(Study type: Blood collected in a completely filled blue-top [3.2% sodium citrate] tube; related body system: Circulatory/hematopoietic system. If the patient’s hematocrit [Hct] exceeds 55%, the volume of citrate in the collection tube must be adjusted. Important Note: The collection tube should be completely filled. When multiple specimens are drawn, the blue-top tube should be collected after sterile [i.e., blood culture] tubes. Otherwise, when using a standard vacutainer system, the blue top is the first tube collected. When a butterfly is used, due to the added tubing, an extra red-top discard tube should be collected before the blue-top tube to ensure complete filling of the blue-top tube.)

Identification of Coagulation Disorders

Activated PTT or aPTT refers to a method change in the 1970s from the original PTT study that was developed in 1953. The most significant modification was the addition of activators to the test reagents, which sped up the reaction time and increased the sensitivity of the procedure. It also allowed for the establishment of a more narrow normal range than was reported with the original PTT. The aPTT, also still called PTT, remains a commonly requested test despite its known shortcomings (e.g., erroneous results due to improper specimen collection/handling, variability of results from different lot numbers of reagents, interfering substances, and unpredictable effects of physiological conditions).

The aPTT evaluates the function of the contact activation pathway (also referred to as the intrinsic pathway: factors XII, XI, IX, VIII, prekallikrein, and high molecular weight kininogen) and the common pathway (factors V, X, II, and I) of the coagulation process. The term intrinsic pathway is still used although mainly for identification of associated coagulation factors. The prothrombin time (PT), a closely related coagulation study, is used to evaluate function of the tissue factor pathway (also referred to as the extrinsic pathway: factor VII, tissue factor, calcium). For additional information on the coagulation process and factor deficiencies, refer to the studies titled “Coagulation Factors,” “Fibrinogen,” and “Prothrombin Time and International Normalized Ratio.” The aPTT represents the time required for formation of a firm fibrin clot after reagents that include activators such as silica or ellagic acid, synthetic phospholipids, and calcium are added to a plasma specimen. The aPTT is abnormal in 90% of patients with coagulation disorders and is prolonged when there is a 30% to 40% deficiency in one of the required factors or when factor inhibitors (e.g., antithrombin, protein C, or protein S) are present. For additional information regarding factor inhibitors, refer to the studies titled “Antithrombin” and “Protein C and Protein S.”

The aPTT and PT studies assist in identifying the cause of or tendency for bleeding as related to coagulation defects. A comparison between the results of aPTT and PT tests allows for some inferences to be made that a factor deficiency exists:

• A normal aPTT with a prolonged PT can occur only with factor VII deficiency.
• A prolonged aPTT with a normal PT could indicate a deficiency in factors XII, XI, IX, VIII, and VIII:C (von Willebrand factor).
• Factors X, V, II, and I are in the common pathway and can be evaluated by either the aPTT or the PT.

Monitoring Anticoagulant Therapy

The aPTT is used to monitor heparin therapy. It may be ordered together with the prothrombin time (PT/INR) to evaluate how the patient’s coagulation pathways facilitate clot formation and cessation of bleeding.

There are two types of blood thinners: anticoagulants that slow blood clot formation by directly or indirectly interfering with the coagulation process and antiplatelet drugs that prevent platelets from clumping and forming clots. For additional information about antiplatelet drugs, refer to the study titled “Platelet Count and Tests of Platelet Function.” There are four types of anticoagulants:

1. Vitamin K antagonists (e.g., warfarin, first introduced in 1954, was the only oral anticoagulant until the development of the direct oral anticoagulants [DOACs]. Warfarin is still recommended for treatment of patients with moderate to severe mitral stenosis or mechanical heart valve) (traditionally monitored by the PT/international normalized ratio [INR])
2. Heparins (UFH traditionally monitored by the aPTT; anti-Xa assay can monitor UFH and LMWHs)
3. Direct thrombin inhibitors (DOACs, e.g., dabigatran) (approved for use without the need for routine monitoring)
4. Factor Xa inhibitors (DOACs, e.g., apixaban, betrixaban, edoxaban, rivaroxaban) (approved for use without the need for routine monitoring)

The heparins are mainly used for prevention or treatment of blood clots related to atrial fibrillation, deep vein thrombosis (DVT), heart attack, pulmonary embolism (PE), obstructed stents or vascular catheters, and stroke. The major anticoagulant effects of heparin are prevention/dissolution of fibrin clot formation by

• inactivation of thrombin (which also inhibits thrombin-induced platelet activation, factor V, and factor VIII)
• inactivation of factor Xa

LMWH produces a more stable, predictable response and requires less-frequent monitoring to maintain its effectiveness. It is designed to last longer than UFH and can be injected under the skin, either at home or in a medical facility. LMWH is also used to “bridge” or transition patients to long-term oral anticoagulant therapy.

Traditionally for the patient on anticoagulant therapy with UFH, therapeutic levels are estimated by adjusting the dosage so the aPTT value is 1.5 to 2.5 times the normal. The aPTT cannot be used to monitor LMWHs (e.g., dalteparin, enoxaparin, or fondaparinux). The aPTT should not be used to monitor DOACs.

Some facilities have replaced the aPTT for monitoring UFH and LMWH anticoagulant therapy with the heparin anti-Xa test. The heparin anti-Xa test is also helpful in situations where the aPTT is affected by interference such as from lupus anticoagulants (autoantibodies that target phospholipids on cell surfaces—or react/interfere with aPTT reagents) or has limited value as demonstrated in patients with heparin resistance and severe kidney or liver dysfunction. The heparin anti-Xa test may not be available in some facilities due to the high cost of the test relative to the cost of the aPTT.

Activated Clotting Time

The activated clotting time (ACT) is point-of-care testing (POCT) used in specialized settings by specifically trained health-care personnel to assess the clotting time in whole blood specimens from patients receiving high-dose anticoagulant therapy (e.g., UFH). Results from the ACT and aPTT are not comparable; they are different methods of measuring clotting time. The aPTT evaluates a simulated or in vitro clotting reaction; extremely high levels of anticoagulant will overwhelm the available aPTT reagents, and the reaction that normally occurs in the absence of or with moderate administration of anticoagulants will not take place—in other words, the high-dose sample will not clot. The ACT evaluates the inhibitory effect that the administered levels of heparin have on the patient’s clotting system; lower ACT measurements will reflect that the heparin dose was insufficient to prevent clot formation, while higher levels will demonstrate that acceptable anticoagulation has been achieved.

One of the limited circumstances in which the ACT is more helpful than aPTT is immediately before, during, and after an open heart bypass when high doses of heparin are used to prevent clot formation as the patient’s blood circulates through an external mechanical device that filters and oxygenates the blood during the surgical procedure. ACT testing is rarely performed in the central laboratory but is performed at the bedside or at a location close to where the surgery or other procedure is being performed. After the procedure, the anticoagulant dosage is reduced, and further monitoring is continued using the aPTT. The aPTT or anti-Xa studies are more commonly used to assess the effectiveness of moderate-level UFH maintenance therapy.

Guidelines for ACT therapeutic level are established by each laboratory licensed to oversee ACT testing and in close collaboration with participating anesthesiologists, surgeons, laboratory directors, and testing personnel. The sensitivity of the test depends on the test method used and the type of medical procedure being performed, as well as the effect the heparin has on each individual patient. Guidelines for unanticoagulated ACT levels also vary by instrument and laboratory; some general estimates are in the range of 70 or 90 to 120 sec. This information seems moot given that the primary clinical use of the ACT is for monitoring the effects of abnormally high doses of anticoagulants. The laboratory/POCT department should be consulted for questions regarding the procedure.