The inactivation of factor VIII in vitro

When normal citrated plasma is stored at 37° C and pH 7.8 the factor VIII activity drops to about 50% of its initial value during the first 8-12 h. In the following 4 days practically no further drop in activity is found. If the logarithm of the factor VIII activity is plotted against time a curve is obtained which can be described as biphasic. To explore the underlying mechanism of this phenomenon the influence of temperature, pH, Ca++ concentration and some other clotting factors was investigated. Between temperatures of 21° C and 45° C the inactivation of factor VIII was biphasic, the decrease of factor VIII being faster in both phases at higher temperatures. The inactivation at these temperatures showed a Q10 of about 2. At 52° C nearly all factor VIII activity disappeared within 8 h. Possibly the precipitation of fibrinogen at this temperature is of influence. Between pH 6.4 and 8.5 the decrease in factor VIII in the first phase was obviously slower at lower pH and the level of the second phase maintained at a higher factor VIII activity. No alteration of the normal inactivation pattern was seen in plasma from patients with congenital deficiencies of factors XII, IX or V or in normal plasma adsorbed with BaS04 which has factors II, VII, IX and X markedly decreased, nor was there any difference between platelet rich and platelet poor plasma. Low calcium concentrations (Resinplasma) markedly increased the rate of inactivation in the first phase, but did not influence the second phase. Four hypotheses are given to explain the biphasic inactivation of factor VIII: a) The presence of an inactivating substance in the first phase or a stabilizing factor in the second phase of factor VIII inactivation. b) The existence of two independent substances with factor VIII activity with different inactivation rates. c) Reversible denaturation of factor VIII in one or more steps. d) Factor VIII exists in plasma in two interdependent molecular forms. It is discussed that in view of the results of the experiments hypotheses a and b are not very likely. At present we cannot differentiate experimentally between c and d

Different properties of factor VIII in Von Willebrand's disease with respect to recovery in cryoprecipitate

The recovery of factor VIII-activity in cryoprecipitate prepared from plasma from six patients with von Willebrand’s disease was low as compared to the recovery from normal and hemophilia-A plasma. The possible cause is briefly discussed

Management of aplastic anemia in a woman during pregnancy: A case report

Introduction. Aplastic anemia is a rare disease caused by destruction of pluripotent stem cells in bone marrow. During pregnancy it could be life-threatening for both mother and child. The only causal therapy for aplastic anemia is bone marrow transplantation, which is contraindicated during pregnancy because of potential embryo toxicity. Treatment options are erythrocytes and platelet transfusions and immunosuppressive therapy. There is, however, no agreement about the optimal supportive care and treatment regime for this disorder during pregnancy. Case Presentation. A 26-year-old nulliparous Asian woman with an uneventful medical history was admitted to the hospital at 14 weeks' gestation because of excessive vomiting. Routine laboratory tests showed pancytopenia (Hb 3.5 mmol/L, leukocytes 3.5 *109/L, platelets 45 *109L). A bone marrow biopsy confirmed aplastic anemia. Methylprednisolon, cyclosporine A, packed cells and platelet transfusions were initiated. At 33 weeks she developed neutropenia (0.1 *109/L) for which oral colistin and tobramycin were given prophylactically. At 35 weeks labor was induced, during which she developed a fever of 38.2°C. She gave birth spontaneously to a healthy son weighing 2415 grams, who had no signs of pancytopenia. After delivery the blood count of the patient did not recover and did not respond to medication. Eighteen weeks after delivery she died of sepsis complicated by cerebral bleeding and infarction due to severe thrombocytopenia and neutropenia, despite optimal supportive treatment. Conclusion: This potential life-threatening disease has a relatively good prognosis for both mother and child after optimal treatment. Transfusion during pregnancy is the first choice treatment with recommended hemoglobin levels of 5.5 mmol/L and platelet counts of20 *109/L. Cyclosporine A seems a reasonable alternative therapy with a reported success rate in non-pregnant patients of 70% when combined with antithymocyte globuline. Our patient died 18 weeks postpartum from cerebral bleeding and infarction due to severe thrombocytopenia despite intensive supportive treatment, methylprednisolon and cyclosporine A

The Effects of Long-Term Graft Preservation on Intraoperative Hemostatic Changes in Liver Transplantation:A Comparison Between Orthotopic and Heterotopic Transplantation in the Pig

We compared hemostatic changes during OLT and HLT after various periods of graft storage, to investigate whether the host liver in HLT protects the recipient from hemostatic deterioration induced by severe graft storage damage. In particular, the mechanism of fibrinolytic deterioration was investigated. The effect of prostaglandin E1 (PGE1) on these parameters was also studied. Material and Methods: 69 pigs underwent either OLT (N = 32) or HLT (N = 37) with a graft stored for 2 hr (N = 31), 24 hr (N = 16), 48 hr (N = 7), or 72 hr (N = 15). PGE1 was given intravenously to both donor and recipient animals and was added to the preservation and flushing solutions. Fibrinolysis (euglobulin clot lysis time, t-PA activity and α2-antiplasmin) and coagulation parameters (activated partial thromboplasmin time, prothrombin time, fibrinogen and platelet count) were measured at several intervals during transplantation. Statistics: Univariate non-parametric tests were used for analysis of coagulation and fibrinolysis parameters. For the three main variables- i.e., the type of transplantation, the use of PGE1, and the preservation time, multiple regression analysis was performed. Results: Fibrinolytic activity increased during the anhepatic period of OLT. Graft reperfusion was followed by a rise in t-PA in both OLT and HLT. In HLT, t-PA quickly returned to normal, whereas a continuous increase was found in OLT. The coagulation parameters, in turn, remained unchanged during the anhepatic period and deteriorated in OLT compared to HLT. The duration of graft storage was directly related to the severity of the hemostatic changes, although this effect was more apparent in OLT than in HLT. Conclusions: Changes in hemostasis are more pronounced in OLT than in HLT. This suggests that the host liver protects the recipient from the effects of graft storage damage, even after long preservation times. Early postreperfusion fibrinolytic activity was presumably due to t-PA release from the graft both in OLT and HLT. The further rise t-PA in OLT might be caused by the release of cytokines from the graft, that subsequently evoke endothelial t-PA release. In HLT, t-PA and cytokines may be cleared by the native liver. No positive or negative effect of PGE1 on coagulation or fibrinolysis parameters was noticed.\</p