Heparin-Induced Thrombocytopaenia (HIT): HIT Happens!

PATHCHAT Edition No. 22
Please contact your local Ampath pathologist for more information.

Introduction

🔹 What is Heparin-Induced Thrombocytopaenia (HIT)?

• HIT is a severe immune-mediated reaction to heparin that can lead to life-threatening thrombosis.
• There are two types of HIT:
  • Type 1 HIT: A mild, transient drop in platelet count seen in most patients receiving heparin. Clinically insignificant.
  • Type 2 HIT: A more severe immune reaction that occurs in 0.3% – 3% of patients, with a 20% mortality rate if untreated.
• Unfractionated heparin has a higher HIT risk (1% – 5%) compared to low molecular weight heparin (0.1% – 1%).

Pathogenesis of HIT

✅ HIT is caused by the formation of antibodies against heparin-platelet factor 4 (PF4) complexes.
✅ These antigen-antibody complexes activate platelets, leading to:

• Platelet activation and release of procoagulant-rich microparticles.
• Coagulation cascade activation via tissue factor, leading to Factor IX and X activation.
• Increased risk of arterial and venous thrombosis.

🚨 HIT is a prothrombotic disorder and requires immediate intervention.

Diagnosis of HIT

🔹 HIT should be diagnosed clinically first, using the 4Ts Scoring System:

✔ 1. Thrombocytopaenia (Platelet Drop)

• Score 2: Platelet count drops by >50%, but remains above 20 × 10⁹/L.
• Score 1: Platelet count drops by 30% – 50% or falls to 10–19 × 10⁹/L.
• Score 0: Platelet count drops by <30% or falls below 10 × 10⁹/L.

✔ 2. Timing of Platelet Drop

• Score 2: Platelet drop occurs 5–10 days after heparin exposure, or within 1 day in patients previously exposed to heparin (past 30 days).
• Score 1: Platelet drop occurs after 10 days, or within 1 day if heparin exposure was more than 30 days ago (past 31–100 days).
• Score 0: Platelet drop occurs before day 4, with no prior heparin exposure.

✔ 3. Thrombosis or Other Complications

• Score 2: Proven new thrombosis, skin necrosis, or acute systemic reaction after intravenous unfractionated heparin (UFH) bolus.
• Score 1: Suspected thrombosis, progressive/recurrent thrombosis, or erythematous skin lesions.
• Score 0: No thrombosis or complications.

✔ 4. Alternative Causes of Thrombocytopaenia

• Score 2: No other evident cause of thrombocytopaenia.
• Score 1: Possible other cause of thrombocytopaenia.
• Score 0: Definite other cause of thrombocytopaenia.

Interpreting the 4Ts Score

✔ High probability (Score 6–8): Strong suspicion of HIT – urgent testing and treatment required.
✔ Intermediate probability (Score 4–5): Possible HIT – further laboratory testing needed.
✔ Low probability (Score 0–3): HIT unlikely – consider other causes of thrombocytopaenia.

📌 A 50% platelet drop (even if still within normal range) is significant for HIT!

Laboratory Diagnosis of HIT

✅ The following tests can help confirm HIT:

1️⃣ ELISA for HIT Antibodies:

• High sensitivity (rules out HIT if negative), but low specificity (false positives possible).
• Best used to exclude HIT rather than confirm it.

2️⃣ Serotonin Release Assay (SRA) (Gold Standard):

• Highly specific for HIT but complex and not routinely available.
• Used mainly in research or specialized centers.

3️⃣ Modified Platelet Aggregation Test:

• High specificity (>90%) but variable sensitivity (50% – 80%).
• Detects platelet activation in the presence of heparin.

Specimen Collection for HIT Testing

🔹 To ensure accurate testing:
✅ Collect blood in a citrate (blue-top) tube.
✅ Include a sample of the heparin infusion used for the patient, if possible.
✅ A positive test is indicated by >20% aggregation of normal platelets in the presence of heparin and patient plasma.

Treatment of HIT

🚨 Immediate Actions When HIT is Suspected:
1️⃣ Stop ALL forms of heparin immediately (including heparin flushes and low molecular weight heparin).
2️⃣ Discontinue warfarin if the patient is already on it.
3️⃣ Administer a non-heparin anticoagulant to reduce clotting risk.

🔹 Recommended Non-Heparin Anticoagulants:
✅ Fondaparinux (Arixtra) (Recommended by British Committee for Standards in Haematology - BCSH).
✅ Lepirudin, Argatroban, or Danaparoid (Recommended by the American College of Chest Physicians - ACCP, but unavailable in South Africa).

Monitoring & Transition to Warfarin

✅ Monitor platelet count closely.
✅ Warfarin should NOT be started until platelet count recovers to at least 150 × 10⁹/L.
✅ Warfarin must overlap with a non-heparin anticoagulant for at least 5 days.
✅ Ensure the INR is within the therapeutic range for two consecutive days before stopping the non-heparin anticoagulant.

Long-Term Considerations

🔹 HIT Patients Should Avoid Heparin for Life:

• Patients must be educated on their HIT history and advised to avoid heparin for at least 3–4 months.
• If heparin is required in the future, a specialist should be consulted.

Key Takeaways for Clinicians

✅ HIT is a life-threatening disorder requiring immediate recognition and intervention.
✅ A clinical 4Ts score is essential before laboratory testing.
✅ Dramatic platelet drops (>50%) are key indicators of HIT.
✅ Discontinue ALL heparin and switch to a non-heparin anticoagulant.
✅ Do NOT start warfarin until platelet counts recover.
✅ Patients should avoid future heparin exposure.

References

1. Arepally GM et al. (2006). Heparin-induced thrombocytopaenia. The New England Journal of Medicine, pp. 809–817.
2. Bain BJ et al. (2012). Dacie and Lewis Practical Haematology (11th edition). Churchill Livingstone, London.
3. Chong BH and Chong JH. (2004). Heparin-induced thrombocytopaenia. Expert Reviews in Cardiovascular Therapy, 2(4), pp. 547–599.
4. Guyatt GH et al. (2012). Antithrombotic therapy and prevention of thrombosis: ACCP Evidence-Based Clinical Practice Guidelines (9th Edition). Chest, 141(2), pp. 7–47.
5. Kelton JG et al. (2013). Non-heparin anticoagulants for HIT. The New England Journal of Medicine, pp. 737–744.
6. Rice L. (2004). Heparin-induced thrombocytopaenia. Archives of Internal Medicine, pp. 1961–1964.