A Naturally Occurring Antibody That Inhibits Fibrin Polymerization

Abstract

A 13-year-old girl with chronic aggressive hepatitis, postnecrotic cirrhosis, ulcerative colitis, and a coagulation defect acquired an antibody that specifically interfered with fibrin formation. We sought to characterize the antibody and determine the mechanism of its inhibitory activity. The patient's purified fibrinogen was functionally normal; however, the antibody inhibited the self-assembly of fibrin and prolonged the clotting times of the patient's plasma. This antibody, which belonged to the IgG class of immunoglobulins, acted early in the polymerization process to inhibit the association of fibrin monomers, as indicated by a prolonged lag time and a decreased slope in the polymerization curves. It did not inhibit fibrinopeptide cleavage or fibrin cross-linking. Affinity chromatography indicated that the antibody bound strongly to both fibrinogen and fibrin monomer.

Acquired Dysfibrinogenemia Secondary to Multiple Myeloma

“…The production of autoantibodies directed against fibrinogen as a cause of dysfibrinogenemia has been observed in the past [3,4,5,6]. Acquired dysfibrinogenemia occurs mainly as a disorder secondary to liver disease [7,8,9], liver cirrhosis [10, 11], multiple myeloma [12,13,14,15], hepatoma [16, 17], paraneoplastic syndrome [18] or digital ischemia and gangrene [19].…”

Spontaneous reversal of acquired autoimmune dysfibrinogenemia probably due to an antiidiotypic antibody directed to an interspecies cross-reactive idiotype expressed on antifibrinogen antibodies.

“…The demonstration of the existence of an autoantibody directed against fibrinogen, which was capable of inhibiting fibrin aggregation during the active phase of the hemorrhagic disease but not while the patient was in clinical remission, strongly suggests that the antifibrinogen autoantibody was the cause of the fibrinogen dysfunction. Other cases of autoimmune dysfibrinogenemia have been reported in the past (12)(13)(14)(15). In some cases the antibody inhibited polymerization of fibrinogen through blocking the cleavage sites for thrombin, while in others the antibody inhibited the aggregation of fibrin monomers after thrombin cleavage.…”

“…In fact, it is presumable that the expression of autoimmune humoral immune responses might be modulated, ita, est, augmented, or depressed, by anti-Id antibodies (6, 9-1 1). The production of autoantibodies directed to fibrinogen as a cause of dysfibrinogenemia has been observed in the past (12)(13)(14)(15). In some instances, these antibodies interfere with fibrinogen clotting by inhibiting the cleavage of fibrinopeptides A and B by thrombin, while in other instances they block the polymerization of fibrin monomers after thrombin cleavage.…”

Acquired dysfibrinogenemia caused by monoclonal production of immunoglobulin light chain

“…3,4 That said, two patients with multiple myeloma 5,6 and three patients with SLE 7,8 have been reported to have prolonged thrombin times caused by anti-fibrinogen autoantibodies. Other disease states associated with autoantibodies toward fibrinogen include renal insufficiency, 9 migratory thrombophlebitis, 10 sarcoidosis with isoniazid therapy, 11 chronic liver disease 12 and Down's syndrome. 13 There are also examples of anti-fibrinogen antibodies developing spontaneously for no determined reason.…”