2B or not to be – The 45-year saga of the Montreal Platelet Syndrome

Man-Chiu Poon; Margaret L. Rand; Shannon C. Jackson

doi:10.1160/TH10-01-0079

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2010; 104(05): 903-910
DOI: 10.1160/TH10-01-0079

Theme Issue Article

Schattauer GmbH

2B or not to be – The 45-year saga of the Montreal Platelet Syndrome

Man-Chiu Poon

¹Division of Hematology and Hematologic Malignancies, Department of Medicine, University of Calgary, Calgary, Alberta, Canada

,

Margaret L. Rand

²Division of Hematology/Oncology, The Hospital for Sick Children, and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada

,

Shannon C. Jackson

³Division of Hematology, Department of Medicine, St. Paul’s Hospital, University of British Columbia, Vancouver, British Columbia, Canada

› Author Affiliations

Abstract

Summary

Over 45 years ago, Montreal Platelet Syndrome was first described as a rare inherited platelet disorder characterised by macrothrombocytopenia with spontaneous platelet clumping, abnormal platelet shape change upon stimulation and a defect in platelet calpain. This syndrome has now been reclassified as type 2B von Willebrand disease with the V1316M VWF mutation in the only kindred ever reported. We herein revisit the historical platelet characteristics originally described in Montreal Platelet Syndrome in light of the new diagnosis. This paper will review the 45-year saga of Montreal Platelet Syndrome, a story that highlights the value of revisiting a rare diagnosis to look for a more common explanation.

Keywords

Von Willebrand factor - Von Willebrand disease - Platelet pathology / inherited and acquired - Thrombocytopenia - Inherited coagulation disorders

Full Text

References

References
1 Waldmann R, Abraham JP, Rebuck JW. et al. Fitzgerald factor: a hitherto unrecognized coagulation factor. Lancet 1975; 01: 949-951.
2 Saito H, Ratnoff OD, Waldmann R. et al. Deficiency of a hitherto unrecognized agent, Fitzgerald Factor, participating in surface-mediated reactions of clotting, fibrinolysis, generation of kinins, and the property of diluted plasma enhancing vascular permeability (PF/Dil). J Clin Invest 1975; 55: 1082-1089.
3 Movat HZ, Poon M-C, Takeuchi Y. The kinin-system of human plasma.#I. Isolation of a low molecular weight activator of prekallikrein. Int Arch Allergy Appl Immunol 1971; 40: 89-112.
4 Zimmerman TS, Ratnoff OD, Powell AE. Immunologic differentiation of classic hemophilia (factor VIII deficiency) and von Willebrand’s disease, with observations on combined deficencies of antihemophilic factor and proaccelerin (factor V) and on an acquired circulating anticoagulant against antihemophilic factor. J Clin Invest 1971; 50: 244-254.
5 Zimmerman TS, Ratnoff OD, Littell AS. Detection of carriers of classic hemophilia using an immunologic assay for antihemophilic factor (factor VIII). J Clin Invest 1971; 50: 255-258.
6 Weiss HJ, Phillips LL, Rosner W. Separation of sub-units of antihemophilic factor (AHF) by agarose gel chromatography. Thromb Diath Haemorrh 1972; 27: 212-219.
7 Owen WG, Wagner RH. Antihemophilic factor: separation of an active fragment following dissociation by salts or detergents. Thromb Diath Haemorrh 1972; 27: 502-515.
8 Zimmerman TS, Edgington TS. Factor VIII coagulant activity and factor VIII-like antigen: independent molecular entities. J Exp Med 1973; 138: 1015-1020.
9 Cooper HA, Griggs TR, Wagner RH. Factor VIII recombination after dissociation by CaCl2. Proc Natl Acad Sci USA 1973; 70: 2326-2329.
10 Ratnoff OD, Slover CC, Poon M-C. Immunologic evidence that the properties of human antihemophilic factor (factor VIII) are attributes of a single molecular species. Blood 1976; 47: 657-667.
11 Poon M-C, Ratnoff OD. Evidence that functional subunits of antihemophilic factor (Factor VIII) are linked by noncovalent bonds. Blood 1976; 48: 87-94.
12 Switzer ME, McKee PA. Studies on human antihemophilic factor. Evidence for a covalently linked subunit structure. J Clin Invest 1976; 57: 925-937.
13 Saito H, Donaldson V. A tribute to Dr. Oscar Ratnoff (1916–2008). J Thromb Haemost 2008; 06: 2004-2005.
14 Krever H. Royal Commission of Inquiry on the Blood System in Canada. (Transcript). July 11, 1995.
15 Davie EW, Ratnoff OD. Waterfall sequence for intrinsic blood clotting. Science 1964; 145: 1310-1312.
16 Cooney KA, Nichols WC, Bruck ME. et al. The molecular defect in type IIB von Willebrand disease: identification of four potential missense mutations within the putative GpIb binding domain. J Clin Invest 1991; 87: 1227-1233.
17 Federici AB, Mannucci PM, Castaman G. et al. Clinical and molecular predictors of thrombocytopenia and risk of bleeding in patients with von Willebrand disease type 2B: A cohort study of 67 patients. Blood 2009; 113: 526-534.
18 Jackson SC, Sinclair GD, Cloutier S. et al. The Montreal Platelet Syndrome kindred has type 2B von willebrand disease with the VWF V1316M mutation. Blood 2009; 113: 3348-3351.
19 Lacombe M, D’Angelo G. Etudes sur une thrombopathie familiale. Nouv Rev Fr Hematol 1963; 03: 611-614.
20 Milton JG, Frojmovic MM. Shape-changing agents produce abnormally large platelets in a hereditary “giant platelets syndrome (MPS)”. J Lab Clin Med 1979; 91: 154-161.
21 Frojmovic MM, Milton JG. Physical, chemical and functional changes following platelet activation in normal and “giant” platelets. Blood Cells 1983; 09: 359-382.
22 Frojmovic MM, Milton JG, Caen JP, Tobelem G. Platelets from “giant platelet syndrome (BSS)” are discocytes and normal-sized. J Lab Clin Med 1978; 91: 109-116.
23 Milton JG, Hutton RA, Tuddenham EGD. et al. Platelet size and shape in hereditary giant platelet syndromes on blood smear and in suspension: evidence for two types of abnormalities. J Lab Clin Med 1985; 106: 326-335.
24 Milton JG, Frojmovic MM, Tang SS. et al. Spontaneous platelet aggregation in a Hereditary Giant Platelet Syndrome (MPS). Am J Pathol 1984; 114: 336-345.
25 Italian Working Group.. Spectrum of von Willebrand’s Disease: a study of 100 cases. Br J Haematol 1976; 35: 101-112.
26 Ruggeri ZM, Pareti FI, Mannucci PM. et al. Heightened interaction between platelets and factor VIII/von Willebrand factor in a new subtype of von Willebrand’s disease. New Engl J Med 1980; 302: 1047-1051.
27 Takahashi H, Sakuragawa N, Shibata A. Von Willebrand disease with an increased ristocetin-induced platelet aggregation and a qualitative abnormality of the factor VIII protein. Am J Hematol 1980; 08: 299-301.
28 Takahashi H, Nagayama R, Hattori A. et al. von Willebrand disease associated with familial thrombocytopenia and increased ristocetin-induced platelet aggregation. Am J Hematol 1981; 10: 89-99.
29 Gralnick HR, Williams SB, Shafer BC. et al. Factor VIII/von Willebrand factor binding to von Willebrand’s disease platelets. Blood 1982; 60: 328-332.
30 Weiss HJ, Meyer D, Rabinowitz I. et al. Pseudo-von Willebrand’s disease. An intrinsic platelet defect with aggregation by unmodified human factor VIII von Willebrand factor and enhanced adsorption of its high-molecular-weight multimers. New Engl J Med 1982; 306: 326-333.
31 Miller JL, Castella A. Platelet-type von Willebrand’s disease: characterization of a new bleeding disorder. Blood 1982; 60: 790-794.
32 Okita JR, Frojmovic MM, Kristopeit S. et al. Montreal Platelet Syndrome: A defect in calpain-activated neutral proteinase (Calpain). Blood 1989; 74: 715-721.
33 Sadler JE, Budde U, Eikenboom JCJ. et al. Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor. J Thromb Haemost 2006; 04: 2103-2114.
34 De Marco L, Girolami A, Zimmerman TS. et al. Interaction of purified type IIb von willebrand factor with the platelet membrane glycoprotein Ib induced fibrinogen binding to the glycoprotein IIbIIIa complex and initiates aggregation. Proc Natl Acad Sci USA 1985; 82: 7424-7428.
35 De Marco L, Mazzucato M, Del Ben MG. et al. Type IIb von willebrand factor with normal sialic acid content induces platelet aggregation in the absence of ristocetin. Role of platelet activation, fibrinogen and two distinct membrane receptors. J Clin Invest 1987; 80: 475-482.
36 Ruggeri ZM, Zimmerman TS. Variant von Willebrand’s disease: Characterization of two subtypes by analysis of multimeric composition of factor VIII/von Wille-brand factor in plasma and platelets. J Clin Invest 1980; 65: 1318-1325.
37 Gralnick HR, Williams SB, McKeown LP. et al. von Willebrand’s disease with spontaneous platelet aggregation induced by an abnormal plasma von Wille-brand factor. J Clin Invest 1985; 76: 1522-1529.
38 Saba HI, Saba SR, Dent JA. et al. Type IIB Tampa: A variant of von Willebrand disease with chronic thrombocytopenia, circulating platelet aggregates, and spontaneous platelet aggregation. Blood 1985; 66: 282-286.
39 Lopez-Fernandez MF, Lopez-Berges C, Martin-Bernal JA. et al. Type IIB von Willebrand’s disease associated with a complex thrombocytopenic thrombocytopathy. Am J Hematol 1988; 27: 291-298.
40 Gralnick HR, McKeown LP, Williams S. et al. Platelet aggregation induced by type IIb platelet von Willebrand factor. Br J Haematol 1989; 71: 253-258.
41 Nurden A, Dupuis D, Kunicki TJ. et al. Analysis of the glycoprotein and protein composition of Bernard-Soulier platelets by single and two dimensional sodium dodecyl-sulfate polyacrylamide gel electrophoresis. J Clin Invest 1981; 67: 1431-1440.
42 Nurden P, Nurden A. Giant platelets, megakaryocytes and the expression of glyco-protein Ib-IX complexes. Comptes Rendus de l‘Académie Des Sciences, Paris 1996; 319: 717-726.
43 Nurden P, Chretien F, Poujol C. et al. Platelet ultrastructural abnormalities in three patients with type 2B von Willebrand disease. Br J Haematol 2000; 110: 704-714.
44 Nurden P. The VWD2B saga continues to Montreal. Blood 2009; 113: 3134-3135.
45 Nurden P, Debili N, Vainchenker W. et al. Impaired megakaryocytopoiesis in type 2B von Willebrand disease with severe thrombocytopenia. Blood 2006; 108: 2587-2595.
46 Nurden P, Gobbi G, Nurden A. et al. Abnormal VWF modifies megakaryocytopoiesis: studies of platelets and megakaryocyte cultures from patients with von Willebrand disease type 2B. Blood 2010; 115: 2649-2656.
47 Nurden P, Nurden A, La Marca S. et al. Platelet morphological changes in 2 patients with von Willebrand disease type 3 caused by large homozygous deletions of the von Willebrand factor gene. Haematologica 2009; 94: 1627-1629.
48 Mekrache M, Bachelot-Loza C, Ajzenberg N. et al. Activation of pp125FAK by type 2B recombinant von Willebrand factor binding to platelet GPIb at a high shear rate occurs independently of αIIbβ3 engagement. Blood 2003; 101: 4363-4371.
49 Meyer D, Girma JP. von Willebrand factor, structure and function. Thromb Haemost 1993; 70: 99-104.
50 Siedlecki CA, Lestini BJ, Kottke-Marchant K. et al. Shear-dependent changes in the three-dimensional structure of human von Willebrand factor. Blood 1996; 88: 2939-2950.
51 Celikel R, Ruggeri ZM, Varughese KI. Von Willebrand factor conformation and adhesive function is modulated by an internalized water molecule. Nature Structural Biol 2000; 07: 881-884.
52 Huizinga EG, Tsuji S, Romijn RAP. et al. Structures of glycoprotein Ibα and its complex with von Willebrand factor A1 domain. Science 2002; 297: 1176-1179.
53 Azam M, Andrabi SS, Sahr KE. et al. Disruption of the mouse u-calpain gene reveals an essential role in platelet function. Mol Cell Biol 2001; 21: 2213-2220.
54 Loffredo G, Baronciani L, Noris P. et al. von Willebrand disease type 2B must always be considered in the differential diagnosis of genetic thrombocytopenia with giant platelets. Platelets 2006; 17: 149-152.
55 Favalaro EJ. von Willebrand disease, type 2B: A diagnosis more elusive than previously thought. Thromb Haemost 2008; 99: 630-631.
56 De Harven E, Leung R, Christensen H. A novel approach for scanning electron microscopy of colloidal gold-labelled cell surfaces. J Cell Biol 1984; 99: 53-57.