Hemophilia is a rare, inherited genetic disorder that prevents blood from clotting properly. This condition is caused by a deficiency in specific clotting factor proteins. The two main types are Hemophilia A (deficiency of Factor VIII) and Hemophilia B (deficiency of Factor IX). Definitive diagnosis through testing is required for proper medical management and to determine the severity of the condition.
Identifying the Need for Testing
The testing process is often triggered by one of three primary scenarios. A clear family history is the most straightforward indicator, leading to testing soon after birth or even prenatally. Newborn screening is important if the mother is a known carrier or if there is a strong history of the disorder among male relatives.
Testing is also necessary when an individual, typically a young boy, displays unexplained symptoms of a bleeding disorder. These signs include easy bruising, prolonged bleeding after minor cuts, or bleeding into joints and muscles. A third scenario involves women who are potential carriers, who may require testing to assess their own bleeding risk, especially before surgery or childbirth.
Initial Clotting Time Screening
Once the need for testing is established, the process begins with preliminary blood tests to assess overall clotting function. Two standard screening tests are the Prothrombin Time (PT) and the Activated Partial Thromboplastin Time (aPTT). These measure the time it takes for a blood sample to clot and evaluate different parts of the coagulation cascade.
For a person with Hemophilia A or B, the PT test result is typically normal because it measures the extrinsic pathway, which does not rely on Factors VIII or IX. The aPTT test assesses the intrinsic pathway, where Factors VIII and IX are involved. A prolonged aPTT, meaning the blood takes longer than normal to clot, is the main indicator of a factor deficiency. This finding suggests a clotting problem but requires further analysis to specify the type or severity of hemophilia.
Confirmatory Factor Assays
The definitive diagnosis and determination of hemophilia type rely on a procedure called a factor assay. This test directly measures the activity level of specific clotting proteins in the patient’s blood. For a suspected diagnosis, the activity of both Factor VIII and Factor IX is measured.
A low Factor VIII activity level confirms Hemophilia A, while a low Factor IX activity level confirms Hemophilia B. The result is reported as a percentage of normal activity, which is used to classify the disease. These assays are the gold standard because they quantify the degree of the factor deficiency. Genetic testing, involving DNA sequencing, may also be used to identify the specific gene mutation, especially for carrier status determination or when factor assay results are unclear.
Interpreting Results and Severity
The numerical results from factor assays classify the severity of hemophilia, which directly influences the patient’s bleeding risk and treatment approach. The normal range for Factor VIII and Factor IX activity is between 50% and 150%. An activity level below 40% is diagnostic for hemophilia.
Hemophilia is classified into three categories based on the factor activity percentage. Mild hemophilia involves factor activity levels between 5% and 40%. Moderate hemophilia is diagnosed when activity falls between 1% and 5%. The most severe classification is reserved for those with less than 1% factor activity, who face the highest risk for spontaneous bleeding episodes.