Hemophilia is a genetic bleeding disorder caused by a deficiency or dysfunction of specific proteins in the blood, known as clotting factors, which impairs the body’s ability to form a proper blood clot. The two most common forms are Hemophilia A (lack of Factor VIII) and Hemophilia B (lack of Factor IX). Testing diagnoses the condition, determines the specific missing factor, and establishes the severity of the disorder.
The diagnostic process involves a series of blood tests, moving from general screening to highly specific factor analysis, to determine the precise cause of bleeding. Classifying the type and severity of hemophilia guides the appropriate treatment strategy, as symptom severity depends directly on the amount of functional clotting factor produced.
Clinical Reasons for Seeking a Test
A doctor typically orders hemophilia testing when a patient presents with excessive, prolonged, or unexplained bleeding. In infants, this concern often arises from prolonged bleeding following circumcision or unusual bruising once the baby begins crawling or standing. Babies born to families with a known history of hemophilia are sometimes tested soon after birth using umbilical cord blood.
In children and adults, signs that trigger testing include frequent, hard-to-stop nosebleeds, extensive bruising, or bleeding into joints (hemarthroses) and muscles. Milder forms may not be diagnosed until later in life, often after excessive bleeding following surgery, dental work, or significant trauma. A strong family history of bleeding disorders or unexplained deaths among male relatives is also a significant reason to investigate hemophilia.
About one-third of newly diagnosed babies have no prior family history, suggesting a spontaneous genetic change or a previously undiagnosed carrier. For women, symptoms like heavy menstrual bleeding or extensive bruising may prompt a diagnosis. These clinical indications guide the physician to initiate general screening bloodwork.
Initial Screening Bloodwork
Laboratory testing begins with general coagulation assays to determine if a bleeding problem exists and which part of the clotting cascade is affected. The two primary screening tests are the Activated Partial Thromboplastin Time (aPTT) and the Prothrombin Time (PT). The aPTT measures the time required for blood to clot through the intrinsic and common pathways.
Factors VIII and IX, the two factors deficient in hemophilia A and B, are part of this intrinsic pathway, so a deficiency in either factor will typically result in a prolonged aPTT result. The degree of aPTT prolongation generally correlates with the severity of the factor deficiency, though a normal aPTT result does not rule out a mild case of hemophilia. Conversely, the PT measures the extrinsic pathway, which does not rely on Factor VIII or IX.
In a patient with hemophilia A or B, the PT result is expected to be normal while the aPTT is prolonged. This pattern strongly suggests an issue with intrinsic pathway factors, pointing toward hemophilia A or B, or a deficiency in Factor XI. If the aPTT is prolonged, a mixing study may be performed to determine if the issue is a factor deficiency or the presence of an inhibitor (antibodies that attack clotting factors).
Confirming the Diagnosis and Determining Severity
If initial screening suggests a factor deficiency, the next step is the Factor Assay Test to confirm the diagnosis and classify the disorder. These assays specifically measure the functional activity of Factor VIII and Factor IX, identifying the deficient factor and distinguishing between Hemophilia A and Hemophilia B.
The factor assay is the definitive diagnostic tool because it measures the exact percentage of clotting factor activity compared to normal levels. This percentage establishes the severity of hemophilia, which directly influences the patient’s bleeding risk and treatment plan. Severity is universally classified into three categories based on factor activity level.
Patients with severe hemophilia have less than 1% factor activity and typically experience spontaneous bleeding into joints and muscles. Moderate hemophilia is defined by 1% to 5% activity, where bleeding usually occurs after minor trauma. Individuals with mild hemophilia have activity greater than 5% but less than 40% and may only experience bleeding after significant injury or surgery. The one-stage clotting assay is the most common measurement method, though chromogenic assays are also used.
Genetic and Prenatal Testing
Beyond diagnosing symptomatic individuals, genetic testing is used for family planning, risk assessment, and identifying carriers. Hemophilia A and B are X-linked recessive disorders, meaning the responsible genes (\(F8\) and \(F9\)) are located on the X chromosome. Carrier testing is typically offered to women in families with a known history of hemophilia to determine if they carry the mutated gene.
Genetic analysis identifies the specific mutation in the \(F8\) or \(F9\) gene, providing a definitive answer about carrier status. This information is valuable for counseling women at risk of having a child with the disorder. While most female carriers are asymptomatic, some may have low factor levels that lead to bleeding symptoms, classifying them as symptomatic carriers.
Prenatal diagnosis is an option for at-risk pregnancies once the specific family mutation is identified. Fetal cells can be collected for genetic testing using chorionic villus sampling (CVS) between 11 and 14 weeks, or amniocentesis, typically from 15 to 20 weeks. Non-invasive prenatal diagnosis (NIPD) for fetal sexing, using a maternal blood sample, can also be performed as early as seven weeks to determine if the fetus is male and therefore at risk.