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Heparin-induced thrombocytopenia (HIT) may be the most important adverse drug reaction encountered in clinical medicine because of its frequency and seriousness. This immunologic reaction is particularly dangerous because of its strong association with the formation of venous or arterial blood clots. Patients with clinical HIT have a 50% chance of developing further thromboemboli if the problem is not promptly recognized and appropriately treated. About 12 million people in the United States are exposed to heparin each year, amounting to one-third of all hospitalized patients. About 1% to 5% of patients receiving full-dose unfractionated heparin treatment will get HIT. With low molecular weight heparin (LMWH), which is used in millions of these patients, HIT occurs one-tenth as often. A conservative overall estimate is that 100,000 people in the U.S. suffer HIT each year.

Who’s at Risk?

It can be challenging for physicians to understand HIT because of many paradoxes that surround it, one being that heparin—a powerful blood thinning medication—can actually cause an extreme hypercoagulable state with an extreme risk for blood clots. Any patient exposed to heparin is at some risk for HIT, even if only a small dose is used only once. Populations at particularly high risk for HIT include patients undergoing heart or orthopedic surgery and surgical patients in general (as compared with medical patients). For these patient groups, it’s particularly important to monitor platelet counts. In patients with heparin exposure, any time the platelet count falls or new blood clots emerge, physicians must at least consider the possibility of HIT and decide to initiate an alternative anticoagulant and/or order confirmatory serologic tests.

Heparin has been a life- and limb-saving medication to millions of patients over the last 70 years, but it has a narrow therapeutic ratio and can be one of the most dangerous drugs in common clinical use. The recent heparin contamination scandal emphasizes this point—it provides another reason to prefer LMWH or fondaparinux to unfractionated heparin because these are more homogenous agents and are manufactured by processes that should entail a lower risk for contamination.

Discover HIT Early

Several medical organizations have published practice guidelines for diagnosing and treating HIT; they are quite similar, advocating platelet count monitoring for higher-risk patients exposed to heparin and emphasizing the need to intervene early when HIT is suspected. There should be a high or moderately-high suspicion of HIT if platelet counts decrease by 50% from baseline, especially 5 to 12 days after beginning heparin, and if there are no better explanations for the platelet fall. At that point, physicians should stop heparin and immediately begin an alternative anticoagulant, even in patients without evidence of a new blood clots (isolated HIT). Confirmatory serologic tests should be ordered, but physicians shouldn’t wait for results before initiating alternative anticoagulant therapy because delays can lead to devastating complications. LMWH and early use of warfarin are contraindicated with early HIT.

Two alternative anticoagulants, both of which are direct-thrombin inhibitors, have been approved by the FDA for use in HIT: lepirudin (a recombinant hirudin) and argatroban. These agents have demonstrated efficacy in improving HIT outcomes. Other alternative anticoagulants are sometimes used off-label for HIT, and newer agents are on the horizon, including oral direct thrombin inhibitors and factor Xa inhibitors. These therapies may soon add to our armamentarium as their place in treating HIT is established. The hope is that currently available therapies, together with emerging anticoagulants, will allow us to better prevent or treat HIT.

Lawrence Rice, MD, has indicated to Physician’s Weekly that he has been a consultant for GlaxoSmithKline, The Medicines Company, Sanofi-Aventis, and Canyon Pharmaceuticals. He has also worked as a paid speaker for GlaxoSmithKline.