Heparin-Induced Thrombocytopenia

Heparin is a highly effective and widely used anticoagulant strategy. In a rather interesting paradox, however, HIT is a prothrombotic response to heparin that can cause serious complications and even be life threatening. HIT is an iatrogenic disorder usually mediated by immunoglobulin G antibodies that bind platelet factor 4-heparin complexes and cause a hypercoagulable state by activating platelets and procoagulant microparticles.2

HIT is relatively uncommon, with an incidence ranging from less than 0.1% to 7% depending on type of heparin, duration of exposure, and patient population. UFH is associated with a tenfold increase in risk for HIT compared with LMWH. When left untreated, HIT carries a 5% to 10% daily risk for thrombosis, amputation, or death.

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The ASH panel agreed on 33 recommendations covering a wide range of areas, including the 5 phases of HIT, screening of asymptomatic patients, diagnosis and initial management of suspected HIT, treatment, and special situations in patients with acute HIT or a history of HIT.

Strong recommendations for HIT include using the 4Ts score instead of a gestalt approach to estimate the pretest probability of HIT and modifying treatment approaches accordingly. The 4Ts score is a risk-predictive model with a high negative predictive value that evaluates presence of thrombocytopenia, timing of platelet count fall, presence of thrombosis or other sequelae, and presence of other possible causes for thrombocytopenia. In patients with a low probability 4Ts score, HIT laboratory testing and empiric treatment should be avoided.

Conditional recommendations include using argatroban, bivalirudin, danaparoid, fondaparinux, or DOACs when choosing a nonheparin anticoagulant for treatment of acute HIT.

Hematology Advisor asked Adam Cuker, MD, MS, chair of the ASH VTE Guidelines Coordination Panel, clinical director of the Penn Blood Disorders Center, and director of the Penn Comprehensive and Hemophilia Thrombosis Program at the University of Pennsylvania in Philadelphia, to discuss how these guidelines may affect clinical practice.

Hematology Advisor: How do the ASH guidelines differ from VTE guidelines put forth by other organizations?

Adam Cuker, MD, MS: The American College of Chest Physicians and British Committee for Standards in Hematology have both published guidelines which were released in 2012, and these are the last guidelines on HIT before this one. Treatment recommendations have focused on conventional therapies that have been used to treat HIT for years, but since that time, there have been several studies and a large amount of new evidence on other treatments, including fondaparinux and DOACs. One of the major differences between the ASH guidelines and previous ones is that the ASH guidelines reflect the latest evidence and include these new options as treatment options for HIT.

Hematology Advisor: Are there any other important differences?

Dr Cuker: Another big difference is that most of the past guidelines assume that the patient has already been diagnosed. What we recognized as a panel is that one of the major challenges facing clinicians is diagnosing HIT. It’s not all that common, but suspected HIT is epidemic, and those who are suspected of having HIT probably outnumber patients who actually have it by about 10 to 1. That’s the situation in my institution and probably around the world.

Making the diagnosis correctly is important. It’s a high stakes diagnosis: if a patient has HIT and appropriate treatment isn’t started promptly, for every day that treatment is delayed, the patient has about a 6% risk for thrombosis, amputation, or death. So there are severe consequences if you miss or delay the diagnosis. On the other hand, the drugs used to treat HIT are toxic and expensive, and there’s a 1% risk for major bleeding, so the last thing we want to do is expose patients who don’t have HIT to unnecessary treatment.

Hematology Advisor: How do these guidelines address diagnosis of HIT?

Dr Cuker: We decided to build a major focus around diagnosis and initial empiric management while awaiting diagnostic confirmation. Step by step recommendations were created, and we built them into an algorithm that guides the clinician from the time HIT is suspected to when it is either refuted or diagnosed. Our guidelines are the first to do that, so that is another major difference from any that have been previously released.

This is an area that is ripe for practice improvement, and we think if clinicians and institutions adopt our recommendations and algorithm, it will lead to better outcomes. Our hope is that it will standardize practice also.

This article is part of a 3-part series on the revisions to the ASH clinical practice guidelines for venous thromboembolism. Use the links below to read more about the new guidelines.

Diagnosis and Prophylaxis

Pregnant and Pediatric Patients


1. Witt DM, Nieuwlaat R, Clark NP, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: optimal management of anticoagulation therapy [published online November 27, 2018]. Blood Adv. doi: 10.1182/bloodadvances.2018024893

2. Cuker A, Arepally GM, Chong BH, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia [published online November 27, 2018]. Blood Adv. doi: 10.1182/bloodadvances.201824489