acenocoumarol and Hemophilia-A

Acquired haemophilia A is a rare disorder caused by spontaneous formation of auto-antibodies (inhibitors) against coagulation factor VIII. This can lead tolife-threatening haemorrhages. Six to twenty-two percent of patients with acquired haemophilia have an underlying malignancy. We describe a 69-year-old woman with metastatic breast cancer and non-small cell lung carcinoma who presented at the emergency room with spontaneous bruising, and who was using a vitamin K antagonist. She had a prolonged activated partial thromboplastin time (aPTT) due to a coagulation factor VIII deficiency caused by factor VIII antibodies. She was treated with prednisone and cyclophosphamide.

Topics: Acenocoumarol; Aged; Anticoagulants; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Female; Hemophilia A; Humans; Lung Neoplasms

Essentials It is unknown if hemophilia patients with atrial fibrillation need anticoagulation. Endogenous thrombin potentials (ETP) in hemophilia patients and patients on coumarins were compared. Severe hemophilia patients had comparable ETP to therapeutic international normalized ratio (INR). In non-severe hemophilia, 33% had higher ETP than therapeutic INR and may need anticoagulation. Click to hear Dr Negrier's perspective on global assays for assessing coagulation SUMMARY: Background It is unknown whether patients with hemophilia A with atrial fibrillation require treatment with vitamin K antagonists (VKAs) to the same extent as the normal population. Objective To compare hemostatic potential in hemophilia patients and patients on VKAs using thrombin generation (TG). Methods In this cross-sectional study, TG, initiated with 1pM tissue factor, was measured in 133 patients with severe (FVIII < 1%, n = 15) and non-severe (FVIII 1-50%, n = 118) hemophilia A, 97 patients on a VKA with an international normalized ratio (INR) ≥ 1.5 and healthy controls. Endogenous thrombin potential (ETP) (nm*min) was compared according to FVIII level (< 1%, 1-19% and 20-50%) with healthy controls and patients with sub-therapeutic INR (1.5-1.9) and therapeutic INR (≥ 2.0). Medians and interquartile ranges (IQRs) were calculated. Results Compared with healthy controls (898 [IQR 803-1004]), both hemophilia patients and patients on VKAs had lower median ETPs at 304 (196-449) and 176 (100-250), respectively. ETP was quite similar in severe hemophilia patients (185 [116-307]) and patients with a therapeutic INR (156 [90-225]). Compared with patients with therapeutic INR, ETP in patients with FVIII 1-19% and patients with FVIII 20-50% was higher at 296 (203-430) and 397 (219-632), respectively. All patients with therapeutic INR had an ETP < 400. Considering this threshold, 93% of severe hemophilia patients, 70% of patients with FVIII 1-19% and 52% of patients with FVIII 20-50% had an ETP < 400. Conclusion In severe hemophilia patients, TG was comparable to that in patients with a therapeutic INR. In one-third of non-severe hemophilia patients, TG was higher. These results suggest that anticoagulation therapy should be considered in a substantial proportion of non-severe hemophilia patients.

Topics: Acenocoumarol; Adolescent; Adult; Aged; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Case-Control Studies; Cross-Sectional Studies; Drug Monitoring; Female; Hemophilia A; Hemostasis; Humans; International Normalized Ratio; Kinetics; Male; Middle Aged; Phenprocoumon; Severity of Illness Index; Thrombin; Vitamin K; Young Adult

Topics: Acenocoumarol; Aged; Anticoagulants; Drug Therapy, Combination; Factor VIII; Follow-Up Studies; Hemophilia A; Humans; Immunosuppressive Agents; Male

We report the case of a 26 year-old woman who developed acquired hemophilia secondary to factor VIII inhibitors, two months after a normal pregnancy. The initial hemorrhagic event was a spontaneous deep muscular hematoma mimicking a deep venous thrombosis. This observation was marqued by the apparition of antibodies against porcin factor VIII under treatment by porcin factor VIII. Intravenous immunoglobulin was ineffective, then cyclophosphamide was necessary to control the disease.

Topics: Acenocoumarol; Adult; Anticoagulants; Blood Coagulation Tests; Diagnosis, Differential; Factor VIII; Female; Hemophilia A; Heparin; Humans; Pregnancy; Puerperal Disorders; Recurrence

Topics: Acenocoumarol; Adult; Factor V; Factor V Deficiency; Female; Glycoproteins; Hemophilia A; Humans; Protein C; Vitamin K

A Normotest (NT)-Thrombotest (TT) discrepancy is claimed to reflect the presence of coumarin-induced inhibitors or intravascular coagulation, or both. The results of this study indicate, however, that a significant NT-TT discrepancy is also present in all plasmas from patients who have congenital coagulation disorders of the prothrombin complex. None of these patients had received an anticoagulant or showed any sign of intravascular clotting; nevertheless the discrepancy observed was similar to that found in plasmas of coumarin-treated patients: average values were 0.437 and 0.450, respectively. As no inhibitor was present in the congenital coagulation disorders, except in hemophilia BM, the phenomenon does not appear to be specific for coumarin plasma. This indicates that the NT/TT discrepancy is a non-specific phenomenon that does not seem to provide any additional information about coumarin-treated patients compared with that obtainable by means of a simple prothrombin time test.

Topics: Acenocoumarol; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Factor X Deficiency; Hemophilia A; Humans; Hypoprothrombinemias; Prothrombin Time