Haemodialysis works for reducing dabigatran levels: Implications for urgent use during bleeding or surgery

April 8, 2013

Dabigatran is one of the new oral anticoagulants which are increasingly used to prevent thrombosis. In case of an emergency (e.g. bleeding or urgent surgery), there are - despite the lack of a specific antidote - effective ways to quickly lower plasma dabigatran concentrations, as now demonstrated by a study published in this month's issue of Thrombosis and Haemostasis by Prof. Harm Peters, MD, Professor of Internal Medicine, Department of Nephrology, Charité - Universitätsmedizin Berlin, Germany.

The absence of a clinically available fast-acting antidote or rapid-elimination procedure is a major drawback for all the new oral anticoagulants. However, as with every anticoagulant, it might become necessary to rapidly reverse its effects in emergency situations, for example, during serious bleeding or urgent surgery.

Dabigatran is a specific reversible oral direct thrombin inhibitor (i.e., the active moiety of the orally available pro-drug dabigatran etexilate) approved for prevention of venous thromboembolism and of stroke in patients with non-valvular . Dabigatran is highly water soluble, has low binding, and a half-life of 12 to 17 hours ( clearance > 60 ml/min) which is roughly doubled in patients with severe (creatinine clearance < 30 ml/min).

Since a specific antidote to reverse dabigatran's effects on haemostasis is currently lacking, substantial clinical experience with non-specific reversal agents such as fresh frozen plasma or factor concentrates (e.g. PCC) are not available, and since haemodialysis data about removing dabigatran at therapeutic levels from the body are sparse, Peters and his team initiated an open-label trial to gather more in-depth information about reductions of the anticoagulatory effects of dabigatran in human beings via haemodialysis. They investigated the pharmacokinetic, and safety profiles of dabigatran and the reduction of dabigatran plasma concentrations after 4-hour haemodialysis sessions in seven clinically stable end-stage renal disease patients without atrial fibrillation. The study was designed to determine the efficiency of a single optimized haemodialysis session in removing dabigatran from the circulation with dabigatran being administered for a period of three days to achieve peak plasma concentrations comparable to those observed in atrial fibrillation patients receiving 150 mg b.i.d. The results revealed that haemodialysis indeed is an effective method to remove dabigatran from the body. A single 4-hour dialysis session will rapidly eliminate at least 50% of dabigatran plasma levels, substantially reducing its anticoagulatory activity. There was a clinically negligible redistribution of dabigatran after haemodialysis.

These findings demonstrate that haemodialysis can be a suitable approach to eliminate dabigatran in emergency situations. The low of dabigatran allows dialysis to be effective for its removal from the body, differing from other new oral anticoagulants that have high amounts of protein binding. Thus patients taking and physicians prescribing dabigatran can probably fall back on a reliable method to reduce its anticoagulatory effects in critical situations.

The current study has some limitations as it only included a relatively small number of clinical stable male patients with relatively few co-morbidities and just 28 haemodialysis sessions. The therapeutic benefit of dialysis still requires confirmation in with bleeding complications or other .

Explore further: Undertreatment of common heart condition persists despite rapid adoption of novel therapies

More information: Khadzhynov D, Wagner F, Formella S, et al. Effective Elimination of Dabigatran by Haemodialysis: A Phase I Single Centre Study in Patients with End Stage Renal Disease. Thromb Haemost 2013; 109: 4. nl5.sitepackage.de/link/2190_s … er.de/d0cc651ad99131

Related Stories

Undertreatment of common heart condition persists despite rapid adoption of novel therapies

September 21, 2012
A novel blood thinner recently approved by the FDA, dabigatran (Pradaxa), has been rapidly adopted into clinical practice, yet thus far has had little impact on improving treatment rates for atrial fibrillation. This is according ...

Irreversible catastrophic brain hemorrhage after minor injury in a patient on dabigatran

March 6, 2012
Clinicians from the University of Utah report the death of a patient who received a mild brain injury from a ground-level fall while taking the new anticoagulant dabigatran etexilate for non–valve related atrial fibrillation. ...

Dabigatran associated with increased risk of acute coronary events

January 9, 2012
The anticoagulant dabigatran is associated with an increased risk of myocardial infarction (heart attack) or acute coronary syndrome in a broad spectrum of patients when tested against some other medicines, according to a ...

Recommended for you

Cholesterol crystals are sure sign a heart attack may loom

August 17, 2017
A new Michigan State University study on 240 emergency room patients shows just how much of a role a person's cholesterol plays, when in a crystallized state, during a heart attack.

How Gata4 helps mend a broken heart

August 15, 2017
During a heart attack, blood stops flowing into the heart; starved for oxygen, part of the heart muscle dies. The heart muscle does not regenerate; instead it replaces dead tissue with scars made of cells called fibroblasts ...

Injectable tissue patch could help repair damaged organs

August 14, 2017
A team of U of T Engineering researchers is mending broken hearts with an expanding tissue bandage a little smaller than a postage stamp.

'Fat but fit' are at increased risk of heart disease

August 14, 2017
Carrying extra weight could raise your risk of heart attack by more than a quarter, even if you are otherwise healthy.

Air pollution linked to cardiovascular disease; air purifiers may lessen impact

August 14, 2017
Exposure to high levels of air pollution increased stress hormone levels and negative metabolic changes in otherwise healthy, young adults in a recent study conducted in China. Air purifiers appeared to lessen the negative ...

Study hints at experimental therapy for heart fibrosis

August 14, 2017
Researchers report encouraging preclinical results as they pursue elusive therapeutic strategies to repair scarred and poorly functioning heart tissues after cardiac injury—describing an experimental molecular treatment ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.