Prothrombin time (PT) is one of several blood tests routinely used in clinical practice to evaluate the coagulation status of patients. More specifically, PT is used to evaluate the extrinsic and common pathways of coagulation, which would detect deficiencies of factors II, V, VII, and X, and low fibrinogen concentrations. PT measures the time, in seconds, for plasma to clot after adding thromboplastin, (a mixture of tissue factor, calcium, and phospholipid) to a patient's plasma sample. Many different preparations of thromboplastin reagents are available which can give different PT results even when using the same plasma. Due to this variability, the World Health Organization (WHO) introduced the international normalized ratio (INR) and has become the standard reporting format for PT results. The INR represents to the ratio of the patient's PT divided by a control PT value obtained by using an international reference thromboplastin reagent developed by the WHO.
Standard laboratory coagulation-based testing has traditionally been used to obtain measurements of PT to ensure reliable results. However, due to the high turnaround time of up to 90 minutes, point-of-care (POC) devices, with a turn-around time of approximately 5 minutes, are becoming more desirable. POC devices are of great value in the emergency and operating room settings where clinical diagnosis and intervention are time-sensitive. With increased prescribing of vitamin K-antagonists (VKAs) like warfarin, point-of-care devices have also been more convenient for patients and general practitioners to monitor medication effectiveness. With point-of-care devices, monitoring anticoagulation therapy can take place at thrombosis centers, primary care provider offices, and even by the patients themselves. Although point-of-care devices have been shown to underestimate hemostatic abnormality, point-of-care devices are generally reliable in non-emergency settings. Coagulation tests must be performed using plasma samples and not serum as clotting factors get removed in serum preparations. Standard percutaneous phlebotomy is the recommended method used to collect venous blood samples. However, blood samples may also be obtained from indwelling intravenous lines when necessary.
Phlebotomists collect venous blood samples in plastic tubes with a light blue top that contains 3.2% sodium citrate. Sodium citrate serves to chelate the calcium in the blood sample and prevents the activation of the coagulation cascade. This chelation keeps the blood sample in stasis until ready to be tested. Tube filling must be to within 90 percent of the full collection volume with blood to sodium citrate ratio of 9 to 1. The tube is then gently inverted a few times to mix the sodium citrate solution with the blood. The tube should not be shaken to avoid hemolysis that would lead to inaccurate results. Once the blood sample is ready to be tested, calcium chloride is then added to restore the calcium required for coagulation activation. Clot formation can then be detected mechanically or optically depending on the instrumentation used.
Indications for obtaining PT are:
Causes for a prolonged PT include:
The reference ranges for PT vary by laboratory since different facilities use reagents or instruments. However, in most laboratories, the normal range for PT is 10 to 13 seconds. The normal INR for a healthy individual is 1.1 or below, and the therapeutic range for most patients on VKAs is an INR of 2.0 to 3.0. An increased PT/INR for patients on VKAs may suggest a super-therapeutic level and will require medication dose adjustments to prevent bleeding.
As the use of VKAs increases, it is vital to educate patients on the importance of routine monitoring of PT/INR. Proper monitoring will allow for medication adjustments and prevention of adverse events. If patients are self-monitoring with POC devices, sufficient education and training is necessary for the patient and/or family members who will assist the patient. The cognitive capacity of patients must also be evaluated to ensure the proper use of POC devices.
PT, along with INR, are important measurements to monitor patient coagulation status, especially patients who are on VKAs. However, although PT/INR is useful in monitoring coagulation status, they are rarely used alone. PT/INR use is typically in conjunction with activated partial thromboplastin time (aPTT), which evaluates the intrinsic and common pathways of coagulation. PT/INR and aPTT results together can help in diagnosing various hematologic disorders.
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