|Year : 2020 | Volume
| Issue : 3 | Page : 205-207
“COVID & The Clots”
Kalkunte R Suresh
Chief Editor – IJVES, Director – JIVAS, Bengaluru, Karnataka, India
|Date of Submission||29-Aug-2020|
|Date of Acceptance||29-Aug-2020|
|Date of Web Publication||12-Sep-2020|
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Suresh KR. “COVID & The Clots”. Indian J Vasc Endovasc Surg 2020;7:205-7
The fabled storytellers who created enchanting fairy tales, be it Hans Christian Anderson, Brothers Grimm, or others, used dual words in many of their titles to convey the gist of their beautiful stories, cherished by young and old alike. I am sure many will recall the headings “Snow White and the Seven Dwarfs,” “Jack and the Beanstalk,” and “Beauty and the Beast,” to name a few. But, the heading of this editorial, though similar in its structure, would not enthrall the reader, but has more ominous forebodings!
There is little doubt the significant pathology of COVID-19's assault on humans is channeled through thrombosis. Before I delve into the possible causes of this thrombotic state, I would like to present to you the travails of one of our young colleagues, as expressed by him:
Living Through Dreads of “COVID AND THE CLOTS”
A Personal Traumatic Encounter
Dr Srujal Shah MS, MCh (Vascular surgery); Indovasc Hospital; Ahmedabad
Being a young Vascular specialist, I was used to getting references and treating thrombosis in vascular tree. Ever since COVID unleashed its fury in Gujarat, I like many, observed an increased trend in DVT, PE and spontaneous arterial thrombosis in all territories. Having performed an emergency brachial thrombectomy in a COVID positive patient, (with Pulmonary Embolism), I had learnt that the thrombus type is typically jelly like in COVID and the thrombogenicity of blood was very high even after therapeutic dose heparinization.
Little did I realize that I would be exposed to the wrath of COVID19 personally. I had to face a situation where my father turned COVID positive and I was actively involved in managing his care, from ward to ICU. The course of the disease was typical with fever, cough, malaise and finally drop in SPO2. Despite timely diagnosis and proactive treatment with Remdesivir, Methyl prednisolone, Tocilizumab and Convalescent Plasma, he continued to worsen and lungs refused to improve! He was shifted from room air to nasal prongs, venti-mask, HFNC and finally to bipap over a period of 12 days.
The viral activity and signs of infective disease, as well as pneumonia, had stabilized and even improved during that period. But the oxygenation at alveolar level kept getting worse. ABGs showed gradual decline to PO2 of 51 on F1O2 of 80%. The respiratory rate and all other parameters were consistent with severe ARDS.
As a son treating his father, who is steadily waning and heading towards irreversible phase, staring at fatality (not to mention the unfathomable misery of the family), I was willing to try anything and everything! After harrowing contemplations, I suspected pulmonary micro thrombosis as primary cause not allowing oxygenation. I had heard and read about dramatic recovery of a COVID positive patient on ventilator when he was thrombolysed for stroke and he recovered from COVID ARDS next day and was out of ventilator. Whether it was leap of faith or (un)educated gamble, thrombolysis was to be tried! I had to sign a form absolving the hospital and others for any adverse outcome since the lytic therapy had no real evidence. Also I had to swim against the tide, when all others recommended intubation and ventilatory support. But the odds of survival, they informed us, in those over 70 years of age was about 2%. This made my resolve even stronger.
We discussed with the team of Pulmonologist, Cardiologist and Intensivist. Although none were convinced (was I??), I went ahead and started systemic lysis in form of Actilyse @ 25 mg/hour followed by 1mg/hour infusion. DIC and sepsis were ruled out by checking Fibrinogen level (260) and Procalcitonin. D -dimer value had risen from 1000 to 10980 in 48 hours; was considered a strong trigger for worsening and despite no PE on 2D ECHO, we went ahead with lysis.
DIC and sepsis were ruled out by checking Fibrinogen level (260) and Procalcitonin. D -dimer value had risen from 1000 to 10980 in 48 hours; was considered a strong trigger for worsening and despite no PE on 2D ECHO, we went ahead with lysis.
On starting lytic therapy, initially SPO2 dropped from 90 to 80%; but after 2 hours there was sustained improvement up to 97% SPO2 on 65% FiO2. At the end of 24 hours he was in stable condition with heart rate of 90, respiratory rate of 25-30, BP 130 systolic and SPO2 of 95-97% on 60% FiO2. Now he could tolerate HFNC again.
We started him on UFH (unfractionated heparin) as per protocol and tried maintaining APTT in therapeutic range. Forty two hours went well. As it was very difficult to monitor APTT in COVID setup, due to delayed lab reports and fluctuation in APTT, I shifted him to LMWH again. But to my surprise, the similar cycle of worsening was noticed on 4th day. Finally I gave a bolus of UFH (6000 IU) at night 11:00 pm and restarted UFH infusion considering its superiority over LMWH and next morning, as I had hoped, he improved again with cuncurrent improvement in chest X-Ray and ABGs.
That day he was shifted to non COVID Pulmonary care ICU and remained on UFH for next 3 days and then placed shifted on venti mask and then nasal prongs. And home eventually!
I strongly believe and recommend the role of anticoagulation in all COVID patients to prevent vascular and respiratory complications and suggest role of thrombolysis when D-dimer levels are high, lungs fall into severe ARDS category and viral activity is under control.
I also strongly hope that nobody will have to go through this distressing experience!
This tale of valor is truly “Bold and Beautiful” – “Bold” the decision taken by the young man and “Beautiful” is the ending!
It is probably prudent to end this piece at this stage! Anything else will be dwarfed by this touching chronicle. But thought I would add a few words about triggers for the COVID-induced clots. These are essentially collated from a swarm of articles available to all readers as most are open-access articles.
In a report of five cases of COVID-19, Magro et al. offer some explanation for microvascular injury and thrombosis in their extremely well-illustrated article. It might be tough for surgical minds to grasp, but the article should be perused by all dealing with thrombotic events in COVID patients. The pathways are well illustrated in a figure from their article [Figure 1].
|Figure 1: Model for AP and LP complement activation by SARS-CoV-2, and its interaction with coagulation cascades – Figure 10|
Click here to view
The above looks complex, but few minutes will clarify the message.
They mention “In conclusion, at least a subset of sustained, severe COVID-19 may define a type of catastrophic microvascular injury syndrome mediated by activation of complement pathways and an associated procoagulant state. It provides a foundation for further exploration of the pathophysiologic importance of complement in COVID-19, and could suggest targets for specific intervention.”
In NEJM Journal watch, George Sakoulas, MD (reviewing Nicolai et al. Circulation 2020 Jul 28) addresses “Immunothrombosis in the pathogenesis of COVID19 Coagulopathy” CPMMENTING ON et al. article which states “ Activated neutrophils and platelets play key roles in the immunologically mediated thrombosis seen in severe COVID-19. SARS-CoV-2 virus causes severe multisystem disease beyond ARDS. The mechanism of nonpulmonary involvement seems to involve a coagulopathy driven by a dysregulated immune response. Saukoulas comments, “This study sheds light in a very clear and direct way on the pathophysiology of severe COVID-19, linking the interaction of activated neutrophils, activated platelets, and dysregulated immunothrombosis that results in systemic organ dysfunction. Future successful COVID-19 therapies will likely be required to address these abnormalities mechanistically.”
In the discussion of “Pathogenesis and Treatment Strategies of COVID-19-Related Hypercoagulant and Thrombotic Complications,” Haimei briefly summarizes that the mechanism of hypercoagulability and thrombotic complications of severe COVID-19 and proposes that blood hypercoagulability and intravascular microthrombosis are the development nodes of severe COVID-19. Therefore, anticoagulation and anti-inflammatory therapy can be used as important treatment strategies for severe COVID-19.”
There are innumerable articles about varied organ thrombosis, and the data/knowledge is still evolving. A vascular surgeon/specialist should be aware of the pathogenesis of COVID-19-induced thrombosis, though we are quite erudite in treating peripheral thrombo-embolic events.
Another pathology vascular surgeons need to be aware of is “COVID TOES” Noted by Dermatologists. These are purplish, nodular lesions and the exact mechanism is unclear.
The range of vascular pathologies caused by COVID-19 is not yet completely known. Vascular surgeons/specialists will likely see increasing numbers of both arterial and venous thrombosis; we need to develop strategies in both diagnosing and treating these patients, which could be at variance with our usual approach to these thrombotic patients.
“THIS TOO WILL PASS…….” To those young surgeons who are at askance about future – your days to bask in finery of your efforts will definitely arrive!
| References|| |
Magro C, Mulvey JJ, Berlin D, Nuovo G, Salvatore S, Harp J, et al
. Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: A report of five cases. Transl Res 2020;220:1-3. Published online 2020 Apr 15. doi: 10.1016/j.trsl.2020.04.007.
Nicolai L, Leunig A, Brambs S, Kaiser R, Weinberger T, Weigand M, et al
. Immunothrombotic dysregulation in COVID-19 pneumonia is associated with respiratory failure and coagulopathy. Circulation doi: 10.1161/CIRCULATIONAHA.120.048488. Online ahead of print. Available from: https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.120.048488
Haimei MA. Pathogenesis and treatment strategies of COVID-19-related hypercoagulant and thrombotic complications. Clin Appl Thromb Hemost 2020;26:1076029620944497. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391437/
. [Last accessed on 2020 Jul 28].