Information on the following diseases can be found in the Related Disorders section of this report:

• Von Willebrand Disease
• Factor IX Deficiency
• Hemophilia
• Henoch-Shonlein Purpura

Factor XIII Deficiency causes internal bleeding. The blood may seep into surrounding soft tissues several days after trauma, even mild trauma such as a bump or bruise. Pain and swelling may occur at the injury site prior to bleeding. If the bleeding continues, large cysts may form in the surrounding tissue that may destroy bone and cause peripheral nerve damage, usually in the thigh and buttocks areas.

At birth, an infant with Factor XIII Deficiency may bleed from the umbilical cord. This rarely occurs in other blood clotting disorders.

The most serious hemorrhaging that can occur in Factor XIII Deficiency is in the central nervous system (i.e., brain and spinal cord) following mild head trauma. This can occur in approximately 25 percent of affected individuals In some cases, hemorrhaging may stop spontaneously without treatment.

Females with Factor XIII Deficiency who become pregnant are at high risk for miscarriage if they do not receive appropriate treatment. Men with this disorder may be sterile or have extremely low sperm counts. Replacing Factor XIII in these men does not correct sterility.

Some of the less frequently seen symptoms of this disorder are poor wound healing, excessive bleeding from wounds, blood blisters attached to the abdominal wall (retroperitoneal hematomas), and/or blood in the urine (hematuria).

Some symptoms are seldom or never seen in people with Factor XIII Deficiency and this may help distinguish it from other bleeding disorders. These may include excessive blood loss during menstruation, hemorrhages within the eye, gastrointestinal bleeding, arthritis caused by an accumulation of blood in the joints, postoperative hemorrhage, bleeding from mucous membranes, and/or tiny red spots on the skin (petechiae).

Factor XIII Deficiency is not generally a threat to patients who need surgery. The small amount of Factor XIII present in blood transfusions generally prevents postoperative hemorrhaging. Excessive bleeding from wounds, abrasions, or even spontaneous abortions is not common unless a person with this disorder uses aspirin or similar medications.

Factor XIII Deficiency is a rare disorder that may be acquired in conjunction with other disorders such as Sickle Cell Disease and Henoch-Shonlein Purpura. It may sometimes occur as a result of cirrhosis or cancer of the liver. In these cases, the levels of Factor XIII may return to normal when the underlying liver disease is treated. People who have been treated with the drug isoiazid or have chronic kidney failure may develop anticoagulation antibodies that impair the clotting function of Factor XIII. (For more information on these disorders, choose "Sickle Cell" and "Henoch-Shonlein Purpura" as your search term in the Rare Disease Database.)

In congenital Factor XIII Deficiency, the disorder is inherited as an autosomal dominant genetic trait. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother. In dominant disorders, a single copy of the disease gene (received from either the mother or father) will be expressed "dominating" the other normal gene and resulting in the appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child. The disease gene for Factor XIII Deficiency is located on the short arm (p) of chromosome 6 (6p25-p24).

Factor XIII Deficiency is a rare disorder that affects males and females in equal numbers. The disorder has been identified in pregnant women who are about to deliver, in newborns, and in people who have undergone major surgery. Factor XIII Deficiency may also occur in people with Sickle Cell Disease and in many children with Hehoch-Shonlein Purpura.

Symptoms of the following disorders can be similar to those of Factor XIII Deficiency. Comparisons may be useful for a differential diagnosis:

Von Willebrand Disease is a rare inherited blood disorder of infancy or childhood characterized by prolonged bleeding and abnormally slow blood clotting time. Symptoms develop due to a deficiency of factor VII and von Willebrand factor, along with a structural defect of platelets in the blood. Symptoms may include heavy nose bleeds and excessive bleeding after injury, menstruation, childbirth, surgery, and/or some dental procedures. (For more information on this disorder, choose "von Willebrand Disease" as your search term in the Rare Disease Database.)

Factor IX Deficiency is a rare inherited blood disorder characterized by severe and prolonged profuse bleeding (hemorrhaging) and in extreme cases, joint pain and bone deformities. Symptoms develop due to a deficiency of Factor IX. This blood factor is a component of thromboplastin which enables the blood to clot. In mild cases of Factor IX Deficiency, patients hemorrhage only after surgery or tooth extractions. In more severe cases, hemorrhage can occur in any part of the body, including the central nervous system and the digestive tract. In extreme cases, internal hemorrhaging occurs in the muscles, joints, and/or bones, resulting in deformity. (For more information on this disorder, choose "Factor IX Deficiency" as your search term in the Rare Disease Database.)

Hemophilia is a rare inherited blood clotting disorder caused by inactive or deficient blood proteins (usually Factor VIII). This disorder is found in males almost exclusively and may be mild, moderate, or severe. The most serious symptom of Hemophilia is uncontrolled internal bleeding that can begin spontaneously without any apparent cause. Internal bleeding may cause permanent damage to joints and muscles. Bruises and trauma can trigger episodes of serious internal bleeding. (For more information on this disorder, choose "Hemophilia" as your search term in the Rare Disease Database.)

Henoch-Shonlein Purpura is a rare inherited disorder of the capillaries characterized by reddish skin lesions and internal hemorrhaging. This disorder can affect the joints, gastrointestinal tract, kidneys, and in some rare cases, the central nervous system. Initial symptoms include red skin, swelling, and hives. Patients may also experience fever and a general feeling of weakness (malaise). Severe localized pain may occur if blood and plasma accumulate in the joints or abdomen. (For more information on this disorder, choose "Henoch-Shonlein Purpura" as your search term in the Rare Disease Database.)

The amount of Factor XIII necessary for a normal response to trauma is only about 10 percent of that in the normal plasma. People with Factor XIII Deficiency are generally given small infusions of fresh or frozen blood plasma (cryoprecipitates), or Factor XIII concentrates every three or four weeks. This has proven to be a highly successful preventive treatment for the disorder. Patients typically have a normal response to trauma while on these transfusions. When patients with Factor XIII Deficiency have a high incidence of bleeding inside the head (intracranial), preventive treatment is necessary.

Pregnant women can be given exogenous Factor XIII to help prevent spontaneous abortion. Genetic counseling may be of benefit for patients and their families. Other treatment is symptomatic and supportive.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

Other information about clinical trials related to factor XIII deficiency may be available from the National Hemophilia Foundation. See contract information for this organization in the Resources section of this report.

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MENDELIAN INHERITANCE IN MAN, 10th Ed.: Victor A. McKusick, Editor: Johns Hopkins University Press, 1992. Pp. 379-381.

CECIL TEXTBOOK OF MEDICINE, 19th Ed.: James B. Wyngaarden, and Lloyd H. Smith, Jr., Editors; W.B. Saunders Co., 1990. Pp. 1010-1011.

HEMATOLOGY, 4th Ed,: William J. Williams, et al., Editors; McGraw-Hill, Inc., 1990. Pp. 1491-1492.

BIRTH DEFECTS ENCYCLOPEDIA, Mary Louise Buyse, M.D., Editor-In-Chief; Blackwell Scientific Publications, 1990. Pp. 680-81.

NEONATAL FACTOR XIII DEFICIENCY: J. Landman et al.; Clin Pediatr (1985 Jun;24(6)). Pp. 352-353.

INHERITED FACTOR XIII DEFICIENCY: D. Waks et al.; Fondu P; Acta Clin Belg (1989;44(1)). Pp. 52-57.