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Heparin-induced thrombocytopenia

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Summary

Heparin-induced thrombocytopenia (HIT type II) is a potentially serious adverse drug effect. Unlike other drug-induced thrombocytopenias which cause bleeding, HIT type II causes thrombosis leading to limb gangrene or even death. HIT type II is mediated by an IgG antibody to the heparin–platelet factor 4 (PF4) complex. The antibody–heparin–PF4 complex binds to platelet surface receptors and induces platelet activation and aggregation, and simultaneously, activates blood coagulation pathways and endothelial tissue factor. Diagnosis of HIT type II is made on clinical criteria, supported whenever possible by laboratory tests. Several approaches are available in the perioperative management of a patient with acute or recent HIT type II presenting for surgery.

Introduction

Heparin, a heterogenous family of negatively charged glycosaminoglycans (3000–30 000 Da), is an anticoagulant released by mast cells and basophils during the normal clotting process. It is also a widely used and effective anticoagulant drug for the treatment and prophylaxis of thromboembolic diseases in medical and surgical patients. Common problems associated with heparin use include interpatient variability in response and potential bleeding complications. Less well appreciated and understood is heparin-induced thrombocytopenia (HIT) and its life threatening complication, HIT with thromboses. A patient with HIT may require emergency surgery (cardiac or vascular procedures) but cannot receive heparin. In this scenario, the anaesthetist is faced with several relevant issues of HIT and the use of alternative anticoagulants in the perioperative period. The literature on the clinico-pathophysiological aspects, management and the approach to the patient requiring intraoperative anticoagulation is reviewed.

Section snippets

Terminology

Heparin causes mild platelet aggregation in vivo especially in patients with activated platelets resulting in increased platelet sequestration in the spleen and thrombocytopenia. However, it can cause thrombocytopenia via non-immune and immune mechanisms. Clinically, there are two types of HIT that can result from heparin administration: HIT type I, a benign non-immune condition in which no heparin-dependent antibodies are present; and HIT type II, a immune-mediated syndrome caused by an

Clinical features

In HIT type I, mild thrombocytopenia occurs within the first two days after the commencement of heparin therapy4 in about 1–4% of patients.5 Platelet counts seldom drop below 80×109 l−1 The patients remain asymptomatic and have no bleeding or thrombosis associated with heparin. The thrombocytopenia resolves spontaneously within a few days even with continued heparin therapy.

In HIT type II thrombocytopenia occurs 5–10 days after exposure to heparin, typically in patients receiving prophylactic

Type I HIT

Early studies (in the 1970s) reported the incidence of HIT to be 10–25%, but subsequent studies found much lower incidences, 1–4%.

Type II HIT

The risk of developing HIT type II varies with the type of heparin used and the patient population. The risk is 1–3% in patients receiving unfractionated heparin (UFH) for more than a week.18, 19 In 10% of patients receiving UFH seroconversion with detectable HIT–IgG can be demonstrated. The factors that influence seroconversion include the length of chains and

Diagnosis

The diagnosis of HIT type II is supported by the presence of thrombocytopenia in the presence of HIT antibodies. Monitoring of platelet counts is useful as relative thrombocytopenia is the most common feature of HIT.

Management

No specific treatment is required in HIT type I.1 In situations where it is difficult to differentiate between types I and II, it is recommended that heparin be stopped immediately and the patients treated as if they had the latter. Heparin should be ceased immediately when HIT type II is suspected, and an alternative anti-coagulant (danaproid, lepirudin or argatroban) should be commenced, even in isolated HIT type II, because of the high risk of thrombosis when heparin is stopped remains high.

The management of the patient with HIT who requires surgery

It is recommended that patients presenting for cardiac surgery with a previous history of HIT should be given standard anti-coagulation with UFH if HIT antibodies are no longer detectable.19 UFH derived from porcine intestinal mucosa would be preferred over UFH obtained from bovine lung, and the patient should be monitored for re-occurrence of HIT. HIT–IgG antibodies are transient and cannot be detected several weeks or months following the episode of HIT type II. HIT–IgG usually are not

Conclusion

Several precautions that should be undertaken in order to minimize the risks of developing HIT type II in patients requiring heparin. ‘Safer’ heparin preparations should be administered. Porcine unfractionated heparin (HIT type II incidence=1.3–8%) should be used instead of bovine heparin (HIT type II incidence=1.9–30.8%). HIT type II occurs 8–10 times less with LMWH compared with unfractionated heparin in postoperative orthopaedic patients. It is associated with a lower risk of HIT–IgG

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