Questionable reversal of anticoagulation in the therapeutic management of cerebral hemorrhage associated with vitamin K antagonists


Is vitamin K really an antidote for serious bleeding with warfarin?

Patients receiving oral anticoagulants should be carefully managed to minimize the risk of bleeding events, in particular since bleeding episodes in the brain triggered by oral anticoagulants is associated with very poor outcomes, a high mortality rate and a high risk of disability and long term dependency risk. Nevertheless, intracranial bleeding events do occur during vitamin K antagonist therapy, and reversal of anticoagulation is recommended by the correction of the international normalized ratio (INR) using Vitamin K.  Does it really work?

Despite current guidelines and recommendations, there seems to be no benefit from anticoagulation reversal when it comes to intracerebral hemorrhage induced by vitamin K antagonist therapy. There are no conclusive data indicating that restoring coagulation by giving vitamin K, fresh frozen plasma, clotting factor VIIa and prothrombin complex concentrates  positively influences hematoma expansion in patients with vitamin-K-antagonists-associated intracerebral hemorrhage (VKA-ICH).

When  the team of María Alonso de Leciñana, MD PhD (Madrid, Spain), tried to prospectively identify the prognostic effect of VKA-ICH treatment by gathering data on therapeutic regimens, hematoma volume and enlargement as well as further parameters in 71 patients, their findings indicated that vitamin-K-antagonist-induced brain hemorrhage has a poor prognosis and that treatment and INR (international normalized ratio) correction did not appear to affect the outcome. They found that hematoma volume correlated with NIHSS (National Institute of Health Stroke Scale) but not with INR values. When anticoagulation reversal therapy was given to the patients, INR values below 1.5 were achieved in 60.7% of the cases. Importantly, baseline INR, anticoagulation reversal and hematoma enlargement were not related to mortality or functional outcome.

The higher the NIHSS score, the higher the probability of death and dependency

de Leciñana  et al concluded that the only independent prognostic factor was clinical severity on admission: baseline NIHSS predicted mortality, independence and neurological recovery. The patients who died were those most severely affected on admission, with the largest hematomas, higher scores on the NIHSS, and with an effect on consciousness.

Certain subgroups, however, may benefit from rapid normalization of coagulation, i.e. patients who are extremely over-anticoagulated, those in which reversal of the anticoagulation is achieved quickly (< six hours), or those with small hematomas and moderate clinical repercussion.

Thus reversal of anticoagulation may be justified only in a carefully selected group of patients as advocating a treatment  that may not be beneficial, can have adverse effects and is costly seems unwarranted at the moment.

Due to the small number of patients in this investigation as well as other limitations of this study, further randomized trials are needed to identify available treatments which may avoid hematoma expansion, to elucidate whether there is a specific window of opportunity for correction of coagulation and to establish whether or not certain subgroups of patients can benefit from the treatment. For now, Vitamin K is not necessarily the answer to serious bleeding from over-anticoagulation with warfarin.

Alonso de Leciñana et al. Opens external link in new windowQuestionable reversal of anticoagulation in the therapeutic management of cerebral hemorrhage associated with vitamin K antagonists. Thromb Haemost 2013; 110: 1145-1151.

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