The most important clue to a clinically significant bleeding disorder in an otherwise healthy patient remains in the history. A history of anemia requiring iron replacement may suggest a bleeding tendency. Prior surgical bleeding, gingival bleeding, easy bruising, epistaxis, or menorrhagia should raise concern. Many tests are available to assess the coagulation system. However, the clinician must remember that the coagulation system is a complex interplay of platelets and coagulation factors.
Activated partial thromboplastin time (aPTT) is performed by adding particulate matter to a blood sample to activate the intrinsic coagulation system. Normal values for the PTT are 22 to 34 seconds, varying according to the reagent and instruments used by the specific laboratory. The aPTT assesses factors in the intrinsic (XI, XII, VIII, IX, and contact factors) and the common (II, V, X, and fibrinogen) coagulation pathways. The test is sensitive to decreased amounts of coagulation factors and is elevated in patients on heparin therapy. The aPTT will be abnormal in patients who have hemophilia or a circulating anticoagulant (e.g., lupus anticoagulant or antibodies to factor VIII). The clinician should remember that an abnormal aPTT does not necessarily correlate with clinical bleeding. Aggressive correction of an abnormal aPTT in surgical patients is not always indicated, unless the patient is actively bleeding.
Prothrombin time is a measure of factors of the extrinsic (VII and tissue factor) and common (see above) coagulation pathways and is measured by adding tissue factor to a blood sample. While both PT and aPTT are affected by levels of factors V and X, prothrombin, and fibrinogen, the PT is specifically sensitive to deficiencies of factor VII. The PT is normal in deficiencies of factors VIII, IX, XI, XII, prekallikrein, and high molecular weight kininogen.
The international normalized ratio (INR) is a means of standardizing PT values to allow comparisons among different laboratories or at different times. It is the ratio of the patient's PT to the control PT value that would be obtained if international reference reagents had been used to perform the test. Oral warfarin anticoagulation therapy may therefore be guided by a target INR value that is independent of the laboratory variability of the PT. For example, an INR of 2.0 to 3.0 is recommended for prophylaxis against thromboembolism in atrial fibrillation.
Activated clotting time (ACT) is a modified whole blood clotting time in which diatomaceous earth (celite) or clay (kaolin) is added to a blood sample to activate the intrinsic clotting system. The ACT is the time until clot formation. A normal ACT is 90 to 130 seconds, depending on the instrument used. The ACT is a relatively easy and expedient test to perform and is useful in monitoring heparin therapy in the operating room (see Chapter 24). Because the ACT is relatively insensitive to lower levels of heparin anticoagulation, it is typically reserved for settings that require full anticoagulation such as cardiopulmonary bypass and extracorporeal membrane oxygenation (ECMO).
Fibrinogen is the precursor protein that is dimerized to form the strong fibrin components of clots. Assaying fibrinogen levels can be helpful when coagulopathy is present or suspected. While the diagnostic specificity of the fibrinogen level is low, it can be helpful to guide further transfusion support (i.e., the administration of FFP or cryoprecipitate).
Thromboelastography (TEG) is available in some centers for clinical use, often as a point-of-care test. TEG is performed by placing a small aliquot of blood into a heated oscillating cup into which is suspended a pin on a torsion wire. Clot formation in the oscillating cup generates torque on the pin, and the torque is measured and converted to an electrical signal. The signal is recorded by a computer, creating a characteristic trace (Fig. 35.1) that may be analyzed for abnormalities of clot formation. By measuring clot formation and viscoelastic clot strength, TEG provides information about the adequacy of clotting factors, fibrin levels, and platelets. In general, R represents the activity of coagulation factors, maximum amplitude the platelet function/number, and the alpha angle the acceleration of fibrin formation. Thromboelastometry or ROTEM uses a similar technology, with similarly measured parameters.
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