FIGURE 9.2 Atherosclerotic tissue is invested with PF4. (A) Photomicrograph (H&E stain) demonstrating the appearance of a group of foamy macrophages, which contain bubbly, vacuolated cytoplasm and indistinct nuclei (arrows). A giant cell is indicated by the arrow-head. (B) Photomicrograph of immunohistochemical staining for CD68, which is specific for cells of the macrophage lineage. Foamy macrophages (arrows) and a giant cell (arrowhead) is indicated. (C) Photomicrograph of immunohistochemical staining for CD41, specific for platelets. A small vessel filled with red blood cells and platelets serves as an internal positive control (inset). (D) This photomicrograph demonstrates the anti-PF4 staining the foamy macrophages. Note that the morphology of these cells is identical to those in panels (A -C), with vacuolated cytoplasm that stains for PF4 (arrows). (E) Photomicrograph demonstrating PF4 staining of an early atherosclerotic lesion from a carotid artery obtained at autopsy. The endothelium (arrowheads) and subendothelial macrophages (arrows) of an early lesion stain intensely positive with anti-PF4. Images are 40X (A-D) or 20X (E) original magnification. Abbreviation: pF4, platelet factor 4.

activated platelets platelet Fc ' receptor

HITT antibody

Heparan Sulfate

activated endothelial cell resting endothelial cell activated endothelial cell

FIGURE 9.3 Model of HIT antibody interactions with endothelial cells. (1) HIT antibodies bind to antigen (multimolecular PF4/heparin complexes) localized to platelets. (2) Platelet activation occurs after Fc receptor binding, leading to platelet granule release. (3) Released PF4 binds to platelets and endothelial cell HS displacing AT from endothelial cells. (4) Antigenic complexes on endothelial cells bind HIT antibodies. (5) HIT antibody binding to endothelial cells leads to endothelial cell activation and further platelet activation. Abbreviations: ADP, adenosine diphosphate; AT, antithrombin; HIT, heparin-induced thrombocytopenia; HS, heparan sulfate; PF4, platelet factor 4.

FIGURE 15.2 Model of the interaction between argatroban and thrombin.
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