Which drug interferes with the final step of platelet aggregation?
Eptifibatide
This is a IIb/IIIa receptor blocker which is the final step of platelet aggregation where fibrin cross linking occurs
T/F: inhibitors of platelet aggregation can decrease risk of stroke, MI and colo-rectal cancer
Si, es verdad
What is the secondary prevention for platelet aggregation inhibitor use?
Prevent RECURRENCES of: TIA, CVA, MI, ACS
What are agents of fibrinolytics?
Alteplase
Urokinase
Reteplase
Tenecteplase
Which drug is a recombinant- tPA (r-tPA)?
Alteplase
What are therapeutic indications for fibrinolytics?
Catheter occlusion
DVT
MI
Peripheral arterial occlusion
PE
Stroke
T/F: Older clots are resistance to t-PA, that is why stroke treatment is very time sensitive
True; older clots are more resistance perhaps due to more fibrin cross-linking
What are agents of fibrinolysis inhibitors?
Aminocaproic acid
Tranexamic acid
What do aminocaproic acid and tranexamic acid do?
They stop fibrinolysis meaning that it prevents the breakdown of the clot and blood continues to coagulate
What is the MOA of aminocaproic acid/ tranexamic acid?
Bind to plasminogen and prevents its conversion to plasmin
T/F: Unfractionated heparin, LMWH and Indirect Factor Xa inhibitor all have similar MOA
True; which is to inactivate thrombin and factor Xa
Heparin molecule must be at least ___ saccharides in length to inactivate thrombin
18
Heparin binds to _____ to speed up the inactivation of these clotting factors:___,___,____,___,____.
Antithrombin
Factor IIa (thrombin)
Factor IXa
Factor Xa
Factor XIa
Factor XIIa
T/F: unfractionated heparin is taken orally
False; parenteral administration: SubQ, IV bolus, constant IV infusion
What is the average elimination half life for heparin?
1.5 hours
Time to steady state with constant IV infusion of heparin is ____ hours
6 (4x the half-life which is 1.5 hours)
Reversal agent for heparin and LMWH is:
Protamine – obtained from sperm of salmon
T/F: when administered alone, protamine has an anticoagulant effect
True; even though when used as a reversal for heparin it losses its anticoagulant activity
T/F: Heparin, LMWH and fondaparinux are safe for pregnant lady
True; these are safe for baby
MOA of Heparin-induced thrombocytopenia: ____ binds onto heparin which binds onto Ig____. The immune complex then bind onto Fc region of_____ which results in removal of it by _____ in the spleen. Can also result in platelet aggregation leading to ____
PF4 (platelet factor 4)
IgG
Platelet
macrophage
thrombosis
If HIT occurs in a patient, use ________, do not use___
IV direct thrombin inhibitor – ie Argatroban
Do not use heparin or LMWH
Which anticoagulant interfere with Vitamin K oxide reductase
Warfarin
Warfarin use would lead to decreased production of which clotting factors? Why?
Factors 7,9,10 and thrombin (IIa) [as well as anticoagulant proteins C and S]
Because these are vitamin K dependent
T/F: Warfarin has effect on already-synthesized clotting factors (2, 7, 9, 10)
False; it cannot affect already synthesized clotting factors that is why therapeutic effects for heparin are not seen until those factors are depleted (usually 3-4 days)
Elimination half lives of Factor II is ___ hours, and Factor X is ____ hours
60
48-72
T/F: Drop in concentration from warfarin action potentially can cause clotting early in therapy
True; warfarin is freaking weird. Early on is prothrombotic which means it can cause blood clots
Dosing of warfarin, must follow ____ result. Which is calculated by_____
INR
INR= (Prothrombin time/ lab normal Prothrombin time)^ISI
ISI= international sensitivity index
Warfarin is metabolized by which organ?
liver
Half life of warfarin is:
36 hours (1.5 days)
Warfarin rescues:
Fresh frozen plasma
Vitamin K : phytonadione
Prothrombin complex concentrate
Factor VIIa
T/F: warfarin is safe to use in pregnant women
False; unlike heparin/LMWH/fondaparinux, warfarin is bad, unless you are a pregnant woman with mechanical heart valves
T/F: vitamin K is fat soluble, so given too much as a warfarin reversal could lead to difficulty to re-anticoagulate for a while
True
For life-threatening bleed from warfarin, what is the treatment?
Give Fresh frozen plasma, prothrombin complex concentrate or factor VIIa in addition to IV vitamin K
Rank from greatest molecular weight to least: LMWH, Fondaparinux and heparin (UFH)
T/F: Fondaparinux can be administered subcutaneously
True; an advantage over heparin
Fondaparinux is ____ (direct/ indirect) Xa inhibitor, given _____, and need dose adjustment in ______, and has ____ (high/ low) incidence of thrombocytopenia
Indirect
Subcutaneously
Renal disease
Very low to rare
T/F: there is usually no coagulation test monitoring required for LMWH and fondaparinux therapy
True; PTT not used
T/F: protamine is a reversal agent used for fondaparinux
False; Factor VIIa is. Protamine is for heparin and most the time for LMWH
What are agents of direct thrombin inhibitors:
Bivalirudin
Argatroban
Dabigatran
What are agents of direct Factor Xa inhibitors:
Rivaroxaban
Apixaban
Edoxaban
Betrixaban
The common -xa name stem means it is a ____
Direct factor Xa inhibitor
T/F: Hirudin is an anticoagulant derived from salmon saliva and it is a direct thrombin inhibitor
False; it is derived from leech saliva, lol. Salmon sperm is protamine which is a UFH/LMWH reversal
Which direct thrombin inhibitor is used in cardiac cath-labs?
Bivalirudin (used IV), alternate anticoagulant when pt has heparin allergy or HIT
Argatroban is a_______
Direct thrombin inhibitor, given IV
Which direct thrombin inhibitor is given orally
Dabigatran
What does DOAC stand for?
Direct-acting oral anticoagulant
Either direct Xa inhibitors or direct thrombin inhibitors
_____ is used to reduce the risk of stroke and systemic embolism in patient with nonvalvular atrial fibrillation
Rivaroxaban (Xarelto is the trade name)
Therapeutic indications for DOACs:
Reduce risk of stroke in nonvalvular a. fib pt
Treatment of DVT, PE, and reduction in risk of recurrence
Prophylaxis of DVT
PROs of DOACs compared to warfarin:
Lower risk of major bleeding
No INR monitoring required
Fewer drug-diet co-morbidity interactions
CONS of DOAC compared to warfarin:
No specific monitoring parament and only dabigatran has reversal agent
Renal monitoring and dose adjustment required (warfarin is eliminated via Liver)
Higher out-of-pocket costs and copays
What is the reversal agent for dabigatran (a direct thrombin inhibitor)
Idarucizumab
What is the reversal agent for direct Xa inhibitors?
Inactivated Factor Xa
What dosage and route of administration of anticoagulant should be given for effective primary prevention of hospital-acquired Venous thromboembolism (VTE)?
Low dose, given subcutaneously
High risk for venous thromboembolism:
Major lower extremity or pelvic orthopedic surgery
Neurosurgery
Major spine surgery
Active cancer
Active stroke
If a pt is high risk for VTE, what is the treatment?
Pharmacologic and mechanical prophylaxis (ie compression hose)
If a patient is hypotensive with PE, what is the primary therapy?
Anticoagulation plus thrombolysis
Embolectomy: catheter/ surgical
Primary therapy for DVT:
Clot dissolution with pharmacochemical therapy that usually includes low-dose catheter-directed thrombolysis
What is warfarin INR goal in patient with PE or DVT?
2-3
Which has a delayed response: warfarin or heparin
Warfarin, so use heparin first with warfarin then transition to just warfarin
T/F: DOACs typically have a quick onset of anticoagulant effect and may not require any lead-in or overlap therapy with an additional injectable anticoagulant
True
First choice of long-term anticoagulant in DVT of leg or PE WITH cancer:
LMWH
First choice of long-term anticoagulant in DVT of leg or PE without cancer:
DOAC
Length of anticoagulation treatment in patients with provoked (known cause) DVT:
