Study of three patients with monoclonal gammopathies and ‘lupus‐like’ anticoagulants

Abstract

In three patients with monoclonal gammopathies: a case of multiple myeloma, a case of monoclonal gammopathy of uncertain significance (MGUS) and a case of monoclonal gammopathy associated with lymphocytic lymphoma, we found the presence of a circulating lupus-like anticoagulant. Coagulative studies showed that the paraproteins: an IgG3k, an IgG1k and an IgMlambda, were responsible for the anticoagulant activity by interacting with the thromboplastin phospholipids. Using isoelectrofocusing we demonstrated that the three monoclonal immunoglobulins had a strong basic charge which may have contributed to determining their interaction with the acidic thromboplastin phospholipids. The binding of various phospholipids to the monoclonal proteins was assessed by the fluorescence quenching method which showed heterogeneous specificity. In order to establish whether the electrical charge is also relevant in cases with polyclonal lupus anticoagulant, the polyclonal immunoglobulins were fractionated according to their charge. The strongest inhibitor activity was found in the most basic immunoglobulins. Monoclonal lupus-like anticoagulants represent useful tools for investigating the heterogeneous world of polyclonal lupus-like anticoagulants.

Increased thromboembolic incidence in anti-cardiolipin-positive patients with malignancy

“…There have been many sporadic reports of the association of APLAs, i.e. ACLAs or LAC, with malignancy such as malignant lymphoma (Mills et al, 1977;Maker et al, 1990;Asherson et al, 1991;Ciaudo et al, 1991;Conlan et al, 1991), plasma cell dyscrasia (Duhrsen et al, 1987;Bellotti et al, 1989;Watts et al, 1989;Wisloff et al, 1991;Glaspy, 1992), leukaemia (Duncombe et al, 1987;Donner et al, 1992) and lung, colonic, cervical, prostatic or liver cancer or thymoma (Kozlowski et al, 1987;Shaukat et al, 1990;Schleider et al, 1976;Meyrier et al, 1991;Park et al, 1991;. All these publications were case reports including fewer than 50 patients.…”

Thrombogenic activity of doxorubicin in myeloma patients receiving thalidomide: implications for therapy

“…2 This hypercoagulability may be related to an impaired fibrinolytic system, to the presence of lupuslike anticoagulant antibodies, [3][4][5][6][7] or to increased levels of proinflammatory procoagulant cytokines (interleukin 6, tumor necrosis factor-␣). 8 Thalidomide is an active agent in refractory MM 9 and is associated with a very low incidence of DVT (2%) when used as a single agent.…”

Multiple Myeloma Presenting as Mesenteric Venous Thrombosis and Intestinal Infarction

“…Duhrsen et al described lupus anticoagulant in a series of patients with multiple myeloma who developed recurrent thromboembolism without other coagulopathy (5). Further case reports, by Yasin et al (6) and Bellotti et al (7), have described the finding of lupus anticoagulant and hypercoagulable tendencies. The mechanism of this hypercoagulable state appears to be associated with exacerbation of APC resistance (8).…”