Standard laboratory INR/APTT tests are difficult to interpret in the presence of the newer oral anti-coagulation medication. Early haematologist consultation is advised to assist interpretation of the results and assess the risk of bleeding.
International Normalised Ratio (INR)
The International Normalised Ratio (INR) is the PT ratio corrected for the sensitivity of the thromboplastin used in the test. INR is a standardised measurement of how long it takes blood to form a clot. The coagulation factors II, VII, IX, and X are dependent on Vitamin K for synthesis and are reflected by the INR. It is used to determine the effects of oral Warfarin on the clotting system and to monitor levels so that a therapeutic range for dosing can be adjusted accordingly. For most warfarin indications, the target INR is 2.0-3.0 (VTE and single MHV excluding mitral). For mechanical mitral valve or combined mitral and aortic, the target INR is 2.5-3.5. The modes of action of DOACs differ from that of warfarin and their effect cannot be determined by INR testing.
Prothrombin Time (PT)
Evaluates coagulation factors VII, X, V, II, and I (fibrinogen). Measures the speed of clotting by means of the extrinsic pathway (also known as the tissue factor pathway). Warfarin typically prolongs the PT alone, but at high levels can prolong aPTT also. For rivaroxaban and apixaban, the PT may be prolonged with the presence of a significant dose of the drug.
Activated Partial Thromboplastin Time (aPTT)
Evaluates coagulation factors XII, XI, IX, X, V, II (prothrombin), and I (fibrinogen). Measures the overall speed at which blood clots by means of reactions known as the intrinsic and common coagulation pathways. The typical reference range is between 30 – 40 seconds. aPTT is moderately sensitive to Dabigatran. At peak therapeutic plasma concentrations, the aPTT is increased up to 2 times and at trough concentrations (e.g., 12 hours after the last dose) it falls to approximately 1.3 times control values9. Trough APTT values greater than 80 seconds are associated with increased bleeding risk 10. The time between the last dose of dabigatran and blood collection must be determined as it will affect the results. The aPTT may also be mildly prolonged in the presence of apixaban and rivaroxaban.
Fibrinogen assay
Fibrinogen is a protein that is essential for blood clot formation and a reflection of clotting ability and activity in the body. Reduced concentrations of fibrinogen may impair the body’s ability to form a stable blood clot and are seen at an early stage in severe haemorrhage.
Viscoelastic tests
Thromboelastography (Rotem or TEG) are point-of-care analysers that provide rapid information on global haemostasis and are used to guide transfusions in perioperative and trauma settings. It provides information on the whole kinetics of haemostasis: clotting time, clot formation, clot stability, and lysis 11. By combining and comparing the results from different ROTEM tests, it is possible to identify single or multiple coagulation factor deficiencies within a few minutes of obtaining samples and goal-directed coagulation therapy can be readily initiated. 12
Interpretation of coagulation screen
Warfarin
- Prolongs the PT more than APTT
- PT/INR is used to monitor anticoagulation
Apixaban/Rivaroxaban/Dabigatran
Early haematologist consultation is advised regarding the effect of these medications and interpretation of coagulation testing as there are no clear correlates.