Hemophilia is a rare, inherited bleeding disorder that prevents blood from clotting correctly, leading to prolonged bleeding after injury or surgery, and sometimes spontaneous bleeding into joints and muscles. The inability to form a stable clot results from a deficiency in specific blood proteins known as coagulation factors. Hemophilia A and Hemophilia B are the most common forms. While both conditions share similar clinical outcomes, the underlying biological defect is distinct and determines the specific diagnosis and treatment plan.
The Fundamental Difference: Missing Clotting Factors
The core distinction between the two types of hemophilia lies in the specific protein that is absent or malfunctioning within the coagulation cascade. Hemophilia A is defined by a deficiency in coagulation Factor VIII (FVIII). This factor plays an important part in the complex series of chemical reactions that lead to blood clot formation.
In contrast, Hemophilia B is caused by a deficiency in coagulation Factor IX (FIX). Both Factor VIII and Factor IX work together within the body’s internal clotting pathway to activate Factor X. When either of these factors is missing or defective, the clotting process is disrupted, resulting in uncontrolled bleeding.
The genes responsible for producing these factors are located on the X chromosome. The F8 gene codes for Factor VIII, and the F9 gene codes for Factor IX. A defect in the F8 gene results in Hemophilia A, and a defect in the F9 gene results in Hemophilia B. The specific gene affected and the resulting missing protein differentiate the two diagnoses.
Prevalence and Genetic Similarity
Hemophilia A is more common than its counterpart, accounting for approximately 80% to 85% of all hemophilia cases worldwide. It affects about one in every 5,000 male births, making it roughly four times more frequent than Hemophilia B. Hemophilia B occurs in about one in every 25,000 to 40,000 male births.
Both conditions share the same inheritance pattern, known as X-linked recessive inheritance. Males, who have only one X chromosome, will develop the condition if that chromosome carries the mutated gene.
Females have two X chromosomes, so they are typically carriers who can pass the gene mutation to their children without having severe symptoms themselves. Approximately 30% of cases for both Hemophilia A and B are the result of a de novo or spontaneous genetic mutation.
Tailored Treatment Approaches
The distinct nature of the missing clotting factors necessitates specific treatment regimens for each condition. The standard therapy for both Hemophilia A and B is factor replacement therapy, where the missing protein is infused directly into the bloodstream. For a patient with Hemophilia A, this treatment involves administering a concentrated form of Factor VIII.
Conversely, a patient diagnosed with Hemophilia B must receive infusions of concentrated Factor IX. Administering the wrong factor would not correct the underlying deficiency and would be ineffective in preventing or treating a bleed. The goal of this replacement therapy is to maintain sufficient levels of the specific factor to allow for normal clotting.
Recent advancements have introduced non-factor therapies that do not directly replace the missing protein but instead target other parts of the coagulation pathway. For instance, a bispecific antibody therapy is available for Hemophilia A that mimics the function of Factor VIII. Other new treatments, including gene therapy, are now available or in development for both types. These offer the potential for a long-term increase in the body’s production of either Factor VIII or Factor IX, depending on the diagnosis.