Anticoagulants: Effects on PT, PTT

Laboratory testing for coagulation studies are commonly performed in a light blue top tube, which has 3.2% sodium citrate added in a specific amount to prevent coagulation of the blood. The tube should be inverted immediately upon adding the blood sample to mix the sodium citrate with the blood, but the sample should not be shaken in order to avoid hemolysis. Of note, polycythemia may artificially alter coagulation tests unless the amount of sodium citrate is corrected for the polycythemia. In the laboratory, calcium is added back to the sample to overcome the sodium citrate, and then an additional reagent (see below) is added to perform the clotting test.

To obtain the prothrombin time (PT), tissue factor and phospholipid are added to the blood sample. The time (in seconds) are counted until a fibrin clot is formed. The number of seconds is the prothrombin time, and this number can be divided by a lab standard to form the International Normalized Ratio (INR). The PT/INR are valuable for evaluating the common and extrinsic coagulation pathways. Warfarin (vitamin K antagonist) prolongs the PT. Direct-acting anticoagulants also prolong the PT. Examples of these are argatroban (direct thrombin inhibitor), dabigatran (direct thrombin inhibitor), rivaroxaban (factor Xa inhibitor), apixaban (factor Xa inhibitor), and edoxaban (factor Xa inhibitor). While heparins (unfractionated and low-molecular weight) indirectly antagonize factor Xa, they typically do not prolong the PT except in cases of a large heparin bolus (i.e. for cardiopulmonary bypass). Fondaparinux also inhibits Xa, but typically does not alter PT or activated Partial Thromboplastin Time (aPTT) (“Fondaparinux …”).

To obtain the activated Partial Thromboplastin Time (aPTT, PTT), a “thromboplastic material” along with a “negatively charged substance” are added to the sample to activate contact factor for coagulation (Zehnder). Again, the PTT is measured in seconds. The PTT reflects coagulation via the common and intrinsic coagulation pathways. Heparin can cause a prolongation of the PTT along with direct thrombin inhibitors and direct Xa inhibitors. It is important to note that the PTT does not reliably reflect the level of anticoagulation that some oral anticoagulants provide. As previously mentioned, fondaparinux typically does not alter PTT, but it may mildly increase the PTT. Warfarin can increase the PTT in supratherapeutic doses.