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]; Rim Halaby, M.D. [3]

Overview

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

Classification

Classification of HIT According to the Onset

  • Typical-onset HIT: within 5 to 10 days following the initiation of heparin
  • Early-onset HIT: within 24 hours following the initiation of heparin
  • Delayed-onset HIT: up to 3 weeks following the discontinuation of heparin[1]

Classification of HIT According to the Presentation

  • HITT: Heparin induced thrombocytopenia with thrombosis
  • Isolated HIT: Heparin induced thrombocytopenia without evidence of thrombosis
  • Subacute HIT: Platelet level is back to normal following an acute episode of HIT; however, HIT antibodies are still positive[1]

Causes

Life Threatening Causes

Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated. HIT is a life-threatening condition and must be treated as such irrespective of the causes.

Common Causes

Management

Screening

Shown below is an algorithm depicting the guidelines for screening for HIT according to the 2012 ACCP evidence based clinical practice guidelines.[1]

 
 
Asses the risk of HIT
 
 
 
 
 
 
 
 
 
 
 
 
Patient Population (Minimum of 4 day exposure)Incidence of HIT, %
Postoperative patients
Heparin prophylactic dose1-5
Heparin therapeutic dose1-5
Heparin flushes0.1-1
LMWH prophylactic or therapeutic dose0.1-1
Cardiac surgery patients1-3
Medical patients
Patients with malignacy1
Heparin prophylactic or therapeutic dose0.1-1
LMWH prophylactic or therapeutic dose0.6
Intensive care unit patients0.4
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

Sown below is the diagnostic algorithm for HIT according to the 2013 Clinical Practice Guideline on the Evaluation and Management of Adults with Suspected Heparin-Induced Thrombocytopenia (HIT).[2] Note that the most studied functional assays for anti-platelet factor 4 antibodies are serotonin release assay (SRA) and heparin induced platelet activation assay (HIPAA).[3]

 
 
 
Thrombocytopenia
❑ Platelet count < 150,000/mm3, OR
❑ Decrease of platelet > 30-50% from baseline
❑ Recent heparin or LMWH use in the previous 5-14 days
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Characterize the symptoms (if present):
❑ Arterial thromboembolism (MI, acute limb ischemia, or stroke)
Venous thromboembolism (DVT or PE)
❑ Unusual manifestations:
❑ Skin necrosis at SC heparin injection sites
❑ Transient global amnesia
❑ Absence of petechiae and/or significant bleeding
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Consider alternative diagnoses:
Infection
❑ Medications other than heparin
❑ DIC
Hemodilution
❑ Intravascular devices
Extracorporeal circuits
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Suspicion of HIT
Assess the probability of HIT by the 4 T's score
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Low clinical probability
 
 
 
Intermediate/high clinical probability
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unlikely HIT
❑ Consider alternative diagnoses
❑ Continue heparin
 
 
 
❑ Discontinue heparin
❑ Begin alternative anticoagulation
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
❑ Order anti-platelet factor 4 antibodies
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderately/strongly positive test
 
Weakly positive test
PLUS
High clinical probability
 
Weakly positive test
PLUS
Intermediate clinical probability
 
Negative
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
❑ Order functional assay
 
 
 
 
 
Unlikely HIT
❑ Consider alternative diagnoses
❑ Continue heparin
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Positive test:
Likely HIT
 
Negative test: Unlikely HIT
❑ Consider alternative diagnoses
❑ Continue heparin
 
 
 
 
 
 
 
 




Therapeutic Approach

 
 
 
High suspicion or confirmed HIT
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HITT
 
 
 
Isolated HIT
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
❑ Perform a lower extremity US to R/O asymptomatic DVT[3]
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Presence of asymptomatic DVT
 
No DVT
 
 
 
 
 
 
 
 
 
 
 
 
 
❑ Discontinue heparin
❑ Administer non heparin anticoagulation:
- Argatroban (can be used in renal insufficiency)
- Lepirudin
- Danaparoid
❑ Transition to VKA and continue VKA for 3-6 months (similar to the duration of treatment of provoked VTE)[3]
 
 
 
❑ Discontinue heparin
❑ Administer non heparin anticoagulation:[3]
- Argatroban (can be used in renal insufficiency)
- Lepirudin
- Danaparoid
❑ Transition to VKA and continue VKA for up to 4 weeks (due to the associated high risk of thrombosis)



Special Considerations

Shown below is a table summarizing the appropriate choice of anticoagulation therapy in special situations.[1]

Special situations Acute HIT or subacute HIT (normal platelets and positive antibodies) Past medical history of HIT
Cardiac surgery Urgent cardiac surgery: Use bivalirudin
Non urgent cardiac surgery: Delay the surgery until HIT has resolved and antibodies are negative
Negative antibodies: Use heparin (short term)
Positive antibodies: Use bivalirudin
PCI Use bivalirudin or argatroban Use bivalirudin or argatroban
Renal replacement therapy Use argatroban or danaparoid Use regional citrate
Pregnancy Use danaparoid -



Dosages of non Heparin Anticoagulants

Agent Dosage
Direct FXa inhibitors
Argatroban Continuous infusion:
♦ Normal organ function: 2 μg/kg per minute
♦ Liver dysfunction (total serum bilirubin 1.5 mg/dL), heart failure, postcardiac surgery, anasarca: 0.5-1.2 μg/kg per minute[3]
Lepirudin Bolus:0.2 mg/kg (only for life- or limb-threatening thrombosis)
Continuous infusion:
♦ Cr < 1.0 mg/dL: 0.10 mg/kg per hour
♦ Cr 1.0-1.6 mg/dL: 0.05 mg/kg per hour
♦ Cr 1.6-4.5 mg/dL: 0.01 mg/kg per hour
♦ Cr > 4.5 mg/dL: 0.005 mg/kg per hour[3]
Bivalirudin Continuous infusion:
♦ Normal organ function: 0.15 mg/kg per hour
♦ Renal or hepatic dysfunction: dose reduction[3]
Indirect factor Xa inhibitors
Danaparoid Bolus:
♦ < 60 kg: 1500 U
♦ 60-75 kg: 2250 U
♦ 75-90 kg: 3000 U
♦ > 90 kg: 3750 U

Accelerated initial infusion: 400 U/hour every 4 hours, then 300 U/hour every 4 hours
Maintenance infusion:

♦ Normal renal function: 200 U/hour
Renal insuficiency: 150 U/hour[3]


4 T's Score

Shown below is the 4T's score used to estimate the probability of HIT. Only one option is selected for each of the 4T's criteria and the scores are added up. The probability of HIT is:

  • Low if score is 1-3
  • Intermediate if score is 4-5
  • High if score is 6-8[4]
Score = 2 Score = 1 Score = 0
Thrombocytopenia ♦ Fall of > 50% in platelet count PLUS platelet nadir of ≥ 20 x 109/L PLUS absence of surgery in the last 3 days ♦ Fall of > 50% in platelet count PLUS surgery in the last 3 days
OR
♦ Fall in platelet count 30-50%
OR
♦ Platelet nadir 10-20 x 109/L with any platelet fall
♦ Fall of< 30% platelet count
OR
♦ Platelet nadir < 10 x 109/L with any platelet fall
Timing (of platelet count fall or thrombosis) ♦ Platelet fall day 5-10 following the initiation of heparin
OR
♦ Platelet fall within 1 day following the initiation of heparin PLUS previous exposure to heparin in the last 5 to 30 days
♦ Unclear platelet fall day 5-10 following the initiation of heparin
OR
♦ Platelet fall within 1 day following the initiation of heparin PLUS previous exposure to heparin in the last 31-100 days
♦ Platelet fall after day 10
♦ Platelet fall ≤ day 4 PLUS no exposure to heparin in the past 100 days
Thrombosis (or other clinical sequelae) ♦ Confirmed new venous or arterial thrombosis
♦ Skin necrosis at injection site
Anaphylactoid reaction to IV heparin bolus
Adrenal hemorrhage
♦ Recurrent venous thrombosis in a patient receiving anticoagulation therapy
♦ Suspected thrombosis (pending investigation results)
♦ Erythematous skin at the injection sites of heparin
♦ None
OTher causes of thrombocytopenia ♦ No alternative etiologies for platelet fall ♦ Possible other etiologies:
Sepsis
♦ Initiation of ventilator
♦ Other
♦ Probable other etiologies:
♦ Surgery in the last 72 hours
Bacteremia/fungemia
Chemotherapy or radiation within past 20 days
DIC
♦ Posttransfusion purpura (PTP)
♦ Other medications
♦ Non-necrotizing skin lesions at injection site
♦ Other


Do's

  • In case of severe thrombocytopenia among patients with HIT, administer platelet transfusions when the patient is bleeding or when performing procedures associated with an elevated risk of bleeding.[1]

References

  1. 1.0 1.1 1.2 1.3 1.4 Linkins LA, Dans AL, Moores LK, Bona R, Davidson BL, Schulman S; et al. (2012). "Treatment and prevention of heparin-induced thrombocytopenia: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines". Chest. 141 (2 Suppl): e495S–530S. doi:10.1378/chest.11-2303. PMC 3278058. PMID 22315270.
  2. Cuker A, Crowther M, 2013 Clinical Practice Guideline on the Evaluation and Management of Adults with Suspected Heparin-Induced Thrombocytopenia. American Society of Hematology
  3. 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 Cuker A, Cines DB (2012). "How I treat heparin-induced thrombocytopenia". Blood. 119 (10): 2209–18. doi:10.1182/blood-2011-11-376293. PMID 22246036.
  4. Warkentin TE, Heddle NM (2003). "Laboratory diagnosis of immune heparin-induced thrombocytopenia". Curr Hematol Rep. 2 (2): 148–57. PMID 12901146.