What Is Factor VIII and Why Is It Measured?
Factor VIII is an essential protein involved in the blood coagulation cascade, a series of steps that lead to the formation of a stable blood clot. A deficiency or abnormality in Factor VIII activity can lead to hemophilia A, the most common severe hereditary bleeding disorder. Measuring Factor VIII levels is a critical step in diagnosing hemophilia A, assessing its severity, and monitoring the effectiveness of treatment. It is also part of a larger diagnostic picture for other bleeding or clotting abnormalities.
The Primary Units of Measurement for Factor VIII
There are two main ways that Factor VIII activity levels are reported by laboratories:
- International Units (IU): This is the most standardized unit for reporting Factor VIII levels. One IU is defined as the amount of Factor VIII activity found in 1 milliliter (mL) of normal, pooled human plasma. The results may be expressed in IU/mL or IU/dL (International Units per deciliter). For example, a result of 0.5 IU/mL is equivalent to 50 IU/dL.
- Percentage of Normal (%): Another common reporting method expresses the level as a percentage relative to the activity found in normal pooled plasma. A result of 100% means the patient has a Factor VIII activity equal to the average of the normal population. A level below 50% can indicate a deficiency.
It is important to note that these units are directly convertible. For instance, a level of 1.0 IU/mL is equivalent to 100 IU/dL, which corresponds to 100% of normal activity. However, labs may use slightly different reference ranges, so it is vital to discuss your specific results with your healthcare provider.
How Factor VIII Levels Are Tested
Testing for Factor VIII activity is a crucial laboratory process performed on a blood sample drawn from a vein. The methodology involves measuring the clotting time of the patient's plasma. There are two primary types of assays used for this purpose, and their use can depend on the lab's equipment and the patient's treatment regimen.
One-Stage Clotting Assay
This is the most widely used method in clinical laboratories.
- Principle: It is based on the activated partial thromboplastin time (aPTT) test. Patient plasma is mixed with Factor VIII-deficient plasma. The time it takes for the mixture to clot is then measured.
- Methodology: The assay relies on the fact that a longer clotting time corresponds to a lower Factor VIII level. A standard curve is created by testing dilutions of a normal reference plasma, which allows for the accurate calculation of Factor VIII activity in the patient's sample.
- Interference: This method is susceptible to interference from certain medications, particularly the bispecific antibody Emicizumab (Hemlibra), which can lead to a falsely elevated Factor VIII result.
Chromogenic Assay
This is another method for determining Factor VIII activity.
- Principle: It is a two-stage assay where the amount of activated Factor X generated is proportional to the amount of Factor VIII present in the test plasma.
- Methodology: The activated Factor X then cleaves a chromogenic substrate, producing a color change that is measured photometrically. The intensity of the color is directly proportional to the Factor VIII activity.
- Advantage: This method is less prone to interference from Emicizumab, making it a more reliable choice for patients on this therapy. However, depending on the reagents used (human vs. bovine), some chromogenic assays can still be affected.
Interpreting Your Factor VIII Level and Hemophilia Severity
Factor VIII levels are a primary determinant of hemophilia A severity. The following table outlines the classifications based on Factor VIII activity.
| Classification | Factor VIII Activity (% of Normal) | Factor VIII Activity (IU/dL or IU/mL) |
|---|---|---|
| Normal Range | 50%–150% | 50–150 IU/dL (0.5–1.5 IU/mL) |
| Mild Hemophilia A | >5% to ≤40% | >5 to ≤40 IU/dL (>0.05 to ≤0.40 IU/mL) |
| Moderate Hemophilia A | 1% to 5% | 1–5 IU/dL (0.01–0.05 IU/mL) |
| Severe Hemophilia A | <1% | <1 IU/dL (<0.01 IU/mL) |
Factors That Can Influence Factor VIII Levels
Beyond hemophilia, several other conditions can impact your Factor VIII levels, leading to either increased or decreased activity.
- Acquired Deficiencies: These can occur due to conditions like myeloproliferative or lymphoproliferative disorders. The presence of Factor VIII inhibitors (autoantibodies) can also cause acquired hemophilia and a corresponding deficiency.
- Elevated Levels: As an acute-phase reactant protein, Factor VIII activity can increase in response to stress, inflammation, and trauma. Pregnancy and the use of oral contraceptives can also lead to higher Factor VIII levels. Elevated levels can increase the risk of venous thromboembolism.
- Specimen Handling: Because Factor VIII is a labile protein, improper specimen collection, handling, and storage can affect test results. Poorly handled samples might show spuriously decreased results.
- von Willebrand Disease (VWD): The von Willebrand factor (VWF) acts as a carrier protein for Factor VIII. In most types of VWD, lower VWF levels lead to a secondary deficiency of Factor VIII. A rare type, VWD type 2N, involves a normal VWF level but a specific binding defect that results in low Factor VIII activity.
Conclusion
Understanding the units of measurement for Factor VIII level is fundamental to interpreting blood test results and managing bleeding disorders. Whether expressed in International Units or as a percentage, these measurements are the cornerstone for diagnosing hemophilia A and assessing its severity. Test results must be considered in the context of the testing method used, any ongoing treatment, and a patient's overall health status. For an accurate interpretation of your specific Factor VIII level, always consult with your healthcare provider to discuss your test results in detail.
For more information on hemophilia and its management, see the resources provided by the World Federation of Hemophilia (WFH) online, a global non-profit organization dedicated to improving the lives of people with hemophilia and other inherited bleeding disorders.
