Recognizing and managing hereditary and acquired thrombotic thrombocytopenic purpura in infants and children

Abstract

We describe how infants and children with hereditary and acquired autoimmune thrombotic thrombocytopenic purpura (TTP) initially present and how they can be promptly diagnosed and effectively managed. These are uncommon disorders that are commonly misdiagnosed and can be rapidly fatal. TTP is caused by a severe deficiency of the plasma protease, A disintegrin and Metalloprotease with a ThromboSpondin type 1 motif, member 13 (ADAMTS13). Measurement of ADAMTS13 activity is becoming easily accessible. A common presentation of hereditary TTP is neonatal severe hemolysis and hyperbilirubinemia. However, the median age of diagnosis is not until 5.5 years. Plasma is effective treatment for exacerbations and for prophylaxis. Plasma may be replaced by recombinant ADAMTS13 when it becomes available. Acquired TTP is more frequent in older children, in whom it is more common in girls and is commonly associated with systemic lupus erythematosus. For acquired TTP, plasma exchange and immunosuppression are the current treatment for acute episodes; caplacizumab is now commonly used in adults and may replace plasma exchange.

Thrombotic thrombocytopenic purpura in pediatrics. A case report

“…Such involvement may be hereditary or acquired due to the formation of autoantibodies (10% versus 90% of cases, respectively). 3 ADAMTS13 is an enzyme necessary for the proteolysis of von Willebrand factor (VWF) after its secretion by endothelial cells; in the absence of the VWF multimer size regulatory mechanism, microvascular platelet thrombosis occurs, resulting in red blood cell fragmentation and platelet consumption by thrombus formation. 1 ADAMTS13 deficiency associated with the absence of anti-ADAMTS13 antibodies suggests congenital TTP, especially when it occurs in the neonatal period, in adult women during pregnancy, or in children or adults with typical presentations associated with triggering events and family history.…”

Ventricular Tachycardia in a Pediatric Patient with High-Risk Thrombotic Thrombocytopenia Purpura

“…ADAMTS13 is a plasma protease responsible for proteolysis of von Willebrand factor (VWF). In its absence, uncleaved VWF multimers circulate in the blood, resulting in platelet binding and increased thrombotic risk [ 1 ].…”

“…While hereditary TTP arises from biallelic ADAMTS13 mutations, acquired TTP is caused by autoantibodies increasing the rate of ADAMTS13 elimination or inhibiting its function [ 1 ]. It is estimated that only ~10% of all TTP cases occur in childhood [ 2 ], with less than one case per million children per year [ 3 , 4 ], and is particularly rare in children younger than 9 years old [ 1 ].…”

Clinical features and neurological outcomes in pediatric immune‐mediated thrombotic thrombocytopenic purpura: A report from a large pediatric hematology center

“…13 Consequently, pediatric iTTP is poorly described in the medical literature, with only 69 children under the age of 18 years reported in the last 20 years. 2 Therefore, the overall response rates, the incidence of refractory or relapsed disease, and long-term morbidity outcomes are mostly extrapolated from adult studies. 14 We aimed to describe our 20-year institutional experience of all patients with iTTP, who were primarily cared for in our institution.…”

“…patients were available for evaluation of long-term neurological outcomes through chart review. Three were not included because of being LTFU(2) and death during initial hospitalization(1). Eleven of the 15 (73%) patients had evidence of psychologic or cognitive abnormalities documented in follow-up clinic visits at least 3 months to 8 years from disease onset.Eleven of 15 patients had neurocognitive sequelae following TTP diagnosis.…”