Anticoagulants

Question 1

Warfarin elimination 1/2 life:

Answer 1

24-36 hrs

Question 2

warfarin reversal

Answer 2

Vitamin K, PCCs for immediate reversal but availability issues(?); FFP (transfusion risk and volume concerns)

Question 3

Dextran MOA

Answer 3

binds to platelets and causes inhibited function

Question 4

ASA MOA

Answer 4

o IRREVERSIBLY inhibits cyclooxygenase –>thromboxane A2 (7-10 days)

Question 5

Thrombolytics

Answer 5

Streptokinase, urokinase, tissue plasminogen activator (tPA) (Alteplase®)

Question 6

Thrombolytics MOA

Answer 6

Activates plasminogen to plasmin & causes clot breakdown

Question 7

Antifibrinolytics MOA

Answer 7

Block conversion of plasminogen to plasmin & causes inhibited clot lysis

Question 8

Antifibrinolytics

Answer 8

Tranexamic acid (TXA) & aminocaproic acid (Amicar®):

Question 9

Aprotinin MOA

Answer 9

Protease inhibitor & causes plasmin inhibition

Question 10

TXA studies:

Answer 10

decrease blood loss and blood products; no increase risk of unwanted thrombi

Question 11

Initiation Phase (Extrinsic)

Answer 11

Vessel damage
-> tissue factor (TF) release which binds with VIIa
-> conversion of X to Xa
->small amount of thrombin

Question 12

Amplification Phase (intrinsic):

Answer 12

Plts, V & XI activated by thrombin

Question 13

Propagation Phase

Answer 13

VIII, IX and calcium on plts ->activation of X
while
thrombin activates plts, V, VIII -> VIIIa-IXa complex
->The VIIIa-IXa complex switches reaction to intrinsic tenase (Xase) pathway -> 50 x more efficient at Xa generation.
->So increased Xa -> large amount of thrombin

Question 14

heparin onset IV

Answer 14

immediate

Question 15

unfractionated heparin MOA

Answer 15

Binds to antithrombin _ enhanced binding with thrombin

Question 16

heparin unit?

Answer 16

1U = volume that prevents 1 mL blood from clotting for 1 hr after combining with Ca++

Question 17

heparin onset sub-cu

Answer 17

1-2 hr

Question 18

heparin aPTT range

Answer 18

1.5 - 2.5 x Normal (N=30-35 sec)

Question 19

low dose heparin monitored with

Answer 19

anti-Xa assay

Question 20

high dose heparin monitored

Answer 20

ACT > 350 – 400 sec (affected by hypothermia and hemodilution)

Question 21

HIT severe

Answer 21

plt ct <100,000 (or 50% drop)

Question 22

HIT associated w/ thrombus after

Answer 22

4-5 days of treatment

Question 23

heparin reversal

Answer 23

protamine - 1 mg for each 100 U circulating heparin

Question 24

warfarin onset

Answer 24

predictable but delayed 8-12 hrs

Question 25

warfarin peak

Answer 25

36-72 hrs, but may take up to 5 days

Question 26

warfarin INR

Answer 26

“Moderate anticoagulation” = INR of 2.0 - 3.0

Question 27

warfarin monitor INR peri-op

Answer 27

d/c 1-3 days pre-op, reinstitute 1-7 days post op, use UFH to bridge high risk clotters

Question 28

protamine clearance

Answer 28

20 mins (risk of heparin rebound)

Question 29

heparin clearance 1/2 life:

Answer 29

1 hr

Question 30

DVT occurs in what percent of gen. surgery?

Answer 30

10-40%, increased with higher acuity

Question 31

PE occurs in?

Answer 31

2 – 22% of traumas. PE is common cause of death after first 24 hours post-trauma.

Question 32

VTE prophylaxis

Answer 32

* Heparin * LMWH (enoxaparin, dalteparin) * Xa inhibitors (fondaparinux, rivaroxaban) * Thrombin inhibitors (dabigatran, argatroban)

Question 33

NOAC - Direct thrombin inhibitors:

Answer 33

dabigatran (Pradaxa®) bivalirudin (Angiomax®) argatroban (Arcova®)

Question 34

NOAC - Direct Xa inhibitors:

Answer 34

rivaroxaban (Xarelto®) apixaban (Eliquis®) fondaparinux (Arixtra®)

Question 35

low risk blood loss on NOACs

Answer 35

D/C 24 hrs pre-op, resume 24 hrs post-op

Question 36

moderate/high risk blood loss on NOACs

Answer 36

D/C 5 days pre-op, resume when risk of bleeding drops

Question 37

elective procedures on NOACs

Answer 37

Bridging probably not required; consider patient-specific risk/benefits

Question 38

ER procedures while on NOACs

Answer 38

Delay as long as possible; do not prophylax with recombinant VIIa (Novo 7®) or PCCs.

Question 39

Life-threatening hemorrhage while on NOACs

Answer 39

Consider recombinant VIIa or PCCs.

Question 40

best testing for NOACs

Answer 40

aPTT and TT

Question 41

Thienopyridines MOA

Answer 41

Binds to P2Y12 receptor-->inhibits platelet activation and aggregation

Question 42

Thienopyridines

Answer 42

Clopidogrel (Plavix®) Prasugrel (Effient®) Ticagrelor (Brilinta®)

Question 43

Dipyridamole (Persantine®) MOA

Answer 43

increase cyclic AMP causes decrease plt function

Question 44

Platelet glycoprotein IIb/IIIa antagonists

Answer 44

abciximab (ReoPro®); tirofiban (Aggrastat®); eptifibatide (Integrilin®)

Question 45

glycoprotein IIb/IIIa antagonists MOA

Answer 45

Bind or inhibit fibrinogen receptor - causes decrease in plt aggregation

Question 46

peri-op recommendations for thienopyridines

Answer 46

D/C 7 days pre-op, avoid neuraxials until drug effects cleared

Question 47

When must TXA be administered?

Answer 47

during first 3 post-injury hours

Question 48

TXA in non-trauma surgery dose

Answer 48

15 mg/kg IV infusion (most efficacious) or 1g is common (regardless of weight)

Question 49

TXA FDA approved use?

Answer 49

-Heavy menstrual bleeding -Short-term hemorrhage prevention with hemophilia

Question 50

TXA off-label use?

Answer 50

* Elective c-sections and PP bleeding * Total knee arthroplasty * Orthognathic and craniofacial surgery * Cardiac surgery * Spinal surgery * (TURP) * Non-traumatic subarachnoid hemorrhage * GI bleeding

Question 51

TXA protocol

Answer 51

* 1 gm preoperatively in holding * Additional 1 gm during closing

Question 52

contraindications for TXA

Answer 52

-Hypersensitivity to antifibinolytics -Acquired color vision deficit -Caution with renal impairment -Caution with thrombus history

Question 53

when does heparin rebound usually occur

Answer 53

2-3 hours post protamine

Question 54

adverse reactions of protamine

Answer 54

- Anaphylaxis, pulmonary vasoconstriction with RV failure, hypotension - ↑ risk with NPH insulin, vasectomy, prior protamine, drug allergies

Question 55

Desmopressin (DDAVP) treats?

Answer 55

- Mild hemophilia A, von Willebrand’s dz, cardiac surgery(?) - infuse slowly to avoid hypotension

Question 56

Normal Fibrinogen

Answer 56

200-400 mg/dL

Question 57

Fibrinogen in pregnancy

Answer 57

>400 mg/dL

Question 58

what is used to treat low fibrinogen?

Answer 58

cryoprecipitate or fibrinogen concentrates (can be refractory to FFP)

Question 59

what indicates low fibrinogen?

Answer 59

elevated PT and PTT

Question 60

Recombinant Factor VIIa (NovoSeven®) use?

Answer 60

For hemophilia; off-label use for life-threatening hemorrhage & CV surgery

Question 61

Factor VIIa (NovoSeven®) cost?

Answer 61

$1,000/mg; average pt: 70 kg ; average dose: $7,000 (100 mcg/kg = 7000 mcg or 7 mg)

Question 62

Factor VIIa (NovoSeven®) average treatment?

Answer 62

Dose every 2-3 hours until hemostasis achieved

Question 63

Prothrombin Complex Concentrates (PCCs) treats?

Answer 63

Warfarin reversal, hemophilia B, various off-labels

Question 64

In U.S. what is commonly used for warfarin reversal versus other countries?

Answer 64

U.S. uses FFP and other countries use more PCCs

Question 65

PCCs are primary treatment for what?

Answer 65

hemorrhage with ↑ INR when urgent reversal needed

Question 66

Compared to FFP, PCCs are?

Answer 66

faster reversal, less volume, no cross-matching