Pathogenesis of Fibrinolysis in Defibrination Syndrome: Effect of Heparin Administration

Abstract

1. Spontaneous local fibrinolysis occurred with, and was probably a consequence of thrombosis, with defibrination in vivo. 2. The efficacy of heparin in the prevention of defibrination was clearly demonstrated; warfarin therapy seemed to be ineffective. 3. The efficacy of heparin in the prevention of the associated fibrinolysis was clearly inferred. 4. Serum immunoelectrophoresis against anti-fibrinogen sera demonstrated abnormal precipitin bands, during defibrination and fibrinolysis, which disappeared during heparin administration. 5. The serum bands showed immunologic identity with in vitro plasmin digests of fibrinogen and the intensity and position of these precipitin bands appeared to depend on the amount of fibrinogen and the duration of the in vivo digestion period. 6. In this hypofibrinogenemic state, defibrination was indicated by markedly reduced levels of anti-hemophilic factor and Factor V and a fall in blood platelets. The presence of fibrinolysis was shown by the lowered levels of plasminogen, streptokinase and urokinase inhibitors, prolonged thrombin clotting times and fibrinolytic breakdown products in the serum even though little or no lysis occurred on fibrin plates and the euglobulin lysis times were within normal limits. 7. The administration of fibrinolytic inhibitors is strongly contraindicated under these circumstances.

The Defibrination Syndrome: Clinical Features and Laboratory Diagnosis

“…Breakdown products of fibrinogen in serum and plasma were studied by immunodiffusion in Ouchterlony plates (Ouchterlony, 1962), by immunoelectrophoresis (Scheidegger, 1955 ;Merskey, Johnson, Pert and Wohl, 1964), and by the tanned red-cell haemagglutination inhibition immunoassay (TRCHII) (Merskey, Kleiner and Johnson, 1966). To avoid in vitro digestion of fibrinogen and fibrin, the blood for fibrinogen determination and for immunologic assays of fibrinolytic split products was usually drawn into tubes containing the fibrinolytic inhibitor Trasylob; ( IOO kallikrein inhibitor unitslml.…”

“…Case 6 : Defbrination associated with disseminated cancer. We previously reported in detail one case of defibrination associated with disseminated cancer (Merskey, Johnson, Pert and Wohl, 1964) and another typical one follows. A 58-year-old man was hospitalized because of a sudden collapse.…”

Report of Two Cases Treated With Isoproterenol and Heparin

“…Heparin was used in an attempt to prevent intravascular coagulation (McGehee, 1965;Merskey, Johnson, Pert, and Wohl, 1964) and thereby minimize some of the pathological lesions associated with the Waterhouse-Friderichsen syndrome. Whatever the significance of the observation, no further skin lesions appeared after the children were heparinized.…”

“…Recent experimental work on endotoxin shock suggests that the administration of isoproterenol hydrochloride (isopropyl-noradrenaline, isoprenaline, 'Isuprel'* ) could be beneficial in the treatment of fulminant meningococcal septicaemia (Halmagyi, Horner, and Starzecki, 1965). It has also been suggested that heparin may prevent the intravascular coagulation (Merskey, Johnson, Pert, and Wohl, 1964) which has been shown to occur in this condition (McGehee, Hjort, and Rapaport, 1965).…”

Obstetric Hypofibrinogenaemia

“…Excessive local fibrin deposits in the intervillous space have, however, been found in two cases (Stouffer and Ashworth, 1958) and evidence of fibrinolysis in others . Such fibrinolysis can occur secondarily to intravascular coagulation (Fletcher et al, 1962), remitting during heparin treatment (Merskey et al, 1964), when it may represent a physiological mechanism for removing fibrin emboli as suggested above.…”