Coagulation 2 PDF

CBL Coagulation 2 After completing this session, you will be able to: Describe how the prothrombin time (PT), international normalized ratio (INR), partial thromboplastin time (PTT), thrombin time (TT), PTT mixing study, and fibrin degradation product (FDP) assay are performed List the s...

CBL Coagulation 2 After completing this session, you will be able to: Describe how the prothrombin time (PT), international normalized ratio (INR), partial thromboplastin time (PTT), thrombin time (TT), PTT mixing study, and fibrin degradation product (FDP) assay are performed List the situations in which you would order each test CASE CONNECTION A 46-year-old woman who comes to the emergency department with chest pain. Her vital signs and physical examination are unremarkable. The electrocardiogram is normal. While she is in the radiology department for a chest x-ray, you ask an intern, “What are you thinking?” She tells you she thinks this is musculoskeletal chest pain and that the probability is very low this is a pulmonary embolism. “But maybe we should get a CT scan anyway. That’ll rule it out for sure,” she says. What test will you recommend to rule out a pulmonary embolism for her? Consider your answer as you read, and we’ll revisit PA at the end. What Are Coagulation Assays? If you want to make a blood clot, you need to do two things: primary hemostasis, and secondary hemostasis. Defects in either primary or secondary hemostasis can lead to poor clot formation and excessive bleeding. So if a patient presents with unexplained bleeding—or if we just want to assess how well a patient can clot (before performing surgery, for example)—the two main things to evaluate are the platelets and the coagulation cascade. In this section, we will focus on assays that evaluate how well the coagulation cascade works—in other words, how well a patient can form fibrin. What Are the Main Coagulation Assays? We will focus on the most commonly used tests, which include the prothrombin time (PT), international normalized ratio (INR), partial thromboplastin time (PTT), and thrombin time (TT). These tests look at different parts of the coagulation cascade  When drawing blood for a coagulation assay, a special tube—which usually has a light blue top—is used. This tube contains citrate, which removes calcium from the blood to prevent clotting. This is important, WHY?  Blood is centrifuged, What will happened ? Now the sample contains just plasma (minus calcium), and it’s ready for any coagulation test.  The prothrombin time (PT) is used to assess the extrinsic and common pathways of the coagulation cascade. The PT is determined by taking the patient’s plasma, adding thromboplastin (a tissue factor–like substance and phospholipid) and calcium, and then measuring the time (in seconds) it takes to form fibrin. The normal PT range is typically 11-14 seconds. The problem with this test is that PT values can fluctuate between hospitals because thromboplastin reagents vary a lot from manufacturer to manufacturer. So the PT conducted at one hospital may produce results quite different from the PT conducted on the same patient at a different hospital.  The international normalized ratio (INR) was developed to standardize the method of presenting the PT value. The INR is derived from a formula using the ratio of the patient’s PT to a standard PT. As a result, the INR value of the patient will be similar at any hospital. The normal range for the INR is 0.8-1.2 seconds. The partial thromboplastin time (PTT) is used to assess the intrinsic and common pathways of the coagulation cascade. The PTT was named this way when it was discovered that fibrin could form by just using part of the thromboplastin reagent. It is now known that the part of the thromboplastin reagent used is the phospholipid (no tissue factor–like substance is present).  The PTT is determined by taking the patient’s plasma, adding phospholipid and calcium, and then measuring the time (in seconds) it takes to form fibrin. This makes sense because normally in the body, tissue factor is necessary to activate the extrinsic pathway, but it is not necessary to activate the intrinsic pathway. The activated partial thromboplastin time (aPTT) is similar to the PTT except that an activator is added to the PTT assay, which helps speed up clot formation and results in a narrower reference range. The aPTT is considered to be more sensitive than the PTT and is used to monitor heparin therapy. The aPTT is more commonly used in the clinical setting. The normal range of the aPTT is 25-35 seconds.  The thrombin time (TT) assesses the conversion of fibrinogen to fibrin. It is determined by taking the patient’s plasma, adding thrombin, and measuring the time (in seconds) it takes to form fibrin. The normal range of the thrombin time is 12-14 seconds. Which pathways of the clotting cascade do the PT and PTT assess? -The PT is used to assess the extrinsic pathway, the PTT is used to assess the intrinsic pathway, and both assess the common pathway. When Are Coagulation Assays Used? Coagulation assays can be used to evaluate patients with bleeding of unknown etiology or to monitor anticoagulant therapy. Determining the cause of abnormal bleeding includes checking for hereditary factor deficiencies, such as hemophilia, as well as checking for acquired bleeding disorders like liver disease, vitamin K deficiency, and disseminated intravascular coagulation.  CLINICAL CORRELATION All of the coagulation factors involved in the coagulation cascade are produced in the liver. Patients with cirrhosis or other advanced liver diseases have an especially high risk of bleeding because they are unable to make coagulation factors at a normal rate. In these cases, all coagulation assays are prolonged (PT, INR, PTT, TT) because all the coagulation factors are decreased.  Warfarin acts as a vitamin K antagonist, decreasing production of vitamin K–dependent clotting factors II, VII, IX, and X. Factor IX is part of the intrinsic cascade, while factor VII is part of the extrinsic cascade, so both the PT and the PTT will be prolonged. However we use the PT/INR study to monitor warfarin therapy because factor VII has the shortest half-life of all the vitamin K–dependent factors. So the effects of warfarin on coagulation are reflected by the PT/INR before the PTT.  On the other hand, heparin indirectly binds to antithrombin to enable antithrombin to inactivate multiple clotting factors, including IIa, VIIa, IXa, Xa, and XIa. Antithrombin acts on both the intrinsic and the extrinsic arms of the clotting cascade. Heparin, however, has more of an effect on the intrinsic arm than it does on the extrinsic arm, so the PTT is used to monitor unfractionated heparin therapy. Which laboratory value is used to monitor warfarin therapy? Which laboratory value is used to monitor heparin therapy? Warfarin is monitored with the INR value, while heparin is monitored with the PTT value. FDP Assay The fibrin degradation product (FDP) assay is used to measure the amount of fibrin degradation products present. Elevated FDPs indicate that fibrinolysis (breaking down of fibrin, typically in clots) is occurring in the body. There is also a D-dimer assay, which measures only chunks of fibrin that have been crosslinked in a clot. So it is a little more specific for fibrin in actual clots than the FDP assay is. The FDP and D-dimer assays can be useful in evaluating for disorders with increased clotting and breakdown, including deep vein thromboses (DVTs), pulmonary embolism (PE), and disseminated intravascular coagulation (DIC). CLINICAL CORRELATION DIC is a disorder in which there is abnormal activation of the coagulation cascade, resulting in widespread microthrombi throughout the vessels. However, because there is such massive activation of the coagulation pathway, clotting factors, fibrin, and platelets are consumed at a fast rate, resulting in hemorrhage, thrombocytopenia, factor deficiencies, and vessel injuries. Both hemorrhage and thrombosis occur simultaneously. DIC is most commonly seen in critically ill people. Coagulation studies supporting DIC include a prolonged PT, PTT, and TT; an elevated FDP or D-dimer assay; and a decreased platelet count. CASE CONNECTION Thinking back to PA, what test do you recommend to rule out a pulmonary embolism? You now know that the FDP assay and D-dimer indicate fibrinolysis (breakdown of clots) and chunks of fibrin crosslinked in a clot, respectively. They are highly sensitive tests. You decide to order a D- dimer, and the result is negative. “A negative test result utilizing a highly sensitive test in a low probability scenario effectively rules out the disease,” What do you think to yourself ? Summary The PT, INR, PTT, and TT tests assess various parts of the coagulation cascade by measuring the amount of time it takes to form fibrin. If the PTT is prolonged, a mixing study can help determine whether the prolonged PTT is due to a factor deficiency or an inhibitor (antiphospholipid antibody). The FDP assay measures products of fibrinolysis (fibrin degradation products).