Association of Heparin Dose, Route, Timing, and Duration With Heparin-Induced Thrombocytopenia

Ann Thorac Surg. 2021 Jul;112(1):32-37. doi: 10.1016/j.athoracsur.2020.09.033. Epub 2020 Nov 18.


Background: The prevalence of heparin-induced thrombocytopenia (HIT) varies by population and the type and duration of heparinoid exposure; however, the association with unfractionated heparin (UFH) dose, route, timing, and duration has not been evaluated in cardiac surgery patients.

Methods: A retrospective case-control study matched HIT-positive adult cardiac surgery patients (positive platelet factor 4 immunoglobulin G and serotonin release assays) 1:1 with HIT-negative controls. Total UFH dose, route, timing, and duration were compared between groups.

Results: The study included 124 patients, 92 male (74%), with mean age of 65 ± 11 years. Significantly more HIT-positive patients received intravenous UFH preoperatively or postoperatively compared with patients without HIT (55 [88.7%] vs 23 [37.1%]; P < .001). There were no significant differences regarding intraoperative or subcutaneous UFH dose or duration. When controlling for obesity and cardiopulmonary bypass duration using multivariable conditional logistic regression, the odds of HIT were increased 10-fold in patients who received preoperative or postoperative intravenous UFH continuous infusion (odds ratio 10.2, 95% confidence interval, 3.1 to 33.7; P < .001). Receiver-operating characteristic curves demonstrated that receiving preoperative or postoperative intravenous UFH infusion total dose greater than 32,000 units (sensitivity 82%, specificity 74%, area under the curve 0.78) or longer than 7 hours (sensitivity 87%, specificity 68%, area under the curve 0.77) was associated with HIT.

Conclusions: Odds of HIT were increased 10-fold in adult cardiac surgery patients receiving preoperative or postoperative intravenous UFH infusion. Intraoperative UFH dose and subcutaneous route were not associated with HIT. Future study should evaluate incorporation of intravenous UFH administration, dose, and duration in HIT scoring tools for cardiac surgery patients.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Anticoagulants / administration & dosage
  • Anticoagulants / adverse effects
  • Cardiac Surgical Procedures*
  • Case-Control Studies
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Heparin / administration & dosage*
  • Heparin / adverse effects
  • Humans
  • Incidence
  • Male
  • Maryland / epidemiology
  • Middle Aged
  • Postoperative Complications / prevention & control*
  • Retrospective Studies
  • Risk Factors
  • Thrombocytopenia / chemically induced*
  • Thrombocytopenia / epidemiology


  • Anticoagulants
  • Heparin