Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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Dr Mohan Z Mani

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Believers Church Medical College,
Thiruvalla, Kerala
On Sep 2018




Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."



Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



Dr Kalyani R
Professor and Head
Department of Pathology
Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
On Sep 2018




Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
‘Knowledge is treasure of a wise man.’ The free access of this journal provides an immense scope of learning for the both the old and the young in field of medicine and dentistry as well. The multidisciplinary nature of the journal makes it a better platform to absorb all that is being researched and developed. The publication process is systematic and professional. Online submission, publication and peer reviewing makes it a user-friendly journal.
As an experienced dentist and an academician, I proudly recommend this journal to the dental fraternity as a good quality open access platform for rapid communication of their cutting-edge research progress and discovery.
I wish JCDR a great success and I hope that journal will soar higher with the passing time."



Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




Dr. Arunava Biswas

"My sincere attachment with JCDR as an author as well as reviewer is a learning experience . Their systematic approach in publication of article in various categories is really praiseworthy.
Their prompt and timely response to review's query and the manner in which they have set the reviewing process helps in extracting the best possible scientific writings for publication.
It's a honour and pride to be a part of the JCDR team. My very best wishes to JCDR and hope it will sparkle up above the sky as a high indexed journal in near future."



Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata




Dr. C.S. Ramesh Babu
" Journal of Clinical and Diagnostic Research (JCDR) is a multi-specialty medical and dental journal publishing high quality research articles in almost all branches of medicine. The quality of printing of figures and tables is excellent and comparable to any International journal. An added advantage is nominal publication charges and monthly issue of the journal and more chances of an article being accepted for publication. Moreover being a multi-specialty journal an article concerning a particular specialty has a wider reach of readers of other related specialties also. As an author and reviewer for several years I find this Journal most suitable and highly recommend this Journal."
Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011
Anuradha

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.


Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Case Series
Year : 2022 | Month : February | Volume : 16 | Issue : 2 | Page : ER04 - ER08 Full Version

Clinicopathological Parameters of Haemolytic Anaemia in COVID-19 Infection: A Series of Three Cases


Published: February 1, 2022 | DOI: https://doi.org/10.7860/JCDR/2022/51186.15960
Rabish Kumar, Sarika Singh, Mradul Kumar Daga, Urmila Jhamb

1. Senior Resident, Department of Pathology, Maulana Azad Medical College, Delhi, India. 2. Professor, Department of Pathology, Maulana Azad Medical College, Delhi, India. 3. Director Professor, Department of Medicine, Maulana Azad Medical College, Delhi, India. 4. Director Professor, Department of Paediatrics, Maulana Azad Medical College, Delhi, India.

Correspondence Address :
Dr. Sarika Singh,
97B, Block C, Express View Apartments, Sector 105, Noida, Uttar Pradesh, India.
E-mail: sarikasingh97b@gmail.com

Abstract

Coronavirus Disease 2019 (COVID-19) patients show various haematological abnormalities like cytopenia and coagulation disorders. Coronavirus can induce an inflammatory state, leading to extensive coagulation manifestations. Association between COVID-19, Autoimmune Haemolytic Anaemia (AIHA) and thrombotic state is still the subject of extensive research. In this study, three cases of haemolytic anaemia are discussed. First case was a 28-year-old female with a history of abruptio placentae who presented with complaints of generalised weakness and oliguria for five days. She was diagnosed as thrombotic microangiopathy based on peripheral smear finding of schistocytes and spherocytes and few polychromatophils and normal prothrombin time (International Normalised Ratio (INR)) with very high D-dimer levels on coagulation profile. Second case was of a 25-year-old female who presented with complaints of fatigue, rashes, dark urine, nausea and abdominal pain. She was diagnosed as a case of AIHA based on peripheral smear finding of Red Blood Cells (RBC) clumping and positive direct coomb test. Third case was of a two-month-old child who presented with respiratory distress and pallor. He was diagnosed as a case of haemolytic anaemia either due to direct effect of COVID-19 infection or Cytomegalovirus (CMV) and mycoplasma infection. Thus, COVID-19 infection can directly or indirectly lead to a wide spectrum of haemolytic manifestations and every patient with anaemia should be thoroughly investigated for early detection and treatment.

Keywords

Coronavirus disease, Haematological manifestations, Inflammation

COVID-19 is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Patients present with fever, cough, myalgias and fatigue (1). Anosmia and ageusia have also been found to be common symptoms. As COVID-19 emerged, many patients also presented with coagulation disorders (2). It is presumed that COVID-19 infection directly and indirectly leads to haemolysis and cytopenia. The high levels of inflammation throughout the body in COVID-19 patients can cause excessive activation of the coagulation cascade leading to extensive coagulation manifestations.

Association between COVID-19, AIHA and thrombotic state is still less understood as available data is incomplete and still emerging. AIHA is an acquired haemolysis in which the host’s immune system attacks its own red cell antigens. Serologically, cases are divided into warm, cold or mixed types (3). Patients may present with symptoms of anaemia such as dizziness, tiredness and dyspnoea, or evidence of haemolysis with jaundice and dark urine. On a blood film, RBC agglutination and spherocytosis may be apparent. The reticulocyte count is usually increased but may be normal in cases of a very short duration of haemolysis or with an underlying bone marrow disorder (4).

There are several causes of AIHA. These include autoimmune, infections (bacterial, viral or parasitic), lymphoproliferative disorders and immunodeficiency states. Out of all viral infections, herpes virus especially Herpes Simplex Virus (HSV) is most notorious (5). Previous, latent or manifested infection in the setting of COVID-19 builds on a milieu for complement and coagulation cascades to get activated unabated. The underlying mechanism of Multiple Organ Dysfunction (MOD) in COVID-19 leading to an outburst of deaths, still ill understood. Various hypothesises proposed under study are direct effect of the virus, cytokine storm, uncontrolled endothelial damage, and autoantibodies against the coronavirus which starts attacking various cells like RBCs and platelets leading to haemolysis, thrombocytopenia and subsequently MOD (6).

Present case series includes three known cases of COVID-19 who presented with haemolytic blood picture due to thrombotic microangiopathy, AIHA and COVID-19 viropathy, respectively.

Case Report

Case 1

A 28-year-old female presented to emergency of Medicine Department with complaints of generalised weakness and reduced urine output for five days. She was admitted to medicine ward and her Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) test for COVID-19 came out to be positive. She had fever with mild cough one week back and a history of preterm vaginal delivery with abruptio placentae 10 days prior to admission. There were no co-morbidities, and her family history was insignificant. On examination there was pallor, but no hepatosplenomegaly or lymphadenopathy. Her Kidney Function Test (KFT) and Liver Function Test (LFT) was deranged, with alanine aminotransferase level of 145 IU/L, alkaline phosphatase level of 359 IU/L, serum urea of 194 mg/dL and serum creatinine of 10.6 mg/dL (Normal serum bilirubin, aspartate aminotransferase). Her inflammatory markers were elevated (HsCRP level of >150 mg/L). Her Complete Blood Count (CBC) showed low haemoglobin (Hb) of 8.3 gm/dL and platelet count of 78,000/mm3 (Table/Fig 1), (Table/Fig 2).

Patient was started on dialysis and 3 units of Packed Cell Volume (PCV) were transfused. On examination of peripheral smear stained with May Grunwald-Giemsa (MGG), there was bicytopenia with reduced red cell mass. RBCs were normocytic normochromic with many schistocytes and spherocytes and few polychromatophils. There was neutrophilic leucocytosis with left shift. Picture was suggestive of thrombotic microangiopathy (Table/Fig 1), (Table/Fig 3). Possibilities suggested were Disseminated Intravascular Coagulation (DIC) and atypical Haemolytic Uremic Syndrome (aHUS) and Thrombotic Thrombocytopenic Purpura (TTP), on further analysis coagulation profile showed normal prothrombin time (12 second) and INR (0.8) but very high D-dimer levels (75000 ng/mL), ruling out DIC (Table/Fig 2). Final diagnosis given was aHUS/TTP. But low PLASMIC score of 3 {INR <1.5, absence of active cancer and no prior stem cell or organ transplantation}, meant low risk of severe ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) deficiency, thus making aHUS most probable diagnosis. Where PLASMIC score was calculated based on the following parameters: Platelet count, combined hemoLysis variable, absence of Active cancer, absence of Stem-cell or solid-organ transplant, MCV, INR, and Creatinine. Her coomb test was negative. She was not investigated for autoimmune status and other viral infections (like Cytomegalovirus (CMV) or mycoplasma). For further management, she was referred out to a non COVID-19 centre when she turned COVID negative.

Case 2

A 25-year-old female presented with complaints of fatigue, rashes, dark urine, nausea and abdominal pain for last seven days. Rashes were seen on the chest and upper back. Abdominal pain was dull, continuous and in right hypochondriac region. On examination, she had icterus and anasarca. She gave a history of anosmia, cough and fever for seven days, 12 days back and became COVID-19 negative five days back. Her initial investigation showed anaemia (Hb of 9.6 gm/dL) and unconjugated hyperbilirubinemia (total and direct bilirubin level being 34.32 mg/dL and 12.23 mg/dL, respectively), and deranged LFT (Table/Fig 1), (Table/Fig 2). On peripheral smear examination, there was neutrophilic leucocytosis with RBC clumping in the background. RBCs were predominately normocytic normochromic with marked anisopoikilocytosis, few microcytic hypochromic cells, few target cells, schistocytes, elliptical cells and occasional leptocytes were seen (Table/Fig 1), (Table/Fig 3). Direct Coomb’s test (DCT) using polyclonal antisera showed grade 2 RBC agglutination. Her pre and post-incubation at 4°C, CBC and peripheral smear showed significant differences (Table/Fig 1), (Table/Fig 3). So, a final diagnosis of AIHA (cold agglutinin induced) was made based on peripheral smear findings and positive DCT test.

Flowcytometry showed T-cell Lymphopenia (absolute T-cell count being 540/mm3) (Reference: 939-3572/mm3) and down regulation of Human Leukocyte Antigen-DR isotype (HLA-DR) on monocytic population with absence of Natural Killer cell (NK cell) population (7). Ultrasound with doppler showed evidence of Hepatitis with hepatomegaly. Magnetic Resonance Imaging (MRI) and Magnetic Resonance Cholangiopancreatography (MRCP) were suggestive of fatty liver and acalculous cholecystitis (Table/Fig 3). Serology was negative for Hepatitis A, Hepatitis B, Hepatitis C, Hepatitis E, Epstein-Barr Virus (EBV), CMV and Human Immunodeficiency Virus (HIV). But she was found to be positive for IgG Hepatitis A virus EBV, CMV and Mycoplasma on repeat testing after three weeks. After starting steroid therapy (Prednisolone 5 mg daily) for five days patient improved both clinically and biochemically. Liver biopsy was performed after patient got stabilised and showed features of acute exacerbation of pre-existing hepatitis with submassive hepatic necrosis. Patient improved on further follow-up for next three months but suddenly deteriorated and succumbed to her illness.

Case 3

A two-month-old COVID-19 positive child presented with shortness of breath and generalised weakness for 10 days. There were no co-morbidities or significant family history. On examination, there was pallor and hepatosplenomegaly. Initial investigation showed anaemia and neutrophilic leucocytosis, which persisted on subsequent work-up (Table/Fig 1), (Table/Fig 2). On peripheral smear, there was neutrophilic leucocytosis (absolute neutrophil count of 71,604/mm3) with reduced RBC mass (2.12 million/mm3). RBCs were predominately normocytic normochromic with moderate anisopoikilocytosis, fair number of schistocytes, occasional tear drop cells and target cells along with spherocytes were noted (Table/Fig 4). His chest radiograph showed ground glass opacity in bilateral upper left and right perihilar region suggestive of indeterminate COVID-19 (Table/Fig 4). In view of persistent leucocytosis and anaemia despite multiple transfusion, patient underwent bone marrow examination which showed pauci particulate hypocellular marrow. Erythroid series was markedly suppressed and showed predominately normoblastic erythroid reaction. Myeloid series showed mild myelodyspoesis in the form of binucleation, doughnut cells, few immature precursors with hypogranulation. Megakaryocytes were adequate in number and showed features of megakaryodyspoesis in form of small dwarf forms with hypolobation (Table/Fig 4). His serology showed positive IgM CMV and Mycoplasma pneumoniae. Final diagnosis was haemolytic blood picture (either due to direct effect of COVID-19 infection or CMV and Mycoplasma induced), neutrophilic leucocytosis and mildly hypocellular marrow for age with erythroblastopenia and trilineage dyspoesis due to congenital CMV infection. Unfortunately, by the time detailed work-up was concluded patient succumbed to his illness.

Discussion

While the main target of COVID-19 remains the lung, with respiratory failure and acute respiratory distress syndrome seen in severe cases, extrapulmonary complications are now increasingly reported. Many patients present with various haematological manifestations like cytopenia (anaemia, lymphopenia and thrombocytopenia) and coagulation disorders. Araya S et al., studied 334 admitted COVID-19 patients for haematological abnormalities. They reported any cytopenia and pancytopenia in 41% and 1.8% patients, respectively. Anaemia, thrombocytopenia, and leukopenia was seen in 24.9%, 21.6%, and 5.4% patients, respectively. Lymphopenia (72.2%) was the most common haematological abnormality (8). It is presumed that COVID-19 infection directly and indirectly leads to haemolysis and cytopenia. Haemolytic anaemia can also occur due to other aetiological agents like accompanying CMV or Mycoplasma infection and it is very important to detect such cases. The high level of inflammatory cytokines throughout the body and direct endothelial injury causes excessive activation of the coagulation and complement cascade, leading to thrombotic complications (9).

First case was of a 28-year-old female, who presented with complaints of generalised weakness and oliguria and antecedent history of preterm vaginal delivery with abruptio placentae 10 days prior to current complaints. On detailed work-up, she was diagnosed as thrombotic microangiopathy with neutrophilic leucocytosis, differentials being TTP, aHUS and DIC. DIC was ruled out as Prothrombin Time test (PT) and INR were within normal limits with extremely high D-dimer levels (75000 ng/mL). Thus, most probable diagnosis being aHUS/TTP. They can be differentiated accurately only after ADAMTS13 activity levels, values <10% indicative of TTP. (Unfortunately, that couldn’t be done as patient was transferred to another institute). But low PLASMIC score of 3 (INR <1.5, absence of active cancer and no prior stem cell or organ transplantation), meant low risk of severe ADAMTS13 deficiency, thus making aHUS most probable diagnosis. In a review article conducted for cases between 1964-2002, it was found that 13% of thrombotic microangiopathic patients were pregnant (10). As pregnancy alone is hypercoagulable state, superimposed abruptio placentae and COVID-19 might act as an amplifier.

Two studies reported by Ville S et al., and Altowyan E et al., were compared to our case (11),(12) (Table/Fig 5). Ville S et al., reported a case of aHUS with COVID-19 infection where a 28-year-old female presented with recurrent, relapsing, and remitting haemolysis since childhood (11). This got exaggerated in current COVID-19 pandemic when she presented with extrauterine pregnancy. This case is an illustration that COVID-19 is to be added to the list of the potential triggers of aHUS relapse. In this setting, the deleterious effect of the COVID-19 may arise from: (i) a direct toxic effect on endothelial cells, as suggested by various autopsy studies; and/or (ii) a complement activation with ultimately complement-mediated endothelial damage, most particularly in patients with a constitutional defect in complement regulation, as in the patient presented herein. Case 1 had similar clinical and laboratory findings with low PLASMIC score of 3 (Table/Fig 5).

Altowyan E et al., reported a 39-year-old man who presented with a history of epigastric pain, nausea and vomiting for approximately seven days before admission (12). He was diagnosed as TTP due to thrombocytopenia, microangiopathic haemolytic anaemia and schistocytes in the peripheral blood film. The PLASMIC score was 6, which meant that the patient had a high risk of severe ADAMTS 13 deficiency. These findings were in conjunction with the present study except there was no prothrombotic risk factor in this case and PLASMIC score (6) was high (Table/Fig 5).

Autoimmune manifestations of COVID-19 includes, autoimmune thrombocytopenia, Guillain–Barre and antiphospholipid syndrome. AIHA is an unusual finding. AIHA is an acquired haemolysis in which the host’s immune system attacks its own red cell antigens. Cold agglutinins are formed when B cells produce IgM autoantibodies with an antigen antibody reaction between 0 to 4°C. These autoantibodies are capable of agglutinating red blood cells, causing complement-mediated extravascular haemolysis and resulting in an AIHA. When cold agglutinin autoantibodies are produced in association with an underlying hematologic malignancy or infection, this is called cold agglutinin syndrome (13). COVID-19 can be associated with cold agglutinin syndrome, just like Mycoplasma pneumoniae, EBV, and CMV (14),(15).

Second case was a 25-year-old female who presented with complaints of fatigue, fever, rashes, icterus and anasarca and final diagnosis given was AIHA induced by cold agglutinin. As patient was positive for IgG HAV, IgG EBV and IgG CMV it is difficult to rule out infective cause of AIHA.

Third case was a two-month-old child who presented with respiratory distress and pallor. On examination, hepatosplenomegaly was also found. Haemogram and blood picture was suggestive of neutrophilic leucocytosis with haemolysis while bone marrow examination showed erythroblastopenia with trilineage dyspoiesis. Child had a COVID-19 positive immune modulated state with CMV and Mycoplasma infection concomitantly. Few case reports were compared to present cases (case 2 and 3) of haemolytic anaemia (Table/Fig 6) (4),(16),(17).

Maslov DV et al., reported a 48-year-old COVID-19 positive male whose neurological status declined three hours after admission (16). Venous Doppler ultrasound of upper extremities revealed clots in bilateral upper extremities. He was diagnosed as AIHA induced by cold agglutinin. Gowda V et al., studied haematological manifestation of nine infants suffering from congenital CMV infection (18). Majority of infants had anaemia. Evidence of haemolysis were present in four (44%) patients in form of marked anisocytosis, poikilocytosis, schistocytosis, fragmented red cells on peripheral blood film examination and raised reticulocyte counts. Unconjugated hyperbilirubinemia was present in two infants. Thrombocytopenia was another striking feature. Almost half (44%) of the patients showed severe thrombocytopenia (platelets <50,000/mm3). Bone marrow examination could be performed in three patients. It revealed erythroid hyperplasia and absence of megakaryocytes in one and paucity of erythroid and megakaryocytic cells in other two. Four of nine infants had conjugated hyperbilirubinemia and raised serum alanine transaminase values. This was similar to the case 3 in this study, with marked erythroblastopenia, megakaryocytopenia and trilineage dyspoiesis, which lead to death of the index case eventually.

Conclusion

COVID-19 infection leads to varied spectrum of haematological manifestation, high index of suspicion and awareness about the same is of utmost importance for better management and saving the life of patient in such an ill understood and fast deteriorating multiorgan involving disease. Time based management, with high index of suspicion in the index cases is highly recommended.

References

1.
Tong JY, Wong A, Zhu D, Fastenberg JH, Tham T. The prevalence of olfactory and gustatory dysfunction in covid-19 patients: A systematic review and meta-analysis. Otolaryngol Head Neck Surg. 2020;163(01):03-11. [crossref] [PubMed]
2.
Gianniis D, Ziogas IA, Gianni P. Coagulationi disorders in coronavirus infected patients: COVID-19, SARS-CoV-1, MERS-CoV and lessons from the past. J Clin Virol. 2020;127:14. [crossref] [PubMed]
3.
Hill QA, Stamps R, Massey E, Grainger JD, Provan D, Hill A; British Society for Haematology. The diagnosis and management of primary autoimmune hemolytic anemia. Br J Haematol. 2017;176:395-411. [crossref] [PubMed]
4.
Jawed M, Hart E, Saeed M. Hemolytic anemia: A consequence of COVID-19. BMJ Case Reports CP. 2020;13:e238118. [crossref] [PubMed]
5.
Davison AJ. Evolution of the herpesviruses. Vet Microbiol. 2002;86(1-2):69-78. [crossref]
6.
Damani J. Disseminated intravascular coagulopathy from warm autoimmune hemolytic anemia in a patient with COVID-19. Chest. 2020;158(4):A397. [crossref] [PubMed]
7.
Valiathan R, Deeb K, Diamante M, Ashman M, Sachdeva N, Asthana D. Reference ranges of lymphocyte subsets in healthy adults and adolescents with special mention of T cell maturation subsets in adults of South Florida. Immunobiology. 2014;219(7):487-96. [crossref] [PubMed]
8.
Araya S, Wordofa M, Mamo MA, Tsegay YG, Hordofa A, Negesso AE, et al. The magnitude of hematological abnormalities among COVID-19 patients in Addis Ababa, Ethiopia. J Multidiscip Healthc. 2021;14:545-54. [crossref] [PubMed]
9.
Hoteit L, Deeb AP, Andraska EA, Yazdani HO, Tohme S, Neal MD, et al. The pathobiological basis for thrombotic complications in COVID-19: A review of the literature [published online ahead of print, 2021 Dec 8]. Curr Pathobiol Rep. 2021;1-11. [crossref] [PubMed]
10.
George JN. The association of pregnancy with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Curr Opin Hematol. 2003;(5):339-44. [crossref] [PubMed]
11.
Ville S, Le Bot S, Chapelet-Debout A, Blancho G, Fremeaux-Bacchi V, Deltombe C, et al. Atypical HUS relapse triggered by COVID-19. Kidney Int. 2021;99(1):267-68. [crossref] [PubMed]
12.
Altowyan E, Alnujeidi O, Alhujilan A, Alkathlan M. COVID-19 presenting as Thrombotic Thrombocytopenic Purpura (TTP). BMJ Case Reports CP. 2020;13:e238026.
13.
Berentsen S. New insights in the pathogenesis and therapy of cold agglutinin-mediated autoimmune hemolytic anemia. Front Immunol. 2020;11:590. [crossref] [PubMed]
14.
Berentsen S. Cold agglutinin disease. Hematology (Am Soc Hematol Educ Program) 2016;2016(01):226-31. [crossref] [PubMed]
15.
Lazarian G, Quinquenel A, Bellal M. Autoimmune hemolytic anemia associated with COVID-19 infection. Br J Haematol. 2020;190(01):29-31. [crossref] [PubMed]
16.
Maslov DV, Simenson V, Jain S, Badari A. COVID-19 and cold agglutinin hemolytic anemia. TH Open. 2020;4(3):e175-77. [crossref] [PubMed]
17.
Capes A, Bailly S, Hantson P, Gerard L, Laterre PF. COVID-19 infection associated with autoimmune hemolytic anemia. Ann Hematol. 2020;99(7):1679-80. [crossref] [PubMed]
18.
Gowda V, Kulhalli P, Vamyanmane D. Neurological manifestations of congenital cytomegalovirus infection at a tertiary care centre from Southern India. Journal of Neurosciences in Rural Practice. 2021;12(1):133-36. [crossref] [PubMed]

DOI and Others

DOI: 10.7860/JCDR/2022/51186.15960

Date of Submission: Aug 01, 2021
Date of Peer Review: Sep 17, 2021
Date of Acceptance: Dec 07, 2021
Date of Publishing: Feb 01, 2022

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. Yes

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Aug 02, 2021
• Manual Googling: Nov 24, 2021
• iThenticate Software: Jan 01, 2022 (15%)

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