Guidelines for Unfractionated Heparin in Thrombocytopenia
Platelet Count Monitoring Requirements
All patients receiving UFH require baseline platelet count before treatment initiation (or within 4 days if urgent start), followed by risk-stratified monitoring. 1
High-Risk Patients (HIT risk >1%)
- Monitor platelet count every other day (or 2-3 times weekly) from day 4 through day 14 of UFH therapy, or until UFH is discontinued. 1
- High-risk scenarios include: 1
- Therapeutic-dose intravenous UFH
- Postoperative orthopedic surgery patients
- Cardiac surgery with cardiopulmonary bypass
- Patients on ECMO requiring UFH
- Medical patients receiving curative intravenous UFH
Intermediate-Risk Patients (HIT risk 0.1-1%)
- Monitor platelet count once to twice weekly from day 4 through day 14, then weekly for one month if UFH continues. 1
- Intermediate-risk scenarios include: 1
- Medical patients receiving prophylactic UFH
- Cardiovascular surgery patients receiving postoperative LMWH (despite intraoperative UFH bolus)
Low-Risk Patients (HIT risk <0.1%)
- No routine platelet monitoring required. 1
Special Monitoring Considerations
- For patients with heparin exposure within the preceding 30 days, begin platelet monitoring on day 0 (the day UFH is initiated) rather than day 4. 1
- After cardiac surgery with CPB, monitor for "biphasic" platelet decline pattern characteristic of rapid-onset HIT. 1
UFH Use When Thrombocytopenia Already Present
Platelet Count ≥50,000/μL
- Full therapeutic-dose UFH can be administered without dose modification or platelet transfusion support. 2, 3
- Standard weight-based dosing: 80 U/kg bolus followed by 18 U/kg/hour infusion, adjusted to aPTT ratio 1.5-2.5. 1
- Monitor aPTT 6 hours after any dose change until therapeutic, then every 24 hours. 1
- Monitor hemoglobin/hematocrit daily to detect occult bleeding. 1, 3
Platelet Count 25,000-50,000/μL
- Reduce UFH to 50% of therapeutic dose OR use prophylactic dosing (5000 units subcutaneous twice daily). 2, 3
- For acute high-risk thrombosis (pulmonary embolism, extensive DVT, arterial thrombosis), consider full-dose UFH with platelet transfusion support to maintain platelets ≥40,000-50,000/μL. 2, 3
- Avoid concomitant antiplatelet agents. 3
Platelet Count <25,000/μL
- Temporarily discontinue all anticoagulation. 2, 3
- Resume full-dose UFH when platelet count rises >50,000/μL without transfusion support. 2, 3
- For life-threatening thrombosis, consider full-dose UFH with aggressive platelet transfusion support to maintain platelets ≥40,000-50,000/μL. 2
Management of Suspected or Confirmed HIT
Immediate Actions
- Calculate 4Ts score rather than using gestalt approach for pretest probability assessment. 1
- If 4Ts score is low (≤3 points), do not order HIT laboratory testing and do not empirically treat for HIT. 1
- If 4Ts score is intermediate (4-5 points) or high (6-8 points), immediately discontinue ALL heparin products (including UFH line flushes) and initiate alternative non-heparin anticoagulant before laboratory confirmation. 1, 4
Alternative Anticoagulants for Acute HIT
For patients with normal renal function, use argatroban, lepirudin, or danaparoid over other agents. 1
For patients with renal insufficiency, use argatroban over other non-heparin anticoagulants. 1
Argatroban Dosing
- Initial dose: 0.5 mcg/kg/minute IV (reduced from standard 2 mcg/kg/minute due to thrombocytopenia considerations). 1
- Adjust to aPTT ratio 1.5-2.5 or plasma concentration 0.5-1.5 mg/mL. 1
- In liver failure (Child-Pugh score >6), elimination half-life increases from 50 to 152 minutes—use lower initial doses. 1
Danaparoid Dosing
- IV route preferred for acute HIT <1 month. 1
- Curative dose adjusted to anti-Xa activity 0.5-0.8 U/mL (danaparoid range). 1
- Monitor closely in renal failure due to accumulation risk. 1
Vitamin K Antagonist Management
- Do not start warfarin until platelet count substantially recovers (usually ≥150,000/μL). 1
- If warfarin already started when HIT diagnosed, administer vitamin K. 1
- When appropriate to start, use low initial doses (maximum 5 mg warfarin) with minimum 5-day overlap with alternative anticoagulant. 1
Platelet Transfusions in HIT
- Give platelet transfusions only for active bleeding or high-risk invasive procedures, not for thrombocytopenia alone. 1
Cardiac Surgery with CPB in Patients with HIT History
Acute or Subacute HIT (<3 months)
- Postpone surgery >1 month after HIT diagnosis (ideally >3 months). 1
- Perform ELISA for anti-PF4/heparin antibodies before surgery. 1
- If antibodies positive (optical density >1), use one of two strategies: 1
- For urgent surgery, favor UFH + IV antiplatelet agent combination. 1
- Define perioperative anticoagulation protocol in multidisciplinary consultation including hematology. 1
Remote HIT (>3 months) with Negative Antibodies
- Short-term re-exposure to UFH for CPB is acceptable. 1
- Limit UFH exposure to intraoperative period only. 1
- Use alternative anticoagulant (danaparoid or fondaparinux) for postoperative prophylaxis. 1
Critical Pitfalls to Avoid
- Never use LMWH as alternative anticoagulant in confirmed or suspected HIT—cross-reactivity occurs in up to 90% of cases. 1
- Never use fondaparinux as first-line treatment for acute HIT—insufficient evidence despite theoretical appeal. 1
- Never normalize platelet counts as treatment goal in HIT—target is resolution of thrombocytopenia (usually >150,000/μL) before starting warfarin, not achieving normal counts. 1
- Never delay discontinuation of UFH while awaiting HIT antibody results if clinical suspicion is intermediate or high. 1
- Never restart UFH in patient with prior HIT unless antibodies documented negative and surgery absolutely requires it. 1
- Do not use direct oral anticoagulants (DOACs) in acute HIT—no safety data and increased bleeding risk with severe thrombocytopenia. 2, 3