Hemophilia is an inherited blood disorder that impairs the body’s ability to form a clot, leading to prolonged or excessive bleeding. This condition occurs due to a deficiency in one of the coagulation factors, proteins necessary for the clotting cascade to function correctly. Hemophilia C is a rarer form of the disorder that differs significantly from the more widely known types, Hemophilia A and Hemophilia B. The specific protein affected and the pattern of inheritance set Hemophilia C apart.
Understanding Hemophilia C and Factor XI Deficiency
Hemophilia C is defined as a deficiency in coagulation Factor XI (FXI), a protein that initiates and amplifies the clotting process. This condition is sometimes referred to as Rosenthal syndrome. FXI acts within the intrinsic pathway of the coagulation cascade, which leads to the formation of a stable fibrin clot.
When FXI is deficient, the cascade is interrupted, making it difficult for the body to stabilize a clot, particularly during surgery or trauma. Hemophilia C is distinct because the two most common forms, Hemophilia A and Hemophilia B, involve deficiencies in Factor VIII and Factor IX, respectively. FXI deficiency is the fourth most common inherited bleeding disorder, following von Willebrand disease, Hemophilia A, and Hemophilia B.
How Hemophilia C is Inherited
The genetic transmission of Hemophilia C is fundamentally different from Hemophilia A and B, which are X-linked disorders that primarily affect males. Hemophilia C is inherited through an autosomal pattern, meaning the gene responsible ($F11$) is located on a non-sex chromosome. This allows the condition to affect both males and females with equal frequency.
The inheritance is often described as autosomal recessive, requiring a person to inherit a mutated $F11$ gene from both parents to experience the most pronounced deficiency. However, the condition is not strictly recessive; individuals who inherit only one copy of the mutated gene can still have reduced FXI levels and may experience bleeding symptoms. This variable pattern means that both men and women can be carriers and can be affected by the disorder.
Recognizing the Symptoms and Confirming Diagnosis
A unique feature of Hemophilia C is that the Factor XI activity level does not reliably predict the severity or frequency of bleeding episodes. Individuals with very low FXI levels may have few symptoms, while others with moderately reduced levels may bleed excessively following certain procedures. Unlike Hemophilia A and B, spontaneous bleeding into the joints or muscles is uncommon.
Bleeding episodes are typically provoked by local trauma or surgical procedures, especially those involving tissues with high fibrinolytic activity, such as the mouth or urinary tract. Common symptoms include prolonged bleeding after dental extractions, persistent nosebleeds, or excessive bleeding following tonsillectomy or other surgeries. Women often experience menorrhagia (abnormally heavy or prolonged menstrual bleeding) or excessive bleeding after childbirth.
Diagnosis of Hemophilia C begins with a patient’s personal and family history of bleeding tendencies. Laboratory testing starts with the Activated Partial Thromboplastin Time (aPTT) test, which measures the time it takes for blood to clot through the intrinsic pathway. A prolonged aPTT suggests a deficiency in one of the factors in this pathway, including FXI.
The definitive diagnosis is confirmed by a specific Factor XI activity assay, which measures the amount of functional FXI present in the plasma. Measuring the FXI level helps determine the severity of the deficiency, but this measurement must be interpreted alongside the patient’s clinical history due to the poor correlation between factor level and bleeding risk. Specialized assays, such as the Thrombin Generation Assay, may also be used to assess overall clotting function.
Treatment and Long-Term Management
Treatment for Hemophilia C is generally not required for day-to-day activities, as spontaneous bleeding is rare. However, treatment becomes necessary to prevent or manage bleeding during surgical procedures or significant trauma. The primary goal is to temporarily raise the Factor XI level to ensure clotting at the site of injury or procedure.
In the United States, Factor XI concentrate is not widely available. Therefore, Fresh Frozen Plasma (FFP) is often the standard therapy when FXI replacement is needed. FFP contains all clotting factors, including FXI, but large volumes may be required to achieve therapeutic levels, which carries risks like fluid overload. Specialized Factor XI concentrates are available in some other countries, offering a more targeted treatment option.
A highly effective treatment for Hemophilia C, especially for mucosal bleeding, involves antifibrinolytic medications like tranexamic acid. These drugs stabilize the clot once it has formed, preventing premature breakdown in areas like the mouth or uterus. Antifibrinolytics are often sufficient for minor procedures, such as dental work, and are used to manage heavy menstrual bleeding in women.
Long-term care involves proactive management and close communication with a hematologist. Patients must be educated on avoiding medications that interfere with clotting, such as nonsteroidal anti-inflammatory drugs (NSAIDs). Prophylactic treatment with FFP or antifibrinolytics is administered only before high-risk procedures, contrasting with the routine prophylaxis often needed for severe Hemophilia A or B.