22. Heparin-Induced Thrombocytopenia (HIT)

Classification: Type 1 vs. Type 2

 Type 1Type 2
  Frequency10-20%1-3%
  Timing1-4 days5-10 days (and even longer)
  Nadir of platelet count100,00030-55,000
  Antibody mediatedNoYes
  Thromboembolic eventsNone30-80%
  Hemorrhagic eventsNoneRarely
  ManagementObserveDiscontinue heparin and start alternate anticoagulant.

Evaluate the pre-test probability of HIT: unfortunately, the laboratory tests to diagnose HIT take at least a few days to come back. Therefore, use the following clinical scoring system (4-T score) to determine the pre-test probability of HIT and the appropriate management plan. Remember to periodically re-assess, as new information can change pre-test probability (e.g. positive blood cultures).

Clinical Factor2 points1 point0 points
Thrombocytopenia

Nadir 20-100, or

>50% platelet fall

Nadir 10-19 or 30-50% platelet fallNadir <10, or <30% platelet fall
Timing of onset of platelet fallDay 5-10, or ≤ day 1 with recent heparin (past 30 days)> day 10 or timing unclear (but fits with HIT)≤ day 1 (no recent heparin)
Thrombosis or other sequelaeProven thrombosis, skin necrosis, or acute systemic reaction following bolus of heparin IVProgressive, recurrent, or silent thrombosis; erythematous skin lesionsNone
Other cause of platelet fallNone evidentPossibleDefinite

Initial Management

  • Based on the total pre-test probability score, come up with a management plan (total score 0 to 8):
    • Score 0-3: continue heparin; no need for further testing.
    • Score 4-5: physician judgment; consider laboratory testing.
    • Score 6-8:
      • Perform laboratory testing for confirmation (see below).
      • Stop all heparin, including heparin flushes and heparin-coated catheters. Give alternative, non-heparin anticoagulant (direct thrombin inhibitor or non-heparin factor Xa inhibitor).
      • Avoid warfarin until platelet count >100,000/μL. Warfarin starting dose should be low and therapy should be overlapped with a direct thrombin inhibitor for a minimum of 5 days.

Laboratory Diagnosis

  • Based on your pre-test probability score, seek further laboratory testing starting with a platelet factor 4 antibody assay (“HIT” antibodies). Proceed as follows:
Pretest Score

PF4Ab

NEGATIVE

PF4Ab

POSITIVE

6-8Send Serotonin Release AssaySTOP. HIT confirmed

4-5

or recent CABG

STOP. No HITSend Serotonin Release Assay
0-3No testing indicatedNo testing indicated

Treatment

  • Includes stopping all heparin products (including heparin flushes and heparin-coated catheters) and instituting alternate anticoagulation, to prevent thrombotic complications. Choices include bivalirudin, lepirudin, or argatroban (direct thrombin inhibitors). 
  • With liver disease best choices are lepirudin, danaparoid, or fondaparinux and with renal disease can use argatroban or lower doses of lepirudin. See section Hematology/Oncology: IV Direct Thrombin Inhibitors.

Key Points

  • Type I is a nonimmune phenomenon and limited while Type II is an antibody-mediated disorder including HIT and requires treatment.
  • If HIT is suspected, assess the pretest probability to guide management.
  • Complications include arterial or venous thromboses; often occur at sites of pre-existing pathology.

 

Alving BM. How I treat heparin-induced thrombocytopenia and thrombosis. Blood 2003;101:31-37.

Rice L, Attisha WK, Drexler A, et al. Delayed-onset heparin-induced thrombocytopenia. Ann Intern Med 2002;136:210-215.

UCSF Comprehensive Hemostasis and Antithrombotic Service (CHAS) guidelines, 2004