Pharm II - DVT/PE

secondary hemostasis

the reaction of the plasma coagulation proteins resulting in cross-linked fibrin which strengthens the platelet plug

fibrinolytic system

a complex system which limits the size of fibrin clot formation

thrombolytic/fibrinolytic agents

dissolve existing thrombi by accelerating conversion of plasminogen to plasmin; induce a systemic fibrinolytic state

thrombin

activated factor II that converts fibrinogen to fibrin during coagulation

tPA

tissue plasminogen activator endogenous in the body; changes plasminogen to plasmin

D-dimer

fibrin clot degradation product; sensitive but not specific

direct oral anticoagulants (DOACs)

vitamin K antagonist (Warfarin)

factor Xa inhibitors (rivaroxaben, apixaban, edoxaban)

direct thrombin inhibitor (dabigatran)

fibrinolytics

alteplase

tenecteplase

aspirin

prophylactic VTE drug, not used for acute treatment

heparin

causes conformational changes in antithrombin so that it binds more avidly to the coagulation factors it inactivates and enhances inactivation

unfractionated heparin

inhibits factors Xa and IIa by potentiation of antithrombin; used in DVT prophylaxis and full anticoagulation

activated partial thromboplastin time (aPTT)

measures the clotting time of intrinsic pathway and common pathway factors; monitored in heparin therapy

activated clotting time (ACT)

used for monitoring when higher doses of heparin are being used; uses clay to activate the intrinsic coagulation cascade

anti-factor Xa units

standardizing reagents and coagulometers by determining the aPTT values that correlate with heparin levels; used to monitor LMWH

enoxaparin (Lovenox)

LMWH; selective inhibitor of Xa > IIa by potentiation of antithrombin; used in prophylaxis & full anticoagulation of VTE

warfarin

affects formation of vitamin K depending clotting factors and natural anticoagulants (protein C, S); treatment overlap with rapid-acting parenteral agent

dabigatran (Pradaxa)

oral direct thrombin (factor II) inhibitor; used for prophylaxis in total knee/hip arthroplasty and full dose anticoagulation following 5 days of parenteral agent

decrease INR

vitamin K rich foods plus warfarin

factor Xa inhibitors

direct inhibitors of factor Xa, preventing activation of thrombin

edoxaban

factor Xa inhibitor, NOT indicated for prophylaxis, used for full anticoagulation dosing in VTE treatment following 5 days of parenteral agent; "Goldilocks Drug"

fibrinolytics

used for unstable PE or severe iliofemoral DVT

LMWH

preferred agent for VTE treatment in patients with cancer

andexanet alfa

used to reverse apixaban and rivaroxaban

deep vein thrombosis (DVT)

clot formation within the venous circulation, most often in the large veins of the legs

pulmonary embolism (PE)

when part of a thrombus breaks away, traveling to the lungs and disrupting or blocking blood flow in a pulmonary artery

blood stasis, vascular injury, hypercoagulability

virchow's triad

primary hemostasis

platelet interaction with subendothelium resulting in the formation of a platelet plug at the site of vascular injury

antiplatelet agents

interfere with platelet activity

anticoagulants

prevent clot formation and extension

protein C, protein S

naturally occurring anticoagulation factors

prostacyclin, nitric oxide

released by normal endothelium to inhibit platelet aggregation

Xa, IIa

activated clotting factors involved in clot formation

plasmin

enzyme responsible for degradation of fibrin and fibrinogen resulting in clot breakdown

oral antiplatelet

aspirin is this type of VTE agent

parenteral anticoagulants

heparin related products (unfractionated heparin, enoxaparin, fondaparinux)

direct thrombin inhibitors (bivalirudin, argatroban)

aspirin

irreversible inhibition of TXA2 via COX1 results in platelet inactivation for the life of the platelet (4-7 days)

TxA2

platelet aggregator and vasoconstrictor

PGI2

prostacyclin; vasodilator and inhibits platelet aggregation

aPTT, anti-Xa, CBC

monitor in heparin therapy

fondaparinux (Arixtra)

heparin-like agent that inhibits factor Xa by potentiation of antithrombin; used in prophylaxis and full anticoagulation of VTE; may be used in HIT

argatraban, bivalirudin

parenteral direct thrombin (factor II) inhibitors

argatraban

parenteral direct thrombin inhibitor metabolized in the liver

bivalirudin

parenteral direct thrombin inhibitor that is renally eliminated

II, VII, IX, X

vitamin K dependent clotting factors

2-3

INR goal of full anticoagulation treatment

bridging

overlap of warfarin with rapid-acting parenteral anticoagulant

flagyl, amiodarone, bactrim, fluconazole, FQs

FAB5; potentiate warfarin effect

factor Xa inhibitors

ribaroxaban (Xarelto)

apixaban (Eliquis)

edoxaban (Savaysa)

rivaroxaban, apixaban

DDI with CYP3A4 inhibitors

apixaban

least renally eliminated agent of the DOACs

rapid agent 5-7 days, full anticoagulation 3-6 months

treatment timeline for VTE

warfarin

traditional VTE agent for patients with severe renal dysfunction

warfarin

crosses placenta, contraindicated in pregnancy but safe during breastfeeding

heparin induced thrombocytopenia (HIT)

rare drug-induced immunologic reaction with heparin; heparin-platelet factor 4 antibody complex

VTE

most common complication of HIT

argatroban, bivalirudin, fondaparinux

anticoagulants used to treat HIT

vitamin K

used to reverse warfarin

protamine sulfate IV

used to reverse UFH and enoxaparin

PCC (Kcentra)

used to reverse DOACs

idarucizumab

used to reverse dabigatran

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