Heparin-induced thrombocytopenia resident survival guide

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Karol Gema Hernandez, M.D. [2]

Definition

Heparin induced thrombocytopenia (HIT) is an antibody-mediated adverse drug reaction that predisposes to elevated risks of arterial and venous thromboembolism.

Causes

Life Threatening Causes

Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated.

• Life threatening cause 1
• Life threatening cause 2
• Life threatening cause 3

Common Causes

• Common cause 1
• Common cause 2
• Common cause 3
• Common cause 4
• Common cause 5

Screening for HIT

❑ Asses the risk of HIT

Patient Population (Minimum of 4-d Exposure) Incidence of HIT, % Postoperative patients Heparin, prophylactic dose 1-5 Heparin, therapeutic dose 1-5 Heparin, flushesa 0.1-1 LMWH, prophylactic or therapeutic dose 0.1-1 Cardiac surgery patients 1-3 Medical patients Patients with cancer 1 Heparin, prophylactic or therapeutic dose 0.1-1 LMWH, prophylactic or therapeutic dose 0.6 Intensive care patients 0.4 Heparin, flushes < 0.1 Obstetrics patients <0.1

Risk <1%

Risk >1%

❑ Do not monitor platelet count

❑ Monitor platelet count every 2 or 3 days from day 4 to day 14 (or until heparin is stopped)

Diagnostic Approach to HIT

Thrombocytopenia ❑ Platelet count <150,000/mm3, OR ❑ >30-50% decrease decrease of platelet from baseline ❑ Recent heparin or LMWH use in the previous 5- 14 days

Characterize the symptoms (if present): ❑ Arterial thromboembolism ❑ Venous thromboembolism ❑ Unusual manifestations: - Skin necrosis at SC heparin injection sites - Transient global amnesia ❑ Absence of petechiae and/or significant bleeding

Suspicion of HIT

Low clinical probability

Intermediate/high clinical probability

Unlikely HIT ❑ Consider alternative diagnoses ❑ Continue heparin

❑ Discontinue heparin ❑ Begin alternative anticoagulation

❑ Order anti PF4 antibodies

Moderately/strongly positive test

Weakly positive test Plus High clinical probability

Weakly positive test PLUS Intermediatre clinical probability

Negative

❑ Order functional assay

Unlikely HIT ❑ Consider alternative diagnoses ❑ Continue heparin

Positive test Likely HIT

Negative test HIT undetermined

Management

Shown below is an algorithm summarizing the approach to heparin induced thrombocytopenia.

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Thrombocytopenia: ❑ Platelet count <150,000/mm3 or ❑ >50% decrease from highest level before initiation of heparin therapy ❑ Making sure patient has received heparin or LMWH in the previous 5- 14 days ❑ And after ruling out other causes of thrombocytopenia

High or intermediate clinical suspicion of HIT ❑ Venous/arterial thrombosis ❑ Unusual manifestations: Skin necrosis at SC heparin injection sites Transient global amnesia ❑ Abscence of petechiae and/or significant bleeding

Discontinue heparin

Lepirudin: ❑Bolus:0.2 mg/kg (only for life- or limb- threatening thrombosis) ❑Continuous infusion: Cr < 1.0 mg/dl → 0.10 mg/kg/h Cr 1.0-1.6 mg/dl → 0.05 mg/kg/h Cr 1.6-4.5 mg/dl → 0.01 mg/kg/h Cr > 4.5 mg/dl → 0.005 mg/kg/h

Measure aPTT 2 hrs after therapy and after each dose adjustment. Optimal aPTT<65 sec. Check baseline before starting warfarin.

Direct thrombin inhibitors

Argatroban: ❑Bolus:None ❑Continuous infusion: Normal organ function → 2 mcg/kg/min Liver dysfunction (total serum bilirubin >1.5 mg/dl), heart failure, post-cardiac surgery, anasarca → 0.5-1.2 mcg/kg/min

Measure aPTT 2 hrs after therapy and after each dose adjustment. Switching to warfarin complicated due to prolonged PT.

Bivalirudin: ❑Bolus: None ❑Continuous infusion: Normal organ function → 0.15 mg/kg/h Renal or hepatic dysfunction → dose reduction may be appropriate

Measure ACT 5 min after completing IV bolus

Initiate alternative anticoagulant therapy for at least 2-3 months

Danaparoid

Monitoring not needed. If needed maintain anti-factor Xa 0.5-0.8 U/mL

Anti-factor Xa therapy

Fondaparinux

Proceed to serologic testing

Positive + high clinical suspicion of HIT

Positive + intermediate suspicion of HIT

Negative + high clinical suspicion of HIT

Negative + intermediate clinical suspicion of HIT

Confirmed HIT

Proceed to functional testing

Indeterminate HIT

Can restart heparin

C-Serotonin Release Assay (SRA)

Heparin induced platelet-activation assays (HIPA)

Rule out other causes of thrombocytopenia

Rule out other causes of thrombocytopenia