Heparin-induced thrombocytopenia
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Background
- Pathologic activation / consumption of platelets due to antibodies against heparin-platelet complex
- Despite the low platelet count, the patient is actually hyper-coagulable and bleeding is unusual. The activated platelets cause blood clot formation and the platelet count falls because the platelets are bound in clots.
- Can be caused by unfrationated or LMWH (10x common in the former)
- 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]
Type 1 HIT
Occurs within the first 48 hours after heparin use with an initial drop in platelet count due to direct effect of heparin on platelet activation. The platelet count normalizes in a few days with continued heparin treatment.[2]
Type 2 HIT
An immune-mediated process which typically occurs 5-10 days after exposure to heparin complicated by thrombosis. [2]
Clinical Features
- Symptoms usually begin 5-10 days after initiation of heparin or can begin within hours if there are already preexisting circulating antibody from prior sensitization
Delayed Symptoms
- >50% decrease in plt count (median nadir is ~60K; rarely <20K)
- DVT or PE
- Cerebral vein or adrenal vein thrombosis
- Limb arterial occlusion
- CVA
- MI
- Skin necrosis
Immediate Symptoms
- Flushing
- Tachycardia
- Hypotension
- Dyspnea
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[3]
- Thrombocytopenia
- 2 patients: plt > 50% fall AND nadir > 20k
- 1 pt: pt 30-50% fall OR nadir 10-19k
- Timing
- 2 patients: clear onset 5-10 days OR plt fall < 1 day with prior heparin exposure within 30 days
- 1 pt: likely onset 5-10 days OR fall < 1 day with prior heparin exposure 30-100 days
- Thrombosis
- 2 patients: new thrombosis or skin necrosis at injection sites
- 1 pt: suspected thrombosis or progressive/recurrent thrombosis
- Likelihood of other causes
- 2 patients: none apparent
- 1 pt: possible
- Scoring
- ≤ 3, low probability (≤5%)
- 4-5, intermediate prob (~15%)
- ≥ 6, high prob (~65%)
Diagnosis
- Serotonin release assay (SRA) = gold standard
- Anti-PF4 plus SRA has combined senativity of 99% [4]
- Positivity determined by optical density (OD) reported w/ 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
Treatment
- 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
Dispostion
- Admit to medicine with a 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.