Emergent Reversal of Anticoagulants Flashcards
Reversal Agents
antiplatelet agents (platelet transfusions)
heparins (protamine)
vitamin K antagonist (warfarin)
- 3 and 4 factor PCC
-vitamin K
direct thrombin inhibitors
-idarucizumab (reversal of dabigatran)
-andexanet alfa (reverses apixaban or rivaroxaban)
emerging agent
- ciraparangtag (reversals UFH, LMWH, fondaparinux, dabigatran, FXa)
FFP
variable but near normal levels of coagulation factors, coagulation inhibitors, albumin, and immunoglobins
Cryoprecipiate
slowly thawing FFP leaves behind a cold-insoluble precipitate which contains fibrinogen, FVIII, vWF and FXIII
Factor concentrates
plasma derived and recombinant (jehovah’s witness)
Coagulation Factors in FFP
2, VII, VIIII, IX,X, XI
Coagulation Factors in PCC
concentrated coagulation factors
II, VII, IX, X, XII, protein C and Protein S
Cryoprecipitate
fibrinogen
von willebrand factor
Fresh Frozen Plasma
thawed FFP contains variable but near normal levels of procoagulant proteins, coagulation inhibitors, albumin, and immunoglobulins
Efficacy of FFP transfusions are assessed by
PT/INR, PTT, fibrinogen level adn platelet count, viscoelastic tests which take about 30-90 minutes
Slowly thawing FFP leaves behind a
cold-insoluble precipitate which contains fibrinogen, FVIII, vWF and FXIII
FFP: Fibrinogen content per vial or unit
Volume per vial or unit
0.5g/250ml per unit
Cryoprecipitate:
Fibrinogen content per vial or unit
Volume per vial or unit
0.3g/20ml per unit
Plasma-derived fibrinogen:
Fibrinogen content per vial or unit
Volume per vial or unit
0.9-1.3g/50ml per vial
Blood Product Compatibility and administration
Filter + warmer
PRBCS, FFP, Cryopreciptate
Platelet Administration
Platelets
Factor Concentrates
Plasma derived and recombinant
Plasma derived
Factor VIII, Factor IX, factor XIII riastap FEIBA profinine kcentra
riastap
fibrinogen concentrate factor I
FEIBA
factor eight inhibitor bypassing activity-mainly contains no activated II, IX, X and mainly activated VII along with heparin, AT and PROC &S
Profinine
factors 2,7 and 10
3 factor complex concentrate which was originally approved for treatment of patients with hemophilia B (factor IX deficiency)
not for warfarin or factor X reversal
kcentra
factors 2, 7, 9 and X
4 factor complex concentrate which is approved for reversal of vitamin K antagonist
contains anti-thrombotic proteins C and S and heparin 8-40 units in 500 unit vials in addition to factors 2, 7, 9 and 10
approved for treatment of adult patients with vitamin K antagonist with an INR >1.5 adn experiencing acute major bleeding
Recombinant
factor VIIa, Factor IX
Patient bleeding from warfarin will administer
kcentra
Riastap Human derived fibrinogen concentrate
fibrinogen concentrate is fractionated from blood and is stored at room temperature for up to 30 month
can be quickly reconstituted and administered IV with no thawing or blood type machine required
Fibrinogen concentrate is standardized in each vial
Factor Complex concentrates
from pooled human plasma
biological product of pooled human plasma with therapeutic concentrations of factors 2, 7, 9, 10
4 factor:
kcentra
FEIBA
3 factor:
profilnine (low amounts of FVII)
Clinical uses of factor complex concentrates
reverses the effects of significant vitamin K antagonism coagulopathy
emergent or urgent surgery
clotting deficiency
Contraindicated in DIC and HIT
Kcentra can help reverse
factor Xa inhibitors like xarelto and eliquis however at higher dosing
KCentra is not used for
patients with INR less then 1.5 on VKAs
elective reversal of anticoagulant therapy
treatment of elevated INRs without bleeding or need for surgical intervention
massive transfusion coagulopathy
coagulopathy associated with hepatic dysfunction
patients with DIC and bleeding diathesis
patiens with history of HIT
Recombinant activated factor 7
novoseven
rFV7 is form of blood factor 7
glycoprotein produced by recombinant DNA technology
used in hemophilia A or B, congenital factor 7 deficiency
Novoseven off label use is
treatment of coagulopathy and major blood loss (postpartum hemorrhage, trauma, reversal of various anticoagulants, and high risk cardiothoracic, spinal, transplant, or vascular surgery
What is increased with rFVIIa?
thrombosis in some settings, particulary in patients who do not have hemophilia
What is rfVIIa an activated form of?
factor VII, which bypasses VIII and IX and causes coagulation without the need for factors VIII and IX
How does does rfVIIa promote hemostasis?
activates the extrinsic pathway of the coagulation cascade by forming a complex tissue factor at teh site of injury activating coagulation factors IX and X which leads to the formation of the hemostatic plug
What does rfVIIa theoretically do?
mechanism that localized the action of factor VIIa to teh site of injury and hence avoid the complications of thrombosis occuring in other vascular beds
used in head bleeds
What are the two pathways of Factor VIIa
site of tissue injury combine with tissue factor to directly activate factor X
platelet surface
Factor VIIa Dosing
20ug/kg over 200ug/kg
90mcg/kg bolus IV
reconstitute with SW
re-dose can occur every 2 hours
Additional considerations of Factor VIIa
risk of thrombotic adverse events
factor VIii will not stop surgical hemorrhage, its a temporizing agent
adequate FFP, cryo and platelets need to be present for full effect
Half life of Factor VII is
2-2.5 hours
