Warfarin Anticoagulation and Fetal Central Nervous System Abnormalities: a Case Report.

BACKGROUND: Anticoagulation of pregnant woman with mechanical prosthetic heart valves is associated with significant maternal and fetal risks. METHODS: We describe a case of dorsal midline dysplasia in a fetus at 11 weeks' gestation. The mother was receiving warfarin therapy at a dose of 7.5 mg daily following a mechanical mitral valve replacement for rheumatic heart disease. RESULTS: Histological assessment revealed a meningocele with hemorrhage. No cerebellar or cerebral tissue was present in the skull confirming anencephaly. CONCLUSIONS: A multidisciplinary approach in pregnant women with mechanical prosthetic heart valves is essential in order to improve fetal outcomes.

Conservative Management of Overanticoagulation in Patients With Low-Moderate Risk for Bleeding Complications.

Despite long-standing experience with warfarin, anticoagulation clinic services are often confronted with the challenging clinical situation of patients with overanticoagulation. This requires repeat international normalized ratio (INR) monitoring and in some cases administration of vitamin K to minimize the risk of bleeding. A study was performed to determine the safety and efficacy of outpatient management in order to provide guidance on the management of patients with prolonged INRs. Patients on stable warfarin therapy for more than 1 month attending a dedicated academic hospital anticoagulation clinic who had an INR ≥5 were identified over a 1-year period. Follow-up INR results and outcomes were recorded for 30 days. One hundred and ninety-five episodes of overanticoagulation in 148 patients were identified. Patients were classified as low risk (n = 85, 57.4%) and moderate risk of bleeding (n = 63, 42.6%). The mean index INR was 7.22 (1.88). Management with low-dose oral vitamin K (n = 32, 16.4%) did not significantly result in a more rapid correction of the INR when compared to conservative management (n = 163, 83.6%; P = .103). Follow-up INR testing was performed at a mean of 11.1 (8.9) days from the index measurement. A mean of 1.6 (0.9) follow-up INR tests were performed per episode. During the 30-day follow-up, there was 1 (0.5%) episode of major bleeding and 1 (0.5%) death. The management of asymptomatic outpatients with overanticoagulation is associated with a low risk of major bleeding within 30 days. Conservative management of overanticoagulation is as effective as utilizing low-dose oral vitamin K.

Predictors of warfarin dose requirements in South African patients attending an anticoagulation clinic.

INTRODUCTION: Warfarin is the most common oral anticoagulant for the treatment and prevention of thromboembolic disease. However, it has a wide interpatient variability in dose requirements due to various genetic and clinical factors. MATERIALS AND METHODS: This study investigated the effect of clinical and genetic factors on the variability of warfarin dose requirements in 147 South African patients (81 white and 66 black). The study was performed at a University Hospital Anticoagulation Clinic managed by nursing sisters at the Charlotte Maxeke Johannesburg Academic Hospital. RESULTS: The most common indication for anticoagulation was atrial fibrillation (n = 55, 37.4%). The mean warfarin dose was significantly higher in black patients as compared to white patients (5.4 ± 2.9 mg/day and 3.8 ± 2.1 mg/day, respectively; P < 0.001). Older age was significantly associated with a lower maintenance warfarin dose (P < 0.001). Drugs which decreased the international normalized ratio (INR) were significantly associated with a higher maintenance warfarin dose of 6.4 ± 3.4 mg/day (P < 0.034). In contrast, there was no significant difference in warfarin dosage requirements in the presence of CYP2C9 and VKORC1 variant alleles (P > 0.05). Patients, however, homozygous for CYP2C9 *1,*3, and VKORC1 required less than 5 mg/day of warfarin to maintain the INR within the therapeutic range. CONCLUSION: In conclusion, this study indicates that clinical characteristics including; age, ethnic group, and drugs which decrease the INR might help to predict better dose requirements in this population group and thereby reduce the risk of bleeding and thrombotic complications.