Desialylation and Apoptosis in Immune Thrombocytopenia: Implications for Pathogenesis and Treatment

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The authors aim to summarize historical and recent evidence concerning the pathophysiology of immune thrombocytopenia with special emphasis on the role of desialylation and apoptosis in platelet destruction and discussing the possible influence of these facts on current clinical practice and therefore improving patient outcomes.
The topic is both original and relevant to this field by addressing and exploring alternative mechanisms in the pathogenesis of ITP beyond the traditional focus on antibody-mediated platelet destruction via the Fc-dependent pathway and therefore might help to understand why some patients do not respond to current or standard therapies for ITP. It is relevant to understand these mechanisms for developing possible targeted therapies especially for patients who are refractory to standard treatments. It is a further step to a possible personalized medicine which should be the goal nowadays and in the future. 
Although already similar paper were already published, this review integrated comprehensively historical discoveries with recent advances in the understanding of desialylation and apoptosis in ITP. It nicely identifies areas requiring further investigation, such as the need for further clinical trials with higher patient numbers to validate the therapeutic potential for targeting new mechanisms like in this case desialylation and apoptosis. 
I have nothing to add as this is a review, not a clinical trial.
The conclusions are consistent with the evidence and arguments presented. In my opinion the authors effectively manage to explain how desialylation and apoptosis contribute to the pathogenesis of ITP and how this might help for potential clinical implications. The literature and conclusions are discussed with summarizing key findings from both historical and recent studies. 
The references are generally appropriate and relevant. The references include a mix of basic science research, clinical studies, case reports, and reviews. The authors cite key historical studies and recent advancements, therefore providing a solid ground for their arguments. 
If the figures are created themselves by the authors I have nothing to add, otherwise references should be added. The tables and figures by itself are adequate. 

This review is nicely written with a thoroughly roundup of a very complex topic. Except for some minor grammatical corrections (e.g. line 290 "...to correlate" instead of "... to correlated") there a no necessary corrections or changes in my opinion.   

Author Response

Please see the attachment

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

The paper describes new insights in the pathogenesis of ITP. Pediatric and adult ITP should be clearly differentiated, in term of etiology, clinical presentation, prognosis and treatment.

Line 37/38 not only early but latest data point the role of autoimmunity in ITP.

Please mention drug-related secondary ITP

Very simple decription of thrombopoiesis should be omitted. Instead, classification (acute-persistent-chronic) should be stated. The regulation of hepatic TPO (platelet c-Mpl receptor-mediated uptake and destruction of TPO) should be replaced (instead of thrombocytosis/thrompocytopenic state). 

While Fc-independent pathway is described (although animal and human studies are not clearly separated), other pathways are not.

Treatment should be classified as first-line, second-line, etc.

Two many references (suggestion < 50). Omit some simple figures.

 

Author Response

Please see the attachment

Author Response File: Author Response.pdf