Haemophilia C (also known as plasma thromboplastin antecedent (PTA) deficiency or Rosenthal syndrome) is a mild form of

haemophilia Haemophilia, or hemophilia (), is a mostly inherited genetic disorder that impairs the body's ability to make blood clots, a process needed to stop bleeding. This results in people bleeding for a longer time after an injury, easy bruising, ...

affecting both sexes, due to factor XI deficiency. It predominantly occurs in

Ashkenazi Jews Ashkenazi Jews ( ; he, יְהוּדֵי אַשְׁכְּנַז, translit=Yehudei Ashkenaz, ; yi, אַשכּנזישע ייִדן, Ashkenazishe Yidn), also known as Ashkenazic Jews or ''Ashkenazim'',, Ashkenazi Hebrew pronunciation: , singu ...

. It is the fourth most common

coagulation Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It potentially results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The mechanism o ...

disorder after

von Willebrand's disease Von Willebrand disease (VWD) is the most common hereditary blood-clotting disorder in humans. An acquired form can sometimes result from other medical conditions. It arises from a deficiency in the quality or quantity of von Willebrand factor ...

and

haemophilia A Haemophilia A (or hemophilia A) is a genetic deficiency in clotting factor VIII, which causes increased bleeding and usually affects males. In the majority of cases it is inherited as an X-linked recessive trait, though there are cases which arise ...

and B. In the United States, it is thought to affect 1 in 100,000 of the adult population, making it 10% as common as haemophilia A.

Signs and symptoms

In terms of the signs/symptoms of haemophilia C, unlike individuals with

Haemophilia A Haemophilia A (or hemophilia A) is a genetic deficiency in clotting factor VIII, which causes increased bleeding and usually affects males. In the majority of cases it is inherited as an X-linked recessive trait, though there are cases which arise ...

and B, people affected by it are not ones to bleed spontaneously. In these cases, haemorrhages tend to happen after a major surgery or injury. However, people affected with haemophilia C might experience symptoms closely related to those of other forms of haemophilia such as the following:

Cause

Human male karyotpe high resolution - Chromosome 4 cropped

Haemophilia C is caused by a deficiency of

factor XI Factor XI or plasma thromboplastin antecedent is the zymogen form of factor XIa, one of the enzymes of the coagulation cascade. Like many other coagulation factors, it is a serine protease. In humans, Factor XI is encoded by the ''F11'' gene. ...

and is distinguished from haemophilia A and B by the fact it does not lead to bleeding into the joints. Furthermore, it has

autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

inheritance, since the gene for factor XI is located on chromosome 4 (near the prekallikrein gene); and it is not completely

recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

, individuals who are

heterozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...

also show increased bleeding. Many mutations exist, and the bleeding risk is not always influenced by the severity of the deficiency. Haemophilia C is occasionally observed in individuals with

systemic lupus erythematosus Lupus, technically known as systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Comm ...

, because of inhibitors to the FXI protein.

Diagnosis

The diagnosis of haemophilia C (factor XI deficiency) is centered on prolonged activated

partial thromboplastin time The partial thromboplastin time (PTT), also known as the activated partial thromboplastin time (aPTT or APTT), is a blood test that characterizes coagulation of the blood. A historical name for this measure is the kaolin-cephalin clotting time ( ...

(aPTT).One will find that the factor XI has decreased in the individuals body. In terms of differential diagnosis one must consider:

haemophilia B Haemophilia B, also spelled hemophilia B, is a blood clotting disorder causing easy bruising and bleeding due to an inherited mutation of the gene for factor IX, and resulting in a deficiency of factor IX. It is less common than factor VIII defi ...

lupus anticoagulant Lupus anticoagulant is an immunoglobulin that binds to phospholipids and proteins associated with the cell membrane. Its name is a partial misnomer, as it is actually a prothrombotic antibody ''in vivo''. Lupus anticoagulant in living systems c ...

and

heparin Heparin, also known as unfractionated heparin (UFH), is a medication and naturally occurring glycosaminoglycan. Since heparins depend on the activity of antithrombin, they are considered anticoagulants. Specifically it is also used in the treatm ...

contamination. The prolongation of the activated partial thromboplastin time should completely correct with a 1:1

mixing study Mixing studies are tests performed on blood plasma of patients or test subjects to distinguish factor deficiencies from factor inhibitors, such as lupus anticoagulant, or specific factor inhibitors, such as antibodies directed against factor VIII ...

with normal plasma if haemophilia C is present; in contrast, if a lupus anticoagulant is present as the cause of a prolonged aPTT, the aPTT will not correct with a 1:1 mixing study.

Treatment

In terms of haemophilia C medication

tranexamic acid Tranexamic acid (TXA) is a medication used to treat or prevent excessive blood loss from major trauma, postpartum bleeding, surgery, tooth removal, nosebleeds, and heavy menstruation. It is also used for hereditary angioedema. It is taken eit ...

is often used for both treatment after an incident of bleeding and as a preventive measure to avoid excessive bleeding during oral surgery. Treatment is usually not necessary, except in relation to operations, leading to many of those having the condition not being aware of it. In these cases,

fresh frozen plasma Fresh frozen plasma (FFP) is a blood product made from the liquid portion of whole blood. It is used to treat conditions in which there are low blood clotting factors (INR > 1.5) or low levels of other blood proteins. It may also be used as the re ...

or recombinant factor XI may be used, but only if necessary. Those affected may often develop nosebleeds, while females can experience unusual menstrual bleeding which can be avoided by taking birth control such as:

IUDs An intrauterine device (IUD), also known as intrauterine contraceptive device (IUCD or ICD) or coil, is a small, often T-shaped birth control device that is inserted into the uterus to prevent pregnancy. IUDs are one form of long-acting revers ...

and oral or injected contraceptives to increase coagulation ability by adjusting hormones to levels similar to pregnancy.

References

External links

{{Medicine Haemophilia