emergent reversal of anticoagulants

Question 1

FFP

Answer 1

contains variable but near-normal levels of coagulation factors, coagulation inhibitors, albumin, and immunoglobulins

large volumes of plasma transfusions are not well-tolerated in patient with little CV/pulm reserve (overload, TRALI)

efficacy is assessed by PT/INR, PTT, fibrinogen, PLT count, viscoelastic test

Question 2

cryoprecipitate

Answer 2

slowly thawing FFR leaves behind a cold-insoluble precipitate which containes fibrinogen, FVIII, vWF, and FXIII

Question 3

factor concentrates

Answer 3

plasma-derived

recombinant

Question 4

which product is it NOT okay to use a warmer?

Answer 4

platelets

Question 5

KCentra

Answer 5

4 factor concentrate that has II, VII, IX, and X

approved for reversal of vit-K antagonists like coumadin with INR > 1.5 and experiencing acute major bleeding

**contains heparin and antithrombotic proteins C and S

at higher doses, may also help reverse factor Xa inhibitors like xarelto and eliquis

Question 6

Riastap

Answer 6

fibrinogen concentrate

it is fractionated from blood and is stored at room temp for up to 30 months

can be quickly reconstituted and administered IV with no thawing or blood-type matching

standardized in each vial

as effective as cryo and more effective than FFP

Question 7

profilnine

Answer 7

3 factor concentrate of II, IX, and X

also called factor IX complex

originally approved for treatment of patients with hemophilia B (factor IX deficiency)

reserved mainly for cardiac cases, not indicated for heparin or other factor X inhibitor reversal

Question 8

recombinant factor concentrates

Answer 8

factor VIIa, factor IX

Question 9

factor complex conentrates (kcentra and profilnine)

Answer 9

reverses the effect of significant vitamin K-antagonism coagulopathy (coumadin reversal)

contraindicated in DIC and HIT

Question 10

dosing of profilnine

Answer 10

10-15u/kg - IBW

max 1000u

Question 11

recombinant activated factor VII (novoseven)

Answer 11

used for hemophilia A (factor 7 deficiency) or B (factor IX deficiency) or congenital factor 7 deficiency

off label - postpartum hemorrhage, trauma, anticoagulant reversal, high risk surgery)

can be associated with increased thrombosis risk especially in patients without hemophilia

works by enhancing the extrinisic pathway (bypasses intrinsic, so good for people with factor VIII and IX deficiency

theoretically should be localized to site of injury because it requires tissue factor to work, which should only be at site of injury

Question 12

factor VII dosing

Answer 12

single dose for 80kg pt is $8,000

90 mcg/kg IV bolus - redose every 2 hours as clinically indicated

supplied in 1mg, 2mg, and 5mg vials

Question 13

factor VII additional considerations

Answer 13

high risk of thrombotic adverse event

will not stop surgical hemorrhage

should not be given instead of other blood products - adequate FFP, cryo, and platelets need to be on board for the full effect because it depends on the function of platelets and fibrinogen

half life is 2-2.5 hours and initial dose may require repeating until bleeding is controlled

Question 14

FCC consideration (why choose it?)

Answer 14

they provide faster correction of coagulopathy as compared to FFP and vit K (30 mins as opposed to >3h)

less risk of overload, TRALI, other transfusion reactions)

Question 15

antifibrinolytic medications MOA

Answer 15

prevents the lysis of fibrin - promotes clot formation
used to treat/prevent excessive bleeding
interferes with formation of plasmin which takes place in lysine rich areas on the surface of fibrin

Question 16

what are the 2 types of antifibrinolytics

Answer 16

lysine analogues (tranexamic acid and aminocaproic acid)
serine protease inhibitors (aprotinin) - no longer available

Question 17

epsilon aminocaproic acid (AMICAR)

Answer 17

FDA approved for use in treatment of acute bleeding d/t elevated fibrinolytic activity

inhibits plasmin

clinical use: trauma, CPB, spinal fusion

Question 18

dosing of amicar

Answer 18

bolus: 5-15g (peds 75-150mg/kg)
infusion: 1-2g/hr (peds 5-30mg/kg/hr)

Question 19

TXA - tranexamic acid (cylokapron

Answer 19

synthetic analog of lysine that inhibits fibrinolysis by competitively binding to the lysine receptor sites on plasminogen, and this prevents plasmin from binding to and degrading fibrin

good for GI, surgical, Trauma bleeding

2 hour half life

8-10x more potent than amicar

Question 20

dose of TXA

Answer 20

10-15mg/kg IV (up to 1g) followed by an a gtt of 1-5 mg/kg/hr

cost of 1g = $50

Question 21

clinical uses of TXA

Answer 21

non-cerebral trauma (only beneficial within the first 3 hours)
pediatrics (spine fusions, craniosynostosis)
ortho (joint procedures)
cardiac (with or without CPB)
OB (massive transfusion algorithm)

Question 22

CRASH-2 trial

Answer 22

20,011 adults with traumatic bleeding showed that TXA reduces death d/t bleeding with no increase in vascular occlusive events

strong evidence of time to treatment - TXA reduced death d/t bleeding by 1/3 when given within 3h but actually increased risk after 3h

Question 23

TXA and post partum hemorrhage

Answer 23

WOMAN study showed that death d/t bleeding was significantly reduced in woman given TXA, especially in those given treatment within 3 hours of giving birth

Question 24

contraindications of TXA

Answer 24

active intravascular clotting (PE, DVT, embolic stroke), anaphylaxis, SAH

Question 25

precautions for TXA use

Answer 25

decrease dosing in renal patients because renally eliminated
UTI - ureteral obstruction d/t clot formation
hypotension with rapid injection
color vision defect - visual changes can indicated toxicity
seizure disorders - increase seizure risk
concomitant administration with factor concentrates

Question 26

protamine

Answer 26

simple proteins obtained from salmon sperm

it is positively charged alkaline and combines with negative acidic heparin to form a stable complex without any anticoag activity

Question 27

protamine dosing

Answer 27

1-1.5mg for every 100u of heparin (over last 2 hours), guided by ACT

Question 28

protamine adverse responses

Answer 28

hypotension with rapid IV injection d/t histamine release

pulmonary HTN d/t complement activation and thromboxane release = constriction

allergic reaction

Question 29

options for patients with allergic reaction to protamine

Answer 29

pretreat with histamine receptor antagonist, followed by a slow trial

completely avoid and wait for effect of heparin to wear off (takes hours)

administer alternative to heparin (bivalirudin)

Question 30

what patients are at risk for a true allergy to protamine

Answer 30

prior protamine reaction
allergy to true vertebrae fish
exposure to NPH insulin
allergy to any drug
prior exposure to protamine

Question 31

DDAVP d-amino-d-arginine vasopressin

Answer 31

aka desmopressin
causes release of endogenous store of vWF
increases platelet adhesion/improves platelet function

Question 32

dose of DDAVP

Answer 32

0.3 mcg/kg IV infusion over 15-30min - platelet adhesion increases within 30 minutes

Question 33

DDAVP vs arginine vasopressin

Answer 33

DDAVP is more potent than arginine vasopressin

the change in structure results in decreased ADH and vasopressor action on smooth muscle and increased function of increasing factor VII in patients with vWD

Question 34

what is the most common side effect of DDAVP

Answer 34

paradoxical hypotension

Question 35

contraindications for DDAVP

Answer 35

hypersensitivity, renal impairment, hyponatremia

Question 36

why is hyponatremia a conraindication for DDAVP

Answer 36

overuse can lead to water retention and dilutional hyponatremia with consequent convulsion

can lead to water intoxication/hyponatremia which can be fatal