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]

Definition

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

Types of HIT according to 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]


Types 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.

Common Causes

Screening for HIT

 
 
Asses the risk of HIT
 
 
 
 
 
 
 
 
 
 
 
 
Patient Population (Minimum of 4-d 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 cancer1
Heparin, prophylactic or therapeutic dose0.1-1
LMWH, prophylactic or therapeutic dose0.6
Intensive care 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)

Algorithm based on the 2012 ACCP evidence based clinical practice guidelines.[1]

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
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Consider alternative diagnoses:
Infection
❑ Medications other than heparin
❑ DIC
Hemodilution
❑ Intravascular devices
Extracorporeal circuits
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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).[2]

The diagnostic algorithm is based on "How I treat heparin-induced thrombocytopenia" from Blood (2012).[2]

Treatment of HIT

 
 
 
High suspicion or confirmed HIT
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIT with thrombosis
 
 
 
Isolated HIT
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
❑ Perform a lower extremity U/S to R/O asymptomatic DVT[2]
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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[2]
 
 
 
❑ Discontinue heparin
❑ Initiate non heparin anticoagulation until platelets are back to normal:[2]
- 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[1]
 
 
 



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 argatraban Use bivalirudin or argatraban
Renal replacement therapy Use argatroban or danaparoid Use regional citrate
Pregnancy Use danaparoid -



Dosages of non Heparin Anticoagulants

Agent Dosage
Direct FXa inhibitors
Argatroban Bolus: None
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[2]
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[2]
Bivalirudin Bolus: None
Continuous infusion:
♦ Normal organ function: 0.15 mg/kg per hour
♦ Renal or hepatic dysfunction: dose reduction may be appropriate[2]
Indirect FXa 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 X 4 hours, then 300 U/hour X 4 hours
Maintenance infusion:

♦ Normal renal function: 200 U/hour
♦ Renal insufficiency: 150 U/hour[2]


4 T's Score

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

  • Low if score is 1-3
  • Intermediate if score is 4-5
  • High if score is 6-8[3]
Score = 2 Score = 1 Score = 0
Thrombocytopenia
(Select only 1 option)
♦ Fall of > 50% in platelet count PLUS nadir of ≥ 20 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 and nadir that do not fit criteria for score 2 or score 0
♦ Fall of< 30% platelet count
♦ Nadir < 10 with any platelet fall
Timing (of platelet count fall or thrombosis)
(Select only 1 option)
♦ Platelet fall day 5-10 following the initiation of heparin
♦ 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
♦ Platelet fall 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)
(Select only 1 option)
♦ 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
♦ Suspected thrombosis
OTher causes of thrombocytopenia
(Select only 1 option)
♦ 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 1.5 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. 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 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.
  3. Warkentin TE, Heddle NM (2003). "Laboratory diagnosis of immune heparin-induced thrombocytopenia". Curr Hematol Rep. 2 (2): 148–57. PMID 12901146.