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Yash J Shetty
Group 531 C
Patients with TTP have unusually large multimers of von Willebrand factor (vWF) in their plasma, and they lack a plasma protease that is responsible for the breakdown of these ultralarge vWF multimers. In the congenital form of TTP, mutations in the gene encoding this protease have been described. In the more common sporadic form, an antibody inhibitor can be isolated in most patients. This protease has been isolated and cloned and is designated ADAMTS13.
Autoimmune
Inhibition of the enzyme ADAMTS13 by antibodies.
ADAMTS13 is a metalloproteinase responsible for the breakdown of von Willebrand factor (vWF), a protein that links platelets, blood clots, and the blood vessel wall in the process of blood coagulation.
Genetic
This condition may also be congenital. Such cases may be caused by mutations in the ADAMTS13 gene.
Secondary
Secondary TTP is diagnosed when the person's history mentions one of the known features associated with TTP. It comprises about 40% of all cases of TTP. Predisposing factors are:
Cancer
Bone marrow transplantation
Pregnancy
Medication use (Eg: Acyclovir)
Neurologic manifestations include alteration in mental status, seizures, hemiplegia, paresthesias, visual disturbance, aphasia, feeling very tired, confusion, and headaches.
Other symptoms include, a fast heart rate or shortness of breath, or pinpoint-sized purple or reddish dots on the skin known as petechiae, larger bruises (ecchymoses) may also develop.
The classic presentation of TTP, which occurs in less than 10% of people, includes five medical signs.
Hemolytic anemia and thrombocytopenia cause pallor, jaundice, and petechiae. Abnormal findings on neurologic examination consist of mental status changes and/or focal neurologic deficits. These defects can be present due to transient ischemic attacks. Organomegaly is not typical.
Laboratory studies for suspected TTP include a CBC, platelet count, blood smears, coagulation studies, BUN creatinine, and serum bilirubin and lactate dehydrogenase.
The exact etiology of TTP is unknown. Most sporadic cases of TTP appear to be associated with severe deficiency of ADAMTS13 activity due to autoantibodies against this protease. Measuring ADAMTS13 activity level may aid in diagnosis.ADAMTS13 is the unique sensitive and specific marker for TTP
Imaging studies and biopsies are not required for diagnosis.
TTP is characterized by thrombotic microangiopathy (TMA), the formation of blood clots in small blood vessels throughout the body, which can lead to microangiopathic hemolytic anemia and thrombocytopenia.
This characteristic is shared by two related syndromes, hemolytic-uremic syndrome (HUS) and atypical hemolytic uremic syndrome (aHUS). Consequently, differential diagnosis of these TMA-causing diseases is essential. In addition to TMA, one or more of the following symptoms may be present in each of these diseases: neurological symptoms (e.g. confusion, cerebral convulsions, seizures); kidney impairment (e.g. elevated creatinine, decreased estimated glomerular filtration rate [eGFR], abnormal urinalysis); and gastrointestinal (GI) symptoms (e.g. diarrhea nausea/vomiting, abdominal pain, gastroenteritis.
Unlike HUS and aHUS, TTP is known to be caused by an acquired defect in the ADAMTS13 protein, so a lab test showing ≤5% of normal ADAMTS13 levels is indicative of TTP.
Treatment of child‐onset acquired thrombotic thrombocytopenic purpura. The standard treatment of the acute phase of child‐onset acquired thrombotic thrombocytopenic purpura (TTP) is based on daily therapeutical plasmatherapy (and steroids) initiated in emergency until remission.
Some TTP children may also be unresponsive, or they may exhibit an exacerbation of the disease. Additional rituximab remains the second‐line treatment usually leading to a complete remission.
Follow‐up of TTP children in remission (medical consultation and ADAMTS13 monitoring) may show either a durable remission or a relapses requiring standard treatment.
ADAMTS13 monitoring is needed to identify a decrease in ADAMTS13 activity less than 10%, in the absence of clinical relapse and preemptive treatment with rituximab should be considered
Plasmatherapy
The first‐line treatment of the acute phase of child‐onset TTP remains an emergency and is based on daily plasma replacement therapy (plasma infusion or plasma exchange), allowing an exogenous supply of ADAMTS13 .
Immunomodulation
In acquired TTP, steroids are usually used as an adjunctive treatment to curative first‐line plasmatherapy.Patients refractory to the first‐line treatment (platelet count which does not double after 4 days of intensive treatment and lactate dehydrogenase above normal value), or in case of exacerbation of the disease (the absence of clinical improvement and/or thrombocytopenia <100 × 109/L for 2 days), immunomodulation with rituximab may be considered
Pediatric TTP is a rare entity within a rare disease and may initially be misdiagnosed as other TMA syndrome, autoimmune cytopenia, and malignant hemopathy. Congenital and acquired forms of child‐onset TTP have distinct biological and demographic features. Clinical, biological, and therapeutic management of children has been significantly improved in the last few years, but international recommendations are still needed. Long‐term follow‐up of patients with a first TTP episode in childhood is highly recommended.