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

Profactor Concentrate (PCC)

• 4 Component PCC contains factors 2, 7, 9, 10 Protein S, Protein C (Trade names are Beriplex in Europe, Kcentra in United States)
• Activated PCC: contains factor 2, activated factors 7, 9 and 10
• 3 fators PCC: contains factors 2, low 7, 9, 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

• Hyperfibrinolysis in trauma (CRASH 2 lancet 2010)
• Data from ortho and CT surgery

Recombinant Factor VIIa

• Only partially effective