الفهرس 
Liver CirrhosisOnly 14 pages are availabe for public view
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Abstract
Cirrhosis is defined histologically as an advanced form of progressive diffuse hepatic fibrosis with distortion of the hepatic architecture and structurally abnormal regenerative nodule formation. It may be due to a variety of causes. It can be diagnosed incidentally on liver biopsy or hepatic imaging studies, or patients may present clinically with one or more features of hepatic failure. Common signs and symptoms may stem from decreased hepatic synthetic function (e.g. coagulopathy), decreased detoxification capabilities of the liver (e.g. hepatic encephalopathy), or portal hypertension (e.g. variceal bleeding).Chronic liver disease is characterized by impaired synthesis of most coagulation factors and prolonged conventional coagulation tests such as the prothrombin and activated partial thromboplastin time.
Recently, the long and widely used belief that there is a causal relationship between abnormal coagulation tests and the risk of bleeding has been challenged by showing that under appropriate experimental conditions, liver disease patients generate as much thrombin as healthy subjects provided that platelets numbers are sufficient (>60 × 109/L) to support the normal thrombin generation elicited by plasma. These observations are in keeping with an earlier observation that patients with chronic liver disease, despite their substantial prolongation of the conventional coagulation times, are not protected from venous thromboembolism (VTE) and with those of a recent population-based case-control study showing that patients with chronic liver disease (both cirrhotic and non-cirrhotic) have a relative risk of VTE nearly two-fold higher than that of the general population.
The detection of the procoagulant versus anticoagulant imbalance might have important practical implications in assessing the risk of VTE, especially in patients with cirrhosis awaiting liver transplantation. On the other hand, chronic liver disease, particularly in the end stage, is characterized by clinical bleeding and decreased levels of most procoagulant factors, with the notable exceptions of factor VIII and von Willebrand factor, which are elevated. Decreased levels of the procoagulants are, however, accompanied by decreases in levels of such naturally occurring anticoagulants as antithrombin and protein C.
Thus far, the laboratory method available to detect the procoagulant imbalance in cirrhosis is the thrombin generation test which requires expertise and equipment that are not readily available in clinical laboratories. Recently, an assay meant to explore the anticoagulant protein C pathway was made available. It is based on the ability of endogenous activated protein C - after its activation by Protac - , to reduce the tissue factor–induced thrombin generation. Results for this test are conveniently expressed as PICI% (i.e., Protac-induced coagulation inhibition percentage), and low PICI% values can be taken as an index of hypercoagulability.
We hypothesized that the above characteristics could make it suitable to investigate the procoagulant versus anticoagulant imbalance that occurs in cirrhosis because of the partial deficiency of protein C combined with the relative increase of factor VIII.
The aim of the study was to assess the imbalance between procoagulant & anticoagulant factors in Egyptian cirrhotic patients by means of a simple standardized laboratory method. A total of 72 subjects were included in the study. Four subjects DROPped out shortly after enrolment in the study due to different technical problems. So, the final number of included patients was 68 subjects. They were divided into two main groups; group I for cirrhotic patients and group II for controls. Group I was further classified into three equal groups according to the severity of disease which was estimated according to the Child-Turcotte-Pugh score. Subjects with the following conditions were excluded from the study; usage of drugs known to interfere with blood coagulation, ongoing bacterial infections, hepatocellular carcinoma or extra hepatic malignancy, pregnancy & childhood (age <18y).
All included subjects were subjected to the following; full medical history taking (with special attention to thromboembolic versus hemorrhagic events and alcohol intake), thorough clinical examination, routine lab investigations, lab investigation needed for Child-Turcotte-Pugh score, MELD & MELD-XI formula, coagulation profile including PT, PTT & INR, lab Investigation for the cause of cirrhosis: Viral markers (HBsAg & HCV Ab) and abdominal Ultrasound to aid the diagnosis of cirrhosis. Specific investigations included; factor VIII assay, protein C assay and Protac Induced Coagulation Inhibition Percentage (PICI %) assay. All data were statistically analyzed. Results were compared to results of similar researches; the current study found that factor VIII was higher, protein C and PICI% were lower among cirrhotic Egyptian patients. This confirm the doubts as regard the elevated rates of venous thrombosis among cirrhotic patients despite the false elongation in clotting times. The study also figured PICI% & the suggested factor VIII/protein C ratio as a promising lab investigation to assess the investigated imbalance and to detect clinical bleeding Vs thrombosis. Especially that both of the suggested tests showed a direct significant correlation with factor VIII (the main powerful procoagulant) and an inverse significant correlation with protein C (the main powerful anticoagulant). However, it was difficult for the study design to assess their ability to predict different types of thrombosis especially venous thrombosis. This necessitates future nationwide prospective follow-up studies with clinical endpoints. However, it is clear now that cirrhotic patients are at least at same risk as normal healthy individuals to develop thrombosis especially venous thrombosis despite of their prolonged conventional coagulation times.