We designed a double-blind trial to study the effect of an "activated" prothrombin-complex concentrate (FEIBA) on joint and muscle bleeding in hemophiliacs with antibodies to factor VIII. Fifteen patients received either FEIBA or the control preparation (a nonactivated prothrombin-complex concentrate) for a total of 150 bleeding episodes (four mucocutaneous bleeding, 117 joint bleeding, and 29 muscle bleeding). In 64 per cent of the episodes, FEIBA was judged by the physician to be effective; the control preparation was perceived as effective in 52 per cent of the episodes in which it was used. Pairwise comparison of FEIBA and the control preparation for bleeding in the same joint or muscle showed a significantly better result with FEIBA (P = 0.0085). Joint mobility after the use of FEIBA was significantly improved (P = 0.006). There was a high incidence of hepatitis (three of the 15 patients) and of transient disturbances of liver function (nine of 15) during the 15-month observation period.

SummaryIn the present study, uremic patients on chronic maintenance hemodialysis were treated with recombinant erythropoietin. Before and after 20 weeks of treatment, platelet adhesion and aggregation were studied with perfusions over a sprayed collagen surface and over matrix of cultured endothelial cells with high tissue factor activity. The influence of the erythropoietin induced raise in hematocrit on platelet transport and adhesion was excluded by performing the perfusions at a standard red blood cell concentration. The present study clearly demonstrates that erythropoietin treatment improves platelet adhesion and aggregation in addition to and independent of its effect on the hematocrit.Studies with control platelets resuspended in plasma of untreated patients showed that a uremic plasma factor reduced adhesion and thrombin- and collagen-dependent aggregation. Patient platelets resuspended in control plasma showed no defects. After erythropoietin treatment, the plasma-induced inhibition of adhesion and aggregation had almost completely disappeared from patient plasma.The beneficial effect of the erythropoietin treatment on uremic hemostasis is therefore twofold. The increase of the red blood cell mass improves transport of platelets, and thus adhesion to the vessel wall. The intrinsic defect due to the presence of an inhibitory toxin in uremic plasma is, in large part, corrected. Improved neutralization of uremic toxins by red blood cells or less production of toxins by better oxygenated tissue might play a role in the observed phenomena.

SummaryEndothelial cells and their extracellular matrix formed in vitro are often used as a model for subendothelium in studies on platelet-vessel wall interaction. We have characterized the influence of culture conditions of endothelial cells on the formation of extracellular matrix and on the interaction of the matrix with platelets. Passage number, time of confluence, serum concentration and the addition of heparin, growth factors and antibiotics to the culture medium were varied and the extracellular matrices were isolated. The amount of fibronectin and von Willebrand factor present in the matrix were measured and the number of platelets adhering to these matrices after perfusion with citrated whole blood at a shear rate of 1000 s-l was determined. A three times increase of the amount of von Willebrand factor in the matrix was found when the serum concentration was increased from 2.5% to 30%. When the passage number of the cells was increased or the period during which the cells were at confluence was extended, the amount of von Willebrand factor in the matrix was decreased up to 50%. Addition of heparin or ECGS (endothelial cell growth supplement) decreased the von Willebrand factor content in the matrix. Addition of penicillin or streptomycin to the culture medium had no influence on the amount of von Willebrand factor deposited in the matrix or secreted into the medium, however, other antibiotics such as gentamycin and neomycin decrease the amount of von Willebrand factor in the matrix. No influence on the amount of fibronectin in the matrix was found under all conditions tested.There was a strong correlation between the amount of von Willebrand factor in the matrix and the number of platelets adhering to the matrix. A decrease or increase of the amount of von Willebrand factor was always correlated with a decrease or increase of the number of platelets adhering to the matrix. These results indicate that the synthesis and deposition of von Willebrand factor in the extracellular matrix by cultured endothelial cells is very sensitive to variations in culture conditions and that the amount of von Willebrand factor in the matrix predominantly determines the reactivity of the matrix for platelets.

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SummaryIn a randomized clinical trial the effect of subcutaneous heparin alone or in combination with dihydroergotamine or sulphinpyrazone in preventing postoperative deep vein thrombosis (DVT) was studied. Sodium heparin (5000 IU) was administered subcutaneously twice daily; dihydroergotamine (1/2 mg) was also administered subcutaneously twice daily, and sulphinpyrazone (400 mg) was administered orally or intravenously twice daily. Administration occurred for at least 7 days. The diagnosis DVT was made with the radiofibrinogen uptake test. 358 patients undergoing major elective abdominal surgery were allocated to three treatment groups: heparin alone (Hep), heparin + dihydroergotamine (DHE-Hep) and heparin + sulphinpyrazone (Sulph-Hep). The frequency of DVT was 14/114 in Hep, 10/115 in DHE-Hep and 20/114 in Sulph-Hep. These differences were not significant. After application of the “logistic regression” procedure of Cox (1) it turned out that the major risk factors for developing DVT were age, sex, weight, type of operation and presence of diabetes mellitus. Also a significant treatment influence was observed (p = 0.001). This treatment effect was most probably due to improvement in the DHE-Hep group.The results in the Sulph-Hep group were not significantly different from those in the Hep group. A risk index was formulated on the basis of the above mentioned risk factors by which the chance of occurrence of DVT during heparin prophylaxis in an individual patient could be predicted. Patients that should receive additional prophylactic treatment can be defined by using this risk index.