Bleeding Prevention and Treatment

By Dr Martínez Selles

The assessment of any kind of bleeding event in a NOACs patient is quite different from an AVK (antivitamin-K) dependent patient. There are questions to take into consideration, such as the onset, the severity and the site of the bleeding, as well as the time-point of last intake of NOACs. And, of course, other factors that can influence the bleeding risk, such as the renal function or other concurrent medications.

On the contrary, in AVKS patients the most important point to take into account is the INR value apart from the characteristics of the bleeding event. In NOAC patients, coagulation tests do not provide much information, and therefore those tests do not have to be performed or used to guide clinical approach, except for activated partial thromboplastin time in the case of dabigatran. More specific coagulation tests do exist but in clinical practice they are often unnecessary for bleeding management. The prevention of bleeding has to be personalized in any patient when surgery or other invasive procedures are planned. The bleeding risk assessment of any type of surgery (major, clinically relevant, moderate or minor bleeding risk) counterpoised by the bleeding and thromboembolic risk of each patient. For any scheduled surgery, it is important to stop the NOACS some days before, depending on the renal function and also the bleeding risk related to the type of surgery.

A controversial issue is the use of low molecular weight heparins as in AVK patients as bridging therapy. Nevertheless, in most of the guidelines, the recommendations are not to use them in the perioperative setting. The treatment of acute bleeding in those patients is based on simple schemes that come from guidelines of international guidelines. The bleeding management should be treated depending on the severity of the bleeding event. Minor bleeding events should be treated with supportive measures, such as mechanical compression or minor surgery to achieve haemostasis and to omit the next dose or so. Moderate bleeding events should be treated by restoring hemostasis with blood transfusions and fluid replacement if needed, and in the meantime treating the cause of the bleeding. Only in severe or life-threatening bleeding events, as well as the need for urgent surgery, reversal of the antithrombotic effect is indicated. Administration of prothrombin complex concentrates may be considered for severe bleeding on NOAC treatment if specific antidotes are not available. Only dabigatran antidote, called Idarucizumab is clinically available. If APTT or thrombin time is prolonged, the use of the antidote is recommended in severe bleeding or urgent surgery, due to its rapid mechanism of action; in general in less than 5 minutes almost all dabigatran is reversed. Andexanet alpha, a modified recombinant human factor Xa reverses the anticoagulant activity of factor Xa antagonists, although it is not still clinically available. Another agent under development is ciraparantag (PER977), an antidote designed to reverse both direct thrombin and factor Xa inhibitors as well as the indirect inhibitor of heparins. The clinical usefulness of these specific antidotes needs further evaluation.


There is a paucity of evidence based on clinical trials for managing either prevention or treatment of patients anticoagulated with NOACs. To establish guidelines in order to achieve a consensus among medical doctors and guarantee personalized medicine will allow the better prevention of bleeding events in case of planned surgery, and also the best management of acute bleeding to avoid unnecessary treatments, such as the reversal agents or prothrombin complex concentrates .

Presented at the 22nd Annual Meeting of the International Society of Cardiovascular Pharmacotherapy (ISCP), 24th-25th August 2017. Barcelona, Spain.