Advanced search
Publication Cover
Critical Reviews in Clinical Laboratory Sciences Volume 59, 2022 - Issue 6
Submit an article Journal homepage
6,132
Views
1
CrossRef citations to date
0
Altmetric
Invited Reviews

Screening and diagnosis of inherited platelet disorders

Alex Bourguignona Department of Pathology and Molecular Medicine, McMaster University, Hamilton, CanadaORCID Iconhttps://orcid.org/0000-0001-7323-0104View further author information
ORCID Icon,
Subia Tasneema Department of Pathology and Molecular Medicine, McMaster University, Hamilton, CanadaORCID Iconhttps://orcid.org/0000-0002-8859-4119View further author information
ORCID Icon &
Catherine P. Haywarda Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada;b Department of Medicine, McMaster University, Hamilton, CanadaCorrespondence[email protected]
ORCID Iconhttps://orcid.org/0000-0002-2843-0817View further author information
ORCID Icon
Pages 405-444 | Received 08 Dec 2021, Accepted 01 Mar 2022, Published online: 28 Mar 2022

References

  • Megy K, Downes K, Simeoni I, et al. Curated disease-causing genes for bleeding, thrombotic, and platelet disorders: communication from the SSC of the ISTH. J Thromb Haemost. 2019;17(8):1253–1260.
  • Downes K, Megy K, Duarte D, et al. Diagnostic high-throughput sequencing of 2396 patients with bleeding, thrombotic, and platelet disorders. Blood. 2019;134(23):2082–2091.
  • Romasko EJ, Devkota B, Biswas S, et al. Utility and limitations of exome sequencing in the molecular diagnosis of pediatric inherited platelet disorders. Am J Hematol. 2018;93(1):8–16.
  • Bastida JM, Lozano ML, Benito R, et al. Introducing high-throughput sequencing into mainstream genetic diagnosis practice in inherited platelet disorders. Haematologica. 2018;103(1):148–162.
  • Simeoni I, Stephens JC, Hu F, et al. A high-throughput sequencing test for diagnosing inherited bleeding, thrombotic, and platelet disorders. Blood. 2016;127(23):2791–2803.
  • Stritt S, Nurden P, Turro E, et al. A gain-of-function variant in DIAPH1 causes dominant macrothrombocytopenia and hearing loss. Blood. 2016;127(23):2903–2914.
  • Noetzli L, Lo RW, Lee-Sherick AB, et al. Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia. Nat Genet. 2015;47(5):535–538.
  • Hayward CPM, Moffat KA, Raby A, et al. Development of North American consensus guidelines for medical laboratories that perform and interpret platelet function testing using light transmission aggregometry. Am J Clin Pathol. 2010;134(6):955–963.
  • Gresele P, Subcommittee on Platelet Physiology of the International Society on Thrombosis and Hemostasis. Diagnosis of inherited platelet function disorders: guidance from the SSC of the ISTH. J Thromb Haemost. 2015;13(2):314–322.
  • Harrison P, Mackie I, Mumford A, et al. Guidelines for the laboratory investigation of heritable disorders of platelet function. Br J Haematol. 2011;155(1):30–44.
  • Cattaneo M, Cerletti C, Harrison P, et al. Recommendations for the standardization of light transmission aggregometry: a consensus of the working party from the platelet physiology subcommittee of SSC/ISTH. J Thromb Haemost. 2013;11(6):1183–1189.
  • Hayward CPM, Moffat KA, Plumhoff E, et al. External quality assessment of platelet disorder investigations: results of international surveys on diagnostic tests for dense granule deficiency and platelet aggregometry interpretation. Semin Thromb Hemost. 2012;38(6):622–631.
  • Lentaigne C, Freson K, Laffan MA, et al. Inherited platelet disorders: toward DNA-based diagnosis. Blood. 2016;127(23):2814–2823.
  • Rust S, Rosier M, Funke H, et al. Tangier disease is caused by mutations in the gene encoding ATP-binding cassette transporter 1. Nat Genet. 1999;22(4):352–355.
  • Bastida JM, Benito R, Janusz K, et al. Two novel variants of the ABCG5 gene cause xanthelasmas and macrothrombocytopenia: a brief review of hematologic abnormalities of sitosterolemia. J Thromb Haemost. 2017;15(9):1859–1866.
  • Wang Z, Cao L, Su Y, et al. Specific macrothrombocytopenia/hemolytic anemia associated with sitosterolemia. Am J Hematol. 2014;89(3):320–324.
  • Latham SL, Ehmke N, Reinke PYA, et al. Variants in exons 5 and 6 of ACTB cause syndromic thrombocytopenia. Nat Commun. 2018;9(1):4250.
  • Kunishima S, Okuno Y, Yoshida K, et al. ACTN1 mutations cause congenital macrothrombocytopenia. Am J Hum Genet. 2013;92(3):431–438.
  • Bottega R, Marconi C, Faleschini M, et al. ACTN1-related thrombocytopenia: identification of novel families for phenotypic characterization. Blood. 2015;125(5):869–872.
  • 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.
  • Pippucci T, Savoia A, Perrotta S, et al. Mutations in the 5′ UTR of ANKRD26, the ankirin repeat domain 26 gene, cause an autosomal-dominant form of inherited thrombocytopenia, THC2. Am J Hum Genet. 2011;88(1):115–120.
  • Kahr WHA, Pluthero FG, Elkadri A, et al. Loss of the Arp2/3 complex component ARPC1B causes platelet abnormalities and predisposes to inflammatory disease. Nat Commun. 2017;8:14816.
  • Takenouchi T, Kosaki R, Niizuma T, et al. Macrothrombocytopenia and developmental delay with a de novo CDC42 mutation: yet another locus for thrombocytopenia and developmental delay. Am J Med Genet. 2015;167(11):2822–2825.
  • Morison IM, Cramer Bordé EM, Cheesman EJ, et al. A mutation of human cytochrome c enhances the intrinsic apoptotic pathway but causes only thrombocytopenia. Nat Genet. 2008;40(4):387–389.
  • Di Paola J, Porter CC. ETV6-related thrombocytopenia and leukemia predisposition. Blood. 2019;134(8):663–667.
  • Stevenson WS, Rabbolini DJ, Beutler L, et al. Paris-Trousseau thrombocytopenia is phenocopied by the autosomal recessive inheritance of a DNA-binding domain mutation in FLI1. Blood. 2015;126(17):2027–2030.
  • 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.
  • Breton-Gorius J, Favier R, Guichard J, et al. A new congenital dysmegakaryopoietic thrombocytopenia (Paris-Trousseau) associated with giant platelet alpha-granules and chromosome 11 deletion at 11q23. Blood. 1995;85(7):1805–1814.
  • 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.
  • Levin C, Koren A, Pretorius E, et al. Deleterious mutation in the FYB gene is associated with congenital autosomal recessive small-platelet thrombocytopenia. J Thromb Haemost. 2015;13(7):1285–1292.
  • Seo A, Gulsuner S, Pierce S, et al. Inherited thrombocytopenia associated with mutation of UDP-galactose-4-epimerase (GALE). Hum Mol Genet. 2019;28(1):133–142.
  • Nichols KE, Crispino JD, Poncz M, et al. Familial dyserythropoietic anaemia and thrombocytopenia due to an inherited mutation in GATA1. Nat Genet. 2000;24(3):266–270.
  • Mehaffey MG, Newton AL, Gandhi MJ, et al. X-linked thrombocytopenia caused by a novel mutation of GATA-1. Blood. 2001;98(9):2681–2688.
  • Monteferrario D, Bolar NA, Marneth AE, et al. A dominant-negative GFI1B mutation in the gray platelet syndrome. N Engl J Med. 2014;370(3):245–253.
  • Izumi R, Niihori T, Suzuki N, et al. GNE myopathy associated with congenital thrombocytopenia: a report of two siblings. Neuromuscul Disord. 2014;24(12):1068–1072.
  • Revel-Vilk S, Shai E, Turro E, et al. GNE variants causing autosomal recessive macrothrombocytopenia without associated muscle wasting. Blood. 2018;132(17):1851–1854.
  • Savoia A, Kunishima S, De Rocco D, et al. Spectrum of the mutations in Bernard-Soulier syndrome. Hum Mutat. 2014;35(9):1033–1045.
  • Othman M. Platelet-type von willebrand disease: a rare, often misdiagnosed and underdiagnosed bleeding disorder. Semin Thromb Hemost. 2011;37(5):464–469.
  • Thompson AA, Nguyen LT. Amegakaryocytic thrombocytopenia and radio-ulnar synostosis are associated with HOXA11 mutation. Nat Genet. 2000;26(4):397–398.
  • Niihori T, Ouchi-Uchiyama M, Sasahara Y, et al. Mutations in MECOM, encoding oncoprotein EVI1, cause radioulnar synostosis with amegakaryocytic thrombocytopenia. Am J Hum Genet. 2015;97(6):848–854.
  • Lentaigne C, Greene D, Sivapalaratnam S, et al. Germline mutations in the transcription factor IKZF5 cause thrombocytopenia. Blood. 2019;134(23):2070–2081.
  • Botero JP, Lee K, Branchford BR, et al. Glanzmann thrombasthenia: genetic basis and clinical correlates. Haematologica. 2020;105(4):888–894.
  • Nurden AT, Pillois X. ITGA2B and ITGB3 gene mutations associated with Glanzmann thrombasthenia. Platelets. 2018;29(1):98–101.
  • Takeichi T, Torrelo A, Lee JYW, et al. Biallelic mutations in KDSR disrupt ceramide synthesis and result in a spectrum of keratinization disorders associated with thrombocytopenia. J Invest Dermatol. 2017;137(11):2344–2353.
  • Boyden LM, Vincent NG, Zhou J, et al. Mutations in KDSR cause recessive progressive symmetric erythrokeratoderma. Am J Hum Genet. 2017;100(6):978–984.
  • Hurtado B, Trakala M, Ximénez-Embún P, et al. Thrombocytopenia-associated mutations in ser/thr kinase MASTL deregulate actin cytoskeletal dynamics in platelets. J Clin Invest. 2018;128(12):5351–5367.
  • Melhem M, Abu-Farha M, Antony D, et al. Novel G6B gene variant causes familial autosomal recessive thrombocytopenia and anemia. Eur J Haematol. 2017;98(3):218–227.
  • Hofmann I, Crispin A, Campagna D, et al. Congenital thrombocytopenia and myelofibrosis due to germline mutations in G6b-B—a megakaryocyte-specific immunoreceptor tyrosine-based inhibitory motif (ITIM) receptor. Blood. 2017;130:1630.
  • Ihara K, Ishii E, Eguchi M, et al. Identification of mutations in the c-mpl gene in congenital amegakaryocytic thrombocytopenia. Proc Natl Acad Sci USA. 1999;96(6):3132–3136.
  • Muraoka K, Ishii E, Tsuji K, et al. Defective response to thrombopoietin and impaired expression of c-mpl mRNA of bone marrow cells in congenital amegakaryocytic thrombocytopenia. Br J Haematol. 1997;96(2):287–292.
  • Seri M, Pecci A, Bari F, et al. MYH9-Related disease: May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are not distinct entities but represent a variable expression of a single illness. Medicine. 2003;82(3):203–215.
  • Bottega R, Pecci A, De Candia E, et al. Correlation between platelet phenotype and NBEAL2 genotype in patients with congenital thrombocytopenia and α-granule deficiency. Haematologica. 2013;98(6):868–874.
  • Nesin V, Wiley G, Kousi M, et al. Activating mutations in STIM1 and ORAI1 cause overlapping syndromes of tubular myopathy and congenital miosis. Proc Natl Acad Sci USA. 2014;111(11):4197–4202.
  • Hayward CPM, Rivard GE. Quebec platelet disorder. Expert Rev Hematol. 2011;4(2):137–141.
  • Manchev VT, Hilpert M, Berrou E, et al. A new form of macrothrombocytopenia induced by a germ-line mutation in the PRKACG gene. Blood. 2014;124(16):2554–2563.
  • Tartaglia M, Mehler EL, Goldberg R, et al. Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome. Nat Genet. 2001;29(4):465–468.
  • Marconi C, Di Buduo CA, LeVine K, et al. Loss-of-function mutations in PTPRJ cause a new form of inherited thrombocytopenia. Blood. 2019;133(12):1346–1357.
  • 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.
  • Heremans J, Garcia-Perez JE, Turro E, et al. Abnormal differentiation of B cells and megakaryocytes in patients with Roifman syndrome. J Allergy Clin Immunol. 2018;142(2):630–646.
  • Song WJ, Sullivan MG, Legare RD, et al. Haploinsufficiency of CBFA2 causes familial thrombocytopenia with propensity to develop acute myelogenous leukaemia. Nat Genet. 1999;23(2):166–175.
  • Kauskot A, Pascreau T, Adam F, et al. A mutation in the gene coding for the sialic acid transporter SLC35A1 is required for platelet life span but not proplatelet formation. Haematologica. 2018;103(12):e613–e617.
  • Fletcher SJ, Johnson B, Lowe GC, et al. SLFN14 mutations underlie thrombocytopenia with excessive bleeding and platelet secretion defects. J Clin Invest. 2015;125(9):3600–3605.
  • Turro E, Greene D, Wijgaerts A, et al. A dominant gain-of-function mutation in universal tyrosine kinase SRC causes thrombocytopenia, myelofibrosis, bleeding, and bone pathologies. Sci Transl Med. 2016;8(328):328ra30.
  • Misceo D, Holmgren A, Louch WE, et al. A dominant STIM1 mutation causes stormorken syndrome. Hum Mutat. 2014;35(5):556–564.
  • Markello T, Chen D, Kwan JY, et al. York platelet syndrome is a CRAC channelopathy due to gain-of-function mutations in STIM1. Mol Genet Metab. 2015;114(3):474–482.
  • Noris P, Marconi C, De Rocco D, et al. A new form of inherited thrombocytopenia due to monoallelic loss of function mutation in the thrombopoietin gene. Br J Haematol. 2018;181(5):698–701.
  • Pleines I, Woods J, Chappaz S, et al. Mutations in tropomyosin 4 underlie a rare form of human macrothrombocytopenia. J Clin Invest. 2017;127(3):814–829.
  • Stritt S, Nurden P, Favier R, et al. Defects in TRPM7 channel function deregulate thrombopoiesis through altered cellular Mg(2+) homeostasis and cytoskeletal architecture. Nat Commun. 2016;7(1):11097.
  • Kunishima S, Kobayashi R, Itoh TJ, et al. Mutation of the beta1-tubulin gene associated with congenital macrothrombocytopenia affecting microtubule assembly. Blood. 2009;113(2):458–461.
  • Jin Y, Mazza C, Christie JR, et al. Mutations of the Wiskott-Aldrich syndrome protein (WASP): hotspots, effect on transcription, and translation and phenotype/genotype correlation. Blood. 2004;104(13):4010–4019.
  • Lanzi G, Moratto D, Vairo D, et al. A novel primary human immunodeficiency due to deficiency in the WASP-interacting protein WIP. J Exp Med. 2012;209(1):29–34.
  • Pecci A, Ragab I, Bozzi V, et al. Thrombopoietin mutation in congenital amegakaryocytic thrombocytopenia treatable with romiplostim. EMBO Mol Med. 2018;10(1):63–75.
  • Wielders SJH, Broers J, ten Cate H, et al. Absence of platelet-dependent fibrin formation in a patient with Scott syndrome. Thromb Haemost. 2009;102(1):76–82.
  • Millington-Burgess SL, Harper MT. Gene of the issue: ANO6 and Scott syndrome. Platelets. 2020;31(7):964–967.
  • Suzuki J, Umeda M, Sims PJ, et al. Calcium-dependent phospholipid scrambling by TMEM16F. Nature. 2010;468(7325):834–838.
  • Berrou E, Soukaseum C, Favier R, et al. A mutation of the human EPHB2 gene leads to a major platelet functional defect. Blood. 2018;132(19):2067–2077.
  • Nagy M, Mastenbroek TG, Mattheij NJA, et al. Variable impairment of platelet functions in patients with severe, genetically linked immune deficiencies. Haematologica. 2018;103(3):540–549.
  • Moser M, Nieswandt B, Ussar S, et al. Kindlin-3 is essential for integrin activation and platelet aggregation. Nat Med. 2008;14(3):325–330.
  • 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.
  • Moroi M, Jung SM, Okuma M, et al. A patient with platelets deficient in glycoprotein VI that lack both collagen-induced aggregation and adhesion. J Clin Invest. 1989;84(5):1440–1445.
  • Jandrot-Perrus M, Hermans C, Mezzano D. Platelet glycoprotein VI genetic quantitative and qualitative defects. Platelets. 2019;30(6):708–713.
  • Merideth MA, Introne WJ, Wang JA, et al. Genetic variants associated with Hermansky-Pudlak syndrome. Platelets. 2020;31(4):544–547.
  • Huizing M, Helip-Wooley A, Westbroek W, et al. Disorders of lysosome-related organelle biogenesis: clinical and molecular genetics. Annu Rev Genomics Hum Genet. 2008;9:359–386.
  • Huizing M, Malicdan MCV, Wang JA, et al. Hermansky-Pudlak syndrome: mutation update. Hum Mutat. 2020;41(3):543–580.
  • Nagle DL, Karim MA, Woolf EA, et al. Identification and mutation analysis of the complete gene for Chediak-Higashi syndrome. Nat Genet. 1996;14(3):307–311.
  • 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.
  • Nurden P, Savi P, Heilmann E, et al. An inherited bleeding disorder linked to a defective interaction between ADP and its receptor on platelets. Its influence on glycoprotein IIb-IIIa complex function. J Clin Invest. 1995;95(4):1612–1622.
  • Lecchi A, Femia EA, Paoletta S, et al. Inherited dysfunctional platelet P2Y12 receptor mutations associated with bleeding disorders. Hamostaseologie. 2016;36(4):279–283.
  • Adler DH, Cogan JD, Phillips JA, et al. Inherited human cPLA(2alpha) deficiency is associated with impaired eicosanoid biosynthesis, small intestinal ulceration, and platelet dysfunction. J Clin Invest. 2008;118(6):2121–2131.
  • Yagmur E, Weiskirchen R, Schedel A, et al. PTGS1 compound heterozygosity impairs gene expression and platelet aggregation and is associated with severe bleeding complications. Thromb Haemost. 2013;110(5):1083–1085.
  • Palma-Barqueros V, Bohdan N, Revilla N, et al. PTGS1 gene variations associated with bleeding and platelet dysfunction. Platelets. 2021;32(5):710–716.
  • Canault M, Ghalloussi D, Grosdidier C, et al. Human CalDAG-GEFI gene (RASGRP2) mutation affects platelet function and causes severe bleeding. J Exp Med. 2014;211(7):1349–1362.
  • Desai A, Bergmeier W, Canault M, et al. Phenotype analysis and clinical management in a large family with a novel truncating mutation in RASGRP2, the CalDAG-GEFI encoding gene. Res Pract Thromb Haemost. 2017;1(1):128–133.
  • Mundell SJ, Mumford A. TBXA2R gene variants associated with bleeding. Platelets. 2018;29(7):739–742.
  • Hirata T, Kakizuka A, Ushikubi F, et al. Arg60 to leu mutation of the human thromboxane A2 receptor in a dominantly inherited bleeding disorder. J Clin Invest. 1994;94(4):1662–1667.
  • 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.
  • Gissen P, Johnson CA, Morgan NV, et al. Mutations in VPS33B, encoding a regulator of SNARE-dependent membrane fusion, cause arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome. Nat Genet. 2004;36(4):400–404.
  • Cullinane AR, Straatman-Iwanowska A, Zaucker A, et al. Mutations in VIPAR cause an arthrogryposis, renal dysfunction and cholestasis syndrome phenotype with defects in epithelial polarization. Nat Genet. 2010;42(4):303–312.
  • Palma-Barqueros V, Revilla N, Sánchez A, et al. Inherited platelet disorders: an updated overview. IJMS. 2021;22(9):4521.
  • Pecci A, Balduini CL. Inherited thrombocytopenias: an updated guide for clinicians. Blood Rev. 2021;48:100784.
  • Bury L, Falcinelli E, Gresele P. Learning the ropes of platelet count regulation: inherited thrombocytopenias. JCM. 2021;10(3):533.
  • Nurden P, Stritt S, Favier R, et al. Inherited platelet diseases with normal platelet count: phenotypes, genotypes and diagnostic strategy. Haematologica. 2021;106(2):337–350.
  • Barbosa MD, Nguyen QA, Tchernev VT, et al. Identification of the homologous beige and Chediak-Higashi syndrome genes. Nature. 1996;382(6588):262–265.
  • Fager Ferrari M, Leinoe E, Rossing M, et al. Germline heterozygous variants in genes associated with familial hemophagocytic lymphohistiocytosis as a cause of increased bleeding. Platelets. 2018;29(1):56–64.
  • Cramer Bordé E, Ouzegdouh Y, Ledgerwood EC, et al. Congenital thrombocytopenia and cytochrome C mutation: a matter of birth and death. Semin Thromb Hemost. 2011;37(6):664–672.
  • Fellner M, Parakra R, McDonald KO, et al. Altered structure and dynamics of pathogenic cytochrome c variants correlate with increased apoptotic activity. Biochem J. 2021;478(3):669–684.
  • Othman M, Kaur H, Emsley J. Platelet-type von Willebrand disease: new insights into the molecular pathophysiology of a unique platelet defect. Semin Thromb Hemost. 2013;39(6):663–673.
  • Bury L, Falcinelli E, Chiasserini D, et al. Cytoskeletal perturbation leads to platelet dysfunction and thrombocytopenia in variant forms of Glanzmann thrombasthenia. Haematologica. 2016;101(1):46–56.
  • Cattaneo M. The P2 receptors and congenital platelet function defects. Semin Thromb Hemost. 2005;31(2):168–173.
  • Nieuwenhuis HK, Akkerman JW, Houdijk WP, et al. Human blood platelets showing no response to collagen fail to express surface glycoprotein Ia. Nature. 1985;318(6045):470–472.
  • Noris P, Guidetti GF, Conti V, et al. Autosomal dominant thrombocytopenias with reduced expression of glycoprotein Ia. Thromb Haemost. 2006;95(3):483–489.
  • Lacruz RS, Feske S. Diseases caused by mutations in ORAI1 and STIM1. Ann N Y Acad Sci. 2015;1356(1):45–79.
  • Liang M, Soomro A, Tasneem S, et al. Enhancer-gene rewiring in the pathogenesis of Quebec platelet disorder. Blood. 2020;136(23):2679–2690.
  • Diamandis M, Adam F, Kahr WHA, et al. Insights into abnormal hemostasis in the Quebec platelet disorder from analyses of clot lysis. J Thromb Haemost. 2006;4(5):1086–1094.
  • 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.
  • Hayward CPM, 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.
  • Quiroga T, Goycoolea M, Panes O, et al. High prevalence of bleeders of unknown cause among patients with inherited mucocutaneous bleeding. A prospective study of 280 patients and 299 controls. Haematologica. 2007;92(3):357–365.
  • Philipp CS, Dilley A, Miller CH, et al. Platelet functional defects in women with unexplained menorrhagia. J Thromb Haemost. 2003;1(3):477–484.
  • Quiroga T, Goycoolea M, Muñoz B, et al. Template bleeding time and PFA-100 have low sensitivity to screen patients with hereditary mucocutaneous hemorrhages: comparative study in 148 patients. J Thromb Haemost. 2004;2(6):892–898.
  • Seravalli V, Linari S, Peruzzi E, et al. Prevalence of hemostatic disorders in adolescents with abnormal uterine bleeding. J Pediatr Adolesc Gynecol. 2013;26(5):285–289.
  • Gupta PK, Charan VD, Saxena R. Spectrum of von Willebrand disease and inherited platelet function disorders amongst Indian bleeders. Ann Hematol. 2007;86(6):403–407.
  • Vo KT, Grooms L, Klima J, et al. Menstrual bleeding patterns and prevalence of bleeding disorders in a multidisciplinary adolescent haematology clinic. Haemophilia. 2013;19(1):71–75.
  • Hayward CPM, Moffat KA, Liu Y. Laboratory investigations for bleeding disorders. Semin Thromb Hemost. 2012;38(7):742–752.
  • Israels SJ, McNicol A, Robertson C, et al. Platelet storage Pool deficiency: diagnosis in patients with prolonged bleeding times and normal platelet aggregation. Br J Haematol. 1990;75(1):118–121.
  • Nieuwenhuis HK, Akkerman JW, Sixma JJ. Patients with a prolonged bleeding time and normal aggregation tests may have storage Pool deficiency: studies on one hundred six patients. Blood. 1987;70(3):620–623.
  • Gresele P, Harrison P, Bury L, et al. Diagnosis of suspected inherited platelet function disorders: results of a worldwide survey. J Thromb Haemost. 2014;12(9):1562–1569.
  • Oved JH, Lambert MP, Kowalska MA, et al. Population based frequency of naturally occurring loss-of-function variants in genes associated with platelet disorders. J Thromb Haemost. 2021;19(1):248–254.
  • Šrámek A. Usefulness of patient interview in bleeding disorders. Arch Intern Med. 1995;155(13):1409.
  • Brunet J, Badin M, Chong M, et al. Bleeding risks for uncharacterized platelet function disorders. Res Pract Thromb Haemost. 2020;4(5):799–806.
  • McKay H, Derome F, Haq MA, et al. Bleeding risks associated with inheritance of the Quebec platelet disorder. Blood. 2004;104(1):159–165.
  • Gresele P, Orsini S, Noris P, et al. Validation of the ISTH/SSC bleeding assessment tool for inherited platelet disorders: a communication from the platelet physiology SSC. J Thromb Haemost. 2020;18(3):732–739.
  • Gresele P, Falcinelli E, Bury L, et al. The ISTH bleeding assessment tool as predictor of bleeding events in inherited platelet disorders: communication from the ISTH SSC Subcommittee on Platelet Physiology. J Thromb Haemost. 2021;19(5):1364–1371.
  • Tosetto A, Rodeghiero F, Castaman G, et al. A quantitative analysis of bleeding symptoms in type 1 von Willebrand disease: results from a multicenter European study (MCMDM-1 VWD). J Thromb Haemost. 2006;4(4):766–773.
  • Page LK, Psaila B, Provan D, et al. The immune thrombocytopenic purpura (ITP) bleeding score: assessment of bleeding in patients with ITP. Br J Haematol. 2007;138(2):245–248.
  • Rodeghiero F, Tosetto A, Abshire T, et al. ISTH/SSC bleeding assessment tool: a standardized questionnaire and a proposal for a new bleeding score for inherited bleeding disorders. J Thromb Haemost. 2010;8(9):2063–2065.
  • Fogarty PF, Tarantino MD, Brainsky A, et al. Selective validation of the WHO bleeding scale in patients with chronic immune thrombocytopenia. Curr Med Res Opin. 2012;28(1):79–87.
  • Mittal N, Naridze R, James P, et al. Utility of a paediatric bleeding questionnaire as a screening tool for von Willebrand disease in apparently healthy children. Haemophilia. 2015;21(6):806–811.
  • Rodeghiero F, Michel M, Gernsheimer T, et al. Standardization of bleeding assessment in immune thrombocytopenia: report from the international working group. Blood. 2013;121(14):2596–2606.
  • Mauer AC, Khazanov NA, Levenkova N, et al. Impact of sex, age, race, ethnicity and aspirin use on bleeding symptoms in healthy adults. J Thromb Haemost. 2011;9(1):100–108.
  • Badin MS, Iyer JK, Chong M, et al. Molecular phenotype and bleeding risks of an inherited platelet disorder in a family with a RUNX1 frameshift mutation. Haemophilia. 2017;23(3):e204–e213.
  • Brunet JG, Iyer JK, Badin MS, et al. Electron microscopy examination of platelet whole mount preparations to quantitate platelet dense granule numbers: implications for diagnosing suspected platelet function disorders due to dense granule deficiency. Int J Lab Hem. 2018;40(4):400–407.
  • Sharma T, Brunet JG, Tasneem S, et al. Thrombin generation abnormalities in commonly encountered platelet function disorders. Int J Lab Hematol. 2021;43(6):1557–1565.
  • Hayward CPM, Moffat KA, George TI, et al. Report on the international society for laboratory hematology survey on guidelines to support clinical hematology laboratory practice. Int J Lab Hematol. 2016;38(Suppl 1):133–138.
  • Castilloux JF, Moffat KA, Liu Y, et al. 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(10):675–682.
  • Briggs C, Longair I, Kumar P, et al. Performance evaluation of the Sysmex haematology XN modular system. J Clin Pathol. 2012;65(11):1024–1030.
  • Schoorl M, Schoorl M, Oomes J, et al. New fluorescent method (PLT-F) on Sysmex XN2000 hematology analyzer achieved higher accuracy in low platelet counting. Am J Clin Pathol. 2013;140(4):495–499.
  • Zandecki M, Genevieve F, Gerard J, et al. Spurious counts and spurious results on haematology analysers: a review. Part I: platelets. Int J Lab Hematol. 2007;29(1):4–20.
  • Baccini V, Geneviève F, Jacqmin H, et al. Platelet counting: ugly traps and good advice. Proposals from the French-Speaking cellular hematology group (GFHC). JCM. 2020;9(3):808.
  • Lardinois B, Favresse J, Chatelain B, et al. Pseudothrombocytopenia—a review on causes, occurrence and clinical implications. JCM. 2021;10(4):594.
  • Payne BA, Pierre RV. Pseudothrombocytopenia: a laboratory artifact with potentially serious consequences. Mayo Clin Proc. 1984;59(2):123–125.
  • Savage RA. Pseudoleukocytosis due to EDTA-induced platelet clumping. Am J Clin Pathol. 1984;81(3):317–322.
  • Zhang L, Xu J, Gao L, et al. Spurious thrombocytopenia in automated platelet count. Lab Med. 2018;49(2):130–133.
  • Cohen AM, Cycowitz Z, Mittelman M, et al. The incidence of pseudothrombocytopenia in automatic blood analyzers. Haematologia. 2000;30(2):117–121.
  • Silvestri F, Virgolini L, Savignano C, et al. Incidence and diagnosis of EDTA-dependent pseudothrombocytopenia in a consecutive outpatient population referred for isolated thrombocytopenia. Vox Sang. 1995;68(1):35–39.
  • Anchinmane VT, Sankhe SV. Utility of peripheral blood smear in platelet count estimation. Int J Res Med Sci. 2019;7(2):434–437.
  • Noris P, Klersy C, Zecca M, et al. Platelet size distinguishes between inherited macrothrombocytopenias and immune thrombocytopenia. J Thromb Haemost. 2009;7(12):2131–2136.
  • Noris P, Biino G, Pecci A, et al. Platelet diameters in inherited thrombocytopenias: analysis of 376 patients with all known disorders. Blood. 2014;124(6):e4–e10.
  • Balduini CL, Pecci A, Loffredo G, et al. Effects of the R216Q mutation of GATA-1 on erythropoiesis and megakaryocytopoiesis. Thromb Haemost. 2004;91(1):129–140.
  • Freson K, Devriendt K, Matthijs G, et al. Platelet characteristics in patients with X-linked macrothrombocytopenia because of a novel GATA1 mutation. Blood. 2001;98(1):85–92.
  • Greinacher A, Pecci A, Kunishima S, et al. Diagnosis of inherited platelet disorders on a blood smear: a tool to facilitate worldwide diagnosis of platelet disorders. J Thromb Haemost. 2017;15(7):1511–1521.
  • Zaninetti C, Greinacher A. Diagnosis of inherited platelet disorders on a blood smear. JCM. 2020;9(2):539.
  • Rodgers RPC, Levin J. A critical reappraisal of the bleeding time. Semin Thromb Hemost. 1990;16(1):1–20.
  • Gewirtz AS, Miller ML, Keys TF. The clinical usefulness of the preoperative bleeding time. Arch Pathol Lab Med. 1996;120(4):353–356.
  • Favaloro EJ, Bonar R. An update on quality control for the PFA-100/PFA-200. Platelets. 2018;29(6):622–627.
  • Favaloro EJ, Facey D, Henniker A. Use of a novel platelet function analyzer (PFA-100) with high sensitivity to disturbances in von Willebrand factor to screen for von Willebrand’s disease and other disorders. Am J Hematol. 1999;62(3):165–174.
  • Kundu SK, Heilmann EJ, Sio R, et al. Description of an in vitro platelet function analyzer-PFA-100. Semin Thromb Hemost. 1995;21(Suppl 2):106–112.
  • Harrison P, Robinson MS, Mackie IJ, et al. Performance of the platelet function analyser PFA-100 in testing abnormalities of primary haemostasis. Blood Coagul Fibrinolysis. 1999;10(1):25–31.
  • Kundu SK, Heilmann EJ, Sio R, et al. Characterization of an in vitro platelet function analyzer, PFA-100™. Clin Appl Thromb Hemost. 1996;2(4):241–249.
  • Poujol C, Nurden A, Paponneau A, et al. Ultrastructural analysis of the distribution of von willebrand factor and fibrinogen in platelet aggregates formed in the PFA-100. Platelets. 1998;9(6):381–389.
  • Edwards A, Jakubowski JA, Rechner AR, et al. Evaluation of the INNOVANCE PFA P2Y test cartridge: sensitivity to P2Y(12) blockade and influence of anticoagulant. Platelets. 2012;23(2):106–115.
  • Scavone M, Germanovich K, Femia EA, et al. Usefulness of the INNOVANCE PFA P2Y test cartridge for the detection of patients with congenital defects of the platelet P2Y₁₂ receptor for adenosine diphosphate. Thromb Res. 2014;133(2):254–256.
  • Koessler J, Ehrenschwender M, Kobsar A, et al. Evaluation of the new INNOVANCE® PFA P2Y cartridge in patients with impaired primary haemostasis. Platelets. 2012;23(8):571–578.
  • Tsantes A, Ikonomidis I, Papadakis I, et al. Evaluation of the role of the new INNOVANCE PFA P2Y test cartridge in detection of clopidogrel resistance. Platelets. 2012;23(6):481–489.
  • Hayward CPM, Harrison P, Cattaneo M, et al. Platelet function analyzer (PFA)-100 closure time in the evaluation of platelet disorders and platelet function. J Thromb Haemost. 2006;4(2):312–319.
  • Favaloro EJ. Clinical utility of closure times using the platelet function analyzer-100/200. Am J Hematol. 2017;92(4):398–404.
  • Podda GM, Bucciarelli P, Lussana F, et al. Usefulness of PFA-100 testing in the diagnostic screening of patients with suspected abnormalities of hemostasis: comparison with the bleeding time. J Thromb Haemost. 2007;5(12):2393–2398.
  • Favaloro EJ. Clinical utility of the PFA-100. Semin Thromb Hemost. 2008;34(8):709–733.
  • Moenen FCJI, Vries MJA, Nelemans PJ, et al. Screening for platelet function disorders with multiplate and platelet function analyzer. Platelets. 2019;30(1):81–87.
  • Born GVR. Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature. 1962;194(4832):927–929.
  • O’brien JR. Platelet aggregation: part I some effects of the adenosine phosphates, thrombin, and cocaine upon platelet adhesiveness. J Clin Pathol. 1962;15(5):446–452.
  • Christie D, Avari T, Carrington L, et al. Platelet function testing by aggregometry: approved guidelines. Vol. 38. Wayne (PA): Clinical and Laboratory Standards Institute; 2008.
  • Hayward CPM, Moffat KA, Brunet J, et al. Update on diagnostic testing for platelet function disorders: what is practical and useful? Int J Lab Hematol. 2019;41(S1):26–32.
  • Althaus K, Zieger B, Bakchoul T, et al. Standardization of light transmission aggregometry for diagnosis of platelet disorders: an inter-laboratory external quality assessment. Thromb Haemost. 2019;119(7):1154–1161.
  • Hendra TJ, Oughton J, Smith CC, et al. Exercise-induced changes in platelet aggregation; a comparison of whole blood and platelet rich plasma techniques. Thromb Res. 1988;52(5):443–451.
  • Wang JS, Jen CJ, Chen HI. Effects of exercise training and deconditioning on platelet function in men. Arterioscler Thromb Vasc Biol. 1995;15(10):1668–1674.
  • Aldemir H, Kiliç N. The effect of time of day and exercise on platelet functions and platelet-neutrophil aggregates in healthy male subjects. Mol Cell Biochem. 2005;280(1–2):119–124.
  • Vicari AM, Margonato A, Macagni A, et al. Effects of acute smoking on the hemostatic system in humans. Clin Cardiol. 1988;11(8):538–540.
  • Bolliger D, Seeberger MD, Tanaka KA, et al. Pre-analytical effects of pneumatic tube transport on impedance platelet aggregometry. Platelets. 2009;20(7):458–465.
  • Lorenzen H, Frøstrup AB, Larsen AS, et al. Pneumatic tube transport of blood samples affects global hemostasis and platelet function assays. Int J Lab Hematol. 2021;43(5):1207–1215.
  • Stegnar M, Knezevic A, Bozic-Mijovski M. The effect of pre-analytical variables on light transmittance aggregometry in citrated platelet-rich plasma from healthy subjects. Clin Chem Lab Med. 2010;48(10):1463–1465.
  • Kaiser AFC, Neubauer H, Franken CC, et al. Which is the best anticoagulant for whole blood aggregometry platelet function testing? Comparison of six anticoagulants and diverse storage conditions. Platelets. 2012;23(5):359–367.
  • Maurer-Spurej E, Pfeiler G, Maurer N, et al. Room temperature activates human blood platelets. Lab Invest. 2001;81(4):581–592.
  • Merolla M, Nardi MA, Berger JS. Centrifugation speed affects light transmission aggregometry. Int J Lab Hematol. 2012;34(1):81–85.
  • Femia EA, Pugliano M, Podda G, et al. Comparison of different procedures to prepare platelet-rich plasma for studies of platelet aggregation by light transmission aggregometry. Platelets. 2012;23(1):7–10.
  • Mani H, Luxembourg B, Kläffling C, et al. Use of native or platelet count adjusted platelet rich plasma for platelet aggregation measurements. J Clin Pathol. 2005;58(7):747–750.
  • Linnemann B, Schwonberg J, Mani H, et al. Standardization of light transmittance aggregometry for monitoring antiplatelet therapy: an adjustment for platelet count is not necessary. J Thromb Haemost. 2008;6(4):677–683.
  • Cattaneo M, Lecchi A, Zighetti ML, et al. Platelet aggregation studies: autologous platelet-poor plasma inhibits platelet aggregation when added to platelet-rich plasma to normalize platelet count. Haematologica. 2007;92(5):694–697.
  • Hayward CPM, Moffat KA, Pai M, et al. An evaluation of methods for determining reference intervals for light transmission platelet aggregation tests on samples with normal or reduced platelet counts. Thromb Haemost. 2008;100(1):134–145.
  • Favaloro EJ, Mohammed S. Platelet function testing: auditing local practice and broader implications. Clin Lab Sci. 2010;23(1):21–31.
  • Hayward CPM, 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(04):726–734.
  • Blavignac J, Bunimov N, Rivard GE, et al. Quebec platelet disorder: update on pathogenesis, diagnosis, and treatment. Semin Thromb Hemost. 2011;37(6):713–720.
  • Faraday N, Scharpf RB, Dodd-O JM, et al. Leukocytes can enhance platelet-mediated aggregation and thromboxane release via interaction of P-selectin glycoprotein ligand 1 with P-selectin. Anesthesiology. 2001;94(1):145–151.
  • Praticò D, Iuliano L, Alessandri C, et al. Polymorphonuclear leukocyte-derived O2-reactive species activate primed platelets in human whole blood. Am J Physiol. 1993;264(5 Pt 2):H1582–1587.
  • Sun P, McMillan-Ward E, Mian R, et al. Comparison of light transmission aggregometry and multiple electrode aggregometry for the evaluation of patients with mucocutaneous bleeding. Int J Lab Hematol. 2019;41(1):133–140.
  • Al Ghaithi R, Drake S, Watson SP, et al. Comparison of multiple electrode aggregometry with lumi-aggregometry for the diagnosis of patients with mild bleeding disorders. J Thromb Haemost. 2017;15(10):2045–2052.
  • Haas T, Cushing MM, Varga S, et al. Usefulness of multiple electrode aggregometry as a screening tool for bleeding disorders in a pediatric hospital. Platelets. 2019;30(4):498–505.
  • Awidi A, Maqablah A, Dweik M, et al. Comparison of platelet aggregation using light transmission and multiple electrode aggregometry in Glanzmann thrombasthenia. Platelets. 2009;20(5):297–301.
  • Albanyan A, Al-Musa A, AlNounou R, et al. Diagnosis of Glanzmann thrombasthenia by whole blood impedance analyzer (MEA) vs. light transmission aggregometry. Int J Lab Hematol. 2015;37(4):503–508.
  • Karkouti K, Callum J, Wijeysundera DN, et al. Point-of-care hemostatic testing in cardiac surgery: a stepped-wedge clustered randomized controlled trial. Circulation. 2016;134(16):1152–1162.
  • McGlasson D, Fritsma G. Whole blood platelet aggregometry and platelet function testing. Semin Thromb Hemost. 2009;35(2):168–180.
  • Sweeney JD, Hoernig LA, Michnik A, et al. Whole blood aggregometry. Influence of sample collection and delay in study performance on test results. Am J Clin Pathol. 1989;92(5):676–679.
  • Dyszkiewicz-Korpanty AM, Frenkel EP, Sarode R. Approach to the assessment of platelet function: comparison between optical-based platelet-rich plasma and impedance-based whole blood platelet aggregation methods. Clin Appl Thromb Hemost. 2005;11(1):25–35.
  • Skipper MT, Rubak P, Stentoft J, et al. Evaluation of platelet function in thrombocytopenia. Platelets. 2018;29(3):270–276.
  • Tiedemann Skipper M, Rubak P, Halfdan Larsen O, et al. Thrombocytopenia model with minimal manipulation of blood cells allowing whole blood assessment of platelet function. Platelets. 2016;27(4):295–300.
  • Moffat K, Ledford-Kraemer M, Nichols W, et al. Variability in clinical laboratory practice in testing for disorders of platelet function: results of two surveys of the North American specialized coagulation laboratory association. Thromb Haemost. 2005;93(3):549–553.
  • Cattaneo M. Light transmission aggregometry and ATP release for the diagnostic assessment of platelet function. Semin Thromb Hemost. 2009;35(2):158–167.
  • 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.
  • Feinman RD, Lubowsky J, Charo I, et al. The lumi-aggregometer: a new instrument for simultaneous measurement of secretion and aggregation by platelets. J Lab Clin Med. 1977;90(1):125–129.
  • Lotta LA, Maino A, Tuana G, et al. Prevalence of disease and relationships between laboratory phenotype and bleeding severity in platelet primary secretion defects. PLoS One. 2013;8(4):e60396.
  • Badin MS, Graf L, Iyer JK, et al. Variability in platelet dense granule adenosine triphosphate release findings amongst patients tested multiple times as part of an assessment for a bleeding disorder. Int J Lab Hematol. 2016;38(6):648–657.
  • De Robertis E. Electron microscope observations of the platelet-fibrin relationship in blood clotting. Blood. 1955;10(5):528–533.
  • Chen D, Uhl CB, Bryant SC, et al. Diagnostic laboratory standardization and validation of platelet transmission electron microscopy. Platelets. 2018;29(6):574–582.
  • Woods GM, Kudron EL, Davis K, et al. Light transmission aggregometry does not correlate with the severity of δ-granule platelet storage Pool deficiency. J Pediatr Hematol Oncol. 2016;38(7):525–528.
  • Israels SJ, Robertson C, Mcnicol A. Identification of patients with storage Pool deficiency using ATP release and dense granule counts. Hematology. 1997;2(2):161–167.
  • Gunning WT, Yoxtheimer L, Smith MR. Platelet aggregation assays do not reliably diagnose platelet delta granule storage Pool deficiency. J Hematol. 2020;10(4):196–201.
  • White JG. The dense bodies of human platelets: inherent electron opacity of the serotonin storage particles. Blood. 1969;33(4):598–606.
  • White JG. Use of the electron microscope for diagnosis of platelet disorders. Semin Thromb Hemost. 1998;24(2):163–168.
  • Weiss HJ, Lages B, Vicic W, et al. Heterogeneous abnormalities of platelet dense granule ultrastructure in 20 patients with congenital storage Pool deficiency. Br J Haematol. 1993;83(2):282–295.
  • Asher L, Hata J. Platelet electron microscopy: utilizing LEAN methodology to optimize laboratory workflow. Pediatr Dev Pathol. 2020;23(5):356–361.
  • Hayward CPM, Moffat KA, Spitzer E, et al. Results of an external proficiency testing exercise on platelet dense-granule deficiency testing by whole mount electron microscopy. Am J Clin Pathol. 2009;131(5):671–675.
  • Westmoreland D, Shaw M, Grimes W, et al. Super-resolution microscopy as a potential approach to diagnosis of platelet granule disorders. J Thromb Haemost. 2016;14(4):839–849.
  • Gunning WT, Calomeni EP. A brief review of transmission electron microscopy and applications in pathology. J Histotechnol. 2000;23(3):237–246.
  • White JG. Electron opaque structures in human platelets: which are or are not dense bodies? Platelets. 2008;19(6):455–466.
  • White JG. Electron microscopy methods for studying platelet structure and function. Methods Mol Biol. 2004;272:47–63.
  • Glauert AM, Lewis PR. Biological specimen preparation for transmission electron microscopy. Princeton, NJ: Princeton University Press; 2014.
  • Sawatzke CL, Solomons CC. Fixation and embedding of small volumes of platelets for transmission electron microscopy. J Clin Pathol. 1980;33(6):600–602.
  • White JG. Effects of ethylenediamine tetracetic acid (EDTA) on platelet structure. Scand J Haematol. 1968;5(4):241–254.
  • White JG. Platelet microtubules and giant granules in the Chediak-Higashi syndrome. Am J Med Technol. 1978;44(4):273–278.
  • White JG. Platelet storage Pool deficiency in Jacobsen syndrome. Platelets. 2007;18(7):522–527.
  • White JG, de Alarcon PA. Platelet spherocytosis: a new bleeding disorder. Am J Hematol. 2002;70(2):158–166.
  • Breton-Gorius J, Vainchenker W, Nurden A, et al. Defective alpha-granule production in megakaryocytes from gray platelet syndrome: ultrastructural studies of bone marrow cells and megakaryocytes growing in culture from blood precursors. Am J Pathol. 1981;102(1):10–19.
  • Mezzano D, Aranda E, Foradori A. Comparative study of size, total protein, fibrinogen and 5-HT content of human and canine platelet density subpopulations. Thromb Haemost. 1986;56(3):288–292.
  • Jedlitschky G, Greinacher A, Kroemer HK. Transporters in human platelets: physiologic function and impact for pharmacotherapy. Blood. 2012;119(15):3394–3402.
  • Maurer-Spurej E, Pittendreigh C, Solomons K. The influence of selective serotonin reuptake inhibitors on human platelet serotonin. Thromb Haemost. 2004;91(01):119–128.
  • Sheridan D, Carter C, Kelton JG. A diagnostic test for heparin-induced thrombocytopenia. Blood. 1986;67(1):27–30.
  • Warkentin TE, Arnold DM, Nazi I, et al. The platelet serotonin-release assay. Am J Hematol. 2015;90(6):564–572.
  • Holmsen H, Ostvold AC, Day HJ. Behaviour of endogenous and newly absorbed serotonin in the platelet release reaction. Biochem Pharmacol. 1973;22(20):2599–2608.
  • Zhou L, Schmaier AH. Platelet aggregation testing in platelet-rich plasma: description of procedures with the aim to develop standards in the field. Am J Clin Pathol. 2005;123(2):172–183.
  • Holmsen H, Dangelmaier CA. Measurement of secretion of serotonin. Methods Enzymol. 1989;169:205–210.
  • Wall JE, Buijs-Wilts M, Arnold JT, et al. A flow cytometric assay using mepacrine for study of uptake and release of platelet dense granule contents. Br J Haematol. 1995;89(2):380–385.
  • Kumar AM, Kumar M, Deepika K, et al. A modified HPLC technique for simultaneous measurement of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in cerebrospinal fluid, platelet and plasma. Life Sci. 1990;47(19):1751–1759.
  • Pussard E, Guigueno N, Adam O, et al. Validation of HPLC-amperometric detection to measure serotonin in plasma, platelets, whole blood, and urine. Clin Chem. 1996;42(7):1086–1091.
  • Ge S, Woo E, White JG, et al. Electrochemical measurement of endogenous serotonin release from human blood platelets. Anal Chem. 2011;83(7):2598–2604.
  • Anderson GM, Hall LM, Yang JX, et al. Platelet dense granule release reaction monitored by high-performance liquid chromatography-fluorometric determination of endogenous serotonin. Anal Biochem. 1992;206(1):64–67.
  • Bossant MJ, Ninio E, Delautier D, et al. Quantitation of paf-acether by release of endogenous platelet serotonin assessed by liquid chromatography with electrochemical detection. Anal Biochem. 1989;182(2):419–423.
  • Torfs SC, Maes AA, Delesalle CJ, et al. Comparative analysis of serotonin in equine plasma with liquid chromatography-tandem mass spectrometry and enzyme-linked immunosorbent assay. J Vet Diagn Invest. 2012;24(6):1035–1042.
  • Ge S, Wittenberg NJ, Haynes CL. Quantitative and real-time detection of secretion of chemical messengers from individual platelets. Biochemistry. 2008;47(27):7020–7024.
  • Kluge H, Bolle M, Reuter R, et al. Serotonin in platelets: comparative analyses using new enzyme immunoassay and HPLC test kits and the traditional fluorimetric procedure. Lab J Lab Med. 1999;23(6):360–364.
  • Sono-Koree NK, Crist RA, Frank EL, et al. A high-performance liquid chromatography method for the serotonin release assay is equivalent to the radioactive method. Int J Lab Hem. 2016;38(1):72–80.
  • Chan SL, Yi X, Wysocki E, et al. Development of a nonradioactive platelet serotonin uptake and release assay by micro-liquid chromatography tandem mass spectrometry using minimal blood volume. Am J Clin Pathol. 2019;152(6):718–724.
  • Chauveau J, Fert V, Morel AM, et al. Rapid and specific enzyme immunoassay of serotonin. Clin Chem. 1991;37(7):1178–1184.
  • Fouassier M, Bourgerette E, Libert F, et al. Determination of serotonin release from platelets by HPLC and ELISA in the diagnosis of heparin-induced thrombocytopenia: comparison with reference method by [C]-serotonin release assay. J Thromb Haemost. 2006;4(5):1136–1139.
  • Holmsen H, Storm E, Day HJ. Determination of ATP and ADP in blood platelets: a modification of the firefly luciferase assay for plasma. Anal Biochem. 1972;46(2):489–501.
  • David JL, Herion F. Assay of platelet ATP and ADP by the luciferase method: Some theoretical and practical aspects. Adv Exp Med Biol. 1972;34:341–354.
  • Weiss HJ, Witte LD, Kaplan KL, et al. Heterogeneity in storage Pool deficiency: studies on granule-bound substances in 18 patients including variants deficient in alpha-granules, platelet factor 4, beta-thromboglobulin, and platelet-derived growth factor. Blood. 1979;54(6):1296–1319.
  • Lages B, Holmsen H, Weiss HJ, et al. Thrombin and ionophore A23187-induced dense granule secretion in storage Pool deficient platelets: evidence for impaired nucleotide storage as the primary dense granule defect. Blood. 1983;61(1):154–162.
  • Cattaneo M, Canciani MT, Lecchi A, et al. Released adenosine diphosphate stabilizes thrombin-induced human platelet aggregates. Blood. 1990;75(5):1081–1086.
  • D’Souza L, Glueck HI. Measurement of nucleotide pools in platelets using high pressure liquid chromatography. Thromb Haemost. 1977;38(04):0990–1001.
  • Leoncini G, Buzzi E, Maresca M, et al. Alkaline extraction and reverse-phase high-performance liquid chromatography of adenine and pyridine nucleotides in human platelets. Anal Biochem. 1987;165(2):379–383.
  • von PM, Gambaryan S, Schütz C, et al. Determination of ATP and ADP secretion from human and mouse platelets by an HPLC assay. Transfus Med Hemother. 2013;40(2):109–116.
  • Blair P, Flaumenhaft R. Platelet alpha-granules: basic biology and clinical correlates. Blood Rev. 2009;23(4):177–189.
  • Ohkawa R, Hirowatari Y, Nakamura K, et al. Platelet release of beta-thromboglobulin and platelet factor 4 and serotonin in plasma samples. Clin Biochem. 2005;38(11):1023–1026.
  • Kaplan KL, Nossel HL, Drillings M, et al. Radioimmunoassay of platelet factor 4 and beta-thromboglobulin: development and application to studies of platelet release in relation to fibrinopeptide a generation. Br J Haematol. 1978;39(1):129–146.
  • Takahashi H, Yoshino N, Shibata A. Measurement of platelet factor 4 and beta-thromboglobulin by an enzyme-linked immunosorbent assay. Clin Chim Acta Int J Clin Chem. 1988;175(1):113–114.
  • Schraw T, Whiteheart S. The development of a quantitative enzyme-linked immunosorbent assay to detect human platelet factor 4. Transfusion. 2005;45(5):717–724.
  • Mumford AD, Frelinger AL, Gachet C, et al. A review of platelet secretion assays for the diagnosis of inherited platelet secretion disorders. Thromb Haemost. 2015;114(1):14–25.
  • Wolfs JLN, Comfurius P, Rasmussen JT, et al. Activated scramblase and inhibited aminophospholipid translocase cause phosphatidylserine exposure in a distinct platelet fraction. Cell Mol Life Sci. 2005;62(13):1514–1525.
  • Agbani EO, Poole AW. Procoagulant platelets: generation, function, and therapeutic targeting in thrombosis. Blood. 2017;130(20):2171–2179.
  • Prodan CI, Stoner JA, Cowan LD, et al. Higher coated-platelet levels are associated with stroke recurrence following nonlacunar brain infarction. J Cereb Blood Flow Metab. 2013;33(2):287–292.
  • Kirkpatrick AC, Stoner JA, Dale GL, et al. Elevated coated-platelets in symptomatic large-artery stenosis patients are associated with early stroke recurrence. Platelets. 2014;25(2):93–96.
  • Kirkpatrick AC, Vincent AS, Dale GL, et al. Coated-platelets predict stroke at 30 days following TIA. Neurology. 2017;89(2):125–128.
  • Zhao L, Bi Y, Kou J, et al. Phosphatidylserine exposing-platelets and microparticles promote procoagulant activity in Colon cancer patients. J Exp Clin Cancer Res. 2016;35:54.
  • Guo L, Tong D, Yu M, et al. Phosphatidylserine-exposing cells contribute to the hypercoagulable state in patients with multiple myeloma. Int J Oncol. 2018;52(6):1981–1990.
  • Panova-Noeva M, Marchetti M, Spronk HM, et al. Platelet-induced thrombin generation by the calibrated automated thrombogram assay is increased in patients with essential thrombocythemia and polycythemia vera. Am J Hematol. 2011;86(4):337–342.
  • Colucci G, Stutz M, Rochat S, et al. The effect of desmopressin on platelet function: a selective enhancement of procoagulant COAT platelets in patients with primary platelet function defects. Blood. 2014;123(12):1905–1916.
  • Wartiovaara-Kautto U, Joutsi-Korhonen L, Ilveskero S, et al. Platelets significantly modify procoagulant activities in haemophilia A. Haemophilia. 2011;17(5):743–751.
  • Santagostino E, Mancuso ME, Tripodi A, et al. Severe hemophilia with mild bleeding phenotype: molecular characterization and global coagulation profile. J Thromb Haemost. 2010;8(4):737–743.
  • Szanto T, Nummi V, Jouppila A, et al. Platelets compensate for poor thrombin generation in type 3 von Willebrand disease. Platelets. 2020;31(1):103–111.
  • Castoldi E, Duckers C, Radu C, et al. Homozygous F5 deep-intronic splicing mutation resulting in severe factor V deficiency and undetectable thrombin generation in platelet-rich plasma. J Thromb Haemost. 2011;9(5):959–968.
  • Duckers C, Simioni P, Spiezia L, et al. Residual platelet factor V ensures thrombin generation in patients with severe congenital factor V deficiency and mild bleeding symptoms. Blood. 2010;115(4):879–886.
  • Rugeri L, Quélin F, Chatard B, et al. Thrombin generation in patients with factor XI deficiency and clinical bleeding risk. Haemophilia. 2010;16(5):771–777.
  • Brunet JG, Sharma T, Tasneem S, et al. Thrombin generation abnormalities in Quebec platelet disorder. Int J Lab Hem. 2020;42(6):801–809.
  • Chelle P, Montmartin A, Damien P, et al. Tissue factor pathway inhibitor is the main determinant of thrombin generation in haemophilic patients. Haemophilia. 2019;25(2):343–348.
  • MacDonald S, White D, Langdown J, et al. Investigation of patients with unclassified bleeding disorder and abnormal thrombin generation for physiological coagulation inhibitors reveals multiple abnormalities and a subset of patients with increased tissue factor pathway inhibitor activity. Int J Lab Hem. 2020;42(3):246–255.
  • Hemker HC, Giesen P, Al Dieri R, et al. Calibrated automated thrombin generation measurement in clotting plasma. Pathophysiol Haemos Thromb. 2003;33(1):4–15.
  • Hemker HC, Giesen PL, Ramjee M, et al. The thrombogram: monitoring thrombin generation in platelet-rich plasma. Thromb Haemost. 2000;83(4):589–591.
  • Rosing J, Bevers E, Comfurius P, et al. Impaired factor X and prothrombin activation associated with decreased phospholipid exposure in platelets from a patient with a bleeding disorder. Blood. 1985;65(6):1557–1561.
  • Tohidi-Esfahani I, Lee CSM, Liang HPH, et al. Procoagulant platelets: laboratory detection and clinical significance. Int J Lab Hematol. 2020;42(S1):59–67.
  • Jennings LK, Ashmun RA, Wang WC, et al. Analysis of human platelet glycoproteins IIb-IIIa and Glanzmann’s thrombasthenia in whole blood by flow cytometry. Blood. 1986;68(1):173–179.
  • Giannini S, Cecchetti L, Mezzasoma AM, et al. Diagnosis of platelet-type von Willebrand disease by flow cytometry. Haematologica. 2010;95(6):1021–1024.
  • Cohn RJ, Sherman GG, Glencross DK. Flow cytometric analysis of platelet surface glycoproteins in the diagnosis of Bernard-Soulier syndrome. Pediatr Hematol Oncol. 1997;14(1):43–50.
  • Marti GE, Magruder L, Schuette WE, et al. Flow cytometric analysis of platelet surface antigens. Cytometry. 1988;9(5):448–455.
  • Halliez M, Fouassier M, Robillard N, et al. Detection of phosphatidyl serine on activated platelets' surface by flow cytometry in whole blood: a simpler test for the diagnosis of Scott syndrome. Br J Haematol. 2015;171(2):290–292.
  • Stenberg PE, McEver RP, Shuman MA, et al. A platelet alpha-granule membrane protein (GMP-140) is expressed on the plasma membrane after activation. J Cell Biol. 1985;101(3):880–886.
  • De Cuyper IM, Meinders M, van de Vijver E, et al. A novel flow cytometry-based platelet aggregation assay. Blood. 2013;121(10):e70–e80.
  • Navred K, Martin M, Ekdahl L, et al. A simplified flow cytometric method for detection of inherited platelet disorders–a comparison to the gold standard light transmission aggregometry. PLoS One. 2019;14(1):e0211130.
  • Vinholt PJ, Frederiksen H, Hvas AM, et al. Measurement of platelet aggregation, independently of patient platelet count: a flow-cytometric approach. J Thromb Haemost. 2017;15(6):1191–1202.
  • Boknäs N, Macwan AS, Södergren AL, et al. Platelet function testing at low platelet counts: when can you trust your analysis? Res Pract Thromb Haemost. 2019;3(2):285–290.
  • Podda G, Scavone M, Femia EA, et al. Aggregometry in the settings of thrombocytopenia, thrombocytosis and antiplatelet therapy. Platelets. 2018;29(7):644–649.
  • Jurk K, Shiravand Y. Platelet phenotyping and function testing in thrombocytopenia. J Clin Med. 2021;10(5):1114.
  • Frelinger AL, Rivera J, Connor DE, et al. Consensus recommendations on flow cytometry for the assessment of inherited and acquired disorders of platelet number and function: communication from the ISTH SSC Subcommittee on Platelet Physiology. J Thromb Haemost. 2021;19(12):3193–3202.
  • Busuttil-Crellin X, McCafferty C, Van Den Helm S, et al. Guidelines for panel design, optimization, and performance of whole blood multi-color flow cytometry of platelet surface markers. Platelets. 2020;31(7):845–852.
  • Andres O, Henning K, Strauß G, et al. Diagnosis of platelet function disorders: a standardized, rational, and modular flow cytometric approach. Platelets. 2018;29(4):347–356.
  • Frelinger AL, Grace RF, Gerrits AJ, et al. Platelet function tests, independent of platelet count, are associated with bleeding severity in ITP. Blood. 2015;126(7):873–879.
  • Boknäs N, Ramström S, Faxälv L, et al. Flow cytometry-based platelet function testing is predictive of symptom burden in a cohort of bleeders. Platelets. 2018;29(5):512–519.
  • van Asten I, Schutgens REG, Baaij M, et al. Validation of flow cytometric analysis of platelet function in patients with a suspected platelet function defect. J Thromb Haemost. 2018;16(4):689–698.
  • Dovlatova N, Lordkipanidzé M, Lowe GC, et al. Evaluation of a whole blood remote platelet function test for the diagnosis of mild bleeding disorders. J Thromb Haemost. 2014;12(5):660–665.
  • Huskens D, Li L, Florin L, et al. Flow cytometric analysis of platelet function to improve the recognition of thrombocytopathy. Thromb Res. 2020;194:183–189.
  • Blair TA, Frelinger AL. Platelet surface marker analysis by mass cytometry. Platelets. 2020;31(5):633–640.
  • Spurgeon BEJ, Naseem KM. High-throughput signaling profiling in blood platelets by multiplexed phosphoflow cytometry. Methods Mol Biol. 2018;1812:95–111.
  • Spurgeon BEJ, Naseem KM. Phosphoflow cytometry and barcoding in blood platelets: Technical and analytical considerations. Cytometry B Clin Cytom. 2020;98(2):123–130.
  • Pasalic L, Pennings GJ, Connor D, et al. Flow cytometry protocols for assessment of platelet function in whole blood. Methods Mol Biol. 2017;1646:369–389.
  • Linden MD. Platelet flow cytometry. Methods Mol Biol. 2013;992:241–262.
  • Michelson AD, Barnard MR, Krueger LA, et al. Evaluation of platelet function by flow cytometry. Methods. 2000;21(3):259–270.
  • Pedersen OH, Nissen PH, Hvas AM. Platelet function investigation by flow cytometry: sample volume, needle size, and reference intervals. Platelets. 2018;29(2):199–202.
  • Ramström S, Södergren AL, Tynngård N, et al. Platelet function determined by flow cytometry: new perspectives? Semin Thromb Hemost. 2016;42(3):268–281.
  • Ritchie JL, Alexander HD, Rea IM. Flow cytometry analysis of platelet P-selectin expression in whole blood-methodological considerations. Clin Lab Haematol. 2000;22(6):359–363.
  • Schmidt V, Hilberg T. ThromboFix platelet stabilizer: advances in clinical platelet analyses by flow cytometry? Platelets. 2006;17(4):266–273.
  • Hu H, Daleskog M, Li N. Influences of fixatives on flow cytometric measurements of platelet P-selectin expression and fibrinogen binding. Thromb Res. 2000;100(3):161–166.
  • Shattil SJ, Hoxie JA, Cunningham M, et al. Changes in the platelet membrane glycoprotein IIb.IIIa complex during platelet activation. J Biol Chem. 1985;260(20):11107–11114.
  • Dovlatova N, May JA, Fox SC. Remote platelet function testing-significant progress towards widespread testing in clinical practice. Platelets. 2015;26(5):399–401.
  • Hagberg IA, Lyberg T. Blood platelet activation evaluated by flow cytometry: optimised methods for clinical studies. Platelets. 2000;11(3):137–150.
  • Huskens D, Sang Y, Konings J, et al. Standardization and reference ranges for whole blood platelet function measurements using a flow cytometric platelet activation test. PLOS One. 2018;13(2):e0192079.
  • Nurden P, Tandon N, Takizawa H, et al. An acquired inhibitor to the GPVI platelet collagen receptor in a patient with lupus nephritis. J Thromb Haemost. 2009;7(9):1541–1549.
  • Giannini S, Mezzasoma AM, Guglielmini G, et al. A new case of acquired Glanzmann's thrombasthenia: diagnostic value of flow cytometry. Cytometry B Clin Cytom. 2008;74(3):194–199.
  • McEver RP, Martin MN. A monoclonal antibody to a membrane glycoprotein binds only to activated platelets. J Biol Chem. 1984;259(15):9799–9804.
  • Metzelaar MJ, Wijngaard PL, Peters PJ, et al. CD63 antigen. A novel lysosomal membrane glycoprotein, cloned by a screening procedure for intracellular antigens in eukaryotic cells. J Biol Chem. 1991;266(5):3239–3245.
  • Rubak P, Nissen PH, Kristensen SD, et al. Investigation of platelet function and platelet disorders using flow cytometry. Platelets. 2016;27(1):66–74.
  • Curvers J, de Wildt-Eggen J, Heeremans J, et al. Flow cytometric measurement of CD62P (P-selectin) expression on platelets: a multicenter optimization and standardization effort. Transfusion. 2008;48(7):1439–1446.
  • Furie B, Furie B, Flaumenhaft R. A journey with platelet P-Selectin: the molecular basis of granule secretion, signalling and cell adhesion. Thromb Haemost. 2001;86(1):214–221.
  • Pasalic L. Assessment of platelet function in whole blood by flow cytometry. Methods Mol Biol. 2017;1646:349–367.
  • Berman CL, Yeo EL, Wencel-Drake JD, et al. A platelet alpha granule membrane protein that is associated with the plasma membrane after activation. Characterization and subcellular localization of platelet activation-dependent granule-external membrane protein. J Clin Invest. 1986;78(1):130–137.
  • Ruf A, Patscheke H. Flow cytometric detection of activated platelets: comparison of determining shape change, fibrinogen binding, and P-selectin expression. Semin Thromb Hemost. 1995;21(2):146–151.
  • Michelson AD, Benoit SE, Kroll MH, et al. The activation-induced decrease in the platelet surface expression of the glycoprotein Ib-IX complex is reversible. Blood. 1994;83(12):3562–3573.
  • Lages B, Shattil SJ, Bainton DF, et al. Decreased content and surface expression of alpha-granule membrane protein GMP-140 in one of two types of platelet alpha Delta storage Pool deficiency. J Clin Invest. 1991;87(3):919–929.
  • Lages B, Sussman II, Levine SP, et al. Platelet alpha granule deficiency associated with decreased P-selectin and selective impairment of thrombin-induced activation in a new patient with gray platelet syndrome (alpha-storage Pool deficiency). J Lab Clin Med. 1997;129(3):364–375.
  • van Velzen JF, Laros-van Gorkom BAP, Pop GAM, et al. Multicolor flow cytometry for evaluation of platelet surface antigens and activation markers. Thromb Res. 2012;130(1):92–98.
  • Gresele P, Falcinelli E, Bury L. Laboratory diagnosis of clinically relevant platelet function disorders. Int J Lab Hematol. 2018;40(Suppl 1):34–45.
  • McEver RP, Cummings RD. Perspectives series: cell adhesion in vascular biology. Role of PSGL-1 binding to selectins in leukocyte recruitment. J Clin Invest. 1997;100(3):485–491.
  • de Gaetano G, Cerletti C, Evangelista V. Recent advances in platelet-polymorphonuclear leukocyte interaction. Haemostasis. 1999;29(1):41–49.
  • Maugeri N, Baldini M, Ramirez GA, et al. Platelet-leukocyte deregulated interactions foster sterile inflammation and tissue damage in immune-mediated vessel diseases. Thromb Res. 2012;129(3):267–273.
  • Brill A, Fuchs TA, Savchenko AS, et al. Neutrophil extracellular traps promote deep vein thrombosis in mice. J Thromb Haemost. 2012;10(1):136–144.
  • Asaduzzaman M, Lavasani S, Rahman M, et al. Platelets support pulmonary recruitment of neutrophils in abdominal sepsis. Crit Care Med. 2009;37(4):1389–1396.
  • Peyton BD, Rohrer MJ, Furman MI, et al. Patients with venous stasis ulceration have increased monocyte-platelet aggregation. J Vasc Surg. 1998;27(6):1109–1115; discussion 1115–1116.
  • Furman MI, Barnard MR, Krueger LA, et al. Circulating monocyte-platelet aggregates are an early marker of acute myocardial infarction. J Am Coll Cardiol. 2001;38(4):1002–1006.
  • Gerrard JM, Lint D, Sims PJ, et al. Identification of a platelet dense granule membrane protein that is deficient in a patient with the Hermansky-Pudlak syndrome. Blood. 1991;77(1):101–112.
  • Nieuwenhuis HK, van Oosterhout JJ, Rozemuller E, et al. Studies with a monoclonal antibody against activated platelets: evidence that a secreted 53,000-molecular weight lysosome-like granule protein is exposed on the surface of activated platelets in the circulation. Blood. 1987;70(3):838–845.
  • Shalev A, Michaud G, Israels SJ, et al. Quantification of a novel dense granule protein (granulophysin) in platelets of patients with dense granule storage Pool deficiency. Blood. 1992;80(5):1231–1237.
  • Nishibori M, Cham B, McNicol A, et al. The protein CD63 is in platelet dense granules, is deficient in a patient with Hermansky-Pudlak syndrome, and appears identical to granulophysin. J Clin Invest. 1993;91(4):1775–1782.
  • Israels SJ, McMillan-Ward EM. CD63 modulates spreading and tyrosine phosphorylation of platelets on immobilized fibrinogen. Thromb Haemost. 2005;93(2):311–318.
  • Pols MS, Klumperman J. Trafficking and function of the tetraspanin CD63. Exp Cell Res. 2009;315(9):1584–1592.
  • Shattil SJ, Cunningham M, Hoxie JA. Detection of activated platelets in whole blood using activation-dependent monoclonal antibodies and flow cytometry. Blood. 1987;70(1):307–315.
  • Abrams CS, Ellison N, Budzynski AZ, et al. Direct detection of activated platelets and platelet-derived microparticles in humans. Blood. 1990;75(1):128–138.
  • Jackson CW, Jennings LK. Heterogeneity of fibrinogen receptor expression on platelets activated in normal plasma with ADP: analysis by flow cytometry. Br J Haematol. 1989;72(3):407–414.
  • Kasahara K, Takagi J, Sekiya F, et al. Analysis of distribution of receptors among platelets by flow cytometry. Thromb Res. 1987;45(6):763–770.
  • Schoolmeester A, Vanhoorelbeke K, Katsutani S, et al. Monoclonal antibody IAC-1 is specific for activated alpha2beta1 and binds to amino acids 199 to 201 of the integrin alpha2 I-domain. Blood. 2004;104(2):390–396.
  • Heilmann E, Hynes LA, Burstein SA, et al. Fluorescein derivatization of fibrinogen for flow cytometric analysis of fibrinogen binding to platelets. Cytometry. 1994;17(4):287–293.
  • Faraday N, Goldschmidt-Clermont P, Dise K, et al. Quantitation of soluble fibrinogen binding to platelets by fluorescence-activated flow cytometry. J Lab Clin Med. 1994;123(5):728–740.
  • Frelinger AL, Cohen I, Plow EF, et al. Selective inhibition of integrin function by antibodies specific for ligand-occupied receptor conformers. J Biol Chem. 1990;265(11):6346–6352.
  • Yaw HP, Van Den Helm S, Linden M, et al. Whole blood flow cytometry protocol for the assessment of platelet phenotype, function, and cellular interactions. Platelets. 2021;32(6):786–793.
  • Ignatova AA, Ponomarenko EA, Polokhov DM, et al. Flow cytometry for pediatric platelets. Platelets. 2019;30(4):428–437.
  • Rendu F, Nurden AT, Lebret M, et al. Relationship between mepacrine-labelled dense body number, platelet capacity to accumulate 14C-5-HT and platelet density in the Bernard-Soulier and Hermansky-Pudlak syndromes. Thromb Haemost. 1979;42(2):694–704.
  • Lorez HP, Da Prada M, Rendu F, et al. Mepacrine, a tool for investigating the 5-hydroxytryptamine organelles of blood platelets by fluorescence microscopy. J Lab Clin Med. 1977;89(1):200–206.
  • Gordon N, Thom J, Cole C, et al. Rapid detection of hereditary and acquired platelet storage Pool deficiency by flow cytometry. Br J Haematol. 1995;89(1):117–123.
  • Ramström AS, Fagerberg IH, Lindahl TL. A flow cytometric assay for the study of dense granule storage and release in human platelets. Platelets. 1999;10(2–3):153–158.
  • van Asten I, Blaauwgeers M, Granneman L, et al. Flow cytometric mepacrine fluorescence can be used for the exclusion of platelet dense granule deficiency. J Thromb Haemost. 2020;18(3):706–713.
  • Cai H, Mullier F, Frotscher B, et al. Usefulness of flow cytometric mepacrine uptake/release combined with CD63 assay in diagnosis of patients with suspected platelet dense granule disorder. Semin Thromb Hemost. 2016;42(3):282–291.
  • The cost of sequencing a human genome. Genome.gov [cited 2021 Nov 21]. Available from: https://www.genome.gov/about-genomics/fact-sheets/Sequencing-Human-Genome-cost
  • Johnson B, Lowe GC, Futterer J, et al. Whole exome sequencing identifies genetic variants in inherited thrombocytopenia with secondary qualitative function defects. Haematologica. 2016;101(10):1170–1179.
  • Johnson B, Doak R, Allsup D, et al. A comprehensive targeted next-generation sequencing panel for genetic diagnosis of patients with suspected inherited thrombocytopenia. Res Pract Thromb Haemost. 2018;2(4):640–652.
  • Andersson NG, Rossing M, Fager Ferrari M, et al. Genetic screening of children with suspected inherited bleeding disorders. Haemophilia. 2020;26(2):314–324.
  • Megy K, Downes K, Morel-Kopp MC, et al. GoldVariants, a resource for sharing rare genetic variants detected in bleeding, thrombotic, and platelet disorders: communication from the ISTH SSC Subcommittee on Genomics in Thrombosis and Hemostasis. J Thromb Haemost. 2021;19(10):2612–2617.
  • Pecci A, Ma X, Savoia A, et al. MYH9: Structure, functions and role of non-muscle myosin IIA in human disease. Gene. 2018;664:152–167.
  • Kosugi S, Momozawa Y, Liu X, et al. Comprehensive evaluation of structural variation detection algorithms for whole genome sequencing. Genome Biol. 2019;20(1):117.
  • 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.
  • Committee on Bioethics, Committee on Genetics, American College of Medical Genetics, et al. Ethical and policy issues in genetic testing and screening of children. Pediatrics. 2013;131(3):620–622.
  • Downes K, Borry P, Ericson K, et al. Clinical management, ethics and informed consent related to multi-gene panel-based high throughput sequencing testing for platelet disorders: communication from the SSC of the ISTH. J Thromb Haemost. 2020;18(10):2751–2758.
  • Greinacher A, Eekels JJM. Diagnosis of hereditary platelet disorders in the era of next-generation sequencing: “primum non nocere”. J Thromb Haemost. 2019;17(3):551–554.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.