CLINICAL-PHARMACY-VENOUS-THROMBOEMBOLISM (3).docx

Prothrombin time

________ and INR monitoring are usually to be performed at baseline and daily when commencing warfarin in the inpatient acute care setting.

Laboratory monitoring

________ is performed by measuring the PT for calculation of the INR.

Estrogen

________- containing oral contraceptives or hormone- replacement therapy.

UNFRACTIONATED HEPARIN therapeutic effect

________ is hastened by administration of a loading dose, which may be empirically selected (e.g., 5000- units bolus given intravenously) or individualized by the patients dosing weight.

vitamin K

(1) The PT is responsive to suppression of three of the four ________- dependent pro- coagulant clotting factors (prothrombin or factors II, VII, and X)

B Warfarin

________ may also be used in patients with valvular heart disease to prevent systemic arterial embolism, although its effectiveness has never been demonstrated by a randomized clinical trial.

LMWHs (low molecular weight heparin)

________ are fragments of standard commercial- grade heparin produced by either chemical or enzymatic depolymerization.

A Warfarin

________, a coumarin compound, is the most widely used oral anticoagulant in North America.

clot bound

The drug binds rapidly and specifically to both free and ________ thrombin whose inhibition results in prevention of thrombus.

oral administration

After ________, the drug is rapidly absorbed, converted to active drug and eliminated primarily by renal excretion, with an onset of action achieved in approximately 1 hr after administration of the dose.

Venous thromboembolic disease

________ (VTED) occurs when one or more of the elements of Virchows triad are present, resulting in deep venous thrombosis (DVT) and /or pulmonary embolism (PE)

Mechanical methods of prophylaxis

________ are recommended, primarily in patients who are at high risk of bleeding, and may include external pneumatic compression, graduated compression stockings, or venous foot pumps.

Oral anticoagulants

________ (e.g., warfarin) are vitamin K antagonists, producing their anticoagulant effect by interfering with the cyclic interconversion of vitamin K and its 2,- 3- epoxide (vitamin K epoxide)

inactivation of thrombin

UFH acts as an anticoagulant by catalyzing the ________ (factor IIa), activated factor X (factor Xa), and activated factor IX (factor IXa) by antithrombin.

Synthetic pentasaccharide

________ is a selective factor Xa inhibitor.

ISI (international sensitivity index)

Where ________ is a measure of the responsiveness of a given thromboplastin to reduction of the vitamin K- dependent coagulation factors.

plasma recoveries

The ________ and pharmacokinetics of LMWHs differ from heparin because of differences in the binding properties of the two sulfated polysaccharides to plasma proteins and endothelial cells.

B UFH

________ is cleared by rapid- phase (cellular) elimination followed by a more gradual (renal) clearance, which can best be explained by a combination of saturable and nonsaturable first- order kinetic models.

aPTT (partial thromboplastin time)

The ________ should be obtained at baseline before commencing therapy and then monitored 6 hrs after commencing heparin therapy.

Risk factors

________ for bleeding include certain medications known, to increase this risk (e.g., antiplatelet agents, heparin, fibrinolytic therapy, chronic use of nonsteroidal anti- inflammatory drugs (NSAIDs), and labor and delivery)

LMWHs

________ are approximately one- third the size of heparin.

oral administration

After ________, the drug is approximately 80 % bioavailable and is rapidly absorbed with an onset of action achieved in approximately 2 to 4 hrs after administration of the dose.

A Warfarin

________ is a racemic mixture of roughly equal amounts of two optically active isomers: the R and S forms.

B Warfarin

________ is rapidly absorbed from the gastrointestinal tract and reaches maximal blood concentrations in healthy volunteers in 90 mins.

(4)Initial heparin weight-based dosing nomograms and subsequent adjustment proto

cols have been developed to assist the initial weight-based dosing efforts

a. Warfarin is a racemic mixture of roughly equal amounts of two optically active isomers

the R and S forms

(2) The common commercial PT reagents vary markedly in their responsiveness to coumarin

induced reduction in clotting factors; therefore, PT results reported using different reagents are not interchangeable among laboratories

The problem of variability in responsiveness of PT reagents has been overcome by the intro

duction of a standardized test known as the INR

where ISI (international sensitivity index) is a measure of the responsiveness of a given thromboplastin to reduction of the vitamin K

dependent coagulation factors

(2) Current recommendations suggest two levels of therapeutic intensity

a less-intense range corresponding to an INR of 2.0 to 3.0, and a more intense range corresponding to an INR of 2.5 to 3.5

(3) Once the desired therapeutic INR has been achieved for 2 consecutive days (e.g., for concomitant heparin plus warfarin overlap therapy), follow-up INR monitoring can be per

formed according to the following protocol

(a) Week 1

monitor INR two or three times

(b) Week 2

monitor INR two times

(c) Weeks 3 to 6

monitor INR once a week

(d) Weeks 7to14

monitor INR once every 2 weeks

(e) Week 15 to end of therapy

monitor INR once every 4 weeks (if INR dose responsiveness remains stable; if dose adjustment is necessary, a more frequent monitoring schedule is employed until stable dose responsiveness is achieved)

(1) Patients with body weight between 50 and 100 kg

7.5 mg

(2) Patients with body weight < 50 kg

5 mg

(3) Patients with body weight > 100 kg

10 mg

(1) Treatment with rivaroxaban is not recommended in the following patients

concomitantly treated systemically with strong concurrent CYP3A4 inhibitor and plasma glycoprotein (P-gp) inhibitors, i.e., azole antimycotics (such as ketoconazole, itraconazole, voriconazole, and posaconazole) or HIV protease inhibitors (e.g., ritonavir); with severe renal impairment (creatinine clearance [Clcr]