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Platelet function and bleeding at different phases of childhood immune thrombocytopenia.

ABSTRACT: Immune thrombocytopenia (ITP) is believed to be associated with platelet function defects. However, their mechanisms are poorly understood, in particular with regard to differences between ITP phases, patient age, and therapy. We investigated platelet function and bleeding in children with either persistent or chronic ITP, with or without romiplostim therapy. The study included 151 children with ITP, of whom 56 had disease duration less than 12 months (grouped together as acute/persistent) and 95 were chronic. Samples of 57 healthy children were used as controls, while 5 patients with leukemia, 5 with aplastic anemia, 4 with MYH9-associated thrombocytopenia, and 7 with Wiskott-Aldrich syndrome were used as non-ITP thrombocytopenia controls. Whole blood flow cytometry revealed that platelets in both acute/persistent and chronic ITP were increased in size compared with healthy donors. They were also pre-activated as assessed by PAC1, CD62p, cytosolic calcium, and procoagulant platelet levels. This pattern was not observed in other childhood thrombocytopenias. Pre-activation by CD62p was higher in the bleeding group in the chronic ITP cohort only. Romiplostim treatment decreased size and pre-activation of the patient platelets, but not calcium. Our data suggest that increased size, pre-activation, and cytosolic calcium are common for all ITP platelets, but their association with bleeding could depend on the disease phase.

SUBMITTER: Ignatova AA

PROVIDER: S-EPMC8087794 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Platelet function and bleeding at different phases of childhood immune thrombocytopenia.

Ignatova Anastasia A AA Suntsova Elena V EV Pshonkin Alexey V AV Martyanov Alexey A AA Ponomarenko Evgeniya A EA Polokhov Dmitry M DM Fedorova Daria V DV Voronin Kirill A KA Kotskaya Natalia N NN Trubina Natalia M NM Krasilnikova Marina V MV Uzueva Selima Sh SS Serkova Irina V IV Ovsyannikova Galina S GS Romanova Ksenia I KI Hachatryan Lili A LA Kalinina Irina I II Matveev Viktor E VE Korsantiya Maya N MN Smetanina Natalia S NS Evseev Dmitry A DA Sadovskaya Maria N MN Antonova Kristina S KS Khoreva Anna L AL Zharkov Pavel A PA Shcherbina Anna A Sveshnikova Anastasia N AN Maschan Aleksey A AA Novichkova Galina A GA Panteleev Mikhail A MA

Scientific reports 20210430 1

Immune thrombocytopenia (ITP) is believed to be associated with platelet function defects. However, their mechanisms are poorly understood, in particular with regard to differences between ITP phases, patient age, and therapy. We investigated platelet function and bleeding in children with either persistent or chronic ITP, with or without romiplostim therapy. The study included 151 children with ITP, of whom 56 had disease duration less than 12 months (grouped together as acute/persistent) and 9 ...[more]

PMID: 33931737

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Project description:BackgroundThis is a review article on heparin-induced thrombocytopenia, an adverse effect of heparin therapy, and vaccine-induced immune thrombotic thrombocytopenia, occurring in some patients administered certain coronavirus vaccines.Main body/textImmune-mediated thrombocytopenia occurs when specific antibodies bind to platelet factor 4 /heparin complexes. Platelet factor 4 is a naturally occurring chemokine, and under certain conditions, may complex with negatively charged molecules and polyanions, including heparin. The antibody-platelet factor 4/heparin complex may lead to platelet activation, accompanied by other cascading reactions, resulting in cerebral sinus thrombosis, deep vein thrombosis, lower limb arterial thrombosis, myocardial infarction, pulmonary embolism, skin necrosis, and thrombotic stroke. If untreated, heparin-induced thrombocytopenia can be life threatening. In parallel, rare incidents of spontaneous vaccine-induced immune thrombotic thrombocytopenia can also occur in some patients administered certain coronavirus vaccines. The role of platelet factor 4 in vaccine-induced thrombosis with thrombocytopenia syndrome further reinforces the importance the platelet factor 4/polyanion immune complexes and the complications that this might pose to susceptible individuals. These findings demonstrate, how auxiliary factors can complicate heparin therapy and drug development. An increasing interest in biomanufacturing heparins from non-animal sources has driven a growing interest in understanding the biology of immune-mediated heparin-induced thrombocytopenia, and therefore, the development of safe and effective biosynthetic heparins.Short conclusionIn conclusion, these findings further reinforce the importance of the binding of platelet factor 4 with known and unknown polyanions, and the complications that these might pose to susceptible patients. In parallel, these findings also demonstrate how auxiliary factors can complicate the heparin drug development.

Dataset Information

Platelet function and bleeding at different phases of childhood immune thrombocytopenia.

Publications

Platelet function and bleeding at different phases of childhood immune thrombocytopenia.

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