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Resuming anticoagulation after hemorrhage: A practical approach

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ABSTRACTMost patients who suffer a hemorrhage while on long-term anticoagulant therapy continue to be at risk of thrombosis. Physicians often need to reconsider the need for anticoagulation in view of the risk of recurrent bleeding, and when anticoagulation needs to be resumed, they must also consider the timing and strategy. Since there are no evidence-based guidelines for these situations, the authors of this paper offer a practical framework for individualizing the resumption of anticoagulation after hemorrhage.

KEY POINTS

  • Not all patients on anticoagulation at the time of a bleeding event have a strong indication to continue anticoagulation afterward.
  • Important considerations when deciding whether to resume anticoagulation after hemorrhage are whether the source of bleeding has been found and controlled and, if the patient is receiving warfarin, whether he or she can be expected to maintain the target international normalized ratio.
  • The newer oral anticoagulants, including factor Xa inhibitors and direct thrombin inhibitors, lack antidotes or reversal agents, and their risk of causing bleeding compared with warfarin varies by site of bleeding.


 

References

If a patient receiving anticoagulant therapy suffers a bleeding event, the patient and physician must decide whether and how soon to restart the therapy, and with what agent.

Foremost on our minds tends to be the risk of another hemorrhage. Subtler to appreciate immediately after an event is the continued risk of thrombosis, often from the same medical condition that prompted anticoagulation therapy in the first place (Table 1).

Complicating the decision, there may be a rebound effect: some thrombotic events such as pulmonary embolism and atrial fibrillation-related stroke may be more likely to occur in the first weeks after stopping warfarin than during similar intervals in patients who have not been taking it.1–3 The same thing may happen with the newer, target-specific oral anticoagulants.4–6

Although we have evidence-based guidelines for initiating and managing anticoagulant therapy, ample data on adverse events, and protocols for reversing anticoagulation if bleeding occurs, we do not have clear guidelines on restarting anticoagulation after a hemorrhagic event.

In this article, we outline a practical framework for approaching this clinical dilemma. Used in conjunction with consideration of a patient’s values and preferences as well as input from experts, this framework can help clinicians guide their patients through this challenging clinical decision. It consists of five questions:

  • Why is the patient on anticoagulation, and what is the risk of thromboembolism without it?
  • What was the clinical impact of the hemorrhage, and what is the risk of rebleeding if anticoagulation is resumed?
  • What additional patient factors should be taken into consideration?
  • How long should we wait before restarting anticoagulation?
  • Would a newer drug be a better choice?

BLEEDING OCCURS IN 2% TO 3% OF PATIENTS PER YEAR

Most of our information on anticoagulation is about vitamin K antagonists—principally warfarin, in use since the 1950s. Among patients taking warfarin outside of clinical trials, the risk of major bleeding is estimated at 2% to 3% per year.7

However, the target-specific oral anticoagulants rivaroxaban (Xarelto), apixaban (Eliquis), dabigatran (Pradaxa) and edoxaban (Savaysa) are being used more and more, and we include them in our discussion insofar as we have information on them. The rates of bleeding with these new drugs in clinical trials have been comparable to or lower than those with warfarin.8 Postmarketing surveillance is under way.

WHY IS THE PATIENT ON ANTICOAGULATION? WHAT IS THE RISK WITHOUT IT?

Common, evidence-based indications for anticoagulation are to prevent complications in patients with venous thromboembolism and to prevent stroke in patients with atrial fibrillation or a mechanical heart valve. Other uses, such as in heart failure and its sequelae, pulmonary hypertension, and splanchnic or hepatic vein thrombosis, have less robust evidence to support them.

When anticoagulation-related bleeding occurs, it is essential to review why the patient is taking the drug and the risk of thromboembolism without it. Some indications pose a higher risk of thromboembolism than others and so argue more strongly for continuing the treatment.

Douketis et al9 developed a risk-stratification scheme for perioperative thromboembolism. We have modified it by adding the CHA2DS2-VASc score (Table 2),9–11 and believe it can be used more widely.

High-risk indications

Conditions that pose a high risk of thrombosis almost always require restarting anticoagulation. Here, the most appropriate question nearly always is not if anticoagulation should be restarted, but when. Examples:

  • A mechanical mitral valve
  • Antiphospholipid antibody syndrome with recurrent thromboembolic events.

Lower-risk indications

Lower-risk indications allow more leeway in determining if anticoagulation should be resumed. The most straightforward cases fall well within established guidelines. Examples:

  • Atrial fibrillation and a CHA2DS2-VASc score of 1. The 2014 guidelines from the American College of Cardiology, American Heart Association, and Heart Rhythm Society10 suggest that patients with nonvalvular atrial fibrillation and a CHA2DS2-VASc score of 1 have three options: an oral anticoagulant, aspirin, and no antithrombotic therapy. If such a patient on anticoagulant therapy subsequently experiences a major gastrointestinal hemorrhage requiring transfusion and intensive care and no definitively treatable source of bleeding is found on endoscopy, one can argue that the risks of continued anticoagulation (recurrent bleeding) now exceed the benefits and that the patient would be better served by aspirin or even no antithrombotic therapy.
  • After 6 months of anticoagulation for unprovoked deep vein thrombosis. Several studies showed that aspirin reduced the risk of recurrent venous thromboembolism in patients who completed an initial 6-month course of anticoagulation.12–15 Though these studies did not specifically compare aspirin with warfarin or target-specific oral anticoagulants in preventing recurrent venous thromboembolism after a hemorrhage, it is reasonable to extrapolate their results to this situation.

If the risk of recurrent hemorrhage on anticoagulation is considered to be too great, then aspirin is an alternative to no anticoagulation, as it reduces the risk of recurrent venous thromboembolism.16 However, we advise caution if the bleeding lesion may be specifically exacerbated by aspirin, particularly upper gastrointestinal ulcers.

Moderate-risk indications

  • After a partial course of anticoagulation for provoked venous thromboembolism. Suppose a patient in the 10th week of a planned 12-week course of anticoagulation for a surgically provoked, first deep vein thrombosis presents with abdominal pain and is found to have a retroperitoneal hematoma. In light of the risk of recurrent bleeding vs the benefit of resuming anticoagulation for the limited remaining period, her 12-week treatment course can reasonably be shortened to 10 weeks.

The risk of recurrent venous thromboembolism when a patient is off anticoagulation decreases with time from the initial event. The highest risk, estimated at 0.3% to 1.3% per day, is in the first 4 weeks, falling to 0.03% to 0.2% per day in weeks 5 through 12, and 0.05% per day thereafter.17–20

The risk of recurrent venous thromboembolism is greatest immediately after the event and decreases over time

Additionally, a pooled analysis of seven randomized trials suggests that patients with isolated, distal deep vein thrombosis provoked by a temporary risk factor did not have a high risk of recurrence after being treated for 4 to 6 weeks.21 These analyses are based on vitamin K antagonists, though it seems reasonable to extrapolate this information to the target-specific oral anticoagulants.

More challenging are situations in which the evidence supporting the initial or continued need for anticoagulation is less robust, such as in heart failure, pulmonary hypertension, or splanchnic and hepatic vein thrombosis. In these cases, the lack of strong evidence supporting the use of anticoagulation should make us hesitate to resume it after bleeding.

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