Introduction
Coagulopathy,
either drug related or multifactoral, is a major contributing factor to bleeding
related mortality in a variety of clinical settings. Standard therapy for
control of coagulopathy related bleeding has traditionally been limited to the
utilization of available blood products, reversal of drug-induced
anticoagulation, and recombinant activated factor VII (rFVIIa). With the
implementation of the difficult to reverse new oral anticoagulants, dabigatran
(Pradaxa®), apixaban
(Eliquis®) and rivaroxaban
(Xarelto®), the need
for a standardized reversal protocol within UKHealthCare is warranted. Praxbind is now approved for reversal of dabigatran but should be used only if dabigatran use is specifically confirmed.
UKHealthcare
has developed the following guideline to standardize the utilization, dosing,
monitoring, and dispensing of agents used in traumatic, life-threatening, or
drug induced coagulopathies.
Indication to Use the Guideline
Obtain
history of possible oral anticoagulant use from patient, family, EMS, or
referring facility when possible. If history is unknown consider the
possibility of their use in patient based on their known past medical history
(i.e. history of atrial fibrillation or deep venous thrombosis). This protocol
is intended to be used for bleeding in the case of:
- Anticoagulant use (see below)
- Antiplatelet use (see below)
- Trauma
- Intracranial hemorrhage
- Stroke
- Emergency surgery
The following
labs should be drawn STAT and repeated as clinically indicated. While
these labs may help to identify the presence or absence of oral anticoagulants
the results of these studies should not delay the anticoagulation reversal
treatment if a history of oral anticoagulant use is present or known.
- CBC
- PT/INR
- BMP
- aPTT
- TT (thrombin time)
Anticoagulant Reversal Agents
Reversal Agent Review
If a drug-induced coagulopathy is suspected and reversal is
indicated, activated prothrombin complex concentrate (aPCC), 4 factor
prothrombin complex concentrate (4PCC) or rFVIIa can be used. For unknown
ingestion of the newer agents, Dabigatran, apixaban, and rivaroxaban, more
complete reversal has been seen with the use of aPCC’s when compared to PCC’s. Dabigitran reversal is now possible with Praxbind (above). The UKHealthcare aPCC on formulary is FEIBA (factor eight
inhibitor bypassing activity) while the 4 factor PCC product is Kcentra. If any
of these therapies are warranted please contact the pharmD on call for indication,
dosing, and administration assistance (pager # 7400).
Comparison of
aPCC and rFVIIa Products
|
|||
Activated PCC
|
4PCC
|
rFVIIa
|
|
Brand Name
|
Feiba®
|
Kcentra®
|
NovoSeven®
|
Factors Provided
|
II, IX, X, VIIa
|
II, IX, X, VII
|
VIIa
|
Activated
|
Yes
|
No
|
Yes
|
Drug Induced Coagulopathy
Reversal
|
|||
Warfarin
|
Yes
|
Yes
|
Yes
|
Dabigatran
|
Yes
|
No
|
No€
|
Rivaroxaban
|
Yes
|
Yes
|
No€
|
Apixaban
|
NA£
|
NA£
|
NA£
|
€ literature is divided between in vitro
and clinical studies
£ newest agent with smallest
amount of data, initial reports put its reversal similar to Rivaroxaban the other
Factor Xa inhibitor
* may repeat dosing up to 3 times
if clinically indicated
Procedure for Ordering and Dispensing
When a patient presents with bleeding and it is determined by
the attending physician that the patient would benefit from either rFVII or
FEIBA a page/call to the PharmD on call will be placed.
·
This will alert the pharmD to come and assess the
patient for their potential risk, assist with laboratory interpretation and
help to decide the appropriateness of reversal.
·
PharmD will discuss with appropriate physician the
appropriateness and which reversal agent would be indicated in this particular
patient.
If the decision is made to give a particular reversal agent, the pharmD
will further assist by bringing the drug to the patient bedside, prepare the
dose for administration, while also prompting discussions on potential
alternative/adjunctive therapies that might impact the efficacy of the agent
selected.
Non-Drug Induced Coagulopathy Reversal
Not all coagulopathies will be drug induced. After the optimization of supportive care measures have been done and drug induced causes have been ruled out it is appropriate to follow previously established protocols (i.e. massive transfusion protocol).
Antiplatelet Reversal
If ingestion of one of the following oral antiplatelet agents is present during coagulopathy consider platelet transfusion. Consider using TEG to assess clot formation, realizing that the reagents used in TEG can overcome the effect of platelet dysfunction in vitro and show a 'falsely normal' TEG.
· Clopidogrel (Plavix®)
· Ticagrelor (Brilinta®)
· Prasugrel (Effient®)
· Ticlopidine (Ticlid®)
