Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis
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Blood Coagul. Fibrinolysis · Mar 1998
ReviewRecombinant activated factor VII as a universal haemostatic agent.
Haemostasis is initiated by the complex formed by tissue factor (TF) and activated factor VII (FVIIa) present in the blood [1% of the factor VII (FVII) protein]. Recombinant FVIIa (rFVIIa), enzymatically active only after complex formation with TF exposed following tissue damage, has been demonstrated to induce haemostasis in haemophilia patients with life- and limb-threatening bleedings with an efficacy rate of 76-84% in patients having failed on other treatment. rFVIIa has been successfully used in patients with congenital FVII deficiency and has been demonstrated to normalize the prolonged prothrombin time in patients with liver disease and in warfarin-treated individuals. ⋯ One patient with Glanzmann's thrombasthenia and three with Type III von Willebrand's disease were successfully treated with rFVIIa. By exploiting the binding capacity of FVIIa to platelets, rFVIIa, may also be used to enhance normal haemostasis in patients without coagulation defects but suffering from bleedings in organs or at sites with limited possibilities for mechanical haemostasis.
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Blood Coagul. Fibrinolysis · Mar 1998
Levels of prothrombin activation peptide F1+2 in patients with a bleeding tendency.
Numerous recent publications point to significant improvements in haemostasis in the bleeding patient suffering from haemophilia with inhibitors when a recombinant activated factor VII (rFVIIa) molecule is administered in high doses. In theory, activated factor VII (FVIIa) is believed to initiate haemostasis through its physiological interaction with tissue factor at sites of cellular injury, whereby factor X (FX) activation and, in consequence, thrombin formation is amplified. There has been speculation, however, whether high circulating FVII procoagulant (FVII:C) levels may induce systemic coagulation activation. ⋯ In FVII-deficient individuals, the mean rise in F1+2 was <0.10 nmol/l. In the control group, the mean elevation of F1+2 was 0.13 nmol/l (range -0.5 to 0.7 nmol/l). Hence, our results show that only discrete changes in F1+2 follow administration of rFVIIa.
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Blood Coagul. Fibrinolysis · Jan 1998
Haemostatic disturbances in burned patients during early excision and skin grafting.
Bleeding is a major problem during early excision of burned skin. Therefore, 13 severely burned adult patients operated on during the first week after the trauma were studied. Blood loss was replaced with crystalloids, colloids and packed red cell concentrates (PRC). ⋯ Thrombelastography showed decreased clot formation rate and impaired fibrin platelet interaction peri- and postoperatively. Fibrinogen and factor VIII activity were high preoperatively (median 6.1 g/l and 253%) and the critical values for normal haemostasis were not reached. Burned patients have a consumption coagulopathy which, in combination with haemodilution during operation, results in a clinically significant deficiency of coagulation factors II, VII and X, in spite of reactive elevation of coagulation factor VIII and fibrinogen.
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A recently-introduced automated method for the determination of plasma fibrinogen is based on the principle of von Clauss, combined with photometric detection: after addition of thrombin, the coagulation time is determined by measuring the change in absorption at 405 nm. This method was evaluated and compared with the original coagulometric Clauss assay and with the prothrombin time (PT)-derived automated method. The inter-assay coefficient of variation of the Clauss-derived assay was lower (14.1, 3.8 and 4.6%) than the PT-derived assay (16.1, 7.5 and 10.5%, respectively) at all three fibrinogen levels tested (1.2, 4.0 and 7.5 g/l). ⋯ The interference of heparin (< 1.5 U/ml), haemoglobin (< 30 micromol/l), bilirubin (< 200 micromol/l) and triglycerides (< 5.5 mmol/l) in the Clauss-derived assay was negligible. The effects of fibrinogen degradation products on the Clauss-derived assay were comparable with the effects on the Clauss assay, in contrast to the effects on the PT-derived assay. In conclusion, the Clauss-derived assay is a specific and precise automated method to determine fibrinogen concentrations in plasma, which is not liable to interference from different pathophysiological substances.
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Blood Coagul. Fibrinolysis · Sep 1997
Increased serum levels of thrombopoietin in patients with thrombotic thrombocytopenic purpura, idiopathic thrombocytopenic purpura, or disseminated intravascular coagulation.
The serum levels of thrombopoietin (TPO) were measured in 16 patients with thrombotic thrombocytopenic purpura (TTP), 12 with hemolytic uremic syndrome (HUS), 10 with aplastic anemia (AA), 10 with disseminated intravascular coagulation (DIC), and 71 with idiopathic thrombocytopenic purpura (ITP). The serum TPO levels were measured with a sensitive sandwich enzyme-linked immunosorbent assay. The serum TPO level in the ITP group (1.68 +/- 0.85 fmol/ml) were not significantly increased compared with those of the normal subjects. ⋯ The patients with AA (12.7 +/- 8.0 fmol/ml) and those with DIC (13.3 +/- 5.7 mol/ml) had significantly higher serum TPO levels than did the normal subjects and ITP patients. The TPO levels were well correlated with the platelet counts in the TTP patients, and were negatively correlated with the platelet counts in the ITP patients. These results suggest that the serum TPO levels in some thrombocytopenic diseases are regulated not only by the platelet count and the megakaryocyte mass, but also by other factors.