Platelet function and bleeding at different phases of childhood immune thrombocytopenia

Ignatova, Anastasia A.; Suntsova, E.V.; Pshonkin, A. V.; Martyanov, A. A.; Пономаренко, Е А; Polokhov, Dmitry M.; Федорова, Д. В.; Voronin, Kirill; Kotskaya, N. N.; Trubina, Natalia M.; Красильникова, Марина; Uzueva, Selima S; Serkova, Irina V.; Ovsyannikova, Galina; Romanova, Ksenia I.; Hachatryan, Lili A.; Калинина, И. И.; Matveev, V.E.; Korsantiya, Maya N.; Smetanina, N.S.; Евсеев, Д. А.; Sadovskaya, M. N.; Антонова, К. С.; Хорева, А. Л.; Zharkov, P. A.; Shcherbina, Anna; Sveshnikova, Anastasia; Maschan, Aleksey; Novichkova, Galina; Panteleev, Mikhail A.

doi:10.1038/s41598-021-88900-6

Cited by 9 publications

(10 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a recent study analysing platelet function in 151 children with ITP, 22 were treated with romiplostim. TPO‐RA treatment was associated with decreased platelet size and reduced preactivation 52 . Integrin (PAC1) activation in the resting state was increased in the untreated group, whereas there was no difference between romiplostim‐treated patients and healthy controls.…”

Section: Discussionmentioning

confidence: 92%

See 1 more Smart Citation

Immunomodulation with romiplostim as a second‐line strategy in primary immune thrombocytopenia: The iROM study

Schifferli,

Rüfer,

Rovo

et al. 2023

Br J Haematol

View full text Add to dashboard Cite

SummaryThrombopoietin receptor agonists (TPO‐RAs) stimulate platelet production, which might restore immunological tolerance in primary immune thrombocytopenia (ITP). The iROM study investigated romiplostim's immunomodulatory effects. Thirteen patients (median age, 31 years) who previously received first‐line treatment received romiplostim for 22 weeks, followed by monitoring until week 52. In addition to immunological data, secondary end‐points included the sustained remission off‐treatment (SROT) rate at 1 year, romiplostim dose, platelet count and bleedings. Scheduled discontinuation of romiplostim and SROT were achieved in six patients with newly diagnosed ITP, whereas the remaining seven patients relapsed. Romiplostim dose titration was lower and platelet count response was stronger in patients with SROT than in relapsed patients. In all patients, regulatory T lymphocyte (Treg) counts increased until study completion and the counts were higher in patients with SROT. Interleukin (IL)‐4, IL‐9 and IL‐17F levels decreased significantly in all patients. FOXP3 (Treg), GATA3 (Th2) mRNA expression and transforming growth factor‐β levels increased in patients with SROT. Treatment with romiplostim modulates the immune system and possibly influences ITP prognosis. A rapid increase in platelet counts is likely important for inducing immune tolerance. Better outcomes might be achieved at an early stage of autoimmunity, but clinical studies are needed for confirmation.

show abstract

Section: Discussionmentioning

confidence: 92%

“…Pro‐coagulant platelets and P‐selectin (CD62p) were increased in all ITP patients regardless of therapy. However, in response to stimulation, romiplostim‐treated patients exhibited decreased activation profiles for PAC1 and CD62p 52 …”

Section: Discussionmentioning

confidence: 98%

Immunomodulation with romiplostim as a second‐line strategy in primary immune thrombocytopenia: The iROM study

Schifferli,

Rüfer,

Rovo

et al. 2023

Br J Haematol

View full text Add to dashboard Cite

show abstract

“…Preactivation of platelets is shown for ITP [135,136]. ITP is a common acquired autoimmune disorder characterized by disrupted platelet clearance and/or thrombopoiesis [137].…”

Section: Disruption Of Platelet Life Cyclementioning

confidence: 99%

Platelet lifespan and mechanisms for clearance

An,

Deppermann

2023

Current Opinion in Hematology

View full text Add to dashboard Cite

Purpose of review Activated or aged platelets are removed from circulation under (patho)physiologic conditions, the exact mechanism of platelet clearance under such conditions remains unclear and are currently being investigated. This review focuses on recent findings and controversies regarding platelet clearance and the disruption of platelet life cycle. Recent findings The platelet life span is determined by glycosylation of platelet surface receptors with sialic acid. Recently, it was shown that platelet activation and granule release leads to desialylation of glycans and accelerated clearance of platelets under pathological conditions. This phenomenon was demonstrated to be a main reason for thrombocytopenia being a complication in several infections and immune disorders. Summary Although we have recently gained some insight into how aged platelets are cleared from circulation, we are still not seeing the full picture. Further investigations of the platelet clearance pathways under pathophysiologic conditions are needed as well as studies to unravel the connection between platelet clearance and platelet production.

show abstract

“…One of them, romiplostim, has recently been shown to cause complete or partial platelet response in 61% of WAS patients 22 . Romiplostim has been reported to affect the functional status of platelets in immune thrombocytopenia, 23,24 but not in WAS 25 . The effect of romiplostim treatment on WAS MKs is still unknown.…”

Section: Introductionmentioning

confidence: 99%

Accelerated death of megakaryocytes from Wiskott–Aldrich syndrome patients

et al. 2023

Self Cite

View full text Add to dashboard Cite

Summary Wiskott–Aldrich syndrome (WAS) is an X‐linked recessive disorder caused by WAS gene mutations resulting in haematopoietic/immune cell defects. Recent studies report accelerated death of WAS platelets and lymphocytes. Data on megakaryocyte (MK) maturation, viability and their possible role in thrombocytopenia development in WAS are limited. In this study we evaluate the MK viability and morphology in untreated, romiplostim‐treated WAS patients compared with normal controls. The study included 32 WAS patients and 17 healthy donors. MKs were captured from bone marrow aspirates by surface‐immobilized anti‐GPIIb‐IIIa antibody. Viability (by phosphatidylserine [PS] externalization), distribution by maturation stages and size of MK were determined by light microscopy. MK distribution by maturation stages in patients differed from controls. 40 ± 22% of WAS MKs versus 23 ± 11% of normal MKs were at maturation stage 3 (p = 0.02), whereas 24 ± 20% in WAS and 39 ± 14% in controls had megakaryoblast morphology (p = 0.05). Romiplostim treatment changed the MK maturation stages distribution close to normal. PS‐positive (PS+) MK in WAS was significantly higher (21 ± 21%) than in healthy controls (2 ± 4%, p < 0.01). WAS patients with more damaging truncating mutations and higher disease score had higher PS+ MK fraction (Spearman r = 0.6, p < 0.003). We conclude that WAS MKs have increased cell death tendency and changes in maturation pattern. Both could contribute to thrombocytopenia in WAS patients.

show abstract

Platelet function and bleeding at different phases of childhood immune thrombocytopenia

Cited by 9 publications

References 39 publications

Immunomodulation with romiplostim as a second‐line strategy in primary immune thrombocytopenia: The iROM study

Immunomodulation with romiplostim as a second‐line strategy in primary immune thrombocytopenia: The iROM study

Platelet lifespan and mechanisms for clearance

Accelerated death of megakaryocytes from Wiskott–Aldrich syndrome patients

Contact Info

Product

Resources

About