Treatment of Heparin-Induced Thrombocytopenia and Associated Thromboses with Fondaparinux.

The mainstay of therapy for patients with HIT or HIT-associated thrombosis consists of initial administration of a direct thrombin inhibitor (DTI), including lepirudin, bivalirudin, and argatroban followed by a vitamin K antagonist upon platelet recovery. However the use of DTIs is cumbersome because it mandates inpatient setting for continuous intravenous infusion of the medication. There is strong clinical and laboratory evidence suggesting that fondaparinux, a synthetic pentasaccharide inhibitor of factor Xa, does not cross react with heparin-associated antibodies, and may be a viable alternative to DTIs. Based on this evidence new guidelines have been adopted at MSKCC in the past 3 years, which incorporate the use of fondaparinux as initial therapy for the management of patients with suspected diagnosis of HIT. The objective of this retrospective study is to analyze the outcome of patients that were treated using this approach.

A search of the MSKCC pharmacy database has identified all patients who have received fondaparinux during inpatient hospitalization for suspected HIT based on the development of thrombocytopenia and recent exposure to heparin, between January 2006 and March 2009. We have reviewed the laboratory data of these patients to identify the subset of patients in whom the diagnosis of HIT was supported by the presence of heparin associated antibodies as confirmed by ELISA assay. We have reviewed the medical records of this subset of patients to determine their outcome using fondaparinux.

We have identified 21 cancer patients treated with fondaparinux for a suspected diagnosis of HIT that was confirmed by the presence of heparin associated antibodies as determined by ELISA assay. Twelve patients had isolated thrombocytopenia, and 9 had thrombocytopenia associated with thromboses. Nineteen patients received therapeutic doses of fondaparinux upon diagnosis while 2 were initially started on lepirudin and then switched to fondaparinux within 10 days. Successful recovery of platelet count was achieved in 15/21 patients (71.4%) with a mean time to platelet recovery of 9.9 days, (range 2 to 23 days). Among these 15 patients, one developed a new DVT on day 16 of fondaparinux treatment in the setting of a sub-therapeutic anti-Xa level, which led to an increase in the fondaparinux dose. The patient's platelet count subsequently recovered without additional thrombotic complications. Five patients (23.8%), all with end stage metastatic disease, died 2 to 9 days after initiation of fondaparinux and prior to recovery of platelet count. Causes of death were thoroughly investigated and were attributed to progression of underlying widespread malignancy and/or pneumonias in all 5 cases, without suspicion or documentation of new thrombotic event or bleeding. One additional patient with advanced glioblastoma multiforme was diagnosed with intracranial bleeding on day 5 of fondaparinux administration and was subsequently transferred to hospice care without further clinical documentation. One out of the 15 successfully treated patients experienced bleeding prior to platelet recovery, requiring temporary withholding of fondaparinux, which was resumed 4 days later without further bleeding complications.

Fondaparinux appears to be an effective alternative treatment in patients with HIT and HIT-associated thromboses. The rates of successful platelet recovery, thrombotic and bleeding complications are comparable to the ones reported with DTI therapy for the treatment of HIT. However, fondaparinux does not require the cumbersome administration and monitoring of DTI therapy and may be the treatment of choice in the management of HIT.

Off Label Use: Treatment of Heparin-Induced Thrombocytopenia and Associated Thromboses with Fondaparinux.