What are the implications of a shortened Bleeding Time (BT), Clotting Time (CT), Prothrombin Time (PT)/International Normalized Ratio (INR)?

From the Guidelines

Bleeding time (BT), clotting time (CT), and prothrombin time/international normalized ratio (PT/INR) are crucial laboratory tests for evaluating hemostasis and coagulation, with BT measuring primary hemostasis, CT assessing the intrinsic coagulation pathway, and PT/INR evaluating the extrinsic and common coagulation pathways. When considering the management of patients on antithrombotic agents undergoing emergency and elective endoscopy, current guidelines recommend reversal of anticoagulation in patients with serious life-threatening bleeding, irrespective of INR levels 1. Key points to consider include:

• Available evidence does not show a correlation between INR at presentation and outcomes of GI bleeding 1.
• A systematic review found that INR at presentation did not predict recurrent non-variceal upper GI bleeding 1.
• The use of prothrombin complex concentrate (PCC) and low-dose vitamin K is recommended for urgent reversal of anticoagulation, with PCC having advantages over fresh frozen plasma, including faster onset of action and minimal risk of fluid overload and transmitting infection 1.
• The optimal doses of vitamin K for normalizing INR are between 1 and 2.5 mg, with low-dose vitamin K (<5 mg) recommended to reduce the risk of hypercoagulopathy, especially in patients requiring early re-anticoagulation 1. In the context of INR targets, there is no high-quality evidence that plasma transfusions reduce bleeding when administered to nonbleeding patients with incidentally abnormal INRs, and the practice lacks biological plausibility 1. Therefore, the management of BT, CT, and PT/INR should prioritize the individual patient's clinical context, with a focus on evidence-based guidelines and a cautious approach to plasma transfusions and anticoagulation reversal. Considerations for clinical practice include:
• Avoiding the use of mildly elevated INR as an indication for plasma transfusion, as it may not provide clinical benefit and can be harmful 1.
• Recognizing the limitations of INR in monitoring warfarin therapy and the potential for overreliance on this test, leading to under- or overtreatment in patients at risk for bleeding and thrombosis 1.

From the FDA Drug Label

The PT reflects the depression of vitamin K dependent Factors VII, X and II. A system of standardizing the PT in oral anticoagulant control was introduced by the World Health Organization in 1983 It is based upon the determination of an International Normalized Ratio (INR) which provides a common basis for communication of PT results and interpretations of therapeutic ranges. The dose of warfarin should be adjusted to maintain a target INR of 2.5 (INR range, 2.0 to 3.0) for all treatment durations.

Key Points:

• PT/INR is used to monitor warfarin therapy.
• The target INR range is 2.0 to 3.0 for most treatment durations.
• Warfarin dosage should be adjusted to maintain the target INR range.
• The PT/INR should be determined daily after the administration of the initial dose until PT/INR results stabilize in the therapeutic range.
• Acceptable intervals for PT/INR determinations are normally within the range of one to four weeks after a stable dosage has been determined 2.
• The target INR may vary depending on the specific condition being treated, such as atrial fibrillation or mechanical heart valves 2.

From the Research

Prothrombin Time (PT) and International Normalized Ratio (INR)

• The prothrombin time (PT) is a commonly used coagulation test in clinical laboratories, which is mathematically converted to the international normalized ratio (INR) for monitoring anticoagulant therapy with vitamin K antagonists such as warfarin 3.
• The INR is created using two major PT 'correction factors', namely the mean normal PT (MNPT) and the international sensitivity index (ISI) 3, 4.

Factors Affecting PT and INR Results

• Manufacturers of reagents and coagulometers have made efforts to harmonize INRs, but laboratories may still report different INR values even when using the same thromboplastin reagent and coagulometer 3.
• ISI values for a specific thromboplastin can vary among different models of coagulometers from a manufacturer using the same method for clot identification, which can be a source of error for INR reporting 3.
• The PT and INR tests are affected by various factors, including the type of thromboplastin used, the instrument used, and the laboratory's calibration and quality control procedures 5, 6.

Clinical Applications of PT and INR

• The PT and INR tests are commonly used to monitor anticoagulant therapy, evaluate hemorrhage, and screen for bleeding disorders 5, 6.
• Abnormal PT and INR results can pose a diagnostic dilemma, and a practical approach to evaluation and reflexive testing is necessary to determine the underlying cause of the abnormal result 5.