الفهرس 
Portal vein thrombosisOnly 14 pages are availabe for public view
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Abstract
Portal vein is a blood vessel that carries blood from the gastrointestinal tract, gallbladder, pancreas and spleen to the liver. In most individuals, the portal vein is formed by the union of the superior mesenteric vein and the splenic vein.
Portal vein thrombosis (PVT) is defined as complete or partial obstruction of blood flow in the portal vein, associated with a thrombus in the vessel lumen. Portal vein thrombosis causes portal hypertension and varix, and if severe, can cause variceal hemorrhage and ischemic bowel disease.
Protein C and protein S system are the major regulatory system of hemostasis. Protein C and protein S are vitamin K dependent proenzymes synthesized in the liver. Thrombin- thrombomodulin complex on the surface of endothelial cells is the site for the interaction with protein C and S. Protein C becomes activated (activated protein C) after binding to these complexes. Protein S acts as a cofactor in this process. Activated protein C inhibits factor VIIIa and factor Va thus exhibiting its anticoagulant property and also enhances fibrinolysis through the inhibition of plasminogen activator inhibitor.
Patients with protein C and S deficiency are at increased risk for venous thromboembolic disease, occasional arterial thrombosis, neonatal purpura fulminans and childhood stroke and even portal vein thrombosis. Acquired causes of protein C and S deficiencies are seen in acquired illness like liver disease, DIC, therapy with L-asparaginase and coumarin, and acute severe bacterial infections etc.
The pathogenesis of portal vein thrombosis has not been identified clearly, but it is related to systemic causes such as protein C, protein S, and antithrombin III deficiency disorder. Antithrombin (AT), protein C (PC) and protein S (PS), deficiencies have been considered the causes of nonmalignant and noncirrhotic PVT. The role of AT, PC and PS in the pathogenesis of cirrhotic PVT is rarely explored. This is primarily because the 3 natural anticoagulant proteins are produced by the hepatocytes and decreased in the setting of liver cirrhosis.
The present study aimed at clarifying the relation of protein C and the pathogenesis of portal vein thrombosis in patients with liver cirrhosis. It was conducted in the Internal Medicine Department, Faculty of Medicine, and Menoufia University Hospitals on 100 subjects. They were 40 cirrhotic patients without PVT and 40 cirrhotic patients with PVT as well as 20 healthy persons of matched age and sex as a control group. They were 73 males and 27 females and their ages ranging from 38 to 75 years. Patients and controls were classified into the following groups:
group 1: Healthy volunteers (control group) (20 patients).
group 2: Cirrhotic patients without PVT (LC group) (40 patients).
group 3: Cirrhotic patients with PVT (LC and PVT group) (40 patients).
Patients with age < 18 years, patients receiving anti-platelet and/or anticoagulant therapy for cardiovascular diseases, patients with infection, patients suffering from inflammation or any blood diseases in previous 2 months, patients with history of personal unprovoked thromboembolism, patients with hepatocellular carcinoma and patients with diabetes mellitus were excluded from the study.
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All patients and controls included in the study had full history taking, complete physical examination, routine laboratory investigations (complete blood picture, PT and liver function tests) and special investigation as plasma protein C.
Regarding spleen size, the mean of spleen diameter was significantly higher in LC group than LC and PVT group (p = 0.010).
Regarding Child-Pugh classification, there was no significant differance between LC group and LC and PVT group regarding Child–Pugh classification (p = 0.790).
Regarding CBC, there was no significant difference between LC group and LC + PVT group as regard Hb level, WBCs and platelet count (P = 0.760), (p = 0.592) and (p = 0.226) respectively.
Regarding PT, the mean of PT was significantly higher in LC group than LC + PVT group (P3 = 0.009).
Regarding serum total bilirubin, the mean of total bilirubin was significantly higher in LC + PVT group than LC group (P3 = 0.029).
There was no significant difference between LC group and LC + PVT group regarding to ALT, AST and serum albumin (P = 0.997), (p =0.786) and (p = 0.999) respectively.
Serum creatinine and blood urea levels were significantly higher in LC group than LC+PVT group (P = 0.001) and (P < 0.0001) respectively.
There was no significant difference between LC group and LC+PVT group regarding to APRI score, FIB-4 score and MELD score (P = 0.166), (P = 0.208) and (P3 = 0.265) respectively.
Regarding protein C level in blood, the mean of protein C was significantly lower in LC group than control group (P1 < 0.0001). The mean of protein C was significantly lower in LC + PVT group than control group (P2 < 0.0001). The mean of protein C was significantly lower in LC + PVT group than LC group (P3 = 0.001).
Our study showed that person correlation between protein C level in blood and age, laboratory data, MELD score, FIB-4 score, APRI score, Child-Pugh score and PVT diameter. In LC group, there was significant positive correlation between protein C and serum albumin (p- value =0.023). There was significant negative correlation between protein C and total bilirubin (p- value = 0.014) and MELD score (p-value =0.015). There was no significant correlation between protein C and Hob level (p- value = 0.886), Plt. (p- value = 0.979), PV diameter (p- value = 0.946), age (p- value = 0.949), PT (p- value = 0.524), AFP (p- value = 0.690), creatinine (p- value = 0.090), urea (p- value = 0.593), WBCs (p- value = 0.152), ALT (p- value = 0.696), AST (p- value = 0.481), FIB-4 score (p- value = 0.425), APRI score ( p- value =0.402) and Child-Pugh score (p- value = 0.131).
In LC+PVT group, there was no significant correlation between protein C and age (p- value = 0.155), PT (p- value = 0.700), AFP (p- value = 0.734), creatinine (p- value = 0.913), urea (p- value = 0.064), albumin (p- value = 0.712), ALT (p- value = 0.930), AST (p- value = 0.848), WBCs (p- value = 0.717), Hb level (p- value = 0.238), Plt. (p- value = 0.348), bilirubin (p- value = 0.159) , PV diameter (p- value =
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0.503), MELD score (p- value = 0.287), FIB-4 score (p- value = 0.591), APRI score (p- value = 0.622) and Child-Pugh score (p- value = 0.130).
Area under the Curve for protein C was 0.97and cut off value was < 8.350 for differentiating L.C group from L.C+PVT group.
Sensitivity and specificity of protein C based on ROC analysis, between L.C group and L.C+PVT group, protein C were 85.0% and 97.0% respectively with 97.0% positive predictive value and 82.0% negative predictive value.
Regarding multiple logistic regression analysis of the relationship between the presence of PVT and other independent variables, protein C, PT, serum creatinine, blood urea and total bilirubin are independent risk factors of PVT in cirrhotic pateints