TRIPASS XR تري باس

 

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p. 173

Venous thromboembolism (VTE), including deep vein thrombosis (DVT)

and pulmonary embolism (PE), is caused by numerous additive risk

factors, with diagnosis based on clinical findings and objective criteria.

Case 11-1 (Questions 1–3),

Case 11-5 (Question 1)

VTE treatment includes parenteral anticoagulants (low-molecular-weight

heparins or fondaparinux) bridging to a therapeutic international

normalized ratio (INR) with warfarin, parenteral anticoagulants given

before transitioning to dabigatran or edoxaban, or as monotherapy with

rivaroxaban or apixaban.

Case 11-1 (Questions 4–6,

9), Case 11-5 (Questions 2,

3)

Unfractionated heparin is monitored with the activated partial

thromboplastin time (aPTT) test; dosing adjustments are used to

maintain the aPTT in therapeutic range, as well as monitoring for

adverse effects, including thrombocytopenia and bleeding.

Case 11-1 (Questions 7, 8,

10–12),

Case 11-2 (Question 1)

Outpatient treatment of VTE is preferred over hospitalization for patients

with DVT and low-risk PE and home circumstances that are adequate.

Case 11-3 (Questions 1, 2)

Anticoagulation prophylaxis should be used in hospitalized patients at risk

of VTE.

Case 11-4 (Question 1)

Warfarin therapy is dosed and monitored according to therapeutic

response as measured by the INR. Monitoring for adverse effects

including hemorrhage is also essential for all anticoagulants.

Case 11-5 (Questions 4–6),

Case 11-6 (Questions 5, 6),

Case 11-7 (Question 1)

Warfarin therapy is influenced by multiple factors, and patients on

warfarin require extensive and ongoing education to maintain safe and

effective anticoagulation.

Case 11-6 (Questions 1–4),

Case 11-8 (Question 1),

Case 11-13 (Question 1),

Case 11-14 (Questions 1, 2)

Warfarin and the direct oral anticoagulants (DOACs) are used for

stroke prevention in nonvalvular atrial fibrillation. Warfarin is the only

long-term oral option for stroke prevention for thrombosis prevention in

patients with artificial heart valve replacement.

Case 11-9 (Questions 1–3),

Case 11-10 (Question 1),

Case 11-11 (Question 1)

Pharmacists can play an important role in the management of

anticoagulant therapy for invasive procedures.

Cases 11-12 (Question 1)

Although the DOACs do not need monitoring to measure their efficacy,

monitoring of baseline renal function and complete blood cell counts are

necessary to ensure appropriateness of dosing and to minimize risk of

anticoagulation-related bleeding complications.

Case 11-3 (Question 1),

Case 11-5 (Questions 2, 6)

GENERAL PRINCIPLES

Thrombosis is the process involved in the formation of a fibrin blood clot. Platelets

and a series of coagulant proteins (clotting factors) contribute to clot formation. An

embolus is a small part of a clot that breaks off and is carried by blood flow to

another part of the vascular system. Damage is caused when the embolus becomes

trapped in a small vessel, causing occlusion and leading to ischemia or infarction of

the surrounding tissue. Normal clot formation maintains the integrity of the

vasculature in response to injury, but pathologic clotting can occur in many clinical

settings. Abnormal thrombotic events include venous thromboembolism (deep venous

thrombosis [DVT] and its primary complication, pulmonary embolism [PE]), as well

as stroke and other systemic manifestations of embolization of clots that form within

the heart. Anticoagulant drug therapy is aimed at preventing pathologic clot formation

in patients at risk and at preventing clot extension and/or embolization in patients

who have experienced thrombosis. This chapter emphasizes arterial and venous

thromboembolic disease and the use of the parenteral anticoagulants (unfractionated

heparin, low-molecular-weight heparins, indirect factor Xa inhibitors, and injectable

direct thrombin inhibitors) and oral agents (vitamin K antagonists, and direct oral

anticoagulants [DOACs], which include the oral direct thrombin inhibitors, and the

oral direct factor Xa inhibitors). Chapter 8, Dyslipidemias, Atherosclerosis, and

Coronary Artery Disease; Chapter 13, Acute Coronary Syndrome, and Chapter 61,

Ischemic and Hemorrhagic Stroke, provide more in-depth discussions of

thrombolytic agents and antiplatelet therapy.

p. 174

p. 175

Figure 11-1 Risk factors for thromboembolism.

Etiology of Thromboembolism

Three primary factors influence the formation of pathologic clots and are described

in a model referred to as Virchow’s triad (Fig. 11-1).

1 Abnormalities of blood flow

that cause venous stasis can result in DVT, which can progress to PE if embolization

occurs. Intracardiac stasis of blood can also result in clot formation within the heart

chambers, and embolization of intracardiac thrombi may lead to stroke or other

systemic manifestations. Abnormalities of blood vessel walls, such as those that

occur in injury or trauma to the vasculature, are a second source of thrombus

formation. The presence of foreign material within the vasculature, including

artificial heart valves and central venous catheters, is also thrombogenic and, like

vascular injury, represents the presence of an abnormal surface in contact with blood.

Finally, hypercoagulability resulting from alterations in the availability or the

integrity of blood-clotting components or naturally occurring anticoagulants also

represents a significant risk factor for thromboembolic disease.

2

Clot Formation

The intact endothelial lining of blood vessels normally repels platelets and inhibits

clot formation through secretion of numerous inhibitory substances. Damage to the

endothelium leads to exposure of circulating blood to subendothelial substances, and

this results in formation of a fibrin clot.

2

PLATELET ADHESION, ACTIVATION, AND AGGREGATION

Endothelial damage leads to exposure of blood to subendothelial collagen and

phospholipids, resulting in platelet adhesion to the surface. Von Willebrand factor

serves as the binding ligand for platelet adhesion, via the glycoprotein I (GPI)

receptor on the platelet surface. Adhered platelets become activated and release

numerous compounds, including adenosine diphosphate and thromboxane A2, which

stimulate platelet aggregation. Fibrinogen serves as the binding ligand for platelet

aggregation, via the GPIIb/IIIa receptor on the platelet surface.