Portal Vein Thrombosis after C-Section in a Patient with Polycythemia Vera (PV) Due to Pregnancy and Iron Deficiency Anemia (IDA)

Round 1

Reviewer 1 Report

The case is interesting because it draws attention to a particular and very specific issue, namely that of splanchnic venous thrombosis in patients with MPN. In this case, the diagnostic suspicion was correct and the JAK2 mutation was correctly looked for. Often, splanchnic thrombosis affects young women with unaltered blood counts.

However, I believe there are methodological mistakes in the diagnosis of PV.

I find the diagnosis of PV to be inaccurate. The term "masked PV" has not been used since 2016, after the new diagnostic criteria of MPNs were created. In addition, the diagnosis should be made by bone marrow biopsy with histological evaluation to assess the grade of fibrosis. The one in the figure is the bone marrow blood smear, which is not useful to make the diagnosis of Polycythemia Vera. Again, the serum erythropoietin level was not reported in the text. Being sideropenic, the patient showed normal hemoglobin levels, but the diagnosis of PV in this case must be corroborated by low erythropoietin levels in addition to the pathologist's assessment. Even wanting to use the diagnostic criteria applicable at the time when the patient was 40 years old, Hb levels must be at least 16.5 g/dl and histological confirmation is mandated.

In the text it is told of the evolution into Myelofibrosis. It is not clear from the patient's characteristics that there was evolution into Myelofibrosis, as splenomegaly and splanchnic thrombosis are not sufficient criteria to make a diagnosis of Myelofibrosis post PV. Grade 3 fibrosis should also be accompanied by other minor criteria that should be added. Regarding the indication for transplantation, more data are needed to justify the indication (IPSS risk, DIPSS).

In line 179, the use of interferon and/or LMWH is recommended. The patient has a high thrombotic risk, which is defined by the presence of a thrombotic history, so cytoreductive therapy is always suggested, which, as well advised, interferon is the only therapy that can be administered in potentially fertile women. Antithrombotic therapy is not an alternative to cytoreductive therapy, but should always be accompanied by it. In the woman who has no gynecological contraindications, low doses of aspirin can be prescribed, which should be replaced with LMWH to reduce the risk of fetal harm, as recommended in line 180. This point needs to be made more explicit.

Ultimately, I believe this study brings no innovation, as it is the common presentation of a patient with MPN and splanchnic thrombosis. The presence of information found before the delivery that may be associated with future thrombosis could be useful to give an interesting point of view to the paper (e.g., ultrasound study of splanchnic vessels during morphologic ultrasound).

Author Response

Dear Reviewer, 

Thank you very much for your kind remarks.

We corrected the used term “masked PV”. We added the histological images of the bone marrow biopsy along the bone marrow blood smear images. We also present the serum erythropoietin level which was not previously reported.

Due to insufficient data to support the diagnosis of Myelofibrosis, we excluded the diagnosis, as well as the indication for transplantation.

In line 179, we highlighted that antithrombotic therapy should be accompanied by cytoreductive therapy.

Unfortunately, we were unable to retrieve information found before the delivery that might be associated with future thrombosis, in order to give an interesting point of view to the paper (e.g., ultrasound study of splanchnic vessels during morphologic ultrasound).

Thank you very much in advance, 

Yours sincerely,

Antonios Koutras

Reviewer 2 Report

Undoubtedly, the case presented is illustrative of a rare disease with a retrospective diagnosis of chronic myeloproliferative neoplasm after extensive splenoportal thrombosis developed in the puerperium.

The case is interesting but the description is rather disorganized. An introduction reflecting the characteristics of Philadelphia-negative chronic myeloproliferative neoplasms is needed. The genetic marker of the disease and the scarce references regarding pregnancy and its complications in these entities.

Although the case is positive for the JAK2V617F variant, at no time of the evolution does it meet the major criterion of hematocrit higher than 48%, so it should meet a minor criteria one, The values of erythropoietin in serum are not detailed or at least justify if this determination has not been performed. The enlarged spleen in this case could be overlapped by extensive portal thrombosis with parenchymal infarcts.

In general, the description of the case should be better organized. The tables should be merged into a single table in which the rows contain the variables determined and the columns contain the different time periods.

The histological image is not very representative, it should be at a lower magnification to appreciate the hypercellularity and add another image with the reticulin fibers.

The discussion has reflected more a treatise about the general diagnosis of PV, recommendations during pregnancy, which in this case had no place since there is no previous diagnosis. There is a lack of discussion of the particularities of the case with what has been published about this myeloproliferative neoplasm, the thrompetic complications in special situations. You need to improve the discussion.

A case with similarities to this one has recently published and should be reviewed and referred it by the authors.

Bohiltea RE, Niculescu-Mizil E, Mihai BM, Furtunescu F, Ducu I, Munteanu O, Georgescu TA, Grigoriu C. Polycythemia vera in pregnancy represents a challenge for a multidisciplinary collaboration: A case report and literature review. Exp Ther Med. 2022 Jan;23(1):19. doi: 10.3892/etm.2021.10941

*It does not appear in the text if informed consent was requested from the patient to publish the case; this should be reflected.

Author Response

Dear Reviewer,

Thank you very much for your kind remarks,

We added an introduction reflecting the characteristics of Philadelphia-negative chronic myeloproliferative neoplasms is needed, highlighting the genetic marker of the disease and the scarce references regarding pregnancy and its complications in these entities.

We added the serum erythropoietin level which was not previously reported, so as two major and one minor criteria are met to support the diagnosis.

We added the histological images of the bone marrow biopsy at a lower magnification to appreciate the hypercellularity and the reticulin fibers.

We updated the discussion and referred to the suggested case recently published.

We added that informed consent was requested from the patient to publish the case.

Thank you very much in advance, 

Yours sincerely, 

Antonios Koutras

Round 2

Reviewer 1 Report

Thank you for following my suggestions.

Unfortunately, this is not such an uncommon case to arouse the interest of hematology colleagues. Diagnosis of PV in young women manifesting SVT at onset is far from rare, however, with proper correction and correct diagnosis, it remains an interesting case report.

 

I would make one last correction to line 153: instead of writing "Due to iron deficiency, normal Hct, low MCH and MCHC and very increased LDH, 153 the patient was suspected of suffering from PV and thus tested for JAK2V617F mutation", I would write that despite normal Hb and HCT levels, due to iron deficiency, elevated LDH and history of portal thrombosis made us suspect MPN, for which JAK2 testing was performed.

 

Having made this correction, it is possible to publish the work.

Thank you very much.

Author Response

Dear reviewer,

Thank you very much for your kind remarks.

We included the correction that you suggested  (line 122 in the newest version) 

Thank you in advance,

Antonios Koutras