Heparin-Induced Thrombocytopenia in Healthy Individuals with Continuous Heparin Infusion

Abstract

The risk for developing heparin-induced thrombocytopenia in healthy individuals is thought to be low, but monitoring recommendations remain controversial. Therefore, a retrospective cohort study was conducted to identify the incidence of thrombocytopenic events in a healthy research population exposed and re-exposed to continuous intravenous (IV) unfractionated heparin. The Division of Sleep Medicine and the Centre for Clinical Investigations at Brigham and Women's Hospital, Boston, Massachusetts, United States, instituted a standardized platelet monitoring procedure for all research protocols that involved heparin to detect platelet count decreases. Protocol-related frequent blood sampling required use of continuous IV unfractionated heparin infusion (5,000 unit/L in 0.45% saline at 40 mL/h) to maintain line patency over extended periods of IV access. From the years 2009 to 2012, a total of 273 healthy volunteers enrolled in Sleep Medicine research protocols met study criteria as having been exposed and/or re-exposed to continuously infused intravenous heparin for at least 4 hours. The mean continuous heparin exposure time was 88 ± 82 SD hours with a total of 397 heparin exposure and re-exposure events. Platelet count measurements were obtained on 629 occasions, representing a range from 2 to 9 draws per participant. No platelet count decrease of more than 50% was detected. There were no detected adverse bleeding or thrombotic events. In this retrospective study of healthy volunteers involved in a rigorously applied inpatient platelet monitoring protocol, heparin exposure and re-exposure did not lower platelet concentration and, therefore, does not appear to be associated with increased risk of HIT in this population.

Keywords

healthy volunteer - heparin - platelets - thrombocytopenia

• References

• 1 Arepally GM, Ortel TL. Clinical practice. Heparin-induced thrombocytopenia. N Engl J Med 2006; 355 (08) 809-817
• 2 Cuker A, Gimotty PA, Crowther MA, Warkentin TE. Predictive value of the 4Ts scoring system for heparin-induced thrombocytopenia: a systematic review and meta-analysis. Blood 2012; 120 (20) 4160-4167
• 3 Lubenow N, Hinz P, Thomaschewski S. , et al. The severity of trauma determines the immune response to PF4/heparin and the frequency of heparin-induced thrombocytopenia. Blood 2010; 115 (09) 1797-1803
• 4 Kelton JG, Warkentin TE, Moore JC. , et al. A prospective study measuring the development of antibodies against platelet factor 4-heparin in healthy males after exposure to heparins. J Thromb Haemost 2012; 10 (07) 1446-1449
• 5 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 (08) 2710-2715
• 6 Greinacher A, Warkentin TE. Risk of heparin-induced thrombocytopenia in patients receiving thromboprophylaxis. Expert Rev Hematol 2008; 1 (01) 75-85
• 7 ACCP Guidelines Bundle: Heparin-induced thrombocytopenia. Available at: http://eguideline.guidelinecentral.com/i/164400-heparin-induced-thrombocytopenia-accp/9 . Accessed May 16, 2017
• 8 Chaturvedi S, Kohli R, McCrae K. Over-testing for heparin induced thrombocytopenia in hospitalized patients. J Thromb Thrombolysis 2015; 40 (01) 12-16
• 9 Beauverd Y, Boehlen F, Tessitore E. , et al. Suspicion of heparin-induced thrombocytopenia in internal medicine: how appropriate is the ordering of anti-PF4/heparin antibody testing?. Platelets 2015; 26 (07) 632-637
• 10 Hicks LK, Bering H, Carson KR. , et al. The ASH Choosing Wisely® campaign: five hematologic tests and treatments to question. Blood 2013; 122 (24) 3879-3883
• 11 Linkins LA, Dans AL, Moores LK. , et al. Treatment and prevention of heparin-induced thrombocytopenia: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (2, Suppl): e495S-e530S
• 12 ten Berg MJ, van den Bemt PM, Huisman A, Schobben AF, Egberts TC, van Solinge WW. Compliance with platelet count monitoring recommendations and management of possible heparin-induced thrombocytopenia in hospitalized patients receiving low-molecular-weight heparin. Ann Pharmacother 2009; 43 (09) 1405-1412
• 13 Klerman H, St Hilaire MA, Kronauer RE. , et al. Analysis method and experimental conditions affect computed circadian phase from melatonin data. PLoS One 2012; 7 (04) e33836
• 14 Buxton OM, Cain SW, O'Connor SP. , et al. Adverse metabolic consequences in humans of prolonged sleep restriction combined with circadian disruption. Sci Transl Med 2012; 4 (129) 129ra43
• 15 Warkentin TE, Greinacher A. Heparin-induced thrombocytopenia: recognition, treatment, and prevention: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126 (3, Suppl): 311S-337S
• 16 Schwartz KA, Royer G, Kaufman DB, Penner JA. Complications of heparin administration in normal individuals. Am J Hematol 1985; 19 (04) 355-363
• 17 Warkentin TE, Sheppard JA, Sigouin CS, Kohlmann T, Eichler P, Greinacher A. Gender imbalance and risk factor interactions in heparin-induced thrombocytopenia. Blood 2006; 108 (09) 2937-2941