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Spontaneous Circulation: Thinning Out the Blood

Bruen, Charles MD

doi: 10.1097/01.EEM.0000456989.36475.22
Spontaneous Circulation

Dr. Bruenis a fellow in critical care medicine and emergency cardiology at Hennepin County Medical Center in Minneapolis. He has special interest in stabilization, resuscitation, hemodynamic evaluation, and emergency cardiovascular care. Visit his website,, follow him @resusreview, and read his past columns at





Early treatment of NSTEMI is directed at minimizing ongoing ischemia by reducing myocardial oxygen demand, limiting the extent of infarct size and preventing expansion of the thrombus. (See table.) The foundational anti-ischemic treatment is antithrombotic therapy (anticoagulation and antiplatelet), and four different anticoagulation agents currently have Class I recommendations.

Heparin provides the benefit of flexibility in dosing and easy reversal. It is protein-bound, however, and has nonlinear pharmacokinetics and dose-response variability, making its anticoagulation effect unpredictable. It also has a narrow therapeutic window dependent on antithrombin, and only provides indirect inhibition of thrombin. Heparin can activate platelets and cause the release of vWF, and carries a risk of inducing thrombocytopenia, which could be life- and limb-threatening.



The low-molecular-weight heparins, enoxaparin and fondaparinux, are useful alternatives to heparin, and have longer half-lives. Both are injected subcutaneously with a weight-based dosing. They can be given and then not worried about until the next dose is required 12 or 24 hours later, making them ideal for the emergency department. Like heparin, they are cleared renally. Enoxaparin, at least in the subcutaneous dosing, is less useful if the patient undergoes PCI because of increased bleeding risk for those treated with an early invasive strategy. Fondaparinux, on the other hand, showed improved outcomes compared with enoxaparin, but its rate of catheter-related thrombosis during PCI is double. Fondaparinux cannot be used alone during PCI, and must be treated with heparin during the procedure.

Bivalirudin, a reversible direct thrombin inhibitor, has a short half-life and is partially cleared renally. It has been shown to have equivalent anti-ischemic benefits to heparin, with fewer bleeding risks. Bivalirudin has been most extensively tested in patients also treated with glycoprotein IIb/IIIa inhibitors, which have generally fallen out of favor as upstream ED treatments. Bivalirudin does have a higher risk of early stent thrombosis, and should only be used when dual antiplatelet therapy is initiated before intervention.

Anticoagulation should be initiated as soon as possible after you make a NSTEMI diagnosis. Unfractionated heparin is best if the patient is going to angiography soon (early invasive approach). Enoxaparin probably has a slightly higher bleeding risk, and fondaparinux is good if you live in Europe or Canada and treat with heparin during the procedure. Consider bivalirudin if it fits within your institution and you are also treating with clopidogrel. Enoxaparin or fondaparinux are generally preferred if a conservative management approach is planned, leaning toward enoxaparin if there is a higher bleeding risk. Both have a slight benefit over heparin, and are much easier to administer.

Find a complete discussion of anticoagulation in the EMN iPad app and in the Spontaneous Circulation blog on, where the EMN app can also be downloaded for free.

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