This case provides useful information on the laboratory evaluation of a prolonged prothrombin time (PT). The great majority of PT prolongations are due to acquired rather than hereditary causes, but diagnosis of hereditary deficiencies when they are present is important for appropriate patient care. Common acquired causes of PT prolongations include warfarin therapy, vitamin K deficiency, decreased hepatic synthesis of coagulation factors, and disseminated intravascular coagulation. In each of these scenarios for acquired PT prolongation, multiple factors are typically deficient. Although mixing studies are useful in the evaluation of a prolonged PT, when multiple factor deficiencies are present the mixing study does not always correct completely into the reference interval. Mixing studies perform more reliably when only a single factor deficiency is present. The reason for the incomplete correction is presumably because, in the resulting mix, multiple factors are present in amounts at the lower end of the reference interval, a situation that can lead to a PT prolongation even though none of the factors are deficient(1).
It is also important to keep in mind the lack of utility of heparinase in the evaluation of a prolonged PT. Heparinase is useful in the evaluation of a prolonged activated partial thromboplastin time (PTT), because if the PTT is normal after treating the specimen with heparinase, then the PTT prolongation can be attributed to heparin. Thus, it is tempting to use heparinase to determine if heparin is also the cause of a prolonged PT. As noted by Hood and Eby, high amounts of heparin can overwhelm the heparin-neutralizing capability of PT reagents, resulting in a PT prolongation. However, in my experience, heparinase is not useful for evaluating prolonged PTs, because even when it is known that the PT prolongation is due to heparin, the heparinase is unable to correct the PT to reference interval values, possibly because of the increase in tissue factor pathway inhibitor that occurs with heparin therapy(2).
Grant/Funding Support: None declared.
Financial Disclosures: None declared.
- © 2008 The American Association for Clinical Chemistry