Bleeding reversal of anticoagulation and antiplatelet in active bleed

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Bleeding in patients on antiplatelet agents often necessitates reversal of the active agent. The risk of ongoing bleeding must be weighed against the risk of precipitating thrombosis in a patient who is anticoagulated.

Reversal of Prasugrel

• Platelets can be administered 2 hours after a maintenance dose, and 4 hours after a loading dose. If platelets are administered earlier, the free drug will bind to the platelets and inhibit them.

Abciximab

• Given that this drug binds more avidly to platelets, new platelets can be infused to reduce bleeding.

Tirofiban

• Given that this drug binds less avidly to platelets than abciximab, a transfusion of new platelets may not be effective in reducing bleeding.

Eptifibatide

• Given that this drug binds less avidly to platelets than abciximab, a transfusion of new platelets may not be effective in reducing bleeding.

Reversal of Anticogulants

General Measures

The following are general measures to reverse anticoagulation:

• Stop drug
• Treat bleeding lesion (mechanical compression, cauterization, coil embolization etc.)
• Administer antidote
• Test integrity of coagulation system, however, risk of bleeding may not parallel levels of assays
• Use non-specific blood thickeners
• Transfuse to replace deficient factors
• Consider dialysis

Reversal of Warfarin

Vitamin K

• Takes time, coagulation factors that were inhibited during anticoagulation must be re-synthesized by body, and this takes time.
• IV vitamin K is faster, there can be allergic reactions, but at one day, the INR may still be elevated despite Vitamin K therapy

Profactor Concentrate (PCC)

• See discussion under Factor Xa inhibitors

Reversal of Factor Xa Inhibitors

For drug development, a pig model of liver trauma/injury may be optimal. Pigs will die if you do not rapidly reverse this. Reversal of coagulation parameters with PCC may not predict bleeding. The site of bleeding with attendant variations in factor levels, may affect mechanism of action of drugs and their reversal.

Profactor Concentrate (PCC)

• 4 Component PCC contains factor 2, factor 7, factor 9, factor 10, Protein S, Protein C (Trade names are Beriplex in Europe, Kcentra in United States)
• Activated PCC: contains factor 2, activated factors 7, factor 9, factor 10
• 3 fators PCC: contains factor 2, low amounts of factor 7, factor 9, factor 10
• PCC vs FFP: Sarode showed that 4 factor Profactor concentrate (PCC) is more rapid that fresh frozen plasma (FFP) Effective hemostasis in 71% with PCC vs 68% with FFP (p=NS). IF there was a visible site of bleeding PCC was more effective than FFP (82.6% vs 50%, p=0.02)
• Despite adminisration of PCC in ICH, there is still a 42% mortality
• Profilnine may reverse thrombin generation better than Beriplex

Tranexamic Acid

• There is a state of hyper - fibrinolysis in trauma ()
• Limited data that exists comes from orthopedic and cardiothoracic surgery

Recombinant Factor VIIa

• Only partially effective