Laboratory prothrombin time

Clark, G.M. A statistical and clinical evaluation of fingerstick and routine laboratory prothrombin time measurements. Pharmacotherapy 1997, 17 (5), 861-866. 

The international normalized ratio (INR) is a method to standardize repotting of the prothrombin time, using the formula, INR = (PTpatie t/PTcontroi)ISI, where PT indicates the prothrombin times (for the patient and the laboratory control), and ISI indicates the international sensitivity index, a value that varies, depending upon the thromboplastin reagent and laboratory instrument used to initiate and detect clot formation, respectively. 

Table 32-3 summarizes laboratory results obtained on patients with three different causes of jaundice—hemolytic anemia (a prehepatic cause), hepatitis (a hepatic cause), and obstruction of the common bile duct (a posthepatic cause). Laboratory tests on blood (evaluation of the possibihty of a hemolytic anemia and measurement of prothrombin time) and on semm (eg, electrophoresis of proteins activities of the enzymes ALT, AST, and alkahne phosphatase) are also important in helping to distinguish between prehepatic, hepatic, and posthepatic causes of jaundice. 

A number of laboratory tests are available to measure the phases of hemostasis described above. The tests include platelet count, bleeding time, activated partial thromboplastin time (aPTT or PTT), prothrombin time (PT), thrombin time (TT), concentration of fibrinogen, fibrin clot stabifity, and measurement of fibrin degradation products. The platelet count quantitates the number of platelets, and the bleeding time is an overall test of platelet function. aPTT is a measure of the intrinsic pathway and PT of the extrinsic pathway. PT is used to measure the effectiveness of oral anticoagulants such as warfarin, and aPTT is used to monitor heparin therapy. The reader is referred to a textbook of hematology for a discussion of these tests. 

Prior to initiating treatment with a LMWH, baseline laboratory tests should include PT (prothrombin time)/INR, aPTT, complete blood cell count (CBC), and serum creatinine. Monitor the CBC every 3 to 4 days during the first 2 weeks of therapy, and every 2 to 4 weeks with extended use.5 Use LMWHs cautiously in patients with renal impairment. Specific dosing recommendations for patients with a creatinine clearance (CrCl) less than 30 mL/minute are currently available for enoxaparin but lacking for other agents of the class (Table 7-3). Current guidelines recommend the use of UFH over LMWH in patients with severe renal dysfunction (CrCl less than 30 mL/minute).8... 

Monitor the following serial laboratories for comparison to baseline values every 6 hours in the first 24 hours and daily thereafter until normalized sodium, serum creatinine, blood urea nitrogen, serum lactate, glucose, bilirubin, hemoglobin, hematocrit, platelets, prothrombin time, partial thromboplastin time, arterial blood gases, and pH. 

International Normalized Ratio (INR) The ratio of the patient s clotting time to the clinical laboratory s mean reference value normalized by raising it to the International Sensitivity Index (ISI) power to account for differences in thromboplastin reagents. Therefore, INR = (patient s prothrombin time/laboratory s mean normal prothrombin time)ISI. 

Pruritus, jaundice, palmar erythema, spider angiomata, hyperpigmentation Gynecomastia, reduced libido Ascites, edema, pleural effusion, and respiratory difficulties Malaise, anorexia, and weight loss Encephalopathy Laboratory tests Hypoalbuminemia Elevated prothrombin time Thrombocytopenia Elevated alkaline phosphatase... 

Baseline laboratory tests should include complete blood cell count, prothrombin time, activated partial thromboplastin time, liver and renal function tests, and serum carcinoembryonic antigen (CEA). Serum CEA can serve as a marker for monitoring colorectal cancer response to treatment, but it is too insensitive and nonspecific to be used as a screening test for early-stage colorectal cancer. 

Monitoring Monitor renal function frequently during amphotericin B therapy. It is also advisable to monitor liver function, serum electrolytes (particularly magnesium and potassium), blood counts, and hemoglobin concentrations on a regular basis. Use laboratory test results as a guide to subsequent dose adjustments. Monitor complete blood count and prothrombin time as medically indicated. 

Laboratory monitoring Partial Thromboplastin Time (PTT) Prothrombin Time (PT)... 

The prothrombin time (PT) is used to monitor anticoagulation. The patient s PT is determined along with that for a control sample of plasma, and the two values are often reported as a ratio. Because this ratio can vary widely between laboratories, the INR system of reporting has been adopted. The INR is the ratio of the patient PT to a control PT obtained by a standard method using a World Health Organisation primary standard (human) thromboplastin. PT measurements are converted to INR measurements by the following equation ... 

Primary prevention of venous thrombosis reduces the incidence of and mortality rate from pulmonary emboli. Heparin and warfarin may be used to prevent venous thrombosis. Subcutaneous administration of low-dose unfractionated heparin, low-molecular-weight heparin, or fondaparinux provides effective prophylaxis. Warfarin is also effective but requires laboratory monitoring of the prothrombin time. 

Quantification of coagulation factors is notoriously difficult, because of the interrelations among the various components of the coagulation cascade, the broad range of normal values, and considerable inter-laboratory variability (52). This variability is illustrated by a WHO study of users of combined oral contraceptives, conducted on several continents, which showed statistically significant differences among clinical centers in prothrombin time, fibrin plate lysis, plasminogen, and activated partial thromboplastin time (SEDA-16, 464). Effects also vary between different populations, users of different doses, users of different products, and tests performed at different periods of the medication cycle (63,69). 

A 31-year-old white man with depression, hepatitis C, and cirrhosis of the liver was hospitalized for alcohol detoxification. He had taken methadone 50 mg bd for opium dependence for 6 months. He developed bilateral pedal edema and 27 kg weight gain. There was no ascites, portal hypertension, or congestive heart failure. Most of his laboratory tests were within the reference ranges, except for reduced prothrombin time and platelet count. After stopping alcohol, his methadone dose was reduced to 60 mg/day his edema resolved 15 days later. When the dose of methadone was increased to 70 mg/day there was a progressive increase in the edema. When methadone was withdrawn his edema completely resolved and he lost 8 kg in 2 weeks. 

While terbinafine had no effect on warfarin in healthy volunteers, it can prolong the prothrombin time in some individuals (74-77), prompting intensification of laboratory control during terbinafine therapy. 

The hematological effects of tumor necrosis factor alfa mostly consist of dose-related thrombocytopenia and granulocytopenia, and decreased monocyte or lymphocyte counts (SED-13, 1111) (11,12). Septic episodes are sometimes associated with leukopenia. Coagulopathy with laboratory evidence of disseminated intravascular coagulopathy was found in 30% of patients and was sometimes associated with thromboembolic events (13). Other coagulation disorders include transient alterations in prothrombin time, and a rise in the plasma concentrations of von Willebrand factor was found in healthy volunteers (14). 

Laboratory tests can identify a faulty component of clotting or whether an elderly patient is required to alter coumarin drug or vitamin K dosages before a tooth is extracted. Samples of the patient s blood are taken and treated in various ways to allow the observation of the appropriate steps in the hemostasis pathways. For example, tissue factor is added to the blood sample for the prothrombin time (PT) test. Alternatively, certain clotting system components in the blood sample are removed or inactivated. These tests can be run quickly on small samples of blood. 

---