Hemophilia C
Definition
Hemophilia is a disease that causes the body lacks the protein needed for blood clotting process when there is bleeding. This protein is commonly called a clotting factor or coagulation factors.
While factor VIII and factor IX deficiencies are the best known and most common types of hemophilia, other clotting factor deficiencies also exist. Low levels of factor XI (FXI) cause hemophilia C
Even in severe deficiency of factor XI, the bleeding tendency is mild. Unlike the bleeding tendency in hemophilia Aor hemophilia B, which is clearly related to the factor level, the bleeding risk in hemophilia C is not always influenced by the severity of the deficiency, especially in individuals with partial deficiency. Indeed, some patients with severe deficiency do not have a bleeding tendency, whereas some patients with mild deficiency bleed excessively.
FXI plays an important role in tissue factor-dependent thrombin generation on the surface of activated platelets.1 The formation of the initiating complex, TF-FVIIa-FXa, results in the generation of a small amount of thrombin. This is insufficient to produce a stable fibrin clot but stimulates a number of reactions in the amplification loop, including the activation of FXI. Subsequent formation of the tenase complex (FIXa-FVIIIa), followed by the prothrombinase complex (FXa-FVa), leads to a large burst of thrombin
This unpredictability, which is not fully understood, makes hemophilia C more difficult to manage than hemophilia A or B.
Severe deficiency is defined as factor XIc activity of 15-20 U/dL or lower. However, this is no longer suitable terminology since the bleeding disorder is not clinically severe, even at very low levels of factor XI. Spontaneous bleeding rarely occurs, but bleeding may occur after surgery, more commonly in those with the lowest levels. The levels in this range, less than about 15 U/dL, generally identify individuals who have 2 FXIgene mutations. Patients with partial deficiency, generally heterozygous with a single FXI gene mutation, have levels of about 20-60 U/dL (ie, the lower limit of the normal range). About 30-50% of individuals with partial deficiency may have excessive bleeding; however, identifying these persons in advance is difficult. Furthermore, normal infants without hemophilia C are likely to have low factor XIc levels until they are older than 6 months.
Bleeding Tendency
Unlike with hemophilia A and hemophilia B, the frequency of bleeding with hemophilia C is not determined by the patient’s factor level.1An unpredictable (or inconsistent) bleeding pattern occurs in people with this disorder.1-4 The inability to predict bleeding complicates treatment. Individuals with hemophilia C do not commonly bleed spontaneously; bleeding tends to occur after surgery or injury, especially to the mucocutaneous lining of the oral or nasal cavities and the urinary tract.
Procedures with an increased risk of bleeding include the following:
- dental extractions
- tonsillectomies
- surgery in the urinary and genital tracts
- nasal surgery
- Additional clotting factor disorders, especially von Willebrand disease, or a more subtle change in hemostatic balance
- Variant factor XI molecules (ie, those with a discrepancy between factor XI clotting activity compared with antigen): These variants are rare, and no correlation between mutation type and bleeding tendency has been identified.
- Increased fibrinolysis at certain surgical sites
Unlike individuals with hemophilia A and hemophilia B, patients with hemophilia C do not commonly experience joint bleeds. They may, however, experience the following: bruising, nosebleeds, or blood in the urine; and for women, menorrhagia and prolonged bleeding after childbirth.1-4Injury may cause bleeding in muscles, joints and other areas.
Diagnosis of Hemophilia C
Obtaining a detailed personal and family bleeding history of a patient is very important in the diagnosis of hemophilia C. Although this condition is found in all racial and ethnic groups, it is helpful to establish the patient’s background, as this may give an indication of the likely disorder. Various screening coagulation tests are utilized to diagnose hemophilia C, the most common being the activated partial thromboplastin time (APTT) and a FXI activity assay
Treatment of Hemophilia C
Patients with severe hemophilia C do not require treatment or prophylactic (preventive) therapy for daily activities. However, replacement therapy is required for dental extractions and surgery, and treatment options depend on the type of procedure.
Fresh frozen plasma, since FXI is not concentrated in fresh frozen plasma, a large volume of this product may be required to raise the FXI activity to a hemostatic level
Patients with severe factor XI deficiency may develop an inhibitor, as seen in hemophilia A or B. The development of an inhibitorgenerally complicates treatment options. Approximately one-third of patients with severe (<1%) FXI deficiency who use plasma product replacement therapy may develop an inhibitor. There are a few case reports describing the successful use of recombinant FVIIa in these patients; however, recombinant FVIIa should be used with caution because thrombotic complications have been reported.
Antifibrinolytic agents such as epsilon aminocaproic acid (Amicar®) or tranexamic acid may be useful for treating mucocutaneous bleeding in individuals with hemophilia C.2Antifibrinolytic agents are generally not used concomitantly with FXI concentrate, because of an increased risk of thrombotic complications. They are also relatively contraindicated in treating bleeding from the urinary tract because of potential clot retention.1 Desmopressin may be used in some cases to produce modest rises in FXI activity in partial deficiency,6but the evidence for efficacy is unconvincing.
Complications of Hemophilia C
The complications of hemophilia C are those primarily associated with the use of fresh frozen plasma. While today’s blood products are much safer than those of the past, transmission of hepatitis A, hepatitis C, and newly discovered blood-borne diseases remain a risk for people treated with plasma-derived products. Immunization against hepatitis A and B is recommended for all individuals with hemophilia. No vaccination currently exists for hepatitis C.
See Also
Source :
http://www.ihtc.org/medical-professionals/blood-disorders/bleeding-disorders/hemophilia-c/
No comments:
Post a Comment