Evaluation of a Prolonged Prothrombin Time

J. L. Hood, C. S. Eby
2008 Clinical Chemistry  
A 47-year-old African American woman was evaluated for a prolonged prothrombin time (PT) result obtained before she underwent right total hip arthroplasty. The patient had no history of gastrointestinal or intracranial bleeding, epistaxis, or hemarthrosis. However, she reported a tendency toward easy limb bruising and menorrhagia, which required iron supplementation. She had a negative family history of abnormal bleeding. Initial laboratory studies included findings within reference intervals
more » ... ference intervals for complete blood cell count and activated partial thromboplastin time (aPTT) (30.8 s, reference interval 23-36 s), prolonged PT (20.3 s, reference interval 11.0 -15.0 s), and International Normalized Ratio (INR) (1.78, reference interval 0.9 -1.2). No preanalytical artifacts were identified, and the result of a repeat PT was also prolonged. DISCUSSION LABORATORY EVALUATION OF PROLONGED RESULTS FOR SCREENING COAGULATION TESTS PT and aPTT are commonly requested screening tests. In vivo, the initiation of coagulation depends on tissue factor-mediated factor VII (FVII) activation, and sustained thrombin generation requires activation of factors XI, IX, VIII, X, and V. For the interpretation of PT and aPTT results, however, coagulation factor activation culminating in a fibrin clot can be organized into intrinsic, extrinsic, and common pathways ( Fig. 1 ). An isolated result showing aPTT prolongation suggests a deficiency or inhibitor of one or more of the intrinsic pathway clotting factors (prekallikrein, high molecular weight kininogen, factors XII, XI, IX, and VIII). An isolated PT prolongation suggests a deficiency or inhibition of the extrinsic pathway (FVII), but mild factor X, V, and II deficiencies are also possible causes. Prolongation of both aPTT and PT suggests a deficiency or inhibition of the common pathway coagulation factors (factor X, V, and II), or a qualitative or quantitative fibrinogen defect. When evaluating an unexpected prolonged aPTT and/or PT result, the first step is to rule out preanalytical causes of inaccuracy (1 ). Anticoagulant contamination due to blood collection from a venous or arterial line flushed with heparin is a common artifact, and although most commercial PT reagents contain a substance capable of neutralizing approximately 2 U/mL of heparin, this capacity can be overwhelmed if blood is collected from heparin-containing catheters. Other preanalytical variables include the use of collection tubes containing a higher sodium citrate anticoagulant concentration (3.8% instead of 3.2%), hemolyzed samples interfering with photo-optical clot detection methods, and a prolonged time lapse between specimen collection and performance of aPTT (Ͼ4 hours) and PT (Ͼ24 hours) assays. An increase of the citrate: plasma ratio, which decreases the ionized calcium concentration [e.g., in samples from patients with high hematocrit (Ͼ55%) or samples collected in underfilled collection tubes] may produce erroneously prolonged PT and aPTT results. The second step in evaluating an unexpected prolonged aPTT and/or PT result should be to repeat the aPTT or PT assay, taking care to eliminate potential sources of preanalytical artifact. If the screening coagulation test continues to show prolonged times, the third step is to perform a mixing study on a 50:50 mixture of patient plasma and normal pooled plasma. Correction to within the reference interval is consistent with a deficiency of one or more factors, and no or partial correction is consistent with inhibitor activity due to an anticoagulant, a factor-specific neutralizing antibody, or a nonspecific lupus anticoagulant. ADDITIONAL PATIENT DATA We performed a mixing study, and the PT was corrected to 14.5 s, a result suggestive of an FVII deficiency because lupus anticoagulant, common pathway, and fibrinogen defects usually prolong the aPTT as well. FVII activity measurement performed on a mechanical clot detection instrument with rabbit thromboplastin activator was 5% (reference interval 60%-150%). Additional investigations ruled out a coexisting common pathway defect (factor V 144%, factor X 86%, factor II not done), fibrinogen deficiency (fibrinogen,
doi:10.1373/clinchem.2007.100818 pmid:18375491 fatcat:secu7jwdzjc5jokd4h464hiqri