Haemostatic Abnormalities and Renal Damage in Sudanese Hypertensive Patients

Abstract

This study was done during the period of October 2003 to February 2007 in Khartoum State Teaching Hospitals (Omdurman, Khartoum, and Soba) to determine the thrombin generation, haemostatic and renal damage markers among Sudanese hypertensive patients. Two hundred patients (200) and fifty normal controls (50) were studied. Patients were those who fulfilled the clinical diagnosis of hypertension of both sex, on or off treatment. The controls were normal, non-hypertensive individuals of either sex. Both patients and control were above 40 years of age. Patients (male and female) with previous history of venous or arterial thrombosis and diabetes mellitus, who received antiplatelet or anticoagulant drugs in the preceding 15 days, were excluded from the study. A structured questionnaire was prepared which included the general information and laboratory investigations. Blood, plasma, serum and urine samples were collected from all patients and controls for use in laboratory investigations. The results showed non significant difference between the mean level of patients and controls in the following parameters: prothrombin time (PT) (p=0.626), activated partial thromboplastin time (APTT) (p=0.272), thrombin time(TT) (p=0.863), fibrinogen level(p=0.455), platelets count (p=0.866), protein S level (p=0.123), protein C level (p=0.653), Prothrombin fragment 1+2 (F1+2) (p=0.925), thrombin antithrombin complex (TAT) (p=0.867), serum urea level (p=0.326) and serum creatinine level (p=0.573). The presence of microalbuminuria was correlated with the age of patients (p=0.000) and the duration (p=0.030) of hypertension. The levels of fibrinogen among hypertensive patients in the present study were strongly related to the development of microalbuminuria (p=0.0000). The results demonstrated a significant difference between patients and controls in the mean level of von Willebrand factor antigen (P=0.000), bleeding time (p=0.042) and plasminogen activator inhibitor-1 (p=0.000). There was no correlation between the age of the patients and serum urea level (p=0.623 ). However, serum creatinine level was related to the age of the patients (p=0.041 ). Fibrinogen level (p=0.011), bleeding time (p=0.021), Plasminogen activator inhibitor-1 level (p=0.0001) and Prothrombin fragment 1+2 level (p= 0.012) were significantly correlated to severity of hypertension(stage II), while thrombin antithrombin complex level did not show significant (p=0.124) correlation to the severity of the disease. Both circulating markers of thrombin generation(Prothrombin fragment 1+2 and thrombin antithrombin complex) were significantly (p=0.000) correlated to the duration of hypertension. The results obtained indicated that measurement of prothrombin time(PT), activated partial thromboplastin time(APTT), Or thrombin time(TT) were unnecessary when evaluating a hypertensive patient in whom there was no clinical evidence of a haemostatic abnormality. An approach would eliminate the need for most of the coagulation tests done in these patients. The results of this study raised the possibility that von Willebrand factor, fibrinogen level and prothrombin fragment 1+2 could be of use in identifying a "high-risk" group of hypertensive patients who were likely to develop thrombotic events. The elevated of PAI-1 would further enhance this prothrombotic tendency. Longitudinal studies would be more informative in this aspect. The positive correlation between the presence of microalbuminuria and the duration of the disease indicated progressive renal disease with longstanding hypertension. This was inspite of the absence of a significant difference in serum urea and serum creatinine levels between patients and controls. Microalbuminuria was found to be directly correlated with fibrinogen and von willebrand factor antigen levels, and this was an indication of a relationship between renal damage and the haemostatic disturbance in hypertension.