RARE DISEASE
Acquired factor X deficiency
Acquired factor X deficiency
Acquired factor X deficiency
Synonyms: aFX
Synonyms: aFX
Synonyms: aFX
Drug discovery
2
drugs
With orphan designations
Overview
Acquired Factor X Deficiency is a rare coagulopathy caused by autoantibodies, adsorption of Factor X (e.g., amyloid fibrils in AL amyloidosis), or reduced synthesis (e.g., liver disease). It presents with bleeding ranging from mucosal hemorrhage to life-threatening intracranial or pulmonary bleeding. Diagnosis requires prolonged PT/aPTT corrected by mixing studies and low Factor X activity. Management combines factor replacement, immunosuppression, and treatment of underlying conditions (e.g., chemotherapy for amyloidosis). Prognosis varies, with spontaneous resolution reported in some cases [1][2][5][7].
Burden
High morbidity due to severe bleeding (20% with musculoskeletal bleeding; 26% with inhibitors) [1][7].
In amyloidosis, coexisting cardiac/renal dysfunction complicates treatment and increases mortality [2][9][17].
Requires frequent coagulation monitoring and factor replacement, with thrombotic risks in amyloidosis patients [2][8][10].
Therapies
Acute bleeding: Fresh frozen plasma, prothrombin complex concentrates (PCC), or high-purity Factor X concentrate (off-label) [2][8][13].
Immunosuppression: High-dose steroids, IV immunoglobulin, or rituximab for autoantibody-mediated cases [3][5][13].
Targeted therapy: Chemotherapy (e.g., bendamustine-rituximab for lymphoma) or stem cell transplantation for amyloidosis [3][9][17].
Categories: rare hematological diseases
Research Papers
41 drug discovery papers about Acquired factor X deficiency, with 1 next-in-class emerging drug candidate forecasted to outperform the average preclinical success rate. Recent publications:
41 drug discovery papers about Acquired factor X deficiency, with 1 next-in-class emerging drug candidate forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2025-03-29 | Acquired FX Deficiency in Multiple Myeloma Without Concomitant Amyloidosis- A Rare Case Report
This case report presents a rare occurrence of acquired Factor X (FX) deficiency in a patient with Multiple myeloma (MM) without concomitant amyloidosis. The patient, a 64-year-old male with prior diagnosis of Smoldering MM, presented with abdominal pain and chronic bloody diarrhea and was diagnosed with severe FX deficiency. Despite initial suspicion of amyloidosis, subsequent investigations ruled out its presence. Treatment with anti-myeloma therapy and supportive measures resulted in the normalization of coagulation parameters. This case underscores the importance of considering acquired FX deficiency in Plasma Cell Dyscrasia patients presenting with coagulopathy.
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.
2023-12-21 | Circulating Inhibitor against Factor X: A Rare Cause of Hemorrhagic Diathesis.
Acquired coagulopathies resulting from factor X deficiency are rare and typically associated with amyloidosis or plasma cell dyscrasia. Factor X plays a pivotal role in the coagulation cascade, converting prothrombin into thrombin and facilitating the formation of fibrinogen and thrombus. While its occurrence following common infections is extremely rare, isolated cases have been documented. We present a rare case of bleeding diathesis in a patient with community-acquired pneumonia, where prolonged activated partial thromboplastin time (aPTT) and prothrombin time (PT) led to the diagnosis of an infectious-triggered acquired circulating inhibitor targeting factor X. Prompt treatment with methylprednisolone effectively controlled the inhibitor without recurrence. This case report provides insights into the diagnostic strategies, differential algorithm, and therapeutic approaches for managing this rare coagulopathy.
2023-11-01 | Acquired factor X deficiency in a multiple myeloma without amyloidosis: a case report.
Multiple myeloma is one of the most common hematologic malignancies. Acquired factor X deficiencies are often observed in primary (AL) amyloidosis and rarely in multiple myeloma. We report a case of an acquired factor X deficiency in a patient with a newly diagnosed IgA lambda multiple myeloma, without any evidence of concomitant amyloidosis. We present the patient's medical history, clinical and physical examinations, laboratory analysis, and outcome. A 76-year-old male presented at the emergency department with ongoing gingival bleeding. Several analytical problems with blood sample analysis arose, which eventually led to the diagnosis of a multiple myeloma. Further exploration revealed an acquired factor X deficiency, explaining the ongoing bleeding. There was no evidence of concomitant amyloidosis. The multiple myeloma was treated, leading to complete remission of the malignancy and bleeding tendency. While coagulopathy is rarely observed in patients diagnosed with multiple myeloma, considering an acquired factor X deficiency becomes relevant when such patient present with bleeding diathesis.
2023-08-18 | Management of Acquired Factor X Deficiency Caused by In Vitro Non-neutralizing Anti-factor X Autoantibodies with Pre-emptive Corticosteroid Therapy.
Coagulation factor X (FX) deficiency causes severe hemorrhagic symptoms. We herein report a 90-year-old man with hemorrhagic symptoms and prolongation of prothrombin time (PT) and activated partial thromboplastin time (APTT). Cross-mixing tests showed a factor deficiency pattern, but administration of plasma products was not effective. Acquired coagulation factor deficiency was suspected, and immunosuppressive therapy was started. After the intervention, his hemorrhagic symptoms improved. A decrease in FX activity was later confirmed, and anti-FX autoantibody was retrospectively detected by an enzyme-linked immunosorbent assay. Immediate intervention is important for patients suspected of having acquired coagulation factor deficiency.
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.
2023-05-15 | Acquired Factor X Deficiency without Amyloidosis Presenting with Massive Hematuria: A Case Report and Review of the Literature
Acquired factor X deficiency is a rare diagnosis, especially without the association of other co-existing conditions such as amyloidosis. The authors report the case of a 34-year-old male with severe frank hematuria found to have markedly prolonged prothrombin time and activated partial thromboplastin time. A mixing study showed correction utilizing normal plasma and a coagulation panel testing revealed decreased factor X activity. The patient was treated with multiple blood transfusions, fresh frozen plasma, high-dose pulse steroids, and rituximab. The patient's condition improved during his 21-day hospital stay and was followed up every 2 weeks for 3 months. The patient's factor X level recovered after two weeks of discharge with no other hemorrhagic episodes.
2021-10-01 | Successful Treatment of Factor X Deficiency in a Patient with Lymphoplasmacytic Lymphoma with Bendamustine Plus Rituximab Regimen: A Case Report and Literature Review
Background: Acquired factor X deficiency is an uncommon condition, and affected individuals have severe and spontaneous bleeding. The associated conditions include malignancy, infection, burn, and inflammatory bowel disease. Many previous studies reported association between lymphoproliferative disease and factor X disappearance. Amyloid deposition causing factor X absorption was the most common mechanism. Here, we report a case of stage IV lymphoplasmacytic lymphoma (LPL) with factor X deficiency who was successfully treated with bendamustine plus rituximab (BR) regimen. Case Presentation: A 52-year-old Thai woman presented with heavy menorrhea, hoarseness, and widespread ecchymosis at her extremities. On physical examination, the patient had bilateral periorbital purpura and vocal cord hematoma. Coagulation testing showed prolonged prothrombin time (PT) and prolonged activated thromboplastin time (aPTT); however, after mixing with 1:1 normal pooled plasma, PT and aPTT were both corrected to normal levels. Factor assays demonstrated markedly decreased factor X levels, but no presence of factor X inhibitor. Bone marrow examination revealed numerous abnormal lymphoplasmacytoid lymphocytes with kappa light chain expression. Serum free light chain assay also showed kappa light chain restriction [kappa 716.16 mg/L, lambda 16.96 mg/L, ratio 42.23 (0.26– 1.65)]. The patient was diagnosed as lymphoplasmacytic lymphoma with factor X deficiency. She received chemotherapy with 6 cycles of bendamustine plus rituximab (BR) regimen. The patient responded favorably to treatment, she remains in lymphoma remission at one year after diagnosis, and her factor X level was more than 20%. Conclusion: We performed a literature review to identify previous case reports about lymphoma-associated factor X deficiency or inhibitor to determine a possible explanation in our patient. It is important to emphasize that when patients present with acquired factor deficiency, including factor X, lymphoproliferative disease is commonly one of the underlying conditions. Furthermore, the recovery of coagulation factor deficiency is possible if successful remission of lymphoma can be achieved. Keywords: factor X, lymphoproliferative disorder, lymphoplasmacytic lymphoma, amyloidosis
2021-05-14 | Response of factor X deficiency to darutumumab in the treatment of AL amyloidosis: a novel finding.
We report a case of progressive light-chain amyloidosis (otherwise known as AL amyloidosis) with acquired factor X (aFX) deficiency with a complete haematological response and rapid normalisation of FX levels following daratumumab monotherapy. To our knowledge, this is the first case report documenting successful treatment with daratumumab of aFX deficiency secondary to AL amyloidosis. The patient responded well to this therapy, with excellent symptomatic and quality of life improvements as well as a reduction in bleeding manifestations. This case highlights the value in considering daratumumab treatment when AL amyloidosis is complicated by FX deficiency.
2017-10-31 | [Acquired, non-amyloid related factor X deficiency: A first case associated with atypical chronic lymphocytic leukemia and literature review].
Acquired factor X deficiency is in most cases associated with AL amyloidosis. Acquired non-amyloid related factor X deficiency (DNAA-FX) has been exceptionally reported in the literature. We report the first case of acquired, non-amyloid related factor X deficiency associated with atypical chronic lymphoid leukemia in a 66-year-old patient with spontaneous hematomas. After therapeutic failure with polyclonal intravenous immunoglobulins, specific lymphoid malignancy treatment allowed symptoms and coagulation disorder resolution. DNAA-FX should be considered in case of bleeding events or coagulation disorders during low-grade hematological malignancies. Its occurrence can be considered as a treatment indication to prevent potentially fatal bleeding complications.
cell therapies
2024-11-05 | Clinical Characteristics and Treatment Outcomes of Patients with AL Amyloidosis with Acquired Factor X Deficiency
Background: Acquired factor X (aFX) deficiency is a rare but significant complication associated with AL Amyloidosis, potentially resulting from FX adsorption by amyloid fibrils. aFX increases the risk of hemorrhagic complications inherent to AL amyloidosis. We aimed to describe the clinical characteristics and outcomes of patients with aFX deficiency and AL amyloidosis evaluated at a tertiary amyloidosis center. Methods: We conducted a retrospective study of patients with FX deficiency evaluated at the Boston University Amyloidosis Center from 2000 to 2023, and collected data on demographics, clinical characteristics, treatments, and outcomes. FX deficiency was defined as a FX activity of ≤50% in absence of any anticoagulation therapy. All patients consented to the use of clinical data in research, and the study was approved by the Institutional Review Board in accordance with the Declaration of Helsinki. Results Among 1956 patients who had at least one FX measurement during the study period, 256 had ≤ 50% FX activity. Of these, 132 patients were excluded due to concomitant anticoagulation therapy and 36 due to incomplete medication history. Thus, 88 patients with FX deficiency were included in this study. 66 (75%) patients were male with a median age of 59 years (range, 36-85) and 18 (21%) self-identified as a non-white race. The most common clinical manifestations were ecchymoses 35%, periorbital ecchymoses 15%, and gastrointestinal bleeding 15%. The median FX activity was 39.5% (range, 5-50%). Seventy-seven patients had AL amyloidosis alone, 10 patients had multiple myeloma associated with AL amyloidosis, and 1 patient had Waldenstrom's macroglobulinemia-associated AL amyloidosis. The light-chain isotype was lambda in 70 (80%) patients. Patients were categorized as having mild (41-50%, n=41), moderate (21-40%, n=33), and severe (≤20%, n=15) FX deficiency. 72 patients (82%) had > 2 organ involvement including renal (n=69, 79%), cardiac (n=64, 73%), nervous system(n=46, 52%), and liver (n=30, 34%). Renal and liver involvement were more frequent in patients with moderate and severe FX deficiency. Longitudinal FX activity levels were available post-initial therapy for thirty patients. First-line treatment regimens included high-dose melphalan followed by autologous stem cell transplantation (HDM/SCT, n=11); cyclophosphamide, bortezomib, and dexamethasone (CyBorD, n=10); daratumumab, cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD, n=4); and others (n=5). Out of eleven patients who underwent the HDM/SCT group, 3 patients had grade 3, and 2 patients had grade 1 bleeding complications within the first month of treatment. Overall, FX activity improved to >50% in 73% (n=22/30) patients, and the median overall survival was 73 months (range, 6-172). Twenty-eight patients were evaluable for hematologic response, with a complete response (hemCR) achieved in 10 (36%) patients at 12 months post-treatment, resulting in a median FX improvement of 42% (range, -15 to 112). In contrast, 18 (64%) patients did not achieve a hemCR and had a median FX improvement of 14% (range, -10 to 64). FX activity increased by a median of 28% at 12 months after HDM/SCT compared to 14% after non-SCT treatment regimens. Conclusion: In AL amyloidosis, aFX deficiency is rare and typically associated with multiple organ involvement. FX levels improve with treatment in most patients and correlate with the depth of hematologic response. HDM/SCT is associated with the highest rates of FX improvement but also a higher risk of hemorrhagic complications during treatment. Further studies are needed to clarify the relationship between Factor X improvement and different treatment regimens.
2018-07-26 | The Long-term Outcomes after VAD plus SCT Therapy in a Patient with AL Amyloidosis and Severe Factor X Deficiency.
A 55-year-old man was admitted to our institute to undergo evaluation for proteinuria (5.4 g/day) with lambda-type Bence-Jones protein (BJP). Primary amyloid light chain (AL) amyloidosis and acquired factor X deficiency were diagnosed. High-dose melphalan combined with autologous stem cell transplantation was performed. After three years, the patient's proteinuria normalized, he was negative for urinary BJP, and his factor X activity improved to 105%. Serial renal biopsy showed no progression of amyloid deposition at a biopsy after 5 years, but showed a slight increase in the amyloid deposition after 11 years. This therapy can improve the prognosis of AL amyloidosis; however, there are limitations to the strategy.
2015-07-25 | Autologous stem cell transplantation in immunoglobulin light chain amyloidosis with factor X deficiency
Acquired factor X deficiency and associated haemorrhage can be consequences of immunoglobulin light chain amyloidosis. There are limited data on the safety and efficacy of autologous stem cell transplant (ASCT) on factor X deficiency. We retrospectively reviewed immunoglobulin light chain amyloidosis patients with factor X levels below 50%, not on chronic anticoagulation who underwent ASCT at the Mayo Clinic, Rochester, Minnesota, USA, between April 1995 and December 2011. Twenty-seven of 358 patients (7.5%) met study criteria. Median pre-ASCT factor X was 36% (range: 2-49%). The most frequent and severe bleeding complications occurred in patients with factor X levels below 10%. Peri-procedural prophylaxis included activated recombinant factor VII, fresh frozen plasma and platelet transfusions. Steady-state post-ASCT factor X levels were determined in 12 patients. Post-ASCT factor X levels increased in 100% of patients, with median factor X improvement of +32% (range: +8 to +92%). About 46.2% of patients were no longer factor X deficient after ASCT. The degree of improvement in factor X levels was correlated with an improvement in markers of renal involvement by amyloid. Improvement in factor X correlated with an improvement in the degree of total serum protein (ρ = 0.54; P = 0.04) and proteinuria (ρ = -0.54; P = 0.04). Our findings support the decision to offer ASCT to factor X-deficient patients as both appropriate and efficacious.
proteins
2025-02-21 | Factor X Concentrate Treatment Schedule and Dosing in Acquired FX Deficiency
This case report adds valuable insight into the management of this rare condition, and how best to utilize FX concentrates in acquired FX deficiency.
small molecules
2025-03-29 | Acquired FX Deficiency in Multiple Myeloma Without Concomitant Amyloidosis- A Rare Case Report
This case report presents a rare occurrence of acquired Factor X (FX) deficiency in a patient with Multiple myeloma (MM) without concomitant amyloidosis. The patient, a 64-year-old male with prior diagnosis of Smoldering MM, presented with abdominal pain and chronic bloody diarrhea and was diagnosed with severe FX deficiency. Despite initial suspicion of amyloidosis, subsequent investigations ruled out its presence. Treatment with anti-myeloma therapy and supportive measures resulted in the normalization of coagulation parameters. This case underscores the importance of considering acquired FX deficiency in Plasma Cell Dyscrasia patients presenting with coagulopathy.
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.
2023-12-21 | Circulating Inhibitor against Factor X: A Rare Cause of Hemorrhagic Diathesis.
Acquired coagulopathies resulting from factor X deficiency are rare and typically associated with amyloidosis or plasma cell dyscrasia. Factor X plays a pivotal role in the coagulation cascade, converting prothrombin into thrombin and facilitating the formation of fibrinogen and thrombus. While its occurrence following common infections is extremely rare, isolated cases have been documented. We present a rare case of bleeding diathesis in a patient with community-acquired pneumonia, where prolonged activated partial thromboplastin time (aPTT) and prothrombin time (PT) led to the diagnosis of an infectious-triggered acquired circulating inhibitor targeting factor X. Prompt treatment with methylprednisolone effectively controlled the inhibitor without recurrence. This case report provides insights into the diagnostic strategies, differential algorithm, and therapeutic approaches for managing this rare coagulopathy.
2023-11-01 | Acquired factor X deficiency in a multiple myeloma without amyloidosis: a case report.
Multiple myeloma is one of the most common hematologic malignancies. Acquired factor X deficiencies are often observed in primary (AL) amyloidosis and rarely in multiple myeloma. We report a case of an acquired factor X deficiency in a patient with a newly diagnosed IgA lambda multiple myeloma, without any evidence of concomitant amyloidosis. We present the patient's medical history, clinical and physical examinations, laboratory analysis, and outcome. A 76-year-old male presented at the emergency department with ongoing gingival bleeding. Several analytical problems with blood sample analysis arose, which eventually led to the diagnosis of a multiple myeloma. Further exploration revealed an acquired factor X deficiency, explaining the ongoing bleeding. There was no evidence of concomitant amyloidosis. The multiple myeloma was treated, leading to complete remission of the malignancy and bleeding tendency. While coagulopathy is rarely observed in patients diagnosed with multiple myeloma, considering an acquired factor X deficiency becomes relevant when such patient present with bleeding diathesis.
2023-08-18 | Management of Acquired Factor X Deficiency Caused by In Vitro Non-neutralizing Anti-factor X Autoantibodies with Pre-emptive Corticosteroid Therapy.
Coagulation factor X (FX) deficiency causes severe hemorrhagic symptoms. We herein report a 90-year-old man with hemorrhagic symptoms and prolongation of prothrombin time (PT) and activated partial thromboplastin time (APTT). Cross-mixing tests showed a factor deficiency pattern, but administration of plasma products was not effective. Acquired coagulation factor deficiency was suspected, and immunosuppressive therapy was started. After the intervention, his hemorrhagic symptoms improved. A decrease in FX activity was later confirmed, and anti-FX autoantibody was retrospectively detected by an enzyme-linked immunosorbent assay. Immediate intervention is important for patients suspected of having acquired coagulation factor deficiency.
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.
2023-05-15 | Acquired Factor X Deficiency without Amyloidosis Presenting with Massive Hematuria: A Case Report and Review of the Literature
Acquired factor X deficiency is a rare diagnosis, especially without the association of other co-existing conditions such as amyloidosis. The authors report the case of a 34-year-old male with severe frank hematuria found to have markedly prolonged prothrombin time and activated partial thromboplastin time. A mixing study showed correction utilizing normal plasma and a coagulation panel testing revealed decreased factor X activity. The patient was treated with multiple blood transfusions, fresh frozen plasma, high-dose pulse steroids, and rituximab. The patient's condition improved during his 21-day hospital stay and was followed up every 2 weeks for 3 months. The patient's factor X level recovered after two weeks of discharge with no other hemorrhagic episodes.
2021-10-01 | Successful Treatment of Factor X Deficiency in a Patient with Lymphoplasmacytic Lymphoma with Bendamustine Plus Rituximab Regimen: A Case Report and Literature Review
Background: Acquired factor X deficiency is an uncommon condition, and affected individuals have severe and spontaneous bleeding. The associated conditions include malignancy, infection, burn, and inflammatory bowel disease. Many previous studies reported association between lymphoproliferative disease and factor X disappearance. Amyloid deposition causing factor X absorption was the most common mechanism. Here, we report a case of stage IV lymphoplasmacytic lymphoma (LPL) with factor X deficiency who was successfully treated with bendamustine plus rituximab (BR) regimen. Case Presentation: A 52-year-old Thai woman presented with heavy menorrhea, hoarseness, and widespread ecchymosis at her extremities. On physical examination, the patient had bilateral periorbital purpura and vocal cord hematoma. Coagulation testing showed prolonged prothrombin time (PT) and prolonged activated thromboplastin time (aPTT); however, after mixing with 1:1 normal pooled plasma, PT and aPTT were both corrected to normal levels. Factor assays demonstrated markedly decreased factor X levels, but no presence of factor X inhibitor. Bone marrow examination revealed numerous abnormal lymphoplasmacytoid lymphocytes with kappa light chain expression. Serum free light chain assay also showed kappa light chain restriction [kappa 716.16 mg/L, lambda 16.96 mg/L, ratio 42.23 (0.26– 1.65)]. The patient was diagnosed as lymphoplasmacytic lymphoma with factor X deficiency. She received chemotherapy with 6 cycles of bendamustine plus rituximab (BR) regimen. The patient responded favorably to treatment, she remains in lymphoma remission at one year after diagnosis, and her factor X level was more than 20%. Conclusion: We performed a literature review to identify previous case reports about lymphoma-associated factor X deficiency or inhibitor to determine a possible explanation in our patient. It is important to emphasize that when patients present with acquired factor deficiency, including factor X, lymphoproliferative disease is commonly one of the underlying conditions. Furthermore, the recovery of coagulation factor deficiency is possible if successful remission of lymphoma can be achieved. Keywords: factor X, lymphoproliferative disorder, lymphoplasmacytic lymphoma, amyloidosis
2021-05-14 | Response of factor X deficiency to darutumumab in the treatment of AL amyloidosis: a novel finding.
We report a case of progressive light-chain amyloidosis (otherwise known as AL amyloidosis) with acquired factor X (aFX) deficiency with a complete haematological response and rapid normalisation of FX levels following daratumumab monotherapy. To our knowledge, this is the first case report documenting successful treatment with daratumumab of aFX deficiency secondary to AL amyloidosis. The patient responded well to this therapy, with excellent symptomatic and quality of life improvements as well as a reduction in bleeding manifestations. This case highlights the value in considering daratumumab treatment when AL amyloidosis is complicated by FX deficiency.
2017-10-31 | [Acquired, non-amyloid related factor X deficiency: A first case associated with atypical chronic lymphocytic leukemia and literature review].
Acquired factor X deficiency is in most cases associated with AL amyloidosis. Acquired non-amyloid related factor X deficiency (DNAA-FX) has been exceptionally reported in the literature. We report the first case of acquired, non-amyloid related factor X deficiency associated with atypical chronic lymphoid leukemia in a 66-year-old patient with spontaneous hematomas. After therapeutic failure with polyclonal intravenous immunoglobulins, specific lymphoid malignancy treatment allowed symptoms and coagulation disorder resolution. DNAA-FX should be considered in case of bleeding events or coagulation disorders during low-grade hematological malignancies. Its occurrence can be considered as a treatment indication to prevent potentially fatal bleeding complications.
cell therapies
2024-11-05 | Clinical Characteristics and Treatment Outcomes of Patients with AL Amyloidosis with Acquired Factor X Deficiency
Background: Acquired factor X (aFX) deficiency is a rare but significant complication associated with AL Amyloidosis, potentially resulting from FX adsorption by amyloid fibrils. aFX increases the risk of hemorrhagic complications inherent to AL amyloidosis. We aimed to describe the clinical characteristics and outcomes of patients with aFX deficiency and AL amyloidosis evaluated at a tertiary amyloidosis center. Methods: We conducted a retrospective study of patients with FX deficiency evaluated at the Boston University Amyloidosis Center from 2000 to 2023, and collected data on demographics, clinical characteristics, treatments, and outcomes. FX deficiency was defined as a FX activity of ≤50% in absence of any anticoagulation therapy. All patients consented to the use of clinical data in research, and the study was approved by the Institutional Review Board in accordance with the Declaration of Helsinki. Results Among 1956 patients who had at least one FX measurement during the study period, 256 had ≤ 50% FX activity. Of these, 132 patients were excluded due to concomitant anticoagulation therapy and 36 due to incomplete medication history. Thus, 88 patients with FX deficiency were included in this study. 66 (75%) patients were male with a median age of 59 years (range, 36-85) and 18 (21%) self-identified as a non-white race. The most common clinical manifestations were ecchymoses 35%, periorbital ecchymoses 15%, and gastrointestinal bleeding 15%. The median FX activity was 39.5% (range, 5-50%). Seventy-seven patients had AL amyloidosis alone, 10 patients had multiple myeloma associated with AL amyloidosis, and 1 patient had Waldenstrom's macroglobulinemia-associated AL amyloidosis. The light-chain isotype was lambda in 70 (80%) patients. Patients were categorized as having mild (41-50%, n=41), moderate (21-40%, n=33), and severe (≤20%, n=15) FX deficiency. 72 patients (82%) had > 2 organ involvement including renal (n=69, 79%), cardiac (n=64, 73%), nervous system(n=46, 52%), and liver (n=30, 34%). Renal and liver involvement were more frequent in patients with moderate and severe FX deficiency. Longitudinal FX activity levels were available post-initial therapy for thirty patients. First-line treatment regimens included high-dose melphalan followed by autologous stem cell transplantation (HDM/SCT, n=11); cyclophosphamide, bortezomib, and dexamethasone (CyBorD, n=10); daratumumab, cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD, n=4); and others (n=5). Out of eleven patients who underwent the HDM/SCT group, 3 patients had grade 3, and 2 patients had grade 1 bleeding complications within the first month of treatment. Overall, FX activity improved to >50% in 73% (n=22/30) patients, and the median overall survival was 73 months (range, 6-172). Twenty-eight patients were evaluable for hematologic response, with a complete response (hemCR) achieved in 10 (36%) patients at 12 months post-treatment, resulting in a median FX improvement of 42% (range, -15 to 112). In contrast, 18 (64%) patients did not achieve a hemCR and had a median FX improvement of 14% (range, -10 to 64). FX activity increased by a median of 28% at 12 months after HDM/SCT compared to 14% after non-SCT treatment regimens. Conclusion: In AL amyloidosis, aFX deficiency is rare and typically associated with multiple organ involvement. FX levels improve with treatment in most patients and correlate with the depth of hematologic response. HDM/SCT is associated with the highest rates of FX improvement but also a higher risk of hemorrhagic complications during treatment. Further studies are needed to clarify the relationship between Factor X improvement and different treatment regimens.
2018-07-26 | The Long-term Outcomes after VAD plus SCT Therapy in a Patient with AL Amyloidosis and Severe Factor X Deficiency.
A 55-year-old man was admitted to our institute to undergo evaluation for proteinuria (5.4 g/day) with lambda-type Bence-Jones protein (BJP). Primary amyloid light chain (AL) amyloidosis and acquired factor X deficiency were diagnosed. High-dose melphalan combined with autologous stem cell transplantation was performed. After three years, the patient's proteinuria normalized, he was negative for urinary BJP, and his factor X activity improved to 105%. Serial renal biopsy showed no progression of amyloid deposition at a biopsy after 5 years, but showed a slight increase in the amyloid deposition after 11 years. This therapy can improve the prognosis of AL amyloidosis; however, there are limitations to the strategy.
2015-07-25 | Autologous stem cell transplantation in immunoglobulin light chain amyloidosis with factor X deficiency
Acquired factor X deficiency and associated haemorrhage can be consequences of immunoglobulin light chain amyloidosis. There are limited data on the safety and efficacy of autologous stem cell transplant (ASCT) on factor X deficiency. We retrospectively reviewed immunoglobulin light chain amyloidosis patients with factor X levels below 50%, not on chronic anticoagulation who underwent ASCT at the Mayo Clinic, Rochester, Minnesota, USA, between April 1995 and December 2011. Twenty-seven of 358 patients (7.5%) met study criteria. Median pre-ASCT factor X was 36% (range: 2-49%). The most frequent and severe bleeding complications occurred in patients with factor X levels below 10%. Peri-procedural prophylaxis included activated recombinant factor VII, fresh frozen plasma and platelet transfusions. Steady-state post-ASCT factor X levels were determined in 12 patients. Post-ASCT factor X levels increased in 100% of patients, with median factor X improvement of +32% (range: +8 to +92%). About 46.2% of patients were no longer factor X deficient after ASCT. The degree of improvement in factor X levels was correlated with an improvement in markers of renal involvement by amyloid. Improvement in factor X correlated with an improvement in the degree of total serum protein (ρ = 0.54; P = 0.04) and proteinuria (ρ = -0.54; P = 0.04). Our findings support the decision to offer ASCT to factor X-deficient patients as both appropriate and efficacious.
proteins
2025-02-21 | Factor X Concentrate Treatment Schedule and Dosing in Acquired FX Deficiency
This case report adds valuable insight into the management of this rare condition, and how best to utilize FX concentrates in acquired FX deficiency.
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Drug Discovery Landscape
2 orphan drug designations for Acquired factor X deficiency.
2 orphan drug designations for Acquired factor X deficiency.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
Human coagulation factor X | proteins | EMA | Kedrion S.p.A. | |
Coagulation Factor X Human | proteins | FDA | Bio Products Laboratory Limited |
“Terminated” – programs with discontinued clinical trials, or with no updates reported for 5 years after completion or 12 years after the last trial started.
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