Hypofibrinogenaemia in metastatic carcinoma of the prostate: suppression of systemic fibrinolysis by heparin

Abstract

SYNOPSIS In a patient with generalized prostatic carcinoma and hypofibrinogenaemia heparin infusion on four occasions abolished systemic fibrinolysis as determined by euglobulin clot lysis time, bovine fibrin plate assay, thromboelastography, and immunoelectrophoretic demonstration of fibrinogen split products.The pathogenesis of hypofibrinogenaemia in cases of prostatic carcinoma and the possibility of a direct heparin effect on fibrinolysis are discussed. Despite the lack of histological evidence for intravascular coagulation, the findings are considered additional evidence for the view that fibrinolysis in this syndrome may be secondary to intravascular coagulation.

Immunobiology of Fibrinogen. EMERGENCE OF NEOANTIGENIC EXPRESSIONS DURING PHYSIOLOGIC CLEAVAGE IN VITRO AND IN VIVO

“…By contrast, when control plasma C100 was exposed to plasmin (4 A'g plasmin/ml plasma at 370C for 3 h), fg-Dneo expression was readily generated as indicated by the competitive inhibition of ["I] fg-D binding. Plasmas from two patients with metastatic carcinoma and moderate levels of serum cleavage products by radial immunodiffusion ( X 100 = 5 mg/100 ml; X 101 = 8 mg/100 ml) were also assayed (8,32,33). Both produced semilogarithmic inhibition parallel to that produced by the in vitro cleaved plasma sample, indicating the appearance in vivo of fg-Dneo indistinguishable from that generated in vitro.…”

“…Plasmas were selected from patients with diseases associated with disseminated intravascular coagulation and the presence of circulating fibrin or fibrinogen cleavage fragments, e.g., metastatic carcinoma (8,32,33), abruptio placentae (6, 34), consumptive coagulopathy (disseminated intravascular coagulation) (8,35,36), meningococcal meningitis (37,38), and endotoxic shock (39,40). Serum cleavage fragments, primary evidence for in vivo fibrinolysis, were present in all (17-300 mg/100 ml).…”

Coagulation and fibrinolysis after injury.

“…It should be emphasized that heparin, in the doses given, would have no direct inhibitory effect on fibrinolysis; this is a biological effect in the intact organism, preventing the formation of fibrin appears to prevent fibrinolysis. In the experimental studies heparin has usually been given before the stimulus to coagulation but there is good evidence that heparin will also correct the changes in fibrinolysis in human patients already suffering from the effects of disseminated intravascular coagulation (Merskey, Johnson, Pert, and Wohl, 1964;Straub, Riedler, and Frick, 1967;Robboy, 1969). An example observed by the author is illustrated in Figure 3.…”

Plasminogen-activator-producing Tumour

“…Elucidation of the pathogenesis is important in view of the different mechanisms which require different therapeutic measures. Straub, Riedler, and Frick (1967) reported disseminated intravascular coagulation with hypofibrinogenaemia and secondary fibrinolysis in a case of generalized prostatic carcinoma which responded to heparin therapy. Tagnon, Schulman, Whitmore, and Leone (1953) found pathological fibrinolysis in a prostatic carcinoma and evidence of proteolytic activity in a bone metastasis.…”

“…According to current concepts (McKay, 1965;Straub et al, 1967) the defibrination syndrome found in malignant disease is usually caused by disseminated intravascular coagulation. Certain cases remain, however, in which this is not a satisfactory explanation, and where investigation indicates primary pathological fibrinolysis as the pathogenetic mechanism.…”