DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for thrombophilia due to thrombin defect — screening already-approved drugs against its 6-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleThrombophilia due to thrombin defect maps to a 6-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for thrombophilia due to thrombin defect is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
methylenetetrahydrofolate reductase (MTHFR) — MTHFR is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet sahdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8QA4 · 2.8 Å · ligand S-ADENOSYL-L-HOMOCYSTEINE (SAH). Experimental structure, not a prediction.
What the evidence adds up to
Five genetic defects are established risk factors for venous thrombosis: deficiencies of protein C, protein S, and antithrombin, plus factor V Leiden and the prothrombin 20210 A allele. Together, factor V Leiden and the prothrombin mutation are found in 63% of thrombophilia families, while the three anticoagulant deficiencies are found in about 15%. In a series of 93 patients with primary thrombophilia and a family history, 24% had protein C deficiency, 24% had antithrombin III deficiency, 18% had factor V Leiden, 10% had protein S deficiency, and 10% had the prothrombin G20210 mutation; 24% had more than one defect. Among 227 patients with acute pulmonary embolism screened for thrombophilia, 108 (47.6%) had a defect, most frequently deficiencies of protein S, protein C, and antithrombin III, while only 7 of 79 tested had factor V Leiden.
In a prospective study of 180 patients with familial thrombophilia (factor V Leiden or deficiencies of protein C, S, or antithrombin) who were not on long-term anticoagulation after a first venous thrombosis, the recurrence rate was 5.0% per year (44 events over a mean follow-up of 5.6 years). Among 124 patients on long-term anticoagulation, the recurrence rate was 1.1% per year (7 events). Long-term anticoagulation reduced recurrent events by 80% but carried a major hemorrhage risk of 0.8% per year. The highest recurrence rates were in men with natural anticoagulant deficiency or multiple defects and in women with antithrombin deficiency. In the pulmonary embolism cohort, overall mortality was 8.4% and was non-significantly higher in patients without thrombophilia.
Congenital antithrombin deficiency is described as the most severe type of thrombophilia, yet it shows remarkable clinical heterogeneity and is probably underdiagnosed. In the primary thrombophilia series, 71% of patients had their first thrombotic episode before age 40, 62% had more than one episode, and 37% had a family history. Among asymptomatic adult relatives of these patients, five had factor V Leiden, four had protein C deficiency, and three had the prothrombin G20210 mutation. The laboratory diagnosis of protein C, protein S, and antithrombin deficiencies is hampered by large genetic heterogeneity, whereas factor V Leiden and the prothrombin mutation can be diagnosed by single-mutation DNA analysis.
What remains missing is prospective data on how to stratify patients by specific defect and clinical history to tailor anticoagulation duration, especially for the less common deficiencies. No randomised trial has compared different anticoagulation strategies in these subgroups, and the underdiagnosis of antithrombin deficiency means its true recurrence risk and optimal management are not established.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Clinical Chemistry · 1997 · 159 citations · open access
Factor V Leiden and other coagulation factor mutations affecting thrombotic risk
AbstractFive genetic defects have been established as risk factors for venous thrombosis. Three are protein C, protein S, and antithrombin deficiencies, defects in the anticoagulant pathways of blood coagulation. Together they can be found in approximately 15% of families with inherited thrombophilia. Their laboratory diagnosis is hampered by the large genetic heterogeneity of these defects. The other two genetic risk factors, resistance to activated protein C associated with the factor V Leiden mutation and increased prothrombin associated with the prothrombin 20210 A allele, are much more prevalent and together can be found in 63% of the thrombophilia families. Because both defects are caused by a single mutation, DNA analysis is the basis of their laboratory diagnosis.
Arteriosclerosis Thrombosis and Vascular Biology · 2005 · 105 citations · open access
Recurrence Rate After a First Venous Thrombosis in Patients With Familial Thrombophilia
AbstractOBJECTIVE: Few comprehensive data are available on the recurrence rate of venous thrombosis in carriers of thrombophilic defects from thrombophilic families. We prospectively determined the recurrence rate after a first venous thrombotic event in patients with familial thrombophilia attributable to factor V Leiden or deficiencies of protein C, S, or antithrombin. METHODS AND RESULTS: Data were gathered during follow-up on the occurrence of risk situations, anticoagulation treatment, and events (eg, venous thrombosis, hemorrhage). Over a mean follow-up period of 5.6 years, 44 of the 180 patients with familial thrombophilia who did not use long-term anticoagulation experienced a recurrent venous thromboembolic event (5.0%/year; 95% CI 3.6 to 6.7) compared with 7 of the 124 patients on long-term anticoagulation (1.1%/year; 95% CI 0.4 to 2.2). Spontaneous events occurred less often in patients on long-term anticoagulation (57%) than in patients without long-term anticoagulation (75%). The highest recurrence rate was found among men with a deficiency in natural anticoagulants or multiple defects and women with antithrombin deficiency. Although long-term anticoagulation treatment decreased the incidence of recurrent events by 80%, it also resulted in a risk of major hemorrhage of 0.8% per year. CONCLUSIONS: Extra care after a first event is required for men with a deficiency in natural anticoagulants or multiple defects and women with antithrombin deficiency.
Polskie Archiwum Medycyny Wewnętrznej · 2020 · 20 citations · open access
Antithrombin deficiency as a still underdiagnosed thrombophilia: a primer for internists
AbstractAntithrombin is a key endogenous anticoagulant that also plays other roles in inflammation, immunity, and other processes. Congenital antithrombin deficiency is the most severe type of thrombophilia, yet characterized by a remarkable clinical heterogeneity. Here, as a primer for internists, we present a practical review of data regarding this disorder, focused on its molecular basis, diagnostic procedures, prognostic implications, and clinical management of patients suffering from this severe, and probably underdiagnosed, type of thrombophilia.
Vascular Health and Risk Management · 2020 · 13 citations · open access
<p>Prevalence and Outcomes of Thrombophilia in Patients with Acute Pulmonary Embolism</p>
AbstractBackground: We aimed to study the prevalence and outcomes of thrombophilia in acute pulmonary embolism. Methods: A retrospective observational study was conducted to include patients with a radiologically confirmed diagnosis of PE screened for thrombophilia from May 2011 to February 2015. Data included patients’ demographics; clinical presentation, risk factors, laboratory investigations, management, and outcome were analyzed and compared in patients with and without thrombophilia. Results: A total of 227 cases of PE were included in the study, of which 108 (47.6%) had thrombophilia. The most frequent coagulopathic abnormality included deficiency of protein S, protein C, and antithrombin III and hyperhomocysteinemia. Only seven out of 79 patients were found to have factor V Leiden. PE patients diagnosed with thrombophilia were 10 years younger in age and peaked in the age range 30– 39 years. Prior history of DVT ( p =0.001) and PE ( p =0.001) were the main significant risk factors in the thrombophilia group. The frequency of different risk categories of clinical probability scores did not differ significantly among those with and without thrombophilia. Pulmonary hypertension was a common complication in the thrombophilia group ( P =0.009). Medications used included warfarin (74.7%), enoxaparin (73.9%), and heparin (55.4%). The overall mortality rate was 8.4%, and was non-significantly higher in the non-thrombophilia group. Conclusion: Deficiencies of protein S, protein C, and antithrombin III are the leading causes of thrombophilic defects. Patients with hereditary thrombophilia are at increased risk of acute PE, particularly among young individuals. Therefore, early detection of thrombophilic defects together with other unprovoked risk factors could reduce the risk of recurrent VTE. Keywords: pulmonary embolism, thrombophilia, risk factors, thromboembolism, outcome
Revista médica de Chile · 2004 · 3 citations · open access
Trombofilia primaria: detección y manifestación clínica en 105 casos
AbstractBACKGROUND: Thrombophilia is defined as an altered hemostasis that predisposes to thrombosis. It can be primary when there is a family clustering of the disease or secondary, when it is associated to an acquired risk factor. AIM: To report clinical features in a series of patients with primary thrombophilia. MATERIAL AND METHODS: Review of clinical records of patients with thrombotic episodes that lead to the suspicions of primary thrombophilia. Analysis of asymptomatic adult close relatives of these patients. RESULTS: We report 93 subjects (56 females, age range 14-77 years) with repeated episodes of thrombosis and a family history of thrombosis and 12 asymptomatic close relatives. Seventy one percent had the first thrombotic episode before the age of 40 years, 62% had more than one thrombotic episode and 37% had a family history of thrombosis. Twenty four percent had protein C deficiency, 24% had antithrombin III deficiency, 18% had resistance to activated C protein by factor V Leiden, 10% had protein S deficiency, and 10% had the G20210 mutation of prothrombin gene. Among acquired defects studied simultaneously, 30% had lupus anticoagulant and 11% had hyperhomocysteinemia. Twenty four percent of cases had more than one thrombophilic risk factor. Among asymptomatic relatives, five had factor V Leiden, four had protein C deficiency and three had the G20210 mutation of prothrombin gene. CONCLUSIONS: Thrombophilia must be suspected in young subjects with thrombotic episodes and a family history. The type of coagulation defect will determine prognosis, and the type of treatment.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
