RARE DISEASE
Hereditary thrombophilia due to congenital antithrombin deficiency
Hereditary thrombophilia due to congenital antithrombin deficiency
Hereditary thrombophilia due to congenital antithrombin deficiency
Synonyms: Hereditary thrombophilia due to congenital antithrombin 3 deficiency
Synonyms: Hereditary thrombophilia due to congenital antithrombin 3 deficiency
Synonyms: Hereditary thrombophilia due to congenital antithrombin 3 deficiency
Drug discovery
6
drugs
With orphan designations
Overview
Hereditary thrombophilia due to congenital antithrombin deficiency is a rare, autosomal dominant disorder caused by SERPINC1 gene mutations, leading to impaired inhibition of thrombin and factor Xa. It confers the highest thrombotic risk among inherited thrombophilias, with venous thromboembolism (VTE) often occurring before age 40 and involving atypical sites (e.g., cerebral, mesenteric veins). Lifelong anticoagulation is frequently required due to high recurrence rates [1][3][4].
Therapies
Acute VTE: Heparin/LMWH combined with antithrombin replacement (plasma-derived concentrates) to overcome heparin resistance [3][7][9].
Long-term prevention: Indefinite anticoagulation (warfarin/DOACs) for recurrent VTE; thromboprophylaxis during high-risk periods (surgery, pregnancy) [3][4][7].
Genetic counseling and family screening recommended [1][13].
Categories: rare bone diseases, rare genetic diseases, rare hematological diseases, rare systemic and rheumatological diseases
Research Papers
28 drug discovery papers about Hereditary thrombophilia due to congenital antithrombin deficiency, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
28 drug discovery papers about Hereditary thrombophilia due to congenital antithrombin deficiency, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-07-28 | Risk and management of congenital thrombophilia in transgender individuals undergoing gender-affirming hormone therapy.
Gender-affirming hormone therapy (GAHT), particularly estrogen-based regimens, is associated with an increased risk of venous thromboembolic events (VTE), which may be exacerbated in individuals with hereditary thrombophilia. Despite this risk, the prevalence and clinical implications of hereditary thrombophilia in transgender individuals remain underexplored. We screened 114 transgender individuals (54 AMAB, 60 AFAB) at the University Hospital of Padua (Italy) for hereditary thrombophilia, including factor V Leiden (FVL), prothrombin G20210A (PT20210A), antithrombin (AT), protein C (PC), and protein S (PS) deficiencies, as well as antiphospholipid antibodies. Hereditary thrombophilia was identified in 9.6% of participants, including two cases of severe thrombophilia. No participants tested positive for antiphospholipid antibodies. Individuals with thrombophilia had a higher prevalence of personal and family history of VTE. Three thrombotic events were recorded prior to GAHT: one transgender woman (heterozygous FVL) with unprovoked lower limb VTE, one transgender man (PC deficiency) with neonatal cerebral ischemia, and one transgender man (heterozygous FVL) with subclavian VTE during chemotherapy. A multidisciplinary approach involving coagulation specialists and endocrinologists was implemented to optimize risk reduction strategies, including tailored GAHT regimens and anticoagulation when necessary. No VTE occurred during a 15-month follow up. These findings highlight the importance of thrombophilia screening to enable individualized care and enhance the safety of GAHT protocols.
2025-12-09 | Refractory perirenal effusion in a pediatric patient with antithrombin III deficiency and KILT syndrome: a case report
Congenital antithrombin III (ATIII) deficiency is a rare hereditary thrombophilia that is caused by SERPINC1 variants. Reports on KILT syndrome, which is defined by the triad of kidney anomaly, inferior vena cava (IVC) anomaly, and leg thrombosis, have been sporadic. We described the case of a 10-year-old boy with a solitary left kidney and IVC agenesis who carried compound heterozygous variants in SERPINC1. He presented with flank pain due to renal infarction and subsequently developed massive perirenal effusion. Despite anticoagulation and prolonged percutaneous drainage, the effusion persisted and was confirmed to be of lymphatic origin. Imaging revealed abnormal lymphatic flow related to venous hypertension in the renal hilum. Complete resolution of the effusion was achieved following four sessions of ethanol sclerotherapy. To the best of our knowledge, this was the first reported case of ATIII deficiency complicated by refractory perirenal lymphatic leakage. The case suggested a potential link between thrombosis and secondary lymphatic dysfunction and demonstrated the effectiveness of repeated sclerotherapy for refractory perirenal effusion. Early recognition of hypercoagulable states in children with IVC and renal anomalies is crucial for the prevention of thromboembolic events.
2023-12-13 | Multiple venous thromboembolisms in a pregnant patient carrying a novel mutation in SERPINC1 (p.M313T) that causes a transient antithrombin deficiency: a case report
Abstract Background Congenital antithrombin deficiency is an autosomal dominant disease that results in deep venous thrombosis and pulmonary embolism, which is mainly caused by mutations in the antithrombin gene ( SERPINC1 ). Since SERPINC1 is highly susceptible to alterations, severe structural and functional changes that promote thrombosis may occur. Clinical presentations vary from different alterations. We report a pregnant case with novel mutation in SERPINC1 presenting transient antithrombin deficiency and multiple venous thromboembolisms. Case presentation We report a case of a 36-year-old pregnant patient who was diagnosed with congenital antithrombin deficiency for carrying a novel heterozygous mutation, NM_000488:exon5:c.T9 38 C:p. M313T in SERPINC1 presenting transient antithrombin deficiency and multiple venous thromboembolisms. Thrombolytic with alteplase and anticoagulant therapies with low-molecular-weight heparin and warfarin were administrated. After confirming the genetic analysis and the termination of pregnancy, rivaroxaban was administrated, and the thrombosis reduced. Conclusions Our study enriched the mutation database of SERPINC1 gene, provided some new theoretical basis for gene diagnosis and genetic counseling of patients with transient antithrombin deficiency. While it still needs for subsequent exploration of molecular pathogenesis.
2022-12-28 | Favourable outcome of multisystem venous thrombosis associated with novel SERPINC1 mutation after treated with dabigatran: a case report with 7-year follow-up
Mutations in SERPINC1 lead to deficiency in antithrombin (AT) which is an endogenous anticoagulant of normal hemostasis and could result in venous thromboembolism (VTE).A 61-year-old male patient with recurrent thrombosis returned to the hospital with multiple cerebral thrombosis after voluntary cessation of dabigatran therapy. Laboratory tests revealed a type I AT deficiency in this patient and further whole exome sequencing (WES) identified a novel heterozygous frameshift duplication (c.233_236dup, p.Val80Alafs*26) in SERPINC1 gene. Long-term dabigatran treatment was given and no recurrence or side effects were found within the followed 5 years.A multisystem VTE patient with a novel SERPINC1 mutation (c.233_236dup, p.Val80Alafs*26) reached a favourable outcome after dabigatran treatment.
2022-11-21 | Evolving Knowledge on Primary and Secondary Prevention of Venous Thromboembolism in Carriers of Hereditary Thrombophilia: A Narrative Review.
The 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.
small molecules
2026-07-28 | Risk and management of congenital thrombophilia in transgender individuals undergoing gender-affirming hormone therapy.
Gender-affirming hormone therapy (GAHT), particularly estrogen-based regimens, is associated with an increased risk of venous thromboembolic events (VTE), which may be exacerbated in individuals with hereditary thrombophilia. Despite this risk, the prevalence and clinical implications of hereditary thrombophilia in transgender individuals remain underexplored. We screened 114 transgender individuals (54 AMAB, 60 AFAB) at the University Hospital of Padua (Italy) for hereditary thrombophilia, including factor V Leiden (FVL), prothrombin G20210A (PT20210A), antithrombin (AT), protein C (PC), and protein S (PS) deficiencies, as well as antiphospholipid antibodies. Hereditary thrombophilia was identified in 9.6% of participants, including two cases of severe thrombophilia. No participants tested positive for antiphospholipid antibodies. Individuals with thrombophilia had a higher prevalence of personal and family history of VTE. Three thrombotic events were recorded prior to GAHT: one transgender woman (heterozygous FVL) with unprovoked lower limb VTE, one transgender man (PC deficiency) with neonatal cerebral ischemia, and one transgender man (heterozygous FVL) with subclavian VTE during chemotherapy. A multidisciplinary approach involving coagulation specialists and endocrinologists was implemented to optimize risk reduction strategies, including tailored GAHT regimens and anticoagulation when necessary. No VTE occurred during a 15-month follow up. These findings highlight the importance of thrombophilia screening to enable individualized care and enhance the safety of GAHT protocols.
2025-12-09 | Refractory perirenal effusion in a pediatric patient with antithrombin III deficiency and KILT syndrome: a case report
Congenital antithrombin III (ATIII) deficiency is a rare hereditary thrombophilia that is caused by SERPINC1 variants. Reports on KILT syndrome, which is defined by the triad of kidney anomaly, inferior vena cava (IVC) anomaly, and leg thrombosis, have been sporadic. We described the case of a 10-year-old boy with a solitary left kidney and IVC agenesis who carried compound heterozygous variants in SERPINC1. He presented with flank pain due to renal infarction and subsequently developed massive perirenal effusion. Despite anticoagulation and prolonged percutaneous drainage, the effusion persisted and was confirmed to be of lymphatic origin. Imaging revealed abnormal lymphatic flow related to venous hypertension in the renal hilum. Complete resolution of the effusion was achieved following four sessions of ethanol sclerotherapy. To the best of our knowledge, this was the first reported case of ATIII deficiency complicated by refractory perirenal lymphatic leakage. The case suggested a potential link between thrombosis and secondary lymphatic dysfunction and demonstrated the effectiveness of repeated sclerotherapy for refractory perirenal effusion. Early recognition of hypercoagulable states in children with IVC and renal anomalies is crucial for the prevention of thromboembolic events.
2023-12-13 | Multiple venous thromboembolisms in a pregnant patient carrying a novel mutation in SERPINC1 (p.M313T) that causes a transient antithrombin deficiency: a case report
Abstract Background Congenital antithrombin deficiency is an autosomal dominant disease that results in deep venous thrombosis and pulmonary embolism, which is mainly caused by mutations in the antithrombin gene ( SERPINC1 ). Since SERPINC1 is highly susceptible to alterations, severe structural and functional changes that promote thrombosis may occur. Clinical presentations vary from different alterations. We report a pregnant case with novel mutation in SERPINC1 presenting transient antithrombin deficiency and multiple venous thromboembolisms. Case presentation We report a case of a 36-year-old pregnant patient who was diagnosed with congenital antithrombin deficiency for carrying a novel heterozygous mutation, NM_000488:exon5:c.T9 38 C:p. M313T in SERPINC1 presenting transient antithrombin deficiency and multiple venous thromboembolisms. Thrombolytic with alteplase and anticoagulant therapies with low-molecular-weight heparin and warfarin were administrated. After confirming the genetic analysis and the termination of pregnancy, rivaroxaban was administrated, and the thrombosis reduced. Conclusions Our study enriched the mutation database of SERPINC1 gene, provided some new theoretical basis for gene diagnosis and genetic counseling of patients with transient antithrombin deficiency. While it still needs for subsequent exploration of molecular pathogenesis.
2022-12-28 | Favourable outcome of multisystem venous thrombosis associated with novel SERPINC1 mutation after treated with dabigatran: a case report with 7-year follow-up
Mutations in SERPINC1 lead to deficiency in antithrombin (AT) which is an endogenous anticoagulant of normal hemostasis and could result in venous thromboembolism (VTE).A 61-year-old male patient with recurrent thrombosis returned to the hospital with multiple cerebral thrombosis after voluntary cessation of dabigatran therapy. Laboratory tests revealed a type I AT deficiency in this patient and further whole exome sequencing (WES) identified a novel heterozygous frameshift duplication (c.233_236dup, p.Val80Alafs*26) in SERPINC1 gene. Long-term dabigatran treatment was given and no recurrence or side effects were found within the followed 5 years.A multisystem VTE patient with a novel SERPINC1 mutation (c.233_236dup, p.Val80Alafs*26) reached a favourable outcome after dabigatran treatment.
2022-11-21 | Evolving Knowledge on Primary and Secondary Prevention of Venous Thromboembolism in Carriers of Hereditary Thrombophilia: A Narrative Review.
The 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.
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Drug Discovery Landscape
6 orphan drug designations for Hereditary thrombophilia due to congenital antithrombin deficiency, including 3 approved therapies.
6 orphan drug designations for Hereditary thrombophilia due to congenital antithrombin deficiency, including 3 approved therapies.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
recombinant human antithrombin [ATryn] | proteins | FDA | 2007-12-07 | 2009-02-06 | GTC Biotherapeutics, Inc. |
Recombinant human antithrombin III | proteins | FDA | 2000-04-06 | — | AT III LLC |
Antithrombin III human | proteins | FDA | 1986-01-02 | — | American National Red Cross |
Antithrombin III (human) concentrate IV | proteins | FDA | 1985-07-02 | — | CSL Behring |
Antithrombin III (human) [ATnativ] | proteins | FDA | 1985-02-08 | 1989-12-13 | Pharmacia & Upjohn AB |
Antithrombin III (human) [Thrombate III] | proteins | FDA | 1984-11-26 | 1991-12-30 | Bayer Corporation |
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