The Role of von Willebrand Factor in Pre-Eclampsia

Summary

The von Willebrand factor (vWF) has gained considerable interest in recent years as a marker of endothelial cell activation or insult and by virtue of its interactions with platelets and vessel walls. Altered patterns of vWF multimers were found to occur frequently in patients with thrombotic thrombocytopenic purpura in the acute and chronic stages. This disorder shares some clinical and laboratory findings with pre-eclampsia, including thrombocytopenia. Recent studies have also suggested that abnormalities of endothelial cell metabolism play a central role in the pathophysiology of pre-eclampsia. In order to determine if vWF could be instrumental in the disease process and the thrombocytopenia of pre-eclampsia we analyzed the ante- and postpartum structural and functional distribution of vWF. This data was correlated with hematological parameters such as platelet counts and the clinical severity of the disease. We found no consistent changes of vWF in association with thrombocytopenia or clinical severity. However, functional vWF was lower in postpartum samples of severely affected pre-eclamptics as compared to normal controls. This finding may reflect endothelial cell exhaustion after stimulation or cellular injury. Elevated titers of fibrin split products and thrombocytopenia were evident in severe pre-eclampsia, as seen in DIC, despite factor VIII coagulant levels within the normal range. Our data is consistent with the hypothesis of endothelial cell dysfunction in pre-eclampsia. However, the mechanism of thrombocytopenia in this disorder does not appear to be related to alterations in the structure or biological function of vWF.

• References

• 1 Handin RI, Wagner DD. Molecular and cellular biology of von Willebrand factor. In: Progress in Hemostasis and Thrombosis, Vol.9.. Coller BS. (ed) W. B. Saunders Company, Philadelphia, PA: 1989. p 233
• 2 Moake JL, Rudy CK. Unusually large plasma factor VIII: von Willebrand factor multimers in chronic relapsing thrombotic thrombocytopenia purpura. N Engl J Med 1982; 307: 1432-3
• 3 Calvin S, Corrigan J, Weinstein L, Jeter M. Factor VIII: von Wille-brand factor patterns in the plasma of patients with pre-eclampsia. Am J Perinatol 1988; 5: 29-32
• 4 Zimmerman TS, Ruggeri ZM, Fulcher CA. Factor VIII/von Wille-brand factor. In: Progress in Hematology; Vol 13.. Brown EB. (ed) Grune and Straton, New York: 1983. pp 279-309
• 5 Rodgers GM, Taylor RN, Roberts JM. Pre-eclampsia is associated with a serum factor cytotoxic to human endothelial cells. Am J Obstet Gynecol 1988; 159: 908-14
• 6 Stubbs TM, Lazarchick J, Horger EO. Plasma fibronectin level in preeclampsia: A possible biochemical marker for vascular endothelial damage. Am J Obstet Gynecol 1984; 150: 885-7
• 7 Bussolino F, Benedetto C, Massobrio M, Camussi G. Maternal vascular prostacyclin activity in preeclampsia. Lancet 1980; 2: 702
• 8 Pritchard JA, Cunningham FG, Mason RA. Coagulation changes in eclampsia: Their frequency and pathogenesis. Am J Obstet Gynecol 1976; 124: 855-64
• 9 Redman CWG, Bonnar J, Beilin L. Early platelet consumption in preeclampsia. Br Med J 1978; 1: 467-9
• 10 Burrows RF, Hunter DJS, Andrew M, Kelton JG. A prospective study investigating the mechanism of thrombocytopenia in preeclampsia. Obstet Gynecol 1987; 70: 334-8
• 11 ACOG Techn Bull No. 91, February 1986.
• 12 Merskey C, Kleiner GJ, Johnson AJ. Quantitative estimation of split products of fibrinogen in human serum, in relation to diagnosis and treatment. Blood 1966; 28: 1-18
• 13 Simone JV, Vanderheiden J, Abilgard CF. A semiautomatic one-stage factor VIII assay with a commercially prepared standard. J Lab Clin Med 1967; 69: 706-12
• 14 Biggs R, MacFarlane RG. Human Blood Coagulation and its Disorders. 3rd ed. F. A. Davis Co., Philadelphia, PA: 1962
• 15 Laurell CB. Quantitative estimation of proteins by electrophoresis in agarose gel containing antibodies. Anal Biochem 1966; 15: 45-52
• 16 Chediak J, Maxey B, Telfer M. Determination of factor VIII related antigen using commercial antisera. Am J Clin Pathol 1977; 67: 462-9
• 17 Weiss HJ, Roger J, Brand H. Defective ristocetin induced platelet aggregation in von Willebrand's disease and its correction by factor-VIII. J Clin Invest 1973; 52: 2697-707
• 18 Ruggeri ZM, Zimmerman TS. The complex multimeric composition of Factor VIII/von Willebrand Factor. Blood 1981; 57: 1140-3
• 19 McConahey PJ, Dixon FJ. Radioiodination of proteins by the use of the chloramine-T-method. In: Methods in Enzymology, Vol 70.. Van Vunalis H, Langone JJ. (eds) Academic Press, New York: 1980. pp 210-3
• 20 Stirling Y, Woolf L, North WRS, Seghatchian MJ, Meade TW. Haemostasis in normal pregnancy. Thromb Haemostas 1984; 52: 176-82
• 21 Scholtes MCW, Gerretsen G, Haak HL. The factor VIII ratio in normal and pathological pregnancies. Eur J Obstet Gynecol Reprod Biol 1983; 16: 89-95
• 22 Girma JP, Meyer D, Verweij CL, Pannekoek H, Sixma JJ. Structure-function relationship of human von Willebrand factor. Blood 1987; 70: 605-11
• 23 Spoon LA, Marder VJ, Wagner DD. Inducible secretion of large, biologically potent von Willebrand factor multimers. Cell 1986; 46: 185-90
• 24 Gralnick HR, Williams SB, Morisato DK. Effect of the multimeric structure of the factor VIII/von Willebrand factor protein on binding to platelets. Blood 1981; 58: 387-97
• 25 Mannucci PM, Canciani MT, Rota L, Donovan BS. Response of factor VIII/von Willebrand factor to DDAVP in healthy subjects and patients with haemophilia A and von Willebrand's disease. Br J Haematol 1981; 47: 283-93
• 26 Musci TJ, Roberts JM, Rodgers GM, Taylor RN. Mitogenetic activity is increased in the sera of preeclamptic women before delivery. Am J Obstet Gynecol 1988; 159: 1446-51
• 27 Taylor RN, Musci TJ, Rodgers GM, Roberts JM. Predelivery preeclamptic sera stimulate platelet-derived growth factor mRNA expression in human endothelial cell cultures. Abstract No. 211, SGI Meeting, 1989
• 28 Denson KWE. The ratio of factor VIII-related antigen and factor VIII biological activity as an index of hypercoagulability and intravascular clotting. Thromb Res 1977; 10: 107-19
• 29 Redman CWG, Beilin LJ, Denson KWE, Bolton FG. Factor VIII consumption in pre-eclampsia. Lancet 1977; 2: 1249-52
• 30 McKay DG. Hematologic evidence of disseminated intravascular coagulation in eclampsia. Obstet Gynecol Surv 1972; 27: 399-417
• 31 Murphy WG, Moore JC, Barr RD, Pai MUR, Kelton JG. Relationship between platelet aggregating factor and von Willebrand factor with thrombotic thrombocytopenia purpura. Br J Haematol 1987; 66: 509-13
• 32 Thorp JR, White GC, Moake JL, Bowes WA. Von Willebrand factor multimeric levels and patterns in patients with severe preclampsia. Obstet Gynecol 1990; 75: 163-7