TTP symptoms vary, but prevention helps control them: Study
Congenital form of disease can look very different in one person than in another
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The congenital form of thrombotic thrombocytopenic purpura (TTP) can look very different in one person than in another, but preventive treatment can help reduce the risk of acute episodes and organ damage in people with the disease, a U.K. registry study found.
“This work … highlights the importance of national and international collaboration and cooperation in diagnosis, characterising, and improving the therapies available to cTTP patients,” the researchers wrote.
The study, “Long term follow-up outcomes in congenital thrombotic thrombocytopenic purpura,” was published in Blood.
TTP is a blood disorder marked by reduced activity of the ADAMTS13 enzyme, which normally helps prevent uncontrolled blood clotting. Lack of functional ADAMTS13 in TTP causes tiny clots to form in blood vessels, ultimately driving disease symptoms.
In most people with TTP, low ADAMTS13 activity is caused by an autoimmune reaction. Congenital TTP, or cTTP, is a rare subtype of the disease caused by mutations in the gene that provides instructions to make ADAMTS13.
Symptoms vary with age, gene mutation
The researchers analyzed outcomes from 104 people with cTTP in the U.K., most of whom are still being followed as part of a national registry. Most of these patients were white, though the study also included patients with African, South Asian, and other ancestries.
There was a lot of variability in the age at which cTTP symptoms first appeared. More than a third of the patients (39.4%) were diagnosed as children, some in infancy and others later in childhood or adolescence. The most common symptoms seen in childhood were low platelet counts (thrombocytopenia) and jaundice (yellowing of the skin and eyes).
The remaining 60.6% of patients weren’t diagnosed until they were adults, often as a result of complications occurring during pregnancy. Common symptoms at the time of cTTP diagnosis included headache and other neurological issues. Abdominal pain was also common.
A total of 71 different mutations in the gene that encodes ADAMTS13 were identified among all these cTTP patients. Sixteen of these mutations had not previously been linked to the disease. Researchers said that the identification of these new mutations may aid in diagnosing future patients, and they noted that mutations affecting a part of the enzyme called the N-terminal domain were generally associated with an earlier age at symptom onset.
Most cTTP patients in the study were receiving some form of prophylactic, or preventive, TTP treatment. As of the latest follow-up, most were being treated with a recombinant (lab-made) version of the ADAMTS13 enzyme for prophylaxis.
Acute TTP episodes and organ damage were more common in patients who weren’t on regular prophylaxis, which the scientists said emphasizes the importance of preventive care for people with the rare genetic condition.
“Reductions in acute cTTP episodes and end organ damage are reported when patients are established on regular prophylaxis,” the researchers wrote, adding that “establishing cTTP patients on regular prophylaxis had a significant effect on cTTP-related symptoms … [including] significant reductions in headache, abdominal pain and fatigue.”
They also said that optimal symptom control was generally achieved when prophylaxis was given weekly, as less frequent dosing was often insufficient to control certain symptoms, especially headache.
“This work provides valuable evidence informing diagnosis and therapeutic responses in cTTP patients and through ongoing analysis and collaborative registries we hope evidence based cTTP patient care can continue to improve, especially with the introduction of recombinant ADAMTS13,” they wrote.
