Review Article
Heparin-Induced Thrombocytopenia: A Review for Cardiac Anesthesiologists and Intensivists

https://doi.org/10.1053/j.jvca.2018.10.035Get rights and content

Abstract

Patients undergoing cardiovascular surgery may be exposed to heparin before surgery, during cardiopulmonary bypass (CPB), or in the immediate postoperative period. For this reason, cardiovascular surgery patients are at increased risk for heparin-induced thrombocytopenia (HIT), occurring in 1 to 3% of patients. The diagnosis of HIT can be difficult, if based solely on the development of thrombocytopenia, because cardiac surgical patients have multiple reasons to be thrombocytopenic. Several clinical scoring systems have been developed to reduce unnecessary testing and better define the pretest probability of HIT, which we will review in detail with a diagnostic algorithm. In addition, we will cover the prevention and treatment HIT.

Section snippets

Types of HIT

HIT is characterized by a precipitous decline in platelet count by more than 50%, typically presenting 5 to 10 days after heparin exposure. The platelet factor 4 (PF4) protein, located on the platelet cell surface, binds to heparin and leads to activation of lymphocytes and subsequent antibody release. The IgG antibodies in turn bind to the heparin/PF4 complexes, resulting in platelet activation.4 This platelet activation generates prothrombotic particles that further enhance the

Risk Factors for HIT and HITT

HIT most commonly is encountered in surgical patients, and more specifically in cardiac surgery, as heparin exposure is virtually universal. The incidence of HIT is about 10 × as high in patients receiving unfractionated heparin compared with patients receiving low-molecular-weight heparin (LMWH). Patients exposed to bovine-derived heparin appear to be at higher risk of HIT than patients exposed to porcine-derived heparin.6 Currently, only porcine-derived heparin is available in the United

Clinical Features of HIT

The diagnosis of HIT can be difficult, if based solely on the development of thrombocytopenia, because cardiac surgical patients have multiple reasons to be thrombocytopenic. Clinical features, such as thrombocytopenia, usually manifest 5 to 10 days after the first dose of heparin.6 The delay in onset after exposure to heparin also applies to patients with a distant history of HIT. During the acute phase of HIT, patients have circulating, active anti-PF4/heparin antibodies with

Clinical Scoring Systems

Acute thrombocytopenia is a common occurrence in cardiovascular surgical patients.5 Several clinical scoring systems have been developed to reduce unnecessary testing and better define the pretest probability of HIT. These include the HIT Expert Probability Score,13 a post-CPB scoring system,14 and the more commonly used Warkentin 4 T's scoring system.15

The HIT Expert Probability Score employed 26 experts’ opinions on the importance of diagnostic variables associated with HIT. The score

Immunoassay

An ideal laboratory test has a high specificity and sensitivity. In the case of HIT diagnosis, both timely and accurate tests results are critical because delays in anticoagulation may increase the risk of thrombotic complications.6 Immunologic assays are usually the first-line test as they are commonly done in hospital laboratories with a relatively short turnaround time. The first test of this kind was the ELISA (enzyme-linked immunosorbent assay), which detects IgG, IgM, and IgA antibodies.19

Diagnostic Algorithm—Putting It All Together

The clinical approach to the patient with thrombocytopenia after cardiac surgery should combine a clinical assessment (usually the 4 T's) and laboratory evaluation. Patients undergoing cardiac surgery should have a daily measurement of platelet count. If the platelet count drops >50% after heparin exposure, the clinician should perform a clinical assessment. Patients assessed as intermediate or high risk for HIT should have the laboratory test performed, including immunoassay and functional

Prevention of HIT

Most of the clinical trials have targeted treatment of HIT once diagnosed or prevention of antibody development in patients with a history of HIT. Some institutions have developed strategies to minimize exposure to unfractionated heparin. It is reasonable to consider LMWH as a first-line agent for venous thromboembolism prophylaxis because this has been shown to reduce the incidence of HIT. A recent Cochrane meta-analysis concluded that 2 cases of HIT could be avoided for every 100 people

Treatment of HIT

After diagnosis of HIT, prompt treatment is essential to interrupt the prothrombotic cascade by eliminating all exposure to heparin and heparin-containing products and rapidly initiating alternate anticoagulants. Practitioners must be particularly vigilant for less obvious sources of heparin exposure, such as heparin-containing intravenous flushes and heparin-coated indwelling catheters or circuits. An alternative anticoagulant should be administered to achieve therapeutic anticoagulation to

Platelet Transfusion in HIT

Because thrombocytopenia is a hallmark of HIT, the question arises whether to treat the existing thrombocytopenia with platelet transfusions. Counterintuitively, spontaneous bleeding is not common despite the low platelet counts and treatment with alternative anticoagulants.39 Initial reports suggested that platelet transfusions in this setting exacerbated the thrombotic sequelae without the expected increase in platelet counts.51, 52 More recently, a series of patients with a high suspicion of

CPB After a Diagnosis of HIT

Often, patients with a history of prior HIT will require cardiac surgery with CPB. In these patients with a remote history of HIT, further testing should be performed before the planned surgery. As described above, ELISA testing for PF4 antibodies is completed first. In the patient with a remote history of HIT, the findings of a normal platelet count and a negative immunologic assay imply that heparin can be given safely for surgery.54 The standard for patients with positive immunologic testing

Management of Other Cardiac Surgeries/Procedures After Diagnosis of HIT

Patients with HIT may require other procedures for which heparin is traditionally part of the treatment protocol. For patients undergoing percutaneous intervention, a meta-analysis by Lee et al. found that bivalirudin had a high procedural success rate and a low risk of major bleeding.71 Likewise, bivalirudin has been used in transcatheter aortic valve implantation procedures with an initial bolus dose, followed by a continuous infusion to maintain the ACT >250.72 Case reports demonstrate the

Conclusion

HIT is a rare but serious risk after cardiac surgery. Early detection is critical to reduce morbidity and mortality. Clinical assessment combined with laboratory evaluation should guide the diagnostic evaluation. Functional assays should be used in addition to immunoassay to diagnose HIT. DTIs are used in the acute phase of the disease with plasma exchange offering utility in select situations. Anticoagulation is recommended after the acute phase of HIT has resolved, commonly with a bridge of

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