Congenital thrombotic thrombocytopenic purpura

Other Names: TTP, congenital; Thrombotic thrombocytopenic purpura, familial; Microangiopathic hemolytic anemia; Upshaw-Schulman syndrome; USS; Schulman-Upshaw syndrome; Upshaw factor, deficiency of; Microangiopathic hemolytic anemia, congenital; Thrombotic microangiopathy, familial; Thrombotic thrombocytopenic purpura, congenital

Congenital thrombotic thrombocytopenic purpura (congenital TTP) is a blood disorder in which blood clots form in the small blood vessels throughout the body.

Epidemiology

Congenital or inherited TTP represents less than 5% of all cases of TTP and the annual incidence is estimated at less than 1/1,000,000.

Cause

Mutations in the ADAMTS13 gene cause the familial form of thrombotic thrombocytopenic purpura. The ADAMTS13 gene provides instructions for making an enzyme that is involved in the normal process of blood clotting. Mutations in this gene lead to a severe reduction in the activity of this enzyme. The acquired form of thrombotic thrombocytopenic purpura also results from a reduction in ADAMTS13 enzyme activity; however, people with the acquired form do not have mutations in the ADAMTS13 gene. Instead, their immune systems make specific proteins called autoantibodies that block the activity of the enzyme.

A lack of ADAMTS13 enzyme activity disrupts the usual balance between bleeding and clotting. Normally, blood clots form at the site of an injury to seal off damaged blood vessels and prevent excess blood loss. In people with thrombotic thrombocytopenic purpura, clots form throughout the body as platelets bind together abnormally and stick to the walls of blood vessels. These clots can block small blood vessels, causing organ damage and the other features of thrombotic thrombocytopenic purpura.

Researchers believe that other genetic or environmental factors may contribute to the onset of signs and symptoms of thrombotic thrombocytopenic purpura. In people with reduced ADAMTS13 enzyme activity, factors such as pregnancy, surgery, and infection may trigger abnormal blood clotting and its associated complications.

Inheritance

Autosomal recessive inheritance, a 25% chance

The familial form of thrombotic thrombocytopenic purpura is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Symptoms

Signs and symptoms typically develop in infancy or early childhood, but in some cases they do not develop until adulthood, particularly during pregnancy in women or after an infection or vaccination. Signs and symptoms generally are due to hemolytic anemia, low platelets (thrombocytopenia), and neurologic dysfunction. Symptoms of anemia can include fatigue, paleness, jaundice, shortness of breath, and a rapid heart rate. Widespread thrombosis (abnormal clotting) can lead to problems with the nervous system (such as personality changes, headaches, confusion, and seizures), abnormal kidney function, heart problems, and gastrointestinal problems. Signs and symptoms often recur on a regular basis but the severity and frequency varies.

Diagnosis

Tests that may be ordered include:

• ADAMTS 13 activity level
• Bilirubin
• Blood smear
• Complete blood count (CBC)
• Creatinine level
• Lactate dehydrogenase (LDH) level
• Platelet count
• Urinalysis
• Haptoglobin
• Coombs test

Treatment

Treatment may involve plasma exchange (also called plasmapheresis) for acute episodes, and prophylactic plasma therapy for those with chronic disease. Women with congenital TTP should receive pregnancy counseling in order to prepare for management during pregnancy. Regular plasma infusions are needed during pregnancy, in addition to close monitoring.

Prognosis

Most people respond well to treatment, which can prevent long-term organ complications due to relapses. However, life expectancy largely depends on severity and whether other underlying conditions are present. Without treatment, congenital TTP is fatal.

NIH genetic and rare disease info

• NIH info on Congenital thrombotic thrombocytopenic purpura

Congenital thrombotic thrombocytopenic purpura is a rare disease.

Congenital thrombotic thrombocytopenic purpura Resources
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