Liver disease prothrombin time

Liver disease Prothrombin time (+) a-Fetoprotein (+ Bilirubin (normal-IOOMmol/l) Succinylacetone (U) (1->1000mmol/mol creatinine) Tyrosinemia type 1... 

Prothrombin time may be prolonged in situations other than vitamin K deficiency. Administration of dicumarol or of large doses of salicylates will be followed by decreased prothrombin activity. In severe liver disease, prothrombin formation is defective and administration of vitamin K is without benefit, which finding is used as a test of liver function. 

Prothrombin time PT is performed by adding thromboplastin (tissue) factor and calcium to citrate-anticoagulated plasma, recalcifying the plasma, and measuring the clotting time. The major utility of PT is to measure the activity of the vitamin K-dependent factors II, VII, and X. The PT is used in evaluation of liver disease, to monitor warfarin anticoagulant effect, and to assess vitamin K deficiency. 

Contraindications to heparin therapy include hypersensitivity to the drug, active bleeding, hemophilia, severe liver disease with elevated prothrombin time (PT), severe thrombocytopenia, malignant hypertension, and inability to meticulously supervise and monitor treatment. 

Routine liver assessment tests include alkaline phosphatase, bilirubin, aspartate transaminase, alanine transaminase, and y-glutamyl transpeptidase (GGT). Additional markers of hepatic synthetic activity include albumin and prothrombin time. The substances are typically elevated in chronic inflammatory liver diseases such as hepatitis C, but may be normal in others with resolved infectious processes. 

The liver is the principal metabolic organ, and hepatic disease or dysfunction may impair drug elimination. Any alteration in the serum albumin or bilirubin levels and in the prothrombin time indicates impaired liver function. Similarly, skin bruising and bleeding tendency indicate decreased production of clotting factors by the liver. 

Milk thistle has been used to treat acute and chronic viral hepatitis, alcoholic liver disease, and toxin-induced liver injury in human patients. Milk thistle has most often been studied in the treatment of alcoholic hepatitis and cirrhosis. In both of these disorders, outcomes have been mixed and reports include significant reductions in markers of liver dysfunction and in mortality, as well as no effect. In acute viral hepatitis, studies have generally involved small sample sizes and have shown mixed outcomes of improved liver function (eg, aminotransferase values, bilirubin, prothrombin time) or no effect. Studies in chronic viral hepatitis and toxin-induced injury have also been of small size but have reported mostly favorable results. Parenteral silybin is marketed and used in Europe as an antidote in Amanitaphalloides mushroom poisoning, based on favorable outcomes reported in case-control studies. 

Most studies investigating paracetamol pharmacokinetics in patients with liver disease used single doses only. A 50% reduction in clearance and a corresponding increase in half-life have been seen in severe acute hepatitis, the longest half-life being seen in patients with a raised prothrombin time (PT). It may therefore be prudent to extend the dose interval in these patients. Cirrhotic patients with a low albumin and a raised PT were also noted to have a prolonged paracetamol half-life, although no accumulation or hepatotoxicity was observed when normal therapeutic doses were administered to these patients for up to five days. In contrast, cirrhotic patients with normal albumin and PT demonstrated... 

In one study, no pharmacokinetic differences were noted when a single 0.15 mg/kg intravenous dose was given to six cirrhotic patients and six healthy subjects. However, tbe cirrhotic patients had no manifestations of end-stage disease, normal prothrombin times and relatively normal liver function tests. Four had experienced prior encephalopathy [58]. 

There are no useful methods to quantify the degree of liver disease that can assist in dosage adjustment. A practical approach involves checking patients for elevated prothrombin time, rising bilirubin levels, and/or falling albumin levels. In such instances, drugs that have an altered response in liver disease or cause hepatotoxicity need to be avoided. 

Isolated coagulation abnormalities with minor prolongation of prothrombin time were consistently observed, in patients given interleukin-4, particularly those with preexisting liver disease (2). 

Prolongation of the prothrombin time can occur (11). Niridazole is contraindicated in liver disease. 

The liver synthesizes fibrinogen factors V, VIII, XI, and XII, and the vitamin K-dependent factors II, VII, IX, and X. Furthermore the liver plays an important role in platelet growth and function. The vitamin K-dependent proteins contain y-carboxy-glutamic acid. Vitamin K is necessary for the carboxylation of these proteins, which facilitate the conversion of prothrombin to thrombin. Patients with severe hepatocellular disease have decreased synthesis of the vitamin K-dependent clotting factors, especially factor VII. Furthermore, patients with cholestatic disease have decreased bile salt secretion, which is necessary for the absorption of vitamin K, leading to failure of activation of factors II, VII, IX, and X. In these patients, unlike those with hepatocellular disease, the prothrombin time can be corrected with an injection of vitamin K. 

The liver synthesizes coagulation factors I, II, V, VII, IX, and X. ° The prothrombin time is prolonged when any of these factors are absent. In acute liver disease the prothrombin time can be used as an outcome measurement in acetaminophen overdose and acute alcoholic hepatitis In chronic liver disease, the prothrombin time is employed as a marker of decreased synthetic capacity. 

Baseline laboratory tests should be obtained and include a complete blood cell (CBC) count, platelet count, prothrombin time, activated partial thromboplastin time, and liver and renal function tests. Abnormal liver function tests may suggest liver involvement with tumor. However, patients with metastatic disease to the liver may have normal liver function tests, and abnormal liver function tests are not always indicative of metastatic disease. 

Accumulated evidence suggests that liver disease is an important dinical risk factor for aminoglycoside nephrotoxicity [32]. This is particularly true of patients with biliary obstruction or cholangitis as distinct from other causes of liver disease such as alcoholic cirrhosis [33]. When hver disease is defined as any three of six criteria consisting of, AST > 2 times normal, total bi-hrubin > 2.5 pg/dl, albumin < 3 g/dl, elevated aUca-hne phosphatase, prothrombin time > 15 seconds or... 

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