The Hematologist

January-February 2017, Volume 14, Issue 1

HIT Me With Your Best Shot: Promising Advances in HIT Prevention and Treatment

Sioban Keel, MD Associate Professor of Medicine
University of Washington School of Medicine, Seattle, WA

Published on: January 01, 2017

Looking back at 2016, a couple of papers related to heparin-induced thrombocytopenia (HIT) are notable for reframing the way in which hematologists might approach this relatively common prothrombotic adverse drug reaction. Dr. Kelly E. McGowan and colleagues1 reported the first study to show the success of a HIT prevention strategy. This elegantly straightforward approach redirects our thinking toward the prevention of, rather than early recognition and treatment of, HIT. The authors developed an institutionwide strategy of replacing unfractionated heparin (UFH) with low-molecular-weight heparin (LMWH) for both therapeutic and prophylactic indications. Most care providers were not aware that heparin was being replaced by LMWH, and none were aware that this practice change was being studied. The five- to 10-fold lower risk of HIT with LMWH as compared to UFH2 provided strong rationale for the study, which was conducted at a single tertiary-care hospital in Toronto, Canada. The Avoid-Heparin Initiative was implemented in 2006. The authors reviewed consecutive cases (from 2003 to 2012) with suspected HIT, defined as a clinical suspicion of HIT and a HIT enzyme-linked immunosorbent assay (ELISA).

Rates of suspected HIT, adjudicated HIT (defined as clinically suspected HIT with a positive serotonin release assay [SRA] or a positive HIT ELISA and SRA not done, and diagnosed and treated as HIT by the hospital’s thromboembolism service, and confirmed as HIT by independent adjudication), HIT with thrombosis, and HIT-related expenditures were compared in the preintervention (2003-2005) and postintervention (2007-2012) phases. The annual incidence of suspected cases of HIT decreased from 85.5 to 49 cases per 10,000 admissions (relative risk reduction [RRR], 42%; p<0.001). The annual incidence of adjudicated cases of HIT decreased from 10.7 to 2.2 per 10,000 admissions (RRR, 79%; p<0.001). The annual incidence of adjudicated cases of HIT with thrombosis decreased from 4.6 to 0.4 per 10,000 admissions (RRR, 90.7%; p<0.001). While the authors additionally reported a cost savings in HIT-related expenditures with implementation of their Avoid-Heparin Initiative, this analysis did not account for the higher unit cost of LMWH compared with UFH3 and is thus subject to further scrutiny.

The recognition, accurate diagnosis, and treatment of HIT are resource intensive. Furthermore, thromboembolic complications are often diagnosed simultaneously with a HIT diagnosis or afterwards while on HIT-safe anticoagulation.1 This work establishes the feasibility and success of a hospitalwide HIT-prevention strategy, potentially generalizable to broader hospital settings.

A second notable paper in the field informs anticoagulant choice considerations to reduce the treatment cost of suspected HIT. Patients with HIT are at a high risk for thromboembolic events; discontinuation of heparin alone is not sufficient and the diagnosis necessitates treatment with an alternative non-heparin anticoagulant. The direct thrombin inhibitors, argatroban and bivalrudin are the two currently available FDA-approved anticoagulants for the management of HIT. These agents are expensive and require intravenous administration and laboratory monitoring. Fondaparinux is a chemically synthesized version of the active pentasacchharide unit of heparin that selectively inhibits coagulation factor Xa. It does not interact with platelet factor 4, and considerable anecdotal evidence suggests that it is a safe and effective anticoagulant in HIT.4,5 It is administered subcutaneously, and laboratory monitoring is not required in routine practice.

Dr. Ahmed Aljabri and colleagues applied a decision-tree model to compare the cost-effectiveness of argatroban, bivalirudin, and fondaparinux in terms of cost per adverse event averted (e.g., HIT-related thromboembolism and major bleeding) in a hypothetical cohort of patients with suspected HIT.6 The patient population was limited to adult men and nonpregnant, non–breast-feeding women with creatinine clearance greater than 50 mL/min and suspected or confirmed HIT (defined as a 4T score ≥ 4 with a positive HIT ELISA and a confirmed SRA). Cost estimates were calculated for six days of treatment to a 80.7-kg adult.

Based on institutional costs, the authors reported a lower total cost for fondaparinux than for argatroban and bivalirudin ($151 vs. $1,250 and $1,466, respectively) and a marginally greater gain in adverse events averted with argatroban therapy (0.9989 vs. 0.9957 and 0.9947, respectively). In a secondary analysis based on average wholesale prices, the advantages of fondaparinux were retained ($555 vs. $3,081 and $2,187, respectively and 0.9989 vs. 0.9957 and 0.9947, respectively). Additional analyses incorporating longer duration of therapy, lower incidence of HIT and variable adverse event rates confirmed the cost-effectiveness advantage of fondaparinux.

While prospective head-to-head trials are needed to confirm the safety and efficacy of fondaparinux in HIT, this work provides a strong economic rationale to pursue such studies. Since few data were previously available on the cost-effectiveness of non-heparin anticoagulants for the treatment of HIT, this paper also addresses a knowledge gap in the field and frames the importance of cost considerations in this disease that may prove relevant as other non-heparin anticoagulants emerge as potential therapeutic options in HIT.7

References

  1. McGowan KE, Makari J, Damantouros A, et al. Reducing the hospital burden of heparin-induced thrombocytopenia: impact of an avoid-heparin program. Blood. 2016;127:1954-1959.
  2. Martel N, Lee J, Wells PS. Risk for heparin-induced thrombocytopenia with unfractionated and low-molecular-weight heparin thromboprophylaxis: a meta-analysis. Blood. 2005;106:2710-2715.
  3. Fowler RA, Mittmann N, Geerts W, et al. Cost-effectiveness of dalteparin vs unfractionated heparin for the prevention of venous thromboembolism in critically ill patients. JAMA. 2014;312:2135-2145.
  4. Warkentin TE, Pai M, Sheppard JI, et al. Fondaparinux treatment of acute heparin-induced thrombocytopenia confirmed by the serotonin-release assay: a 30-month, 16-patient case series. J Thromb Haemost. 2011;9:2389-2396.
  5. Lobo B, Finch C, Howard A, et al. Fondaparinux for the treatment of acute heparin-induced thrombocytopenia. Thromb Haemost. 2008;99:208-214.
  6. Aljabri A, Huckleberry Y, Karnes J, et al. Cost-effectiveness of anticoagulants for the management of suspected heparin-induced thrombocytopenia in the US. Blood. 2016;pii:blood-2016-07-728030. [Epub ahead of print].
  7. Linkins LA, Warkentin TE, Pai M, et al. Rivaroxaban for treatment of suspected or confirmed heparin-induced thrombocytopenia study. J Thromb Haemost. 2016;14:1206-1210.

Conflict of Interests

Dr. Keel indicated no relevant conflicts of interest. back to top