How do you diagnose Heparin-Induced Thrombocytopenia (HIT)?

From the Guidelines

Diagnosing Heparin-Induced Thrombocytopenia (HIT) requires a clinical assessment using the 4Ts score, followed by laboratory testing with an immunoassay and functional assay if necessary, as recommended by the American Society of Hematology 2018 guidelines 1. To diagnose HIT, first suspect it when a patient on heparin therapy develops a significant platelet count drop or new thrombosis 5-10 days after starting heparin. The 4T score is a useful clinical tool that evaluates the degree of thrombocytopenia, timing of platelet fall, presence of thrombosis, and alternative causes of thrombocytopenia.

Key Steps in Diagnosing HIT

• Use the 4Ts score to estimate the probability of HIT, rather than a gestalt approach 1.
• If the 4Ts score indicates an intermediate- or high-probability of HIT, order an immunoassay to detect anti-PF4/heparin antibodies.
• If the immunoassay is positive, consider a functional assay like serotonin release assay (SRA) or heparin-induced platelet activation (HIPA) test to confirm the diagnosis.
• While awaiting results, if HIT is strongly suspected, immediately discontinue all heparin products and start a non-heparin anticoagulant such as argatroban, bivalirudin, or fondaparinux. Some important considerations in diagnosing HIT include:
• The choice of assay may be influenced by diagnostic accuracy, availability, cost, feasibility, and turnaround time 1.
• A functional assay may not be necessary for patients with a high-probability 4Ts score and very strongly positive immunoassay 1.
• HIT occurs when heparin binds to platelet factor 4, forming complexes that trigger antibody production, leading to platelet activation, consumption, and paradoxical thrombosis despite low platelet counts. It is also worth noting that other studies, such as the one published in the Journal of Thrombosis and Haemostasis in 2016, discuss the use of multi-electrode aggregometry for HIT testing 1. However, the American Society of Hematology 2018 guidelines provide the most recent and comprehensive recommendations for diagnosing HIT 1.

From the FDA Drug Label

If the platelet count falls below 100,000/mm3 or if recurrent thrombosis develops, promptly discontinue heparin, evaluate for HIT and HITT, and, if necessary, administer an alternative anticoagulant. HIT or HITT can occur up to several weeks after the discontinuation of heparin therapy Patients presenting with thrombocytopenia or thrombosis after discontinuation of heparin sodium should be evaluated for HIT or HITT.

To diagnose Heparin-Induced Thrombocytopenia (HIT), you should:

• Monitor platelet counts before and periodically during heparin therapy
• Evaluate patients for HIT and HITT if the platelet count falls below 100,000/mm3 or if recurrent thrombosis develops
• Consider discontinuing heparin and administering an alternative anticoagulant if necessary
• Be aware that HIT or HITT can occur up to several weeks after the discontinuation of heparin therapy 2

From the Research

Diagnosis of Heparin-Induced Thrombocytopenia (HIT)

To diagnose HIT, the following steps can be taken:

• Utilize the "4 Ts" score to evaluate the likelihood of HIT: thrombocytopenia, timing of platelet count fall, thrombosis or other complications, and other causes for thrombocytopenia 3, 4
• Perform an HIT antibody test to support the clinical diagnosis 3
• Use a screening immunoassay or confirmatory functional assay for further laboratory testing, although this is not recommended for individuals with a low 4Ts score 4
• Employ the 14C-serotonin release assay (14C-SRA) as the gold standard for diagnosing HIT, which has high sensitivity and specificity but is technically demanding and time-consuming 3

Laboratory Testing

Laboratory testing for HIT includes:

• Screening immunoassay to detect HIT antibodies 4
• Confirmatory functional assay, such as the 14C-SRA, to confirm a positive immunoassay result 3, 4
• The 4Ts score can be used to guide the decision to perform laboratory testing 4

Clinical Evaluation

Clinical evaluation of HIT involves:

• Monitoring platelet counts in patients receiving heparin, especially if the risk of HIT is > 1.0% 5
• Investigating for a diagnosis of HIT if the platelet count falls by ≥ 50%, and/or a thrombotic event occurs, between days 5 and 14 following initiation of heparin 5
• Discontinuing heparin exposure in patients with suspected or confirmed HIT and initiating treatment with a non-heparin alternative 3, 5, 4