Abnormal Structure of von Willebrand Factor in Myeloproliferative Syndrome Is Associated to Either Thrombotic or Bleeding Diathesis

Summary

The multimeric and subunit patterns of plasma von Willebrand factor (vWF) were analyzed in eight patients with myeloproliferative syndrome (MS) in order to investigate the possible existence of heterogeneity in the “in vivo” proteolytic cleavage of the protein, previously observed in this entity. Six patients lacked large vWF multimers, five of them having normal bleeding times (BT) and clinically documented episodes of thrombotic origin, whereas one patient had long BT and bleeding symptoms. Seven patients showed a relative increase in the 176 kDa subunit fragment while the 189 kDa polypeptide was increased in only one. In addition, another patient (and prior to any therapy) showed the presence of a new fragment of approximately 95 kDa which disappeared after Busulfan therapy. The collection of blood from these patients with proteinase inhibitors did not correct the abnormalities.

The infusion of DDAVP to two patients with abnormal vWF was accompanied by: the appearance of larger vWF multimers which disappeared rapidly from plasma; an increase in the relative proportion of the satellite bands of each multimer and a further increase of the 176 kDa fragment. These data point to some heterogeneity in the vWF abnormality present in MS which may be related in part to a variable degree of proteolysis of vWF occurring “in vivo” rather than “in vitro”, and which may be associated to either a thrombotic or a bleeding diathesis. They also suggest that despite the presence of abnormal, already proteolyzed vWF, DDAVP-enhanced proteolysis occurs in MS to a similar extent to what is described in normal individuals.

Keywords

von Willebrand factor - Myeloproliferative syndrome -DDAVP - Desmopressin

• References

• 1 Budde V, Shaefer G, Mueller N, Egli H, Dent J, Ruggeri ZM, Zimmerman TS. sAcquired von Willebrand’s disease in the myeloproliferative syndrome. Blood 1984; 64: 981-985
• 2 Fabris F, Casonato A, Del Ben MG, De Marco L, Girolami A. Abnormalities of von Willebrand factor in myeloproliferative disease: a relationship with bleeding diathesis. Br J Haematol 1986; 63: 75-83
• 3 Zimmerman TS, Dent J, Ruggeri ZM, Nannini LH. Subunit composition of plasma von Willebrand factor. Cleavage is present in normal individuals, increased in IIA and IIB von Willebrand disease, but minimal in variants with aberrant structure of individual oligomers (Types IIC, IID, and HE). J Clin Invest 1986; 77: 947-951
• 4 Budde V, Dent J, Berkowitz SD, Ruggeri ZM, Zimmerman TS. Subunit composition of plasma von Willebrand factor in patients with myeloproliferative syndrome. Blood 1986; 68: 1213-1217
• 5 Batlle J, López-Fernández MF, López-Berges C, Dent J, Berkowitz SD, Zimmerman TS. Proteolytic degradation of von Willebrand factor after DDAVP administration in normal individuals. Blood 1986; 68: 329a (abstract)
• 6 Batlle J, López-Fernández MF, Lasierra J, Fernández-Villamor A, López-Berges C, López-Borrasca A, Ruggeri ZM, Zimmerman TS. Von Willebrand disease type IIC with different abnormalities of von Willebrand factor in the same sibship. Am J of Hematol 1986; 21: 177-188
• 7 Triplett DA, Harms CS. Procedures for the coagulation laboratory. ASCP Press. Chicago: 1981 (Manual)
• 8 Zimmerman TS, Roberts JR. Factor VILI-related antigen. In: Immunoassays: clinical laboratories techniques for the 1980’s. Nakamura RM, Dilo WR, Tucker III ES. (eds) Alan R Liss, Inc; New York: 1980. p 339
• 9 Zimmerman TS, Batlle J, Ruggeri ZM, Roberts JR. Multimeric analysis of factor VUI/von Willebrand factor in the diagnosis of von Willebrand’s disease. In: Clinical Laboratory Assays: New Technology and future directions. Nakamura RM, Dito WR, Tucker III ES. (eds) Masson Publishing, Inc; New York: 1983. p 249
• 10 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
• 11 Batlle J, López-Fernandez MF, Campos M, Justiga B, Berges C, Navarro JL, Diaz-Cremades JM, Casper CK, Dent JD, Ruggeri ZM, Zimmerman TS. The heterogeneity of Type IIA von Willebrand disease: Studies with protease inhibitors. Blood 1986; 68: 1207-1212