_resolve 33773635 · The Lancet. Public health (2021) — Periods of altered risk for non-fatal drug overdose: a self-controlled case series.
does_not_resolve 40818314 · Vaccine (2025) — COVID-19 vaccination and the risk of abnormal uterine bleeding: A nationwide self-controlled case series study.
does_not_resolve 38089855 · European heart journal open (2023) — Risk of arrhythmias following COVID-19: nationwide self-controlled case series and matched cohort study.
does_not_resolve 37223097 · Frontiers in immunology (2023) — Safety of COVID-19 vaccine in patients with myasthenia gravis: a self-controlled case series study.
does_not_resolve 40440921 · Vaccine (2025) — Risk of Guillain-Barré syndrome after COVID-19 vaccination or SARS-CoV-2 infection: A multinational self-controlled case series study.
ambiguous 35504917 · Signal transduction and targeted therapy (2022) — COVID-19 vaccine development: milestones, lessons and prospects.
B10 · Formulation / component changeno_data
Measure: Risk tracks a formulation change Comparator: Pre- vs post-change formulation Hit rule: Risk change tracks a documented formulation / component change over time
Finding: Retrieved evidence includes only a few review articles that mention COVID-19 vaccine-associated thrombocytopenia as a rare adverse event (e.g., PMID 35504917, PMID 36265409, PMID 38841785), but none of the retrieved studies provide epidemiological data comparing risk changes across different vaccine formulations or component changes over time, and no self-controlled case series or risk-interval analysis directly addresses whether risk of thrombocytopenia tracks a documented formulation/component change.
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia Formulation / component change incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia no association OR null OR no increased risk Formulation / component change pubmed · 88729 hits · run 2026-09-07
9 retrieved record(s)
does_not_resolve 30172612 · American journal of infection control (2019) — Antibiotic exposure and risk of community-associated Clostridium difficile infection: A self-controlled case series analysis.
does_not_resolve 38089855 · European heart journal open (2023) — Risk of arrhythmias following COVID-19: nationwide self-controlled case series and matched cohort study.
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 38875047 · The International journal of risk & safe (2024) — Self-controlled risk interval study of rotavirus vaccine safety: Findings and implications.
ambiguous 35504917 · Signal transduction and targeted therapy (2022) — COVID-19 vaccine development: milestones, lessons and prospects.
supports_node 36265409 · Thrombosis research (2022) — Vaccine-associated thrombocytopenia.
refutes_node 34477808 · JAMA (2021) — Surveillance for Adverse Events After COVID-19 mRNA Vaccination.
Measure: Risk shifts with a formulation change in the field Comparator: Pre- vs post-change formulation Hit rule: Observed risk tracks a real-world formulation change (natural experiment)
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia Formulation natural experiment intervention OR treatment OR reversal pubmed · 15141378 hits · run 2026-09-07
Measure: Risk signal appears/disappears across a pause or policy change Comparator: Pre- vs post-pause period Hit rule: The signal appears or disappears coherently with a rollout / pause (H4)
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia Policy / pause signal intervention OR treatment OR reversal pubmed · 15141378 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia Policy / pause signal no effect intervention pubmed · 0 hits (0 hits — negative) · run 2026-09-07
I3 · Infection coherenceno_data
Measure: Pattern is coherent with or distinct from infection Comparator: Infection-matched comparison Hit rule: The post-vaccine pattern is coherent with (or clearly distinct from) the infection pattern
Finding: The retrieved review focuses on stroke after COVID-19 vaccination, not specifically thrombocytopenia, and it does not provide coherence patterns between post-vaccine thrombocytopenia and infection-related thrombocytopenia.
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia Infection coherence coherence OR latency OR susceptibility pubmed · 870022 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia Infection coherence inconsistent OR contradicts pubmed · 27612 hits · run 2026-09-07
1 retrieved record(s)
does_not_resolve 35339857 · Journal of stroke and cerebrovascular di (2022) — Stroke Associated with COVID-19 Vaccines.
Mediator & biological gradient 24/24 evaluated
C1n · Dose strength gradientno_data
Measure: Risk vs dose strength (dose size) Comparator: Lower dose strength Hit rule: Monotonic dose-response in dose strength (larger dose -> higher risk)
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia Dose strength gradient dose-response OR dose effect pubmed · 1299132 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia no dose effect OR no dose-response Dose strength gradient pubmed · 345 hits · run 2026-09-07
5 retrieved record(s)
does_not_resolve 39082700 · The Journal of infectious diseases (2025) — Effectiveness of MenB-4C Vaccine Against Gonorrhea: A Systematic Review and Meta-analysis.
does_not_resolve 34477808 · JAMA (2021) — Surveillance for Adverse Events After COVID-19 mRNA Vaccination.
supports_node 36988252 · Immunity, inflammation and disease (2023) — Adverse events following COVID-19 mRNA vaccines: A systematic review of cardiovascular complication, thrombosis, and thrombocytopenia.
ambiguous 35339857 · Journal of stroke and cerebrovascular di (2022) — Stroke Associated with COVID-19 Vaccines.
supports_node 36494147 · Best practice & research. Clinical haema (2022) — Vaccine-induced immune thrombotic thrombocytopenia.
C2n · Dose number gradientno_data
Measure: Risk vs dose number (1st vs 2nd vs 3rd) Comparator: First dose Hit rule: Risk increases (or shows a defined pattern) with dose number
Finding: The retrieved evidence does not address the dose number gradient (1st vs 2nd vs 3rd dose) for thrombocytopenia after COVID-19 vaccination. One case report describes thrombocytopenia after the first dose of Moderna vaccine, but no comparative risk by dose number is reported.
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia Dose number gradient dose-response OR dose effect pubmed · 1299132 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia no dose effect OR no dose-response Dose number gradient pubmed · 789 hits · run 2026-09-07
7 retrieved record(s)
does_not_resolve 39082700 · The Journal of infectious diseases (2025) — Effectiveness of MenB-4C Vaccine Against Gonorrhea: A Systematic Review and Meta-analysis.
does_not_resolve 36090988 · Frontiers in immunology (2022) — A comprehensive analysis of the efficacy and effectiveness of COVID-19 vaccines.
refutes_node 34477808 · JAMA (2021) — Surveillance for Adverse Events After COVID-19 mRNA Vaccination.
does_not_resolve 36988252 · Immunity, inflammation and disease (2023) — Adverse events following COVID-19 mRNA vaccines: A systematic review of cardiovascular complication, thrombosis, and thrombocytopenia.
does_not_resolve 35339857 · Journal of stroke and cerebrovascular di (2022) — Stroke Associated with COVID-19 Vaccines.
supports_node 36494147 · Best practice & research. Clinical haema (2022) — Vaccine-induced immune thrombotic thrombocytopenia.
supports_node 35795543 · Case reports in hematology (2022) — Immune Thrombocytopenia following COVID-19 Vaccine.
C3n · Measured-exposure tertilesno_data
Measure: Risk vs measured exposure tertile Comparator: Lowest-exposure tertile Hit rule: Risk ordered by measured-exposure tertile (high > mid > low)
Finding: Two studies report thrombocytopenia following COVID-19 vaccination: one case of immune thrombocytopenia after Moderna mRNA vaccine (PMID 35795543) and a systematic review mentioning thrombocytopenia as an adverse event after mRNA vaccines (PMID 36988252). A third study reviews vaccine-induced immune thrombotic thrombocytopenia (VITT) associated with adenoviral vector vaccines (PMID 36494147). None of the retrieved evidence provides data on risk ordered by measured-exposure tertiles.
supporting: COVID-19 vaccine Thrombocytopenia Measured-exposure tertiles dose-response OR dose effect pubmed · 1299132 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia no dose effect OR no dose-response Measured-exposure tertiles pubmed · 234 hits · run 2026-09-07
7 retrieved record(s)
does_not_resolve 39082700 · The Journal of infectious diseases (2025) — Effectiveness of MenB-4C Vaccine Against Gonorrhea: A Systematic Review and Meta-analysis.
does_not_resolve 36090988 · Frontiers in immunology (2022) — A comprehensive analysis of the efficacy and effectiveness of COVID-19 vaccines.
does_not_resolve 34477808 · JAMA (2021) — Surveillance for Adverse Events After COVID-19 mRNA Vaccination.
ambiguous 36988252 · Immunity, inflammation and disease (2023) — Adverse events following COVID-19 mRNA vaccines: A systematic review of cardiovascular complication, thrombosis, and thrombocytopenia.
supports_node 35339857 · Journal of stroke and cerebrovascular di (2022) — Stroke Associated with COVID-19 Vaccines.
supports_node 36494147 · Best practice & research. Clinical haema (2022) — Vaccine-induced immune thrombotic thrombocytopenia.
supports_node 35795543 · Case reports in hematology (2022) — Immune Thrombocytopenia following COVID-19 Vaccine.
C4n · Organoid concentration curveno_data
Measure: Effect vs antigen concentration in organoid Comparator: Vehicle / zero antigen Hit rule: Dose-dependent effect across a graded concentration curve
Finding: No retrieved evidence specifically reports a dose-dependent effect of COVID-19 vaccine across a graded concentration curve in organoid models of thrombocytopenia.
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia Organoid concentration curve dose-response OR dose effect pubmed · 1299132 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia no dose effect OR no dose-response Organoid concentration curve pubmed · 245 hits · run 2026-09-07
7 retrieved record(s)
does_not_resolve 39082700 · The Journal of infectious diseases (2025) — Effectiveness of MenB-4C Vaccine Against Gonorrhea: A Systematic Review and Meta-analysis.
does_not_resolve 36090988 · Frontiers in immunology (2022) — A comprehensive analysis of the efficacy and effectiveness of COVID-19 vaccines.
does_not_resolve 34477808 · JAMA (2021) — Surveillance for Adverse Events After COVID-19 mRNA Vaccination.
ambiguous 36988252 · Immunity, inflammation and disease (2023) — Adverse events following COVID-19 mRNA vaccines: A systematic review of cardiovascular complication, thrombosis, and thrombocytopenia.
supports_node 35339857 · Journal of stroke and cerebrovascular di (2022) — Stroke Associated with COVID-19 Vaccines.
supports_node 36494147 · Best practice & research. Clinical haema (2022) — Vaccine-induced immune thrombotic thrombocytopenia.
supports_node 35795543 · Case reports in hematology (2022) — Immune Thrombocytopenia following COVID-19 Vaccine.
C5n · EC50 vs Cmax coherenceno_data
Measure: Measured exposure reaches effect threshold Comparator: Pharmacokinetic Cmax vs EC50 Hit rule: Achieved exposure (Cmax/tissue) plausibly reaches the in-vitro EC50
Finding: Two retrieved studies (PMID 36494147, PMID 35795543) report thrombocytopenia following COVID-19 vaccination, including vaccine-induced immune thrombotic thrombocytopenia (VITT) after adenoviral vector vaccines and a case of immune thrombocytopenia after mRNA vaccination, but no retrieved study provides pharmacokinetic/pharmacodynamic data (EC50 or Cmax) needed to assess EC50 vs Cmax coherence.
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia EC50 vs Cmax coherence dose-response OR dose effect pubmed · 1299132 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia no dose effect OR no dose-response EC50 vs Cmax coherence pubmed · 234 hits · run 2026-09-07
7 retrieved record(s)
does_not_resolve 39082700 · The Journal of infectious diseases (2025) — Effectiveness of MenB-4C Vaccine Against Gonorrhea: A Systematic Review and Meta-analysis.
does_not_resolve 36090988 · Frontiers in immunology (2022) — A comprehensive analysis of the efficacy and effectiveness of COVID-19 vaccines.
refutes_node 34477808 · JAMA (2021) — Surveillance for Adverse Events After COVID-19 mRNA Vaccination.
does_not_resolve 36988252 · Immunity, inflammation and disease (2023) — Adverse events following COVID-19 mRNA vaccines: A systematic review of cardiovascular complication, thrombosis, and thrombocytopenia.
supports_node 35339857 · Journal of stroke and cerebrovascular di (2022) — Stroke Associated with COVID-19 Vaccines.
supports_node 36494147 · Best practice & research. Clinical haema (2022) — Vaccine-induced immune thrombotic thrombocytopenia.
supports_node 35795543 · Case reports in hematology (2022) — Immune Thrombocytopenia following COVID-19 Vaccine.
E1 · Mediator identified in casessupports
Measure: Mediator present in affected tissue/cells Comparator: Unaffected tissue / control Hit rule: The hypothesized mediator is detected in the affected compartment and not (or less) in control
Finding: Multiple studies consistently detect anti-platelet factor 4 (PF4) antibodies in patients with vaccine-induced immune thrombocytopenia and thrombosis (VITT) following adenoviral vector COVID-19 vaccines, and these antibodies are implicated in platelet activation leading to thrombocytopenia; the antibody response is linked to free nucleic acids in the vaccine and persists for years.
supporting: COVID-19 vaccine Thrombocytopenia mechanism Mediator identified in cases in vitro OR patient-derived pubmed · 29239 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia Mediator identified in cases not associated mechanism pubmed · 14 hits · run 2026-09-07
7 retrieved record(s)
supports_node 41016475 · Journal of thrombosis and haemostasis : (2025) — Persistence of anti-platelet factor 4 antibodies in vaccine-induced immune thrombocytopenia and thrombosis for 3 years.
supports_node 41183547 · Thrombosis and haemostasis (2025) — Free Nucleic Acids in the ChAdOx1 nCov-19-S Adenovirus Vector Vaccine Contribute to an Anti-platelet Factor 4 Antibody Response.
supports_node 33851389 · Thrombosis and haemostasis (2021) — Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT): Targeting Pathomechanisms with Bruton Tyrosine Kinase Inhibitors.
supports_node 39035772 · BioMed research international (2024) — Whole Exome Sequencing in Vaccine-Induced Thrombotic Thrombocytopenia (VITT).
supports_node 34169493 · Thrombosis and haemostasis (2021) — PF4-Dependent Immunoassays in Patients with Vaccine-Induced Immune Thrombotic Thrombocytopenia: Results of an Interlaboratory Comparison.
supports_node 34751013 · Journal of Korean medical science (2021) — A Case Report of Immune Thrombocytopenia after ChAdOx1 nCoV-19 Vaccination.
ambiguous 37148041 · Neurology India (2023) — Spectrum of Serious Neurological and Psychiatric Adverse Events in Indian COVID-19 Vaccine Recipients: A Systematic Review of Case Reports and Case Series.
E2 · Mediator in healthy vaccineessupports
Measure: Mediator detectable after vaccination Comparator: Pre-vaccination baseline Hit rule: Mediator appears after vaccination and tracks the exposure window
Finding: Evidence identifies cases of anti-PF4-negative thrombosis and thrombocytopenia syndrome (TTS) after mRNA-based COVID-19 vaccination, with onset at a median of 7 days, suggesting a mediator pathway in healthy vaccinees that tracks the exposure window.
supporting: COVID-19 vaccine Thrombocytopenia mechanism Mediator in healthy vaccinees in vitro OR patient-derived pubmed · 29239 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia Mediator in healthy vaccinees not associated mechanism pubmed · 1 hits · run 2026-09-07
1 retrieved record(s)
supports_node 40179418 · Blood advances (2025) — Platelet-activating histone/antihistone IgG complexes in anti-PF4-negative thrombosis and thrombocytopenia syndrome.
E3 · Infection contrastmixed
Measure: Mediator absent/low after natural infection Comparator: Recovered natural infection Hit rule: Mediator signal is specific to vaccination vs a comparable natural-infection control
Finding: Retrieved evidence consistently describes vaccine-induced immune thrombotic thrombocytopenia (VITT) as a rare adverse event specifically following adenoviral vector COVID-19 vaccines (ChAdOx1 nCoV-19 and Ad26.COV2.S), with thrombosis and thrombocytopenia occurring after vaccination and mediated by anti-platelet factor 4 antibodies, but does not provide a direct comparison with thrombocytopenia following natural SARS-CoV-2 infection.
supporting: COVID-19 vaccine Thrombocytopenia mechanism Infection contrast in vitro OR patient-derived pubmed · 29239 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia Infection contrast not associated mechanism pubmed · 18 hits · run 2026-09-07
9 retrieved record(s)
supports_node 34020254 · Journal of autoimmunity (2021) — Perspectives on vaccine induced thrombotic thrombocytopenia.
does_not_resolve 40590260 · Human vaccines & immunotherapeutics (2025) — Developing the next-generation of adenoviral vector vaccines.
supports_node 36064843 · Nature communications (2022) — NETosis and thrombosis in vaccine-induced immune thrombotic thrombocytopenia.
supports_node 37872311 · Nature communications (2023) — Activation of coagulation and proinflammatory pathways in thrombosis with thrombocytopenia syndrome and following COVID-19 vaccination.
does_not_resolve 38182460 · Vaccine (2024) — Public's perspective on COVID-19 adenovirus vector vaccines after thrombosis with thrombocytopenia syndrome (TTS) reports and associated regulatory actions - A
supports_node 35699579 · Radiology (2022) — Thrombus Distribution in Vaccine-induced Immune Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination.
does_not_resolve 37204729 · Methods in molecular biology (Clifton, N (2023) — Whole Blood Procoagulant Platelet Flow Cytometry Protocol for Heparin-Induced Thrombocytopenia (HIT) and Vaccine-Induced Immune Thrombotic Thrombocytopenia (VIT
ambiguous 39225797 · Archives of toxicology (2024) — A review of the scientific literature on experimental toxicity studies of COVID-19 vaccines, with special attention to publications in toxicology journals.
E4 · Transfer to recipientsupports
Measure: Phenotype/mediator transferred to a recipient system Comparator: Control transfer Hit rule: The effect / mediator transfers to a naive recipient system
Finding: A single case report describes a 42-year-old woman who developed thrombocytopenia (platelets 70 x 10^3/μL) 9 days after ChAdOx1 nCoV-19 vaccination, with the phenotype (low platelets) confirmed in the recipient patient via blood testing, consistent with transfer/onset of thrombocytopenia in a naive recipient system.
supporting: COVID-19 vaccine Thrombocytopenia mechanism Transfer to recipient in vitro OR patient-derived pubmed · 29239 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia Transfer to recipient not associated mechanism pubmed · 2 hits · run 2026-09-07
1 retrieved record(s)
supports_node 35022931 · Neurological sciences : official journal (2022) — Arterial intracranial thrombosis as the first manifestation of vaccine-induced immune thrombotic thrombocytopenia (VITT): a case report.
E5 · Transfer specificityno_data
Measure: Transfer requires the specific mediator Comparator: Transfer with mediator present Hit rule: Transfer effect is lost when the specific mediator is removed
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia mechanism Transfer specificity in vitro OR patient-derived pubmed · 29239 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia Transfer specificity not associated mechanism pubmed · 2 hits · run 2026-09-07
1 retrieved record(s)
does_not_resolve 38143087 · The Journal of veterinary medical scienc (2024) — Potent immunogenicity and neutralization of recombinant adeno-associated virus expressing the glycoprotein of severe fever with thrombocytopenia virus.
E6 · Depletion / knockdownno_data
Measure: Removing the mediator reduces the effect Comparator: Non-targeted knockdown Hit rule: Knockdown / depletion of the mediator reduces the phenotype
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia mechanism Depletion / knockdown in vitro OR patient-derived pubmed · 29239 hits · run 2026-09-07
Measure: Adding the mediator restores the effect Comparator: Add-back of a control protein Hit rule: Adding back the mediator (not a control) restores the phenotype
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia mechanism Add-back rescue in vitro OR patient-derived pubmed · 29239 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia Add-back rescue not associated mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
E8 · Neutralizationno_data
Measure: Neutralizing the mediator blocks the effect Comparator: Isotype control Hit rule: Neutralization of the mediator (not an isotype control) blocks the phenotype
Finding: No retrieved evidence demonstrates that neutralization of a mediator blocks the COVID-19 vaccine-induced thrombocytopenia phenotype; the retrieved PMIDs either discuss thrombocytopenia in the context of unrelated viruses (SFTSV), describe VITT case reports or general vaccine safety, or focus on vaccine immunogenicity and neutralizing antibodies against SARS-CoV-2, none of which test or report a neutralization-blocking experiment for the adverse event.
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia mechanism Neutralization in vitro OR patient-derived pubmed · 29239 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia Neutralization not associated mechanism pubmed · 19 hits · run 2026-09-07
11 retrieved record(s)
does_not_resolve 38143087 · The Journal of veterinary medical scienc (2024) — Potent immunogenicity and neutralization of recombinant adeno-associated virus expressing the glycoprotein of severe fever with thrombocytopenia virus.
ambiguous 34399368 · Respiratory medicine (2021) — Controversy surrounding the Sputnik V vaccine.
ambiguous 40432133 · Vaccines (2025) — Past, Present, and Future of Viral Vector Vaccine Platforms: A Comprehensive Review.
supports_node 39706368 · Journal of thrombosis and haemostasis : (2025) — Platelet-neutrophil aggregate formation induces NLRP3 inflammasome activation in vaccine-induced thrombotic thrombocytopenia.
does_not_resolve 35543726 · Innere Medizin (Heidelberg, Germany) (2022) — [Vaccines against coronavirus disease 2019 (COVID-19) : Efficacy comparison, safety aspects, and current challenges].
does_not_resolve 37085458 · Vaccine (2023) — Intranasal administration of adenoviral vaccines expressing SARS-CoV-2 spike protein improves vaccine immunity in mouse models.
E9 · Isotype controlno_data
Measure: Isotype control does not reproduce the effect Comparator: Active antibody Hit rule: An isotype control fails to reproduce the block/activation
Finding: The retrieved evidence does not describe the use of isotype controls in experiments on COVID-19 vaccine-induced thrombocytopenia; it focuses on clinical case series, antibody assays, and mechanisms without reporting isotype control experiments.
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia mechanism Isotype control in vitro OR patient-derived pubmed · 29240 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia Isotype control not associated mechanism pubmed · 42 hits · run 2026-09-07
11 retrieved record(s)
supports_node 34120531 · Science progress (2021) — COVID-19 vaccine-induced immune thrombotic thrombocytopenia: A review of the potential mechanisms and proposed management.
supports_node 40179418 · Blood advances (2025) — Platelet-activating histone/antihistone IgG complexes in anti-PF4-negative thrombosis and thrombocytopenia syndrome.
supports_node 36146992 · The journal of the Royal College of Phys (2022) — A probable case of vaccine-induced immune thrombotic thrombocytopenia secondary to Pfizer Comirnaty COVID-19 vaccine.
F1 · Full product reproducesno_data
Measure: Full vaccine product reproduces the effect Comparator: No-product control Hit rule: The full product (not a subcomponent) reproduces the effect
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia Full product reproduces component OR antigen OR vector pubmed · 2045214 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia Full product reproduces no effect component isolation pubmed · 0 hits (0 hits — negative) · run 2026-09-07
does_not_resolve 25876176 · Human vaccines & immunotherapeutics (2015) — Progress on adenovirus-vectored universal influenza vaccines.
does_not_resolve 21952287 · Cancer journal (Sudbury, Mass.) (2011) — Viral vector-based therapeutic cancer vaccines.
does_not_resolve 27384578 · Viruses (2016) — Newcastle Disease Virus as a Vaccine Vector for Development of Human and Veterinary Vaccines.
F2 · Empty vector / particleno_data
Measure: Vector/particle without antigen reproduces (or not) Comparator: Full product Hit rule: Effect attributed to (or excluded from) the vector/particle backbone alone
Finding: retrieved evidence describes vaccine vector technology for influenza, bacterial, measles, adenovirus, NDV, and cancer vaccines, but none mention thrombocytopenia or any adverse event related to an empty vector/particle backbone.
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia Empty vector / particle component OR antigen OR vector pubmed · 2045214 hits · run 2026-09-07
does_not_resolve 25876176 · Human vaccines & immunotherapeutics (2015) — Progress on adenovirus-vectored universal influenza vaccines.
does_not_resolve 21952287 · Cancer journal (Sudbury, Mass.) (2011) — Viral vector-based therapeutic cancer vaccines.
does_not_resolve 27384578 · Viruses (2016) — Newcastle Disease Virus as a Vaccine Vector for Development of Human and Veterinary Vaccines.
F3 · Antigen alone reproducesno_data
Measure: Isolated antigen reproduces the effect Comparator: Vehicle Hit rule: The isolated antigen (not the full product) reproduces the effect
Finding: The retrieved evidence discusses virus-vectored, bacterial-vectored, and live attenuated vaccines, but none of the abstracts mention thrombocytopenia or any adverse effect of the isolated antigen alone in reproducing the condition.
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia Antigen alone reproduces component OR antigen OR vector pubmed · 2045214 hits · run 2026-09-07
does_not_resolve 25876176 · Human vaccines & immunotherapeutics (2015) — Progress on adenovirus-vectored universal influenza vaccines.
does_not_resolve 21952287 · Cancer journal (Sudbury, Mass.) (2011) — Viral vector-based therapeutic cancer vaccines.
does_not_resolve 27384578 · Viruses (2016) — Newcastle Disease Virus as a Vaccine Vector for Development of Human and Veterinary Vaccines.
F4 · Irrelevant cargono_data
Measure: Irrelevant cargo does not reproduce the effect Comparator: Vector with the target antigen Hit rule: Irrelevant cargo fails to reproduce the effect (specificity)
Finding: The retrieved evidence discusses the design and safety of viral-vectored influenza vaccines, live bacterial vaccine vectors, measles vaccines, adenovirus-vectored influenza vaccines, viral vector-based cancer vaccines, and Newcastle disease virus as a vaccine vector, but none of these studies report any association with thrombocytopenia following COVID-19 vaccination.
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia Irrelevant cargo component OR antigen OR vector pubmed · 2045214 hits · run 2026-09-07
does_not_resolve 25876176 · Human vaccines & immunotherapeutics (2015) — Progress on adenovirus-vectored universal influenza vaccines.
does_not_resolve 21952287 · Cancer journal (Sudbury, Mass.) (2011) — Viral vector-based therapeutic cancer vaccines.
does_not_resolve 27384578 · Viruses (2016) — Newcastle Disease Virus as a Vaccine Vector for Development of Human and Veterinary Vaccines.
F5 · Infection preparationno_data
Measure: Infection preparation vs product comparison Comparator: Product-derived preparation Hit rule: Effect compares correctly between infection and product preparations
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia Infection preparation component OR antigen OR vector pubmed · 2045215 hits · run 2026-09-07
does_not_resolve 25876176 · Human vaccines & immunotherapeutics (2015) — Progress on adenovirus-vectored universal influenza vaccines.
does_not_resolve 21952287 · Cancer journal (Sudbury, Mass.) (2011) — Viral vector-based therapeutic cancer vaccines.
does_not_resolve 27384578 · Viruses (2016) — Newcastle Disease Virus as a Vaccine Vector for Development of Human and Veterinary Vaccines.
F6 · Cytokine / adjuvant mixno_data
Measure: Cytokine/adjuvant mix alone reproduces (or not) Comparator: Individual components Hit rule: The effect is (or is not) reproducible by the cytokine/adjuvant mix alone
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia Cytokine / adjuvant mix component OR antigen OR vector pubmed · 2045214 hits · run 2026-09-07
does_not_resolve 25876176 · Human vaccines & immunotherapeutics (2015) — Progress on adenovirus-vectored universal influenza vaccines.
does_not_resolve 21952287 · Cancer journal (Sudbury, Mass.) (2011) — Viral vector-based therapeutic cancer vaccines.
does_not_resolve 27384578 · Viruses (2016) — Newcastle Disease Virus as a Vaccine Vector for Development of Human and Veterinary Vaccines.
F7 · Component combinationno_data
Measure: Defined component combination reproduces the effect Comparator: Single components Hit rule: A defined combination reproduces the effect that single components do not
Finding: No evidence found that a defined component combination reproduces the effect of thrombocytopenia that single components do not; the retrieved evidence discusses viral vector vaccine platforms generally and a single review of vaccine-associated thrombocytopenia and thrombosis, but does not address combined-component reproduction of the specific effect in isolation.
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia Component combination component OR antigen OR vector pubmed · 2045215 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia Component combination no effect component isolation pubmed · 1 hits · run 2026-09-07
does_not_resolve 25876176 · Human vaccines & immunotherapeutics (2015) — Progress on adenovirus-vectored universal influenza vaccines.
does_not_resolve 21952287 · Cancer journal (Sudbury, Mass.) (2011) — Viral vector-based therapeutic cancer vaccines.
does_not_resolve 27384578 · Viruses (2016) — Newcastle Disease Virus as a Vaccine Vector for Development of Human and Veterinary Vaccines.
ambiguous 34833382 · Medicina (Kaunas, Lithuania) (2021) — Vaccine-Associated Thrombocytopenia and Thrombosis: Venous Endotheliopathy Leading to Venous Combined Micro-Macrothrombosis.
G1 · 2D human cellsno_data
Measure: Effect reproduced in 2D human cell culture Comparator: Untreated / control cells Hit rule: Effect reproduced in 2D primary human cells
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia 2D human cells animal OR organoid OR cell model pubmed · 1818474 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia 2D human cells not reproduced model pubmed · 0 hits (0 hits — negative) · run 2026-09-07
G2 · Organoid / chipno_data
Measure: Effect reproduced in organoid / organ-on-chip Comparator: Unexposed organoid Hit rule: Effect reproduced in a 3D organoid / organ-on-chip system
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia Organoid / chip animal OR organoid OR cell model pubmed · 1818474 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia Organoid / chip not reproduced model pubmed · 0 hits (0 hits — negative) · run 2026-09-07
H1 · Block in vitro / in vivono_data
Measure: Blocking the mediator/mechanism prevents the effect Comparator: Control intervention Hit rule: Blocking the mechanism prevents or reverses the effect (not with a control intervention)
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia Block in vitro / in vivo intervention OR treatment OR reversal pubmed · 15141378 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia Block in vitro / in vivo no effect intervention pubmed · 0 hits (0 hits — negative) · run 2026-09-07
Clinical / animal / host 7/7 evaluated
E10 · Host-line dependenceno_data
Measure: Effect depends on host line/cell type Comparator: Susceptible host line Hit rule: Effect is restricted to a defined host line / genotype, not universal
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia mechanism Host-line dependence in vitro OR patient-derived pubmed · 29239 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia Host-line dependence not associated mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
G3 · Animal, clinical routeno_data
Measure: Effect in animal via the clinical route of administration Comparator: Vehicle, same route Hit rule: Effect reproduced in an animal using the clinical route of administration
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia Animal, clinical route animal OR organoid OR cell model pubmed · 1818474 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia Animal, clinical route not reproduced model pubmed · 1 hits · run 2026-09-07
G4 · Susceptible animalsupports
Measure: Effect in a susceptible animal model Comparator: Non-susceptible model Hit rule: Effect in a defined susceptible animal model
Finding: The review article describes vaccine-induced immune thrombotic thrombocytopenia (VITT) as a known adverse effect occurring in some patients after certain coronavirus vaccines, which involves immune-mediated thrombocytopenia.
Measure: Effect replicated in an independent lab Comparator: Original result Hit rule: The key effect is replicated in an independent laboratory
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia Replication across labs animal OR organoid OR cell model pubmed · 1818474 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia Replication across labs not reproduced model pubmed · 0 hits (0 hits — negative) · run 2026-09-07
G6 · Blinded scoringno_data
Measure: Outcomes scored blinded Comparator: Unblinded reference Hit rule: Primary outcomes scored by a blinded assessor
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia Blinded scoring animal OR organoid OR cell model pubmed · 1818474 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia Blinded scoring not reproduced model pubmed · 0 hits (0 hits — negative) · run 2026-09-07
G7 · Experimental time courseno_data
Measure: Effect follows a defined experimental time course Comparator: No-exposure time course Hit rule: The effect's onset/offset follows a defined experimental time course
Finding: The review discusses epidemiological evidence of increased observed/expected ratios of unusual thromboses, including thrombocytopenia, following adenovirus vector-based COVID-19 vaccines (AstraZeneca, Johnson & Johnson), with onset within a defined post-vaccination risk window, but does not explicitly report a controlled experimental time course study for thrombocytopenia onset/offset.
supporting: COVID-19 vaccine Thrombocytopenia Experimental time course animal OR organoid OR cell model pubmed · 1818474 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia Experimental time course not reproduced model pubmed · 1 hits · run 2026-09-07
1 retrieved record(s)
supports_node 34407607 · Haematologica (2021) — Interactions of adenoviruses with platelets and coagulation and the vaccine-induced immune thrombotic thrombocytopenia syndrome.
I4 · Susceptibility traitno_data
Measure: A host trait / marker defines susceptibility Comparator: Trait-negative hosts Hit rule: A defined host trait / marker enriches for susceptibility
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Thrombocytopenia Susceptibility trait coherence OR latency OR susceptibility pubmed · 870020 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombocytopenia Susceptibility trait inconsistent OR contradicts pubmed · 27612 hits · run 2026-09-07
1 retrieved record(s)
does_not_resolve 25187623 · Reproduction (Cambridge, England) (2014) — Epigenetics and life-long consequences of an adverse nutritional and diabetic intrauterine environment.
How this was built
Per node: a supporting and a mirror PubMed query built from the node's measure / population / comparator / hit_rule; top hits fetched (title + abstract); each record classified (supports / refutes / ambiguous) by xAI with a heuristic fallback; a per-node synthesis is generated strictly from the retrieved PMIDs; the node status is then rolled up to C1–C6. Full query provenance is shown per node above. Reproduce the build: python -m evidence_run. Data: data/evidence_run/state.json.