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, flushes 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)

Algorithm based on the 2012 ACCP evidence based clinical practice guidelines.

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

The most studied functional assays are serotonin release assay (SRA) and Heparin induced platelet activation assay (HIPA).

The diagnostic algorithm is based on "How I treat heparin-induced thrombocytopenia" from Blood (2012).

Treatment of HIT

High suspicion or confirmed HIT

HIT with thrombosis

Isolated HIT

❑ Perform a lower extremity U/S to R/O asymptomatic DVT

Presence of asymptomatic DVT

No DVT

❑ Discontinue heparin ❑ Initiate non heparin anticoagulation for 3-6 months: - Argatroban (can be used in renal insufficiency) - Lepirudin - Danaparoid

❑ Discontinue heparin ❑ Initiate non heparin anticoagulation until platelets are back to normal: - Argatroban (can be used in renal insufficiency) - Lepirudin - Danaparoid

❑ Check if patient is/needs to be on VKA

❑ Don't start VKA until the platelet count goes back to normal, after which initiate VKA at low doses ❑ When VKA is to be started, overlap it with non heparin anticoagulant for at least 5 days until INR is within the target range ❑ If VKAis started when patient is diagnosed with HIT, administer vitamin K

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