RARE DISEASE
Congenital factor VII deficiency
Congenital factor VII deficiency
Congenital factor VII deficiency
Synonyms: Congenital proconvertin deficiency, Hypoproconvertinemia
Synonyms: Congenital proconvertin deficiency, Hypoproconvertinemia
Synonyms: Congenital proconvertin deficiency, Hypoproconvertinemia
Drug discovery
9
drugs
With orphan designations
Overview
Congenital Factor VII Deficiency is a rare autosomal recessive bleeding disorder caused by mutations in the F7 gene, leading to deficient or dysfunctional coagulation factor VII. Prevalence ranges from 1/300,000 to 1/500,000, with higher rates in consanguineous populations [1][2][16]. Clinical presentation varies widely, from asymptomatic cases to severe bleeding (e.g., intracranial, gastrointestinal, or joint hemorrhages) [1][6][9]. Diagnosis involves isolated prolonged prothrombin time (PT) and confirmation via FVII activity assays [1][2]. Treatment centers on recombinant activated FVII (rFVIIa), plasma-derived products, and fresh frozen plasma (FFP) [3][6][8].
Population
Prevalence: 1/300,000–500,000 globally; higher in regions with consanguinity [1][2][19].
Affects both sexes equally, though women often present earlier due to menorrhagia [6][9][16].
Severe cases typically diagnosed neonatally (e.g., CNS bleeds), while milder forms may remain undetected until adulthood [1][6][11].
Burden
Clinical heterogeneity: No consistent correlation between FVII levels and bleeding severity [1][9][16].
Severe complications: Life-threatening hemorrhage (e.g., intracranial), recurrent hemarthroses, and iron-deficiency anemia [1][4][6].
Psychosocial impact: Reduced quality of life, employment challenges, and activity restrictions (e.g., contact sports) [9][16].
Categories: rare genetic diseases, rare hematological diseases
Research Papers
475 drug discovery papers about Congenital factor VII deficiency, with 1 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
475 drug discovery papers about Congenital factor VII deficiency, with 1 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-06-15 | Perioperative management in a patient with congenital factor VII deficiency following mechanical valve replacement: a case report.
Congenital factor VII deficiency (CFVIID) is a rare hemorrhagic disorder which elevates perioperative bleeding risks. Mechanical prosthesis mandates lifelong anticoagulation, while international normalized ratio (INR) of CFVIID deviates significantly from the normal range which could not accurately reflect the real anticoagulation. Perioperative management for CFVIID patients undergoing mechanical valve replacement are highly challenging, with no clinical guidelines currently available. We reported a 59-year-old CFVIID patient undergoing mechanical valve replacement. Perioperative recombinant activated factor VII (rFVIIa) replacement secured hemostasis. After postoperative cerebral thrombosis, anticoagulation of warfarin was initiated and guided by factor Ⅱ/Ⅹ activity (30-45%) rather than INR. No bleeding or recurrent thrombosis was observed. Perioperative rFVIIa replacement guarantees hemostatic safety for cardiac surgery. Lifelong warfarin anticoagulation is essential for CFVIID patient with mechanical prosthesis. Monitoring factor Ⅱ/Ⅹ activity instead of INR can balance bleeding and thrombosis risks for such cases.
2026-03-22 | Managing heavy menstrual bleeding in adolescents with bleeding disorders: Outcomes from a pragmatic LMIC approach.
Heavy menstrual bleeding (HMB) a common manifestation of bleeding disorders in adolescents contributes to anemia, transfusions, and impaired quality-of-life (QOL). Evidence supporting practical management strategies in resource-limited settings remains limited. This observational study in adolescents with confirmed bleeding disorders with HMB at a tertiary hemophilia treatment centre evaluated menstrual blood loss and QOL after a standard regimen of progesterone, tranexamic acid and iron; blood products or clotting factor concentrates were reserved for refractory bleeding. Twenty adolescents were included (2020-2025); von Willebrand disease (n = 11), chronic immune thrombocytopenia (n = 4), congenital aplastic anemia (n = 3), afibrinogenemia (n = 1), and factor VII deficiency (n = 1). Median PBAC score at presentation was 300 (range 190-500). Eighteen patients (90%) had anemia and prior transfusion exposure. After therapy, median PBAC declined to 100 (range 60-150). Hemoglobin improved steadily and no patient required further red cell transfusion during a median follow-up of four years. Hemostatic products were required only in two patients while on this regimen. Quality-of-life scores improved across physical, emotional, and social domains. A low-cost regimen combining progesterone, antifibrinolytic therapy, and iron effectively controls HMB, corrects anemia, reduces transfusion and factor utilization, and improves QOL in adolescents with bleeding disorders in resource-constrained settings.
2026-02-01 | Vitamin K1 and K2 supplementation in VKCFD1 patients
Introduction Vitamin K dependent clotting factor deficiency type1 (VKCFD1) is a rare congenital disorder caused by mutations in the γ-glutamyl carboxylase ( GGCX ) gene. VKCFD1 patients are homozygous or compound heterozygous. GGCX is essential for the post-translational activation of all vitamin K–dependent proteins (VKDPs), including the coagulation factors II, VII, IX, and X, as well as proteins C, S and Z. In addition, GGCX is required for the activation of VKDPs unrelated to coagulation, such as matrix Gla protein (MGP) and osteocalcin (OC), whose impairment contributes to severe phenotypes, including midfacial hypoplasia and hearing loss. Treatment strategies for VKCFD1 have primarily focused on correcting the coagulation defects through the daily supplementation of phylloquinone (vitamin K₁). Here, we present a therapeutic protocol with supplementation of Vitamin K1 and MK-4, addressing both clotting- and non–clotting-related manifestations in 2 children with VKCFD1. Method Patient 1 is a 3-year-old girl compound heterozygous forc.944G>A (p.Trp315Ter) and c.1A>G, (p.Ala2_Met75del). At 31 weeks of gestation, midface hypoplasia, polyhydramnios and micromelia were noted. Soon after birth, she developed extensive subdural, subarachnoid, and epidural hemorrhages with impending herniation. She has spinal punctiform calcifications. Her atlas arch is hypoplastic without brain stem compression. She shows mild vertebral anomalies. She has hearing loss and relevant pulmonary artery stenosis. Patient 2 is a 4-year-old girl compound heterozygous for c.1616dup (p.His539GlnfsTer8); c.1790C>A (p.Ser597Tyr) and c.1822G>C (p.Glu608Gln). At 32 weeks of gestation, amniocentesis was performed because of facial dysplasia and polyhydramnios. She has a small nasal bridge, hypoplastic alae nasi, protruding forehead, shortned limbs, fingers, atlas arch with narrowing of the craniocervical junction without brainstem compression, mild vertebral anomalies, hearing loss and asymptomatic pulmonary artery stenosis. Plasma uncarboxylated OC (ucOC) was measured using the ELISA kit from Takara (#MK118). Plasma ucMGP levels were determined using the CE-marked chemiluminescent InaKtif MGP assay on the IDS-iSYS system (IDS, Boldon, UK). Results Supplementation with vitamin K₁ (K₁) (10 mg/day) improved activities of vitamin K–dependent (VKD) clotting factors. However, for the non-hematological VKDPs, markedly elevated pathological levels of ucOC and ucMGP were detected in plasma. Therefore, a stepwise increase in the concentration of the vitamin K₂ derivative menaquinone-4 (MK-4) was considered as an adjunct therapy. Following MK-4 supplementation, both patients exhibited improved carboxylation of the non-hepatic VKD proteins MGP and OC ([ Fig. 1 ]). Fig. 1 Patient data Conclusion Here, for the first time we present a treatment protocol for VKCFD1 patients that includes supplementation of Vitamin K1 and additionally MK-4 that improves both, the activity of VKD clotting factors and the γ-carboxylation of non-hematological VKDPs. Publication History Article published online: 17 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
2026-01-22 | Congenital factor VII deficiency as a cause of postpartum hemorrhage: A case report.
Obstetric hemorrhage is one of the leading causes of maternal morbidity and mortality worldwide. However, coagulation disorders as an etiology are rare, with a prevalence of less than 1 %. This report concerns the case of a 24-year-old patient with no previous history of bleeding who presented with postpartum hemorrhage at 38.6 weeks of pregnancy after a normal vaginal delivery. The hemorrhage was refractory to the use of uterotonics and compression maneuvers. In the absence of uterine atony, retained products of conception, or obvious trauma, the possibility of an underlying coagulopathy was considered. Initial studies showed an isolated prolongation of prothrombin time, with activated partial thromboplastin time within normal parameters. A correction test with a normal plasma pool was performed, which showed complete correction of prothrombin time. Specific factor quantification confirmed a severe and isolated factor VII deficiency.
2026-01-19 | Factor VII deficiency is more prevalent than previously reported.
The prevalence of factor (F)VII deficiency is estimated at approximately 1 of 500,000 individuals. However, low FVII activity (FVII:C) is frequently observed in a population of <500,000 in the region of Östergötland, Sweden. To estimate the prevalence and bleeding tendency of adult FVII-deficient patients in Östergötland, Sweden. In this retrospective cross-sectional study, the laboratory information system was used to identify adult patients with at least one FVII:C result ≤ 0.50 kilo International Units per Liter (kIU/L) between January 1, 2017, and December 31, 2022. The most likely cause was established, and in patients with a FVII deficiency, as defined by the Nordic Hemophilia Council (FVII:C < 0.35 kIU/L) or low FVII level (0.35-0.50 kIU/L), the bleeding tendency was evaluated. FVII:C ≤ 0.50 kIU/L was identified in 97 patients residing in Östergötland. Of these, 21 had FVII deficiency, and 39 had low FVII level, corresponding to a prevalence of at least 1 of 17,800 and 1 of 9600 in the adult population in Östergötland, respectively. Patients with FVII deficiency differed significantly from patients with low FVII level in bleeding symptoms (P = .01). Of the FVII-deficient patients, 38% were asymptomatic, while 19% and 24% had experienced minor and major spontaneous bleedings, respectively. The prevalence of FVII deficiency was estimated to be at least 1 of 17,800 adults, which is 28 times higher than the internationally claimed prevalence. Spontaneous bleeding occurred in 43% of these individuals.
2026-06-15 | Perioperative management in a patient with congenital factor VII deficiency following mechanical valve replacement: a case report.
Congenital factor VII deficiency (CFVIID) is a rare hemorrhagic disorder which elevates perioperative bleeding risks. Mechanical prosthesis mandates lifelong anticoagulation, while international normalized ratio (INR) of CFVIID deviates significantly from the normal range which could not accurately reflect the real anticoagulation. Perioperative management for CFVIID patients undergoing mechanical valve replacement are highly challenging, with no clinical guidelines currently available. We reported a 59-year-old CFVIID patient undergoing mechanical valve replacement. Perioperative recombinant activated factor VII (rFVIIa) replacement secured hemostasis. After postoperative cerebral thrombosis, anticoagulation of warfarin was initiated and guided by factor Ⅱ/Ⅹ activity (30-45%) rather than INR. No bleeding or recurrent thrombosis was observed. Perioperative rFVIIa replacement guarantees hemostatic safety for cardiac surgery. Lifelong warfarin anticoagulation is essential for CFVIID patient with mechanical prosthesis. Monitoring factor Ⅱ/Ⅹ activity instead of INR can balance bleeding and thrombosis risks for such cases.
2026-03-22 | Managing heavy menstrual bleeding in adolescents with bleeding disorders: Outcomes from a pragmatic LMIC approach.
Heavy menstrual bleeding (HMB) a common manifestation of bleeding disorders in adolescents contributes to anemia, transfusions, and impaired quality-of-life (QOL). Evidence supporting practical management strategies in resource-limited settings remains limited. This observational study in adolescents with confirmed bleeding disorders with HMB at a tertiary hemophilia treatment centre evaluated menstrual blood loss and QOL after a standard regimen of progesterone, tranexamic acid and iron; blood products or clotting factor concentrates were reserved for refractory bleeding. Twenty adolescents were included (2020-2025); von Willebrand disease (n = 11), chronic immune thrombocytopenia (n = 4), congenital aplastic anemia (n = 3), afibrinogenemia (n = 1), and factor VII deficiency (n = 1). Median PBAC score at presentation was 300 (range 190-500). Eighteen patients (90%) had anemia and prior transfusion exposure. After therapy, median PBAC declined to 100 (range 60-150). Hemoglobin improved steadily and no patient required further red cell transfusion during a median follow-up of four years. Hemostatic products were required only in two patients while on this regimen. Quality-of-life scores improved across physical, emotional, and social domains. A low-cost regimen combining progesterone, antifibrinolytic therapy, and iron effectively controls HMB, corrects anemia, reduces transfusion and factor utilization, and improves QOL in adolescents with bleeding disorders in resource-constrained settings.
2026-02-01 | Vitamin K1 and K2 supplementation in VKCFD1 patients
Introduction Vitamin K dependent clotting factor deficiency type1 (VKCFD1) is a rare congenital disorder caused by mutations in the γ-glutamyl carboxylase ( GGCX ) gene. VKCFD1 patients are homozygous or compound heterozygous. GGCX is essential for the post-translational activation of all vitamin K–dependent proteins (VKDPs), including the coagulation factors II, VII, IX, and X, as well as proteins C, S and Z. In addition, GGCX is required for the activation of VKDPs unrelated to coagulation, such as matrix Gla protein (MGP) and osteocalcin (OC), whose impairment contributes to severe phenotypes, including midfacial hypoplasia and hearing loss. Treatment strategies for VKCFD1 have primarily focused on correcting the coagulation defects through the daily supplementation of phylloquinone (vitamin K₁). Here, we present a therapeutic protocol with supplementation of Vitamin K1 and MK-4, addressing both clotting- and non–clotting-related manifestations in 2 children with VKCFD1. Method Patient 1 is a 3-year-old girl compound heterozygous forc.944G>A (p.Trp315Ter) and c.1A>G, (p.Ala2_Met75del). At 31 weeks of gestation, midface hypoplasia, polyhydramnios and micromelia were noted. Soon after birth, she developed extensive subdural, subarachnoid, and epidural hemorrhages with impending herniation. She has spinal punctiform calcifications. Her atlas arch is hypoplastic without brain stem compression. She shows mild vertebral anomalies. She has hearing loss and relevant pulmonary artery stenosis. Patient 2 is a 4-year-old girl compound heterozygous for c.1616dup (p.His539GlnfsTer8); c.1790C>A (p.Ser597Tyr) and c.1822G>C (p.Glu608Gln). At 32 weeks of gestation, amniocentesis was performed because of facial dysplasia and polyhydramnios. She has a small nasal bridge, hypoplastic alae nasi, protruding forehead, shortned limbs, fingers, atlas arch with narrowing of the craniocervical junction without brainstem compression, mild vertebral anomalies, hearing loss and asymptomatic pulmonary artery stenosis. Plasma uncarboxylated OC (ucOC) was measured using the ELISA kit from Takara (#MK118). Plasma ucMGP levels were determined using the CE-marked chemiluminescent InaKtif MGP assay on the IDS-iSYS system (IDS, Boldon, UK). Results Supplementation with vitamin K₁ (K₁) (10 mg/day) improved activities of vitamin K–dependent (VKD) clotting factors. However, for the non-hematological VKDPs, markedly elevated pathological levels of ucOC and ucMGP were detected in plasma. Therefore, a stepwise increase in the concentration of the vitamin K₂ derivative menaquinone-4 (MK-4) was considered as an adjunct therapy. Following MK-4 supplementation, both patients exhibited improved carboxylation of the non-hepatic VKD proteins MGP and OC ([ Fig. 1 ]). Fig. 1 Patient data Conclusion Here, for the first time we present a treatment protocol for VKCFD1 patients that includes supplementation of Vitamin K1 and additionally MK-4 that improves both, the activity of VKD clotting factors and the γ-carboxylation of non-hematological VKDPs. Publication History Article published online: 17 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
2026-01-22 | Congenital factor VII deficiency as a cause of postpartum hemorrhage: A case report.
Obstetric hemorrhage is one of the leading causes of maternal morbidity and mortality worldwide. However, coagulation disorders as an etiology are rare, with a prevalence of less than 1 %. This report concerns the case of a 24-year-old patient with no previous history of bleeding who presented with postpartum hemorrhage at 38.6 weeks of pregnancy after a normal vaginal delivery. The hemorrhage was refractory to the use of uterotonics and compression maneuvers. In the absence of uterine atony, retained products of conception, or obvious trauma, the possibility of an underlying coagulopathy was considered. Initial studies showed an isolated prolongation of prothrombin time, with activated partial thromboplastin time within normal parameters. A correction test with a normal plasma pool was performed, which showed complete correction of prothrombin time. Specific factor quantification confirmed a severe and isolated factor VII deficiency.
2026-01-19 | Factor VII deficiency is more prevalent than previously reported.
The prevalence of factor (F)VII deficiency is estimated at approximately 1 of 500,000 individuals. However, low FVII activity (FVII:C) is frequently observed in a population of <500,000 in the region of Östergötland, Sweden. To estimate the prevalence and bleeding tendency of adult FVII-deficient patients in Östergötland, Sweden. In this retrospective cross-sectional study, the laboratory information system was used to identify adult patients with at least one FVII:C result ≤ 0.50 kilo International Units per Liter (kIU/L) between January 1, 2017, and December 31, 2022. The most likely cause was established, and in patients with a FVII deficiency, as defined by the Nordic Hemophilia Council (FVII:C < 0.35 kIU/L) or low FVII level (0.35-0.50 kIU/L), the bleeding tendency was evaluated. FVII:C ≤ 0.50 kIU/L was identified in 97 patients residing in Östergötland. Of these, 21 had FVII deficiency, and 39 had low FVII level, corresponding to a prevalence of at least 1 of 17,800 and 1 of 9600 in the adult population in Östergötland, respectively. Patients with FVII deficiency differed significantly from patients with low FVII level in bleeding symptoms (P = .01). Of the FVII-deficient patients, 38% were asymptomatic, while 19% and 24% had experienced minor and major spontaneous bleedings, respectively. The prevalence of FVII deficiency was estimated to be at least 1 of 17,800 adults, which is 28 times higher than the internationally claimed prevalence. Spontaneous bleeding occurred in 43% of these individuals.
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Drug Discovery Landscape
9 orphan drug designations for Congenital factor VII deficiency, including 2 approved therapies.
9 orphan drug designations for Congenital factor VII deficiency, including 2 approved therapies.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Humanised IgG4 monoclonal antibody against activated protein C | antibodies | EMA | 2026-06-19 | — | Parexel International (IRL) Limited |
Humanised IgG4 monoclonal antibody against activated protein C | antibodies | EMA | 2026-06-19 | — | Parexel International (IRL) Limited |
Marzeptacog alfa (activated) | proteins | FDA | 2021-09-27 | — | USWM Development Co., LLC |
Adeno-associated viral vector serotype 8 containing the human factor VII gene | gene therapies | EMA | 2015-01-15 | — | UCL Research Limited |
Recombinant factor VIIa modified with three terminal repeats derived from the ß chain of human chorionic gonadotropin | proteins | EMA | 2014-08-22 | — | Eirgen Pharma Limited |
Recombinant fusion protein linking coagulation factor VIIa with albumin | proteins | EMA | 2013-10-07 | — | CSL Behring GmbH |
recombinant fusion protein linking coagulation factor VIIa with albumin (rVIIa-FP) | proteins | FDA | 2013-05-06 | — | CSL Behring |
Coagulation factor VIIa (recombinant) [NovoSeven] | proteins | FDA | 2004-09-10 | 2005-07-11 | Novo Nordisk, Inc. |
Coagulation factor VIIa (recombinant) [NovoSeven] | proteins | FDA | 2004-09-10 | 2005-07-11 | Novo Nordisk, Inc. |
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