Learn how to pinpoint the cause of prolonged PT and investigate bleeding in patients with normal PT. In this video from our Hematology and Coagulation Essentials course, you'll learn the mechanisms behind PT tests and how to interpret the results. You will be able to formulate a common differential diagnosis of prolonged PT and understand which tests to order next.
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Demystify hematology and coagulation with our fascinating Hematology and Coagulation Essentials course! Hematological and coagulation disorders can be difficult to diagnose. By the end of this course, you'll be able to confidently assess the most important diagnostic aspects of hematology and coagulation and shine during your next night on call. Never again will you wonder what a prolonged PTT really means, how to differentiate between a factor deficiency and an inhibitor, or what tests to order next.
[00:00:00] Here, we're going to discuss the prothrombin time or PT for short. Prothrombin time is a common test for secondary hemostasis. To test for PT, the patient's blood is collected in a citrate tube. The blood is centrifuged to separate the plasma. Testing will be done on the plasma portion. To the patient's plasma, we add thromboplastin, also known as factor 3 and calcium. The blood clots and
[00:00:30] the time to clot is prothrombin time or PT and is measured in seconds. However, since the thromboplastin used in the lab, may vary from lab to lab and country to country, the prothrombin time is best reported as INR. INR stands for international normalized ratio. This value is obtained from a formula, which is shown. The INR is calculated from the patient's prothrombin time and the mean normal prothrombin time. ISI stands for
[00:01:00] international standardized index, which is obtained from the package inside of the reagent. You will never have to calculate this value. It is done at the lab. Prothrombin time or PT measures the integrity of the extrinsic pathway and the common pathway. Another test called PTT measures the integrity of the intrinsic and the common pathway. If we have a patient with isolated prolonged PT, then the defect must belong in the extrinsic pathway.
[00:01:30] The extrinsic pathway involves factor 3, which is thromboplastin as well as factor 7. But when the lab performs the test PT, thromboplastin is added, therefore, the only cause of prolonged PT, with normal PTT, is abnormality of factor 7. This can be due to factor 7 deficiency or the presence of an inhibitor to factor 7 which, however, is very rare. Factor 7 deficiency may be inherited, which is again
[00:02:00] rare or the deficiency may be acquired. Causes of acquired deficiency of factor 7 include liver disease, vitamin K deficiency, and patients on the drug warfarin. So, how does vitamin K deficiency cause prolonged prothrombin time? There are some clotting factors, which are vitamin K dependent. With vitamin K deficiency, these factor levels will be low. Since factor 7
[00:02:30] has the shortest half-life, the manifestation of this deficiency is seen early and is persistent. Factor 7 is part of the extrinsic pathway, and with a defect in the intrinsic pathway, the PT will be prolonged due to vitamin K deficiency. Why does warfarin cause vitamin K deficiency? There are two forms of vitamin K: the functionally active vitamin K and the non-functional form, vitamin K epoxide. Reductase
[00:03:00] enzyme converts vitamin K epoxide to functional vitamin K, warfarin blocks this reductase enzyme. Non-functional vitamin K epoxide accumulates, thus, levels of functional vitamin K are reduced. Vitamin K is required for clotting factors 2, 7, 9, and 10 and so with reduced vitamin K, levels of these clotting factors are reduced. As we know, factor 7 is part of the extrinsic pathway and when the extrinsic pathway is
[00:03:30] inhibited, PT is prolonged. So, in patients who are taking warfarin, vitamin K is reduced and PT should be prolonged. So, with the prolonged prothrombin time, what should we do next? As we know, there are two broad categories of prolonged prothrombin time. One is deficiency of clotting factor 7 and the second is inhibitor to clotting factor 7. The next test to order is a mixing study.
[00:04:00] This will be discussed in a separate lesson.