Heparin-induced thrombocytopenia: Difference between revisions
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==Background== | ==Background== | ||
*Pathologic activation / consumption of platelets due to antibodies against heparin-platelet complex | *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 unfranctionated) | |||
*Can be caused by | |||
*Occurs in 0.5-5% of patients treated with heparin<ref name="Lovecchio"> Lovecchio F. Heparin-induced thrombocytopenia. Clin Toxicol (Phila). 2014 Jul;52(6):579-83</ref> | *Occurs in 0.5-5% of patients treated with heparin<ref name="Lovecchio"> Lovecchio F. Heparin-induced thrombocytopenia. Clin Toxicol (Phila). 2014 Jul;52(6):579-83</ref> | ||
*Thrombosis occurs in 35-75% of patients ; 20-30% die within 1 month<ref name="Lovecchio"></ref> | *Thrombosis occurs in 35-75% of patients ; 20-30% die within 1 month<ref name="Lovecchio"></ref> | ||
*HYPER-coagulable, ''despite'' low platelet count | |||
**activated platelets bound in clot, thus low platelet count | |||
**bleeding is unusual | |||
===Type 1 HIT=== | ===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<ref name="guidelines hit">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</ref> | |||
===Type 2 HIT=== | ===Type 2 HIT=== | ||
*Immune-mediated process | |||
*Onset typically 5-10 days after exposure to heparin | |||
*Complicated by thrombosis<ref name="guidelines hit"></ref> | |||
==Clinical Features== | ==Clinical Features== | ||
*The 4 Ts | |||
**[[Thrombocytopenia|'''T'''hrombocytopenia]] | |||
**'''T'''iming (5-14d) | |||
**[[thromboembolism|'''T'''hrombosis]] | |||
**No o'''T'''her cause | |||
===Immediate Symptoms=== | |||
*Flushing | |||
*[[Tachycardia]] | |||
*[[Hypotension]] | |||
*[[Dyspnea]] | |||
===Delayed Symptoms=== | ===Delayed Symptoms=== | ||
| Line 18: | Line 34: | ||
*[[DVT]] or [[PE]] | *[[DVT]] or [[PE]] | ||
*Cerebral vein or adrenal vein thrombosis | *Cerebral vein or adrenal vein thrombosis | ||
*Limb arterial occlusion | *[[Acute arterial ischemia|Limb arterial occlusion]] | ||
*[[CVA]] | *[[CVA]] | ||
*[[MI]] | *[[MI]] | ||
*Skin necrosis | *Skin necrosis | ||
==Differential Diagnosis== | ==Differential Diagnosis== | ||
| Line 36: | Line 46: | ||
==Pre-test Probability Scoring<ref>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.</ref>== | ==Pre-test Probability Scoring<ref>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.</ref>== | ||
*Thrombocytopenia | *Thrombocytopenia | ||
**2 | **2 points: platelets > 50% fall AND nadir > 20k | ||
**1 | **1 points: patient 30-50% fall OR nadir 10-19k | ||
*Timing | *Timing | ||
**2 | **2 points: clear onset 5-10 days OR platelet fall < 1 day with prior heparin exposure within 30 days | ||
**1 | **1 point: likely onset 5-10 days OR fall < 1 day with prior heparin exposure 30-100 days | ||
*Thrombosis | *Thrombosis | ||
**2 | **2 points: new thrombosis or skin necrosis at injection sites | ||
**1 | **1 point: suspected thrombosis or progressive/recurrent thrombosis | ||
*Likelihood of other causes | *Likelihood of other causes | ||
**2 | **2 points: none apparent | ||
**1 | **1 point: possible | ||
*Scoring | *Scoring | ||
**≤ 3, low probability (≤5%) | **≤ 3, low probability (≤5%) | ||
| Line 52: | Line 62: | ||
**≥ 6, high prob (~65%) | **≥ 6, high prob (~65%) | ||
== | ==Evaluation== | ||
*Serotonin release assay (SRA) = gold standard | *Serotonin release assay (SRA) = gold standard | ||
*Anti-PF4 plus SRA has combined senativity of 99% <ref> | *Anti-PF4 plus SRA has combined senativity of 99% <ref> | ||
| Line 62: | Line 72: | ||
==Management== | ==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 | *Admit (with hematology consult) | ||
==See Also== | ==See Also== | ||
*[[Unfractionated | *[[Unfractionated heparin]] | ||
*[[Low | *[[Low molecular weight heparin]] | ||
*[[Coagulopathy ( | *[[Coagulopathy (main)]] | ||
*[[Hirudins]] | |||
==References== | ==References== | ||
Revision as of 00:56, 1 October 2019
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 unfranctionated)
- 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 Ts
- Thrombocytopenia
- Timing (5-14d)
- Thrombosis
- No oTher cause
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[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 senativity 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.