Heparin Induced Thrombocytopenia Clinical Review

Internal Medicine Based Clinical Pharmacy Review

Overview

Heparin Induced Thrombocytopenia is a complication that results from heparin therapy. Clinical manifestation in patients results in an increased likelihood to clot.

In addition to Heparin, other drugs may also initiate a similar response and may include:

Lorazepam
Phenytoin
Bactrim
Vancomycin

Major Variations

2 Major Types

Type 1 (non-immune mediated): Immediate thrombocytopenia (within 48 hours) but normalization of platelets occurs over duration of heparin treatment

Type 2 (immune mediated): Presents between 4–10 days of heparin therapy and is considered life threatening with no intervention

Primary Factors

Distinguishing features includes platelets dropping below 150K or 50% reduction in platelets from baseline (even if total platelets remain >150K).

Complications

Severe complication with HIT may result in conversion to Heparin Induced Thrombocytopenia + Thrombosis (HITT). This conversion is rare and occurs in around ¼ of patients of all patients how experience HIT.

HIT Development

Antibodies produced by the immune system binds to heparin and platelet factor 4 (PF4). Formed complex causes platelet activation, release of pro-coagulant particles, platelet consumption, and ultimately thrombocytopenia.

How To Treat

  1. Discontinue heparin ASAP!
  2. Initiate alternative anticoagulant therapies
  3. FDA Approved: Argatroban (Preferred Therapy)
  4. Non-FDA Approved: Bivalirudin or Fondaparinux
  5. Transition to Warfarin once platelets have recovered and patient is clinically stable
https://www.drugs.com/pro/images/fa216f49-0e26-4ad8-b2a2-fb7e250d2d15/image-06.jpg

Key Clinical Pearls

If patients are positive for renal dysfunction: Argatroban is preferred.

If patients are positive for hepatic dysfunction: Bivalirudin (or dose adjusted Argatroban) is preferred.

If undergoing cardiac surgery: Bivalirudin is preferred.

If patient is pregnant: Fondaparinux is preferred.

Bridging Process

Platelets are preferred to be > 150K (although many institutions have different protocols and varying cut offs so don’t take this value to literally).

Bridge warfarin with Argatroban x 5 days ensuring INR is therapeutic (INR>4) for a minimum of 24 hours.

Warfarin duration with HIT: no less than 1 month

Warfarin duration with HITT: no less than 3 months

Platelet Recovery

After discontinuation of heparin, average time for platelets to recover levels >150K is typically 4 days.

In severe cases, can take up to 2 weeks.

Summary of Key Clinical Points

Although predominantly associated with heparin, thrombocytopenia may also occur with other drugs such as vancomycin or lorazepam.

Platelets dropping to less than 150K or a sudden 50% reduction of platelets is the distinguishing sign of HIT.

First line alternative upon discontinuing heparin is argatroban.

5 days of argatroban x warfarin bridge is important to prevent microvascular clots.

Comprehension Review

Which of the following statements is correct?

  1. Most patients present with HITT as oppose to HIT
  2. Bridging for 2 days with argatroban and warfarin is needed to prevent microvascular clots
  3. Fondaparinux is preferred in female HIT patients who may also be pregnant
  4. There is no risk of thrombocytopenia with any other drugs other than heparin

References

  1. Konkle BA. Disorders of Platelets and Vessel Wall. In: Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J. eds. Harrison’s Principles of Internal Medicine, 19e. New York, NY: McGraw-Hill; 2015. http://accesspharmacy.mhmedical.com/content.aspx?bookid=1130&Sectionid=79732426. Accessed October 24, 2016.
  2. Hematologist. Heparin-Induced Thrombocytopenia being Treated with Argatroban with Persistent Thrombocytopenia. http://www.hematology.org/Thehematologist/Ask/1187.aspx. Accessed October 24, 2016.
  3. Medscape. Heparin-Induced Thrombocytopenia. http://emedicine.medscape.com/article/1357846-overview#showall. Accessed October 24, 2016.