Use of recombinant factor VIIa (NovoSeven) in patients with Glanzmann thrombasthenia.

Recombinant factor VIIa (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark) appears effective and relatively safe for the treatment of bleeding and for surgical prophylaxis in patients with Glanzmann thrombasthenia as reported to the International Registry on rFVIIa and Congenital Platelet Disorders. One of the shortcomings of the Registry data is the heterogeneity of treatment protocol, including dosage, number of doses used, duration of treatment before declaration of failure, and mode of rFVIIa administration (bolus v continuous infusion). The data are not yet sufficient to define optimal regimens for various indications such as the type of bleeding or the type of procedures. The place of this drug compared to platelet transfusion in the overall management of patients with Glanzmann thrombasthenia will need to be determined in relationship to a number of challenges and unresolved issues in the clinical care of these patients. These issues include: how to improve local measures for patients with mucosal bleeds, optimal management of young women during menarche, optimal platelet transfusion regimens for various indications, the relationship between antiplatelet antibodies detected by monoclonal antibody-specific immobilization of platelet antigens (MAIPA) and effectiveness of platelet transfusion, whether there are other biological tests that may correlate with effectiveness of platelet transfusion, and management of pregnancy and delivery regarding antiplatelet immunization.

Pregnancy in essential thrombocythaemia: treatment and outcome of 17 pregnancies.

OBJECTIVE: To evaluate treatment and outcome of 17 pregnancies in nine patients with essential thrombocythaemia (ET) seen at our institution from 1988 to 1998. METHODS: Treatment and outcome of 17 pregnancies in nine ET patients were retrospectively analyzed. RESULTS: Seventeen pregnancies in nine patients with ET resulted in 11 (65%) live births and ended in six (35%) spontaneous abortions. Abortion could not be predicted from ET-associated complications before (p= 0.23) or during (p = 0.39) pregnancy. Maternal complications occurred during six pregnancies (35%): Three major bleedings in two patients with an acquired von Willebrand disease and two minor bleedings in patients treated with low-dose acetylsalicylic acid (ASA) were observed during pregnancy or at term; one patient suffered from transient visual loss while pausing low-dose ASA. Platelet counts prior to pregnancy were significantly higher as compared to the platelet nadir observed during pregnancy (p = 0.0017). Postpartum clinical course was uneventful in all patients. No specific treatment was given during 11 pregnancies. Six women received low-dose ASA during pregnancy followed by low-molecular-weight heparin until the end of the sixth week postpartum in five cases. This treatment was correlated with a favourable outcome (live birth versus abortion) when compared to no treatment (p=0.04). CONCLUSION: Pregnancy in ET can be complicated by first trimester abortion and/or maternal haemorrhage. Our limited observation suggest a positive impact of low-dose ASA during pregnancy followed by low-molecular-weight heparin postpartum on pregnancy outcome in ET; nevertheless, confirmation by prospective documentation is mandatory.

Acquired haemophilia: experiences with a standardized approach.

Acquired haemophilia is a rare, life-threatening, acquired bleeding diathesis. No general consensus exists on the best therapeutic approach. We report on the standardized approach at our institution evaluated in ten patients with acquired haemophilia. Factor VIII inhibitors were found in all patients, activities ranging from 1 to 648 Bethesda units (BU). Eight of the ten patients presented with severe bleeding. Two patients died during the acute phase, one from intracranial bleeding and one due to Mycoplasma pneumonia. One patient with mild bleeding was treated with immunosuppression alone. Two patients with factor VIII inhibitor activities below 5 BU were started on factor VIII concentrate therapy. Therapy was successful in one and was changed to recombinant human activated factor VII infusion (rFVIIa) in the other, owing to insufficient factor VIII recovery. Six patients with factor VIII inhibitor activities above 5 BU were started on activated prothrombin complex concentrate (APCC) therapy. APCC treatment was successful initially in all six patients and was changed to rFVIIa infusion in one for rebleeding. One patient did not receive any specific therapy. Immunosuppression with prednisolone (2 mg kg(-1)) was begun in nine patients and was continued with cyclophosphamide (2 mg kg(-1)) in six. A complete remission of the acquired haemophilia was found in seven of the eight patients surviving the acute phase, one had a partial remission. All patients with acquired haemophilia could be managed effectively following our standardized approach. Routine administration of immunosuppression was associated with high inhibitor elimination rates.

Proximal gastric motility functions are normal in severe obesity.

The role of altered gastric motor functions for the development of obesity is still unclear. In this study, we investigated whether severe obesity is related to gastric dysfunctions or to abnormal perception in response to distension. 31 obese patients and 20 healthy volunteers were studied using an electronic barostat. Basal gastric tone, gastric accommodation, and perception in response to distension were not altered in obese patients. The median minimal distending pressure, reflecting the intra-abdominal pressure, was significantly elevated in obese patients, being 12 versus 7 mm Hg, respectively (p < 0.0001). We conclude that the proximal gastric motility, including perception and accommodation in response to intragastric distension, is not impaired in severe obesity. Whether disturbances of gastric reflex relaxation in response to a meal are involved in the pathogenesis of obesity remains to be established.