Page 1856 - Williams Hematology ( PDFDrive )

1830 Part XII: Hemostasis and Thrombosis Chapter 112: Platelet Morphology, Biochemistry, and Function 1831

B

Leukocyte

Tissue factor
vesicle PSGL-1 DOWNSTREAM
P-selectin
Platelet-leukocyte
aggregates

Platelet aggregates

Platelet microparticles

Thrombin

TXA 2 and LTs
Serotonin

C
Figure 112–1. B. Platelet aggregation occurs when the multivalent adhesive glycoproteins bind simultaneously to integrin α β receptors on two
IIb 3
different platelets, resulting in receptor crosslinking. Clustering of the receptors probably also contributes to the stability of the aggregates (not shown).
C. After platelets adhere and aggregate, they help to initiate coagulation by binding tissue factor-containing vesicles circulating in the plasma, exposing
negatively charged phospholipids on their surface (not shown), releasing platelet factor V (not shown), and releasing procoagulant microparticles. Acti-
vated platelets also express P-selectin on their surface, which leads to recruitment of leukocytes via interactions between platelet P-selectin and P-selectin
glycoprotein ligand-1 (PSGL-1) expressed on the surface of leukocytes. Other interactions between platelets and leukocytes are detailed in Fig. 112–9.
Thrombus formation is a dynamic cyclical process, with platelets repeatedly adhering, aggregating, and then breaking off and embolizing downstream.
Platelet–leukocyte aggregates, platelet aggregates, platelet microparticles, thrombin, thromboxane A (TXA ), leukotrienes (LTs), and serotonin prob-
2
2
ably all go downstream and affect the microvasculature. Ultimately, the vessel either becomes fully occluded or loses its thrombogenic reactivity;
that is, it becomes passivated.
as a function of distance from the blood vessel wall, vary considerably Willebrand factor (VWF) binding to glycoprotein (GP) Ib/IX followed
throughout the vasculature, being highest in small arterioles and low- by intracellular signaling, leading to activation of integrin α β . 13–16
IIb 3
est in large arteries and veins; very high rates are observed at the tips Platelets contribute more significantly to arterial thrombi than to
of severely stenotic atherosclerotic arteries. 6,11,12 Very high shear rates venous thrombi, perhaps as a result of differences in the shear rates in
can cause platelets to aggregate via a mechanism that involves von the different beds. 5

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