Although thrombotic thrombocytopenic purpura (TTP) is rarely seen in pediatric patients, failure to recognize this condition often leads to severe consequences and poor outcomes. Classic features of TTP include thrombocytopenia, microangiopathic hemolytic anemia, acute kidney injury, fever, and central nervous system involvement. However, patients suffering from this condition may not present with all of the symptoms simultaneously. Therefore, it is of utmost importance for healthcare providers to have a high index of suspicion. Laboratory investigations may reveal the presence of schistocytes on peripheral blood smear, negative Coombs test, high lactate dehydrogenase levels and severely low platelet counts. The etiology of TTP is mainly due to insufficient cleavage of the large multimers of von Willebrand factor (vWF) secondary to decreased activity of ADAMTS13 (a disintegrin and metalloprotease with Thrombospondin type 1 repeats, member 13). TTP can be broadly classified into familial TTP (Upshaw Schulman syndrome) and non-familial TTP. Familial TTP is due to a congenital deficiency of ADAMTS13. Its mainstay of therapy is initiation of plasmapheresis during the acute phase, followed by regular fresh frozen plasma (FFP) infusions. Alternatively, non-familial TTP is due to a decrease in ADAMTS13 activity secondary to the presence of anti-ADAMTS13 antibodies. Once again, the primary treatment is plasmapheresis; however, recent anecdotal data also supports the use of rituximab in select cases.
ADAM Proteins ; genetics ; ADAMTS13 Protein ; Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; Child ; Humans ; Plasmapheresis ; Purpura, Thrombotic Thrombocytopenic ; etiology ; therapy ; Rituximab

Objective: To report the clinical manifestations and laboratory features of five patients with congenital thrombotic thrombocytopenic purpura (cTTP) and explore its standardized clinical diagnosis and treatment along with a review of literature. Methods: Clinical data of patients, such as age of onset, disease manifestation, personal history, family history, and misdiagnosed disease, were collected. Treatment outcomes, therapeutic effects of plasma infusion, and organ function evaluation were observed. The relationship among the clinical manifestations, treatment outcomes, and ADAMTS13 gene mutation of patients with cTTP was analyzed. Additionally, detection of ADAMTS13 activity and analysis of ADAMTS13 gene mutation were explored. Results: The age of onset of cTTP was either in childhood or adulthood except in one case, which was at the age of 1. The primary manifestations were obvious thrombocytopenia, anemia, and different degrees of nervous system involvement. Most of the patients were initially suspected of having immune thrombocytopenia. Acute cTTP was induced by pregnancy and infection in two and one case, respectively. ADAMTS13 gene mutation was detected in all cases, and there was an inherent relationship between the mutation site, clinical manifestations, and degree of organ injury. Therapeutic or prophylactic plasma transfusion was effective for treating cTTP. Conclusions: The clinical manifestations of cTTP vary among individuals, resulting in frequent misdiagnosis that delays treatment. ADAMTS13 activity detection in plasma and ADAMTS13 gene mutation analysis are important bases to diagnose cTTP. Prophylactic plasma transfusion is vital to prevent the onset of the disease.
Female ; Pregnancy ; Humans ; Adult ; Blood Component Transfusion ; Plasma ; Purpura, Thrombotic Thrombocytopenic/therapy* ; Mutation ; Purpura, Thrombocytopenic, Idiopathic ; ADAMTS13 Protein/therapeutic use*

Objective: To observe the efficacy and adverse reactions of a combination therapy regimen based on bortezomib and glucocorticoids in recurrent/refractory immune thrombocytopenic purpura (iTTP) . Methods: Six patients with recurrent/refractory TTP were included and treated with a glucocorticoid and two courses of bortezomib-based regimen. The clinical remission status of patients, changes in ADAMTS13 activity/ADAMTS13 inhibitor, and the occurrence of treatment-related adverse reactions were observed. Results: Of the 6 patients, 2 were males and 4 were females, with a median age of 21.5 (18-68) years. Refractory TTP was found in 1 case and recurrent TTP in 5 cases. Glucocorticoids were administered with reference to prednisone at 1 mg·kg(-1)·d(-1), and gradually reduced in dosage after achieving clinical remission. Bortezomib is subcutaneously administered at 1.3 mg/m(2) on days 1, 4, 8, and 11 with a 28-day treatment course consisting of 2 courses. Six patients achieved clinical remission after receiving bortezomib as the main treatment. ADMATS13 activity returned to normal in all patients with TTP after treatment, and the ADAMTS13 inhibitor turned negative. Thrombocytopenia is the most common adverse reaction after treatment, with other adverse reactions, including peripheral neuritis and abdominal pain, but ultimately all patients returned to normal. In a median follow-up of 26 (9-41) months, 5 patients maintained sustained remission, and 1 patient relapsed after 16 months of bortezomib treatment. Conclusion: Combination therapy of bortezomib and glucocorticoids has a satisfactory therapeutic effect and controllable adverse reactions for recurrent/refractory iTTP.
Male ; Female ; Humans ; Young Adult ; Adult ; Middle Aged ; Aged ; Bortezomib/therapeutic use* ; Glucocorticoids/therapeutic use* ; Rituximab/therapeutic use* ; Purpura, Thrombotic Thrombocytopenic/drug therapy* ; Purpura, Thrombocytopenic, Idiopathic/drug therapy* ; ADAMTS13 Protein/therapeutic use*