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Heparin-induced thrombocytopenia

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:

September 28, 2022

Summary

Definition

Epidemiology

Epidemiological data refers to the US, unless otherwise specified.

Etiology

Pathophysiology

• Heparin and platelet factor 4 (PF4) form a complex → production of IgG antibodies against the heparin /PF4 complex → IgG antibody - heparin /PF4 immunocomplex binds on platelet surface → platelet activation and aggregation → consumption of platelets ( thrombocytopenia ) and arterial/venous thrombosis
• Thrombocytopenia also occurs due to phagocytosis of IgG antibody-heparin/PF4 immunocomplex-bound platelets by macrophages in the spleen, liver, and bone marrow.

Clinical features

Management

Diagnostics

Initial diagnostics

• CBC: PLT < 50% of the baseline count at heparin initiation
  • Timing of PLT decline: usually within 5–7 days of heparin initiation ; can occur rapidly (within 1–3 days ) ^{[2] [4] [7]}
  • Typical PLT nadir: 40,000–80,000 mm^{3 [4]}
• Coagulation studies: ↑ PTT, ↑ INR, and ↓ fibrinogen may be seen in DIC or massive thrombosis.
• Tests to rule out differential diagnoses
  • Peripheral blood smear: to exclude pseudothrombocytopenia and other findings consistent with an alternative diagnosis
  • Renal function tests: may be abnormal in other causes of thrombocytopenia (e.g., HUS and TTP)
  • Liver chemistries: may be abnormal in other causes of thrombocytopenia (e.g., chronic alcohol abuse, cirrhosis, HELLP syndrome)

A rapidly falling platelet count in a patient with recent heparin exposure should raise concern for HIT, even if the platelet count is still within the normal range.

HIT rarely causes platelet counts to decrease below 20,000 platelets/mm³ . ^[4]

Calculate the 4Ts score in any patient with current or recent heparin exposure who develops significant thrombocytopenia and/or thrombosis. ^{[1] [4]}

Do not wait for diagnostic confirmation; start empirical treatment of HIT immediately in patients with an intermediate or high 4Ts score!

Confirmatory testing is indicated in patients with an intermediate or high PTP of HIT and is a two-stage process. ^[1]

Step one: Order PF4 heparin immunoassay (e.g., ELISA).

Step two: Order functional platelet activation assay (e.g., serotonin release assay).

Screening for asymptomatic deep vein thrombosis (DVT) ^[1]

Additional imaging based on clinical suspicion ^[4]

Treatment

Acute management checklist

• Calculate the 4Ts score in all heparin-exposed patients who develop new-onset thrombocytopenia and/or thrombosis.
• A score ≥ 4 indicates that HIT is likely. Initiate the following urgently.
• Immediately discontinue all heparin products.
• Discontinue vitamin K antagonists and consider reversal with vitamin K.
• Initiate a nonheparin anticoagulant.
• Obtain HIT-specific diagnostic tests.
• Obtain venous compression sonography to screen for asymptomatic DVT in the lower extremities and in any upper extremity with a central venous catheter.
• Consider a hematology consult.

Differential diagnoses

The differential diagnoses listed here are not exhaustive.

References

1. Salter BS, Weiner MM, Trinh MA, et al. Heparin-Induced Thrombocytopenia. J Am Coll Cardiol. 2016; 67 (21): p.2519-2532. doi: 10.1016/j.jacc.2016.02.073 . | Open in Read by QxMD
2. Greinacher A. Heparin-Induced Thrombocytopenia. N Engl J Med. 2015; 373 (3): p.252-261. doi: 10.1056/nejmcp1411910 . | Open in Read by QxMD
3. Warkentin TE, Kelton JG. Temporal Aspects of Heparin-Induced Thrombocytopenia. N Engl J Med. 2001; 344 (17): p.1286-1292. doi: 10.1056/nejm200104263441704 . | Open in Read by QxMD
4. Cuker A, Arepally GM, Chong BH, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia. Blood Advances. 2018; 2 (22): p.3360-3392. doi: 10.1182/bloodadvances.2018024489 . | Open in Read by QxMD
5. 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): p.4160-4167. doi: 10.1182/blood-2012-07-443051 . | Open in Read by QxMD
6. Diagnosis and Management of Heparin-Induced Thrombocytopenia (HIT). https://www.hematology.org/education/clinicians/guidelines-and-quality-care/pocket-guides. Updated: December 1, 2018. Accessed: November 15, 2020.
7. Warkentin TE, Pai M, Linkins L-A. Direct oral anticoagulants for treatment of HIT: update of Hamilton experience and literature review. Blood. 2017; 130 (9): p.1104-1113. doi: 10.1182/blood-2017-04-778993 . | Open in Read by QxMD
8. Caligiuri M, Levi MM, Kaushansky K, et al. Williams Hematology, 9E. McGraw-Hill Education / Medical ; 2015
9. Szokol JW. Heparin-Induced Thrombocytopenia. Semin Cardiothorac Vasc Anesth. 2010; 14 (1): p.73-74. doi: 10.1177/1089253210362795 . | Open in Read by QxMD
10. Kurtz LE, Yang S. Bilateral adrenal hemorrhage associated with heparin induced thrombocytopenia. Am J Hematol. 2007; 82 (6): p.493-494. doi: 10.1002/ajh.20884 . | Open in Read by QxMD
11. Fesler MJ, Creer MH, Richart JM, et al. Heparin-Induced Thrombocytopenia and Cerebral Venous Sinus Thrombosis: Case Report and Literature Review. Neurocrit Care. 2010; 15 (1): p.161-165. doi: 10.1007/s12028-009-9320-y . | Open in Read by QxMD

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