In certain situations the prothrombin time can be a useful liver test. The liver synthesizes prothrombin but needs vitamin K to do so. Vitamin K is a fat-soluble vitamin that is present in most adequate diets and is also synthesized by intestinal bacteria; in either case, it is absorbed from the small bowel in combination with dietary fat molecules. Consequently, interference with vitamin K metabolism can take place because of (1) lack of vitamin K due to dietary deficiency, destruction of intestinal bacteria, or defective intestinal absorption due to lack of bile salts or through primary small bowel malabsorption; (2) inadequate utilization secondary to destruction of liver parenchyma; or (3) drugs, due to coumarin anticoagulants or certain cephalosporin antibiotics. Normally, the body has considerable tissue stores of vitamin K, so that it usually takes several weeks to get significant prothrombin deficiency on the basis of inadequate vitamin K alone. However, as noted in the discussion of PT in Chapter 8, low vitamin K intake because of anorexia or prolonged IV feeding can be potentiated by antibiotics, other medications, or poor absorption. Nevertheless, the usual cause of prothrombin abnormality is liver disease. In most cases it takes very severe liver disease, more often chronic but sometimes acute, before prothrombin levels become significantly abnormal. In the usual case of viral hepatitis, the PT is either normal or only slightly increased. In massive acute hepatocellular necrosis the PT may be significantly elevated, but it seems to take a few days to occur. In mild or moderate degrees of cirrhosis the PT is usually normal. In severe end-stage cirrhosis the PT is often elevated. The test most often used to differentiate PT elevation due to liver cell damage from other conditions that affect vitamin K supply or metabolism is to administer an intravenous or intramuscular dose of vitamin K and then repeat the PT 24-48 hours later. PT elevation due to liver cell damage usually does not respond to parenteral vitamin K therapy, whereas the PT will return to reference range in other conditions affecting vitamin K. In metastatic carcinoma the PT is usually normal unless biliary tract obstruction is present.

Some Etiologies for Gamma-Glutamyltransferase (GGT) Elevation
Liver space-occupying lesions (M-H)* (88%, 45%-100%)†
Alcoholic active liver disease (M, occ H) (85%, 63%-100%)
Common bile duct obstruction (M-H) (90%, 62%-100%)
Intrahepatic cholestatis (M-H) (90%, 83%-94%)
Biliary tract acute inflammation (M-H) (95%, 90%-100%)
Acute hepatitis virus hepatitis (M, occ H) (95%, 89%-100%)
Infectious mononucleosis (M/S, occ H) (90%)
Cytomegalovirus acute infection (S/M) (75%)
Acute pancreatitis (M, occ H) (85%, 71%-100%)
Active granulation tissue formation (S-M)
Acetaminophen overdose (S/M)
Dilantin therapy (S, occ M) (70%, 58%-90%)
Phenobarbitol (similar to Dilantin)
Severe liver passive congestion (S) (60%)
Reye’s syndrome (S) (63%)
Other; all usually S elevations
Acute MI (5%-30%)
Tegretol (30%)
Hyperthyroidism (0%-62%)
Epilepsy (50%-85%)
Brain tumor (57%)
Diabetes mellitus (24%-57%)
Non-alcohol fatty liver
*S, Small (1-3X upper limit); M, Moderate (3-5X); H, High (over 5X)
†Percentage of patients, with literature range

Certain conditions not involving liver disease or vitamin K absorption can affect the PT. Anticoagulant therapy with coumarin drugs or heparin is discussed in Chapter 8. Heparin flushes, blood with a very high hematocrit level, and severe hyperlipemia (when photo-optical readout devices are used) can produce artifactually elevated PT results. Various medications can affect the PT.