Hemophilia C is a rare, inherited bleeding disorder caused by insufficient levels of coagulation factor XI (FXI), a protein essential for blood clotting. It is also called Factor XI deficiency or Rosenthal syndrome. Hemophilia C generally results in milder bleeding tendencies compared to other hemophilias, though excessive bleeding following trauma or surgery remains a concern.
Factor XI and Genetic Transmission
Factor XI plays a role in the intricate process of blood coagulation, where it helps sustain the fibrin clot once initial clotting has begun. FXI helps to generate thrombin, a protein that works to convert fibrinogen into fibrin, which is the stable mesh that ultimately traps platelets and stabilizes the blood clot. A deficiency in this factor can compromise the body’s ability to maintain a robust clot, leading to prolonged bleeding.
The deficiency is caused by mutations in the F11 gene, located on autosome 4. This autosomal inheritance pattern explains why the condition affects both males and females equally, unlike X-linked Hemophilia A and B. Severe Factor XI deficiency is typically inherited in an autosomal recessive manner, requiring an individual to inherit two copies of the mutated gene, one from each parent.
Individuals who inherit only one copy of the mutated F11 gene are considered heterozygous and generally have Factor XI levels between 25% and 70% of normal. While those with two mutated copies (homozygous) often have Factor XI levels below 15%, even heterozygotes are at risk of bleeding after procedures. The severity of the deficiency, however, does not always correlate directly with the risk of bleeding, making the clinical outcome often unpredictable based on factor level alone.
Recognizing Symptoms
The clinical presentation of Hemophilia C is highly variable, with many affected individuals remaining asymptomatic until they undergo a medical procedure or experience significant trauma. When symptoms do occur, they are generally less severe than those seen in Hemophilia A or B. Spontaneous bleeding into joints or muscles, a common and damaging feature of severe Hemophilia A and B, is rare in Hemophilia C.
The most typical bleeding events involve mucosal surfaces, such as the mouth, nose, and urinary tract, which are areas with high fibrinolytic activity. Patients often experience prolonged or excessive bleeding following trauma, dental extractions, or surgery, such as tonsillectomy. Other common signs include frequent nosebleeds (epistaxis) and easy bruising.
For female patients, heavy menstrual bleeding (menorrhagia) is a significant and frequent symptom that can lead to anemia. Postpartum hemorrhage, which is excessive bleeding after childbirth, is also a serious concern for women with Factor XI deficiency. The poor correlation between Factor XI activity levels and the severity of clinical bleeding means a patient’s personal and family history of bleeding is often a better predictor of their risk than a lab test alone.
Confirmation and Treatment
The diagnosis of Hemophilia C requires specific laboratory testing because standard screening tools are often insufficient to capture the full picture. An initial test, the activated Partial Thromboplastin Time (aPTT), which measures the time it takes for blood to clot, may be prolonged in severe deficiency but can be normal or only slightly prolonged in individuals with mild or heterozygous forms.
A definitive diagnosis is confirmed by a specific Factor XI activity assay, which directly measures the functional level of the factor in the patient’s plasma. Individuals with a confirmed deficiency must proactively manage their condition, especially before any planned surgical or dental procedures. The treatment strategy focuses on preventing or stopping bleeding by replacing the missing factor and stabilizing the clot.
Treatment Options
Since a purified Factor XI concentrate is not widely available, the most common replacement therapy is Fresh Frozen Plasma (FFP). FFP contains all clotting factors, including FXI, but requires large infusion volumes and carries the risk of allergic reactions. For bleeding involving mucosal tissues, antifibrinolytic agents like tranexamic acid or aminocaproic acid are highly effective and may be used alone for minor procedures like dental extractions. Desmopressin (DDAVP), used for mild Hemophilia A, is not considered an effective treatment for Hemophilia C, as it does not significantly increase Factor XI levels.