1-Desamino-8-D-Arginine Vasopressin (DDAVP) Infusion in Type IIB von Willebrand’s Disease: Shortening of Bleeding Time and Induction of a Variable Pseudothrombocytopenia

Alessandra Casonato; M Teresa Sartori; Luigi de Marco; Antonio Girolami

doi:10.1055/s-0038-1647265

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1990; 64(01): 117-120
DOI: 10.1055/s-0038-1647265

Original Article

Schattauer GmbH Stuttgart

1-Desamino-8-D-Arginine Vasopressin (DDAVP) Infusion in Type IIB von Willebrand’s Disease: Shortening of Bleeding Time and Induction of a Variable Pseudothrombocytopenia

Alessandra Casonato

The University of Padua Medical School, Institute of Medical Semeiotics and Second Chair of Medicine, Padua, Italy

,

M Teresa Sartori

The University of Padua Medical School, Institute of Medical Semeiotics and Second Chair of Medicine, Padua, Italy

,

Luigi de Marco

^*The Centro di Riferimento Oncologico, USL 11, Aviano Pordenone, Italy

,

Antonio Girolami

The University of Padua Medical School, Institute of Medical Semeiotics and Second Chair of Medicine, Padua, Italy

› Author Affiliations

Abstract

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Summary

We have investigated the effects of 1-desamino-8-D-arginine vasopressin (DDAVP) infusion on platelet count and bleeding time in 4 patients with type IIB von Willebrand’s disease (vWd). Three of four patients showed a normalization of the bleeding time within 1 h after the infusion, while bleeding time was not modified in the fourth. In accordance with the literature, thrombocytopenia was observed after DDAVP infusion, but this thrombocytopenia was due to the anticoagulants used for blood collection. In two patients (F. I., G. F.) no thrombocytopenia was observed when platelets were counted by fingerstick method but there was a 20% platelet decrease in blood samples collected in sodium citrate and a 50% decrease in samples collected in EDTA. Dramatic falls in platelet counts (70–95%) were observed in the additional two patients (C. A., D.Z.) after DDAVP infusion, when both sodium citrate or EDTA were used as anticoagulants. In the latter two patients there was also a 50% decrease in platelet count when the fingerstick method was used. The decrease in the patient’s platelet count in EDTA samples after DDAVP infusion could be prevented, in part, by the previous additions of an anti GPIb monoclonal antibody and an anti GPIIb-IIIa monoclonal antibody.

Thus, the thrombocytopenia observed in the four IIB vWd patients studied after DDAVP infusion seems to be, at least partially, a pseudothrombocytopenia depending on the calcium concentration in the blood samples and the availability of GPIb and GPIIb-IIIa receptors. These findings and the normalization of the bleeding time observed in three of the four patients has led us to reconsider the possible use of DDAVP in the treatment of our IIB vWd patients.

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References

References
1 Ruggeri ZM, Pareti FI, Mannucci PM, Ciavarella N, Zimmerman TS. Heightened interaction between platelets and factor VUI/von Willebrand factor in a new subtype of von Willebrand’s disease. N Engl J Med 1980; 302: 1047-1051
2 Ruggeri ZM, Zimmerman TS. Variant von Willebrand’s disease: characterization of two subtypes by analysis of multimeric composition of factor VIH/von Willebrand factor in plasma and platelets. J Clin Invest 1980; 65: 1318-1325
3 Ruggeri ZM, Lombardi R, Gatti L, Bader R, Valsecchi C, Zimmerman TS. Type IIB von Willebrand’s disease: differential clearance of endogenous versus transfused large multimer von Willbrand factor. Blood 1982; 60: 1453-1456
4 De MarcoL, Mazzuccato M, Del Ben MG, Budde U, Federici AB, Girolami A, Ruggeri ZM. Type IIB von Willebrand factor with normal sialic acid content induces platelet aggregation in the absence of ristocetin. J Clin Invest 1987; 80: 475-482
5 Donner M, Holmberg L, Nilsson IM. Type IIB von Willebrand’s disease with probable autosomal recessive inheritance and presenting as thrombocytopenia in infancy. Br J Haematol 1987; 66: 349-354
6 Saba HI, Saba SR, Dent J, Ruggeri ZM, Zimmerman TS. Type IIB Tampa: A variant of von Willebrand disease with chronic thrombocytopenia, circulating platelet aggregates and spontaneous platelet aggregation. Blood 1985; 66: 282-286
7 Gralnick HR, Williams SB, McKeown LP, Rick ME, Maisonneuve P, Jenneau C, Sultan Y. Von Willebrand’s disease with spontaneous platelet aggregation induced by an abnormal plasma von Willebrand factor. J Clin Invest 1985; 76: 1522-1529
8 Gralnick HR, McKeown LP, Williams SB, van MourikJ. Platelet von Willebrand factor-induced spontaneous platelet aggregation in von Willebrand’s disease. Thromb Haemostas 1987; 58: 357 (Abstr 1296)
9 Gralnick HR, McKeown LP, Williams S, Jenneau C, Sultan Y, van MourickJ. Platelet aggregation induced by type IIB platelet von Willebrand factor. Br J Haematol 1989; 71: 253-258
10 Gralnick HR, Williams SB, McKeown LP, Rick ME, Maisonneuve JenneauC, Sultan Y. Von Willebrand’s disease with spontaneous platelet aggregation induced by an abnormal plasma von Willebrand factor. J Clin Invest 1985; 76: 1522-1529
11 Nilsson IM, Holmberg L, Aberg M, Vilhardt H. The release of plasminogen activator and factor VIII after injection of DDAVP in healthy volunteers and in patients with von Willebrand’s disease. Scand J Haematol 1980; 24: 351-359
12 Mannucci PM, Ruggeri ZM, Pareti FI, Capitanio A. 1-deamino-8-D-arginine vasopressin: a new pharmacological approach to the management of haemophilia and von Willebrand’s disease. Lancet 1977; i: 869-72
13 Holmberg L, Nilsson IM, Borge L, Gunnarsson M, Sjorin E. Platelet aggregation induced by l-desamino-8-D-arginine vasopressin (DDAVP) in type IIB von Willebrand’s disease. N Engl J Med 1983; 309: 816-21
14 Fabris F, Casonato A, Del Ben MG, De MarcoL, Girolami A. Abnormalities of von Willebrand factor in myeloproliferative disease: a relationship with bleeding diathesis. Br J Haematol 1986; 63: 75-83
15 Evy PL, Prowse SJ, Jenkins CR. Isolation of pure IgG 1, IgG 2a and IgG 2 b immunoglobulins from mouse serum using protein A-sephar-ose. Immunochemistry 1978; 15: 429-436
16 Handa M, Titani K, Holland LL, Roberts JR, Ruggeri ZM. The von Willebrand factor binding domain of platelet membrane glycoprotein Ib. Characterization by monoclonal antibodies and partial aminoacid sequence analysis of proteolytic fragment. J Biol Chem 1986; 261: 12579-12585
17 Niiya K, Hodson E, Bader R, Byers-Ward V, Koziol JA, Plow EF, Ruggeri ZM. Increased surface expression of the membrane glycoprotein GPIIb-IIIa complex induced by platelet activation. Relationship to the binding of fibrinogen and platelet aggregation. Blood 1987; 70: 475-483
18 Casonato A, Fabris F, Vicariotto M, Girolami A. The evaluation of factor VIII antigen by means of a simple slide test. Am J Clin Pathol 1985; 84: 107-111
19 Girolami A, Sticchi A, Barbui T, Bareggi G. Factor VIII immunological assay. An evaluation of several methods using whole plasma. Blut 1974; 29: 309-316
20 Girolami A, Molaro G, Lazzarin M, Scarpa R, Brunetti A. A new congenital haemorrhagic condition due to the presence of abnormal factor X (factor X Friuli): study of a large kindred. Br J Haematol 1970; 19: 179592
21 Miller JL, Kupinski JM, Castella A, Ruggeri ZM. Von Willebrand factor binds to platelets and induces platelet aggregation in platelet-type but not type IIB von Willebrand’s disease. J Clin Invest 1983; 72: 1532-1542
22 Ruggeri ZM, Mannucci PM, Federici AB, Lombardi R, Zimmerman TS. Multimeric composition of factor VIH/von Willebrand factor following administration of DDAVP: implications for pathophysiology and therapy of von Willebrand’s disease subtypes. Blood 1982; 59: 1272-1278
23 Kyrle PA, Niessner H, Dent J. Von Willebrand’s disease: pathogenic and therapeutic studies. Br J Haematol 1988; 69: 55-59
24 Fowler WE, Berkowitz LR, Roberts HR. DDAVP for type IIB von Willebrand’s disease. Blood 1989; 74: 1859
25 Ruggeri ZM, Zimmerman TS. Von Willebrand factor and von Willebrand disease. Blood 1987; 70: 895-904
26 De MarcoL, Girolami A, Zimmerman TS, Ruggeri ZM. Interaction of purified type IIB von Willebrand factor with the platelet membrane glycoprotein Ib induces fibrinogen binding to the glycoprotein IIb/ IIIa complex and initiates aggregation. Proc Natl Acad Sci 1985; 82: 7424-7428
27 Pidard D, Didry D, Kunicki T, Nurden A. Temperature-dependent effects of EDTA on the membrane glycoprotein IIb-IIIa complex and platelet aggregability. Blood 1986; 67: 604-611