Hemostatic changes by thrombopoietin-receptor agonists in immune thrombocytopenia patients
Blood reviews. 2020;:100774
Thrombopoietin receptor agonist (TPO-RA) treatment increases the thrombosis rate in immune thrombocytopenia (ITP). We hypothesize that TPO-RAs influence platelet function, global and secondary hemostasis and/or fibrinolysis. A systematic review was performed. If possible, data were compared between responders (relevant increase in platelet count), and non-responders. Twelve observational studies with 305 patients were included (responders (127/150 (85%))). There were indications that TPO-RA treatment enhanced platelet function, with respect to platelet-monocyte aggregates, soluble P-selectin, GPVI expression, and adhesion under flow. Studies addressing global and secondary hemostasis and fibrinolysis were scarce. Overall, no changes were found during TPO-RA treatment, apart from an accelerated clot formation and conflicting data on levels of plasminogen activator inhibitor (PAI)-1. The parameters that increased have previously been associated with thrombosis in other patient groups, and might contribute to the increased rate of thrombosis observed in TPO-RA-treated ITP patients.
Anti-Platelet Antibodies in Childhood Immune Thrombocytopenia: Prevalence and Prognostic Implications
Journal of thrombosis and haemostasis : JTH. 2020
BACKGROUND Anti-platelet antibody testing may be useful for the diagnosis and management of childhood immune thrombocytopenia (ITP). OBJECTIVES Here we aimed to assess the prevalence and prognostic significance of anti-platelet glycoprotein-specific IgM and IgG antibodies. METHODS Children with newly diagnosed ITP were included at diagnosis and randomized to an intravenous immunoglobulins (IVIg) or careful observation group (TIKI trial). In this well-defined and longitudinally followed cohort (N = 179), anti-platelet glycoprotein-specific IgM and IgG antibodies were determined by MAIPA. RESULTS The dominant circulating anti-platelet antibody class in childhood ITP was IgM (62% of patients); but IgG antibodies were also found (10%). Children without IgM platelet antibodies were older and more often female. There was weak evidence for an association between IgM anti-GP IIb/IIIa antibodies and an increased bleeding severity (P=0.03). The IgM and IgG anti-platelet responses partially overlapped, and reactivity was frequently directed against multiple glycoproteins. During one year follow-up, children with IgM antibodies in the observation group displayed a faster platelet recovery compared to children without IgM, also after adjustment for age and preceding infections (P=7.1x10(-5) ). The small group of patients with detectable IgG anti-platelet antibodies exhibited an almost complete response to IVIg treatment (N=12; P=0.02), suggesting that IVIg was particularly efficacious in these children. CONCLUSIONS Testing for circulating anti-platelet antibodies may be helpful for the clinical prognostication and the guidance of treatment decisions in newly diagnosed childhood ITP. Our data suggest that the development of even more sensitive tests may further improve the clinical value of antibody testing.
Intravenous immunoglobulin versus observation in childhood immune thrombocytopenia: a randomized controlled trial
Management of children with newly diagnosed immune thrombocytopenia (ITP) consists of careful observation or immunomodulatory treatment. Observational studies suggest a lower risk of chronic ITP in children after intravenous immunoglobulin (IVIg) treatment. In this multicenter randomized trial, children aged 3 months-16 years with newly diagnosed ITP, platelet counts ≤20 x 10(9)/L and mild to moderate bleeding were randomly assigned to receive either a single infusion of 0.8 g/kg IVIg or careful observation. Primary outcome was development of chronic ITP, at time of study initiation defined as a platelet count < 150 x 10(9)/L after 6 months. Two hundred and six children were allocated to receive IVIg (n=102) or careful observation (n=104). Chronic ITP occurred in 18.6% in the IVIg group and in 28.9% in the observation group (relative risk [RR] 0.64; 95% confidence interval [CI] 0.38-1.08). Platelet counts < 100 x 10(9)/L at 12 months (current definition of chronic ITP) were observed in 10% children in the IVIg group and in 12% in the observation group (RR 0.83; 95% CI 0.38-1.84). Complete response rates in the first three months were significantly higher in the IVIg group. IgG- Fc receptor IIb genetic variations were associated with early complete response in both groups. Grade 4-5 bleeding occurred in 9% in the observation group versus 1% in the IVIg group. IVIg treatment at diagnosis in children with ITP did not result in a lower rate of chronic ITP. In the IVIg group higher early complete response rates and less bleeding events were observed. This trial was registered at www.trialregister.nl as NTR 1563.