DVT/PE

Question 1

Prophylaxis & acute mgt of DVT (2)

Answer 1

UFH/LMWH

Question 2

Category & ex’s (2) of drugs for long-term DVT prevention

Answer 2

Oral anticoagulants: Warfarin & Rivaroxaban

Question 3

Virchow’s Triad

Answer 3

“SHE”
Stasis: post-op/long drive or flight

Hyper coagulability: coagulation cascade problem
(ie: Factor V Leiden mutation)

Endothelial damage (i.e.: exposed collagen that triggers clotting cascade)

Question 4

Imaging test of choice for DVT

Answer 4

Compression ultrasound w/ Doppler

Question 5

Imaging test of choice for PE

Answer 5

CT pulmonary angiography

Question 6

Factor Xa Anticoagulant w/ greatest efficacy & 2 examples

Answer 6

LMWH (dalteparin, enoxaparin)

Question 7

Direct Xa Inhibitors (2)

Answer 7

Apixaban, Rivaroxaban

Question 8

Factor IIa (Thrombin) Anticoagulant w/ greatest efficacy

Answer 8

Heparin

Question 9

Direct Thrombin Inhibitors (3)

Answer 9

Argatroban, Dabigatran, Bivalirudin,

Question 10

Prophylaxis and Acute Mgmt of DVT

Answer 10

UFH or LMWH (eg: enoxaparin)

Question 11

Tx & Long term prevention of DVT

Answer 11

Oral anticoagulants (eg: warfarin, rivaroxaban)

Question 12

Indirectly lowers activity of thrombin and factor Xa w/ short T1/2

Answer 12

UFH

Question 13

Clinical Use of Heparin

Answer 13

Immediate anticoagulation for pulmonary embolism

acute coronary syndrome, MI, DVT

Question 14

Anticoagulant that doesn’t cross placenta & monitored via PTT

Answer 14

Heparin

Question 15

AE of Heparin

Answer 15

Bleeding, Thrombocytopenia (HIT), osteoporosis, hypoaldosteronism, hyperkalemia, drug-drug interactions

Question 16

Rapid reversal agt vs. Heparin

Answer 16

Protamine Sulfate: (+) charged molecule that binds (-) charged Heparin

Question 17

Heparin class that acts predominantly on Factor Xa (#1-w/ 2ex’s) and only on Factor Xa(#2)

Answer 17

1) LMWH (eg: enoxaparin, dalteparin)

2) Fondaparinux

Question 18

MOA of Heparin-induced Thrombocytopenia (HIT)

Answer 18

dev of IgG ab’s vs. heparin bound PT factor 4 (PF4)

ab-Hep-PF4 complex activates PT’s->Thrombosis & Thrombocytopenia

Question 19

Only PO direct thrombin inhibitor

Answer 19

Dabigatran

Question 20

Clinical use of direct thrombin inhibitor

Answer 20

VTE, a fib, HIT

doesn’t require lab monitoring

Question 21

What can reverse dabigatran (direct thrombin inhibitor)?

Answer 21

idarucizumab

Question 22

MOA of Warfarin

What is its metabolism affected by?

Answer 22

interferes w/ Y-carboxylation of vit K dep clotting factors (II, VII, IX, X) and proteins C & S

metabolism influenced by polymorphisms in gene for vit k epoxide reductase complex (VKORC1)

Question 23

What is the effect of warfarin in a laboratory assay?

Answer 23

effect on extrinsic pathway, ↑ PT and w/ long T1/2

Question 24

Clinical Uses of Warfarin (2)

Answer 24

Chronic anticoagulation (eg: VTE prophylaxis) & stroke prevention in a fib

Question 25

CI of Warfarin

Answer 25

Pregnant women bc crosses placenta; follow PT/INR

Question 26

AE of Warfarin

Answer 26

Bleeding, teratogenic, skin/tissue necrosis* (due to small vessel micro thrombosis*)

Question 27

Explain the early transient hyper coagulability w/ warfarin use

Answer 27

Factors C & S with shorter T1/2 than clotting factors II, VII, IX, X

Question 28

Warfarin reversal (a) & rapid reversal (b)

Answer 28

Vit K (a)/FFP or PCC (b)

Question 29

What is heparin "bridging" & why is it imp?

Answer 29

Heparin frequently used when starting warfarin Heparin's activation of antithrombin enables anticoagulation during initial transient hyper coagulable state caused by warfarin Initial heparin Tx ↓ risk of recurrent VTE & skin/tissue necrosis

Question 30

Compare route of admin, site of action & onset of action in Heparin vs. Warfarin

Answer 30

Heparin: Parenteral (IV, SC) Blood Rapid (secs) Warfarin: PO Liver Slow, limited by half lives of normal clotting factors

Question 31

Direct Factor Xa Inhibitors (2)

Answer 31

Apixaban, Rivaroxaban

Question 32

Clinical use of direct Factor Xa inhibitors (2)

Answer 32

Tx and prophylaxis of DVT & PE , stroke paralysis in patients w/ a fib

Question 33

+ of oral anticoagulant agents?

Answer 33

Don't usually require monitoring

Question 34

AE & limitation of direct factor Xa inhibitors

Answer 34

Bleeding; not easily reversible

Question 35

Grade the reversibility of the heparin classes

Answer 35

UFH: Robust LMWH: Moderate FPX: Little, if any

Question 36

What are HIT paradoxes?

Answer 36

``` Anticoagulant-induced thrombosis Clotting, not bleeding disorder PT transfusions can ↑ thrombosis risk Simply stopping heparin may not prevent thrombosis Warfarin CI as acute monotherapy ```

Question 37

How might HIT present clinically?

Answer 37

Drop in PT count & or new thrombosis

Question 38

Describe the nature of heparin exposure in HIT in terms of a) Heparin Class b) Dose/Duration c) Route of admin d) Clinical Setting

Answer 38

a) UFH>LMWH b) High>Low dose c) Long term>Short term IV>SC, flushes, heparin coated devices d) cardiac, orthopedic or ICU

Question 39

Derivation & action of Argatroban

Answer 39

L arginine; Univalent inhibitor of thrombin, inhibiting clot bound & soluble thrombin

Question 40

Indication of Argatroban

Answer 40

Anticoagulant for prophylaxis/Tx of thrombosis, or PCI in patients w/ HIT*

Question 41

Anticoagulant w/o cross-reactivity w/ heparin induced antibodies

Answer 41

Argatroban

Question 42

Limitation of Argatroban

Answer 42

No known antidote

Question 43

Therapeutic Effect of Argatroban

Answer 43

Rapid, ~30 mins (IV but no bolus)

Question 44

Argatroban Elimination

Answer 44

Hepatic metabolism; T1/2 ↑ in patients w/ mild hepatic impairment

Question 45

Given the challenging transition from Argatroban, what other drug may be beneficial?

Answer 45

Direct Factor Xa Inhibitors

Question 46

What are 2 imp points to remember during Argatroban therapy transition?

Answer 46

1) Don't rely on warfarin alone until HIT is adequately controlled 2) Give several days for warfarin to attain its therapeutic effect

Question 47

What are some criteria that have to be met before Argatroban is discontinued? (5)

Answer 47

- INR>4.0^2 - Obtain INR 4-6 hours after Argatroban discontinued - Absence of new TEC's - PT recovery - Restart Argatroban Tx if INR falls below therapeutic range

Question 48

What are 2 anticoagulants that are CI in acute HIT?

Answer 48

a) Warfarin | b) LMWH: cross-reactive w/ heparin antibodies

Question 49

What is one + of Fondaparinux?

Answer 49

Rarely cross reacts w/ heparin ab's | No EBM but anecdotal support

Question 50

3 +/- of Oral Xa Inhibitors

Answer 50

+: PO Easy dosing No routine monitoring -: $ No antidote Renal clearance

Question 51

Why is warfarin not used in acute thrombotic settings?

Answer 51

Bc it requires 3-4 days to have anticoagulant effects