Pharmacology · Year 2 · from Pharmacology
Case 3: Heparin-Induced Thrombocytopenia (HIT)
Clinical Scenario
A 67-year-old male develops new thrombosis and falling platelet count 8 days after starting heparin for a pulmonary embolism.
Patient Demographics
- Age: 67 years
- Sex: Male
- Weight: 85 kg
Chief Complaint
Painful, swollen left arm with darkened skin
History of Present Illness
The patient was admitted 10 days ago with pulmonary embolism and started on unfractionated heparin infusion, later transitioned to warfarin. His INR is now therapeutic at 2.5. Over the past 2 days, he developed progressive pain and swelling in his left arm with bluish discoloration. His platelet count has dropped from 245,000 to 68,000 over the past 4 days.
Physical Examination
- Vital Signs: BP 135/82 mmHg, HR 88 bpm, RR 18, T 37.8C
- General: Anxious, uncomfortable
- Left upper extremity:
- Tense swelling from hand to upper arm
- Bluish-purple discoloration of fingers
- Diminished radial pulse
- Tender to palpation
- Skin: Erythema and induration at heparin injection sites on abdomen
Workup and Results
| Test | Result | Reference Range |
|---|---|---|
| Platelet count (Day 1) | 245,000/mcL | 150,000-400,000/mcL |
| Platelet count (Day 6) | 156,000/mcL | - |
| Platelet count (Day 10) | 68,000/mcL | - |
| 4Ts Score | 7 (high probability) | - |
| Anti-PF4/heparin antibody | Positive (OD 2.4) | <0.4 |
| Serotonin release assay | 95% release | <20% |
| INR | 2.5 | 2.0-3.0 |
Doppler ultrasound: Acute thrombosis of left axillary and subclavian veins
Diagnosis
Heparin-Induced Thrombocytopenia type II (HIT) with limb-threatening venous thrombosis
Cardiovascular Pharmacology Principles Illustrated
- Immune-mediated mechanism: Antibodies form against complexes of heparin and platelet factor 4 (PF4).
- Paradoxical thrombosis: Despite thrombocytopenia, HIT causes thrombosis (not bleeding) through platelet activation.
- Timing: Typically occurs 5-10 days after heparin exposure (or earlier with prior exposure).
- All heparins implicated: UFH > LMWH, but both can cause HIT.
- Warfarin contraindicated: Can worsen thrombosis during acute HIT by depleting protein C.
Treatment
- Stop ALL heparin immediately (including flushes, coated catheters)
- Stop warfarin (can cause venous limb gangrene in acute HIT)
- Vitamin K 10 mg PO to reverse warfarin
- Start alternative anticoagulant:
- Argatroban (direct thrombin inhibitor) - preferred in hepatic impairment concerns
- Bivalirudin
- Fondaparinux (off-label but commonly used)
- Continue anticoagulation until platelet recovery and therapeutic on long-term agent
- DO NOT transfuse platelets (fuels thrombosis)
- Vascular surgery consultation for limb-threatening ischemia
- Transition to DOAC (not warfarin) for long-term anticoagulation
Key Learning Points
- HIT is a hypercoagulable state despite low platelets
- 4Ts score helps estimate pretest probability
- Never use heparin (including LMWH) in patients with HIT history
- Argatroban monitoring uses aPTT; transitions to warfarin are complex
- Document HIT allergy prominently in medical record