Plasma cross-linked fibrin degradation product (XLFbDP) assays in an in vivo model of fibrinolysis.
Assumptions regarding the elaboration of plasma cross-linked fibrin degradation products (XLFbDPs) in vivo were tested using an experimental model in which particulate human fibrin was infused into rabbits and the products of lysis monitored with an immunoassay utilizing DD-3B6/22, a monoclonal antibody to human cross-linked derivatives. XLFbDPs were generated following the infusion of a suspension of cross-linked fibrin, attaining a peak between 40 and 60 min, then falling at a rate approximating a plasma half-life of 2 h. The major in vivo products of lysis of cross-linked fibrin, identified by SDS-PAGE of immunoextracted plasma, were D-dimer and high-molecular-weight moieties. Peak levels of XLFbDPs achieved correlated with the amount of fibrin administered. Since XLFbDP levels were no higher when fibrin infusion was followed by infusions of streptokinase and human plasminogen, it is concluded that endogenous mechanisms of lysis were already maximally stimulated. Infusions of non-cross-linked (NXL) fibrin or of fibrinogen led to much smaller, but measurable, rises in XLFbDP. In the latter group, XLFbDP levels rose further following fibrinolytic therapy. Treatment with epsilon aminocaproic acid (EACA) caused partial (greater than 50%) inhibition of lysis while pre-treatment with nitrogen mustard, inducing leucopenia, virtually abolished the appearance of XLFbDPs in the circulation. This implies that fibrinolytic responses are substantially dependent upon cellular functions sensitive to nitrogen mustard.
Rowbotham
B J
BJ
Department of Pathology, University of Queensland, Brisbane, Australia.
Whitaker
A N
AN
Masci
P P
PP
D015119:Aminocaproic Acid / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D005337:Fibrin / Q000378:metabolism*; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis* / Q000276:immunology; D005342:Fibrinolysis; D006801:Humans; D007118:Immunoassay; D007962:Leukocytes / Q000502:physiology; D007970:Leukopenia / Q000097:blood / Q000139:chemically induced; D008168:Lung / Q000737:chemistry; D008297:Male; D008466:Mechlorethamine / Q000494:pharmacology / Q000633:toxicity; D008954:Models, Biological; D010958:Plasminogen / Q000494:pharmacology; D011817:Rabbits; D013300:Streptokinase / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D005338:Fibrin Fibrinogen Degradation Products; D008466:Mechlorethamine; D005337:Fibrin; D010958:Plasminogen; D013300:Streptokinase; D015119:Aminocaproic Acid