Aggressive Vaccine-Induced Immune Thrombocytopenia and Thrombosis in a Young Woman with a Past Mild SARS-CoV-2 Infection

Round 1

Reviewer 1 Report

Thank you for asking me to review this interesting paper. I have a few questions as detailed below:

1. Did the patient have any family history of thrombotic events?

2. What was the patient's fibrinogen level?

3. Was plasma exchange considered as part of the management?

4. Whilst I accept they are unlikely, were other commoner causes of new onset arterial thrombosis in a young person ruled out including cardiac structural anomalies, antiphospholipid syndrome and PNH?

If these issues can be addressed I think publication of the potential link with the vaccine would be worthwhile. 

Author Response

We would like to thank the reviewer for careful and thorough reading of this manuscript and for the thoughtful comments and constructive suggestions, which help to improve the quality of this manuscript. Our response follows (the reviewer’s comments are in italics).

1. Did the patient have any family history of thrombotic events?

We thank the reviewer for this observation. The family history of the patient was negative for the occurrence of thrombotic events. This information has been addressed in the revised version of the manuscript.

2. What was the patient's fibrinogen level?

We thank the reviewer for pointing this out and have updated the table 1. As reported the patient's fibrinogen level was in the normal range.

3. Was plasma exchange considered as part of the management?

We appreciate the reviewer’s insightful suggestion and agree that it would be useful in the management of VITT. We didn’t consider this approach since it potential use in severe VITT requires further validation.

4. Whilst I accept, they are unlikely, were other commoner causes of new onset arterial thrombosis in a young person ruled out including cardiac structural anomalies, antiphospholipid syndrome and PNH?

We thank the reviewer for these observations. Anamnestic and laboratory results allowed us to rule out cardiac structural anomalies, PNH and antiphospholipid syndrome. These findings have been addressed in the revised manuscript (highlighted in red) while antibody titer to cardiolipin and to β2-Glycoprotein-I is reported in table 1.

We would thank the reviewer again for his time and consideration in reviewing the manuscript.

Reviewer 2 Report

Dear authors, I appreciate your scientific work and effort

below I write down some notes

Author Response

Reviewer #2

We would like to thank the reviewer for taking the time to assess our manuscript and for the thoughtful comments and constructive suggestions, which help to improve the quality of this manuscript. Our response follows (the reviewer’s comments are in italics).

No 29. It is better to avoid use name of drugs companies.

We thank the reviewer for pointing this out and have removed the name of drug company.

Lines: 30 To use term (the patient); 88:  ??? (to use term, the patient); 164 and 165: Needs to be more clear abbreviation; 186 ???; 193 150x10⁹ /L; 197 To explain abbreviation.

We thank the reviewer for these observations, and we have made the change (highlighted in red)

Line 35. The conclusion needs to be more informative.

We are grateful to the reviewer for this comment, and we modified the conclusion in the revised version of the manuscript (highlighted in red)

Line 73 What is criteria of severe cerebral venous thrombosis?

Severe CVT is characterized by cerebral venous infarction or hemorrhage, seizures, or disturbance of consciousness, it has more severe clinical manifestations and a worse prognosis. The pathogenetic core of severe CVT is the fast activation of inflammatory response.

Line 183 What is outcome of the patients?

The patient died because of respiratory arrest 48 hours after decompressive neurosurgery (line 183)

Lines 237-243 Repetition to what was mentioned in the results.

We agree and we have revised the paragraph (highlighted in red)

We would thank again the reviewer for his time and consideration in reviewing the manuscript.

Reviewer 3 Report

Thank you for the opportunity to review the article ''Aggressive Vaccine- Induced Immune Thrombocytopenia and Thrombosis-VITT- in a Young Woman with a Past Mild SARS-CoV-2 Infection''. The article is comprehensive and well written, the topic is still very relevant and has significant scientific significance.

However, the authors need to make a few corrections, and provide additional explanations.

On pg. 2, line 51 there is a typo, please correct - ''paroxysmal
nocturnal hemoglobinuria, myeloproliferative disorders''

Also, I would like to ask the authors to explain the possible reasons for normocytic anemia in this patient. I would suggest to include all laboratory parameters significant to the case in the table (i.e. is glycemia necessary?), and also provide additional parameters to explain anemia (i.e. LDH, haptoglobin, bilirubin, etc.)

Overall I find this article worth publishing, after these minor changes have been made.  

Author Response

Reviewer #3

We would like to thank the reviewer for the positive and insightful comments on the manuscript.

Below is our response to the issues raised in the review (in italics reviewer’s comments)

On pg. 2, line 51 there is a typo, please correct - ''paroxysmal nocturnal hemoglobinuria, myeloproliferative disorders.''

The correction has been made.

Also, I would like to ask the authors to explain the possible reasons for normocytic anemia in this patient. I would suggest to include all laboratory parameters significant to the case in the table (i.e. is glycemia necessary?), and also provide additional parameters to explain anemia (i.e. LDH, haptoglobin, bilirubin, etc.)

We appreciate the reviewer’s comment. A possible reason for normocytic normochromic anemia in this patient could be the development of hypothyroidism (i.e. Hashimoto thyroiditis) as suggested by the increase of both anti-thyroglobulin and thyroid peroxidase antibodies titer with concomitant level of TSH-receptor antibodies in the normal range. A further possible reason for the occurrence of normocytic normochromic anemia in this patient could be conditions such as hypermenorrhea in a cycle of normal duration or menorrhagia. We ruled out a process of hemolysis since both bilirubin and haptoglobin levels were in the normal range. We included these observations in the revised manuscript (highlighted in red). As suggested by the reviewer all laboratory parameters significant to the case were added to the table 1 (i.e. anti-thyroglobulin and thyroid peroxidase antibodies titer; TSH-receptor antibodies titer; bilirubin and haptoglobin values, Fibrinogen; antibody titer to both cardiolipin and to β2-Glycoprotein-I)

We would thank again the reviewer for his time and consideration in reviewing the manuscript.

Round 2

Reviewer 2 Report

thanks for your effort 

Reviewer 3 Report

The requested minor changes in the manuscript have been made. I find this article worth publishing.