Sudan Journal of Medical Sciences Volume 14, Issue no. 3, DOI 10.18502/sjms.v14i3.5209 Production and Hosting by Knowledge E Research Article Assessment of Plasma von Willebrand Factor Antigen in Non-metastatic Prostate Cancer Patients: A Cross-sectional Study of the Sudanese Population Mohammed Othman Hashim1, Gad Allah Modawe2, and Ibrahim Khider Ibrahim1 1Department of Haematology, Faculty of Medical Laboratory Sciences, Al Neelain University, Khartoum, Sudan 2Omdurman Islamic university, Faculty of Medicine and Health Sciences, Department of Biochemistry Abstract Backgrounds: Von Willebrand disease (VWD) is reportedly the most common inherited bleeding disorder and can also arise as an acquired syndrome (AVWS). These disorders arise due to defects and/or deficiency of the plasma protein von Willebrand factor (VWF). High plasma VWF concentrations have been reported in patients with various types of cancer, such as prostatic cancer. Metastasization may be associated with activation of hemostatic processes resulting in increased levels of circulating factor VIII-related antigen (FVIIIRAg) (von Willebrand factor antigen). Objective: To evaluate the status of VWF antigen in Sudanese patients with prostate cancer attending RICK hospital. Methods: This is a cross-sectional study carried out in Khartoum state at Khartoum oncology (RICK) hospital, during the period from April to June 2018, 45 samples were collected from patients with non-metastatic CA prostate, their ages ranged from 51 to 82 yr. The VWF level was measured using Enzyme-linked immunosorbent assay (ELISA). Data were analyzed by the statistical package for social science (SPSS). Results: Serology for VWF antigen was done for 45 cases of prostate cancer. According to the age, 2 (8%) patients with age 51–66 yr had a high concentration of VWF, while 24 (92%) had normal VWF antigen concentration; of those with age 67–82 yr, 4 (21%) had high VWF antigen and 15 (79%) had normal antigen. Conclusion: The study revealed that more than 80% of Sudanese patients with non- metastatic prostate cancer have a normal concentration of VWF. Keywords: VWF, prostate cancer, age, ELISA 1. Introduction The glycoprotein von Willebrand factor (VWF) mediates the adhesion of platelets to subendothelial surfaces in primary hemostasis in case of vascular injury [1]. Plasma How to cite this article: Mohammed Othman Hashim, Gad Allah Modawe, and Ibrahim Khider Ibrahim (2019) “Assessment of Plasma von Willebrand Factor Antigen in Non-metastatic Prostate Cancer Patients: A Cross-sectional Study of the Sudanese Population,” Sudan Journal of Medical Sciences, vol. 14, issue no. 3, pages 97–102. DOI 10.18502/sjms.v14i3.5209 Page 97 Corresponding Author: Mohammed Othman Hashim Received 21 February 2019 Accepted 12 May 2019 Published 30 September 2019 Production and Hosting by Knowledge E Mohammed Othman Hashim et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. Editor-in-Chief: Prof. Mohammad A. M. Ibnouf http://www.knowledgee.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ Sudan Journal of Medical Sciences Mohammed Othman Hashim et al VWF levels vary over a very broad range extending from 40 to 240% of the mean value [2]. A major determinant of plasma VWF levels is the ABO blood group, but several clinical conditions, such as myocardial infarction, diabetes mellitus, liver disease, and acute infections, induce increased plasma VWF concentrations [3–8]. There are some studies describing a correlation of VWF with different cancers like prostate cancer, cervical and ovarian cancer, head and neck cancer, larynx cancer, and colorectal cancer (CRC) [9–15]. Experimental models favor the hypothesis that VWF connects tumor cells to platelets and so assists during the pathogenesis of metastases. It is supposed that these VWF-tumor-cell-emboli are hardly detected by the immune system [16–18]. As VWF levels increase with progressive disease [14, 15], it is considered as a potential clinical marker in CRC. Metastasizing may be associated with activation of hemostatic processes resulting in increased levels of circulating von Willebrand factor antigen. The objective of this study was to evaluate the status of VWF Ag in Sudanese patients with non-metastatic prostate cancer attending RICK. 2. Methods This is a retrospective cross-sectional study in which a total of 45 (non-metastatic) PC patients were recruited at the RICK hospital, in the period from April to June 2018. A venous blood sample (3 ml) was taken from each subject into a tube containing 3.8% trisodium citrate, platelet poor plasma was prepared and used for the assessment of VWF level. The VWF level was measured using Enzyme-linked immunosorbent assay (ELISA) according to the manufacturer’s instructions (TECHNOZYM, Austria). 2.1. Ethical consideration Ethical clearance was obtained from the Institutional Review Board at Al Neelain Univer- sity. Principal investigator obtained written informed consent from all participants prior to their inclusion in the study. 2.2. Data analysis All obtained results were analyzed using Statistical Package for the Social Sciences (SPSS) version 20.0, with Pearson’s chi-square test used to assess intergroup signifi- cance and t-test used to determine differences in means, other variables frequencies DOI 10.18502/sjms.v14i3.5209 Page 98 Sudan Journal of Medical Sciences Mohammed Othman Hashim et al and odd ratio calculated for comparison and presented in form of figures and tables. P-value and odd ratio were used to assess the significance of the results. 3. Results and Discussion High-plasma VWF concentrations have been reported in patients with several types of cancers, such as prostatic cancer head and neck and laryngeal cancer, probably representing an acute phase reactant. In the present study, we evaluated the status of VWF antigen (VWF:Ag) in 45 patients diagnosed with prostate cancer (non-metastatic). Their mean age was 66.5 yr, 26/45 (58/%) patients were 51–66 years old, and 19/45 (42%) were 67–82 Years old. The patient’s marital status: 34/54 (76%) of them were married and 11/45 (24%) were unmarried; 12/45 (27%) patients had hypertension and 4/45 (9%) had diabetes mellitus. Serology for VWF antigen was done in 45 cases of prostate cancer. According to the age, 2 (8%) with age 51–66 yr had high concentration of VWF, 24 (92%) with same age had normal VWF antigen, and those with age 67–82 yr, 4 (21%) with high VWF antigen and 15 (79%) with normal antigen. In association with marital status: 5 (15%) of the married patients had high VWF antigen and 29 (85%) were normal. In unmarried men, 1 (9%) was found to have high Ag level and 10 (91%) with normal Ag level. In association with hypertension and diabetes mellites, 2 (17%) of the hyper-tensive patients had high antigen and 10 (83%) had normal antigen concentration. Among the non-hypertensive patients, 4 (12%) had high concentration and the other 29 (88%) had normal Ag concentration. Of the diabetic patients, 4 (100%) had normal antigen concentration and among the non-diabetic patients, 6 (15%) had high concentration and other 35 (85%) had normal value. 4. Conclusion The study revealed that more than 80% of Sudanese patients with non-metastatic prostate cancer presented with a normal concentration of VWF. DOI 10.18502/sjms.v14i3.5209 Page 99 Sudan Journal of Medical Sciences Mohammed Othman Hashim et al Table 1: Demographic and clinical data in the population study. Variables Frequency Percentage (%) Age 51–66 Years 26 58 67–82 Years 19 42 Marital status Married 34 76 Unmarried 11 24 HT Yes 12 27 No 33 73 DM Yes 4 9 No 41 91 Total 45 100 Figure 1: Distribution of Von Willebrand factor antigen in Sudanese Prostate Cancer patients. References [1] Ruggeri, Z. M. (1991). Structure and function of von Willebrand factor: relationship to von Willebrand’s disease. Mayo Clinic Proceedings, vol. 66, pp. 847–861. [2] Sadler, J. E., Mannucci, P. M., Berntorp, E., et al. (2000). Impact, diagnosis and treatment of von Willebrand disease. Thrombosis and Haemostasis, vol. 84, pp. 160–174. DOI 10.18502/sjms.v14i3.5209 Page 100 Sudan Journal of Medical Sciences Mohammed Othman Hashim et al Table 2: Correlation between variables and study parameters. Variables vWF Ag P-value OR CI Lower CI Upper High Normal Age 51–66 Years 2 (8%) 24 (92%) 0.195 0.313 0.051 1.921 67–82 Years 4 (21%) 15 (79%) Marital status Married 5 (15%) 29 (85%) 0.541 1.724 0.179 16.591 Unmarried 1 (9%) 10 (91%) HT Yes 2 (17%) 10 (83%) 0.541 1.450 0.230 9.160 No 4 (12%) 29 (88%) DM Yes 0 (0.0%) 4 (100%) 0.552 1.171 1.032 1.330 No 6 (15%) 35 (85%) [3] Gallinaro, L., Cattini, M. G., Sztukowska, M., et al. (2008). A shorter von Willebrand factor survival in O blood group subjects explains how ABO determinants influence plasma von Willebrand factor. Blood, vol. 111, pp. 3540–3545. [4] Shima, M., Fujimura, Y., Nishiyama, T., et al. (1995). ABO blood group genotype and plasma von Willebrand factor in normal individuals. Vox Sanguinis, vol. 68, pp. 236– 240. [5] Lufkin, E. G., Fass, D. N., O’Fallon, W. M., et al. (1979). Increased von Willebrand factor in diabetes mellitus. Metabolism, vol. 28, pp. 63–66. [6] Giustolisi, R., Musso, R., Cacciola, E., et al. (1984). Abnormal plasma levels of factor VIII/von Willebrand factor complex in myocardial infarction-expression of acute phase reaction or index of vascular endothelium damage? Thrombosis and Haemostasis, vol. 51, p. 408. [7] Castillo, R., Maragall, S., Rodes, J., et al. (1977). Increased factor VIII complex and defective ristocetin-induced platelet aggregation in liver disease. Thrombosis Research, vol. 11, pp. 899–906. [8] Sousa, N. C., Anicchino-Bizzacchi, J. M., Locatelli, M. F., et al. (2007). The relationship between ABO groups and subgroups, factor VIII and von Willebrand factor. Haematologica, vol. 92, pp. 236–239. [9] Ablin, R. J., Bartkus, J. M., and Gonder, M. J. (1988). Immuno-quantitation of factor VIII- related antigen (von Willebrand factor antigen) in prostate cancer. Cancer Letters, vol. 40, pp. 283–289. DOI 10.18502/sjms.v14i3.5209 Page 101 Sudan Journal of Medical Sciences Mohammed Othman Hashim et al [10] Facchini, V., Gadducci, A., Baicchi, U., et al. (1988). Factor VIIIR:Ag plasma levels in patients with cervical and ovarian carcinoma. European Journal of Gynaecological Oncology, vol. 9, pp. 87–93. [11] Gadducci, A., Baicchi, U., Marrai, R., et al. (1993). Pretreatment plasma levels of fibrinopeptide-A (FPA), D-dimer (DD), and von Willebrand factor (vWF) in patients with operable cervical cancer: influence of surgical-pathological stage, tumor size, histologic type, and lymph node status. Gynecologic Oncology, vol. 49, pp. 354–258. [12] Sweeney, J. D., Killion, K. M., Pruet, C. F., et al. (1990). von Willebrand factor in head and neck cancer. Cancer, vol. 66, pp. 2387–2389. [13] Paczuski, R., Bialkowska, A., Kotschy, M., et al. (1999). Von Willebrand factor in plasma of patients with advanced stages of larynx cancer. Thrombosis Research, vol. 95, pp. 197–200. [14] Damin, D. C., Rosito, M. A., Gus, P., et al. (2002). Von Willebrand factor in colorectal cancer. International Journal of Colorectal Disease, vol. 17, pp. 42–45. [15] Wang, W. S., Lin, J. K., Lin, T. C., et al. (2005). Plasma von Willebrand factor level as a prognostic indicator of patients with metastatic colorectal carcinoma. World J Gastroenterology, vol. 11, pp. 2166–2170. [16] Gasic, G. J., Gasic, T. B., Galanti, N., et al. (1973). Platelet-tumor-cell interactions in mice. The role of platelets in the spread of malignant disease. International Journal of Cancer, vol. 11, pp. 704–718. DOI 10.18502/sjms.v14i3.5209 Page 102 Introduction Methods Ethical consideration Data analysis Results and Discussion Conclusion References