Page 2118 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 125 Molecular Basis of Platelet Function 1881

GP6
Defective response to collagen
TMEM16F (ANO6)
ITGA2B. ITGB3 CLEC-2 Scott syndrome:
Glanzmann thrombasthenla: CD36 GPVI decreased
thrombin formation
no aggregation with CD9
natural agonists

αIIbβ3
ITGA2 α6β1
SNPs control density
and collagen response
α2β1
α5β1

P2X1 PECAM-1
IX

V Ibβ
P2RY12,TBXA2R, F2RL3 P2Y1, P2Y12
TP, PAR1, PAR4 GPIBA, GPIBB, GP9
Defective response to stimuli: Ibα Bernard-Souller
ADP, TxA 2 , thrombin (PAR4) GPIBA syndrome: lack of adhesion
Platelet-type VWD: to VWF and abnormal
spontaneous binding response to thrombin
A to VWF to GPIbα
α Granules
Gray platelet syndrome (NBEAL2, GFI1B)
ARC syndrome (VPS33B, VIPAS39/VPS16B)
Quebec platelet disorder (PLAU)

CLEC-2 GPVI
Integrin-activating proteins
FERMT3 (kindlin-3) CD36 CD9
RASGRP2 (CalDAG-GEFI)
αIIbβ3
α6β1
Lipid metabolism
PLA2G4A (cPLA )
2
TBXAS1 (TxA synthase)
2
α2β1
α5β1
Stormorken syndrome
York platelet syndrome
STIM1 P2X1 PECAM-1
2+
(Ca regulation) IX
Signaling pathways
G proteins (GNASXL)
V Ibβ Protein kinases (PRKACG)
Dense granules P2Y1, P2Y12 Tyrosine kinases
Hermansky-Pudlak syndrome TP, PAR1, PAR4 Ibα
(HPS1, AP3B1/HPS2, HPS3-9) Cytoskeleton
Chediak-Higashi syndrome MYH9-related disease
(LYST) FLNA- filamin A ∗ Mutations or haploinsufficiency of
TUBB1- tubulin β1 transcription factors (e.g. GATA1, FLI1
Wiskott- Aldrich syndrome (WAS) or RUNX1) may have secondary effects
B on protein expression
Fig. 125.6 GENETIC CAUSES OF INHERITED PLATELET DISORDERS. (A) Surface membrane
receptor defects and (B) granule and intracellular protein defects. ARC, Arthrogryposis-renal dysfunction-
2+
cholestasis; cPLA 2 , cytosolic phospholipase A 2 ; CalDAG-GEF, Ca and diacylglycerol-regulated guanine
nucleotide exchange factor; GP, glycoprotein; PAR, protease-activated receptor; PECAM, platelet-endothelial
cell adhesion molecule; SNP, single-nucleotide polymorphism; TxA 2 , thromboxane A 2 ; VWD, von Willebrand
disease; VWF, von Willebrand factor. (Adapted, with permission, from Nurden AT, Nurden P: Inherited disorders of
platelet function. J Thromb Haemost 13(Suppl 1):S2, 2015.)