Activated 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

Blood Coagul Fibrinolysis. 2002 Apr;13(3):187-92. doi: 10.1097/00001721-200204000-00003.

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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Activated Protein C Resistance / epidemiology
  • Activated Protein C Resistance / etiology*
  • Activated Protein C Resistance / genetics
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Blood Coagulation Tests
  • Cisplatin / administration & dosage
  • Combined Modality Therapy
  • Cyclophosphamide / administration & dosage
  • Dexamethasone / administration & dosage
  • Doxorubicin / administration & dosage
  • Etoposide / administration & dosage
  • Factor V / analysis
  • Female
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Incidence
  • Life Tables
  • Male
  • Middle Aged
  • Multiple Myeloma / blood*
  • Multiple Myeloma / complications
  • Multiple Myeloma / drug therapy
  • Multiple Myeloma / therapy
  • Risk
  • Thalidomide / administration & dosage
  • Thalidomide / adverse effects
  • Thalidomide / pharmacology
  • Thrombophilia / etiology*
  • Venous Thrombosis / epidemiology*
  • Vincristine / administration & dosage

Substances

  • factor V Leiden
  • Thalidomide
  • Vincristine
  • Etoposide
  • Dexamethasone
  • Doxorubicin
  • Cyclophosphamide
  • Factor V
  • Cisplatin

Supplementary concepts

  • CAD protocol 3
  • DCEP protocol
  • VAD protocol