Bleeding and Thrombosis Risks in Plasma Cell Dyscrasias

Abstract

Major, spontaneous bleeding is uncommon in patients with plasma cell dyscrasias despite frequent abnormal screening hemostasis tests. However, acquired von Willebrand deficiency and light-chain (AL) amyloidosis, and amyloidosis complicating multiple myeloma can present with serious hemorrhagic complications that are challenging to manage. While patients with monoclonal gammapathy of undetermined significance and multiple myeloma share an intrinsic increased risk of venous thromboembolic events (VTE), treatment with thalidomide and lenalidomide increases the incidence of VTE in certain multiple myeloma patient subsets. Our understanding of the complex interactions among malignant plasma cells, inflammatory and hemostasis pathways, and treatment modalities that combine to produce thrombotic complications is incomplete. Prospective, randomized trials are clearly needed to assist clinicians in providing optimal VTE prophylaxis to their patients with plasma cell dyscrasias. Hemorrhagic ComplicationsWhile overt bleeding is a relatively uncommon presenting symptom of monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM), Waldenström macroglobulinemia, and other B-cell malignancies, pathophysiologic interactions between paraproteins and coagulation factors, platelets, and vessels can produce hemostasis abnormalities. The consequences are often incidental, abnormal hemostasis test results, but overt bleeding and thrombotic presentations occur as well. 1 IncidenceRelying on distant, retrospective surveys, bleeding complications are more likely with IgM and IgA paraproteins than with IgG, and are associated with higher concentrations of serum immunoglobins, higher serum viscosity, and prolonged bleeding time, but not with decreased platelet counts or prolonged prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin time.2,3 More contemporary reviews report symptomatic bleeding at presentation in 0% of multiple myeloma, 4 and 17% of Waldenström's macroglobulinemia. 5 Bleeding complications are a more common cause of morbidity and death during treatment of plasma cell dyscrasias 6 due to progression of disease, renal insufficiency, infections, therapy related toxicity, and invasive procedures rather than a direct consequence of the paraprotein.

Treatment Options for Relapsed and Refractory Multiple Myeloma

“…Individuals with a prior history of VTE should be fully anticoagulated, as should patients with other risk factors for the development of VTE. The use of aspirin, low molecular weight heparin (LMWH), and warfarin have all been evaluated (59), and the IMWG has published guidelines on the basis of a risk assessment model; specifically, LMWH, equivalent to enoxaparin 40 mg per day, has been recommended for patients with more than 1 risk factor, whereas aspirin (ASA) can be considered for those with lower risk profiles (60). In a randomized trial from Palumbo and colleagues, patients who were receiving IMiD-based therapy (including thalidomide) were randomized to receive either LMWH, warfarin, or ASA.…”

“…However, it is associated with an increased risk of VTE, just like thalidomide, and thromboprophylaxis is required, typically with ASA (59,60). A retrospective analysis from Nooka and colleagues sought to validate the IMWG guidelines for lenalidomide thromboprophylaxis (87).…”

Clinical and prognostic implications of low or high level of von Willebrand factor in patients with Waldenström macroglobulinemia

“…1,2 Among these manifestations, the occurrence of acquired von Willebrand syndrome (AVWS) is a rare event, characterized by bleeding related to the decrease of von Willebrand factor (VWF) activity, without any personal or family history of bleeding, by contrast with congenital von Willebrand disease. [3][4][5][6] VWF, an adhesive glycoprotein produced by the vascular endothelium and megakaryocytes, plays a key role in primary hemostasis. VWF derives from the pro-VWF, a large 360-kDa precursor.…”

Echocardiography as the first diagnostic clue to rapidly progressive systemic AL amyloidosis associated with multiple site thrombosis. A case report

“…As in many other cancer types, patients with myeloma are at high risk for thrombosis and thromboembolic events, the most frequently involved factors being immobility, malignant cells, central venous catheters, inflammation-induced prothrombotic states and chemotherapy effects [9].…”