CHAPTER 45: ANTICOAGULANT, ANTIPLATELETS, AND -Does not cross the placental barrier, unlike warfarin

THROMBOLYTICS - heparinase - liver enzyme that destroys heparin

- Anticoagulants - prevent the formation of clots that inhibit - Poorly absorbed in GI (kaya given SQ or IV)

circulation
- Partial thromboplastin time (PTT) and activated partial
- Antiplatelets - prevent platelet aggregation (clumping together to thromboplastin time (aPTT) - lab tests used to detect
form a clot)
deficiencies of certail clotting factors

- Thrombolytics (clot busters) - attack and dissolve blood clots that - Can decrease platelet count = thrombocytopenia

have already formed

- Protamine sulfate - anticoagulant din pero antagonist ng
heparin, binibigay pagnagkableeding na kasi narereverse Niya
Pathophysiology: Thrombus formation
yung effects ng heparin

- Thrombosis - formation of a clot in an arterial or venous vessel, - Low-molecular-weight heparins (LMWH)- used to prevent
caused by blood stasis (decreased circulation), platelet aggregation, venous thromboembolism, thus lowering risk of bleeding

or blood coagulation
- Inactivates Xa factor but is less able to inactivate thrombin

- Arterial clots - made up of both WBC, RBC and platelets trapped in - Longer hl than heparin

fibrin mesh
- Not for those with peptic ulcers, strokes, blood anomalies

- Venous clots - yung fibring yung nag aattach sa RBC

- Not for those having eye, brain, spinal surgery

- Embolus - dislodged thrombus traveling the circulation

- Fondaparinux (Arixtra) - synthetically engineered antithrombotic
- Platelets only bind pag may sira yung endothelum ng blood vessel related to heparin and LMWH, to prevent DVT and acute
tapos nagsesynthesize sila ng thromboxane A2, a product of pulmonary embolism after orthopedic or abdominal surgery

prostaglandins and a potent stimulus for platelet aggre

- Enoxaparin - hip/knee replacement anticoagulant

- glycoproteinIIb/IIIa - platelet receptor protein rgar binds fibrinogen,

promote p. Aggre, increased activation by thromboxane A2 and DIRECT THROMBIN INHIBITORS: PARENTERAL
adenosine diphosphate (ADP)
ANTICOAGULANTS II
- Tissue ischemia - results from the blockage of thrombus
- directly inhibit thrombin from converting fibrinogen to fibrin

- Warfarin and heparin - oral and parenteral anticoagulants - DOC to - Given thru IV:

prevent venous thrombosis

- Argatroban (Acova)

- Antiplatelet drugs - prevent arterial thrombosis

- Bivilirudin (Angiomax) - binds with and inhibits free flowing
thrombin

ANTICOAGULANTS - Lepirudin (Refludan)

- inhibits clot formation, prophylaxis only

- Desirudin (Iprivask) - thru IV

- Does not dissolve clots that have already formed

- Dabigatran (Pradaxa) - PO

- Used in patients with venous (deep vein thrombosis, pulmonary

embolism) and arterial (coronary thrombosis, MI, cerebrovascular ORAL ANTICOAGULANTS
accidents (stroke)) disorders that are at risk for clot formation
Warfarin (Coumadin)- from the coumarin drug family, synthezised from
dicumarol, before it was used to kill rats

HEPARIN - Inhibit hepatic synthesis of vit K thus effecting the clotting factors II,
- introduced in 1938, natural substance in the liver
VII, IX, X

- For rapid anticoagulant effect

- used mainly to prevent thrombophlebitis, pulmonary embolism
- Used in open-heart surgery to prevent blood from clotting fot pt caused by a fib > stroke (CVA)

with disseminated intravascular coagulation

- well absorbed thru GI

- DIC - occurs when fibrin clots form within the vascular system, - Food will delay but not inhibit absorption

consume proteins and platelets, depleting clotting factors and - Prothrombin time (PT)- lab test that measures the time it takes for
causing excess bleeding
blood to clot in the presence of certain clotting factors which warfarin
- Main use is to prevent venous thrombosis
affects

- Combines with antithrombin III to inactivate factor Xa and - PT level should be 1.5 -2 times the reference value in order to be
thrombin, which accelerates the anticoagulant cascade of therapeutic

reactions that prevents thrombosis formation. By inhibiting the - International normalized ratio (INR) - lab test most frequently used
action of thrombin, conversion of fibrinogen to fibrin does not to report PT result kasi Iba Iba yugn reference ng PT sa Iba ibang
occur and the formation of a fibrin clot is prevented
clinic

- INR should be 2-3

- Vitamin K - antidote for warfarin, but it takes 2 days to be effective

- Highly protein bound

- Effective for long-term anticoagulant therapy

- Not recommended for pregnant woman

SEAAR

- bleeding (hemorrhage) - adverse effect of warfarin

Drug interactions

- aspirin, NSAIDS, sulfo, phenytoin, cimetidine, allopurinol, oral

hypogly drugs displace warfarin from the protein-bound site

- Acetaminophen should be used instead of aspirin

Xa inhibitor: Oral anticoagulants

- Rivaroxaban (Xarelto) and apixaban (Eliquis) - mga bagong drugs

ANTICOAGULANT ANTAGONISTS
- Vitamine K1 (phytonadione) - antagonist of warfarin, used for
uncontrollable bleeding, usually 1- 10mg and binibigay at once, pag
di nagwork, blood or frozen plasma or platelets na ang binibigay

ANTIPLATELET DRUGS
- used to prevent thrombosis in the arteries by suppressing platelet
aggregation

- Prophylaxis for:

• Prevention of (repeat) MI or CVA for pt with fam hx

• Prevention of CVA for pt having transient ischemic attacks (TIAs)

- Aspirin - low dose lang, suppresses platelet aggregation, inhibits

cyclooxygenase, an enzyme needed by platelets to sythesize
thromboxane A2

- Pero dapat itigil at least 7 days before surgery kasi may

prolonged antiplatelet activity ito

- Ticagrelor - taken with aspirin in a maintenance regime

- Clopidogrel (Plavix) - used after MI or CVA to prevent it happening

again, pwedeng in itself or with aspirin (para mas effective)

- Prevents platelet aggregation bu blocking the binding of ADP to

the platelet ADP receptor na nag aactivate sa glycoprotein IIb/IIIa

THROMBOLYTICS
• thromboembolism - occlusion of an artery or vein caused by a
thrombus or embolus, results in ischemia (deficient blood flow) that
causes necrosis (death of the tissue in the ostructed area)

• It takes 1-2 wks for blood clot to disintegrade

- Thrombolytics - used since 1980s to promote the fibrinolytic

mechanism (converting plasminogen to plasmin which destroys the
fibrin in the blood clot, within 4h after MI.

- Should be administered within 3h of a thrombolic stroke

- Streptokinase and urokinase - enzymes that act systemically to

promote the conversion of plasminogen to plasmin

- Altepase - (tissue plasminogen activator or tPA) clot-specific and

binds to fibrin surface of a clot promoting conversion pf plasminogen
to plasmin

- Plasmin - enzyme that digests the fibrin in the clot, degrades

fibrinogen, prothrombin, and other clotting factors

- Fibrinolysis - fibrin breakdown

SEAAR

- anaphylaxis (vascular collapse) occurs freq in strepto than with other

thrombolytics

- Hemorrhagic infarction, reperfusion dysrhythmia, myocardial necrosis

- Hemorrhage talaga