Page 2121 - Hematology_ Basic Principles and Practice ( PDFDrive )

1884 Part XII Hemostasis and Thrombosis

ACTN1- and FLNA-Related Thrombocytopenias Bryckaert M, Rosa JP, Denis CV, et al: Of von Willebrand factor and platelets.
These result from mutations in the genes that encode α-actinin or Cell Mol Life Sci 72(2):307–326, 2015.
filamin A, both functioning as cross-linking proteins in the actin- Franco AT, Corken A, Ware J: Platelets at the interface of thrombosis, inflam-
based cytoskeleton. Filamin A is also critical in binding the cytoplas- mation, and cancer. Blood 126(5):582–588, 2015.
mic tail of GPIbα to the filamentous actin network. Monoallelic Freson K, Wijgaerts A, van Geet C: Update on the causes of platelet dis-
mutations in either gene result in abnormalities of proplatelet forma- orders and functional consequences. Int J Lab Hematol 36(3):313–325,
tion and variable degrees of macrothrombocytopenia. 86 2014.
Harrison P, Lordkipanidze M: Testing platelet function. Hematol Oncol Clin
Wiskott-Aldrich Syndrome and X-linked North Am 27(3):411–441, 2013.
Thrombocytopenia Harrison P, Mackie I, Mumford A, et al: Guidelines for the laboratory
Wiskott-Aldrich syndrome (WAS) and X-linked thrombocytopenia investigation of heritable disorders of platelet function. Br J Haematol
(XLT) are caused by mutations in the WAS gene. Mutations that 155(1):30–44, 2011.
result in nonexpression of WASp cause WAS that manifests as severe Heemskerk JW, Mattheij NJ, Cosemans JM: Platelet-based coagulation: dif-
immune dysregulation, in addition to thrombocytopenia. XLT is ferent populations, different functions. J Thromb Haemost 11(1):2–16,
caused by mutations that decrease expression of the normal protein. 2013.
These syndromes have the unique characteristic of microthrombocy- Huizing M, Helip-Wooley A, Westbroek W, et al: Disorders of lysosome-
topenia. WASp is involved in regulation of actin polymerization; the related organelle biogenesis: clinical and molecular genetics. Annu Rev
defect in platelet production may be the result of ectopic platelet Genomics Hum Genet 9:359–386, 2008.
shedding by megakaryocytes. 85,93 Italiano JE, Jr, Richardson JL, Patel-Hett S, et al: Angiogenesis is regulated
by a novel mechanism: pro- and antiangiogenic proteins are organized
Bernard-Soulier Syndrome into separate platelet alpha granules and differentially released. Blood
In addition to the functional adhesive defect (described in the section 111(3):1227–1233, 2008.
on Abnormalities of Platelet Adhesion), patients have thrombocyto- Kunishima S, Saito H: Advances in the understanding of MYH9 disorders.
penia and giant platelets. Abnormalities in proplatelet formation Curr Opin Hematol 17(5):405–410, 2010.
resemble those seen in mutations of cytoskeletal proteins, suggesting Li R, Emsley J: The organizing principle of the platelet glycoprotein Ib-IX-V
that the anchoring of the actin filament network by GPIbα to the complex. J Thromb Haemost 11(4):605–614, 2013.
plasma membrane is a required part of this process, disrupted by McFadyen JD, Kaplan ZS: Platelets are not just for clots. Transfus Med Rev
deficiency of the GPIb–IX–V transmembrane protein complex. 15,86 29(2):110–119, 2015.
Most heterozygotes do not have macrothrombocytopenia, but there Nieuwland R, van der Pol E, Gardiner C, et al: Platelet-derived microparticles.
are exceptions where specific mutations (e.g., p.A156V, the Bolzano In Michelson AD, editor: Platelets, ed 3, San Diego, 2013, Academic
mutation) or monoallelic BSS (e.g., Velo-Cardio-Facial syndrome) Press, pp 453–467.
cause mild macrothrombocytopenia. Notarangelo LD, Ochs HD: Wiskott-Aldrich Syndrome: a model for defec-
tive actin reorganization, cell trafficking and synapse formation. Curr
ITGA2B/ITGB3-Related Thrombocytopenias Opin Immunol 15(5):585–591, 2003.
These are rare macrothrombocytopenias with functional defects Nurden AT, Nurden P: Congenital platelet disorders and understanding of
associated with specific monoallelic mutations in ITGA2B or ITGB3 platelet function. Br J Haematol 165(2):165–178, 2014.
that are distinct from the mutations that cause GT, described previ- Nurden AT, Nurden P: Inherited disorders of platelet function: selected
ously. These mutations result in constitutive activation of αIIbβ3 and updates. J Thromb Haemost 13(Suppl 1):S2–S9, 2015.
downstream effectors, defects in actin-myosin reorganization, and Nurden AT, Pillois X, Fiore M, et al: Glanzmann thrombasthenia-like
abnormalities of proplatelet formation. 94 syndromes associated with Macrothrombocytopenias and mutations in
the genes encoding the alphaIIbbeta3 integrin. Semin Thromb Hemost
TUBB1-Related Thrombocytopenia 37(6):698–706, 2011.
This is caused by mutations in the gene for β1-tubulin and is associ- Pecci A, Balduini CL: Lessons in platelet production from inherited throm-
ated with platelets that are spherical rather than discoid, the result of bocytopenias. Br J Haematol 165(2):179–192, 2014.
95
abnormalities of the microtubule coil (see also Chapter 124). Ruggeri ZM: Platelet adhesion under flow. Microcirculation 16(1):58–83,
2009.
PRKACG-Related Macrothrombocytopenia Senis YA, Mazharian A, Mori J: Src family kinases: at the forefront of platelet
This is the result of a germ-line mutation in the gene encoding the activation. Blood 124(13):2013–2024, 2014.
γ-catalytic subunit of the cAMP-dependent protein kinase (PK), Seward SL, Jr, Gahl WA: Hermansky-Pudlak syndrome: health care through-
PKA. There is a defect in proplatelet formation and a low level of out life. Pediatrics 132(1):153–160, 2013.
filamin A in megakaryocytes. 96 Tijssen MR, Ghevaert C: Transcription factors in late megakaryopoiesis and
related platelet disorders. J Thromb Haemost 11(4):593–604, 2013.
Varga-Szabo D, Braun A, Nieswandt B: STIM and Orai in platelet function.
SUGGESTED READINGS Cell Calcium 50(3):270–278, 2011.
Versteeg HH, Heemskerk JW, Levi M, et al: New fundamentals in hemosta-
Bertozzi CC, Schmaier AA, Mericko P, et al: Platelets regulate lymphatic sis. Physiol Rev 93(1):327–358, 2013.
vascular development through CLEC-2-SLP-76 signaling. Blood Watson SP, Farndale RW, Moroi M, et al: Platelet collagen receptors. In
116(4):661–670, 2010. Marder VJ, Aird WC, Bennett JS, et al, editors: Hemostasis and thrombosis.
Blair P, Flaumenhaft R: Platelet alpha-granules: basic biology and clinical Basic principles and clinical practice, ed 6, Philadelphia, 2013, Lippincott
correlates. Blood Rev 23(4):177–189, 2009. Williams & Wilkins, pp 420–430.
Bledzka K, Smyth SS, Plow EF: Integrin alphaIIbbeta3: from discovery to Wei AH, Schoenwaelder SM, Andrews RK, et al: New insights into the
efficacious therapeutic target. Circ Res 112(8):1189–1200, 2013. haemostatic function of platelets. Br J Haematol 147(4):415–430,
Boilard E, Nigrovic PA, Larabee K, et al: Platelets amplify inflammation 2009.
in arthritis via collagen-dependent microparticle production. Science
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