Comprehensive Study of Haemostasis in Chronic Uraemia

Abstract

A comprehensive study of haemostasis has been performed in a homogeneous group of 25 adult patients with conservatively treated chronic uraemia. We have found prolonged bleeding time, impaired platelet adhesiveness and aggregation, and decreased platelet factor 3 activity, increased values of fibrinogen, of factor VIII activity and related antigen, and of combined levels of factors II, VII and X. Non-significantly abnormal concentrations of factor XIII and of plasminogen and significantly lower values of plasminogen activators and higher values of urokinase inhibitors and anti-plasmin have also been found. Fibrinogen degradation products were detected in the urine of some patients.

Bleeding and Thrombosis in Chronic Uremia

“…43] The hemorrhagic diathesis in chronic uremia mainly stems from a defect in primary' hemostasis. Both vascular and platelet abnormalities seem to concur to the bleeding tendency, whereas the overall tests for blood coagulation, namely activated partial thromboplastin time, prothrom bin time, and thrombin time, are usually normal as well as clottable factor XIII [21,22], As a general rule, the risk of bleeding markedly in creases paralleling blood urea nitrogen concentration increment. A prolonged skin bleeding time is the laborato ry hallmark of the hemorrhagic diathesis of uremia [2][3][4][5][6].…”

“…32] Reduction of platelet glycoprotein lb [33] Marked reduction in platelet von Willebrand factor [34] Reduction in dense granule content of ADP and serotonin [35][36][37] impaired platelet aggregation in response to high concentrations of aggregating agents ADP. arachidonic acid, epinephrine, thrombin and collagen [3,22,23. 37] Diminished thromboxane A; generation in response to thrombin [38][39][40] Decreased platelet factor 3 availability [41] Rise in cytosol levels of free calcium ions and cyclic AM P [42.…”

“…Mean platelet count in hemodialysis patients, although within the normal range, is usually significantly lower than that of healthy controls, suggesting platelet overcon sumption with inadequate production [22]. Indeed, re duced survival of circulating platelets has been docu mented in hemodialysis patients [46].…”

“…Global coagulation tests (activated partial thrombo plastin time, prothrombin time, and thrombin time) are generally within the normal range in patients with endstage renal failure [21,22], Significant alterations in the plasma level of coagulation factors and natural anticoagu lants have been reported in urémies on conservative treat ment or on maintenance hemodialysis: high plasma levels of fibrinogen, factor VII activity, factor VIII procoagu lant, factor XIII. von Willcbrand factor, and tissue factor pathway inhibitor [ On the basis of recent advances in the biochemistry of the hemostatic system reactions and in the measurement of the molecular markers formed during these reactions [120], it has been possible to determine plasma parame ters that directly reflect an activation of the coagulation system, namely prothrombin fragment 1 +2 (FI +2) [121.…”

“…Fibrinolytic System Activity Total fibrinolytic activity determined by diluted blood clot lysis time, euglobulin lysis time, fibrin plate method or amidolytic activity on chromogenic substrate, is usual ly reduced in uremic patients [21,22,131,132], in the face of hypercoagulation.…”