Semin Thromb Hemost 2013; 39(03): 291-305
DOI: 10.1055/s-0033-1334466
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Genetic Loci Associated with Platelet Traits and Platelet Disorders

Natalia Bunimov
1   Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
,
Nola Fuller
1   Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
,
Catherine P. M. Hayward
1   Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
2   Department of Medicine, McMaster University, Hamilton, Ontario, Canada
3   Hamilton Regional Laboratory Medicine Program, Hamilton, Ontario, Canada
› Author Affiliations
Further Information

Publication History

Publication Date:
06 March 2013 (online)

Abstract

Genetic investigations have led to important advances in our knowledge of genes, proteins, and microRNA that influence circulating platelet counts, platelet size, and function. The application of genome-wide association studies (GWAS) to platelet traits has identified multiple loci with a significant association to platelet number, size, and function in aggregation and granule secretion assays. Moreover, the genes altered by disease-causing mutations have now been identified for several platelet disorders, including X-linked recessive, autosomal dominant, and autosomal recessive platelet disorders. Some mutations that cause inherited platelet disorders involve genes that GWAS have associated to platelet traits. Although disease-causing mutations in many rare and syndromic causes of platelet disorders have now been characterized, the genetic mutations that cause common inherited platelet disorders, and impair platelet aggregation and granule secretion, are largely unknown. This review summarizes current knowledge on the genetic loci that influence platelet traits, including the genes with well-characterized mutations in certain inherited platelet disorders.

 
  • References

  • 1 Gresele P, Page CP, Fuster V, Vermylen J. Platelets in Thrombotic and Non-thrombotic Disorders. Cambridge, UK: Cambridge University Press; 2002: 1-1124
  • 2 Michelson AD. Platelets. 3rd ed. Philadelphia, PA: Elsevier/Academic Press; 2013. (in press)
  • 3 Marder VJ, Aird WC, Bennett JS, Schulman S, White II GC. Hemostasis and Thrombosis: Basic Principles and Clinical Practice. 6th ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2012: 1-1592
  • 4 Rowley JW, Oler AJ, Tolley ND , et al. Genome-wide RNA-seq analysis of human and mouse platelet transcriptomes. Blood 2011; 118 (14) e101-e111
  • 5 Gnatenko DV, Dunn JJ, Schwedes J, Bahou WF. Transcript profiling of human platelets using microarray and serial analysis of gene expression (SAGE). Methods Mol Biol 2009; 496: 245-272
  • 6 Senzel L, Gnatenko DV, Bahou WF. The platelet proteome. Curr Opin Hematol 2009; 16 (5) 329-333
  • 7 Bahou WF. Platelet systems biology using integrated genetic and proteomic platforms. Thromb Res 2012; 129 (Suppl. 01) S38-S45
  • 8 García A, Prabhakar S, Brock CJ , et al. Extensive analysis of the human platelet proteome by two-dimensional gel electrophoresis and mass spectrometry. Proteomics 2004; 4 (3) 656-668
  • 9 García A, Prabhakar S, Hughan S , et al. Differential proteome analysis of TRAP-activated platelets: involvement of DOK-2 and phosphorylation of RGS proteins. Blood 2004; 103 (6) 2088-2095
  • 10 García A, Zitzmann N, Watson SP. Analyzing the platelet proteome. Semin Thromb Hemost 2004; 30 (4) 485-489
  • 11 Watson SP, Bahou WF, Fitzgerald D, Ouwehand W, Rao AK, Leavitt AD. ISTH Platelet Physiology Subcommittee. Mapping the platelet proteome: a report of the ISTH Platelet Physiology Subcommittee. J Thromb Haemost 2005; 3 (9) 2098-2101
  • 12 Gaxiola B, Friedl W, Propping P. Epinephrine-induced platelet aggregation. A twin study. Clin Genet 1984; 26 (6) 543-548
  • 13 Kunicki TJ, Williams SA, Nugent DJ. Genetic variants that affect platelet function. Curr Opin Hematol 2012; 19 (5) 371-379
  • 14 Ferreira MA, Hottenga JJ, Warrington NM , et al. Sequence variants in three loci influence monocyte counts and erythrocyte volume. Am J Hum Genet 2009; 85 (5) 745-749
  • 15 Meisinger C, Prokisch H, Gieger C , et al. A genome-wide association study identifies three loci associated with mean platelet volume. Am J Hum Genet 2009; 84 (1) 66-71
  • 16 Guerrero JA, Rivera J, Quiroga T , et al. Novel loci involved in platelet function and platelet count identified by a genome-wide study performed in children. Haematologica 2011; 96 (9) 1335-1343
  • 17 Mathias RA, Kim Y, Sung H , et al. A combined genome-wide linkage and association approach to find susceptibility loci for platelet function phenotypes in European American and African American families with coronary artery disease. BMC Med Genomics 2010; 3: 22
  • 18 Kamatani Y, Matsuda K, Okada Y , et al. Genome-wide association study of hematological and biochemical traits in a Japanese population. Nat Genet 2010; 42 (3) 210-215
  • 19 Soranzo N, Rendon A, Gieger C , et al. A novel variant on chromosome 7q22.3 associated with mean platelet volume, counts, and function. Blood 2009; 113 (16) 3831-3837
  • 20 Yang Q, Kathiresan S, Lin JP, Tofler GH, O'Donnell CJ. Genome-wide association and linkage analyses of hemostatic factors and hematological phenotypes in the Framingham Heart Study. BMC Med Genet 2007; 8 (Suppl. 01) S12
  • 21 Lo KS, Wilson JG, Lange LA , et al. Genetic association analysis highlights new loci that modulate hematological trait variation in Caucasians and African Americans. Hum Genet 2011; 129 (3) 307-317
  • 22 Gieger C, Radhakrishnan A, Cvejic A , et al. New gene functions in megakaryopoiesis and platelet formation. Nature 2011; 480 (7376) 201-208
  • 23 Soranzo N, Spector TD, Mangino M , et al. A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium. Nat Genet 2009; 41 (11) 1182-1190
  • 24 Qayyum R, Snively BM, Ziv E , et al. A meta-analysis and genome-wide association study of platelet count and mean platelet volume in African Americans. PLoS Genet 2012; 8 (3) e1002491
  • 25 Johnson AD, Yanek LR, Chen MH , et al. Genome-wide meta-analyses identifies seven loci associated with platelet aggregation in response to agonists. Nat Genet 2010; 42 (7) 608-613
  • 26 Goodall AH, Burns P, Salles I , et al; Bloodomics Consortium. Transcription profiling in human platelets reveals LRRFIP1 as a novel protein regulating platelet function. Blood 2010; 116 (22) 4646-4656
  • 27 Snoep JD, Gaussem P, Eikenboom JC , et al. The minor allele of GP6 T13254C is associated with decreased platelet activation and a reduced risk of recurrent cardiovascular events and mortality: results from the SMILE-Platelets project. J Thromb Haemost 2010; 8 (11) 2377-2384
  • 28 Edelstein LC, Luna EJ, Gibson IB , et al. Human genome-wide association and mouse knockout approaches identify platelet supervillin as an inhibitor of thrombus formation under shear stress. Circulation 2012; 125 (22) 2762-2771
  • 29 Nagalla S, Shaw C, Kong X , et al. Platelet microRNA-mRNA coexpression profiles correlate with platelet reactivity. Blood 2011; 117 (19) 5189-5197
  • 30 Bray PF, Mathias RA, Faraday N , et al. Heritability of platelet function in families with premature coronary artery disease. J Thromb Haemost 2007; 5 (8) 1617-1623
  • 31 Herrera-Galeano JE, Becker DM, Wilson AF , et al. A novel variant in the platelet endothelial aggregation receptor-1 gene is associated with increased platelet aggregability. Arterioscler Thromb Vasc Biol 2008; 28 (8) 1484-1490
  • 32 Faraday N, Yanek LR, Yang XP , et al. Identification of a specific intronic PEAR1 gene variant associated with greater platelet aggregability and protein expression. Blood 2011; 118 (12) 3367-3375
  • 33 Hayward CP, Pai M, Liu Y , et al. Diagnostic utility of light transmission platelet aggregometry: results from a prospective study of individuals referred for bleeding disorder assessments. J Thromb Haemost 2009; 7 (4) 676-684
  • 34 Pai M, Wang G, Moffat KA , et al. Diagnostic usefulness of a lumi-aggregometer adenosine triphosphate release assay for the assessment of platelet function disorders. Am J Clin Pathol 2011; 136 (3) 350-358
  • 35 Lo KA, Bauchmann MK, Baumann AP , et al. Genome-wide profiling of H3K56 acetylation and transcription factor binding sites in human adipocytes. PLoS ONE 2011; 6 (6) e19778
  • 36 Kunicki TJ, Nugent DJ. The genetics of normal platelet reactivity. Blood 2010; 116 (15) 2627-2634
  • 37 Ballmaier M, Germeshausen M. Congenital amegakaryocytic thrombocytopenia: clinical presentation, diagnosis, and treatment. Semin Thromb Hemost 2011; 37 (6) 673-681
  • 38 Hirsch E, Bosco O, Tropel P , et al. Resistance to thromboembolism in PI3Kgamma-deficient mice. FASEB J 2001; 15 (11) 2019-2021
  • 39 Pozgajová M, Sachs UJ, Hein L, Nieswandt B. Reduced thrombus stability in mice lacking the alpha2A-adrenergic receptor. Blood 2006; 108 (2) 510-514
  • 40 Kauskot A, Di Michele M, Loyen S, Freson K, Verhamme P, Hoylaerts MF. A novel mechanism of sustained platelet αIIbβ3 activation via PEAR1. Blood 2012; 119 (17) 4056-4065
  • 41 Wang W, Gilligan DM, Sun S, Wu X, Reems JA. Distinct functional effects for dynamin 3 during megakaryocytopoiesis. Stem Cells Dev 2011; 20 (12) 2139-2151
  • 42 Jedlitschky G, Cattaneo M, Lubenow LE , et al. Role of MRP4 (ABCC4) in platelet adenine nucleotide-storage: evidence from patients with delta-storage pool deficiencies. Am J Pathol 2010; 176 (3) 1097-1103
  • 43 Côté GP. Structural and functional properties of the non-muscle tropomyosins. Mol Cell Biochem 1983; 57 (2) 127-146
  • 44 Lang NN, Guðmundsdóttir IJ, Newby DE. Vascular PAR-1: activity and antagonism. Cardiovasc Ther 2011; 29 (6) 349-361
  • 45 García P, Berlanga O, Vegiopoulos A, Vyas P, Frampton J. c-Myb and GATA-1 alternate dominant roles during megakaryocyte differentiation. J Thromb Haemost 2011; 9 (8) 1572-1581
  • 46 Schmitz G, Schambeck CM. Molecular defects in the ABCA1 pathway affect platelet function. Pathophysiol Haemost Thromb 2006; 35 (1–2) 166-174
  • 47 Fock EL, Yan F, Pan S, Chong BH. NF-E2-mediated enhancement of megakaryocytic differentiation and platelet production in vitro and in vivo. Exp Hematol 2008; 36 (1) 78-92
  • 48 Castermans D, Volders K, Crepel A , et al. SCAMP5, NBEA and AMISYN: three candidate genes for autism involved in secretion of large dense-core vesicles. Hum Mol Genet 2010; 19 (7) 1368-1378
  • 49 Israels SJ, McMillan-Ward EM. Platelet tetraspanin complexes and their association with lipid rafts. Thromb Haemost 2007; 98 (5) 1081-1087
  • 50 Mangin PH, Kleitz L, Boucheix C, Gachet C, Lanza F. CD9 negatively regulates integrin alphaIIbbeta3 activation and could thus prevent excessive platelet recruitment at sites of vascular injury. J Thromb Haemost 2009; 7 (5) 900-902
  • 51 Kojima H, Kanada H, Shimizu S , et al. CD226 mediates platelet and megakaryocytic cell adhesion to vascular endothelial cells. J Biol Chem 2003; 278 (38) 36748-36753
  • 52 Gekas C, Rhodes KE, Gereige LM , et al. Mef2C is a lineage-restricted target of Scl/Tal1 and regulates megakaryopoiesis and B-cell homeostasis. Blood 2009; 113 (15) 3461-3471
  • 53 Antl M, von Brühl ML, Eiglsperger C , et al. IRAG mediates NO/cGMP-dependent inhibition of platelet aggregation and thrombus formation. Blood 2007; 109 (2) 552-559
  • 54 Buitrago L, Tsygankov A, Sanjay A, Kunapuli SP. Cbl proteins in platelet activation. Platelets 2012; (August) 29
  • 55 Derbent M, Öncel Y, Tokel K , et al. Clinical and hematologic findings in Noonan syndrome patients with PTPN11 gene mutations. Am J Med Genet A 2010; 152A (11) 2768-2774
  • 56 Catani L, Sollazzo D, Ricci F , et al. The CD47 pathway is deregulated in human immune thrombocytopenia. Exp Hematol 2011; 39 (4) 486-494
  • 57 Josefsson EC, James C, Henley KJ , et al. Megakaryocytes possess a functional intrinsic apoptosis pathway that must be restrained to survive and produce platelets. J Exp Med 2011; 208 (10) 2017-2031
  • 58 Hayward CP, Favaloro EJ. Diagnostic evaluation of platelet disorders: the past, the present, and the future. Semin Thromb Hemost 2009; 35 (2) 127-130
  • 59 Nurden A, Nurden P. Advances in our understanding of the molecular basis of disorders of platelet function. J Thromb Haemost 2011; 9 (Suppl. 01) 76-91
  • 60 Nurden AT, Freson K, Seligsohn U. Inherited platelet disorders. Haemophilia 2012; 18 (Suppl. 04) 154-160
  • 61 Dumont B, Lasne D, Rothschild C , et al. Absence of collagen-induced platelet activation caused by compound heterozygous GPVI mutations. Blood 2009; 114 (9) 1900-1903
  • 62 Hermans C, Wittevrongel C, Thys C, Smethurst PA, Van Geet C, Freson K. A compound heterozygous mutation in glycoprotein VI in a patient with a bleeding disorder. J Thromb Haemost 2009; 7 (8) 1356-1363
  • 63 Nurden AT, Pillois X, Fiore M, Heilig R, Nurden P. Glanzmann thrombasthenia-like syndromes associated with Macrothrombocytopenias and mutations in the genes encoding the αIIbβ3 integrin. Semin Thromb Hemost 2011; 37 (6) 698-706
  • 64 Navarro-Núñez L, Teruel R, Antón AI , et al. Rare homozygous status of P43 β1-tubulin polymorphism causes alterations in platelet ultrastructure. Thromb Haemost 2011; 105 (5) 855-863
  • 65 Kunishima S, Kobayashi R, Itoh TJ, Hamaguchi M, Saito H. Mutation of the beta1-tubulin gene associated with congenital macrothrombocytopenia affecting microtubule assembly. Blood 2009; 113 (2) 458-461
  • 66 Hirano K, Kuwasako T, Nakagawa-Toyama Y, Janabi M, Yamashita S, Matsuzawa Y. Pathophysiology of human genetic CD36 deficiency. Trends Cardiovasc Med 2003; 13 (4) 136-141
  • 67 Castilloux JF, Moffat KA, Liu Y, Seecharan J, Pai M, Hayward CP. A prospective cohort study of light transmission platelet aggregometry for bleeding disorders: is testing native platelet-rich plasma non-inferior to testing platelet count adjusted samples?. Thromb Haemost 2011; 106 (4) 675-682
  • 68 Hayward CP, Moffat KA, Castilloux JF , et al. Simultaneous measurement of adenosine triphosphate release and aggregation potentiates human platelet aggregation responses for some subjects, including persons with Quebec platelet disorder. Thromb Haemost 2012; 107 (4) 726-734
  • 69 Gnatenko DV, Perrotta PL, Bahou WF. Proteomic approaches to dissect platelet function: Half the story. Blood 2006; 108 (13) 3983-3991
  • 70 Gnatenko DV, Zhu W, Bahou WF. Multiplexed genetic profiling of human blood platelets using fluorescent microspheres. Thromb Haemost 2008; 100 (5) 929-936
  • 71 O'Neill EE, Brock CJ, von Kriegsheim AF , et al. Towards complete analysis of the platelet proteome. Proteomics 2002; 2 (3) 288-305
  • 72 Perrotta PL, Bahou WF. Proteomics in platelet science. Curr Hematol Rep 2004; 3 (6) 462-469
  • 73 Maynard DM, Heijnen HF, Horne MK, White JG, Gahl WA. Proteomic analysis of platelet alpha-granules using mass spectrometry. J Thromb Haemost 2007; 5 (9) 1945-1955
  • 74 Parguiña AF, Rosa I, García A. Proteomics applied to the study of platelet-related diseases: aiding the discovery of novel platelet biomarkers and drug targets. J Proteomics 2012; 76 (Spec No) 275-286
  • 75 Balduini CL, Pecci A, Norris P. Diagnosis and management of inherited thrombocytopenias. Semin Thromb Hemost 2013; ; doi:http://dx.doi.org/ 10.1055/s-0032-1333540
  • 76 Hayward CP, Bunimov N. Thrombocytopenic platelet disorders. Semin Thromb Hemost 2011; 37 (6) 617-620
  • 77 Althaus K, Greinacher A. MYH9-related platelet disorders. Semin Thromb Hemost 2009; 35 (2) 189-203
  • 78 Balduini CL, Pecci A, Savoia A. Recent advances in the understanding and management of MYH9-related inherited thrombocytopenias. Br J Haematol 2011; 154 (2) 161-174
  • 79 Nurden AT, Fiore M, Nurden P, Pillois X. Glanzmann thrombasthenia: a review of ITGA2B and ITGB3 defects with emphasis on variants, phenotypic variability, and mouse models. Blood 2011; 118 (23) 5996-6005
  • 80 Noris P, Guidetti GF, Conti V , et al. Autosomal dominant thrombocytopenias with reduced expression of glycoprotein Ia. Thromb Haemost 2006; 95 (3) 483-489
  • 81 Cattaneo M. The platelet P2Y12 receptor for adenosine diphosphate: congenital and drug-induced defects. Blood 2011; 117 (7) 2102-2112
  • 82 Oury C, Toth-Zsamboki E, Van Geet C , et al. A natural dominant negative P2X1 receptor due to deletion of a single amino acid residue. J Biol Chem 2000; 275 (30) 22611-22614
  • 83 Kamae T, Kiyomizu K, Nakazawa T , et al. Bleeding tendency and impaired platelet function in a patient carrying a heterozygous mutation in the thromboxane A2 receptor. J Thromb Haemost 2011; 9 (5) 1040-1048
  • 84 Mumford AD, Dawood BB, Daly ME , et al. A novel thromboxane A2 receptor D304N variant that abrogates ligand binding in a patient with a bleeding diathesis. Blood 2010; 115 (2) 363-369
  • 85 Fuse I, Higuchi W, Aizawa Y. Pathogenesis of a bleeding disorder characterized by platelet unresponsiveness to thromboxane A2. Semin Thromb Hemost 2000; 26 (1) 43-45
  • 86 Higuchi W, Fuse I, Hattori A, Aizawa Y. Mutations of the platelet thromboxane A2 (TXA2) receptor in patients characterized by the absence of TXA2-induced platelet aggregation despite normal TXA2 binding activity. Thromb Haemost 1999; 82 (5) 1528-1531
  • 87 Hirata T, Kakizuka A, Ushikubi F, Fuse I, Okuma M, Narumiya S. Arg60 to Leu mutation of the human thromboxane A2 receptor in a dominantly inherited bleeding disorder. J Clin Invest 1994; 94 (4) 1662-1667
  • 88 Nurden P, Debili N, Coupry I , et al. Thrombocytopenia resulting from mutations in filamin A can be expressed as an isolated syndrome. Blood 2011; 118 (22) 5928-5937
  • 89 Cramer Bordé E, Ouzegdouh Y, Ledgerwood EC, Morison IM. Congenital thrombocytopenia and cytochrome C mutation: a matter of birth and death. Semin Thromb Hemost 2011; 37 (6) 664-672
  • 90 Geneviève D, Proulle V, Isidor B , et al. Thromboxane synthase mutations in an increased bone density disorder (Ghosal syndrome). Nat Genet 2008; 40 (3) 284-286
  • 91 Michaud J, Wu F, Osato M , et al. In vitro analyses of known and novel RUNX1/AML1 mutations in dominant familial platelet disorder with predisposition to acute myelogenous leukemia: implications for mechanisms of pathogenesis. Blood 2002; 99 (4) 1364-1372
  • 92 Millikan PD, Balamohan SM, Raskind WH, Kacena MA. Inherited thrombocytopenia due to GATA-1 mutations. Semin Thromb Hemost 2011; 37 (6) 682-689
  • 93 Thompson AA, Nguyen LT. Amegakaryocytic thrombocytopenia and radio-ulnar synostosis are associated with HOXA11 mutation. Nat Genet 2000; 26 (4) 397-398
  • 94 Kahr WH, Hinckley J, Li L , et al. Mutations in NBEAL2, encoding a BEACH protein, cause gray platelet syndrome. Nat Genet 2011; 43 (8) 738-740
  • 95 Gunay-Aygun M, Falik-Zaccai TC, Vilboux T , et al. NBEAL2 is mutated in gray platelet syndrome and is required for biogenesis of platelet α-granules. Nat Genet 2011; 43 (8) 732-734
  • 96 Albers CA, Cvejic A, Favier R , et al. Exome sequencing identifies NBEAL2 as the causative gene for gray platelet syndrome. Nat Genet 2011; 43 (8) 735-737
  • 97 Abu-Sa'da O, Barbar M, Al-Harbi N, Taha D. Arthrogryposis, renal tubular acidosis and cholestasis (ARC) syndrome: two new cases and review. Clin Dysmorphol 2005; 14 (4) 191-196
  • 98 Meng R, Wang Y, Yao Y , et al. SLC35D3 delivery from megakaryocyte early endosomes is required for platelet dense granule biogenesis and is differentially defective in Hermansky-Pudlak syndrome models. Blood 2012; 120 (2) 404-414
  • 99 Masliah-Planchon J, Darnige L, Bellucci S. Molecular determinants of platelet delta storage pool deficiencies: an update. Br J Haematol 2013; 160 (1) 5-11
  • 100 Wei ML. Hermansky-Pudlak syndrome: a disease of protein trafficking and organelle function. Pigment Cell Res 2006; 19 (1) 19-42
  • 101 Badolato R, Prandini A, Caracciolo S , et al. Exome sequencing reveals a pallidin mutation in a Hermansky-Pudlak-like primary immunodeficiency syndrome. Blood 2012; 119 (13) 3185-3187
  • 102 Blavignac J, Bunimov N, Rivard GE, Hayward CP. Quebec platelet disorder: update on pathogenesis, diagnosis, and treatment. Semin Thromb Hemost 2011; 37 (6) 713-720
  • 103 Hayward CP, Rivard GE. Quebec platelet disorder. Expert Rev Hematol 2011; 4 (2) 137-141
  • 104 Paterson AD, Rommens JM, Bharaj B , et al. Persons with Quebec platelet disorder have a tandem duplication of PLAU, the urokinase plasminogen activator gene. Blood 2010; 115 (6) 1264-1266
  • 105 Van Geet C, Izzi B, Labarque V, Freson K. Human platelet pathology related to defects in the G-protein signaling cascade. J Thromb Haemost 2009; 7 (Suppl. 01) 282-286
  • 106 Gabbeta J, Vaidyula VR, Dhanasekaran DN, Rao AK. Human platelet Galphaq deficiency is associated with decreased Galphaq gene expression in platelets but not neutrophils. Thromb Haemost 2002; 87 (1) 129-133
  • 107 Freson K, Thys C, Wittevrongel C , et al. Pseudohypoparathyroidism type Ib with disturbed imprinting in the GNAS1 cluster and Gsalpha deficiency in platelets. Hum Mol Genet 2002; 11 (22) 2741-2750
  • 108 Noé L, Di Michele M, Giets E , et al. Platelet Gs hypofunction and abnormal morphology resulting from a heterozygous RGS2 mutation. J Thromb Haemost 2010; 8 (7) 1594-1603
  • 109 Jurk K, Schulz AS, Kehrel BE , et al. Novel integrin-dependent platelet malfunction in siblings with leukocyte adhesion deficiency-III (LAD-III) caused by a point mutation in FERMT3. Thromb Haemost 2010; 103 (5) 1053-1064
  • 110 Hayward CP. Diagnostic evaluation of platelet function disorders. Blood Rev 2011; 25 (4) 169-173
  • 111 Kuijpers TW, van de Vijver E, Weterman MA , et al. LAD-1/variant syndrome is caused by mutations in FERMT3. Blood 2009; 113 (19) 4740-4746
  • 112 Defreyn G, Machin SJ, Carreras LO, Dauden MV, Chamone DA, Vermylen J. Familial bleeding tendency with partial platelet thromboxane synthetase deficiency: reorientation of cyclic endoperoxide metabolism. Br J Haematol 1981; 49 (1) 29-41
  • 113 Di Paola J, Johnson J. Thrombocytopenias due to gray platelet syndrome or THC2 mutations. Semin Thromb Hemost 2011; 37 (6) 690-697
  • 114 Lhermusier T, Chap H, Payrastre B. Platelet membrane phospholipid asymmetry: from the characterization of a scramblase activity to the identification of an essential protein mutated in Scott syndrome. J Thromb Haemost 2011; 9 (10) 1883-1891
  • 115 Weiss HJ. Impaired platelet procoagulant mechanisms in patients with bleeding disorders. Semin Thromb Hemost 2009; 35 (2) 233-241
  • 116 Albers CA, Paul DS, Schulze H , et al. Compound inheritance of a low-frequency regulatory SNP and a rare null mutation in exon-junction complex subunit RBM8A causes TAR syndrome. Nat Genet 2012; 44 (4) 435-439 , S1–S2
  • 117 Huizing M, Parkes JM, Helip-Wooley A, White JG, Gahl WA. Platelet alpha granules in BLOC-2 and BLOC-3 subtypes of Hermansky-Pudlak syndrome. Platelets 2007; 18 (2) 150-157
  • 118 Thrasher AJ. New insights into the biology of Wiskott-Aldrich syndrome (WAS). Hematology (Am Soc Hematol Educ Program) 2009; 1: 132-138
  • 119 Othman M. Platelet-type Von Willebrand disease: three decades in the life of a rare bleeding disorder. Blood Rev 2011; 25 (4) 147-153
  • 120 Owen C. Insights into familial platelet disorder with propensity to myeloid malignancy (FPD/AML). Leuk Res 2010; 34 (2) 141-142
  • 121 Raslova H, Komura E, Le Couédic JP , et al. FLI1 monoallelic expression combined with its hemizygous loss underlies Paris-Trousseau/Jacobsen thrombopenia. J Clin Invest 2004; 114 (1) 77-84
  • 122 Favier R, Jondeau K, Boutard P , et al. Paris-Trousseau syndrome : clinical, hematological, molecular data of ten new cases. Thromb Haemost 2003; 90 (5) 893-897
  • 123 Noris P, Perrotta S, Seri M , et al. Mutations in ANKRD26 are responsible for a frequent form of inherited thrombocytopenia: analysis of 78 patients from 21 families. Blood 2011; 117 (24) 6673-6680
  • 124 Mezzano D, Quiroga T, Pereira J. The level of laboratory testing required for diagnosis or exclusion of a platelet function disorder using platelet aggregation and secretion assays. Semin Thromb Hemost 2009; 35 (2) 242-254
  • 125 Quiroga T, Goycoolea M, Matus V , et al. Diagnosis of mild platelet function disorders. Reliability and usefulness of light transmission platelet aggregation and serotonin secretion assays. Br J Haematol 2009; 147 (5) 729-736
  • 126 Hayward CP, Moffat KA, Liu Y. Laboratory investigations for bleeding disorders. Semin Thromb Hemost 2012; 38 (7) 742-752
  • 127 Gunay-Aygun M, Huizing M, Gahl WA. Molecular defects that affect platelet dense granules. Semin Thromb Hemost 2004; 30 (5) 537-547
  • 128 Sandrock K, Zieger B. Current Strategies in Diagnosis of Inherited Storage Pool Defects. Transfus Med Hemother 2010; 37 (5) 248-258
  • 129 Corral J, González-Conejero R, Pujol-Moix N, Domenech P, Vicente V. Mutation analysis of HPS1, the gene mutated in Hermansky-Pudlak syndrome, in patients with isolated platelet dense-granule deficiency. Haematologica 2004; 89 (3) 325-329
  • 130 Cattaneo M, Lecchi A, Lombardi R, Gachet C, Zighetti ML. Platelets from a patient heterozygous for the defect of P2CYC receptors for ADP have a secretion defect despite normal thromboxane A2 production and normal granule stores: further evidence that some cases of platelet 'primary secretion defect' are heterozygous for a defect of P2CYC receptors. Arterioscler Thromb Vasc Biol 2000; 20 (11) E101-E106
  • 131 Jagadeeswaran P. Zebrafish: a tool to study hemostasis and thrombosis. Curr Opin Hematol 2005; 12 (2) 149-152
  • 132 Dubé JN, Drouin J, Aminian M, Plant MH, Laneuville O. Characterization of a partial prostaglandin endoperoxide H synthase-1 deficiency in a patient with a bleeding disorder. Br J Haematol 2001; 113 (4) 878-885
  • 133 Isidor B, Dagoneau N, Huber C , et al. A gene responsible for Ghosal hemato-diaphyseal dysplasia maps to chromosome 7q33-34. Hum Genet 2007; 121 (2) 269-273
  • 134 Pham A, Wang J. Bernard-Soulier syndrome: an inherited platelet disorder. Arch Pathol Lab Med 2007; 131 (12) 1834-1836
  • 135 Toriello HV. Thrombocytopenia-absent radius syndrome. Semin Thromb Hemost 2011; 37 (6) 707-712
  • 136 Huizing M, Helip-Wooley A, Westbroek W, Gunay-Aygun M, Gahl WA. Disorders of lysosome-related organelle biogenesis: clinical and molecular genetics. Annu Rev Genomics Hum Genet 2008; 9: 359-386