Heparin-induced thrombocytopenia risk factors

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Heparin-induced thrombocytopenia

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2], Aric C. Hall, M.D., [3] Shyam Patel [4]

Overview

Increased risk for heparin-induced thrombocytopenia depends on type of heparin (unfractionated heparin more than low molecular weight heparin), duration of therapy, females, and type of patients (commoner in surgical patients that require large amount of heparin), and other factors. Protective risk factors include use of low molecular weight heparin, low PF4 antibody titers, and others.

Risk factors

Adverse risk factors

  • Duration of heparin treatment: A long duration of heparin expsosure, such as 2 weeks, is associated with the greatest risk.[1]
  • Type of heparin: Unfractionated heparin (UFH) has a greater risk than low molecular weight heparin (LMWH. Bovine heparin carries a higher risk for HIT than porcine heparin.[2]
  • Type of patient: Surgical patients are at higher risk than medical; cardiac surgical patients have the highest risk of all.[3] This is though to be related to differences in basal level of circulating platelet factor 4 (PF4) and platelet activation in these various populations. The incidence of HIT in cardiac surgery or orthopedic surgery patients is 1-5%.[4]
  • Sex: Females have a higher risk than males. The odds ratio (OR) is 2.4:1.[3] This is thought to be related to higher predilection for autoimmune tendencies in females compared to males.
  • Race: African Americans are more prone to HIT than Caucasians.[3]
  • PF4 optical density (OD): The degree of elevation of the OD valve of the PF4 IgG is directly correlated with the risk for HIT. For patients with a Pf4 IgG OD of < 0.4, the risk of HIT is typically < 5%. No follow up testing is required. For patients with a PF4 IgG OD of > 1.0, the risk of HIT is signicantly higher (3.4-6-fold increase risk of thrombosis), requiring follow up testing with a functional assay such as the 14C-serotonin release assay or the heparin-induced platelet aggregation assay.[2]
  • Genetic polymorphisms: Polymorphisms in the crystallized fragment (Fc) gamma receptor have been suggested to play in role in the risk for HIT. It is presumed that high affinity receptors result in stronger IgG binding to platelet membranes, allowing for the release of procoagulants.
  • There is no increase in risk of HIT with genetic risk factors for thrombosis such as factor V Leiden, prothrombin gene mutation, methylenetetrahydrofolate reductase (MTHFR) polymorphism and platelet-receptor polymorphisms.

Protective risk factors

  • Type of heparin: Use of low molecular weight heparin such as enoxaparin carries a lower risk for HIT. Porcine heparin carries a lower risk for HIT compared to bovine heparin.[2]
  • Type of patient: Pediatric or obstetric patients have a lower risk for HIT than medical or surgical patients. Obstetrics patients have a 0.1-1% risk of developing HIT, as compared to 1-5% risk in surgical patients.[4]
  • PF4 optical density: A low PF4 IgG OD of less than 0.4 suggests a very low risk for HIT.

Reference

  1. Warkentin TE, Sheppard JA, Sigouin CS, Kohlmann T, Eichler P, Greinacher A. Gender imbalance and risk factor interactions in heparin-induced thrombocytopenia. Blood 2006;108:2937-41. PMID 16857993.
  2. 2.0 2.1 2.2 Arepally GM, Ortel TL (2010). "Heparin-induced thrombocytopenia". Annu Rev Med. 61: 77–90. doi:10.1146/annurev.med.042808.171814. PMC 4153429. PMID 20059332.
  3. 3.0 3.1 3.2 Lee GM, Arepally GM (2013). "Diagnosis and management of heparin-induced thrombocytopenia". Hematol Oncol Clin North Am. 27 (3): 541–63. doi:10.1016/j.hoc.2013.02.001. PMC 3668315. PMID 23714311.
  4. 4.0 4.1 Linkins LA, Dans AL, Moores LK, Bona R, Davidson BL, Schulman S; et al. (2012). "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. 141 (2 Suppl): e495S–e530S. doi:10.1378/chest.11-2303. PMC 3278058. PMID 22315270.

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