Page 2062 - Hematology_ Basic Principles and Practice ( PDFDrive )

C H A P T E R 122

OVERVIEW OF HEMOSTASIS AND THROMBOSIS

James C. Fredenburgh and Jeffrey I. Weitz

Hemostasis preserves vascular integrity by balancing the physiologic coagulation; and fibrinolytic agents that induce fibrin degradation
processes that maintain blood in a fluid state under normal circum- (see Chapter 149). With the predominance of platelets in arterial
stances and prevent excessive bleeding after vascular injury. Preserva- thrombi, strategies to inhibit or treat arterial thrombosis focus mainly
tion of blood fluidity depends on an intact vascular endothelium and on antiplatelet agents, although in the acute setting, strategies often
a complex series of regulatory pathways that maintain platelets in a include anticoagulants and fibrinolytic agents. When arterial thrombi
quiescent state and keep the coagulation system in check. In contrast, are occlusive and rapid restoration of blood flow is imperative,
arrest of bleeding requires rapid formation of hemostatic plugs at mechanical and pharmacologic methods enable thrombus extraction,
sites of vascular injury to prevent exsanguination. Perturbation of compression, or degradation. Although rarely used for this indication,
hemostasis can lead to bleeding or thrombosis. Bleeding will occur anticoagulants can also prevent recurrent ischemic events after acute
if there is failure to seal vascular leaks either because of defective myocardial infarction. Anticoagulants are the mainstay for prevention
hemostatic plug formation or because of premature breakdown of and treatment of venous thromboembolism because fibrin is the
the plugs. In contrast, thrombosis may occur if prothrombotic stimuli predominant component of venous thrombi (see Chapter 142).
are unregulated. Antiplatelet drugs are less effective than anticoagulants because of the
Thrombosis can occur in arteries or veins and is a major cause of limited platelet content of venous thrombi. Selected patients with
morbidity and mortality. Arterial thrombosis is the most common venous thromboembolism benefit from fibrinolytic therapy—for
cause of acute coronary syndromes, ischemic stroke, and limb gan- example, patients with massive or submassive pulmonary embolism
grene, whereas thrombosis in the deep veins of the leg leads to achieve more rapid restoration of pulmonary blood flow with systemic
postthrombotic syndrome and pulmonary embolism, which can be or catheter-directed fibrinolytic therapy than with anticoagulant
fatal. therapy alone. Certain patients with extensive deep vein thrombosis
Most arterial thrombi form on top of disrupted atherosclerotic in the iliac and/or femoral veins may also have a better outcome with
plaques, because plaque rupture exposes thrombogenic material in catheter-directed fibrinolytic therapy and/or mechanical thrombus
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the plaque core to the blood. This material then triggers platelet extraction in addition to anticoagulants (see Chapter 143).
aggregation and fibrin formation, which results in the generation of This chapter provides an overview of hemostasis and thrombosis
a platelet-rich thrombus that temporarily or permanently occludes by highlighting the processes involved in platelet activation and
blood flow. Temporary occlusion of blood flow in coronary arteries aggregation, blood coagulation, and fibrinolysis.
may trigger unstable angina, whereas persistent obstruction causes
myocardial infarction. The same processes can occur in the cerebral
circulation, where temporary arterial occlusion may manifest as a HEMOSTATIC SYSTEM
transient ischemic attack, and persistent occlusion can lead to a
stroke. Likewise, critical limb ischemia can occur if there is superim- The major components of the hemostatic system are the vascular
posed thrombosis on ruptured atherosclerotic plaques in the major endothelium, platelets, and the coagulation and fibrinolytic systems.
arteries supplying blood to the lower extremities.
In contrast to arterial thrombi, venous thrombi rarely form at sites
of obvious vascular disruption. Although they can develop after surgi- Vascular Endothelium
cal trauma to veins, or secondary to indwelling venous catheters, they
usually originate in the valve cusps of the deep veins of the calf or in A monolayer of endothelial cells lines the intimal surface of the cir-
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the muscular sinuses, where there is stasis. Sluggish blood flow in culatory tree and separates the blood from the prothrombotic suben-
these veins reduces the oxygen supply to the avascular valve cusps. dothelial components of the vessel wall (see Chapter 123). As such,
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Hypoxemia induces endothelial cells lining the valve cusps to become the vascular endothelium encompasses about 10 cells and covers a
activated and express adhesion molecules onto their surfaces. Tissue vast surface area. Rather than serving as a static barrier, the healthy
factor–bearing leukocytes and microparticles adhere to these activated vascular endothelium is a dynamic organ (Fig. 122.1) that actively
cells and induce coagulation. Impaired blood flow exacerbates local regulates hemostasis by inhibiting platelets, suppressing coagulation,
thrombus formation by reducing clearance of activated clotting promoting fibrinolysis, and modulating vascular tone and permeabil-
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factors. These responses constitute the three axes of the Virchow triad ity. Defective vascular function can lead to bleeding if the endothe-
associated with development of thrombosis: stasis, hypercoagulability lium becomes more permeable to blood cells, if vasoconstriction does
of the blood, and activation or disruption of the endothelium. Calf not occur, or if premature degradation of hemostatic plugs reopens
vein thrombi that extend into the proximal veins of the leg can dis- repaired vasculature.
lodge and travel to the lungs to produce pulmonary embolism. 3
Arterial and venous thrombi contain platelets and fibrin, but the
proportions differ. Arterial thrombi are rich in platelets because of Platelet Inhibition
the high shear on this side of the circulatory system. In contrast,
venous thrombi, which form under low shear conditions, contain Endothelial cells synthesize prostacyclin and nitric oxide and release
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relatively few platelets and consist mostly of fibrin and trapped red them into the blood. These agents not only serve as potent vasodila-
blood cells. Because of the predominance of platelets, arterial thrombi tors but also inhibit platelet activation and subsequent aggregation
appear white, whereas venous thrombi appear red. by stimulating adenylate cyclase and increasing intracellular levels
The antithrombotic drugs used for prevention and treatment of of cyclic adenosine monophospahte (cAMP). In addition, endothe-
thrombosis target components of thrombi and include antiplatelet lial cells express CD39 on their surfaces, a membrane-associated
drugs, which inhibit platelets; anticoagulants, which attenuate ecto-adenosine diphosphatase (ADPase). By degrading adenosine

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