Published: 8 December 2016

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Don't get HIT: Heparin-induced Thrombocytopenia

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Prescriber Update 37(4): 59-60
December 2016

What is HIT?

Heparin-induced thrombocytopenia (HIT) is a potentially fatal antibody-mediated adverse reaction that occurs in up to 5% of patients exposed to heparin^1,2. A mortality rate of 2–20% has been reported¹.

Thrombocytopenia (a platelet count of <150 x 10⁹/l or a ≥ 50% reduction in platelets) occurs in >90% of patients with HIT³. In 60% of cases, thrombocytopenia occurs 5 to 10 days after exposure to heparin^3,4,5. However, the onset can be rapid (30%) with an immediate fall in platelets, or delayed (10%) where thrombocytopenia can occur up to three weeks post-exposure to heparin^3,4,5.

Approximately 25% of cases will have thrombosis at the time of their diagnosis³. However, it is estimated that up to 50% of patients with untreated HIT will develop a thrombotic complication^2,3,4. These include skin necrosis, pulmonary embolism, mesenteric ischaemia, ischaemic limb necrosis, gangrene, acute myocardial infarction, and stroke⁴.

HIT may also present with anaphylaxis, even in the absence of thrombocytopenia³.

Diagnosis

Diagnosis is based on the presence of clinical features of HIT (as described above) and laboratory confirmation of HIT antibodies^1,2. The presence of risk factors (Table 1) increases the possibility of HIT. However, differentiating HIT from other causes of thrombocytopenia can be difficult. Clinical prediction tools, such as the 4Ts probability scale (www.uptodate.com/contents/clinical-presentation-and-diagnosis-of-heparin-induced-thrombocytopenia#H13466287) can be used to estimate the probability of HIT in an individual patient, and provide guidance on the management until laboratory confirmation of the diagnosis is available^2,3.

Table 1: Risk factors for HIT^2,3,4

Risk factor for HIT	Details
Previous history of HIT	Particularly if heparin is reused for more than four days
Type of heparin	A meta-analysis of 15 controlled trials reported the following risks for HIT6: • UFH – 2.6% (95% CI 1.5-3.8) • LMWH – 0.2% (95% CI 0.1-0.4)
Heparin dose	HIT has been reported with all heparin doses. A higher incidence of HIT has been reported with therapeutic doses than prophylactic doses of heparin.
Gender	Multiple studies have reported that women have a higher risk of HIT than men.
Indication for heparin	A higher risk of HIT in surgical patients, compared to medical patients, has been reported.
Age	HIT appears to be rare in patients aged <40 years.

CI, confidence interval; UFH, unfractionated heparin; LMWH, low molecular weight heparin

New Zealand case reports

Since 2000, the Centre for Adverse Reactions Monitoring (CARM) has received 51 reports consistent with HIT including 28 reports which documented the presence of HIT antibodies. Both UFH (31) and LMWH (29) were implicated; nine reports documented usage of both UFH and LMWH (enoxaparin).

The majority of reports were in men (31) with a mean age of 67 years. Most cases (80%) were serious including seven cases considered to be life-threatening and two cases of death. Thrombotic complications were confirmed in seven reports: pulmonary embolism (three), deep vein thrombosis (two), intracardiac thrombosis (one) and peripheral gangrene (two). In one report, a patient who had received warfarin prior to the diagnosis of HIT required a below knee amputation after developing venous gangrene of the foot.

Management

Specialist advice should be sought from a haematologist if HIT is suspected¹. Management includes stopping all sources of heparin and starting a non-heparin anticoagulant to prevent ongoing thrombosis.

Warfarin should NOT be used until the patient has been adequately anticoagulated and platelet levels have normalised (due to a risk of venous gangrene resulting from the rapid lowering of protein C levels)¹.

Heparin should be avoided in the future, except in exceptional circumstances and upon the advice of a haematologist. Patients should be advised that they are allergic to heparin and should avoid it in the future^1,2.

All cases of HIT should be reported to CARM, so that heparin allergy can be added to the Medical Warnings System.

References

1. Coutre S. 2016. Management of heparin-induced thrombocytopenia. 03 August 2016. URL: www.uptodate.com/contents/management-of-heparin-induced-thrombocytopenia (accessed 12 October 2016)
2. Linkins LA. 2015. Heparin induced thrombocytopenia. BMJ. 350: g7566.
3. Coutre S. 2016. Clinical presentation and diagnosis of heparin-induced thrombocytopenia. 12 October 2016. URL: www.uptodate.com/contents/clinical-presentation-and-diagnosis-of-heparin-induced-thrombocytopenia (accessed 12 October 2016)
4. Salter B, Weiner M, Trinh M, et al. 2016. Heparin-induced thrombocytopenia: a comprehensive clinical review. Journal of the American College of Cardiology. 67(21): 2519-2532.
5. Greinacher A. 2015. Heparin-induced thrombocytopenia. The New England Journal of Medicine. 373(3): 252-261.
6. Martel N, Lee J, Wells P. 2005. Risk for heparin-induced thrombocytopenia with unfractioned and low-molecular-weight heparin thromboprophylaxis: a meta-analysis. Blood. 106(8): 2710-2715.