Heparin-Induced Thrombocytopenia in Liver Transplant Recepients

Heparin-induced thrombocytopenia (HIT) is an adverse immune-mediated drug reaction, resulting in a platelet count decrease of 50% within 5 to 10 days after heparin administration. HIT is often associated with venous and/or arterial thrombosis (HITT). The clinical course of HIT developing after liver transplantation (LT) had not been reported. Direct thrombin inhibitors (DTI) were reported to be safe and efficacious in patients who developed HIT yet their safety and efficacy had not been determined in patients who had LT. Also, the optimal management of HIT developing after LT has not been defined.

To evaluate the incidence and the clinical course of patients who developed HIT after LT and the safety of use of DTI in this population.

We performed a retrospective analysis of all patients who had a LT and had clinical HIT confirmed by the anti-PF4/heparin (HIT) antibody by ELISA at our institution between January 2006 and July 2011. A positive test is defined as optical density of > 0.4 with > 50% inhibition. Bleeding was defined per GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries) scale. Alternate causes of thrombocytopenia were excluded by relevant hematologic testing.

During the study period, 438 patients received LT and163 patients were diagnosed with clinical HIT in our 689 bed hospital. Clinical HIT was confirmed in 11 LT patients (2.5%) based on a positive HIT antibody. LT cases constitute 11/163 (6.75%) of all HIT diagnosed in our center. Clinical characteristics of these are described in attached table. Previous thrombosis was reported in 7/11 (63%) patients, of these 5/11 (46%) received prior therapeutic anticoagulation. Baseline thrombocytopenia below 150K was present in 10/11 (90%) cases and 7/11 (63%) had INR prolongation ≥ 1.5. HIT was documented in 2 patients before LT, in 3 patients within 14 days of surgery and in 6 patients more than 14 days post LT. Six (54%) developed HITT and 7/11 (63%) were treated with a DTI (bivalirudin in 6 cases and argatroban in 1 case). On discharge 2/11 (18%) received fondaparinux and 5/11 (45%) received warfarin. Median dose of IV bivalirudin was 0.3 (0.09-0.89) mg/kg/hr. Platelet recovery was noted in all patients at mean of 9.8 (3-30) days. Progressive thrombosis was noted in 2/11 (18%). Moderate bleeding events within 40 days of LT included 2 gastrointestinal bleeds and one episode of epistaxis. Two traumatic bleeds occurred with prolonged anticoagulation for HITT. No deaths or amputations were documented as a direct consequence of HIT. Only one patient with HIT and LT died as a complication of sepsis.

Clinical characteristics of HIT in LT patients: n=11

HIT is common (2.5%) in LT recipients despite low rates of deep venous thromboprophylaxis with heparin due to underlying coagulopathy. Basal thrombocytopenia is frequent in these patients and widely accepted 4T probability score has low predictive value. The risk of HITT and progressive thrombosis is high. Despite baseline coagulopathy, in our experience the use of DTI, especially bivalirudin, seems to be well tolerated and efficacious in this population. Future studies are needed to optimize dosing to reduce bleeding risk.

Off Label Use: Use of bivalirudin and fondaparinaux in the treatment of heparin-induced thrombocytopenia.