Acquired immune-mediated thrombophilia in lymphoproliferative disorders

Abstract

We analyzed 66 cases of immune-mediated thrombophilia in patients with lymphoma reported in the literature. Sixty-one cases had a lupus anticoagulant, three an antibody to protein S, one to protein C, and one to ADAMTS 13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13). Lupus anticoagulants occurred in all histological subtypes of non-Hodgkin lymphoma, except mantle cell lymphoma, MALT (mucosa-associated lymphoid tissue) lymphoma, and angioimmunoblastic T-cell lymphoma, and rarely in Hodgkin lymphoma. The largest number of cases was described in splenic marginal zone and lymphoplasmacytic lymphoma. Lupus anticoagulants were highly associated with immunoglobulin M (IgM) paraproteinemia, autoimmune hemolytic anemia, and immune thrombocytopenia. About half of the patients had thrombotic events (antiphospholipid antibody syndrome). Venous thromboembolism was more than twice as common as arterial thrombosis; 6.5% had a catastrophic antiphospholipid antibody syndrome. The lupus anticoagulant could be eliminated by lymphoma treatment (chemoimmunotherapy or splenectomy) in more than one-third of patients. It is suggested that a search for lupus anticoagulant should be done in all patients with lymphoma, because a diagnosis of lupus anticoagulant may influence the management of lymphomas in some patients.

Incidence of a first thromboembolic event in carriers of isolated lupus anticoagulant

“…However, on multivariate analysis, aspirin treatment was not found to have an effect on thrombosis incidence. Isolated LAC positivity might be explained with conditions as cancer [27] and infections or chronic illness [28]. These findings further support the current guidelines on LAC testing [14], in which it is stated that testing should be limited to young patients.…”

The Paradox of the Lupus Anticoagulant: History and Perspectives

“…Due to laboratory pitfalls in detecting LA, isolated LA positivity is of uncertain diagnostic value in patients with thrombosis and pregnancy loss or in carriers (those with positive laboratory profile but without overt disease). Isolated LA positivity might be present in other pathologic conditions such as cancer 46 and infections or chronic illness. 47 We have recently shown that as opposed to carriers of a full laboratory profile, carriers of isolated LA positivity are at low risk of thromboembolic events.…”

ADAMTS13 Endopeptidase Protects against Vascular Endothelial Growth Factor Inhibitor–Induced Thrombotic Microangiopathy

“…Autoantibodies against the enzyme have been described in isolated cancer cases, 55,56 yet in the majority, reduced production through liver dysfunction and/or increased clearance (possibly through consumption in a prothrombotic state) has been suggested as the main cause. 11,53 However, our results suggest that low ADAMTS13 enzyme activity can lead to severe clinical consequences when exposed to anti-VEGF state.…”