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

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Dr Mohan Z Mani

"Thank you very much for having published my article in record time.I would like to compliment you and your entire staff for your promptness, courtesy, and willingness to be customer friendly, which is quite unusual.I was given your reference by a colleague in pathology,and was able to directly phone your editorial office for clarifications.I would particularly like to thank the publication managers and the Assistant Editor who were following up my article. I would also like to thank you for adjusting the money I paid initially into payment for my modified article,and refunding the balance.
I wish all success to your journal and look forward to sending you any suitable similar article in future"



Dr Mohan Z Mani,
Professor & Head,
Department of Dermatolgy,
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 : 2023 | Month : February | Volume : 17 | Issue : 2 | Page : OR01 - OR04 Full Version

Multifaceted COVID-19 Associated Coagulopathy: A Case Series


Published: February 1, 2023 | DOI: https://doi.org/10.7860/JCDR/2023/61329.17462
Manisha Bhardwaj, Pratibha Himral, Deepak Aggarwal

1. Assistant Professor, Department of Pulmonary Medicine, Shri Lal Bahadur Shastri Government Medical College and Hospital Mandi at Ner Chowk, Mandi, Himachal Pradesh, India. 2. Associate Professor, Department of Internal Medicine, Shri Lal Bahadur Shastri Government Medical College and Hospital Mandi at Ner Chowk, Mandi, Himachal Pradesh, India. 3. Associate Professor, Department of Pulmonary Medicine, Government Medical College and Hospital, Chandigarh, India.

Correspondence Address :
Dr. Manisha Bhardwaj,
Assistant Professor, Department of Pulmonary Medicine, Shri Lal Bahadur Shastri Government Medical College and Hospital Mandi at Ner Chowk, District Mandi-175021, Himachal Pradesh, India.
E-mail: mbgmch@gmail.com

Abstract

The pathophysiology behind Coronavirus Disease-2019 (COVID-19) has remained blur even after more than two years of onset of the pandemic. Apart from pulmonary parenchymal involvement, widespread vascular thrombosis affecting both pulmonary and extra-pulmonary systems has also been seen to contribute to COVID-19 associated morbidity. This vascular manifestation often remains undiagnosed due to non specific and varied symptoms that range from asymptomatic detection to life threatening presentations. A series of six COVID-19 positive (three male and three female) cases who presented with thrombosis of pulmonary, coronary and cerebral vessels despite being on thromboprophylaxis are reported herein. The age of patients ranged from 32 to 80 years. Out of six patients, three had co-morbidities. The most common complication was Pulmonary Thromboembolism (PTE, n=3) followed by Brain infarct (n=2) and Myocardial Infarction (MI, n=1). Out of three patients with PTE, one patient had concurrent Deep Vein Thrombosis (DVT). All patients were managed as per guidelines issued by the Ministry of Health and Family Welfare for severe COVID-19 disease. Out of six patients, three patients died and three were discharged. The series highlights the need for high index of suspicion on the part of the treating physician that could aid in early detection and successful management of this potentially fatal condition.

Keywords

Complications, Coronavirus disease 2019, Thrombosis

The spectrum of COVID-19 Associated Coagulopathy (CAC) is wide and can involve both arteries and veins. Besides Deep Vein Thrombosis (DVT), it may present as life threatening conditions like Cerebrovascular Accident (CVA), MI and massive Pulmonary Thromboembolism (PTE) (1),(2). A study by Bilaloglu S et al., revealed the incidence of ischaemic stroke and MI in COVID-19 as 0.9-4.6% and 1.1-8.9%, respectively. The mortality was almost double in patients with thrombotic events (43.2%) (3). A recent meta-analysis reported that the pooled incidence of PTE was 21% (4).

The exact pathophysiology of CAC is still not known even after more than two years of onset of the pandemic. However, several theories have been postulated. Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has affinity towards Angiotensin Converting Enzyme-2 (ACE-2) receptors which are commonly present in lungs. Other sites include vascular endothelial cells, kidney, heart, and brain. Virus induced endothelial damage leads to raised levels of von Willebrand factor and activation of neutrophils and macrophages in multiple vascular beds. Cytokine release syndrome and formation of Neutrophil Extracellular Traps (NETs) are also linked to thrombotic complications in COVID-19 patients (4),(5),(6).

Commonly, elderly patients with co-morbidities who are on immunosuppressive therapy develop CAC. But infrequently, young patients may also deteriorate rapidly due to thromboembolic complications even in absence of any predisposing factors (2),(3),(7). So, one should have a high index of suspicion to identify uncommon presentations irrespective of age, gender and underlying health conditions.

A series of six cases aged 32 to 80 years with COVID-19 who presented with varied thromboembolic complications reported to our institution from March-July 2021. None of the patients had any history of malignancy, long haul travel or previous immobilisation. It is pertinent to understand that CAC as an entity is not so rare and the clinician should be aware of its varied presentations. Details of patients are summarised in (Table/Fig 1).

Case Report

Case 1

A 68-year-old COVID-19 positive male got admitted with complaints of Shortness of Breath (SOB), chest pain and pain in the right lower limb for the last five days. He was a known diabetic and hypertensive since three years and on oral therapy (metformin 500 mg twice daily and amlodipine 10 mg once daily). Three months back, he had been successfully treated for moderate COVID-19.

On admission, his vitals were stable with percent Oxygen Saturation (SpO2) of 96% at Room Air (RA). Chest X Ray (CXR) was normal. Venous Doppler Ultrasonography (VD-USG) revealed DVT in right femoro-popliteal veins. He was started on therapeutic anticoagulation (Low Molecular Weight Heparin; LMWH subcutaneous, SC; 0.6 mL twice daily) along with supportive treatment as per the guidelines issued by the Ministry of Health and Family Welfare (8). On day 5, he developed sudden increase in SOB with hypoxemia (SpO2 86% RA). Computed Tomography with Pulmonary Angiography (CTPA) showed acute PTE in left lobar and right and left segmental pulmonary arteries. He gradually improved with therapeutic anticoagulation. He was later discharged on oral rivaroxaban (20 mg once daily) for three months. He did not report for scheduled follow-up.

Case 2

A 58-year-old COVID-19 positive female, presented with complaints of fever, cough, and SOB for five days and poor food intake for two days. She was a known case of hypertension (seven years) and Coronary Artery Disease (CAD) (three years) on oral drugs; metoprolol (25 mg), aspirin (75 mg) and atorvastatin (20 mg).

On admission, she was delirious (Glasgow Coma Scale; GCS-11/15). Her vitals were: Blood Pressure (BP)- 150/100 mmHg, Pulse Rate (PR)- 120/minute, and SpO2-80% RA. She was started on remdesivir (i.v.; 200 mg once daily on day 1 followed by 100 mg for next four days), dexamethasone (6 mg i.v. twice daily), LMWH (0.6 mL s.c. twice daily) and oxygen therapy (non rebreathing mask, NRM; FiO2 0.80-1.0) as per the guidelines. Investigations revealed dyselectrolemia (serum Na+- 98 mEq/L, K+- 3 mEq/L) and right bundle branch block on Electrocardiogram (ECG). She improved with electrolyte supplementation. On day 7, she developed acute confusional state. Repeat blood investigations were normal. Magnetic Resonance Imaging (MRI) of brain was done to rule out Central Pontine Myelinolysis (CPM) which showed partial sigmoid sinus thrombosis with acute infarct involving bilateral frontal lobes. She was referred to a higher centre where she died before any intervention could be done.

Case 3

A 38-year-old COVID-19 positive unvaccinated male with no co-morbidities presented with complaints of cough and SOB for the last five days. On examination, he was tachypneic (respiratory rate; RR-28 per minute) with SpO2 of 75% at RA. CXR revealed bilateral peripheral patchy infiltrates. He was managed with remdesivir, dexamethasone, LMWH and oxygen therapy as per protocol.

On day 3, he complained of severe retrosternal chest pain. ECG showed findings of anterior wall ST segment elevated MI. He was immediately started on anti-platelets and clopidogrel and shifted to cardiac-care-unit for thrombolysis, however he had a fatal cardiac arrest on the same day.

Case 4

An 80-year-old COVID-19 positive female was admitted with complaints of SOB for four days. CXR revealed bilateral pneumonia. She was a diabetic and was receiving metformin (500 mg once daily) and vildagliptin (50 mg once daily) for 12 years. Her vitals were: BP-150/80 mmHg, PR- 110/minute, RR- 32/minute, and SpO2 of 80% at RA. Blood investigations revealed Acute Kidney Injury (AKI) (serum urea- 89 mg/dL, creatinine-1.1mg/dL) with normal electrolytes, mild hepatitis (aspartate transaminase, AST; 49U/L, alanine transaminase, ALT; 88U/L), and normal total leucocyte count (TLC; 9300/μL). She was managed on lines of severe COVID-19 as per protocol. She showed some initial signs of stabilisation, however, on tenth day, she became drowsy with GCS of 10/15. Non Contrast Computed Tomography (NCCT) head revealed right ischaemic cerebellar infarct (Table/Fig 2). Due to persistent worsening, she was put on a ventilator. However, she died after two days.

Case 5

A 32-year-old female was admitted in severe acute respiratory infection ward with chief complaints of SOB and cough since 10 days. On examination, her BP was 124/80 mmHg, PR- 99/min, RR-24/min and SpO2 89% at RA. She had a history of recent contact with COVID-19 positive patient in her family however her Reverse Transcription-Polymerase Chain Reaction (RT-PCR) report for SARS-CoV-2 came out negative. CXR was suggestive of bilateral pneumonia. COVID-19 Reporting And Data System (CORADS) score on High Resolution CT (HRCT) of the thorax was 5 out of 6.

She was extensively evaluated to rule out alternative causes. Her serology for H1N1 influenza, dengue, leptospira, and scrub typhus was negative. Sputum for Acid Fast Bacilli (AFB) and Cartridge Based Nucleic Acid Amplification Test (CBNAAT) was negative. No growth was seen on blood culture. Based on high clinical suspicion and CORADS score, possibility of COVID-19 was kept. She was treated on lines of moderate illness with steroids (i.v. dexamethasone 6 mg twice daily), prophylactic anticoagulation (LMWH 0.4 mL once daily), and supplemental oxygen therapy. She reported worsening of symptoms on third day.

On evaluation, ECG was normal but CXR showed worsening. She was shifted on NRM (FiO2-0.08, Flow-12 LPM). CTPA showed thrombus involving bilateral pulmonary arteries and right inferior pulmonary vein [Table/Fig-3a,b]. She was started on LMWH at therapeutic doses (0.6 mL S/C twice a day) and respiratory support was continued. She showed gradual improvement. She was discharged after two weeks on rivaroxaban but lost to follow-up.

Case 6

A 49-year-old male presented with complaints of fever, SOB and cough for 15 days. RT-PCR for COVID-19 was negative. On admission vitals were; BP-100/70 mmHg, PR-99/min and SpO2 85% on RA. Laboratory investigations showed anaemia (Hb 9.8 g/dL) and raised TLC (14500/μL; lymphocytes 11%, granulocytes 85%) with normal renal and liver function tests. Nasopharyngeal Swab (NPS) for H1N1 influenza was negative and IgM antibodies for typhoid, leptospirosis and scrub typhus were not detected. Sputum for CBNAAT was negative. CORADS score on HRCT chest was 5/6.

He was treated as probable case of severe COVID-19 illness with steroids (dexamethasone; 8 mg i.v. twice a day) and LMWH (0.6 mL twice a day). The patient was put on high flow nasal cannula (HFNC; FiO2-1.0, Flow-40 LPM) for respiratory support. In view of persistent respiratory distress, he was initiated on mechanical ventilator as per ARDS-net protocol. VD-USG of lower limbs and echocardiography was normal. CTPA chest showed bilateral pneumonia and partial thrombosis of right pulmonary artery (Table/Fig 4)a,b. He was continued on ventilator (ratio of arterial oxygen partial pressure to fractional inspired oxygen; P/F ratio-180) and discharged after 56 days on rivaroxaban. Follow-up CT after three months showed no evidence of residual thrombosis and the patient was doing well.

Discussion

In this series, three out of six patients had PTE while one each had MI and cerebellar infarct, respectively. Estimated incidence of ischaemic stroke and MI in COVID-19 is 0.9-4.6%, and 1.1-8.9%, respectively (1),(3),(7),(9). In a meta-analysis, pooled incidence of PTE was 21% with higher rates in Intensive Care Unit (ICU) than non ICU patients (4). Pulmonary Embolism (PE) patients were older, with lower P/F ratios and higher levels of D-dimer and C-Reactive Protein (CRP) (5). Two patients had no underlying risk factors for PE in this 3series. Lari E et al., also reported severe vascular complications in healthy individuals (2). Out of three patients who presented with PE, only one had evidence of DVT in this series. These findings were consistent with a study from Germany (10). So, pulmonary thrombosis rather than embolism may be the underlying pathology in such cases and can occur despite thromboprophylaxis (10),(11).

Several markers like CRP and D-dimer, P/F ratios and VD-USG have been utilised to rule out DVT, however none could be finalised for routine screening of CAC. CRP at admission was found to be one of the strongest predictors for developing PE in a multivariate analysis, but being a non-specific inflammatory marker, it is of limited utility (5),(6). The sensitivity and specificity of D-dimer levels at 3 μg/mL was 76.9% and 94.9%, respectively with negative predictive value (NPV) of 92.5% to predict venous thromboembolism (12). Several other studies found that higher D-dimer levels correlated with lower P/F ratios, higher CRP levels and worse outcomes (5),(7). Coagulation/inflammatory markers like ferritin, D-dimer, Lactate Dehydrogenase (LDH) and Interleukin-6 (IL-6) levels could not be assessed due to lack of availability in the institution. However, all the patients presented in this series had positive CRP levels (qualitative assay). All the patients were hypoxemic at the time of referral from peripheral centres. Each of them was put on appropriate oxygen delivery device at admission, only one developed ARDS who was put on ventilator and survived later. VD-USG is less reliable in patients without symptoms of DVT; sensitivity 50% as opposed to >90% in symptomatic patients (13). In this series also, only one patient who had symptoms of DVT was detected on VD-USG. The direct cause of deaths in this series was most likely CAC.

Two out of six patients in this series were managed on clinico-radiological grounds. As the virus advances towards alveoli, it may be undetectable in NPS, however can be detected on bronchoalveolar lavage (14). So NPS negativity should not deter the clinician to suspect and treat patients as COVID-19.

The pathophysiology of CAC is multifactorial. Virus induced endothelitis, cytokine release syndrome and formation of NET generate prothrombotic milieu in pulmonary and extra-pulmonary vascular beds. Use of mechanical ventilation, central venous catheters and immobilisation also play a role in CAC (4),(5),(6). The CAC may be under-reported due to lack of knowledge and infrastructural/financial constraints especially in developing countries.

Conclusion

Thromboembolic complications of COVID-19 are a major cause of morbidity and mortality. Old age, severe illness and co-morbidities are common risk factors. However, clinicians should be aware of the possibility of unusual thromboembolic presentations in relatively young and healthy individuals. In view of the lack of affordable objective markers with high sensitivity and specificity, high degree of clinical suspicion should be adopted in diagnosing CAC. Long term impact of thromboembolic and cardiovascular complications is largely unknown and warrants further analysis.

References

1.
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DOI and Others

DOI: 10.7860/JCDR/2023/61329.17462

Date of Submission: Nov 07, 2022
Date of Peer Review: Jan 09, 2023
Date of Acceptance: Jan 14, 2023
Date of Publishing: Feb 01, 2023

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

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Dec 12, 2022
• Manual Googling: Jan 10, 2023
• iThenticate Software: Jan 13, 2023 (4%)

ETYMOLOGY: Author Origin

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