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Factor VIII coagulant activity and factor VIII-related antigen released from isolated perfused human spleens.

Eight human spleens were perfused for up to 65 h at normothermia and the coagulant Factor VIII activity measured in the perfusate. In addition, in three experiments Factor VIII-related antigen was determined in the perfusate. Although the spleens were pathologically enlarged and the normal structure involved by different diseases, all spleens released Factor VIII coagulant activity and Factor VIII-related antigen. On average the total amount of Factor VIII coagulant activity released was equivalent to that of 3.5 l of human plasma.

Antigens

Factor VIII coagulant activity in an African population in relation to a recognized standard.

The normal range of factor VIII coagulant activity (derived from log potency ratio) in some sections of the Nigerian population has been established at 0.65--5.55 iu/ml with a geometric mean of 1.90 iu/ml. This was determined against an acceptable standard (MRC Human 68/413 with activity o.66 iu/ml). The distribution of the potency ratio was log normal. The level was not affected by age or an abnormal haemoglobin (Hb A + S or A + C). The mean activity in females was significantly higher than the mean value in male subjects. With the use of a stable standard, our results show that the conclusions of some previous studies in respect of some of the parameters such as population distribution but which did not use a recognized standard, were valid. Within the age limits of our subjects, age did not affect the population level of factor VIII coagulant activity.

Adolescent

Generation of factor VIII coagulant activity by isolated, perfused neonatal pig livers and adult rat livers.

Isolated, normal, neonatal pig livers released VIII:C into perfusates of porcine von Willebrand blood lacking VIIIR:AG and VIII:RWF. Neonatal von Willebrand livers released VIII:C only when partially purified VIIIR:AG was added to the von Willbrand blood. Adult rat livers, perfused with frozen-thawed erythrocytes suspended in Tyrode's solution containing 6% bovine serum albumin and hence no VIIIR:AG released VIII:C only when serum, adsorbed serum or cryoprecipitate from rat plasma was added to the perfusate. Cycloheximide blocked the release of VIII:C from rat liver.

Animals

Factor VIII-related antigen and factor VIII coagulant activity in normal and pre-eclamptic pregnancy.

The changes in the ratio between factor VIII-related antigen and factor VIII activity were compared in ten patients with normal pregnancies and in ten patients with severe pre-eclampsia. In the patients with pre-eclampsia, a highly significant increase in the ratio was observed during the third trimester. No difference in the ratio between the two groups was found on day 7 of the puerperium. In the pre-eclamptic patients, the highest ratios for factor VIII-related antigen to factor VIII activity were associated with either a perinatal death or with the delivery of a severely growth retarded infant. These findings are in keeping with an increased rate of thrombin production in women with pre-eclampsia, and suggest that the ratio of factor VIII-related antigen to factor VIII activity may reflect the severity of the effect of the disease process on the fetus.

Antigens

[Precision control of a single step determination of blood coagulation factor VIII in the plasma].

The findings of a precision control are reported for a one-stage determination of the factor VIII activity in the plasma for a period of 6 months. The storage property of the reagents was achieved by storing them in fluid nitrogen. Coefficients of variation under 55 were achieved at controlling the normal range as well as the pathological one. Thus the precision of this method may be compared with that of clinicochemical examinations.

Blood Coagulation Tests

Mesterolone: thrombosis during treatment, and a study of its prothrombotic effects.

1. We describe a patient who developed deep vein thrombosis after commencing treatment with the synthetic androgen, mesterolone (Pro-Viron). 2. To investigate the potential thrombogenic action of this drug, a 21 day course of mesterolone (100 mg/day) was given to nine healthy male volunteers. 3. No significant change after treatment occurred in any of the blood tests performed (clotting times, Factor VIII coagulant activity, Factor VIII related antigen, antithrombin III activity, fibrinogen, fibrinogen-fibrin degradation products, plasminogen, euglobulin lysis time, urokinase sensitivity, platelet count, haematocrit, whole blood viscosity and plasma viscosity). 4. We conclude that in a conventional dose taken for 3 weeks mesterolone does not produce a consistent measurable prothrombotic state, nor does it enhance fibrinolysis.

Adult

Platelet function, factor VIII, fibrinogen, and fibrinolysis in Nigerians and Europeans in relation to atheroma and thrombosis.

Platelet function, factor VIII, fibrinogen levels, and fibrinolysis were studied in Europeans and in two groups of Nigerians living in Zaria, northern Nigeria, in order to see whether differences could help to explain the low incidence of atheroma and thrombosis in Nigerians. We confirmed the relative thrombocytopenia and observed a rapid disaggregation after ADP-induced platelet aggregation in Nigerians. The most striking difference was a reduced or absent ristocetin-induced platelet aggregation in Nigerian platelet-rich plasma, probably due to a plasma component interacting with the von Willebrand activity (VWF), since factor VIII coagulant activity, factor VIII related antigen, and isolated VWF were normal or high by European standards. Group II (rural population), but not group I (senior university staff in Zaria) of the Nigerians, tended to have high serum fibrinogen concentrations. Spontaneous fibrinolytic activity was enhanced in most Nigerians compared to the Europeans and was normally increased after venostasis in proportion to the initial activity. Fibrinolysis and ristocetin-induced platelet aggregation values for the Nigerians in group I were intermediate between European and Nigerian in the group II values, suggesting that differences were due more to environmental than to genetic factors.Relative thrombocytopenia, disaggregation after ADP-induced aggregation, inhibition of ristocetin-induced platelet aggregation, and active fibrinolysis help to explain the infrequency of thrombotic disease in Africans. Also the low incidence of atheroma may follow from less platelet adherence and less platelet release of mitogenic factors, which cause intimal hyperplasia.

Arteriosclerosis

Problems in the detection of carriers of hemophilia A: the influence of stress and thrombin.

After exposure to stress, factor VIII coagulant activity and factor VIII antigen were determined in healthy volunteers for about 3 days. Three out of four volunteers at different time showed results resembling a carrier state. In vitro incubation of plasma with thrombin in decreasing concentrations showed increased factor VIII coagulant activity, although no fibrin clot or fibrin monomers were formed. The concentration of factor VIII antigen remained constant. The action of thrombin can explain the misclassification of known carriers.

Adult

Factor VIII inhibitor postpartum.

Acquired factor VIII deficiency in women postpartum due to a factor VIII inhibitor is rare and the etiology is unknown. In this study a case report and a review of the literature are given. The haemorrhagic diathesis resembles classic haemophilia, with the exception that ecchymoses and tissue bleeding occur more frequently. The potency of the inhibitor may vary from weak to strong and the inactivation of factor VIII coagulant activity (factor VIII-C) by the inhibitor is of a non-linear type. Severe bleeding has been fatal in a few cases, but factor VIII concentrate substitution has usually been successful without anamnestic response of inhibitor activity. There is no convincing evidence that immunosuppression is effective, also because the natural history of the disease is characterised by a spontaneous disappearance of the factor VIII-C inhibitor. Treatment of bleeding symptoms with factor VIII concentrate should therefore not be reserved for life threatening haemorrhages only.

Adult