PONE-D-20-07037

Clinical course and short-term outcome of postsplenectomy reactive thrombocytosis in children without myeloproliferative disorders: A single institutional experience from a developing country

PLOS ONE

Dear Dr. Vranic,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

The article is an interesting issue. However, it cannot be accepted at its current content because it cannot fulfill the following acceptance criteria " Conclusions are presented in an appropriate fashion and are supported by the data." and "The article is presented in an intelligible fashion and is written in standard English. " 

Our reviewers raised several important comments. We look for the author could specifically reply it and make corresponding revision appropriately in response to the comments. 

Please submit your revised manuscript by Jul 23 2020 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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We look forward to receiving your revised manuscript.

Kind regards,

Chun Chieh Yeh, M.D., Ph.D.

Academic Editor

PLOS ONE

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Additional Editor Comments (if provided):

The article is an interesting issue. However, it cannot be accepted at its current content because it cannot fulfill the following acceptance criteria " Conclusions are presented in an appropriate fashion and are supported by the data." and "5. The article is presented in an intelligible fashion and is written in standard English. "

Our reviewer raised several important comments. We look for the author could specifically reply it and make corresponding revision appropriately in response to the comments.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: No

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This is a retrospective single institution review of 52 pediatric open splenectomies, divided into non-hematologic (n=34) and hematologic non-neoplastic (n=18) indications. Ninety four percent of the sample developed post-splenectomy thrombocytosis but no thrombotic complications were reported.

The article is generally well written. However, important data are missing and the conclusion that post-splenectomy reactive thrombocytopenia “…is not associated with thrombotic or hemorrhagic complications in children without underlying haematological malignancies” is inadequately supported by the data (see below).

1. Severe spleen trauma was commonest indication for splenectomy (56%) – this is surprising as >90% of blunt pediatric splenic trauma can be successfully managed conservatively. Perhaps this was penetrating trauma?

2. What was the protocol for recording postoperative platelet counts? Table 2 values are not meaningful unless they refer to peak postoperative platelet counts and the accuracy of the data depends on the frequency of blood sampling. Presumably, the figures in this table are means?

3. There are no data on spleen size, which is a factor in postoperative thrombotic complications.

4. Did any of the patients receive any postoperative anticoagulant or antiplatelet therapy? The discussion suggests that 20% of the extreme thrombocytosis group did receive treatment.

5. The authors only report clinically evident thrombotic complications. No routine postoperative ultrasound scans were performed to check for occult splenic and portal vein thrombosis (see Stringer MD, Lucas N. Thrombocytosis and portal vein thrombosis after splenectomy for paediatric haemolytic disorders: How should they be managed? J Paediatr Child Health. 2018;54(11):1184-1188).

6. Figure 1 axis labelling is incomplete

Reviewer #2: Title:

Clinical course and short-term outcome of postsplenectomy reactive thrombocytosis in children without myeloproliferative disorders: A single institutional experience from a developing country

Outlines:

The authors conduct a retrospective review of 52 children aged younger than 16 years with postsplenectomy reactive thrombocytosis. They found postsplenectomy reactive thrombocytosis is not associated thrombotic or hemorrhagic complications in children without underlying hematological malignancies.

The following are some comments and questions for the authors:

1. Page 8, line 170. The authors mentioned the platelet count decreased in patients in the non-neoplastic hematology group. But in Table 3, it was reversed. The platelet count increased in patients in the non-neoplastic hematology group after postsplenectomy day 1. Please clarify for the readers.

2. Page 8, line 172-173. The authors mentioned that RT has reported in the non-neoplastic hematology group from 5th to 10th day. But in Table 3, thrombocytosis (>500,000/uL) was observed from postsplenectomy day 3 to 9. Please clarify for the readers.

3. Page 9, line 175-176. The authors mentioned that maximal platelet count was recorded on the 14th day. But in Table 3, the highest platelet count in the non-hematology group is on postsplenectomy day 11. Please clarify for the readers.

4. I can’t understand Figure 1. What does X-axis indicate? What does Y-axis indicate? How to interpret the relationship between INR and platelet count based on the present figure (only 2 points and 1 line)?

5. Page 11, line 226. Please cite references about postsplenectomy thromboembolic complications in children.

6. There are several language flaws in the article needs to be polished further.

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If you choose “no”, your identity will remain anonymous but your review may still be made public.

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Reviewer #1: No

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PONE-D-20-07037R1

Clinical course and short-term outcome of postsplenectomy reactive thrombocytosis in children without myeloproliferative disorders: A single institutional experience from a developing country

PLOS ONE

Dear Dr. Vranic,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

==============================

I wish you could make appropriate response to the reviewer-1 comments. Decision will be made after your revision.

==============================

Please submit your revised manuscript by Aug 23 2020 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Chun Chieh Yeh, M.D., Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (if provided):

Thanks to your appropriate response and revision to the reviewers' comments. The reviewer-1 still raised a suggestion for minor revision. I wish you could consider and make appropriate response to this suggestion. Decision will be made based on your response. Thanks.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: No

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors have responded appropriately to my comments BUT their conclusions are based on just 52 patients and are invalid. They did NOT routinely use postoperative ultrasound assessment of the portal and splenic vein nor did they record data on spleen size.

Nevertheless, I think the article would be valid if the conclusions are changed in both the Abstract and Discussion.

The following is suggested:

“We confirm that RT is a very common event following splenectomy, but IN THIS STUDY IT WAS not associated with CLINICALLY EVIDENT thrombotic or hemorrhagic complications in children undergoing splenectomy for trauma, structural lesions or non-neoplastic hematological disorders.”

Reviewer #2: Thanks the authors for the revision. The manuscript looks better and more clear to me. I have no other comments.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Clinical course and short-term outcome of postsplenectomy reactive thrombocytosis in children without myeloproliferative disorders: A single institutional experience from a developing country

PONE-D-20-07037R2

Dear Dr. Vranic,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Chun Chieh Yeh, M.D., Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Thanks for your appropriate response specific to reviewers' comments. I think the work is worthy of acceptance. Congratulation.

Reviewers' comments: