Overview
Heparin-Induced Thrombocytopenia (HIT)
Topic Overview
Summary
Heparin-induced thrombocytopenia (HIT) is an immune-mediated prothrombotic disorder caused by antibodies to platelet factor 4 (PF4)-heparin complexes. It typically occurs 5-10 days after heparin exposure. Despite low platelets, the main risk is thrombosis (HITT), not bleeding. HIT is a clinical emergency requiring immediate cessation of all heparin and initiation of alternative anticoagulation. Diagnosis is clinical (4Ts score) plus laboratory confirmation (anti-PF4 antibodies, functional assays).
Key Facts
- Mechanism: Antibodies to PF4-heparin complexes → platelet activation → thrombosis
- Timing: 5-10 days after heparin exposure (or earlier if prior exposure)
- Platelet drop: Over 50% from baseline (nadir usually 20-150)
- Main risk: Thrombosis (30-50% if untreated), NOT bleeding
- Treatment: STOP all heparin + start alternative anticoagulant (argatroban, fondaparinux)
Clinical Pearls
HIT causes THROMBOSIS despite low platelets — it's a prothrombotic state
> 4Ts score: Use to assess clinical probability BEFORE sending lab tests
UFH causes HIT more often than LMWH, but LMWH still causes HIT
Why This Matters Clinically
HIT is paradoxically thrombotic despite thrombocytopenia. Missing it leads to limb-threatening or life-threatening thrombosis. All platelet drops on heparin must be evaluated for HIT.
Visual Summary
Visual assets to be added:
- HIT pathophysiology diagram
- 4Ts score table
- HIT timing graph
- HIT management algorithm
Epidemiology
Incidence
- UFH: 1-5% of exposed patients
- LMWH: 0.1-0.5%
- Higher in surgical (especially cardiac surgery) than medical patients
Risk Factors
| Factor | Notes |
|---|---|
| Heparin type | UFH over LMWH |
| Duration | Over 4 days |
| Surgery | Especially cardiac, orthopaedic |
| Female sex | Slightly higher risk |
| Prior heparin exposure | Rapid onset HIT |
Pathophysiology
Mechanism
- Heparin binds platelet factor 4 (PF4) on platelet surface
- Conformational change exposes neoepitope
- IgG antibodies form to PF4-heparin complex
- Immune complexes bind FcγRIIA on platelets
- Platelet activation → thrombosis + platelet consumption
- Thrombin generation → hypercoagulable state
Why Thrombosis Not Bleeding
- Platelets are ACTIVATED, not just destroyed
- Massive thrombin generation
- Procoagulant microparticles released
Timing
- Typical onset: 5-10 days after heparin start
- Rapid onset (under 24h): Prior heparin exposure within 100 days
- Delayed onset: Rare; occurs after heparin stopped
Clinical Presentation
Platelet Count
Thrombosis (HITT)
Other Features
Red Flags
| Finding | Significance |
|---|---|
| Over 50% platelet drop | Classic HIT |
| New clot on heparin | HITT — urgent |
| Skin necrosis | HIT |
| Rapid platelet drop (under 24h) | Prior exposure |
Fall over 50% from baseline
Common presentation.
Nadir typically 20-150 × 10⁹/L
Common presentation.
Rarely under 20 (consider other causes)
Common presentation.
Clinical Examination
General
- Signs of thrombosis (swollen limb, dyspnoea, stroke)
- Skin examination (necrosis at injection sites)
Cardiovascular
- DVT (leg swelling, tenderness)
- PE (tachycardia, hypoxia)
Skin
- Necrosis at heparin injection sites
- Livedo reticularis
Investigations
4Ts Score — Clinical Probability
| Feature | 2 Points | 1 Point | 0 Points |
|---|---|---|---|
| Thrombocytopenia | Over 50% fall, nadir 20-100 | 30-50% fall, nadir 10-19 | Under 30% fall, nadir under 10 |
| Timing | Day 5-10, or under 1 day if prior heparin | Consistent but unclear | Under 4 days, no prior heparin |
| Thrombosis | New thrombosis, skin necrosis | Progressive or recurrent | None |
| Other causes | None apparent | Possible | Definite |
- Score 0-3: Low probability — HIT unlikely
- Score 4-5: Intermediate — test and consider treatment
- Score 6-8: High probability — treat as HIT pending results
Laboratory Tests
| Test | Notes |
|---|---|
| Anti-PF4/heparin antibody (ELISA) | High sensitivity, moderate specificity |
| Serotonin release assay (SRA) | Gold standard; confirms functional antibodies |
| Heparin-induced platelet activation (HIPA) | Functional assay |
Imaging
- Doppler USS for DVT
- CTPA for PE
- As indicated for other thrombosis
Classification & Staging
Types
| Type | Features |
|---|---|
| HIT Type I | Non-immune; mild platelet drop; benign; no treatment needed |
| HIT Type II | Immune-mediated; serious; requires treatment |
With or Without Thrombosis
- HIT: Thrombocytopenia only
- HITT: HIT with thrombosis
Management
Immediate — STOP All Heparin
| Action | Details |
|---|---|
| Stop ALL heparin | UFH, LMWH, heparin flushes, heparin-coated lines |
| Do NOT wait for lab confirmation | If clinical probability intermediate or high |
| Do NOT give platelet transfusions | May worsen thrombosis ("adding fuel to fire") |
| Do NOT give warfarin until platelets over 150 | Risk of warfarin-induced skin necrosis |
Alternative Anticoagulation
| Agent | Notes |
|---|---|
| Argatroban | Direct thrombin inhibitor; IV infusion; first-line |
| Fondaparinux | Factor Xa inhibitor; SC; widely used off-label |
| Bivalirudin | Direct thrombin inhibitor; short half-life |
| DOACs | Can use for long-term (after acute phase) |
Transition to Long-Term Anticoagulation
- Start warfarin ONLY when platelets over 150
- Overlap with non-heparin anticoagulant for at least 5 days
- Total anticoagulation: 4 weeks (isolated HIT), 3 months (HITT)
Future Heparin Avoidance
- Document HIT in medical records
- Avoid heparin in future (unless life-threatening and no alternative)
- Can use heparin for cardiac surgery if HIT antibodies negative
Complications
Of HIT
- Venous thromboembolism (DVT, PE)
- Arterial thrombosis (stroke, MI, limb ischaemia)
- Limb amputation
- Death
Of Treatment
- Bleeding (excessive anticoagulation)
- Warfarin-induced skin necrosis (if started before platelets recover)
Prognosis & Outcomes
Thrombosis Risk
- 30-50% if untreated
- Reduced to under 10% with appropriate treatment
Mortality
- 5-10% with treatment
- Higher if delayed diagnosis
Platelet Recovery
- Usually recovers within days of stopping heparin
Evidence & Guidelines
Key Guidelines
- BCSH Guideline on Diagnosis and Management of HIT
- ASH Guidelines on HIT
Key Evidence
- 4Ts score is validated for clinical probability assessment
- Argatroban and fondaparinux are effective alternatives
Patient & Family Information
What is HIT?
HIT is an allergic reaction to the blood thinner heparin. It causes low platelets AND an increased risk of blood clots.
Why is it Serious?
Despite having low platelets, HIT causes blood clots, not bleeding. These clots can be dangerous.
Treatment
- Stop heparin immediately
- Use a different blood thinner
- Monitor for blood clots
What Happens Next?
- You will need blood thinners for weeks to months
- You should avoid heparin in the future
- Carry documentation of your HIT diagnosis
Resources
References
Primary Guidelines
- Watson H, et al. Guidelines on the diagnosis and management of heparin-induced thrombocytopenia. Br J Haematol. 2012;159(5):528-540. PMID: 23043677
- Cuker A, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia. Blood Adv. 2018;2(22):3360-3392. PMID: 30482768
Key Reviews
- Arepally GM. Heparin-induced thrombocytopenia. Blood. 2017;129(21):2864-2872. PMID: 28416506