DeCure for Hereditary thrombophilia due to congenital histidine-rich (poly-L) glycoprotein deficiency
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hereditary thrombophilia due to congenital histidine-rich (poly-L) glycoprotein deficiency — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHereditary thrombophilia due to congenital histidine-rich (poly-L) glycoprotein deficiency maps to a 1-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 hereditary thrombophilia due to congenital histidine-rich (poly-l) glycoprotein deficiency 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.
What the evidence adds up to
A 1992 study measured plasma beta-2-glycoprotein I levels in healthy volunteers and four groups of patients with familial thrombophilia. The prevalence of beta-2-GP I deficiency (antigen less than 77%) was similar across all groups, ranging from 6.8% to 12.5%, with no statistically significant difference. One thrombophilic patient was homozygous deficient for beta-2-GP I; his brother, also homozygous deficient, remained free of thromboembolic complications at age 35. In a panel of 70 unrelated patients with clinically dominant protein C deficiency, the prevalence of beta-2-GP I deficiency was 12.8%, again similar to other groups, and there was no difference in deficiency frequency between symptomatic and asymptomatic protein C deficient patients. The authors concluded that beta-2-GP I deficiency in itself is not a risk factor for thrombosis.
Two 1987 papers describe a patient with spontaneous venous thrombotic events, myocardial infarction, and a positive family history of thrombosis who was found to have abnormally high levels of histidine-rich glycoprotein. No other prothrombotic abnormality was identified. Elevated histidine-rich glycoprotein levels appeared in four other family members over two generations, suggesting a hereditary disorder. The authors called for further study on the relation between elevated histidine-rich glycoprotein levels and thrombosis.
A 2023 report on congenital antithrombin deficiency notes that it carries the highest thrombotic risk among inherited thrombophilias, with heterogeneous clinical presentation depending on family history and mutation type. The authors state that patients with congenital AT deficiency require indefinite anticoagulation due to high recurrence rates, and that studying first-degree relatives, even asymptomatic ones, is essential for establishing thromboprophylaxis. A 2022 narrative review summarises that knowledge of hereditary hypercoagulability has improved greatly since antithrombin deficiency was first described in 1965, and that interactions between thrombophilia and other genetic and acquired risk factors are important determinants of VTE risk. A 2024 case report describes a 39-year-old hypertensive woman with superior mesenteric artery thrombosis and protein S deficiency (free protein S 15%), managed with streptokinase lysis and anticoagulation, who remained free of abdominal complaints at 24-month follow-up.
What is still missing is prospective data on the natural history of isolated histidine-rich glycoprotein deficiency or elevation, and on whether specific anticoagulation strategies reduce thrombotic events in these patients beyond what is known for other thrombophilias. No randomised trials have tested direct oral anticoagulants specifically in histidine-rich glycoprotein-related thrombophilia, and the rarity of the condition makes adequately powered studies difficult without multi-centre collaboration and dedicated funding. Patient stratification by concomitant thrombophilic defects and by quantitative thresholds of histidine-rich glycoprotein remains unaddressed.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Thrombosis and Haemostasis · 1992 · 114 citations
β2-Glycoprotein I Deficiency and the Risk of Thrombosis
Abstractbeta 2-glycoprotein I (beta 2-GP I) is a plasma protein with a high affinity for negatively charged surfaces. In vitro this protein shows a variety of anticoagulant properties (inhibition of contact activation and platelet dependent prothrombinase activity). Therefore we studied the possibility that a hereditary beta 2-GP I deficiency is a risk factor for (familial) thrombophilia. Plasma beta 2-GP I levels were measured in healthy volunteers and four different groups of patients with (familial) thrombophilia. In these 5 groups the prevalence of beta 2-GP I deficiency (i.e. beta 2-GP I antigen less than 77%) was found to be very similar (6.8-12.5%) and statistically not significantly different. This observation suggests that beta 2-GP I deficiency in itself is not a risk factor for thrombosis. One thrombophilic patient was found to be homozygous deficient of beta 2-GP I. The transmission of the defect in his family followed autosomal inheritance. One of his brothers was also homozygous deficient and at the age of 35 years still free of thromboembolic complications. The possibility that beta 2-GP I deficiency could be an additional risk factor for the development of thrombophilia in families with protein C deficiency was evaluated in a panel of 70 unrelated patients with clinically dominant protein C deficiency. The prevalence of beta 2-GP I deficiency in this group of patients (12.8%) was very similar to that in other groups of normals and patients. Moreover, there was no difference in the frequency of beta 2-GP I deficiency in symptomatic and asymptomatic protein C deficient patients.
British Journal of Haematology · 1987 · 61 citations
Familial elevation of plasma histidine-rich glycoprotein in a family with thrombophilia
AbstractA patient with spontaneous venous thrombotic events, myocardial infarction and a positive family history of thrombosis was investigated for underlying disorders of haemostasis. Abnormally high levels of histidine-rich glycoprotein were found. No other abnormality known or suspected of increasing the risk for thrombosis was present. Elevated levels of histidine-rich glycoprotein appeared to be present in four other members of the family over two generations suggesting a hereditary disorder. Further study on the relation of elevated histidine-rich glycoprotein levels and thrombosis is indicated.
British Journal of Haematology · 1987 · 10 citations
Familial elevation of plasma histidine‐rich glycoprotein in a family with thrombophilia
AbstractSummary A patient with spontaneous venous thrombotic events, myocardial infarction and a positive family history of thrombosis was investigated for underlying disorders of haemostasis. Abnormally high levels of histidine‐rich glycoprotein were found. No other abnormality known or suspected of increasing the risk for thrombosis was present. Elevated levels of histidine‐rich glycoprotein appeared to be present in four other members of the family over two generations suggesting a hereditary disorder. Further study on the relation of elevated histidine‐rich glycoprotein levels and thrombosis is indicated.
Journal of Blood Medicine · 2023 · 10 citations · open access
Antithrombin Deficiency and Thrombosis: A Wide Clinical Scenario Reported in a Single Institution
AbstractCongenital antithrombin (AT) deficiency represents the form of thrombophilia with the highest thrombotic risk. It is characterized by a heterogeneous clinical presentation, depending mostly on the family history of thrombosis and type of genetic mutation. Inherited AT deficiency promotes idiopathic thrombosis at an early age (even in the pediatric population) and at atypical sites. Therefore, a positive family background necessitates ruling out this high-risk thrombophilia at a young age. Studying first-degree relatives, even if they are asymptomatic, is essential to establish thromboprophylaxis and a proper therapeutic approach in case of thrombosis. Patients with congenital AT deficiency require indefinite anticoagulation owing to the high thrombotic recurrence rate. Here, we present four unrelated cases reported in our institution who were diagnosed with hereditary AT deficiency, with a contrasting clinical evolution.
Seminars in Thrombosis and Hemostasis · 2022 · 9 citations
Evolving Knowledge on Primary and Secondary Prevention of Venous Thromboembolism in Carriers of Hereditary Thrombophilia: A Narrative Review
AbstractThe association between heritability of venous thromboembolism (VTE) and thrombophilia was first reported clinically in 1956, later followed by the first description of a congenital cause of hypercoagulability-antithrombin deficiency-in 1965. Since then, our knowledge of hereditary causes of hypercoagulability, which may predispose carriers to VTE has improved greatly. Novel genetic defects responsible for severe thrombophilia have been recently identified and we have learned that a wide range of interactions between thrombophilia and other genetic and acquired risk factors are important determinants of the overall individual risk of developing VTE. Furthermore, therapeutic strategies in thrombophilic patients have benefited significantly from the introduction of direct oral anticoagulants. The present review is an overview of the current knowledge on the mechanisms underlying inherited thrombophilia, with a particular focus on the latest achievements in anticoagulation protocols and prevention strategies for thrombosis in carriers of this prothrombotic condition.
International Journal of Surgery Case Reports · 2024 · 0 citations · open access
Acute mesenteric ischemia due to superior mesenteric artery thrombosis in a patient with protein S deficiency: A case report
AbstractINTRODUCTION: Protein S deficiency resulting in mesenteric vein thrombosis has been reported in previous studies however those causing SMA thrombosis has been rarely reported. Multidisciplinary approach involving general surgeon, a vascular surgeon, an interventional radiologist, and an intensivist are crucial for management of SMA thrombosis. CASE PRESENTATION: A 39-year-old non-smoker hypertensive female who was diagnosed with partially occlusive thrombus in the superior mesenteric artery via Contrast-enhanced computed tomography (CECT) re-presented after 5 days and CECT revealed a partially occlusive thrombus in the superior mesenteric artery and Protein S deficiency (free protein S:15 %). She was managed by lysis of thrombus with streptokinase by interventional radiology team. The patient is on anticoagulants and without abdominal complaints on follow-up at 24 months. DISCUSSION: Computed tomography angiography should be done immediately in any patient suspected of AMI since delay in diagnosis accounts for high mortality rates of 30-70 %. The surgical treatment of the condition is well established and consists of revascularization and/or resection of nonviable bowel. Endovascular techniques have emerged as an alternative for occlusion of the SMA. Patients with protein C and/or S deficiency treated for AMI require lifelong anticoagulant/antiplatelet therapy to prevent relapse. CONCLUSION: Hereditary thrombophilia should be suspected in young people with unusual thrombotic presentations. Earlier diagnosis and aggressive antithrombotic therapy in individuals with hypercoagulable states can improve outcomes. Treatment involving a multidisciplinary approach improves outcomes.
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.
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