COVID-19 vaccine → Thrombosis with Thrombocytopenia Syndrome
Evidence dossier · candidate cand-covid-thrombosis-with-thrombocytopenia-syndrome · CICP program · · DRAFT — not a determination
This is a draft research-tracking dossier, not a determination that COVID-19 vaccine causes Thrombosis with Thrombocytopenia Syndrome, 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
contested
C4
Consistency / replication
contested
C5
Specificity (product / dose)
supported
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: Brighton Collaboration (named in spec §1: TTS/VITT) — 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 reportsmixed
Measure: New definite object in risk window T Comparator: Pre-vaccination baseline Hit rule: Definite object present, onset in window, competing causes considered
Finding: Two case reports describe thrombosis with thrombocytopenia syndrome (TTS) after COVID-19 vaccination: one reports pulmonary embolism and deep vein thrombosis after mRNA vaccine (PMID 37376463), and another reports vaccine-induced thrombotic thrombocytopenia after COVID-19 vaccine (PMID 35611033). A third article (PMID 36212779) discusses VITT in a single-center experience. However, no retrieved study provides a definite case of Thrombosis with Thrombocytopenia Syndrome meeting the specified working definition (new definite object in risk window with competing causes considered).
supporting: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome case report OR case series Case reports pubmed · 66238 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome alternative diagnosis OR not vaccine-related pubmed · 4054 hits · run 2026-09-07
13 retrieved record(s)
ambiguous 37376463 · Vaccines (2023) — Pulmonary Embolism after Vaccination with the COVID-19 Vaccine (Pfizer, BNT162b2): A Case Report.
supports_node 36212779 · Case reports in hematology (2022) — A Single-Centre Experience of Post-COVID-19 Vaccine-Related Immune-Mediated Complications.
supports_node 35611033 · Cureus (2022) — A Rare Case of COVID-19 Vaccine-Induced Thrombotic Thrombocytopenia in a Young Patient.
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.
does_not_resolve 40902666 · Journal of the American Academy of Derma (2026) — Drug and vaccine-associated pemphigoid in patients aged 50 years and older: A pharmacovigilance study.
A2 · Series with objective confirmationmixed
Measure: Definite object plus objective test Comparator: Reference range / diagnostic criteria Hit rule: Objective confirmation in >=1 case per the working definition
Finding: One case report describes pulmonary embolism and deep vein thrombosis after mRNA COVID-19 vaccination (Pfizer, BNT162b2), but the authors explicitly state that the association with mRNA vaccines has not been proven and that confirmed TTS cases have been documented only for viral vector vaccines.
supporting: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome case report OR case series Series with objective confirmation pubmed · 5725 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome alternative diagnosis OR not vaccine-related pubmed · 4054 hits · run 2026-09-07
12 retrieved record(s)
ambiguous 37376463 · Vaccines (2023) — Pulmonary Embolism after Vaccination with the COVID-19 Vaccine (Pfizer, BNT162b2): A Case Report.
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.
ambiguous 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.
does_not_resolve 30000765 · (2006) — Human Papillomavirus Vaccines.
does_not_resolve 38500249 · Journal of movement disorders (2024) — COVID-19 Vaccine-Related Movement Disorders: A Systematic Review.
A3 · Onset histogramno_data
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: The retrieved evidence includes case reports and studies describing thrombosis with thrombocytopenia syndrome (TTS) after COVID-19 vaccination, with onset typically within 5–30 days post-vaccination, but the evidence does not provide a systematic onset histogram or formal distribution analysis for this specific node.
Cited: (none)
supporting: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome case report OR case series Onset histogram pubmed · 86 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome alternative diagnosis OR not vaccine-related pubmed · 4054 hits · run 2026-09-07
18 retrieved record(s)
does_not_resolve 37376463 · Vaccines (2023) — Pulmonary Embolism after Vaccination with the COVID-19 Vaccine (Pfizer, BNT162b2): A Case Report.
ambiguous 36212779 · Case reports in hematology (2022) — A Single-Centre Experience of Post-COVID-19 Vaccine-Related Immune-Mediated Complications.
supports_node 35611033 · Cureus (2022) — A Rare Case of COVID-19 Vaccine-Induced Thrombotic Thrombocytopenia in a Young Patient.
supports_node 38586737 · Cureus (2024) — Post-COVID-19 Vaccine Thromboembolic Complication in the Setting of Newly Diagnosed May-Thurner Syndrome.
supports_node 35814246 · Frontiers in pharmacology (2022) — Profiling COVID-19 Vaccine Adverse Events by Statistical and Ontological Analysis of VAERS Case Reports.
ambiguous 37087559 · The American journal of case reports (2023) — Kidney Transplantation from a Deceased Donor with COVID-19 Ad26.COV2-S Vaccine-Induced Thrombotic Thrombocytopenia.
supports_node 35004085 · Cureus (2022) — Post COVID-19 Vaccine Related Cerebral Venous Sinus Thrombosis and Thrombocytopenia.
ambiguous 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
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: Retrieved evidence includes multiple case reports and reviews documenting thrombosis with thrombocytopenia syndrome (TTS) or vaccine-induced immune thrombotic thrombocytopenia (VITT) occurring within days to weeks after COVID-19 vaccination, with onset latencies (e.g., 5–30 days, within a week of second dose) consistent with the known pathophysiology of TTS.
supporting: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome case report OR case series Temporal plausibility pubmed · 115 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome alternative diagnosis OR not vaccine-related pubmed · 4054 hits · run 2026-09-07
16 retrieved record(s)
ambiguous 37376463 · Vaccines (2023) — Pulmonary Embolism after Vaccination with the COVID-19 Vaccine (Pfizer, BNT162b2): A Case Report.
supports_node 36212779 · Case reports in hematology (2022) — A Single-Centre Experience of Post-COVID-19 Vaccine-Related Immune-Mediated Complications.
supports_node 35611033 · Cureus (2022) — A Rare Case of COVID-19 Vaccine-Induced Thrombotic Thrombocytopenia in a Young Patient.
supports_node 38586737 · Cureus (2024) — Post-COVID-19 Vaccine Thromboembolic Complication in the Setting of Newly Diagnosed May-Thurner Syndrome.
ambiguous 35814246 · Frontiers in pharmacology (2022) — Profiling COVID-19 Vaccine Adverse Events by Statistical and Ontological Analysis of VAERS Case Reports.
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.
A5 · Onset-interval documentationno_data
Measure: Onset interval documented in source Comparator: Dose date Hit rule: Onset interval is recorded (not imputed) in a primary source
Finding: No retrieved evidence explicitly documents the onset interval for Thrombosis with Thrombocytopenia Syndrome attributed to COVID-19 vaccine as recorded (not imputed) in a primary source.
Cited: (none)
supporting: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome case report OR case series Onset-interval documentation pubmed · 84 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome alternative diagnosis OR not vaccine-related pubmed · 4054 hits · run 2026-09-07
19 retrieved record(s)
ambiguous 37376463 · Vaccines (2023) — Pulmonary Embolism after Vaccination with the COVID-19 Vaccine (Pfizer, BNT162b2): A Case Report.
supports_node 36212779 · Case reports in hematology (2022) — A Single-Centre Experience of Post-COVID-19 Vaccine-Related Immune-Mediated Complications.
supports_node 35611033 · Cureus (2022) — A Rare Case of COVID-19 Vaccine-Induced Thrombotic Thrombocytopenia in a Young Patient.
supports_node 38586737 · Cureus (2024) — Post-COVID-19 Vaccine Thromboembolic Complication in the Setting of Newly Diagnosed May-Thurner Syndrome.
supports_node 35814246 · Frontiers in pharmacology (2022) — Profiling COVID-19 Vaccine Adverse Events by Statistical and Ontological Analysis of VAERS Case Reports.
supports_node 41427155 · The Pan African medical journal (2025) — Vaccine-induced immune thrombotic thrombocytopenia in Tunisia following AstraZeneca COVID-19 vaccination: a case report.
supports_node 37087559 · The American journal of case reports (2023) — Kidney Transplantation from a Deceased Donor with COVID-19 Ad26.COV2-S Vaccine-Induced Thrombotic Thrombocytopenia.
supports_node 35004085 · Cureus (2022) — Post COVID-19 Vaccine Related Cerebral Venous Sinus Thrombosis and Thrombocytopenia.
A6 · Differential diagnosis excludedno_data
Measure: Competing causes assessed and excluded Comparator: Likely alternative diagnoses Hit rule: Pre-specified competing causes ruled out per the working definition
Finding: The retrieved evidence includes no case reports, studies, or diagnostic guidance specifically addressing the exclusion of competing causes of Thrombosis with Thrombocytopenia Syndrome after COVID-19 vaccination; the closest reference is a brief mention of vaccine-related clots (PMID 34854882), but no details on differential diagnosis are provided.
supporting: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome case report OR case series Differential diagnosis excluded pubmed · 511 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome alternative diagnosis OR not vaccine-related pubmed · 4054 hits · run 2026-09-07
10 retrieved record(s)
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.
does_not_resolve 40902666 · Journal of the American Academy of Derma (2026) — Drug and vaccine-associated pemphigoid in patients aged 50 years and older: A pharmacovigilance study.
does_not_resolve 30000765 · (2006) — Human Papillomavirus Vaccines.
does_not_resolve 35355663 · Respirology case reports (2022) — COVID-19 mRNA vaccine-related interstitial lung disease: Two case reports and literature review.
does_not_resolve 38500249 · Journal of movement disorders (2024) — COVID-19 Vaccine-Related Movement Disorders: A Systematic Review.
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: No retrieved evidence describes a case of Thrombosis with Thrombocytopenia Syndrome recurring after a subsequent COVID-19 vaccine dose (rechallenge). Most reports involve first-dose events, and one case report (PMID 38586737) explicitly involved a first dose only.
Cited: (none)
supporting: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome case report OR case series Rechallenge / re-exposure pubmed · 86 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome alternative diagnosis OR not vaccine-related pubmed · 4054 hits · run 2026-09-07
19 retrieved record(s)
ambiguous 37376463 · Vaccines (2023) — Pulmonary Embolism after Vaccination with the COVID-19 Vaccine (Pfizer, BNT162b2): A Case Report.
supports_node 36212779 · Case reports in hematology (2022) — A Single-Centre Experience of Post-COVID-19 Vaccine-Related Immune-Mediated Complications.
supports_node 35611033 · Cureus (2022) — A Rare Case of COVID-19 Vaccine-Induced Thrombotic Thrombocytopenia in a Young Patient.
supports_node 38586737 · Cureus (2024) — Post-COVID-19 Vaccine Thromboembolic Complication in the Setting of Newly Diagnosed May-Thurner Syndrome.
supports_node 35814246 · Frontiers in pharmacology (2022) — Profiling COVID-19 Vaccine Adverse Events by Statistical and Ontological Analysis of VAERS Case Reports.
supports_node 41427155 · The Pan African medical journal (2025) — Vaccine-induced immune thrombotic thrombocytopenia in Tunisia following AstraZeneca COVID-19 vaccination: a case report.
supports_node 37087559 · The American journal of case reports (2023) — Kidney Transplantation from a Deceased Donor with COVID-19 Ad26.COV2-S Vaccine-Induced Thrombotic Thrombocytopenia.
supports_node 35004085 · Cureus (2022) — Post COVID-19 Vaccine Related Cerebral Venous Sinus Thrombosis and Thrombocytopenia.
A8 · Adjudicated by criteria (Brighton Collaboration)no_data
Measure: Object adjudicated by published criteria Comparator: Published clinical / Brighton criteria Hit rule: Cases adjudicated to 'definite' by a published criterion set
Finding: The retrieved evidence includes a few case reports describing thrombosis with thrombocytopenia after COVID-19 vaccination, but none adjudicate cases as 'definite' by a published criterion set; most reports describe VITT/TTS clinically without applying a formal case definition or adjudication process.
Cited: (none)
supporting: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome case report OR case series Adjudicated by criteria pubmed · 123 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome alternative diagnosis OR not vaccine-related pubmed · 4054 hits · run 2026-09-07
18 retrieved record(s)
ambiguous 37376463 · Vaccines (2023) — Pulmonary Embolism after Vaccination with the COVID-19 Vaccine (Pfizer, BNT162b2): A Case Report.
supports_node 36212779 · Case reports in hematology (2022) — A Single-Centre Experience of Post-COVID-19 Vaccine-Related Immune-Mediated Complications.
supports_node 35611033 · Cureus (2022) — A Rare Case of COVID-19 Vaccine-Induced Thrombotic Thrombocytopenia in a Young Patient.
supports_node 38586737 · Cureus (2024) — Post-COVID-19 Vaccine Thromboembolic Complication in the Setting of Newly Diagnosed May-Thurner Syndrome.
supports_node 35814246 · Frontiers in pharmacology (2022) — Profiling COVID-19 Vaccine Adverse Events by Statistical and Ontological Analysis of VAERS Case Reports.
supports_node 37087559 · The American journal of case reports (2023) — Kidney Transplantation from a Deceased Donor with COVID-19 Ad26.COV2-S Vaccine-Induced Thrombotic Thrombocytopenia.
supports_node 35004085 · Cureus (2022) — Post COVID-19 Vaccine Related Cerebral Venous Sinus Thrombosis and Thrombocytopenia.
ambiguous 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
A9 · Natural-history consistencyno_data
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: The retrieved evidence includes case reports and reviews of thrombosis with thrombocytopenia syndrome (TTS) and vaccine-induced immune thrombotic thrombocytopenia (VITT) after COVID-19 vaccination, but onset timing, clinical course, and natural history details are insufficiently described to systematically assess consistency with the natural history of TTS; no study specifically evaluates whether the clinical course (onset, peak, recovery) of TTS attributed to COVID-19 vaccine matches the natural history of the syndrome.
Cited: (none)
supporting: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome case report OR case series Natural-history consistency pubmed · 187 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome alternative diagnosis OR not vaccine-related pubmed · 4054 hits · run 2026-09-07
13 retrieved record(s)
ambiguous 37376463 · Vaccines (2023) — Pulmonary Embolism after Vaccination with the COVID-19 Vaccine (Pfizer, BNT162b2): A Case Report.
supports_node 36212779 · Case reports in hematology (2022) — A Single-Centre Experience of Post-COVID-19 Vaccine-Related Immune-Mediated Complications.
supports_node 35611033 · Cureus (2022) — A Rare Case of COVID-19 Vaccine-Induced Thrombotic Thrombocytopenia in a Young Patient.
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.
A10 · No confounding objectno_data
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: The retrieved evidence consists only of case reports and reviews, several of which explicitly state that vaccine-induced immune thrombotic thrombocytopenia (VITT) is predominantly associated with adenoviral vector vaccines (e.g., ChAdOx1, Ad26.COV2.S), while the association with mRNA vaccines (e.g., BNT162b2) has not been proven. One case report describes pulmonary embolism after mRNA vaccination but does not confirm thrombocytopenia or exclusion of co-occurring conditions. No retrieved study provides systematic, controlled evidence that new Thrombosis with Thrombocytopenia Syndrome is attributable to COVID-19 vaccines after competing causes are assessed.
Cited: (none)
supporting: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome case report OR case series No confounding object pubmed · 103 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome alternative diagnosis OR not vaccine-related pubmed · 4054 hits · run 2026-09-07
20 retrieved record(s)
ambiguous 37376463 · Vaccines (2023) — Pulmonary Embolism after Vaccination with the COVID-19 Vaccine (Pfizer, BNT162b2): A Case Report.
ambiguous 36212779 · Case reports in hematology (2022) — A Single-Centre Experience of Post-COVID-19 Vaccine-Related Immune-Mediated Complications.
supports_node 35611033 · Cureus (2022) — A Rare Case of COVID-19 Vaccine-Induced Thrombotic Thrombocytopenia in a Young Patient.
supports_node 35512656 · Cerebrovascular diseases (Basel, Switzer (2022) — Ischemic Stroke and Vaccine-Induced Immune Thrombotic Thrombocytopenia following COVID-19 Vaccine: A Case Report with Systematic 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 36483810 · World journal of clinical cases (2022) — Case mistaken for leukemia after mRNA COVID-19 vaccine administration: A case report.
supports_node 38586737 · Cureus (2024) — Post-COVID-19 Vaccine Thromboembolic Complication in the Setting of Newly Diagnosed May-Thurner Syndrome.
supports_node 35814246 · Frontiers in pharmacology (2022) — Profiling COVID-19 Vaccine Adverse Events by Statistical and Ontological Analysis of VAERS Case Reports.
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 Thrombosis with Thrombocytopenia Syndrome anatomic localization Predicted site of injury mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome 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 Thrombosis with Thrombocytopenia Syndrome 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 Thrombosis with Thrombocytopenia Syndrome anatomic localization Local vs systemic distribution mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome 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 Thrombosis with Thrombocytopenia Syndrome anatomic localization Kinetics class mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome 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 Thrombosis with Thrombocytopenia Syndrome anatomic localization Platform-mechanism match mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome 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 Thrombosis with Thrombocytopenia Syndrome Targeted treatment reverses intervention OR treatment OR reversal pubmed · 15141378 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Targeted treatment reverses no effect intervention pubmed · 0 hits (0 hits — negative) · run 2026-09-07
I1 · No internal contradictionno_data
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 Thrombosis with Thrombocytopenia Syndrome No internal contradiction coherence OR latency OR susceptibility pubmed · 870020 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome No internal contradiction inconsistent OR contradicts pubmed · 27612 hits · run 2026-09-07
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 Thrombosis with Thrombocytopenia Syndrome Analogy to a known object coherence OR latency OR susceptibility pubmed · 870020 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Analogy to a known object inconsistent OR contradicts pubmed · 27612 hits · run 2026-09-07
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 Thrombosis with Thrombocytopenia Syndrome Latency coherence coherence OR latency OR susceptibility pubmed · 870020 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome 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 Thrombosis with Thrombocytopenia Syndrome Pre-specification pre-specified OR adjudicated pubmed · 13548 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Pre-specification post-hoc OR hypothesis-generating only pubmed · 1698 hits · run 2026-09-07
2 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.
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 evidence found
Cited: (none)
supporting: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Contrary-evidence log pre-specified OR adjudicated pubmed · 13548 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome 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 Thrombosis with Thrombocytopenia Syndrome No temporality-only claim pre-specified OR adjudicated pubmed · 13549 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome No temporality-only claim 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
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 Thrombosis with Thrombocytopenia Syndrome Passive-surveillance role pre-specified OR adjudicated pubmed · 13548 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome 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 38983297 · Radiology case reports (2024) — Identification of perineural invasion at imaging staging as a novel potential risk factor in rectal cancer: A case report.
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: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Dose mapping pre-specified OR adjudicated pubmed · 13548 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Dose mapping post-hoc OR hypothesis-generating only pubmed · 1698 hits · run 2026-09-07
2 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
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: No retrieved evidence directly addresses whether COVID-19 vaccination increases the excess risk of Thrombosis with Thrombocytopenia Syndrome (TTS) compared to baseline using the specified hit rule (RR/IRR > 1 with CI excluding 1 after confounder adjustment). Several studies use self-controlled case series designs for other outcomes (e.g., mortality, arrhythmias, Guillain-Barré syndrome, seizure, abnormal uterine bleeding) but none report RR/IRR for TTS specifically. One study (PMID 34774202) describes VITT pathophysiology and case reports but does not provide a controlled epidemiological estimate.
Cited: (none)
supporting: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Excess vs baseline incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome no association OR null OR no increased risk Excess vs baseline pubmed · 88650 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 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.
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 35489031 · Journal of clinical psychopharmacology (2022) — Prescription Stimulants and the Risk of Psychosis: A Systematic Review of Observational Studies.
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: No retrieved evidence provides an SCCS risk ratio > 1 with CI excluding 1 for the specific pair of COVID-19 vaccine and Thrombosis with Thrombocytopenia Syndrome. The retrieved SCCS studies address other outcomes (e.g., abnormal uterine bleeding, arrhythmias, myasthenia gravis exacerbation), and the VITT-specific articles (e.g., PMID 34774202, 34698582, 40573981) are reviews or case series, not SCCS analyses.
Cited: (none)
supporting: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome SCCS incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome no association OR null OR no increased risk SCCS pubmed · 88756 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 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 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.
does_not_resolve 34477808 · JAMA (2021) — Surveillance for Adverse Events After COVID-19 mRNA Vaccination.
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 relevant studies directly estimate an incidence rate ratio (IRR) for Thrombosis with Thrombocytopenia Syndrome (TTS) after COVID-19 vaccination using a cohort or risk-interval design with the specified stratification. The retrieved evidence includes reviews and case series on TTS and vaccine-induced immune thrombotic thrombocytopenia, but none provide the required IRR estimate with a confidence interval excluding 1 in a pre-specified window stratified by age/sex.
Cited: (none)
supporting: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Cohort / risk-interval incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome no association OR null OR no increased risk Cohort / risk-interval pubmed · 88259 hits · run 2026-09-07
12 retrieved record(s)
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 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.
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 34477808 · JAMA (2021) — Surveillance for Adverse Events After COVID-19 mRNA Vaccination.
Measure: Pooled effect across studies Comparator: Pooled estimate with heterogeneity Hit rule: Pooled estimate > 1 (or < 1) with quantified heterogeneity (I2)
Finding: No retrieved study provides a pooled meta-analytic estimate with quantified heterogeneity (I²) for the association between COVID-19 vaccination and Thrombosis with Thrombocytopenia Syndrome. The evidence consists of case series, narrative reviews, and studies of other outcomes or vaccines.
Cited: (none)
supporting: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Meta-analysis / pooling incidence risk cohort OR self-controlled case series pubmed · 947 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome no association OR null OR no increased risk Meta-analysis / pooling pubmed · 112088 hits · run 2026-09-07
10 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 34477808 · JAMA (2021) — Surveillance for Adverse Events After COVID-19 mRNA Vaccination.
supports_node 41848549 · Human vaccines & immunotherapeutics (2026) — Hematologic adverse events following COVID-19 vaccination and revaccination in persons aged 12 and above: A Canadian Immunization Research Network study.
supports_node 34698582 · Clinical and applied thrombosis/hemostas (2021) — COVID-19 Vaccine-Associated Thrombosis With Thrombocytopenia Syndrome (TTS): A Systematic Review and Post Hoc Analysis.
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 evidence found.
Cited: (none)
supporting: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Negative-control outcomes incidence risk cohort OR self-controlled case series pubmed · 946 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome no association OR null OR no increased risk Negative-control outcomes pubmed · 88460 hits · run 2026-09-07
7 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 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 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.
refutes_node 34477808 · JAMA (2021) — Surveillance for Adverse Events After COVID-19 mRNA Vaccination.
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: No retrieved evidence directly compares the risk of Thrombosis with Thrombocytopenia Syndrome (TTS) following COVID-19 vaccination against a different-antigen comparator. The retrieved studies describe TTS as a rare adverse event associated with adenoviral vector COVID-19 vaccines, but none use a comparator vaccine targeting a different antigen.
Cited: (none)
supporting: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Other-antigen comparison incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome no association OR null OR no increased risk Other-antigen comparison pubmed · 88223 hits · run 2026-09-07
11 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 34477808 · JAMA (2021) — Surveillance for Adverse Events After COVID-19 mRNA Vaccination.
does_not_resolve 40573981 · Vaccines (2025) — VITT Pathophysiology: An Update.
supports_node 34698582 · Clinical and applied thrombosis/hemostas (2021) — COVID-19 Vaccine-Associated Thrombosis With Thrombocytopenia Syndrome (TTS): A Systematic Review and Post Hoc Analysis.
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: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Absolute risk incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome no association OR null OR no increased risk Absolute risk pubmed · 111489 hits · run 2026-09-07
14 retrieved record(s)
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 38875047 · The International journal of risk & safe (2024) — Self-controlled risk interval study of rotavirus vaccine safety: Findings and implications.
refutes_node 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.
does_not_resolve 29211679 · The New England journal of medicine (2017) — Contemporary Hormonal Contraception and the Risk of Breast Cancer.
does_not_resolve 23484825 · The New England journal of medicine (2013) — Risk of ischemic heart disease in women after radiotherapy for breast cancer.
B8 · Platform splitmixed
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: The retrieved evidence includes review articles and case series describing Thrombosis with Thrombocytopenia Syndrome (TTS) specifically following adenovirus-vector COVID-19 vaccines (ChAdOx1 nCoV-19 and AD26.COV2·S), consistent with a platform-specific risk, but no formal epidemiological study directly estimating the attributable risk by platform for this outcome was retrieved.
supporting: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Platform split incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome no association OR null OR no increased risk Platform split pubmed · 88288 hits · run 2026-09-07
12 retrieved record(s)
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.
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 34477808 · JAMA (2021) — Surveillance for Adverse Events After COVID-19 mRNA Vaccination.
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: Retrieved evidence for node B9 (Host-structure stratification) primarily describes risk factors and demographic characteristics from case series and reviews of Thrombosis with Thrombocytopenia Syndrome following COVID-19 vaccination, but no study directly quantifies or compares risk by age/sex across multiple stable sources or systematically stratifies risk within defined host subgroups.
Cited: (none)
supporting: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Host-structure stratification incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome no association OR null OR no increased risk Host-structure stratification pubmed · 88221 hits · run 2026-09-07
11 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 34477808 · JAMA (2021) — Surveillance for Adverse Events After COVID-19 mRNA Vaccination.
supports_node 41848549 · Human vaccines & immunotherapeutics (2026) — Hematologic adverse events following COVID-19 vaccination and revaccination in persons aged 12 and above: A Canadian Immunization Research Network study.
supports_node 40573981 · Vaccines (2025) — VITT Pathophysiology: An Update.
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: No retrieved evidence directly addresses whether the risk of Thrombosis with Thrombocytopenia Syndrome (TTS) after COVID-19 vaccination tracks a documented formulation or component change over time. Two retrieved reviews (PMID 34774202, PMID 40573981) describe VITT/TTS pathophysiology in association with adenoviral vector vaccines but do not examine temporal risk changes linked to formulation/component changes.
Cited: (none)
supporting: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Formulation / component change incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome no association OR null OR no increased risk Formulation / component change pubmed · 88383 hits · run 2026-09-07
11 retrieved record(s)
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.
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 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 Thrombosis with Thrombocytopenia Syndrome Formulation natural experiment intervention OR treatment OR reversal pubmed · 15141378 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Formulation natural experiment no effect intervention pubmed · 0 hits (0 hits — negative) · run 2026-09-07
H4 · Policy / pause signalno_data
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 Thrombosis with Thrombocytopenia Syndrome Policy / pause signal intervention OR treatment OR reversal pubmed · 15141378 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome 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: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Infection coherence coherence OR latency OR susceptibility pubmed · 870020 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Infection coherence inconsistent OR contradicts pubmed · 27612 hits · run 2026-09-07
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 Thrombosis with Thrombocytopenia Syndrome Dose strength gradient dose-response OR dose effect pubmed · 1299132 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome no dose effect OR no dose-response Dose strength gradient pubmed · 185 hits · run 2026-09-07
8 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 34776011 · Infectious diseases of poverty (2021) — Effectiveness and safety of SARS-CoV-2 vaccine in real-world studies: a systematic review and meta-analysis.
does_not_resolve 34477808 · JAMA (2021) — Surveillance for Adverse Events After COVID-19 mRNA Vaccination.
supports_node 34176415 · Expert review of vaccines (2021) — COVID-19 vaccines and thrombosis with thrombocytopenia syndrome.
supports_node 37517912 · Vaccine (2023) — Thrombosis with thrombocytopenia syndrome: A database review of clinical trial and post-marketing experience with Ad26.COV2.S.
supports_node 35611033 · Cureus (2022) — A Rare Case of COVID-19 Vaccine-Induced Thrombotic Thrombocytopenia in a Young Patient.
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: No evidence found
Cited: (none)
supporting: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Dose number gradient dose-response OR dose effect pubmed · 1299132 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome no dose effect OR no dose-response Dose number gradient pubmed · 629 hits · run 2026-09-07
8 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.
supports_node 34176415 · Expert review of vaccines (2021) — COVID-19 vaccines and thrombosis with thrombocytopenia syndrome.
supports_node 37517912 · Vaccine (2023) — Thrombosis with thrombocytopenia syndrome: A database review of clinical trial and post-marketing experience with Ad26.COV2.S.
supports_node 35611033 · Cureus (2022) — A Rare Case of COVID-19 Vaccine-Induced Thrombotic Thrombocytopenia in a Young Patient.
supports_node 35512656 · Cerebrovascular diseases (Basel, Switzer (2022) — Ischemic Stroke and Vaccine-Induced Immune Thrombotic Thrombocytopenia following COVID-19 Vaccine: A Case Report with Systematic Review of the Literature.
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: No retrieved evidence directly addresses risk of Thrombosis with Thrombocytopenia Syndrome ordered by measured-exposure tertile of COVID-19 vaccine. The available studies describe TTS/VITT as a rare adverse event after adenoviral vector vaccines, but none stratify risk by measured-exposure tertile.
Cited: (none)
supporting: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Measured-exposure tertiles dose-response OR dose effect pubmed · 1299132 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome no dose effect OR no dose-response Measured-exposure tertiles pubmed · 74 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 34477808 · JAMA (2021) — Surveillance for Adverse Events After COVID-19 mRNA Vaccination.
supports_node 34176415 · Expert review of vaccines (2021) — COVID-19 vaccines and thrombosis with thrombocytopenia syndrome.
supports_node 37517912 · Vaccine (2023) — Thrombosis with thrombocytopenia syndrome: A database review of clinical trial and post-marketing experience with Ad26.COV2.S.
supports_node 35611033 · Cureus (2022) — A Rare Case of COVID-19 Vaccine-Induced Thrombotic Thrombocytopenia in a Young Patient.
ambiguous 33851389 · Thrombosis and haemostasis (2021) — Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT): Targeting Pathomechanisms with Bruton Tyrosine Kinase Inhibitors.
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 reports dose-dependent effects of COVID-19 vaccine antigen concentration in organoids on Thrombosis with Thrombocytopenia Syndrome.
Cited: (none)
supporting: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Organoid concentration curve dose-response OR dose effect pubmed · 1299132 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome no dose effect OR no dose-response Organoid concentration curve pubmed · 85 hits · run 2026-09-07
9 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.
supports_node 34176415 · Expert review of vaccines (2021) — COVID-19 vaccines and thrombosis with thrombocytopenia syndrome.
supports_node 35989136 · Vaccine (2022) — Thrombosis with thrombocytopenia after AZD1222 (ChAdOx1 nCov-19) vaccination: Case characteristics and associations.
supports_node 37517912 · Vaccine (2023) — Thrombosis with thrombocytopenia syndrome: A database review of clinical trial and post-marketing experience with Ad26.COV2.S.
supports_node 35611033 · Cureus (2022) — A Rare Case of COVID-19 Vaccine-Induced Thrombotic Thrombocytopenia in a Young Patient.
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: Retrieved evidence includes only case reports and reviews of vaccine-induced thrombotic thrombocytopenia (VITT) following adenoviral COVID-19 vaccines (e.g., PMID 34176415, 35446471, 37517912, 35611033, 35512656, 36483810), but none report relevant in-vitro EC50 or Cmax exposure data for the COVID-19 vaccine–TTS pair.
Cited: (none)
supporting: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome EC50 vs Cmax coherence dose-response OR dose effect pubmed · 1299132 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome no dose effect OR no dose-response EC50 vs Cmax coherence pubmed · 74 hits · run 2026-09-07
8 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.
does_not_resolve 34176415 · Expert review of vaccines (2021) — COVID-19 vaccines and thrombosis with thrombocytopenia syndrome.
supports_node 37517912 · Vaccine (2023) — Thrombosis with thrombocytopenia syndrome: A database review of clinical trial and post-marketing experience with Ad26.COV2.S.
supports_node 35611033 · Cureus (2022) — A Rare Case of COVID-19 Vaccine-Induced Thrombotic Thrombocytopenia in a Young Patient.
supports_node 35512656 · Cerebrovascular diseases (Basel, Switzer (2022) — Ischemic Stroke and Vaccine-Induced Immune Thrombotic Thrombocytopenia following COVID-19 Vaccine: A Case Report with Systematic Review of the Literature.
ambiguous 36483810 · World journal of clinical cases (2022) — Case mistaken for leukemia after mRNA COVID-19 vaccine administration: A case report.
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: PMID 33851389 describes platelet-activating antibodies to platelet factor 4 as a key mediator detected in affected patients with vaccine-induced immune thrombotic thrombocytopenia (VITT), consistent with the hypothesized mediator being present in affected tissue/blood in cases.
supporting: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome mechanism Mediator identified in cases in vitro OR patient-derived pubmed · 29239 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Mediator identified in cases not associated mechanism pubmed · 4 hits · run 2026-09-07
3 retrieved record(s)
ambiguous 33851389 · Thrombosis and haemostasis (2021) — Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT): Targeting Pathomechanisms with Bruton Tyrosine Kinase Inhibitors.
does_not_resolve 37716365 · The Lancet. Respiratory medicine (2023) — Efficacy of a bivalent (D614 + B.1.351) SARS-CoV-2 recombinant protein vaccine with AS03 adjuvant in adults: a phase 3, parallel, randomised, modified double-bl
does_not_resolve 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 vaccineesno_data
Measure: Mediator detectable after vaccination Comparator: Pre-vaccination baseline Hit rule: Mediator appears after vaccination and tracks the exposure window
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome mechanism Mediator in healthy vaccinees in vitro OR patient-derived pubmed · 29239 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Mediator in healthy vaccinees not associated mechanism pubmed · 1 hits · run 2026-09-07
E3 · Infection contrastno_data
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: The retrieved evidence does not compare mediator levels (e.g., anti-PF4 antibodies) after natural SARS-CoV-2 infection versus vaccination, which is required to assess whether the mediator signal is specific to vaccination. Two articles (PMID 36082668, 34029848) describe TTS after COVID-19 vaccination but lack a natural-infection comparator; PMID 37872311 compares mRNA and adenovirus vector vaccines but does not include natural infection; PMID 38182460 surveys public perception and does not address mediator specificity.
Cited: (none)
supporting: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome mechanism Infection contrast in vitro OR patient-derived pubmed · 29239 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Infection contrast not associated mechanism pubmed · 6 hits · run 2026-09-07
4 retrieved record(s)
supports_node 36082668 · Stroke (2022) — Outcomes of Cerebral Venous Thrombosis due to Vaccine-Induced Immune Thrombotic Thrombocytopenia After the Acute Phase.
ambiguous 34029848 · Thrombosis research (2021) — Hypotheses behind the very rare cases of thrombosis with thrombocytopenia syndrome after SARS-CoV-2 vaccination.
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
E4 · Transfer to recipientno_data
Measure: Phenotype/mediator transferred to a recipient system Comparator: Control transfer Hit rule: The effect / mediator transfers to a naive recipient system
Finding: no evidence found
Cited: (none)
supporting: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome mechanism Transfer to recipient in vitro OR patient-derived pubmed · 29239 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Transfer to recipient not associated mechanism pubmed · 1 hits · run 2026-09-07
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 Thrombosis with Thrombocytopenia Syndrome mechanism Transfer specificity in vitro OR patient-derived pubmed · 29239 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Transfer specificity not associated mechanism pubmed · 1 hits · run 2026-09-07
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 Thrombosis with Thrombocytopenia Syndrome mechanism Depletion / knockdown in vitro OR patient-derived pubmed · 29239 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Depletion / knockdown not associated mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
E7 · Add-back rescueno_data
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 Thrombosis with Thrombocytopenia Syndrome mechanism Add-back rescue in vitro OR patient-derived pubmed · 29239 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome 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: None of the retrieved abstracts describe neutralization experiments in which blocking the mediator (e.g., anti-PF4 antibodies) prevents the thrombotic thrombocytopenic phenotype. The evidence consists of clinical reviews and an inactivated vaccine trial that do not test neutralization of a mediator.
Cited: (none)
supporting: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome mechanism Neutralization in vitro OR patient-derived pubmed · 29239 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Neutralization not associated mechanism pubmed · 4 hits · run 2026-09-07
does_not_resolve 37325662 · Frontiers in immunology (2023) — Effect of an inactivated coronavirus disease 2019 vaccine, CoronaVac, on blood coagulation and glucose: a randomized, controlled, open-label phase IV clinical t
does_not_resolve 35358170 · MMWR. Morbidity and mortality weekly rep (2022) — Effectiveness of Homologous and Heterologous COVID-19 Booster Doses Following 1 Ad.26.COV2.S (Janssen [Johnson & Johnson]) Vaccine Dose Against COVID-19-Associa
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: No retrieved evidence directly addresses whether an isotype control fails to reproduce the block or activation in the context of COVID-19 vaccine-associated Thrombosis with Thrombocytopenia Syndrome.
Cited: (none)
supporting: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome mechanism Isotype control in vitro OR patient-derived pubmed · 29239 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Isotype control not associated mechanism pubmed · 12 hits · run 2026-09-07
10 retrieved record(s)
supports_node 34373413 · Rinsho shinkeigaku = Clinical neurology (2021) — [Cerebral vein/venous sinus thrombosis with thrombocytopenia syndrome after COVID-19 vaccination].
supports_node 34374713 · JAMA cardiology (2021) — Clinical Characteristics and Pharmacological Management of COVID-19 Vaccine-Induced Immune Thrombotic Thrombocytopenia With Cerebral Venous Sinus Thrombosis: A
supports_node 35679071 · Blood (2022) — The interaction between anti-PF4 antibodies and anticoagulants in vaccine-induced thrombotic thrombocytopenia.
supports_node 34461442 · Journal of stroke and cerebrovascular di (2021) — Treatment of ChAdOx1 nCoV-19 Vaccine-Induced Immune Thrombotic Thrombocytopenia Related Acute Ischemic Stroke.
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: The retrieved evidence discusses recombinant virus-vectored vaccines for influenza, cancer, and measles, and an adenovirus-vectored COVID-19 vaccine for inhalation, but none report or assess thrombosis with thrombocytopenia syndrome (TTS) attributed to a COVID-19 vaccine.
Cited: (none)
supporting: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Full product reproduces component OR antigen OR vector pubmed · 2045214 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome 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 40276512 · Frontiers in immunology (2025) — Development of a novel adenovirus type 4 vector as a promising respiratory vaccine vehicle.
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: No evidence retrieved directly addresses Thrombosis with Thrombocytopenia Syndrome (TTS) attributed to any vaccine vector/particle backbone. The retrieved PMIDs discuss influenza, bacterial, measles, adenoviral, NDV, and cancer vaccine vectors but do not report on TTS or any thrombotic adverse event.
Cited: (none)
supporting: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Empty vector / particle component OR antigen OR vector pubmed · 2045214 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Empty vector / particle 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.
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 describes various virus-vectored and bacterial-vectored vaccines for influenza, measles, and cancer, but none mention COVID-19 vaccine, Thrombosis with Thrombocytopenia Syndrome, or any adverse event of thrombosis. No evidence addresses the specificity or irrelevance of cargo in reproducing TTS.
Cited: (none)
supporting: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Irrelevant cargo component OR antigen OR vector pubmed · 2045214 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Irrelevant cargo 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.
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: The retrieved evidence discusses the use of viral vectors (e.g., adenovirus, measles virus) in vaccine development for influenza, cancer, and respiratory diseases, but none address Thrombosis with Thrombocytopenia Syndrome, COVID-19 vaccines, or any comparison of infection preparation versus product preparation for this adverse event.
Cited: (none)
supporting: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Infection preparation component OR antigen OR vector pubmed · 2045215 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Infection preparation 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 40276512 · Frontiers in immunology (2025) — Development of a novel adenovirus type 4 vector as a promising respiratory vaccine vehicle.
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 Thrombosis with Thrombocytopenia Syndrome Cytokine / adjuvant mix component OR antigen OR vector pubmed · 2045214 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Cytokine / adjuvant mix 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 40276512 · Frontiers in immunology (2025) — Development of a novel adenovirus type 4 vector as a promising respiratory vaccine vehicle.
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
Cited: (none)
supporting: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Component combination component OR antigen OR vector pubmed · 2045215 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome 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 34833382 · Medicina (Kaunas, Lithuania) (2021) — Vaccine-Associated Thrombocytopenia and Thrombosis: Venous Endotheliopathy Leading to Venous Combined Micro-Macrothrombosis.
does_not_resolve 21952287 · Cancer journal (Sudbury, Mass.) (2011) — Viral vector-based therapeutic cancer vaccines.
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 Thrombosis with Thrombocytopenia Syndrome 2D human cells animal OR organoid OR cell model pubmed · 1818474 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome 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 Thrombosis with Thrombocytopenia Syndrome Organoid / chip animal OR organoid OR cell model pubmed · 1818474 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome 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 Thrombosis with Thrombocytopenia Syndrome Block in vitro / in vivo intervention OR treatment OR reversal pubmed · 15141378 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome 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 Thrombosis with Thrombocytopenia Syndrome mechanism Host-line dependence in vitro OR patient-derived pubmed · 29239 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome 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 Thrombosis with Thrombocytopenia Syndrome Animal, clinical route animal OR organoid OR cell model pubmed · 1818474 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Animal, clinical route not reproduced model pubmed · 0 hits (0 hits — negative) · run 2026-09-07
G4 · Susceptible animalno_data
Measure: Effect in a susceptible animal model Comparator: Non-susceptible model Hit rule: Effect in a defined susceptible animal model
Finding: The review discusses vaccine-induced immune thrombotic thrombocytopenia (VITT) as a rare adverse event following certain coronavirus vaccines, mentioning that antibodies to platelet factor 4/polyanion complexes can trigger platelet activation and thrombosis, which aligns with the Thrombosis with Thrombocytopenia Syndrome phenotype, but no direct evidence from a susceptible animal model is provided.
Cited: (none)
supporting: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Susceptible animal animal OR organoid OR cell model pubmed · 1818475 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Susceptible animal not reproduced model pubmed · 1 hits · run 2026-09-07
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 Thrombosis with Thrombocytopenia Syndrome Replication across labs animal OR organoid OR cell model pubmed · 1818474 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome 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 Thrombosis with Thrombocytopenia Syndrome Blinded scoring animal OR organoid OR cell model pubmed · 1818474 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome 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 retrieved evidence is a review discussing the epidemiological observation of an increased observed/expected ratio of unusual thromboses, including cerebral vein sinus thrombosis, following adenovirus-vector COVID-19 vaccines, but does not provide a defined experimental time course for onset or offset of Thrombosis with Thrombocytopenia Syndrome.
supporting: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Experimental time course animal OR organoid OR cell model pubmed · 1818474 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome 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 Thrombosis with Thrombocytopenia Syndrome Susceptibility trait coherence OR latency OR susceptibility pubmed · 870020 hits · run 2026-09-07
mirror: COVID-19 vaccine Thrombosis with Thrombocytopenia Syndrome Susceptibility trait inconsistent OR contradicts pubmed · 27612 hits · run 2026-09-07
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.