Saturday, July 05, 2014

Bleeding associated with target specific oral anticoagulants (TSOACs): what the hospitalist needs to know

Treating the patient with bleeding related to TSOACs is problematic. There is little in terms of pathophysiologic rationale for antidotes, many of whose components work “upstream” from the site of action of the TSOAC. Moreover, no approach to TSOAC associated bleeding has been subjected to high level research. A systematic review would conclude that there is insufficient evidence to guide clinicians. Nevertheless when confronted with a patient on a TSOAC who is bleeding clinicians need a management approach.

In the recent past I've linked to a number of articles that touch on this topic but they only talk around it. This review from the journal Blood, an expert based review from the How I Treat series, does the best job of any paper I've seen in summarizing the relevant information and outlining a specific (suggested) approach. It is a reference every hospitalist should have quick access to. Key points are listed below but the paper is worth reading in the original and is available at the link above as free full text.

Laboratory measurement of anticoagulant effect is difficult.

Readily available tests in community hospitals are not optimal. At best they provide only a “guestimate” of drug on board and are not very reliable. By way of a rundown form the article: dabigatran prolongs the aPTT and may prolong or have no effect on the PT. Rivaroxaban and apixaban may prolong or have no effect on both tests.

Minor bleeding is managed primarily by local measures.

Brief drug discontinuation may or may not be necessary.

Moderate bleeding is managed by standard supportive measures and temporary drug discontinuation.

If normal pharmacokinetics prevail anticoagulant effects diminish fairly rapidly.

Severe or life threatening bleeding implies the need for an attempt at anticoagulant reversal.

Acknowledging the lack of high level evidence, the review authors drilled down (way down) to formulate a summary of the best we now know and came up with some specific suggestions for reversal:

In addition to the maximum supportive measures described above, nonspecific reversal therapies may be considered based on available, but limited, evidence. aPCC (80 U/kg) is weakly preferred over PCC for dabigatran-associated bleeding, whereas 4-factor PCC (50 U/kg) is weakly preferred over aPCC for rivaroxaban- or apixaban-associated bleeding; however, use of either agent is based on poor-quality data and as such should not be considered a requirement in the setting of severe or life-threatening bleeding. Hemodialysis may be a useful adjunctive therapy for dabigatran removal, when feasible.

aPCC is also known as factor 8 inhibitor bypassing activity. Although hemodialysis accelerates the removal of dabigatran and may be an important part of the management of the bleeding patient it is not very useful for the other two TSOACs due to their degree of protein binding.

No comments: