Assessment of the role of some haemostatic parameters in patients with cryptogenic stroke

Cryptogenic stroke [CS] is a stroke of unexplained aetiology, in 1/3 the of cases, the cause of stroke remains undetermined inspite of full investigations. Patient with CS are thought to have a state of hypercoagulablity. To unmask some of the pathogenic mechanisms underlying cryptogenic stroke through assessment of some genetic disorders including C6[77]T mutation methyl-enetetrahydrofolate reductase gene, activated protein C [APC] resistance and role of thrombin anti-thrombin complex concentration [TAT] in plasma as indicators of hypecoagulable state. The study was conducted on 20 Egyptian patients divided into 2 groups, group I included 10 patients [6 males and 4 females] with cryptogenic stroke aged less than 50 years and group II included 10 age and sex matched patients with non-cryptogenic stroke. All of the 20 cases studied were subjected to panel of investigations including routine laboratory tests and imaging studies in orders to exclude any risk factors for stroke in group I patients and to determine risk factor of stroke in group II. Both groups were investigated for C6[77]T mutation in methylenetetrahydrofolate reductase gene, activated protein C [APC] resistance and thrombin anti-thrombin complex concentration [TAT] in plasma. No statistical significant difference was found between the two groups as regard C6[77]T mutation in methylenetetrahydrofolate reductase gene, [APC] resistance and TAT concentration in plasma [p value >0.05]. However, TAT level was found to be positively correlated with the clinical severity in non-cryptogenic stroke [p value <0.05]. C6[77]T mutation in methylenetetrahydrofolate gene, [APC] resistance and TAT concentration in plasma are not independent risk factors for cryptogenic stroke. TAT could be used as indicator of clinical severity and prognosis in patient with non-cryptogenic stroke

Protein C, protein S and antithrombin III assessment in Egyptian thalassemic children

Enhanced years of survival have led to the unmasking of management related complications with the recognition of the existence of a chronic hypercoagulable state in thalassemic patients. This study aims at determining the levels of the three main antithrombophilic factors namely protein C, protein S and antithrombin III in Egyptian children with beta thalassemia major. Sixty children with beta thalassemia major with a mean age of 12.2 +/- 1.88 years and male: female ratio 1.7: 1 were enrolled in the study. They were subjected to history taking, clinical examination and laboratory investigations including levels of ferritin by IRMA, protein C, protein S, and antithromobin III by ELISA. Protein C was deficient in 16 [26.7%] of cases, protein S was deficient in 8 [13.3%] of cases while none had deficiency of antithrombin III. None of our cases had a history of thromboembolic events. These abnormalities were not related to the state of HCV infection or to the type of chelation whether oral or subcutaneous. Protein C deficiency was present more in older patients. Abnormalities in protein C, protein S are frequently observed even without manifesting hypercoagulable states in our studied thalassemia major children

Coexistence of hyperhomocysteinemia and protein C deficiency in the development of sinus thrombosis: a case report

Hyperhomocysteinemia is a rare autosomal recessive inherited metabolic disorder. The main clinical manifestations of hyperhomocysteinemia include mental retardation, psychological disturbance, thromboembolic events and skeletal abnormalities. The case reported here is of a 28 year-old man admitted in hospital with recurrent seizures. In the brain MRI, areas of venous infarction were seen and MRA revealed thrombosis in brain venous sinuses. Lab investigation showed increases in serum level of homocystein and protein C deficiency. The patient had no family history of genetic disease or cerebrovascular attack. As sinus thrombosis is a multifactorial disease, Protein C deficiency can be one of aggravating causes of thromboembolic events in patients with hyperhomocysteinemia

Platelet aggregation and physiological anticoagulants in sickle-cell disease

During the period January 2002- December 2004, we assessed 30 sickle- cell anaemia patients admitted to hospital in Al Khobar with vaso- occlusive crisis for levels of antithrombin [AT] III, protein C [PC] and protein S [PS]. We also did platelet aggregation studies. Steady state levels were assessed during follow- up and compared with 36 adult controls. Levels of PC, PS and AT III in the group were significantly higher than in those in vaso- occlusive crisis and those in steady state control [P < 0.001]. There was a statistically significant difference between controls and patients for all platelet factors except adrenaline. There was no significant difference between the levels of PC, PS, aggregation AT III and platelet aggregation variables in patients in the steady state and in vaso- occlusive crisi

Study of serum protein C level in a group of neonates with sepsis

Sepsis associated with acute organ dysfunction results from a generalized inflammatory and procoagulant response to an infection. Activated protein C, an endogenous protein that promotes fibrinolysis and inhibits thrombosis and inflammation, is an important modulator of coagulation and inflammation associated with severe sepsis. The study was conducted on twenty neonates fulfilling criteria of neonatal sepsis clinically and by laboratory investigations. Twenty healthy neonates were assigned as control group. We measured protein C level by enzyme immunoassay in both cases and control groups within 24 hours of diagnosis. Results of this study showed that there was decrease in level of protein C in neonates with sepsis when compared to control group, and this difference was statistically significant, although there was no cases in our study suffering from frank coagulation disturbances. Also gestational age, birth weight, and duration of illness were predictors of lower protein C level in study cases when doing regression analysis. We recommend larger study with measurement of levels of other protein C system in serum like active protein C and thrombomodulin assays

Diagnostic value of PRO C global test in patients with deep vein thrombosis

This study was carried out to evaluate pro C Global [PCG] test in clinical routine with special regard to its sensitivity and specificity for factor V [FV] leiden as well as the deficiency of protein C [PC] and protein S [PS]. 70 adult patients with documented diagnosis of deep vein thrombosis [DVT] by Doppler ultrasonography were chosen from those were attending the emergency unit of Alexandria main university hospital and Alexandria armed forces hospital in addition to 30 age and sex matched healthy controls were evaluated for PCG test in relation to gold standard tests i.e. PC activity, PS activity and activated protein C resistance [APCR]. Also determination of lupus anticoagulants [LA] was done for all subjects under study. The sensitivity and specificity of PCG test were [100% and 100%] for FV leiden, [87.5% and 82.3%] for PC and [80% and 78.5%] for PS. The negative predictive value was [100%, 98.1% and 98.1%] for FV leiden, PC and PS respectively. The positive predictive value was [100%, 38.9% and 22.2%] for FV leiden, PC and PS respectively. Also, the diagnostic accuracy was [100%, 82.9% and 78.6%] for FV leiden, PC and PS respectively. The results of LA were negative in all patients and controls. However, the normalized ratio [NR] of PCG test was decreased in [14.8%] of patients group without any detectable defect in PC system and their results were significantly lower than control group [P=0.000]. On the other side, the results were considerably higher than those for the patients with a proven defect in PC system. Pro C Global test is sensitive, specific, less time consuming and can be performed on a routine base. Because of the high negative predictive value, we recommend the use of Pro C Global test in the screening of thrombophilic patients and further determination of F V leiden, PC activity and PS activity is only indicated in case of abnormal Pro C Global results

Coagulating like conditions thrombophilia

Fluidity of blood inside the vessels on one hand, and formation of thrombus just at the site of vessel injury on the other hand, is the result of an exact interactive equilibrium of multiple procoagulant and anticoagulant factors, and their activators and inhibitors. Destruction or stimulation of endothelial cells and platelets, and contact of blood and platelets with subendothelial tissues are among the main procoagulant factors. Integrity and function of endothelial cells, washing property of blood stream, fibrinolysis system [plasminogen] and thrombomodulin system, protein C and antithrombin are the most important anticoagulant factors. Dysfunction of procoagulant factors leads to bleeding tendency, whereas dysfunction of anticoagulant factors causes predisposition to the thrombosis [thrombophilia]. Despite recent progresses, we can only diagnose half of hereditary thrombophilias, among these, the factor V Leiden, antithrombin deficiency; protein C deficiency and protein S deficiency are more common. Elevation of plasma factor VIII levels has been considered as a common but weak risk factor for hereditary thrombophilia. Mutation of prothrombin G20210A which leads to elevation of prothrombin levels, has the same importance as the factor VIII elevation. Presence of hereditary thrombophilia in an individual does not inevitably end up in the formation of pathologic thrombosis, for clinical presentation of thromboembolic syndromes, coincidence of one [or more] hereditary thrombophilia along with one [or more] acquired thrombophilia [such as pregnancy, immobility, surgery, OCP use] are usually evident. Individuals with hereditary thrombophilia are more prone to the recurrence of thrombosis than normal individuals, so long term use of anticoagulant drugs in such patients is recommended. Screening for hereditary thrombophilia must be considered when [1] there is not an acceptable acquired risk factor for thrombosis in history and physical examination; [2]venous thrombosis before age 40, [3]recurrent thrombosis, [4]arterial thrombosis before age 30, [5]family history of thrombosis, [6]thrombosis in unusual sites such as mesenteric or cerebral veins

Protein c as an earlier diagnostic marker for some coronary heart disease

This work aimed to evaluate the role of protein C, some of the coagulation cascade proteins and lipids profile in ischemic heart disease [IHD] and myocardial infarction [MI]. The present study included 40 men selected from ICU Matareya Educational Hospital and classified into 20 cases suffering from ischemic heart disease [IHD group], 20 patients suffering from myocardial infarction [MI group] and a control group comprising 20 healthy normal males. Prothrombin time [IT] prothrombin [P] concentration, activated partial thromboplastin time [APTT], plasma fibrinogen concentration [PF] and protein C [PC] activity were measured in plasma. In serum, creatine kinase [CK], creatine kinase-MB [CK-MB], lactate dehydrogenase [LDH] activities, total lipids [T lipids], phospholipids, triacylglycerol [TAG], total cholesterol [TC], cholesterol-low density lipoprotein [LDL-C] and cholesterol-high density lipoprotein [HDL-C] were measured. The results of the study showed a positive relationship between the levels of plasma clotting factors and hyperlipidemic status, where there may be an interaction between plasma lipoproteins and procoagulant factors. Also, the hypothesis that MoL-C downregulates the thrombin generation via the PC pathway was supported

Protein C, protein S and antithrombin III in children with complicated congenital heart diseases

This study was carried out on 40 patients with congenital heart disease [CHD] aged three months to seven years and divided into two groups: The first included 28 patients with complicated CHD and the second group included 12 patients with uncomplicated CHD. Ten healthy children were chosen as controls. A coagulation profile consisting of protein C, protein S, antithrombin III, factor V and factor VIII were evaluated in all patients and controls. The mean values of protein C, protein S, antithrombin III, factor V and factor VIII were significantly decreased in patients with complicated CHD compared with both uncomplicated cases and controls. Eighteen out of twenty-two patients with complicated CHD had low protein C levels [2 standard deviations below the normal mean value of the controls]. Of these children, three developed thrombotic complications and eight had evidences suggestive of consumption coagulopathy [decreased factors V and VIII]. It was concluded that decreased levels of coagulation inhibitors protein C, protein S and antithrombin III were observed in ill children with complicated CHD. With reduced levels of protein C, children with complicated CHD might have a tendency toward thrombotic complications

Levels of natural anticoagulants, antithrombin III and protein C in diabetic vascular disease

Accelerated micro and macro vascular thrombotic disease is characteristic of diabetes mellitus. A hypercoagulable state is appreciated in this disease. We studied levels of natural anticoagulants such as Antithrombin III[AT III] and protein C which are factors to counteract the effects of hypercoagulable state. Both AT III and protein C levels were found decreased in diabetics with macrovascular disease suggesting that natural mechanism of anticlot formation are also affected in these patients, thus may be contributing to the thrombotic complications

Protein C activity in children with hepatitis

In the present study protein C activity was assessed in 40 children with acute hepatitis whose ages ranged between 4-12 years. The severity of hepatitis was judged by a prolonged prothrombin time in the severe cases and a normal range prothrombin time in the milder cases in comparison to the control group value. In the severely affected group [26 cases] SGPT and serum bilirubin were significantly increased compared to the control value [p<0.00l] while serum albumin was significantly decreased [P<0.001]. PTT and PT were significantly prolonged [P< 0.001]. In the milder 14 cases, SGPT and serum bilirubin were significantly increased [P<0.001], while serum albumin was statistically insignificantly changed [P>0.05]. PTT was significantly prolonged [P<0.001] and PT was within normal range. Protein C activity was significantly decreased [P<0.001] in both severely and mildly affected patients. PC activity can be used as a sensitive and early parameter for hepatocellular damage in acute hepatitis. Its value as an early indicator of recovery is to be investigated