Abnormal Fibrin Ultrastructure, Polymerization, and Clot Retraction in Multiple Myeloma*

Abstract

We have investigated two patients with multiple myeloma who had a prolonged thrombin clotting time and absent clot retraction but no haemorrhagic diathesis. Coagulation and platelet function studies, as well as electron microscopy of the fibrin clot, indicate abnormal fibrin polymerization; adherence of myeloma protein to very thin fibrin strands results in a rigid translucent clot which fails to retract. This abnormality is not necessarily associated with a haemorrhagic diathesis.

Identification of a Monoclonal Thrombin Inhibitor Associated with Multiple Myeloma and a Severe Bleeding Disorder

“…Reptilase directly activates fibrinogen by cleaving fibrinopeptide A so that inhibitors of thrombin should have a normal reptilase time (Funk et al, 1971). In comparison, inhibition of fibrin polymerization by paraproteins can prolong the reptilase time as well as the thrombin time (Lackner et al, 1970). The IgG isolated from this patient immunoprecipitated thrombin, but not reptilase or fibrinogen, and the thrombin time was slightly prolonged at very low concentrations, suggesting a specific interaction with thrombin.…”

“…Bleeding syndromes have been described infrequently in plasma cell dyscrasias (Feinstein, 1995) and include acquired von Willebrand disease (Sampson et al, 1983), factor X deficiency (Furie et al, 1981), inhibition of fibrin polymerization (Lackner et al, 1970), and circulating heparin-like anticoagulants (Tefferi et al, 1990). In addition, haemorrhage in multiple myeloma may not be directly due to an effect of the monoclonal protein, but may be related to other complications of the disease such as thrombocytopenia.…”

Circulating heparan sulfate proteoglycan anticoagulant from a patient with a plasma cell disorder.

“…Prolongation of prothrombin and partial thromboplastin times have generally been attributed to nonspecific interference of the monoclonal proteins, although in certain instances specific coagulation factor antibodies have been elaborated in myelomna (1). In several studies (4,5,38), an antithrombin role has been assigned to a protein in the plasma which may, or may not, have been the monoclonial immunoglobulini molecule. In two studies (39,40) heparin-like activity for an anticoagulant was suggested but fu-rther analyses were not conducted to specifically identify the nature of the anticoagulant activity.…”

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]. It was reported that acquired dysfibrinogenemia may be associated with drug usage [20, 21], antifibrinogen antibody presence [4] or allogeneic bone marrow transplantation [22].…”