Low Molecular Weight Heparin in Sufficient Dose of ≥70 IU/kg as an Effective and Safe Thromboprophylaxis in Patients with Newly Diagnosed Multiple Myeloma during Conventional VAD Induction Therapy.

Background: The patients with multiple myeloma (MM) have an increased risk of venous thromboembolism (VTE), particularly during the induction phase of therapy. Low molecular weight heparins (LMWH) seem to be useful for thromboprophylaxis in these patients. We analyzed prophylactic efficiency of LMWH based on dose either lower or higher than 70 IU/kg of body weight.

Patients and Methods: 223 patients with newly diagnosed MM were treated with induction chemotherapy consisting of vincristine, doxorubicin and dexamethasone (VAD) or vincristine, idarubicin and dexamethasone (VID) as a part of multicenter CMG 2002 trial. The first cohort of 137 patients received no systematic thromboprophylaxis. After a high incidence of thrombotic complications has been reported, the thromboprophylaxis with different doses of LMWHs was used in 86 consecutive patients for 4 months of induction therapy. Finally, 101 patients enrolled to the CMG 2002 trial in single centre were analyzed retrospectively, based on dose either lower or higher than 70 IU/kg of body weight. From this 101 patients 34% (34/101) received no systematic thromboprophylaxis, 38% (39/101) received LMWH (dalteparin) daily dose lower than 70 IU/kg, and 28% (28/101) received LMWHs daily dose higher than 70 IU/kg. The efficacy and safety of this treatment were analyzed. The chi-square test was used for statistical analysis.

Results: Incidence of VTE was significantly reduced in the group of 86 patients receiving the recommended thromboprophylaxis, as compared to 137 patients without prophylaxis (1.2% vs. 12.4%, p=0.003, risk reduction 11.25%). Single centre analysis showed that no VTE was developed in the group of 28 patients receiving more than 70 IU/kg of LMWH daily. It was significantly different from the 34 patients without prophylaxis (0% vs. 15%, p=0.002). The incidence of VTE in 39 patients with LMWHs daily dose lower than 70 IU/kg was reduced to 7.6%, which is still clinicaly significant as compared to cohort of 28 patients receiving more than 70 IU/kg of LMWH daily (0% vs. 7.6%, p=0.05). No case of major bleeding was developed in any group.

Conclusions: Thromboprophylaxis with LMWHs is effective in patients with newly diagnosed multiple myeloma during the induction chemotherapy only if the LMWH dose is sufficient. Our date shown that minimal sufficient dose seems to be more than 70 IU/kg of LMWH daily, as in this cohort of patients no case of VTE was developed.