VTE Prophylaxis with Desirudin in Patients with Thrombocytopenia: Insights From the DESIRABLE Trial,

Prophylaxis for venous thromboembolism (VTEP) is recommended for critically ill patients with limited mobility or those undergoing major surgery. Commonly used agents are heparin-based therapies (unfractionated or low-molecular-weight heparin (H); fondaparinux) which are of limited utility in patients with thrombocytopenia (TCP) due to concerns about bleeding risk and the possibility of heparin-induced thrombocytopenia (HIT). The DESIRABLE trial was designed to examine the safety profile of desirudin (Iprivask^®, recombinant hirudin), the only parenteral heparin alternative approved for VTEP in the US, in a broad range of perioperative and critically ill patients requiring VTEP. DESIRABLE was a multicenter, open-label, single-arm study which enrolled 516 subjects at 19 centers. Desirudin was administered for as long as clinically required at 15 mg Q12H SC. Patients with uncontrolled bleeding were excluded. The primary endpoint was Major Bleeding; secondary endpoints included incidence of new symptomatic VTE. The present analysis was performed to evaluate the safety profile of desirudin in DESIRABLE patients who were thrombocytopenic at enrollment.

Case report forms were reviewed to identify subjects with TCP, defined as having a platelet count of <150 × 10⁶/mL. Demographic characteristics, incidence of Major Bleeding, VTE, and serious adverse events were determined for comparison to the overall cohort.

Analysis of case report forms identified 93 subjects with TCP (<150 × 10⁶/mL), 50 (54%) of whom had a platelet count <100 × 10⁶/mL. Compared to subjects with normal platelet counts, TCP subjects were older (median age 66 vs. 59), more likely to be male (65% vs 34%) and underweight (BMI <25: 37% vs 23%), and less likely to be morbidly obese (BMI >35, 14% vs 31%). TCP subjects were also more likely to have a recent (<3 months or concurrent) history of cardiac surgery (CABG or valve, 24% vs 3%), coronary artery disease (47% vs 20%), congestive heart failure (18% vs 7%) and/or atrial fibrillation (16% vs 4%). HIT was suspected in 27 (29%) of TCP subjects, although the presence of HIT was not confirmed by SRA testing. No subjects had clinical evidence of thrombosis at enrollment. Treatment duration was similar between TCP subjects and the overall cohort (5.1±3.3 days vs 4.9±3.2 days, p=NS). The incidence of new VTE was similar between TCP and non-TCP subjects: 2 (2.2%) TCP subjects developed a VTE vs 6 of 423 non-TCP subjects (1.4%, p=NS). There were no bleeding events meeting criteria for the Primary Endpoint in either group. Serious adverse events occurred in 16 (17%) TCP subjects, all considered unrelated to study drug. Serious adverse events were reported in 64 (15%) non-TCP subjects, 5 of which were considered “possibly related” to study drug.

DESIRABLE demonstrated the clinical utility and safety of desirudin in a broad population of critically ill perioperative and medical patients. The present subanalysis indicates that this finding holds true for hospitalized TCP patients, suggesting that desirudin may be a useful alternative for VTE prophylaxis patients for whom HIT is suspected or heparin-based therapies are considered inappropriate. Additional randomized trials in TCP patients are needed to confirm these findings.

Levy:Canyon Pharmaceuticals: Consultancy. Off Label Use: Desirudin is approved for VTE prophylaxis following elective hip arthroplasty. Data presented may describe use of desirudin for VTE prophylaxis in patients who did not undergo total hip arthroscopy. Kurz:Canyon Pharmaceuticals: Employment. Marder:Canyon Pharmaceuticals: Clinical Trial Steering Committee.