What Are the Diagnostic Tests for Hemophilia?

Hemophilia is a group of inherited bleeding disorders characterized by impaired blood coagulation. The primary issue lies in the defective formation of active thromboplastin, leading to prolonged clotting time and a lifelong tendency to bleed even after minor injuries. In severe cases, spontaneous bleeding can occur without any obvious trauma. Early and accurate diagnosis is essential for effective management and improved quality of life. This article explores the key diagnostic methods used to identify hemophilia and differentiate it from similar conditions.

Initial Screening Tests for Hemophilia

Diagnosing hemophilia begins with a series of screening tests that evaluate basic blood clotting functions. In patients suspected of having hemophilia, typical findings include normal platelet count, bleeding time, and clot retraction—indicating that platelet function is intact. However, abnormalities appear in coagulation-related parameters: activated partial thromboplastin time (aPTT) is significantly prolonged, and prothrombin time (PT) may be normal or slightly shortened. Additionally, the thromboplastin generation time is extended, pointing toward a deficiency in intrinsic pathway factors, particularly Factor VIII or IX.

Confirmatory and Typing Tests

To confirm the diagnosis and determine the specific type of hemophilia, more specialized assays are required. One of the most definitive procedures is the simple thromboplastin generation test (STGT) along with correction studies. These tests assess whether the clotting defect can be corrected using normal plasma components:

Differentiating Hemophilia A, B, and C

Hemophilia A (Factor VIII deficiency): The clotting defect is corrected by adding normal barium sulfate-adsorbed plasma but not by normal serum—confirming a lack of Factor VIII.

Hemophilia B (Factor IX deficiency): The defect is corrected by normal serum but not by barium sulfate-adsorbed plasma, indicating a deficiency in Factor IX.

Hemophilia C (Factor XI deficiency): The abnormality is corrected by both normal adsorbed plasma and normal serum, helping to distinguish this rarer form of the disease.

Differential Diagnosis: Distinguishing from von Willebrand Disease

Several bleeding disorders mimic hemophilia, making differential diagnosis crucial. A common condition often confused with hemophilia is von Willebrand disease (vWD). Unlike hemophilia, which primarily affects males due to X-linked inheritance, vWD follows an autosomal dominant pattern—meaning both men and women can be affected equally, and either parent can pass on the gene.

Clinically, vWD typically presents with mucosal and skin bleeding, such as nosebleeds, gum bleeding, or heavy menstrual periods. Joint and muscle bleeds are less common, and joint deformities are rare. Diagnostic clues include prolonged bleeding time and a positive aspirin tolerance test. Laboratory results often show reduced levels of von Willebrand factor antigen (vWF:Ag), ristocetin cofactor activity (vWF:RCo), and sometimes decreased Factor VIII:C activity.

Identifying Variant and Rare Forms

In some atypical cases, a variant form of von Willebrand disease may follow an autosomal recessive pattern. Parents might show no symptoms or have no family history, yet the child exhibits severe bleeding tendencies. While bleeding time and certain factor levels may appear normal, specialized testing like crossed immunoelectrophoresis can reveal structural abnormalities in the von Willebrand factor, aiding in accurate differentiation from true hemophilia.

Hemophilia A: The Most Common Type

Hemophilia A is the most prevalent form, accounting for about 80% of all cases. It results from a deficiency in clotting Factor VIII and manifests primarily through recurrent bleeding episodes—especially into joints and muscles. Without timely intervention, repeated joint hemorrhages can lead to chronic pain, swelling, and long-term disability.

Currently, there is no cure for hemophilia, but treatment has advanced significantly. While blood transfusions were once the mainstay, modern therapy focuses on factor replacement therapy—administering concentrated clotting factors intravenously to prevent or control bleeding. Prophylactic treatment regimens have greatly improved patient outcomes and reduced complications.

Early detection through comprehensive laboratory evaluation remains vital. With proper diagnosis and personalized care plans, individuals with hemophilia can lead active, fulfilling lives. Awareness, genetic counseling, and access to specialized hematology centers play a key role in managing this lifelong condition effectively.