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:
categories:
Small molecules
small molecules
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
2025-07-22 | Coagulation proteases modulate nucleic acid uptake and cGAS-STING-IFN induction in the tumor microenvironment
Malignancies increase the risk for thrombosis and metastasis dependent on complex interactions of innate immune cells, platelets, and the coagulation system. Immunosuppressive functions of platelets and macrophage-derived coagulation factors in the tumor microenvironment (TME) drive tumor growth. Here, we show that patients with malignancies and tumor-bearing mice have increased levels of coagulation factor (F) X-expressing circulating monocytes engaged in platelet aggregate formation. This interaction and resulting thrombin generation on platelets interferes with monocyte differentiation and antigen uptake of antigen-presenting cells (APCs). Myeloid cell-specific deletion of FX or abrogated FXa signaling via protease activated receptor 2 (PAR2) averts the suppressive activity of platelets on tumor cell debris uptake and promotes the immune stimulatory activity of APCs in the TME. Myeloid cell FXa-PAR2 signaling deficiency specifically enhances activation of the cGAS-STING-IFN-I pathway with a resulting expansion of antigen experienced progenitor exhausted CD8+ T cells. Pharmacological blockade of FXa with direct oral anticoagulants expands T cell priming-competent immune cells in the TME and synergizes with the reactivation of exhausted CD8+ T cells by immune checkpoint inhibitors for improved antitumor responses. These data provide mechanistic insights into the emerging clinical evidence demonstrating the translational potential of FXa inhibition to synergize with immunotherapy.
2025-03-01 | Twenty Years of the Four-Factor Prothrombin Complex Concentrate Octaplex/Balfaxar: A Narrative Review
Prothrombin complex concentrate (PCC) is used to boost thrombin potential, support clot formation, and aid in the treatment and prophylaxis of bleeding. The two main forms of PCC are three-factor (3 F-PCC; comprising coagulation factors II, IX, and X) and four-factor (4F-PCC; factors II, VII, IX, X), which contain 25 times the clotting factors found in human plasma. This narrative review summarizes published efficacy and safety data on one 4F-PCC (Octaplex/Balfaxar, Octapharma) within its recognized uses and explores potential applications across different clinical contexts. Clinically available for > 20 years, Octaplex/Balfaxar is supplied as a freeze-dried powder for reconstitution and intravenous infusion. This 4F-PCC contains non-activated forms of coagulation factors as well as anticoagulant proteins C and S, potentially affording a balanced hemostatic effect and mitigating thrombosis risk. Production involves two virus inactivation/removal steps: solvent/detergent treatment and nanofiltration. 4F-PCC is approved for acquired deficiency of vitamin K-dependent clotting factors, such as those induced by vitamin K antagonists (VKAs, e.g., warfarin), and for congenital deficiency of factors II and X. Five published trials in 444 adult patients demonstrated the efficacy of 4F-PCC in VKA reversal, reducing the international normalized ratio (INR) with only two potentially treatment-related thrombotic events reported. While 4F-PCC dosing is currently indicated to be INR-guided, emerging evidence supports fixed dosing as an alternative to conventional weight-based dosing for VKA reversal. Recent guidelines support 4 F-PCC use for direct oral anticoagulant-associated bleeding, cardiac surgery and trauma/emergencies. Ongoing studies will further clarify the efficacy and safety of 4 F-PCC beyond its approved indications.
2025-02-25 | Factor XI and XII inhibitors–Dawn of a new era
The history of coagulation cascade dates back to 17th century. The extrinsic and intrinsic pathways were proposed in 1998. Extrinsic pathway includes the tissue factor and stable factor which activates factor X and with help of factor V, this converts prothrombin to thrombin which is stabilised by factor XIII. This helps to seal the bleeding vessel and is a physiological process as there is only "limited" production of thrombin which doe not expand beyond the damaged site due to absence of tissue factor. On the other hand intrinsic pathway is activated by polyanions, neutrophilic extracellular traps which are present during infection and inflammation. These activate factor XI which activates factor X with the help of factor IX and VIII and then the common pathway ensues. But newer discoveries have shown that this is a very simplified way of explaining the coagulation system. The researches propose that haemostasis is divided into initiation, amplification and propagation phase. Also, the factor VII-tissue factor complex formed activates factor IX and leads to sustained thrombin production as the amount of thrombin produced by extrinsic pathway alone is not sufficient to form a haemostatic plug. Thrombin also activates factor XI and lead to self perpetuation of intrinsic pathway. All the anticoagulants have an inherent property of bleeding. So the newer factor XI and XII inhibitors focus to inhibit the excessive thrombin production without hampering the physiological haemostasis process. This is supported by the fact that congenital factor XI and XII deficiency does not cause excessive bleeding but increased levels did make patients more vulnerable to thromboembolism. This review shall focus on the various factor XI and XII inhibitors which are in the pipeline.
2024-07-01 | Efficacy and safety of HaemoCer, a local hemostatic agent, in patients with congenital bleeding disorders: a case series
Aim To evaluate the efficacy and safety of HaemoCer in the management of bleeding symptoms in patients with congenital bleeding disorders. Methods In this case series, 11 patients with hereditary bleeding disorders (6 Hemophilia A, 3 Glanzmann thrombasthenia, one Von Willebrand disease, and one Factor X deficiency) were investigated between April and September 2021. All patients were registered at the Hemophilia Center affiliated with Shiraz University of Medical Sciences, Shiraz, Southern Iran. The outcome of all patients was assessed after administration of HaemoCer™ PLUS Absorbable Polysaccharide Haemostat (APH), a plant-based hemostatic powder that augments the natural clotting cascade. Results The median age of the patients was 13 (range: 5–66) years, eight males and three females. The most common presenting symptoms at referral were epistaxis (63.6%) followed by gingival bleeding (18.2%). Overall, three (27.2%) patients (two with epistaxis and one with gingival bleeding) responded to HaemoCer without the need to any additional treatment. The rest of the patients needed further treatment for managing bleeding symptoms. The patients were followed for three months without the occurrence of any adverse events. Bleeding symptoms occurred in 10 patients during the follow-up period, only four patients agreed to use HaemoCer again, and two of them responded and needed no further treatment. Conclusion It seems that efficacy of HaemoCer is not optimal to use alone for the management of the local bleeding symptoms in all patients with congenital bleeding disorders, but it may work in some patients. However, it seems to be safe based on this study.
proteins
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.
oligonucleotides
2024-07-11 | Fitusiran reduces bleeding in factor X-deficient mice.
Factor X (FX) deficiency is a rare bleeding disorder manifesting a bleeding tendency caused by low FX activity levels. We aim to explore the use of fitusiran (an investigational small interfering RNA that silences antithrombin expression) to increase thrombin generation and the in vivo hemostatic potential under conditions of FX deficiency. We therefore developed a novel model of inducible FX deficiency, generating mice expressing <1% FX activity and antigen (f10low mice). Compared with control f10WT mice, f10low mice had sixfold and fourfold prolonged clotting times in prothrombin time and activated partial prothrombin time assays, respectively (P < .001). Thrombin generation was severely reduced, irrespective of whether tissue factor or factor XIa was used as an initiator. In vivo analysis revealed near-absent thrombus formation in a laser-induced vessel injury model. Furthermore, in 2 distinct bleeding models, f10low mice displayed an increased bleeding tendency compared with f10WT mice. In the tail-clip assay, blood loss was increased from 12 ± 16 μL to 590 ± 335 μL (P < .0001). In the saphenous vein puncture (SVP) model, the number of clots generated was reduced from 19 ± 5 clots every 30 minutes for f10WT mice to 2 ± 2 clots every 30 minutes (P < .0001) for f10low mice. In both models, bleeding was corrected upon infusion of purified FX. Treatment of f10low mice with fitusiran (2 × 10 mg/kg at 1 week interval) resulted in 17 ± 6% residual antithrombin activity and increased thrombin generation (fourfold and twofold to threefold increase in endogenous thrombin potential and thrombin peak, respectively). In the SVP model, the number of clots was increased to 8 ± 6 clots every 30 minutes (P = .0029). Altogether, we demonstrate that reduction in antithrombin levels is associated with improved hemostatic activity under conditions of FX deficiency.
antibodies
2025-11-01 | HTRS2025.P1.47 Procoagulant Enhancement of Inherited Factor X Deficiency with Emicizumab
Non-adherence to DOACs was defined as PDC < 0.80.Recurrent thrombosis, stroke, major bleeding and clinically relevant non-major bleeding (CRNMB) events were collected.Results: 57 patients were started on DOACs: 53 (93%) were treated with rivaroxaban and 4 (7%) with apixaban.46 (81%) were for the indication of venous thromboembolism, 5 (9%) were for stroke, 4 (7%) were for venous malformation, and 2 (3%) were for atrial fibrillation.The median age was 14 years (range: 0.6-17), and the mean duration of treatment exposure was 6.7 months ( 4.5).The mean PDC was 0.87 (0.17); 26.3% were non-adherent patients (PDC < 0.80).Eight (14%) patients prematurely self-discontinued DOACs during their treatment period.Two of these patients experienced recurrent thrombotic events (one had recurrent stroke, the other had recurrent venous thromboembolism) and resumed their DOAC during the hospital admission.There were no major bleeding events; eight (14%) experienced CRNMB.Seven (37%) of 19 post-menarchal patients experienced heavy menstrual bleeding which accounted for 89% of the CRNMB events.Conclusions: Our ongoing real-world study suggests more than one quarter of patients had poor DOAC adherence.Premature self-discontinuation of DOAC may lead to recurrent thrombotic events.Targeted interventions to enhance DOAC adherence in children are urgently needed.Other: 1.
small molecules
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
2025-07-22 | Coagulation proteases modulate nucleic acid uptake and cGAS-STING-IFN induction in the tumor microenvironment
Malignancies increase the risk for thrombosis and metastasis dependent on complex interactions of innate immune cells, platelets, and the coagulation system. Immunosuppressive functions of platelets and macrophage-derived coagulation factors in the tumor microenvironment (TME) drive tumor growth. Here, we show that patients with malignancies and tumor-bearing mice have increased levels of coagulation factor (F) X-expressing circulating monocytes engaged in platelet aggregate formation. This interaction and resulting thrombin generation on platelets interferes with monocyte differentiation and antigen uptake of antigen-presenting cells (APCs). Myeloid cell-specific deletion of FX or abrogated FXa signaling via protease activated receptor 2 (PAR2) averts the suppressive activity of platelets on tumor cell debris uptake and promotes the immune stimulatory activity of APCs in the TME. Myeloid cell FXa-PAR2 signaling deficiency specifically enhances activation of the cGAS-STING-IFN-I pathway with a resulting expansion of antigen experienced progenitor exhausted CD8+ T cells. Pharmacological blockade of FXa with direct oral anticoagulants expands T cell priming-competent immune cells in the TME and synergizes with the reactivation of exhausted CD8+ T cells by immune checkpoint inhibitors for improved antitumor responses. These data provide mechanistic insights into the emerging clinical evidence demonstrating the translational potential of FXa inhibition to synergize with immunotherapy.
2025-03-01 | Twenty Years of the Four-Factor Prothrombin Complex Concentrate Octaplex/Balfaxar: A Narrative Review
Prothrombin complex concentrate (PCC) is used to boost thrombin potential, support clot formation, and aid in the treatment and prophylaxis of bleeding. The two main forms of PCC are three-factor (3 F-PCC; comprising coagulation factors II, IX, and X) and four-factor (4F-PCC; factors II, VII, IX, X), which contain 25 times the clotting factors found in human plasma. This narrative review summarizes published efficacy and safety data on one 4F-PCC (Octaplex/Balfaxar, Octapharma) within its recognized uses and explores potential applications across different clinical contexts. Clinically available for > 20 years, Octaplex/Balfaxar is supplied as a freeze-dried powder for reconstitution and intravenous infusion. This 4F-PCC contains non-activated forms of coagulation factors as well as anticoagulant proteins C and S, potentially affording a balanced hemostatic effect and mitigating thrombosis risk. Production involves two virus inactivation/removal steps: solvent/detergent treatment and nanofiltration. 4F-PCC is approved for acquired deficiency of vitamin K-dependent clotting factors, such as those induced by vitamin K antagonists (VKAs, e.g., warfarin), and for congenital deficiency of factors II and X. Five published trials in 444 adult patients demonstrated the efficacy of 4F-PCC in VKA reversal, reducing the international normalized ratio (INR) with only two potentially treatment-related thrombotic events reported. While 4F-PCC dosing is currently indicated to be INR-guided, emerging evidence supports fixed dosing as an alternative to conventional weight-based dosing for VKA reversal. Recent guidelines support 4 F-PCC use for direct oral anticoagulant-associated bleeding, cardiac surgery and trauma/emergencies. Ongoing studies will further clarify the efficacy and safety of 4 F-PCC beyond its approved indications.
2025-02-25 | Factor XI and XII inhibitors–Dawn of a new era
The history of coagulation cascade dates back to 17th century. The extrinsic and intrinsic pathways were proposed in 1998. Extrinsic pathway includes the tissue factor and stable factor which activates factor X and with help of factor V, this converts prothrombin to thrombin which is stabilised by factor XIII. This helps to seal the bleeding vessel and is a physiological process as there is only "limited" production of thrombin which doe not expand beyond the damaged site due to absence of tissue factor. On the other hand intrinsic pathway is activated by polyanions, neutrophilic extracellular traps which are present during infection and inflammation. These activate factor XI which activates factor X with the help of factor IX and VIII and then the common pathway ensues. But newer discoveries have shown that this is a very simplified way of explaining the coagulation system. The researches propose that haemostasis is divided into initiation, amplification and propagation phase. Also, the factor VII-tissue factor complex formed activates factor IX and leads to sustained thrombin production as the amount of thrombin produced by extrinsic pathway alone is not sufficient to form a haemostatic plug. Thrombin also activates factor XI and lead to self perpetuation of intrinsic pathway. All the anticoagulants have an inherent property of bleeding. So the newer factor XI and XII inhibitors focus to inhibit the excessive thrombin production without hampering the physiological haemostasis process. This is supported by the fact that congenital factor XI and XII deficiency does not cause excessive bleeding but increased levels did make patients more vulnerable to thromboembolism. This review shall focus on the various factor XI and XII inhibitors which are in the pipeline.
2024-07-01 | Efficacy and safety of HaemoCer, a local hemostatic agent, in patients with congenital bleeding disorders: a case series
Aim To evaluate the efficacy and safety of HaemoCer in the management of bleeding symptoms in patients with congenital bleeding disorders. Methods In this case series, 11 patients with hereditary bleeding disorders (6 Hemophilia A, 3 Glanzmann thrombasthenia, one Von Willebrand disease, and one Factor X deficiency) were investigated between April and September 2021. All patients were registered at the Hemophilia Center affiliated with Shiraz University of Medical Sciences, Shiraz, Southern Iran. The outcome of all patients was assessed after administration of HaemoCer™ PLUS Absorbable Polysaccharide Haemostat (APH), a plant-based hemostatic powder that augments the natural clotting cascade. Results The median age of the patients was 13 (range: 5–66) years, eight males and three females. The most common presenting symptoms at referral were epistaxis (63.6%) followed by gingival bleeding (18.2%). Overall, three (27.2%) patients (two with epistaxis and one with gingival bleeding) responded to HaemoCer without the need to any additional treatment. The rest of the patients needed further treatment for managing bleeding symptoms. The patients were followed for three months without the occurrence of any adverse events. Bleeding symptoms occurred in 10 patients during the follow-up period, only four patients agreed to use HaemoCer again, and two of them responded and needed no further treatment. Conclusion It seems that efficacy of HaemoCer is not optimal to use alone for the management of the local bleeding symptoms in all patients with congenital bleeding disorders, but it may work in some patients. However, it seems to be safe based on this study.
proteins
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.
oligonucleotides
2024-07-11 | Fitusiran reduces bleeding in factor X-deficient mice.
Factor X (FX) deficiency is a rare bleeding disorder manifesting a bleeding tendency caused by low FX activity levels. We aim to explore the use of fitusiran (an investigational small interfering RNA that silences antithrombin expression) to increase thrombin generation and the in vivo hemostatic potential under conditions of FX deficiency. We therefore developed a novel model of inducible FX deficiency, generating mice expressing <1% FX activity and antigen (f10low mice). Compared with control f10WT mice, f10low mice had sixfold and fourfold prolonged clotting times in prothrombin time and activated partial prothrombin time assays, respectively (P < .001). Thrombin generation was severely reduced, irrespective of whether tissue factor or factor XIa was used as an initiator. In vivo analysis revealed near-absent thrombus formation in a laser-induced vessel injury model. Furthermore, in 2 distinct bleeding models, f10low mice displayed an increased bleeding tendency compared with f10WT mice. In the tail-clip assay, blood loss was increased from 12 ± 16 μL to 590 ± 335 μL (P < .0001). In the saphenous vein puncture (SVP) model, the number of clots generated was reduced from 19 ± 5 clots every 30 minutes for f10WT mice to 2 ± 2 clots every 30 minutes (P < .0001) for f10low mice. In both models, bleeding was corrected upon infusion of purified FX. Treatment of f10low mice with fitusiran (2 × 10 mg/kg at 1 week interval) resulted in 17 ± 6% residual antithrombin activity and increased thrombin generation (fourfold and twofold to threefold increase in endogenous thrombin potential and thrombin peak, respectively). In the SVP model, the number of clots was increased to 8 ± 6 clots every 30 minutes (P = .0029). Altogether, we demonstrate that reduction in antithrombin levels is associated with improved hemostatic activity under conditions of FX deficiency.
antibodies
2025-11-01 | HTRS2025.P1.47 Procoagulant Enhancement of Inherited Factor X Deficiency with Emicizumab
Non-adherence to DOACs was defined as PDC < 0.80.Recurrent thrombosis, stroke, major bleeding and clinically relevant non-major bleeding (CRNMB) events were collected.Results: 57 patients were started on DOACs: 53 (93%) were treated with rivaroxaban and 4 (7%) with apixaban.46 (81%) were for the indication of venous thromboembolism, 5 (9%) were for stroke, 4 (7%) were for venous malformation, and 2 (3%) were for atrial fibrillation.The median age was 14 years (range: 0.6-17), and the mean duration of treatment exposure was 6.7 months ( 4.5).The mean PDC was 0.87 (0.17); 26.3% were non-adherent patients (PDC < 0.80).Eight (14%) patients prematurely self-discontinued DOACs during their treatment period.Two of these patients experienced recurrent thrombotic events (one had recurrent stroke, the other had recurrent venous thromboembolism) and resumed their DOAC during the hospital admission.There were no major bleeding events; eight (14%) experienced CRNMB.Seven (37%) of 19 post-menarchal patients experienced heavy menstrual bleeding which accounted for 89% of the CRNMB events.Conclusions: Our ongoing real-world study suggests more than one quarter of patients had poor DOAC adherence.Premature self-discontinuation of DOAC may lead to recurrent thrombotic events.Targeted interventions to enhance DOAC adherence in children are urgently needed.Other: 1.
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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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