Published: 8 December 2016
Prescriber Update 37(4): 59-60
Heparin-induced thrombocytopenia (HIT) is a potentially fatal antibody-mediated adverse reaction that occurs in up to 5% of patients exposed to heparin1,2. 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 heparin3,4,5. 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 heparin3,4,5.
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 complication2,3,4. 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 is based on the presence of clinical features of HIT (as described above) and laboratory confirmation of HIT antibodies1,2. 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 available2,3.
|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
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.
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 future1,2.
All cases of HIT should be reported to CARM, so that heparin allergy can be added to the Medical Warnings System.