Hamostaseologie 2016; 36(04): 265-278
DOI: 10.5482/HAMO-16-02-0002
Review
Schattauer GmbH

Inherited platelet function disorders

Diagnostic approach and managementAngeborene PlättchenfunktionsstörungenDiagnostik und Management
Paolo Gresele
1   Division of Internal and Cardiovascular Medicine, Department of Medicine, University of Perugia, Italy
,
Emanuela Falcinelli
1   Division of Internal and Cardiovascular Medicine, Department of Medicine, University of Perugia, Italy
,
Loredana Bury
1   Division of Internal and Cardiovascular Medicine, Department of Medicine, University of Perugia, Italy
› Author Affiliations
Further Information

Publication History

Received 08 February 2016

Accepted in revised form: 16 July 2016

Publication Date:
18 December 2017 (online)

Summary

Inherited platelet function disorders (IPFDs) make up a significant proportion of congenital bleeding diatheses, but they remain poorly understood and often difficult to diagnose. Therefore, a rational diagnostic approach, based on a standardized sequence of laboratory tests, with consecutive steps of increasing level of complexity, plays a crucial role in the diagnosis of most IPFDs.

In this review we discuss a diagnostic approach through platelet phenotyping and genotyping and we give an overview of the options for the management of bleeding in these disorders and an account of the few systematic studies on the bleeding risk associated with invasive procedures and its treatment.

Zusammenfassung

Angeborene Plättchenfunktionsstörungen (IPFD) machen einen Großteil der kongenitalen Gerinnungsstörungen aus, sie werden aber nach wie vor kaum verstanden und sind oft schwierig zu diagnostizieren. Daher spielt ein rationales diagnostisches Vorgehen, basierend auf einer standardisierten Abfolge von Labor-untersuchungen mit konsekutiven, immer komplexer werdenden Schritten, eine zentrale Rolle bei der Diagnose der meisten IPFD.

In dieser Übersicht diskutieren wir einen diagnostischen Ansatz mit Phäno- und Geno-typisierung der Plättchen, geben einen Überblick über Möglichkeiten, wie Blutungen bei diesen Erkrankungen zu managen sind, und berichten über die wenigen systematischen Studien zum Blutungsrisiko in Zusammenhang mit invasiven Maßnahmen sowie deren Behandlung.

 
  • References

  • 1 Israels SJ, Kahr WH, Blanchette VS. et al. Platelet disorders in children: A diagnostic approach. Pediatr Blood Cancer 2011; 56: 975-983.
  • 2 Srivastava A, Rodeghiero F. Epidemiology of von Willebrand disease in developing countries. Semin Thromb Hemost 2005; 31: 569-576.
  • 3 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: 357-365.
  • 4 Sánchez-Guiu I, Torregrosa JM, Velasco F. et al. Hermansky-Pudlak syndrome. Overview of clinical and molecular features and case report of a new HPS-1 variant. Hamostaseologie 2014; 34: 301-309.
  • 5 Gresele P, Harrison P, Bury L. et al. Diagnosis of inherited platelet function disorders: results of a worldwide survey. J Thromb Haemost 2014; 12: 1562-1569.
  • 6 Gresele P. Subcommittee on Platelet Physiology.. Diagnosis of inherited platelet function disorders: guidance from the SSC of the ISTH. J Thromb Haemost 2015; 13: 314-322.
  • 7 Streif W, Oliveri M, Weickardt S. et al. Thromkid Study Group of GTH. Testing for inherited platelet defects in clinical laboratories in Germany, Austria and Switzerland. Results of a survey carried out by the Permanent Paediatric Group of the German Thrombosis and Hemostasis Research Society (GTH). Platelets 2010; 21: 470-478.
  • 8 Hayward CP, Moffat KA, Plumhoff E, Van Cott EM. Approaches to investigating common bleeding disorders: an evaluation of North American coagulation laboratory practices. Am J Hematol 2012; 87: S45-S50.
  • 9 Bolton-Maggs PH, Chalmers EA, Collins PW. et al. UKHCDO. A review of inherited platelet disorders with guidelines for their management on behalf of the UKHCDO. Br J Haematol 2006; 135: 603-633.
  • 10 Harrison P, Mackie I, Mumford A. et al. British Committee for Standards in Haematology. Guidelines for the laboratory investigation of heritable disorders of platelet function. Br J Haematol 2011; 155: 30-44.
  • 11 Watson S, Daly M, Dawood B. et al. Phenotypic approaches to gene mapping in platelet function disorders – identification of new variant of P2Y12, TxA2 and GPVI receptors. Hämostaseologie 2010; 30: 29-38.
  • 12 Hayward CP, 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: 955-963.
  • 13 Gresele P, Bury L, Falcinelli E. Inherited Platelet Function Disorders: algorithms for Phenotypic and Genetic Investigation. Semin Thromb Hemost 2016; 42: 292-305.
  • 14 Rodeghiero F, Tosetto A, Abshire T. et al. ISTH/ SSC joint VWF and Perinatal/Pediatric Hemostasis Subcommittees Working Group. 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: 2063-2065.
  • 15 Federici AB, Bucciarelli P, Castaman G. et al. The bleeding score predicts clinical outcomes and replacement therapy in adults with von Willebrand disease. Blood 2014; 123: 4037-4044.
  • 16 Bidlingmaier C, Grote V, Budde U. et al. Prospective evaluation of a pediatric bleeding questionnaire and the ISTH bleeding assessment tool in children and parents in routine clinical practice. J Thromb Haemost 2012; 10: 1335-1341.
  • 17 Lowe GC, Lordkipanidzé M, Watson SP. UK GAPP study group.. Utility of the ISTH bleeding assessment tool in predicting platelet defects in participants with suspected inherited platelet function disorders. J Thromb Haemost 2013; 11: 1663-1668.
  • 18 Biss TT, Blanchette VS, Clark DS. et al. Use of a quantitative pediatric bleeding questionnaire to assess mucocutaneous bleeding symptoms in children with a platelet function disorder. J Thromb Haemost 2010; 8: 1416-1419.
  • 19 Elbatarny M, Mollah S, Grabell J. et al. Normal range of bleeding scores for the ISTH-BAT: adult and pediatric data from the merging project. Haemophilia 2014; 20: 831-835.
  • 20 Noris P, Schlegel N, Klersy C. et al. European Hematology Association – Scientific Working Group on Thrombocytopenias and Platelet Function Disorders. Platelet size for distinguishing between inherited thrombocytopenias and immune thrombocytopenia: a multicentric, real life study. Br J Haematol 2013; 162: 112-119.
  • 21 Pecci A, Biino G, Fierro T. et al. Italian Registry for MYH9-releated diseases. Platelet diameters in inherited thrombocytopenias: analysis of 376 patients with all known disorders. Blood 2014; 124: e4-e10.
  • 22 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: 892-898.
  • 23 Hayward CP, Harrison P, Cattaneo M. et al. Platelet Physiology Subcommittee of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Platelet function analyzer (PFA)-100 closure time in the evaluation of platelet disorders and platelet function. J Thromb Haemost 2006; 4: 312-319.
  • 24 Rubak P, Nissen PH, Kristensen SD, Hvas AM. Investigation of platelet function and platelet disorders using flow cytometry. Platelets 2016; 27: 66-74.
  • 25 Lordkipanidzé M, Lowe GC, Kirkby NS. et al. UK Genotyping and Phenotyping of Platelets Study Group. Characterization of multiple platelet activation pathways in patients with bleeding as a high-throughput screening option: use of 96-well Optimul assay. Blood 2014; 123: e11-e22.
  • 26 De Witt SM, Swieringa F, Cavill R. et al. Identification of platelet function defects by multi-parameter assessment of thrombus formation. Nat Commun 2014; 5: 4257.
  • 27 Dawood BB, Lowe GC, Lordkipanidzé M. et al. Evaluation of participants with suspected heritable platelet function disorders including recommendation and validation of a streamlined agonist panel. Blood 2012; 120: 5041-5049.
  • 28 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: 1183-1189.
  • 29 Lin TM, Lin JS, Tseng JY. et al. Impaired responsiveness of platelets to epinephrine due to 2A adrenoreceptor deficiency in Male Chinese. Platelets 2015; 19: 1-6.
  • 30 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: 350-358.
  • 31 Mumford AD, Frelinger 3rd AL, Gachet C. et al. A review of platelet secretion assays for the diagnosis of inherited platelet secretion disorders. Thromb Haemost 2015; 114: 14-25.
  • 32 Shattil SJ, Hoxie JA, Cunningham M, Brass LF. Changes in the platelet membrane glycoprotein IIb.IIIa complex during platelet activation. J Biol Chem 1985; 260: 11107-11114.
  • 33 Giannini S, Cecchetti L, Mezzasoma AM, Gresele P. Diagnosis of platelet-type von Willebrand disease by flow cytometry. Haematologica 2010; 95: 1021-1024.
  • 34 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 doi: 10.1111/bjh.13391.
  • 35 Daskalakis M, Colucci G, Keller P. et al. Decreased generation of procoagulant platelets detected by flow cytometric analysis in patients with bleeding diathesis. Cytometry B Clin Cytom 2014; 86: 397-409.
  • 36 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: 380-385.
  • 37 Villeneuve J, Block A, Le Bousse-Kerdilès MC. et al. Tissue inhibitors of matrix metalloproteinases in platelets and megakaryocytes: a novel organization for these secreted proteins. Exp Hematol 2009; 37: 849-856.
  • 38 De Candia E, Pecci A, Ciabattoni G. et al. Defective platelet responsiveness to thrombin and protease-activated receptors agonists in a novel case of gray platelet syndrome: correlation between the platelet defect and the alpha-granule content in the patient and four relatives. J Thromb Haemost 2007; 5: 551-559.
  • 39 Clauser S, Cramer-Borde E. Role of platelet electron microscopy in the diagnosis of platelet disorders. Semin Thromb Hemost 2009; 35: 213-223.
  • 40 Simeoni I, Stephens JC, Hu F. et al. A comprehensive high-throughput sequencing test for the diagnosis of inherited bleeding, thrombotic and platelet disorders. Blood 2016; 127: 2791-2803.
  • 41 Albers CA, Cvejic A, Favier R. et al. Exome sequencing identifies NBEAL2 as the causative gene for gray platelet syndrome. Nature Genetics 2011; 43: 735-737.
  • 42 Gunay-Aygun M, Falik-Zaccai TC, Vilboux T. et al. NBEAL2 is mutated in gray platelet syndrome and is required for biogenesis of platelet alpha-granules. Nature Genetics 2011; 43: 732-734.
  • 43 Kahr WH, Hinckley J, Li L. et al. Mutations in NBEAL2, encoding a BEACH protein, cause gray platelet syndrome. Nature Genetics 2011; 43: 738-740.
  • 44 Stevenson WS, Morel-Kopp MC, Chen Q. et al. GFI1B mutation causes a bleeding disorder with abnormal platelet function. J Thromb Haemost 2013; 11: 2039-2047.
  • 45 Monteferrario D, Bolar NA, Marneth AE. et al. A dominant-negative GFI1B mutation in the gray platelet syndrome. N Engl J Med 2014; 370: 245-253.
  • 46 Kunishima S, Okuno Y, Yoshida K. et al. ACTN1 mutations cause congenital macrothrombocytopenia. Am J Hum Genet 2013; 92: 431-438.
  • 47 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: 4197-4202.
  • 48 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: 474-482.
  • 49 Fletcher SJ, Johnson B, Lowe GC. et al. UK Geno-typing and Phenotyping of Platelets study group. SLFN14 mutations underlie thrombocytopenia with excessive bleeding and platelet secretion defects. J Clin Invest 2015; 125: 3600-3605.
  • 50 Buitrago L, Rendon A, Liang Y. et al. ThromboGenomics Consortium, Filizola M, Ouwehand WH, Coller BS. IIb 3 variants defined by next-generation sequencing: predicting variants likely to cause Glanzmann thrombasthenia. Proc Natl Acad Sci USA 2015; 112: E1898-E1907.
  • 51 Miller JL, Lyle VA, Cunningham D. Mutation of leucine-57 to phenylalanine in a platelet glycoprotein Ib alpha leucine tandem repeat occurring in patients with an autosomal dominant variant of Bernard-Soulier disease. Blood 1992; 79: 439-446.
  • 52 Savoia A, Balduini CL, Savino M. et al. Autosomal dominant macrothrombocytopenia in Italy is most frequently a type of heterozygous Bernard-Soulier syndrome. Blood 2001; 97: 1330-1335.
  • 53 Othman M. Platelet-type von Willebrand disease: three decades in the life of a rare bleeding disorder. Blood Rev 2011; 25: 147-153.
  • 54 Othman M, Kaur H, Favaloro EJ. et al. for the Subcommittees on von Willebrand Disease and Platelet Physiology. Platelet type von Willebrand disease and registry report: communication from the SSC of the ISTH. J Thromb Haemost 2016; 14: 411-414.
  • 55 Nurden AT, Fiore M, Nurden P, Pillois X. Glanz-mann thrombasthenia: a review of ITGA2B and ITGB3 defects with emphasis on variants, phenotypic variability, and mouse models. Blood 2011; 118: 5996-6005.
  • 56 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: 46-56.
  • 57 Hermans C, Wittevrongel C, Thys C. et al. A compound heterozygous mutation in glycoprotein VI in a patient with a bleeding disorder. J Thromb Haemost 2009; 7: 1356-1363.
  • 58 Noris P, Guidetti GF, Conti V. et al. Autosomal dominant thrombocytopenias with reduced expression of glycoprotein Ia. Thromb Haemost 2006; 95: 483-489.
  • 59 Matus V, Valenzuela G, Sáez CG. et al. An adenine insertion in exon 6 of human GP6 generates a truncated protein associated with a bleeding disorder in four Chilean families. J Thromb Haemost 2013; 11: 1751-1759.
  • 60 Diaz-Ricart M, Tandon NN, Carretero M. et al. Platelets lacking functional CD36 (glycoprotein IV) show reduced adhesion to collagen in flowing whole blood. Blood 1993; 82: 491-496.
  • 61 Yamamoto N, Ikeda H, Tandon NN, Herman J, Tomiyama Y, Mitani T, Sekiguchi S. et al. A platelet membrane glycoprotein (GP) deficiency in healthy blood donors: Naka- platelets lack detectable GPIV (CD36). Blood 1990; 76: 1698-1703.
  • 62 Cattaneo M. The platelet P2Y[one.inferior][two.inferior] receptor for adenosine diphosphate: congenital and drug-induced defects. Blood 2011; 117: 2102-2112.
  • 63 Cattaneo M, Zighetti ML, Lombardi R. et al. Molecular bases of defective signal transduction in the platelet P2Y12 receptor of a patient with congenital bleeding. Proc Natl Acad Sci USA 2003; 100: 1978-1983.
  • 64 Cattaneo M, Lecchi A, Lombardi R. et al. 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 舘primary secretion defect’ are heterozygous for a defect of P2CYC receptors. Arterioscler Thromb Vasc Biol 2000; 20: E101-E106.
  • 65 Zighetti ML, Carpani G, Sinigaglia E, Cattaneo M. Usefulness of a flow cytometric analysis of intra-platelet vasodilator-stimulated phosphoprotein phosphorylation for the detection of patients with genetic defects of the platelet P2Y12 receptor for ADP. J Thromb Haemost 2010; 8: 2332-2334.
  • 66 Ushikubi F, Okuma M, Kanaji K. et al. Hemorrhagic thrombocytopathy with platelet thromboxane A2 receptor abnormality: defective signal transduction with normal binding activity. Thromb Haemost 1987; 57: 158-164.
  • 67 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: 1662-1667.
  • 68 Rao AK, Willis J, Kowalska MA. et al. Differential requirements for epinephrine induced platelet aggregation and inhibition of adenylate cyclase. Studies in familial a2-adrenergic receptor defect. Blood 1988; 71: 494-501.
  • 69 Tamponi G, Pannocchia A, Arduino C. et al. Congenital deficiency of a-2-adrenoreceptors on human platelets: description of two cases. Thromb Haemost 1987; 58: 1012-1016.
  • 70 Morrissey JH, Choi SH, Smith SA. Polyphosphate: an ancient molecule that links platelets, coagulation, and inflammation. Blood 2012; 119: 5972-5979.
  • 71 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: 1097-1103.
  • 72 http://liweilab.genetics.ac.cn/hpsd
  • 73 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.
  • 74 Aminkeng F. GFI1B mutation causes autosomal dominant gray platelet syndrome. Clin Genet 2014; 85: 534-535.
  • 75 Nurden AT, Nurden P. The gray platelet syndrome: clinical spectrum of the disease. Blood Rev 2007; 21: 21-36.
  • 76 Hayward CP, Rivard GE, Kane WH. et al. An auto-somal dominant, qualitative platelet disorder associated with multimerin deficiency, abnormalities in platelet factor V, thrombospondin, von Willebrand factor, and fibrinogen and an epinephrine aggregation defect. Blood 1996; 87: 4967-4978.
  • 77 Diamandis M, Paterson AD, Rommens JM. et al. Quebec platelet disorder is linked to the urokinase plasminogen activator gene (PLAU) and increases expression of the linked allele in megakaryocytes. Blood 2009; 113: 1543-1546.
  • 78 Kim SM, Chang HK, Song JW. et al. Severance Pediatric Liver Disease Research Group. Agranular platelets as a cardinal feature of ARC syndrome. J Pediatr Hematol Oncol 2010; 32: 253-258.
  • 79 White JG, Keel S, Reyes M, Burris SM. Alpha-delta platelet storage pool deficiency in three generations. Platelets 2007; 18: 1-10.
  • 80 Rao AK, Jalagadugula G, Sun L. Inherited defects in platelet signaling mechanisms. Semin Thromb Hemost 2004; 30: 525-535.
  • 81 Zwaal RF, Comfurius P, Bevers EM. Scott syndrome, a bleeding disorder caused by defective scrambling of membrane phospholipids. Biochim Biophys Acta 2004; 1636: 119-128.
  • 82 Stormorken H, Holmsen H, Sund R. et al. Studies on the haemostatic defect in a complicated syndrome. An inverse Scott syndrome platelet membrane abnormality? Thromb Haemost 1995; 74: 1244-1251.
  • 83 Solum NO. Procoagulant expression in platelets and defects leading to clinical disorders. Arterioscler Thromb Vasc Biol 1999; 19: 2841-2846.
  • 84 Nichols KE, Crispino JD, Poncz M. et al. Familial dyserythropoietic anaemia and thrombocytopenia due to an inherited mutation in GATA1. Nat Genet 2000; 24: 266-270.
  • 85 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: 166-175.
  • 86 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: 1805-1814.
  • 87 Stockley J, Morgan NV, Bem D. et al. UK Genotyping and Phenotyping of Platelets Study Group. Enrichment of FLI1 and RUNX1 mutations in families with excessive bleeding and platelet dense granule secretion defects. Blood 2013; 122: 4090-4093.
  • 88 Berrou E, Adam F, Lebret M. et al. Heterogeneity of platelet functional alterations in patients with filamin A mutations. Arterioscler Thromb Vasc Biol 2013; 33: e11-e18.
  • 89 http://structure.bmc.lu.se/idbase/WASbase
  • 90 Shcherbina A, Cooley J, Lutskiy MI. et al. WASP plays a novel role in regulating platelet responses dependent on alphaIIbbeta3 integrin outside-in signaling. Br J Haematol 2010; 148: 416-427.
  • 91 Noris P, Biino G, Pecci A. et al. Platelet diameters in inherited thrombocytopenias: analysis of 376 patients with all known disorders. Blood 2014; 124: e4-e10.
  • 92 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: 1285-1292.
  • 93 Marconi C, Di Buduo CA, Barozzi S. et al. SLFN14-related thrombocytopenia: identification within a large series of patients with inherited thrombocytopenia. Thromb Haemost 2016; 115: 1076-1079.
  • 94 Makris M, Conlon CP, Watson HG. Immunization of patients with bleeding disorders. Haemophilia 2003; 9: 541-546.
  • 95 Alamelu J, Liesner R. Modern management of severe platelet function disorders. Br J Haematol 2010; 149: 813-23.
  • 96 Sogut O, Erdogan MO, Kose R. et al. Hemostatic efficacy of a traditional medicinal plant extract (Ankaferd Blood Stopper) in bleeding control. Clin Appl Thromb Hemost 2015; 21: 348-353.
  • 97 Nurden P, Youlouz-Marfak I, Siberchicot F. et al. Use of autologous platelet-rich clots for the prevention of local injury bleeding in patients with severe inherited mucocutaneous bleeding disorders. Haemophilia 2011; 17: 620-624.
  • 98 Coppola A, Di Minno G. Desmopressin in inherited disorders of platelet function. Haemophilia 2008; 14 (Suppl. 01) 31-39.
  • 99 Kumar S, Randhawa MS, Ganesamoni R, Singh SK. Tranexamic acid reduces blood loss during percutaneous nephrolithotomy: a prospective randomized controlled study. J Urol 2013; 189: 1757-1761.
  • 100 Vujkovac B, Sabovic M. A successful treatment of life-threatening bleeding from polycystic kidneys with antifibrinolytic agent tranexamic acid. Blood Coagul Fibrinolysis 2006; 17: 589-591.
  • 101 Mannucci PM, Ruggeri ZM, Pareti FI, Capitanio A. DDAVP: a new pharmacological approach to the management of hemophilia and von Wille-brand disease. Lancet 1977; 1: 869-872.
  • 102 Cattaneo M, Pareti FI, Zighetti ML. et al. Platelet aggregation at high shear is impaired in patients with congenital defects of platelet secretion and is corrected by DDAVP: correlation with bleeding time. J Lab Clin Med 1995; 125: 540-547.
  • 103 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: 1905-1916.
  • 104 Rao AK, Ghosh S, Sun L. et al. Mechanisms of platelet dysfunction and response to DDAVP in patients with congenital platelet function defects. Thromb Haemost 1995; 74: 1071-1078.
  • 105 Schulman S, Johmsson H, Egberg N, Blomback M. DDAVP-induced correction of prolonged bleeding time in patients with congenital platelet function defects. Thromb Res 1987; 45: 165-174.
  • 106 Di Michele DM, Hathaway WE. Use of DDAVP in inherited and acquired platelet dysfunction. Am J Hematol 1990; 33: 39-45.
  • 107 Lisman T, De Groot PG. Mechanism of action of recombinant factor VIIa. J Thromb Haemost 2003; 1: 1138-1139.
  • 108 Poon MC. The evidence for the use of recombinant human activated factor VII in the treatment of bleeding patients with quantitative and qualitative platelet disorders. Transfus Med Rev 2007; 21: 223-236.
  • 109 Franchini M. The use of recombinant activated factor VII in the treatment of bleeding patients with quantitative and qualitative platelet disorders. Transfus Med Rev 2007; 21: 223-236.
  • 110 Levi M, Levy JH, Andersen HF, Truloff D. Safety of recombinant activated factor VII in randomized clinical trials. N Engl J Med 2010; 363: 1791-1800.
  • 111 Demers C, Derzko C, David M, Douglas J. Gynaecological and obstetric management of women with inherited bleeding disorders. Int J Gynaecol Obstet 2006; 95: 75-87.
  • 112 Seligsohn U. Treatment of inherited platelet disorders. Haemophilia 2012; 18 (Suppl. 04) 161-165.
  • 113 Nurden AT, Pillois X, Wilcox DA. Glanzmann thrombasthenia: state of the art and future directions. Semin Thromb Hemost 2013; 39: 642-655.
  • 114 Locatelli F, Rossi G, Balduini CL. Hematopoietic stem-cell transplantation for the Bernard–Soulier syndrome. Ann Intern Med 2003; 138: 79.
  • 115 Rieger C, Rank A, Fiegl M. et al. Allogeneic stem cell transplantation as a new treatment for patients with severe Bernard–Soulier syndrome. Thromb Haemost 2006; 95: 190-191.
  • 116 Wilcox DA, White GC. Gene therapy for platelet disorders: studies with Glanzmann’s thrombasthenia. J Thromb Haemost 2003; 1: 2300-2311.
  • 117 Fang J, Hodivala-Dilke K, Johnson BD. et al. Therapeutic expression of the platelet-specific integrin, alphaIIb-beta3, in a murine model for Glanzmann thrombasthenia. Blood 2005; 106: 2671-2679.
  • 118 Kanaji S, Kuether EL, Fahs SA. et al. Correction of murine Bernard-Soulier syndrome by lentivirus-mediated gene therapy. Mol Ther 2012; 20: 625-632.
  • 119 Hacein-Bey Abina S, Gaspar HB, Blondeau J. et al. Outcomes following gene therapy in patients with severe Wiskott-Aldrich syndrome. JAMA 2015; 313: 1550-1563.
  • 120 Prabu P, Parapia LA. Bernard–Soulier syndrome in pregnancy. Clin Lab Haemat 2006; 28: 198-201.
  • 121 Civaschi E, Klersy C, Melazzini F. et al. Analysis of 65 pregnancies in 34 women with 5 different forms of inherited platelet function disorders. Br J Haematol 2015; 170: 559-563.
  • 122 Noris P, Schlegel N, Klersy C. et al. Analysis of 339 pregnancies in 181 women with 13 different forms of inherited thrombocytopenia. Haematologica 2014; 99: 1387-1394.
  • 123 Poon MC, d’Oiron R, Zotz RB. et al. Glanzmann Thrombasthenia Registry Investigators. The international, prospective Glanzmann Thrombasthenia Registry: treatment and outcomes in surgical intervention. Haematologica 2015; 100: 1038-1044.
  • 124 Gresele P, Noris P, Orsini S. et al. Bleeding risk of surgery in patients with inherited platelet function disorders (IPFD): outcome of 389 surgeries in 205 patients. Hematologica 2015; 100 s1 186.