High Levels of Plasma FVIII and vWF in the Toxic Epidemic Syndrome Patients

Summary

Factor VIII and von Willebrand factor proteins were evaluated in 115 patients having the chronic phase of the Toxic Epidemic Syndrome (TES), a new multisystemic disease probably caused by the ingestion of denatured rapeseed oil, and in 50 control volunteers. Higher circulating levels of factor VIII procoagulant activity (VIII :C) (158 ± 58.4 U/dl), von Willebrand factor antigen (vWF: Ag) (166.1 ± 55.5 U/dl) and von Willebrand factor ristocetin cofactor activity (vWF:RCo) (178.7 ± 55.2 U/dl) were seen in TES patients (p < 0.001, TES patients versus control subjects, for each parameter). The increased levels of vWF:Ag and vWF:RCo observed in TES patients correlated with the scleroderma like lesion of the skin, with the sicca syndrome and with Raynaud's phenomenon (p < 0.01), but not with other clinical manifestations. The multimeric analysis of vWF in 92% of the TES patients was similar to that found in normal plasma, but in the remaining 8% a very slight increase of larger vWF multimers in plasma were observed. The raised levels of vWF found in TES patients in the chronic phase may reflect an “in vivo” vascular injury.

Keywords

von Willebrand factor - FVIII - Epidemic toxic syndrome - Scleroderma-like lesions

• References

• 1 Tabuenca JM. Toxic allergic syndrome caused by the ingestion of rapeseed oil denatured with aniline. Lancet 1981; II: 567-568
• 2 Center for Disease Control. International notes: Atypical pneumonie-Spain. Morb Mortal Weekly Res 1981; 30: 237-238
• 3 Center for Disease Control. International notes: Follow-up on toxic pneumonie-Spain. Morb Mortal Weekly Res 1981; 30: 436-438
• 4 Toxic Epidemic Syndrome Study group. Toxic epidemic syndrome in Spain 1981. Lancet 1982; II: 697-702
• 5 Martíncz-Tello FJ, Navas-Palacios LL, Ricoy JR, Gil-Martín R, Conde-Zurita JM, Colina-Ruiz-Delgado F, Tellez T, Cabello A, Madero-García S. Pathology of a new toxic syndrome caused by the ingestion of adulterated oil in Spain. Virchows Arch Pathol Anat 1982; 397: 261-285
• 6 Wencel-Drake JD, Plow EF, Zimmerman TS, Painter RG, Ginsberg MH. Immunofluorescent localization of adhesive glycoproteins in resting and thrombin stimulated platelets. Am J Pathol 1984; 115: 156-164
• 7 Nachman IR, Levine R, Jaffe EA. Synthesis of factor VIII antigen by cultured guinea pig megakaryocytes. J Clin Invest 1977; 60: 914-921
• 8 Jaffe EA, Hoyer LW, Nachman IR. Synthesis of antihemophilic factor antigen by cultured human endothelial cells. J Clin Invest 1973; 52: 2757-2764
• 9 Zimmerman TS, Ruggeri ZM, Fulcher C. Factor VUI/von Willebrand factor. Prog Hematol 1983; XIII: 279-309
• 10 Kahaleh MB, Osborn I, LeRoy EC. Increased factor VIII/von Willebrand factor antigen and von Willebrand factor activity in Scleroderma and in Raynaud's phenomenon. Ann Intern Med 1981; 94: 482-484
• 11 Nusinow SR, Federici AB, Zimmerman TS, Curd JG. Increased von Willebrand factor antigen in the plasma of patients with vasculitis. Arthritis Rheum 1984; 27: 1405-1410
• 12 Federici AB, Fox RI, Espinoza LR, Zimmerman TS. Elevation of von Willebrand factor is independent of erythrocyte sedimentation rate and persists after glucocorticoid treatment in giant cell arteritis. Arthritis Rheum 1984; 27: 1046-1049
• 13 Lufkin EG, Fass DN, O'Fallon WM, Bowie EJ W. Increased von Willebrand factor in diabetes mellitus. Metabolism 1979; 28: 63-66
• 14 Ingram GI. Blood coagulation factor VIII: genetics physiological control and bioassay. Adv Clin Chem 1956; 8: 101-112
• 15 Zimmerman TS, Roberts JR. Factor VIII related antigen. Immunoassays. In: Clinical Laboratory Techniques for the 1980s. Nakamura RM, Dito WR, Tucker III ES. (eds) Alan R. Liss; New York: 1980: 9-49
• 16 Macfarlane DE, Stibbe J, Kirby EP, Zucker MB, Grant RA, McPherson J. A method for assaying von Willebrands factor (ristocetin cofactor). Thromb Diath Haemorrh 1975; 34: 306-308
• 17 Batlle J, Lopez Fernández MF. Laboratory assays for von Willebrand factor. In: Coagulation and Bleeding Disorders. The Role of Factor-VIII and von Willebrand Factor. Zimmerman TS, Ruggeri ZM. (eds) Marcel Dekker; New York: 1989: 325-342
• 18 Snedecor GW, Cochran WG. (eds) Statistical Methods. Iowa University Press; Ames, Iowa: 1980: 234-264
• 19 López-Femández MF, Ginsberg MH, Ruggeri ZM, Batlle J, Zimmerman TS. Multimeric structure of platelets factor VIII/von Willebrand factor: the presence of larger multimers and their reassociation with thrombin stimulated platelets. Blood 1982; 60: 1132-1138
• 20 Bennett B, Ratnoff OD, Levin J. Immunologic studies in von Willebrands disease. Evidence that the antihemophilic factor (AHF) produced after transfusions lacks an antigen associated with normal AHF and the inactive njaterial produced by patients with classic hemophilia. J Clin Invest 1972; 51: 2597-601
• 21 Masi AT, Rodnan GP, Medsger TA. et al. Preliminary criteria for the classification of systemic sclerosis (scleroderma). Arthritis Rheum 1980; 23: 581-590
• 22 Rocco VK, Hurd ER. Scleroderma and scleroderma like disorders. Semin Arthrit Rheum 1986; 16: 22-69
• 23 Kahaleh MB, Sherer GK, LeRoy EC. Endothelial injury in scleroderma. J Exp Med 1979; 149: 1326-1335
• 24 Demopoulos MB, Flamm ES, Peitronigro DD, Seligman MI. The free radical pathology and the microcirculation in the major central nervous system disorders. Acta Physiol Scand 1980; 492 Supply 91-119