RARE DISEASE
Acquired factor VII deficiency
Acquired factor VII deficiency
Acquired factor VII deficiency
Drug discovery
0
drugs
With orphan designations
Overview
Acquired Factor VII Deficiency is a rare bleeding disorder caused by reduced factor VII activity due to liver disease, vitamin K deficiency, malignancies, sepsis, or anticoagulant use. It presents with variable bleeding severity, from asymptomatic cases to life-threatening hemorrhage (e.g., intracranial, gastrointestinal). Diagnosis involves isolated prolonged PT with normal aPTT; management includes recombinant factor VIIa (rFVIIa), plasma products, and addressing underlying causes [1][2][6].
Therapies
rFVIIa: First-line for acute bleeding/prophylaxis (15–90 µg/kg) [3][8].
FFP/PCCs: Alternative options with variable efficacy due to low FVII content [1][16].
Supportive care: Antifibrinolytics (e.g., tranexamic acid), vitamin K for deficiency, and treatment of underlying conditions (e.g., chemotherapy for malignancies) [6][10].
Categories: rare hematological diseases
Research Papers
59 drug discovery papers about Acquired factor VII deficiency, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
59 drug discovery papers about Acquired factor VII deficiency, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
proteins
2026-01-10 | Use of Plasma-Derived FVII Concentrate in Surgical Patients with Factor VII Deficiency: A Case Series.
Congenital factor VII (FVII) deficiency is the most common rare hemorrhagic disorder. Acquired FVII deficiency can be isolated or associated with other low coagulation factor levels. FVII levels do not accurately predict a patient's bleeding risk. In the case of surgery, the perioperative management needs to be evaluated on a case-by-case basis, considering the patient's bleeding history and the type of surgery. We present 12 patients with congenital or acquired FVII deficiency and describe the perioperative management with plasma-derived nonactivated FVII (pd-FVII) concentrate. Patients with factor VII deficiency treated with pd-FVII for perioperative hemostasis, between April 2022 and May 2025. We report thirteen procedures in 12 patients (11 males and 1 female; age range: 15-78 years). Two patients were affected by acquired deficiency, and 10 patients presented congenital deficiency. Perioperative prophylaxis with pd-FVII was performed at doses ranging from 20 to 40 IU/kg/dose. Total pd-FVII consumption ranged between 20 and 320 IU/kg. During and after surgery, there were no major bleeding or thrombotic events. In the postoperative period, only one patient presented with hematuria.
2025-12-22 | Experience in Pediatric Bleeding Disorders in Tertiary Care Health Services from Southern Region of Saudi Arabia: Single Center Retrospective Study
Abstract: Background: Bleeding disorders are commonly encountered in clinical practice worldwide. In Saudi Arabia, such disorders are witnessed as a notable entity in clinical practice. They encompass a variable group of disorders categorized into acquired and congenital. Notable among them are hemophilia, von Willebrand disease (vWD), platelet-function defects, clotting factor deficiencies and immune thrombocytopenia (ITP). Objective: To describe the various bleeding disorders among Pediatric population and its related clinical features, diagnostics and management modalities adhered to. Materials and Methods: Retrospective cross-sectional study was carried out in Pediatric Medicine Department, Armed Forces Hospital Southern Region (AFHSR), Khamis Mushait, Kingdom of Saudi Arabia. The data was gathered for last five years – 1st May 2020 to 30th April 2025, as pediatric patients were included who were diagnosed with a bleeding disorder while aged up till fourteen years. Pertinent details subject to relevant history, clinical course and laboratory investigations like blood indices, prothrombin time (PT), activated partial thromboplastin time (PTTK) and accordingly relevant investigations notably factor assay and platelet-function tests were recorded. Result: During the last five years, 205 patients were evaluated by Pediatric Hematology team in regards to suspicion for a bleeding disorder. Out of these, 21% cases (44 patients) were confirmed with a definite bleeding disorder. Among these 44 patients, 24 (54%) patients being male and 20 (46%) female, all with Saudi ethnicity with their average age of 8 years 4 months. They were diagnosed with a bleeding disorder at average age of 4 years 10 months. 18 (41%) were having an acquired disorder while 26 (59%) were diagnosed with congenital disorder. Chronic ITP was observed in 9 cases while 5 cases were witnessed for each of acute ITP, vWD and factor VII deficiency. The most frequent presenting symptom was petechiae (25% patients) followed by epistaxis in 16% and ecchymosis in 11%, with no significant variation observed in congenital vs acquired disorders. Each patient had an average of one admission during the course of the disease. Thrombocytopenia was the most common laboratory abnormality identified (52% cases). This was followed by abnormal clotting factor levels (27% patients), raised PTTK in 25% and high INR in 14%. Furthermore, WES (whole exome sequencing) was performed in selected cases and genetic mutations were found in 41%. IVIG (intravenous immunoglobulin) was the most common intervention adopted. Conclusion: We were able to identify a specific bleeding disorder in 21% of cases who were worked up for a suspected bleeding disorder. Among the pediatric population from southern region of Saudi Arabia, chronic ITP was most frequent (20%), followed by 11% cases each for acute ITP, vWD and factor VII deficiency. Awareness strategies aimed towards bleeding disorders accompanied by swift diagnosis, appropriate therapeutics and genetic counseling is indispensable in averting morbidity. Keywords: Bleeding disorders, Clotting factor, Coagulation profile, Hemophilia, Platelets, von Willebrand disease.
2025-11-27 | Real-World Experience with Eptacog Beta for On-Label and Off-Label Indications: The Spanish Experience.
Background: Eptacog beta is a novel recombinant activated factor VII (rFVIIa). Preclinical studies have shown the product has a similar profile to eptacog alfa. The PERSEPT 1 and PERSEPT 3 trials proved the efficacy and safety of eptacog beta for surgical prophylaxis and treatment of bleed in patients with haemophilia A or B with inhibitors. This led to approval of the product by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Recently, real-world data have been published on the use of eptacog beta on this population which has provided positive outcomes. Given the similar in vitro and in vivo profile of eptacog beta and eptacog alfa positive outcomes could be expected not only in patients with haemophilia and inhibitors, but also in other situations where eptacog alfa is a therapeutic option. Methods: We report on the use of this product for on-label and off-label populations in two Spanish hospitals. Results: We describe four cases in an on-label population (haemophilia A with inhibitors) and four cases in another population (one with acquired haemophilia and three with mild factor VII deficiency). Conclusions: Our experience provides further evidence of the efficacy and safety of eptacog beta for surgical prophylaxis and treatment of bleeding in patients with haemophilia A with inhibitors, but also in those with factor VII deficiency. To our knowledge, this is the first report to describe the use of eptacog beta for factor VII deficiency and acquired haemophilia.
2025-09-19 | Evaluation of Deficiency and Excessive Condition of Thrombin Burst Using Laboratory Tests.
Thrombin burst is an important mechanism for hemostasis, which is enhancement and amplification of the coagulation cycle, especially activation of coagulation factors XI, VIII, and V by thrombin on the activated platelets. Thrombin burst monitoring has been performed using hemostatic molecular markers, thrombin generation test (TGT), thromboelastography (TEG), and clot waveform analysis (CWA). In particular, CWA is a routine laboratory test that is neither time consuming nor expensive. Arterial thromboses, such as acute myocardial thrombosis and acute cerebral thrombosis, are associated with excessive condition of thrombin burst, and clotting time using a small amount of thrombin in CWA can detect activated or procoagulant platelets. Thrombin burst deficiency is caused by abnormalities of platelets such as thrombocytopenia or clotting factors such as hemophilia and acquired clotting factor deficiency, showing different CWA patterns. Patients with clotting factor VIII inhibitors are treated with bypass therapy, such as recombinant activated clotting factor VII and activated prothrombin complex concentrate, which can be monitored by CWA, TEG, or TGT.
2025-06-27 | Coagulation Factor VII Deficiency: A Review of the Clinical Implications and Approaches to Replacement Therapy and Prophylaxis.
Factor VII (FVII) deficiency is a rare bleeding disorder that can present as either inherited or acquired. Inherited FVII deficiency arise from mutations in the F7 gene, resulting in a highly heterogeneous and wide range of phenotypic expressions from asymptomatic individuals to those experiencing severe and life-threatening hemorrhagic episodes. Notably, the severity of symptoms is typically not correlated with plasma FVII levels. Diagnosis generally involves a combination of coagulation assays, including prothrombin time (PT), assessment of FVII activity and antigenic levels, and a thorough consideration of the patient's clinical context. Management of FVII deficiency requires personalized treatment strategies. For inherited forms, on-demand replacement therapy is commonly employed, utilizing recombinant activated FVII, plasma-derived FVII, prothrombin complex concentrates, or fresh frozen plasma during bleeding episodes, as well as for prophylactic measures. Long-term prophylaxis is particularly critical for patients with severe deficiencies who have a history of central nervous system or gastrointestinal bleeding, especially those at an elevated risk of subsequent major or potentially life-threatening bleeding events. This review evaluates current therapeutic approaches, highlights emerging challenges in the management of FVII deficiency, and underscores the importance of tailored treatment strategies aimed at optimizing patient outcomes.
small molecules
2025-11-03 | A 10-year retrospective review of the effectiveness and safety of tranexamic acid in women with inherited bleeding disorders in the peripartum setting
Abstract Background: PPH occurs at a rate of nearly 11% globally and is a major cause of maternal mortality worldwide (Carroli, 2008.) Women with inherited bleeding disorders such as hemophilia carriers and those with von Willebrand disease (VWD) are at a substantially greater risk of postpartum hemorrhage (PPH) (Abdul-Kadir, 2014.) TXA use for treatment of PPH has been shown to reduce major bleeding risk without increasing the risk of thromboembolism in patients (Li, 2017). However, the effects of its prophylactic use in patients with bleeding disorders has not been extensively described. The aim of this study was to investigate the effectiveness and safety of prophylactic TXA use in peripartum patients with inherited bleeding disorders. Methods: A retrospective chart review was conducted for all patients with an inherited bleeding disorder cared for by the Multidisciplinary Clinic for Women with Bleeding Disorders (MCWBD) at St. Michael's Hospital (SMH) between 2014 and 2024. We performed descriptive statistical analysis to summarize findings related to bleeding and thrombotic events in patients treated with TXA in the puerperium. Results: There were 296 total patients managed over the course of pregnancy to labour and delivery in the MCWBD over this 10 year time period. 205 had an inherited bleeding disorder (the remainder had an acquired disorder and were not included in the analysis). The median age of patients was 32 (range 18-42). 32% had von Willebrand's Disease, 17% platelet function disorder, 1% hemophilia A,10% symptomatic hemophilia A or B carrier, 18% Bleeding Disorder of Undetermined Cause and 14% rare single clotting factor deficiency. 61% of patients had vaginal delivery, 39% had a C-section. We had access to complete labour and delivery records for 144 patients to allow for reporting of bleeding events. 95% of patients received TXA at some point during delivery. 68% patients received TXA during and after delivery, 11% received TXA only during delivery and 16% received TXA only after delivery. 31% patients also received an additional hemostatic agent (17% received DDAVP, 15% received factor concentrate -VWF:FVIII, FXI, FVIII, rFVIIa and FIX). 17% of patients experienced postpartum hemorrhage (PPH) and of those 88% had primary PPH. 12% of patients with PPH did not use any TXA prophylactically. Two patients who received TXA experienced a thrombotic event post-partum (2/205, 0.98%). One patient with severe factor VII deficiency developed pulmonary embolism 14 days after delivery during which she was being treated with a tapering regimen of rFVIIa and TXA. She had 3 risk factors for VTE: morbid obesity, varicose veins and heterozygosity for factor V leiden mutation. The other patient developed a superficial venous thrombus 1 day after delivery, she had 2 risk factors for VTE: morbid obesity and varicose veins. Conclusions: This data suggests that TXA is associated with very low risk of thrombosis when used as prophylactic treatment for PPH among patients with inherited bleeding disorders in the puerperium. Under 1% of patients over 10 years experienced a thrombotic event and had two or more risk factors for VTE. In contrast, at least 17% had PPH despite provision of preventative peripartum hemostatic therapy that almost always included TXA. This suggests that on balance, TXA should be provided to patients with inherited bleeding disorders with the goal of PPH prevention but caution should be used in those with 2 or more risk factors for thrombosis. Prospective studies on the use of prophylactic TXA in this setting is warranted.
2024-10-14 | Severe acquired Factor VII deficiency complicating an aplastic anemia, successfully treated with corticosteroids.
Factor VII deficiency is a rare hemostatic disorder that can lead to severe clinical outcomes. Due to the scarcity of reported cases, treatment guidelines for this condition remain unclear. In this report, we present a case of acquired factor VII deficiency (aFVII) in an elderly female with medullary aplasia. The initial clinical manifestation was hemarthrosis, accompanied by a rapid increase in prothrombin time. Prompt intervention involved supplementation to address the deficiency. Subsequent laboratory testing failed to detect any specific factor VII inhibitor. Considering the patient's frailty, immunosuppressive therapy comprising only corticosteroids was administered. The potential triggering mechanisms may include recurrent episodes of sepsis or an underlying autoimmune condition. Further research is necessary to better understand the etiology and optimal management of aFVII deficiency.
2023-11-06 | Acquired Factor VII Deficiency Associated With Chronic Myeloid Leukemia Blast Crisis.
Factor VII (FVII) is an important, vitamin K-dependent clotting factor. Acquired FVII deficiency is a rare entity that is associated with serious bleeding complications. We report a case of acquired FVII deficiency in a patient with recurrent chronic myeloid leukemia in blast crisis who developed bilateral retinal hemorrhages. The coagulopathy was corrected with the initiation of chemotherapy and subsequent reduction in peripheral blast count.
2019-09-09 | Acute Myelogenous Leukemia With Trisomy 8 and Concomitant Acquired Factor VII Deficiency
Acquired isolated factor VII deficiency is a rare bleeding disorder and has been reported in 31 cases. This is in contrast to congenital factor VII deficiency, which while also infrequent is the most common rare congenital bleeding disorder. Acquired isolated factor VII deficiency has been described primarily in patients with solid malignancies, sepsis, and in the presence of anti-factor VII autoantibodies. We report a case of acute myelogenous leukemia with an associated trisomy 8 cytogenetic abnormality presenting with factor VII deficiency. The factor VII deficiency cleared after induction chemotherapy and with the disappearance of the cytogenetic and molecular abnormalities. We discuss a possible link between trisomy 8 and vitamin K metabolism, which might result in acquired factor VII deficiency in acute myelogenous leukemia.
2005-07-20 | Cyclosporine controls epidermolysis bullosa acquisita co‐occurring with acquired factor VIII deficiency
Abstract Background Epidermolysis bullosa acquisita (EBA) is a rare antibody‐mediated autoimmune blistering disease of adults. Likewise, acquired factor VIII deficiency is a rare antibody‐mediated disease of adulthood. Both diseases can be exceedingly difficult to treat and refractory to immunomodulatory therapies. Methods Herein, we report a challenging case of EBA and acquired factor VIII deficiency in the same patient. Results Cyclosporine 4 mg/kg/day rapidly controlled both disease processes after the patient failed to respond to prednisone, colchicine, and pulse cyclophosphamide. The EBA relapsed when the cyclosporine was decreased to 2 mg/kg/day and the patient wore snuggly fitting new shoes, but it cleared quickly when the dose was increased. Cyclosporine has since been decreased gradually to 1.5 mg/kg/day without relapse of either condition or detectable side‐effects. Conclusions Cyclosporine should be considered when EBA and/or acquired factor VIII deficiency fail to respond to conservative therapy. Both conditions usually respond rapidly to cyclosporine 4–6 mg/kg/day.
antibodies
2025-08-05 | PO27 | B-cell lymphoproliferative disorder and acquired coagulopathy: an insidious link
Background: Acquired coagulation factor inhibitors are autoantibodies that may develop in individuals with autoimmune or neoplastic disorders and should be assessed in patients without personal or familiar history of bleeding disorders. These inhibitors most commonly target factor VIII (FVIII) or von Willebrand factor (VWF), resulting in acquired haemophilia A or acquired von Willebrand disease, respectively and may occasionally interfere with the normal activity of other coagulation factors. Case Report: An 81-year-old female presented with recurrent episodes of anterior epistaxis and ecchymoses, without history of personal bleeding disorders. Laboratory testing revealed deficiencies in vitamin K–dependent factors (except for factor IX) in the absence of liver dysfunction or other known causes of coagulopathy, raising suspicion of an acquired haemorrhagic disorder. Past medical history included an indolent B-cell lymphoproliferative disorder, under haematological follow-up and arterial hypertension. Clinically, the patient exhibited persistent mucocutaneous bleeding associated with progressive anaemia and transient memory deficits. Due to suspected central nervous system involvement, an MRI was performed, revealing a small haemorrhagic area in the fornix of the limbic system. At the admission, coagulation studies confirmed markedly abnormal coagulation parameters: PT/INR 5.36 and aPTT 1.56. The mixing test showed suboptimal correction. The laboratory evaluation revealed: Factor IX 171%, Factor II 5%, Factor VII 17%, Factor X 7%, Protein S 51%, and Protein C 24%. Mixing studies for Factors II and VII demonstrated suboptimal correction, suggesting the presence of inhibitors. Lupus anticoagulant and antiphospholipid antibodies were negative. According to these results, we hypnotized the presence of a poly-specific serum para-protein interfering with clotting factors. Intravenous vitamin K (Konakion 10 mg) induced a not significant resolution of PT prolongation followed by a rebound increase to 4.66 and 5.27. PIVKA-II levels were 41 AU/mL (negative), supporting the lack of a functional vitamin K deficiency. Immunosuppressive steroid therapy with prednisone was started at the time of admission. Given the known lymphoproliferative disorder, the possibility of a neoplastic trigger for the coagulation abnormality was considered. Flow cytometry confirmed the presence of a B-cell clone expressing CD20, with a 2% blast count. After 15 days of steroid therapy without clinical improvement, a pharmacokinetic assessment was conducted following the administration of a 4-factor prothrombin complex concentrate (PCC). Factor levels were measured at baseline and several time points post-infusion (30 min, 1h, 2h, 4h, 12h, 24h). A marked decline in circulating coagulation factors was noted after 4 hours, with the greatest reduction observed for Factor II, suggesting preferential inhibitory activity against this factor, likely due to the presence of a neoplastic paraprotein. Therapy with rituximab (anti-CD20 monoclonal antibody) was then introduced at the standard dose of 375 mg/m² weekly for four weeks with complete normalisation of coagulation. Conclusions: This case highlights the diagnostic and therapeutic challenges posed by rare coagulation inhibitors. The successful use of rituximab underscores the relevance of B-cell–directed immunosuppression in managing such complex cases, particularly in the context of clonal B-cell disorders.
2022-03-14 | A low-dose rituximab regimen for first-line treatment of acquired haemophilia A.
A low-dose rituximab regimen for first-line treatment of acquired haemophilia A. Acquired haemophilia A (AHA) is a rare disease caused by the development of autoantibodies against FVIII. Diagnosis involves confirmation of FVIII deficiency and the presence of an inhibitor via the Bethesda assay. Severe bleeding is often managed with bypassing agents such as recombinant factor VII. This is then followed by eradication of the inhibitor with immunosuppression which typically includes a corticosteroid backbone. Review the current management and outcomes of AHA in Queensland, Australia. Determine the incidence, demographics and clinical characteristics of AHA patients. Retrospective case series of AHA diagnosed between May 2014 and August 2018. Data were derived from the Australian Bleeding Disorders Registry and state-wide pathology database. Data collection proforma was completed by the treating haematologist and reviewed/compiled centrally. 24 patients were identified (incidence 1 in 1.27 million). The median age was 76.5 years. Median follow-up was 20 months. Index bleed was atraumatic and skin/soft tissue in the majority of patients. Recombinant FVIIa was the most commonly used haemostatic therapy and effective in 85% of patients. Immunosuppression and steroid usage were uniform. Upfront second agent was used in 75% of patients and was most commonly rituximab. 87.5% of patients achieved a complete remission in a median time of 48 days. Low-dose rituximab was frequently used and equally as efficacious as standard dose. Immunosuppression with combination therapy, notably rituximab, appears to be non-inferior and has a favourable side effect profile.
proteins
2026-01-10 | Use of Plasma-Derived FVII Concentrate in Surgical Patients with Factor VII Deficiency: A Case Series.
Congenital factor VII (FVII) deficiency is the most common rare hemorrhagic disorder. Acquired FVII deficiency can be isolated or associated with other low coagulation factor levels. FVII levels do not accurately predict a patient's bleeding risk. In the case of surgery, the perioperative management needs to be evaluated on a case-by-case basis, considering the patient's bleeding history and the type of surgery. We present 12 patients with congenital or acquired FVII deficiency and describe the perioperative management with plasma-derived nonactivated FVII (pd-FVII) concentrate. Patients with factor VII deficiency treated with pd-FVII for perioperative hemostasis, between April 2022 and May 2025. We report thirteen procedures in 12 patients (11 males and 1 female; age range: 15-78 years). Two patients were affected by acquired deficiency, and 10 patients presented congenital deficiency. Perioperative prophylaxis with pd-FVII was performed at doses ranging from 20 to 40 IU/kg/dose. Total pd-FVII consumption ranged between 20 and 320 IU/kg. During and after surgery, there were no major bleeding or thrombotic events. In the postoperative period, only one patient presented with hematuria.
2025-12-22 | Experience in Pediatric Bleeding Disorders in Tertiary Care Health Services from Southern Region of Saudi Arabia: Single Center Retrospective Study
Abstract: Background: Bleeding disorders are commonly encountered in clinical practice worldwide. In Saudi Arabia, such disorders are witnessed as a notable entity in clinical practice. They encompass a variable group of disorders categorized into acquired and congenital. Notable among them are hemophilia, von Willebrand disease (vWD), platelet-function defects, clotting factor deficiencies and immune thrombocytopenia (ITP). Objective: To describe the various bleeding disorders among Pediatric population and its related clinical features, diagnostics and management modalities adhered to. Materials and Methods: Retrospective cross-sectional study was carried out in Pediatric Medicine Department, Armed Forces Hospital Southern Region (AFHSR), Khamis Mushait, Kingdom of Saudi Arabia. The data was gathered for last five years – 1st May 2020 to 30th April 2025, as pediatric patients were included who were diagnosed with a bleeding disorder while aged up till fourteen years. Pertinent details subject to relevant history, clinical course and laboratory investigations like blood indices, prothrombin time (PT), activated partial thromboplastin time (PTTK) and accordingly relevant investigations notably factor assay and platelet-function tests were recorded. Result: During the last five years, 205 patients were evaluated by Pediatric Hematology team in regards to suspicion for a bleeding disorder. Out of these, 21% cases (44 patients) were confirmed with a definite bleeding disorder. Among these 44 patients, 24 (54%) patients being male and 20 (46%) female, all with Saudi ethnicity with their average age of 8 years 4 months. They were diagnosed with a bleeding disorder at average age of 4 years 10 months. 18 (41%) were having an acquired disorder while 26 (59%) were diagnosed with congenital disorder. Chronic ITP was observed in 9 cases while 5 cases were witnessed for each of acute ITP, vWD and factor VII deficiency. The most frequent presenting symptom was petechiae (25% patients) followed by epistaxis in 16% and ecchymosis in 11%, with no significant variation observed in congenital vs acquired disorders. Each patient had an average of one admission during the course of the disease. Thrombocytopenia was the most common laboratory abnormality identified (52% cases). This was followed by abnormal clotting factor levels (27% patients), raised PTTK in 25% and high INR in 14%. Furthermore, WES (whole exome sequencing) was performed in selected cases and genetic mutations were found in 41%. IVIG (intravenous immunoglobulin) was the most common intervention adopted. Conclusion: We were able to identify a specific bleeding disorder in 21% of cases who were worked up for a suspected bleeding disorder. Among the pediatric population from southern region of Saudi Arabia, chronic ITP was most frequent (20%), followed by 11% cases each for acute ITP, vWD and factor VII deficiency. Awareness strategies aimed towards bleeding disorders accompanied by swift diagnosis, appropriate therapeutics and genetic counseling is indispensable in averting morbidity. Keywords: Bleeding disorders, Clotting factor, Coagulation profile, Hemophilia, Platelets, von Willebrand disease.
2025-11-27 | Real-World Experience with Eptacog Beta for On-Label and Off-Label Indications: The Spanish Experience.
Background: Eptacog beta is a novel recombinant activated factor VII (rFVIIa). Preclinical studies have shown the product has a similar profile to eptacog alfa. The PERSEPT 1 and PERSEPT 3 trials proved the efficacy and safety of eptacog beta for surgical prophylaxis and treatment of bleed in patients with haemophilia A or B with inhibitors. This led to approval of the product by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Recently, real-world data have been published on the use of eptacog beta on this population which has provided positive outcomes. Given the similar in vitro and in vivo profile of eptacog beta and eptacog alfa positive outcomes could be expected not only in patients with haemophilia and inhibitors, but also in other situations where eptacog alfa is a therapeutic option. Methods: We report on the use of this product for on-label and off-label populations in two Spanish hospitals. Results: We describe four cases in an on-label population (haemophilia A with inhibitors) and four cases in another population (one with acquired haemophilia and three with mild factor VII deficiency). Conclusions: Our experience provides further evidence of the efficacy and safety of eptacog beta for surgical prophylaxis and treatment of bleeding in patients with haemophilia A with inhibitors, but also in those with factor VII deficiency. To our knowledge, this is the first report to describe the use of eptacog beta for factor VII deficiency and acquired haemophilia.
2025-09-19 | Evaluation of Deficiency and Excessive Condition of Thrombin Burst Using Laboratory Tests.
Thrombin burst is an important mechanism for hemostasis, which is enhancement and amplification of the coagulation cycle, especially activation of coagulation factors XI, VIII, and V by thrombin on the activated platelets. Thrombin burst monitoring has been performed using hemostatic molecular markers, thrombin generation test (TGT), thromboelastography (TEG), and clot waveform analysis (CWA). In particular, CWA is a routine laboratory test that is neither time consuming nor expensive. Arterial thromboses, such as acute myocardial thrombosis and acute cerebral thrombosis, are associated with excessive condition of thrombin burst, and clotting time using a small amount of thrombin in CWA can detect activated or procoagulant platelets. Thrombin burst deficiency is caused by abnormalities of platelets such as thrombocytopenia or clotting factors such as hemophilia and acquired clotting factor deficiency, showing different CWA patterns. Patients with clotting factor VIII inhibitors are treated with bypass therapy, such as recombinant activated clotting factor VII and activated prothrombin complex concentrate, which can be monitored by CWA, TEG, or TGT.
2025-06-27 | Coagulation Factor VII Deficiency: A Review of the Clinical Implications and Approaches to Replacement Therapy and Prophylaxis.
Factor VII (FVII) deficiency is a rare bleeding disorder that can present as either inherited or acquired. Inherited FVII deficiency arise from mutations in the F7 gene, resulting in a highly heterogeneous and wide range of phenotypic expressions from asymptomatic individuals to those experiencing severe and life-threatening hemorrhagic episodes. Notably, the severity of symptoms is typically not correlated with plasma FVII levels. Diagnosis generally involves a combination of coagulation assays, including prothrombin time (PT), assessment of FVII activity and antigenic levels, and a thorough consideration of the patient's clinical context. Management of FVII deficiency requires personalized treatment strategies. For inherited forms, on-demand replacement therapy is commonly employed, utilizing recombinant activated FVII, plasma-derived FVII, prothrombin complex concentrates, or fresh frozen plasma during bleeding episodes, as well as for prophylactic measures. Long-term prophylaxis is particularly critical for patients with severe deficiencies who have a history of central nervous system or gastrointestinal bleeding, especially those at an elevated risk of subsequent major or potentially life-threatening bleeding events. This review evaluates current therapeutic approaches, highlights emerging challenges in the management of FVII deficiency, and underscores the importance of tailored treatment strategies aimed at optimizing patient outcomes.
small molecules
2025-11-03 | A 10-year retrospective review of the effectiveness and safety of tranexamic acid in women with inherited bleeding disorders in the peripartum setting
Abstract Background: PPH occurs at a rate of nearly 11% globally and is a major cause of maternal mortality worldwide (Carroli, 2008.) Women with inherited bleeding disorders such as hemophilia carriers and those with von Willebrand disease (VWD) are at a substantially greater risk of postpartum hemorrhage (PPH) (Abdul-Kadir, 2014.) TXA use for treatment of PPH has been shown to reduce major bleeding risk without increasing the risk of thromboembolism in patients (Li, 2017). However, the effects of its prophylactic use in patients with bleeding disorders has not been extensively described. The aim of this study was to investigate the effectiveness and safety of prophylactic TXA use in peripartum patients with inherited bleeding disorders. Methods: A retrospective chart review was conducted for all patients with an inherited bleeding disorder cared for by the Multidisciplinary Clinic for Women with Bleeding Disorders (MCWBD) at St. Michael's Hospital (SMH) between 2014 and 2024. We performed descriptive statistical analysis to summarize findings related to bleeding and thrombotic events in patients treated with TXA in the puerperium. Results: There were 296 total patients managed over the course of pregnancy to labour and delivery in the MCWBD over this 10 year time period. 205 had an inherited bleeding disorder (the remainder had an acquired disorder and were not included in the analysis). The median age of patients was 32 (range 18-42). 32% had von Willebrand's Disease, 17% platelet function disorder, 1% hemophilia A,10% symptomatic hemophilia A or B carrier, 18% Bleeding Disorder of Undetermined Cause and 14% rare single clotting factor deficiency. 61% of patients had vaginal delivery, 39% had a C-section. We had access to complete labour and delivery records for 144 patients to allow for reporting of bleeding events. 95% of patients received TXA at some point during delivery. 68% patients received TXA during and after delivery, 11% received TXA only during delivery and 16% received TXA only after delivery. 31% patients also received an additional hemostatic agent (17% received DDAVP, 15% received factor concentrate -VWF:FVIII, FXI, FVIII, rFVIIa and FIX). 17% of patients experienced postpartum hemorrhage (PPH) and of those 88% had primary PPH. 12% of patients with PPH did not use any TXA prophylactically. Two patients who received TXA experienced a thrombotic event post-partum (2/205, 0.98%). One patient with severe factor VII deficiency developed pulmonary embolism 14 days after delivery during which she was being treated with a tapering regimen of rFVIIa and TXA. She had 3 risk factors for VTE: morbid obesity, varicose veins and heterozygosity for factor V leiden mutation. The other patient developed a superficial venous thrombus 1 day after delivery, she had 2 risk factors for VTE: morbid obesity and varicose veins. Conclusions: This data suggests that TXA is associated with very low risk of thrombosis when used as prophylactic treatment for PPH among patients with inherited bleeding disorders in the puerperium. Under 1% of patients over 10 years experienced a thrombotic event and had two or more risk factors for VTE. In contrast, at least 17% had PPH despite provision of preventative peripartum hemostatic therapy that almost always included TXA. This suggests that on balance, TXA should be provided to patients with inherited bleeding disorders with the goal of PPH prevention but caution should be used in those with 2 or more risk factors for thrombosis. Prospective studies on the use of prophylactic TXA in this setting is warranted.
2024-10-14 | Severe acquired Factor VII deficiency complicating an aplastic anemia, successfully treated with corticosteroids.
Factor VII deficiency is a rare hemostatic disorder that can lead to severe clinical outcomes. Due to the scarcity of reported cases, treatment guidelines for this condition remain unclear. In this report, we present a case of acquired factor VII deficiency (aFVII) in an elderly female with medullary aplasia. The initial clinical manifestation was hemarthrosis, accompanied by a rapid increase in prothrombin time. Prompt intervention involved supplementation to address the deficiency. Subsequent laboratory testing failed to detect any specific factor VII inhibitor. Considering the patient's frailty, immunosuppressive therapy comprising only corticosteroids was administered. The potential triggering mechanisms may include recurrent episodes of sepsis or an underlying autoimmune condition. Further research is necessary to better understand the etiology and optimal management of aFVII deficiency.
2023-11-06 | Acquired Factor VII Deficiency Associated With Chronic Myeloid Leukemia Blast Crisis.
Factor VII (FVII) is an important, vitamin K-dependent clotting factor. Acquired FVII deficiency is a rare entity that is associated with serious bleeding complications. We report a case of acquired FVII deficiency in a patient with recurrent chronic myeloid leukemia in blast crisis who developed bilateral retinal hemorrhages. The coagulopathy was corrected with the initiation of chemotherapy and subsequent reduction in peripheral blast count.
2019-09-09 | Acute Myelogenous Leukemia With Trisomy 8 and Concomitant Acquired Factor VII Deficiency
Acquired isolated factor VII deficiency is a rare bleeding disorder and has been reported in 31 cases. This is in contrast to congenital factor VII deficiency, which while also infrequent is the most common rare congenital bleeding disorder. Acquired isolated factor VII deficiency has been described primarily in patients with solid malignancies, sepsis, and in the presence of anti-factor VII autoantibodies. We report a case of acute myelogenous leukemia with an associated trisomy 8 cytogenetic abnormality presenting with factor VII deficiency. The factor VII deficiency cleared after induction chemotherapy and with the disappearance of the cytogenetic and molecular abnormalities. We discuss a possible link between trisomy 8 and vitamin K metabolism, which might result in acquired factor VII deficiency in acute myelogenous leukemia.
2005-07-20 | Cyclosporine controls epidermolysis bullosa acquisita co‐occurring with acquired factor VIII deficiency
Abstract Background Epidermolysis bullosa acquisita (EBA) is a rare antibody‐mediated autoimmune blistering disease of adults. Likewise, acquired factor VIII deficiency is a rare antibody‐mediated disease of adulthood. Both diseases can be exceedingly difficult to treat and refractory to immunomodulatory therapies. Methods Herein, we report a challenging case of EBA and acquired factor VIII deficiency in the same patient. Results Cyclosporine 4 mg/kg/day rapidly controlled both disease processes after the patient failed to respond to prednisone, colchicine, and pulse cyclophosphamide. The EBA relapsed when the cyclosporine was decreased to 2 mg/kg/day and the patient wore snuggly fitting new shoes, but it cleared quickly when the dose was increased. Cyclosporine has since been decreased gradually to 1.5 mg/kg/day without relapse of either condition or detectable side‐effects. Conclusions Cyclosporine should be considered when EBA and/or acquired factor VIII deficiency fail to respond to conservative therapy. Both conditions usually respond rapidly to cyclosporine 4–6 mg/kg/day.
antibodies
2025-08-05 | PO27 | B-cell lymphoproliferative disorder and acquired coagulopathy: an insidious link
Background: Acquired coagulation factor inhibitors are autoantibodies that may develop in individuals with autoimmune or neoplastic disorders and should be assessed in patients without personal or familiar history of bleeding disorders. These inhibitors most commonly target factor VIII (FVIII) or von Willebrand factor (VWF), resulting in acquired haemophilia A or acquired von Willebrand disease, respectively and may occasionally interfere with the normal activity of other coagulation factors. Case Report: An 81-year-old female presented with recurrent episodes of anterior epistaxis and ecchymoses, without history of personal bleeding disorders. Laboratory testing revealed deficiencies in vitamin K–dependent factors (except for factor IX) in the absence of liver dysfunction or other known causes of coagulopathy, raising suspicion of an acquired haemorrhagic disorder. Past medical history included an indolent B-cell lymphoproliferative disorder, under haematological follow-up and arterial hypertension. Clinically, the patient exhibited persistent mucocutaneous bleeding associated with progressive anaemia and transient memory deficits. Due to suspected central nervous system involvement, an MRI was performed, revealing a small haemorrhagic area in the fornix of the limbic system. At the admission, coagulation studies confirmed markedly abnormal coagulation parameters: PT/INR 5.36 and aPTT 1.56. The mixing test showed suboptimal correction. The laboratory evaluation revealed: Factor IX 171%, Factor II 5%, Factor VII 17%, Factor X 7%, Protein S 51%, and Protein C 24%. Mixing studies for Factors II and VII demonstrated suboptimal correction, suggesting the presence of inhibitors. Lupus anticoagulant and antiphospholipid antibodies were negative. According to these results, we hypnotized the presence of a poly-specific serum para-protein interfering with clotting factors. Intravenous vitamin K (Konakion 10 mg) induced a not significant resolution of PT prolongation followed by a rebound increase to 4.66 and 5.27. PIVKA-II levels were 41 AU/mL (negative), supporting the lack of a functional vitamin K deficiency. Immunosuppressive steroid therapy with prednisone was started at the time of admission. Given the known lymphoproliferative disorder, the possibility of a neoplastic trigger for the coagulation abnormality was considered. Flow cytometry confirmed the presence of a B-cell clone expressing CD20, with a 2% blast count. After 15 days of steroid therapy without clinical improvement, a pharmacokinetic assessment was conducted following the administration of a 4-factor prothrombin complex concentrate (PCC). Factor levels were measured at baseline and several time points post-infusion (30 min, 1h, 2h, 4h, 12h, 24h). A marked decline in circulating coagulation factors was noted after 4 hours, with the greatest reduction observed for Factor II, suggesting preferential inhibitory activity against this factor, likely due to the presence of a neoplastic paraprotein. Therapy with rituximab (anti-CD20 monoclonal antibody) was then introduced at the standard dose of 375 mg/m² weekly for four weeks with complete normalisation of coagulation. Conclusions: This case highlights the diagnostic and therapeutic challenges posed by rare coagulation inhibitors. The successful use of rituximab underscores the relevance of B-cell–directed immunosuppression in managing such complex cases, particularly in the context of clonal B-cell disorders.
2022-03-14 | A low-dose rituximab regimen for first-line treatment of acquired haemophilia A.
A low-dose rituximab regimen for first-line treatment of acquired haemophilia A. Acquired haemophilia A (AHA) is a rare disease caused by the development of autoantibodies against FVIII. Diagnosis involves confirmation of FVIII deficiency and the presence of an inhibitor via the Bethesda assay. Severe bleeding is often managed with bypassing agents such as recombinant factor VII. This is then followed by eradication of the inhibitor with immunosuppression which typically includes a corticosteroid backbone. Review the current management and outcomes of AHA in Queensland, Australia. Determine the incidence, demographics and clinical characteristics of AHA patients. Retrospective case series of AHA diagnosed between May 2014 and August 2018. Data were derived from the Australian Bleeding Disorders Registry and state-wide pathology database. Data collection proforma was completed by the treating haematologist and reviewed/compiled centrally. 24 patients were identified (incidence 1 in 1.27 million). The median age was 76.5 years. Median follow-up was 20 months. Index bleed was atraumatic and skin/soft tissue in the majority of patients. Recombinant FVIIa was the most commonly used haemostatic therapy and effective in 85% of patients. Immunosuppression and steroid usage were uniform. Upfront second agent was used in 75% of patients and was most commonly rituximab. 87.5% of patients achieved a complete remission in a median time of 48 days. Low-dose rituximab was frequently used and equally as efficacious as standard dose. Immunosuppression with combination therapy, notably rituximab, appears to be non-inferior and has a favourable side effect profile.
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