Heparin-induced thrombocytopenia

Background

  • Pathologic activation / consumption of platelets due to antibodies against heparin-platelet complex
  • Can be caused by unfractionated heparin or LMWH (10 times more common in unfractionated)
  • Occurs in 0.5-5% of patients treated with heparin[1]
  • Thrombosis occurs in 35-75% of patients ; 20-30% die within 1 month[1]
  • HYPER-coagulable, despite low platelet count
    • activated platelets bound in clot, thus low platelet count
    • bleeding is unusual

Type 1 HIT

  • Onset within 48h of initiating heparin
  • Drop in platelet count due to platelet activation by heparin
  • Platelet count usually normalizes in a few days with continued heparin treatment[2]

Type 2 HIT

  • Immune-mediated process
  • Onset typically 5-10 days after exposure to heparin
  • Complicated by thrombosis[2]

Clinical Features

Gangrenous right hand and left foot in a patient with antibody-confirmed HIT.
Ischaemic changes in the right hand (A), right foot (B), and left food (C) from HIT.
Lower extremity gangrene secondary to both arterial and venous thrombosis.

Immediate Symptoms

Delayed Symptoms

Differential Diagnosis

Thrombocytopenia

Decreased production

Increased platelet destruction or use

Drug Induced

Comparison by Etiology

ITP TTP HUS HIT DIC
↓ PLT Yes Yes Yes Yes Yes
↑PT/INR No No No +/- Yes
MAHA No Yes Yes No Yes
↓ Fibrinogen No No No No Yes
Ok to give PLT Yes No No No Yes

Microangiopathic Hemolytic Anemia (MAHA)

Evaluation

  • Serotonin release assay (SRA) = gold standard
  • Anti-PF4 plus SRA has combined sensitivity of 99% [3]
  • Positivity determined by optical density (OD) reported with assay (same concept as a titer)
    • OD <1 = <5% chance of HIT
    • OD 1.4 = 50% chance of HIT
    • OD >2 = 90% chance of HIT

Pre-test Probability Scoring (The 4 T Score)[4]

  • Thrombocytopenia
    • 2 points: platelets > 50% fall AND nadir > 20k
    • 1 points: patient 30-50% fall OR nadir 10-19k
  • Timing
    • 2 points: clear onset 5-10 days OR platelet fall < 1 day with prior heparin exposure within 30 days
    • 1 point: likely onset 5-10 days OR fall < 1 day with prior heparin exposure 30-100 days
  • Thrombosis
    • 2 points: new thrombosis or skin necrosis at injection sites
    • 1 point: suspected thrombosis or progressive/recurrent thrombosis
  • Likelihood of other causes
    • 2 points: none apparent
    • 1 point: possible
  • Scoring
    • ≤3 is low risk and do not require further testing or heparin discontinuation
    • ≥4 should have serologic testing performed, heparin discontinued, and alternative anticoagulation started

Management

  • Discontinue all heparin products [5]
  • Do not give platelets (may precipitate thrombosis)
  • Start anticoagulation with no heparin based compound such as a direct thrombin inhibitor: [lepirudin (unless renal failure), argatroban (unless hepatobiliary disease), bivalirudin] or direct Xa inhibitor (fondaparinux, danaparoid)
    • 4T Score ≥4 with/without thrombosis and average bleeding risk should receive therapeutic dose
    • 4T Score ≥4 with/without thrombosis and high bleeding risk should receive prophylactic dose
  • Avoid warfarin until platelets >100K-150K
    • Those already on warfarin should receive vitamin K to restore protein C & S levels

Disposition

  • Admit (with hematology consult)

See Also

References

  1. 1.0 1.1 Lovecchio F. Heparin-induced thrombocytopenia. Clin Toxicol (Phila). 2014 Jul;52(6):579-83
  2. 2.0 2.1 Warkentin T. et al. Heparin-induced thrombocytopenia: recognition, treatment, and prevention: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004 Sep;126(3 Suppl):311S-337S
  3. Warkentin TE, et al. Chest. 2008;133(6 Suppl):340S-380S.
  4. Janz TG, Hamilton GC: Disorders of Hemostasis, in Marx JA, Hockberger RS, Walls RM, et al (eds): Rosen’s Emergency Medicine: Concepts and Clinical Practice, ed 7. St. Louis, Mosby, Inc., 2010, (Ch) 120: p 1578-1589.
  5. Cuker A, Arepally GM, Chong BH, Cines DB, Greinacher A, Gruel Y, Linkins LA, Rodner SB, Selleng S, Warkentin TE, Wex A, Mustafa RA, Morgan RL, Santesso N. American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia. Blood Adv. 2018 Nov 27;2(22):3360-3392. doi: 10.1182/bloodadvances.2018024489. PMID: 30482768; PMCID: PMC6258919.