Hemophilia is diagnosed through a combination of blood tests that measure how long your blood takes to clot and how much clotting factor is actually present. The process typically starts with screening tests, then moves to specific factor level measurements that confirm the diagnosis and classify its severity. In some cases, genetic testing is also used to identify the exact mutation involved.
What Triggers a Diagnostic Workup
Hemophilia often comes to light in one of two ways. If there’s a known family history, testing can happen before or shortly after birth. But in about a third of cases, there’s no family history at all, and the condition is discovered when unusual bleeding occurs.
In newborns, doctors may suspect hemophilia if there’s excessive bleeding during routine procedures like circumcision or a heel-prick blood draw. In older infants and toddlers, easy bruising or prolonged bleeding from minor injuries raises suspicion. Severe hemophilia tends to be caught early, often in the first year of life, while mild hemophilia can go undetected until a surgery, dental procedure, or injury causes unexpectedly heavy bleeding, sometimes not until adulthood.
Initial Screening Tests
The first step is a set of standard blood tests that help narrow down where the clotting problem lies. Three tests form the backbone of this screening:
- Activated partial thromboplastin time (aPTT): This measures how long it takes blood to clot through one of the body’s main clotting pathways, the one that involves the factors affected in hemophilia. In people with hemophilia A or B, this result comes back longer than normal.
- Prothrombin time (PT): This tests a different clotting pathway. In most people with hemophilia A or B, the PT result is normal. A normal PT combined with a prolonged aPTT is a classic pattern that points toward hemophilia.
- Complete blood count (CBC): Platelet counts and other blood cell levels are typically normal in hemophilia. However, if someone has been bleeding heavily or for a long time, their red blood cell count and hemoglobin may be low from blood loss.
These screening tests don’t confirm hemophilia on their own. A prolonged aPTT with a normal PT signals that the problem is in the right part of the clotting system, but further testing is needed to pin down exactly which clotting factor is deficient and by how much.
Clotting Factor Activity Tests
The definitive step in diagnosing hemophilia is measuring the activity level of specific clotting factors in the blood. Hemophilia A involves a deficiency in factor VIII, while hemophilia B involves factor IX. A one-stage clotting assay is the most common method used to measure how much functional factor is circulating.
The factor activity level also determines how severe the condition is, which has a major impact on what symptoms to expect and how treatment is managed:
- Severe hemophilia: Less than 1% of normal factor activity. Spontaneous bleeding into joints and muscles is common, even without injury.
- Moderate hemophilia: 1% to 5% of normal factor activity. Bleeding typically happens after minor injuries, though occasional spontaneous bleeding can occur.
- Mild hemophilia: 6% to 50% of normal factor activity. Bleeding problems usually only surface after surgery, dental work, or significant trauma.
This classification stays with a person for life. Someone with severe hemophilia will always have severe hemophilia, because the underlying genetic cause doesn’t change.
Genetic Testing
Genetic testing analyzes the specific genes responsible for producing clotting factors. Hemophilia A is caused by variants in the F8 gene, and hemophilia B by variants in the F9 gene. Both are located on the X chromosome, which is why hemophilia predominantly affects males.
Identifying the exact genetic variant serves several purposes beyond confirming the diagnosis. It enables carrier testing for female relatives who may carry one copy of the altered gene without showing symptoms themselves. It also helps predict the risk of developing inhibitors, which are antibodies the immune system sometimes produces against replacement clotting factor, a complication that makes treatment significantly harder. In mild hemophilia A, knowing the specific mutation can even help predict whether certain treatments will be effective.
Genetic testing has become a standard part of hemophilia care. Once a mutation is identified in one family member, other relatives can be tested with a simple blood sample.
Diagnosis in Women and Girls
Because hemophilia is X-linked, women who carry one altered copy of the F8 or F9 gene are often called “carriers.” But this label can be misleading, because carrying the gene doesn’t always mean being symptom-free. Roughly 30% of female carriers of hemophilia A have factor VIII levels below 40%, which puts them at risk for bleeding symptoms consistent with mild hemophilia.
This means diagnosis in women can be delayed or missed entirely if clinicians assume hemophilia only affects males. Women with unexplained heavy menstrual bleeding, prolonged bleeding after surgery, or easy bruising should have their factor levels checked, especially if there’s any family history of bleeding disorders. Both factor activity testing and genetic testing play a role in identifying women who need monitoring or treatment.
Prenatal and Newborn Testing
When a family has a known hemophilia mutation, testing can happen before birth. Two prenatal methods are available. Chorionic villus sampling can be performed after the 11th week of pregnancy, when a small tissue sample is taken from the placenta and analyzed for the known genetic variant. Amniocentesis, typically done later in pregnancy, involves withdrawing a small amount of the fluid surrounding the baby for genetic analysis. These tests are only performed when a specific mutation has already been identified in a parent or close relative.
After birth, if hemophilia is suspected, a blood sample from the newborn can be tested for factor activity levels. Factor VIII levels in healthy newborns are close to adult levels, so hemophilia A can be reliably diagnosed at birth. Factor IX levels, however, are naturally lower in newborns and don’t reach adult range until around six months of age, which can complicate early diagnosis of hemophilia B. In those cases, repeat testing may be needed.
Acquired Hemophilia: A Different Diagnosis
Not all hemophilia is inherited. Acquired hemophilia A is a rare condition that develops when the immune system mistakenly produces antibodies that attack factor VIII. It typically appears in older adults with no prior bleeding history and can cause severe, sudden bleeding episodes. Joint bleeding, the hallmark of congenital hemophilia, is uncommon in acquired cases.
The initial lab picture looks similar: a prolonged aPTT with a normal PT. But the key difference is the presence of autoantibodies against factor VIII, which are detected using a test called the Bethesda assay. This assay measures how much of the antibody is present by quantifying how effectively it neutralizes factor VIII in a lab sample. One Bethesda unit represents the amount of antibody that knocks out 50% of factor VIII activity. A refined version called the Nijmegen modification improves accuracy when antibody levels are low.
Mixing studies can also help distinguish acquired hemophilia from a simple factor deficiency. In a mixing study, the patient’s blood is mixed with normal blood. If the clotting time corrects immediately, it suggests a factor deficiency. If it doesn’t correct, or if it initially corrects but then worsens after being incubated for two hours, that pattern points toward an inhibitor. These mixing studies aren’t perfectly standardized, so the Bethesda assay remains the gold standard for confirmation.
Half of acquired hemophilia A patients have factor VIII activity below 1%, and 75% have levels below 5%, making it a potentially dangerous condition that requires prompt recognition.