Heparin-induced thrombocytopenia
Revision as of 14:04, 20 May 2023 by Athorne (talk | contribs) (→Pre-test Probability ScoringJanz TG, Hamilton GC: Disorders of Hemostasis, in Marx JA, Hockberger RS, Walls RM, et al (eds): Rosen’s Emergency Medicine: Concepts and Clinical Practice, ed 7. St. Louis, Mosby, Inc., 2010, (Ch) 120: p 1578-1589.)
Background
- Pathologic activation / consumption of platelets due to antibodies against heparin-platelet complex
- Can be caused by unfractionated heparin or LMWH (10 times more common in unfractionated)
- Occurs in 0.5-5% of patients treated with heparin[1]
- Thrombosis occurs in 35-75% of patients ; 20-30% die within 1 month[1]
- HYPER-coagulable, despite low platelet count
- activated platelets bound in clot, thus low platelet count
- bleeding is unusual
Type 1 HIT
- Onset within 48h of initiating heparin
- Drop in platelet count due to platelet activation by heparin
- Platelet count usually normalizes in a few days with continued heparin treatment[2]
Type 2 HIT
- Immune-mediated process
- Onset typically 5-10 days after exposure to heparin
- Complicated by thrombosis[2]
Clinical Features
- The 4 T Score: 0-2 points assigned to each
- Thrombocytopenia
- Timing (5-14d)
- Thrombosis
- No oTher cause
- ≤3 is low risk and do not require further testing or heparin discontinuation
- ≥4 should have serologic testing performed, heparin discontinued, and alternative anticoagulation started
Immediate Symptoms
- Flushing
- Tachycardia
- Hypotension
- Dyspnea
Delayed Symptoms
- >50% decrease in platelet count (median nadir is ~60K; rarely <20K)
- DVT or PE
- Cerebral vein or adrenal vein thrombosis
- Limb arterial occlusion
- CVA
- MI
- Skin necrosis
Differential Diagnosis
Thrombocytopenia
Decreased production
- Marrow infiltration (tumor or infection)
- Viral infections (rubella, HIV)
- Marrow suppression (commonly chemotherapy or radiation)
- Congenital thrombocytopenia
- Fanconi anemia
- Alport syndrome
- Bernand Soulier
- Vitamin B12 and/or folate deficiency
Increased platelet destruction or use
- Idiopathic thrombocytopenic purpura
- Thrombotic Thrombocytopenic Purpura (TTP)
- Hemolytic Uremic Syndrome (HUS)
- Disseminated Intravascular Coagulation (DIC)
- Viral infections (HIV, mumps, varicella, EBV)
- Drugs (heparin, protamine)
- Postransfusion or Posttransplantation
- Autoimmune destruction (SLE or Sarcoidosis)
- Mechanical destruction
- Artificial valves
- ECMO
- HELLP syndrome
- Excessive hemorrhage
- Hemodialysis, extracorporeal circulation
- Splenic Sequestration
- Occurs in Sickle cell disease and Cirrhosis
Drug Induced
- sulfa antibiotics, ETOH, ASA, thiazide diuretics/furosemide
Comparison by Etiology
| ITP | TTP | HUS | HIT | DIC | |
|---|---|---|---|---|---|
| ↓ PLT | Yes | Yes | Yes | Yes | Yes |
| ↑PT/INR | No | No | No | +/- | Yes |
| MAHA | No | Yes | Yes | No | Yes |
| ↓ Fibrinogen | No | No | No | No | Yes |
| Ok to give PLT | Yes | No | No | No | Yes |
Microangiopathic Hemolytic Anemia (MAHA)
- Disseminated Intravascular Coagulation (DIC)
- Thrombotic Thrombocytopenic Purpura (TTP)
- Hemolytic Uremic Syndrome (HUS)
- HELLP syndrome
- Heparin-Induced Thrombocytopenia (HIT)
- Hereditary spherocytosis
- Paroxysmal nocturnal hemoglobinuria (PNH)
- Malignant hypertension
- Scleroderma
- Antiphospholipid Syndrome (APS)
- Other medical causes: malignancy, renal allograft rejection, vasculitides like polyarteritis nodosa and Wegener's granulomatosis
- Drugs: chemotherapy; Clopidogrel (Plavix) associated with TTP
- Nonvascular causes: prosthetic valve (more common with mechanical, more common at aortic valve), LVAD, TIPS, coil embolization, patched AV shunt, AVM
Pre-test Probability Scoring (The 4 T Score)[3]
- Thrombocytopenia
- 2 points: platelets > 50% fall AND nadir > 20k
- 1 points: patient 30-50% fall OR nadir 10-19k
- Timing
- 2 points: clear onset 5-10 days OR platelet fall < 1 day with prior heparin exposure within 30 days
- 1 point: likely onset 5-10 days OR fall < 1 day with prior heparin exposure 30-100 days
- Thrombosis
- 2 points: new thrombosis or skin necrosis at injection sites
- 1 point: suspected thrombosis or progressive/recurrent thrombosis
- Likelihood of other causes
- 2 points: none apparent
- 1 point: possible
- Scoring
- ≤ 3, low probability (≤5%)
- 4-5, intermediate prob (~15%)
- ≥ 6, high prob (~65%)
Evaluation
- Serotonin release assay (SRA) = gold standard
- Anti-PF4 plus SRA has combined sensitivity of 99% [4]
- Positivity determined by optical density (OD) reported with assay (same concept as a titer)
- OD <1 = <5% chance of HIT
- OD 1.4 = 50% chance of HIT
- OD >2 = 90% chance of HIT
Management
- Discontinue all heparin products
- Do not give platelets (may precipitate thrombosis)
- Start anticoagulation with no heparin based compound such as a direct thrombin inhibitor: [lepirudin (unless renal failure), argatroban (unless hepatobiliary disease), bivalirudin] or direct Xa inhibitor (fondaparinux, danaparoid)
- Avoid warfarin until platelets >100K-150K
Disposition
- Admit (with hematology consult)
See Also
References
- ↑ 1.0 1.1 Lovecchio F. Heparin-induced thrombocytopenia. Clin Toxicol (Phila). 2014 Jul;52(6):579-83
- ↑ 2.0 2.1 Warkentin T. et al. Heparin-induced thrombocytopenia: recognition, treatment, and prevention: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004 Sep;126(3 Suppl):311S-337S
- ↑ Janz TG, Hamilton GC: Disorders of Hemostasis, in Marx JA, Hockberger RS, Walls RM, et al (eds): Rosen’s Emergency Medicine: Concepts and Clinical Practice, ed 7. St. Louis, Mosby, Inc., 2010, (Ch) 120: p 1578-1589.
- ↑ Warkentin TE, et al. Chest. 2008;133(6 Suppl):340S-380S.