What is the workup for a clotting factor (coagulation factor) study?

From the Guidelines

A clotting factor study workup should begin with a Complete Blood Count (CBC), Prothrombin Time (PT) and International Normalized Ratio (INR), Activated Partial Thromboplastin Time (aPTT), and Fibrinogen level, followed by individual factor assays, particularly for factors VIII, IX, and von Willebrand factor, as recommended by the most recent study 1. The initial tests help assess overall blood cell counts, evaluate the extrinsic and common pathways of coagulation, and assess the intrinsic and common pathways.

• The CBC helps assess overall blood cell counts and can indicate anemia or platelet abnormalities.
• PT/INR evaluates the extrinsic and common pathways of coagulation, while aPTT assesses the intrinsic and common pathways.
• Fibrinogen level is important as it's the precursor to fibrin, essential for clot formation. Individual factor assays are crucial for diagnosing specific factor deficiencies, such as hemophilia A (factor VIII deficiency) or hemophilia B (factor IX deficiency), and should be performed using the most accurate and reliable methods available, such as the chromogenic assay (CHR) 1.
• The CHR assay is an alternative approach to the one-stage clotting assay (OSCA) and has several advantages, including removing the variable of patient plasma and isolating the two clotting factors that are pathologically deficient in hemophilia. It's essential to note that certain medications (e.g., anticoagulants) and medical conditions can affect these test results, so a thorough medical history should be taken alongside the laboratory workup, and the diagnosis of factor X deficiency may be confirmed by quantifying plasma FX:C through serial dilutions with factor X–deficient plasma 1. The workup should be guided by the clinical presentation and medical history of the patient, and further specific factor assays may be ordered based on the results of the initial tests, as recommended by studies 1.

From the Research

Coagulation Factor Study Workup

The workup for a clotting factor (coagulation factor) study involves several tests to evaluate the intrinsic and extrinsic pathways of coagulation.

• The prothrombin time (PT) is used to monitor warfarin anticoagulant therapy and to evaluate the extrinsic pathway of coagulation 2.
• The activated partial thromboplastin time (aPTT) is used to evaluate the intrinsic and common pathways of coagulation and to monitor unfractionated heparin therapy 2, 3.
• The mixing study is used to assess an abnormally prolonged PT or aPTT and to differentiate between factor deficiencies and inhibitors 2, 4, 5.
• Factor activity assays are used to measure the activity of specific clotting factors, such as factors VIII, IX, and XI 2.
• The Clauss assay is used to measure fibrinogen levels 2.

Interpretation of Test Results

The interpretation of test results involves evaluating the PT, aPTT, and factor activity levels to determine the presence of clotting factor deficiencies or inhibitors.

• A prolonged PT or aPTT may indicate a clotting factor deficiency or the presence of an inhibitor 2, 3, 4, 5.
• The mixing study can help to differentiate between factor deficiencies and inhibitors 4, 5.
• The estimated factor correction (EFC) method can be used to interpret mixing study results and to determine the presence of factor deficiencies or inhibitors 4.

Clinical Applications

The workup for a clotting factor study has several clinical applications, including:

• Monitoring warfarin anticoagulant therapy 2.
• Evaluating the intrinsic and extrinsic pathways of coagulation 2, 3.
• Diagnosing clotting factor deficiencies or inhibitors 2, 4, 5.
• Monitoring unfractionated heparin therapy 2, 3.
• Evaluating patients with prolonged PT or aPTT 5.
• Assessing the risk of thrombosis or bleeding 3, 6.