RARE DISEASE
Congenital factor X deficiency
Congenital factor X deficiency
Congenital factor X deficiency
Synonyms: Congenital Stuart factor deficiency, Stuart-Prower factor deficiency
Synonyms: Congenital Stuart factor deficiency, Stuart-Prower factor deficiency
Synonyms: Congenital Stuart factor deficiency, Stuart-Prower factor deficiency
Drug discovery
2
drugs
With orphan designations
Overview
Congenital factor X deficiency is a rare autosomal recessive bleeding disorder caused by mutations in the F10 gene, leading to reduced factor X (FX) activity/antigen. Severity correlates with FX levels (<1 IU/dL: severe; 1-40 IU/dL: moderate; >40-65 IU/dL: mild). Clinical manifestations range from mucosal bleeding, hemarthrosis, and menorrhagia to life-threatening intracranial or gastrointestinal hemorrhages. Diagnosis involves prolonged PT/aPTT/RVVT and FX assays. Management relies on replacement therapy, with plasma-derived FX concentrate (e.g., Coagadex®) as first-line when available [1][3][6][8].
Burden
Clinical: High risk of life-threatening bleeds (e.g., intracranial, postpartum); 75% of patients experience >12 bleeds/year without prophylaxis [4][9][12].
Quality of Life: Reduced well-being due to recurrent bleeds, treatment complexity, and diagnostic delays (50% report difficult diagnosis pathways) [4][13][14].
Caregiver Impact: Significant emotional and logistical burden, though some report positive coping resilience [4][14].
Therapies
Replacement: Plasma-derived FX concentrate (preferred), prothrombin complex concentrates (PCCs), or fresh frozen plasma (FFP) [3][8][11].
Prophylaxis: Recommended for severe cases to prevent bleeding (e.g., Coagadex®) [3][13].
Adjuncts: Antifibrinolytics (tranexamic acid) for mucosal bleeding; hormonal therapy for menorrhagia [6][11].
Categories: rare genetic diseases, rare hematological diseases
Research Papers
131 drug discovery papers about Congenital factor X deficiency, with 7 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
131 drug discovery papers about Congenital factor X deficiency, with 7 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-06-08 | Plain language summary: What have research studies shown about plasma-derived human factor X concentrate treatment for people living with hereditary factor X deficiency?
What are these studies about? Researchers looked at the latest research studies about plasma-derived human factor X concentrate (pdFX for short) for people living with hereditary factor X deficiency (HFXD for short). These people's health and daily lives were impacted in different ways by HFXD, and their condition was classified as mild, moderate, or severe. The researchers assessed information from 5 clinical trials and 1 case series that described the bleeding symptoms and treatment that a group of people living with HFXD had. What were the results? Researchers found that pdFX has been successfully used in adults and children with HFXD to treat bleeds when they happen, to prevent bleeds, and to manage bleeding around having surgery. Researchers found that people living with HFXD had minimal side effects when they received pdFX. What do the results mean? Research studies to date have shown that pdFX is safe and effective as a treatment for people living with mild, moderate, or severe HFXD. This information will help healthcare experts to develop recommendations based on research results about pdFX treatment for people living with HFXD. What is the purpose of this plain language summary? The purpose of this plain language summary is to help you to understand the findings from recent research.
2026-05-24 | Molecular Modeling of Protein-Peptide Complexes Mimicking Factor Xa-Prothrombin Using AlphaFold-Multimer and Molecular Dynamics Simulations for Functional Prediction.
Accurately predicting how point mutations influence protease activity is a major challenge in protein engineering and in the study of coagulation disorders. Factor Xa (FXa) catalyzes the proteolytic activation of prothrombin, a critical step in thrombin generation, yet the molecular details of direct enzyme-substrate recognition and the impact of pathogenic variants remain incompletely defined. Here, we combined AlphaFold-Multimer modeling with explicit-solvent molecular dynamics (MD) simulations to investigate simplified FXa-substrate interactions using prothrombin-derived peptides encompassing the Arg271 and Arg320 cleavage sites in the absence of the full prothrombinase complex. AlphaFold predictions identified catalytically competent peptide orientations, while subsequent MD simulations and free energy analyses identified key contributions of the P1 and P4 cleavage site residues to FXa binding. Distinct stability and affinity differences between the two cleavage sites were highlighted. Active site variants associated with factor X deficiency demonstrated variant-specific disruptions in peptide engagement, implicating key residues within the FXa active site as critical determinants of catalytic activity. Experimental validation with recombinant FXa variants was consistent with the computational predictions, indicating comparable inhibition by the prothrombin peptides. Together, these findings establish an integrative computational-experimental framework for probing local protease-substrate recognition, rationalizing the effects of disease-causing mutations, and guiding the design of therapeutic protease variants.
2026-03-16 | Surgical management of pseudotumor secondary to Factor X deficiency: a case report.
Pseudotumor is a rare but serious complication of bleeding disorders. Its occurrence in Factor X (FX) deficiency is exceptionally uncommon. This report highlights a rare case of FX deficiency presenting as a large pseudotumor managed successfully by surgical excision. A 31-year-old man presented with a painful, progressively enlarging swelling over the left flank. Imaging revealed a large retroperitoneal mass with erosion of the left iliac bone. Coagulation studies showed prolonged prothrombin time and reduced FX activity, confirming FX deficiency. He was treated perioperatively with prothrombin complex concentrate (PCC) and fresh frozen plasma (FFP), followed by open surgical evacuation of an organized hematoma. Postoperative recovery was uneventful, with no recurrence at 2-month follow-up. Pseudotumor secondary to FX deficiency is extremely rare and can mimic soft tissue or bone malignancy. Early imaging and biopsy are essential for diagnosis. Definitive management involves factor replacement and surgical excision in large or symptomatic cases. In centers where FX concentrate is unavailable, PCC and FFP provide effective hemostatic coverage. This case underscores the importance of a multidisciplinary approach and resource-adapted management, which can achieve favorable outcomes even in low-resource settings. Surgical excision with adequate perioperative PCC/FFP support remains a safe and effective strategy for large pseudotumors secondary to FX deficiency.
2026-03-12 | Severe Congenital Factor X Deficiency in an Indian Child With a Concomitant Novel ITGA2 Variant
The authors declare no conflicts of interest. Supporting data is available with the corresponding author and will be made available upon reasonable request
2026-03-06 | Inherited Bleeding Disorders in Pregnancy: Obstetric Management and Outcomes From a Tertiary Care Centre
Some women have inherited conditions that affect how their blood clots, called hereditary coagulation factor deficiencies. During pregnancy and childbirth, these conditions may increase the risk of bleeding for both mothers and babies. We reviewed the medical records of 17 pregnant women with different types of inherited clotting factor deficiencies who gave birth at a large tertiary care hospital between 2015 and 2025. The women had conditions such as von Willebrand disease and deficiencies of Factors VII, X, XI and XIII. We found that pregnancy and delivery outcomes were very different from one woman to another. Some women with very low clotting factor levels experienced no bleeding problems, while others had significant bleeding despite having near-normal levels. Careful planning and teamwork between specialists-including obstetricians, haematologists and anaesthesiologists-were essential to ensure safe deliveries. Treatments such as factor replacement, Haemate-P and fresh frozen plasma were used when necessary. Our study highlights the importance of individualized care for pregnant women with rare bleeding disorders. Early involvement of a multidisciplinary team and close monitoring before, during and after childbirth can help prevent complications and improve outcomes for both mothers and babies.
2026-06-08 | Plain language summary: What have research studies shown about plasma-derived human factor X concentrate treatment for people living with hereditary factor X deficiency?
What are these studies about? Researchers looked at the latest research studies about plasma-derived human factor X concentrate (pdFX for short) for people living with hereditary factor X deficiency (HFXD for short). These people's health and daily lives were impacted in different ways by HFXD, and their condition was classified as mild, moderate, or severe. The researchers assessed information from 5 clinical trials and 1 case series that described the bleeding symptoms and treatment that a group of people living with HFXD had. What were the results? Researchers found that pdFX has been successfully used in adults and children with HFXD to treat bleeds when they happen, to prevent bleeds, and to manage bleeding around having surgery. Researchers found that people living with HFXD had minimal side effects when they received pdFX. What do the results mean? Research studies to date have shown that pdFX is safe and effective as a treatment for people living with mild, moderate, or severe HFXD. This information will help healthcare experts to develop recommendations based on research results about pdFX treatment for people living with HFXD. What is the purpose of this plain language summary? The purpose of this plain language summary is to help you to understand the findings from recent research.
2026-05-24 | Molecular Modeling of Protein-Peptide Complexes Mimicking Factor Xa-Prothrombin Using AlphaFold-Multimer and Molecular Dynamics Simulations for Functional Prediction.
Accurately predicting how point mutations influence protease activity is a major challenge in protein engineering and in the study of coagulation disorders. Factor Xa (FXa) catalyzes the proteolytic activation of prothrombin, a critical step in thrombin generation, yet the molecular details of direct enzyme-substrate recognition and the impact of pathogenic variants remain incompletely defined. Here, we combined AlphaFold-Multimer modeling with explicit-solvent molecular dynamics (MD) simulations to investigate simplified FXa-substrate interactions using prothrombin-derived peptides encompassing the Arg271 and Arg320 cleavage sites in the absence of the full prothrombinase complex. AlphaFold predictions identified catalytically competent peptide orientations, while subsequent MD simulations and free energy analyses identified key contributions of the P1 and P4 cleavage site residues to FXa binding. Distinct stability and affinity differences between the two cleavage sites were highlighted. Active site variants associated with factor X deficiency demonstrated variant-specific disruptions in peptide engagement, implicating key residues within the FXa active site as critical determinants of catalytic activity. Experimental validation with recombinant FXa variants was consistent with the computational predictions, indicating comparable inhibition by the prothrombin peptides. Together, these findings establish an integrative computational-experimental framework for probing local protease-substrate recognition, rationalizing the effects of disease-causing mutations, and guiding the design of therapeutic protease variants.
2026-03-16 | Surgical management of pseudotumor secondary to Factor X deficiency: a case report.
Pseudotumor is a rare but serious complication of bleeding disorders. Its occurrence in Factor X (FX) deficiency is exceptionally uncommon. This report highlights a rare case of FX deficiency presenting as a large pseudotumor managed successfully by surgical excision. A 31-year-old man presented with a painful, progressively enlarging swelling over the left flank. Imaging revealed a large retroperitoneal mass with erosion of the left iliac bone. Coagulation studies showed prolonged prothrombin time and reduced FX activity, confirming FX deficiency. He was treated perioperatively with prothrombin complex concentrate (PCC) and fresh frozen plasma (FFP), followed by open surgical evacuation of an organized hematoma. Postoperative recovery was uneventful, with no recurrence at 2-month follow-up. Pseudotumor secondary to FX deficiency is extremely rare and can mimic soft tissue or bone malignancy. Early imaging and biopsy are essential for diagnosis. Definitive management involves factor replacement and surgical excision in large or symptomatic cases. In centers where FX concentrate is unavailable, PCC and FFP provide effective hemostatic coverage. This case underscores the importance of a multidisciplinary approach and resource-adapted management, which can achieve favorable outcomes even in low-resource settings. Surgical excision with adequate perioperative PCC/FFP support remains a safe and effective strategy for large pseudotumors secondary to FX deficiency.
2026-03-12 | Severe Congenital Factor X Deficiency in an Indian Child With a Concomitant Novel ITGA2 Variant
The authors declare no conflicts of interest. Supporting data is available with the corresponding author and will be made available upon reasonable request
2026-03-06 | Inherited Bleeding Disorders in Pregnancy: Obstetric Management and Outcomes From a Tertiary Care Centre
Some women have inherited conditions that affect how their blood clots, called hereditary coagulation factor deficiencies. During pregnancy and childbirth, these conditions may increase the risk of bleeding for both mothers and babies. We reviewed the medical records of 17 pregnant women with different types of inherited clotting factor deficiencies who gave birth at a large tertiary care hospital between 2015 and 2025. The women had conditions such as von Willebrand disease and deficiencies of Factors VII, X, XI and XIII. We found that pregnancy and delivery outcomes were very different from one woman to another. Some women with very low clotting factor levels experienced no bleeding problems, while others had significant bleeding despite having near-normal levels. Careful planning and teamwork between specialists-including obstetricians, haematologists and anaesthesiologists-were essential to ensure safe deliveries. Treatments such as factor replacement, Haemate-P and fresh frozen plasma were used when necessary. Our study highlights the importance of individualized care for pregnant women with rare bleeding disorders. Early involvement of a multidisciplinary team and close monitoring before, during and after childbirth can help prevent complications and improve outcomes for both mothers and babies.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
2 orphan drug designations for Congenital factor X deficiency, including 2 approved therapies.
2 orphan drug designations for Congenital factor X deficiency, including 2 approved therapies.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Coagulation factor X (human) [COAGADEX] | proteins | FDA | 2007-11-08 | 2015-10-20 | Bio Products Laboratory Limited |
Human coagulation factor X [Coagadex] | proteins | EMA | 2007-09-17 | 2016-03-18 | Kedrion S.p.A. |
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