Actiated protein C resistance in the absence of factor V Leiden mutation is a common finding in multiple myeloma and is associated with an increased risk of thrombotic complications

Abstract

Thromboembolism is not uncommon in multiple myeloma (MM) patients on treatment, but its pathogenesis remains poorly understood. We report the results of a prospective randomized trial of 62 newly diagnosed MM patients tested at baseline for hypercoagulability and treated with intensive chemotherapy with or without thalidomide in a randomized fashion. During the induction phase, 12 patients (19%) developed evidence of deep venous thrombosis (DVT), which was significantly more common in the thalidomide arm (36%) than in the control group (3%) (P = 0.001). Fourteen patients (23%) were found to have a baseline-reduced response to activated protein C (APC) in the absence of factor V Leiden mutation. Using a Kaplan-Meier analysis, a significantly higher proportion of patients with APC resistance developed DVT (5/14 versus 7/38; P = 0.04) irrespective of thalidomide administration. The risk of DVT was highest (50%) in patients with APC resistance on thalidomide. None of the patients with normal APC response and not receiving thalidomide developed DVT. In conclusion, in this series, acquired APC resistance was present in almost one-quarter of newly diagnosed myeloma patients and significantly increased the risk of DVT.

First-line thalidomide–dexamethasone therapy in preparation for autologous stem cell transplantation in young patients (<61 years) with symptomatic multiple myeloma

“…Among these first 13 patients, 2 (15.3%) had symptomatic DVT. 15 In accordance with a prior study, 27 we found that activated protein C resistance in the absence of factor V Leiden mutation was associated with an increased risk of thrombotic complications in patients with MM receiving first-line thalidomide-dexamethasone therapy. 15 Because of the high rate of DVT observed in the first group, therapeutic doses of prophylactic anticoagulation with acenocoumarol were given for the remaining 47 patients.…”

“…Number of days to ANC4500/ml 11 (9-16) PLTC420 000/ml 14 (10-22) PLTC450 000/ml 17 (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) PLT transfusions (no.) 3 (0-16) RBC transfusions (no.)…”

Hyperfractionated cyclophosphamide in combination with pulsed dexamethasone and thalidomide (HyperCDT) in primary refractory or relapsed multiple myeloma

“…In particular, there was no evidence of activated protein C resistance in the presence or absence of factor V Leiden mutation (Zangari et al, 2002a).…”

Examining the Involvement of Erythropoiesis-Stimulating Agents in Tumor Proliferation (Erythropoietin Receptors, Receptor Binding, Signal Transduction), Angiogenesis, and Venous Thromboembolic Events

“…This might be a contributing factor in chemotherapyinduced thrombophilia [35]. In 62 patients with multiple myeloma, 23% had APC resistance at baseline and 50% of these patients developed a VTE [36]. The incidence of VTEs was higher in the thalidomide group of patients [36].…”

“…In 62 patients with multiple myeloma, 23% had APC resistance at baseline and 50% of these patients developed a VTE [36]. The incidence of VTEs was higher in the thalidomide group of patients [36]. In 1,178 patients with solid tumors, 109 had resistance to APC; of these, 36 patients had the factor V Leiden mutation and were excluded from the analysis [37].…”