Thank you Abdul Hadi Al-Qahtani this is an excellent summary of the current understanding of the clinically relevant pathophysiology of thrombosis in Covid-19.

Please provide the references for these statements.

Cher Collègue bonjour merci pour ces précisions

Pouvez vous nous donner vos références ? Est ce une méta analyse ?

Thank you Dr. Rajkumar Rajendram , Dr. M. Chahim , & Dr. Neha Gupta .

Regarding related references, I reviewed related topics from the following links:

* https://www.uptodate.com/

* https://www.ncbi.nlm.nih.gov/pubmed?term=32291094

* https://www.ncbi.nlm.nih.gov/pubmed?term=32302453

* https://www.ncbi.nlm.nih.gov/pubmed?term=32271988

* https://www.ncbi.nlm.nih.gov/pubmed?term=32320517

* https://www.nejm.org/doi/full/10.1056/NEJMc2009787

* https://www.esicm.org/wp-content/uploads/2020/04/863_author_proof.pdf

COVID-19 affected patients may suffer from dehydration at one point in the disease course resulting in high hematocrit associated with hypercoagulability. And thereby, severe stroke/embolus phenomenon is one of the potential causes of the sudden death of COVID-19 patients. At this point, serum ferritin and liver enzymes may be elevated. Here, there are roles in using:

• deferoxamine (an iron-chelating agent),
• prophylactic enoxaparin (low molecular weight heparin),
• L-Omithine+L-Aspartate ((converts toxic ammonia to non-toxic urea),
• ursodeoxycholic acid (suppresses synthesis and secretion of cholesterol from liver & reduces cholesterol absorption from intestines) and
• target-controlled hydration.
• The above-mentioned are all supportive but not definitive management. But, we had to use those in some patients and got good results. They all are cured & well now. Thanks.

Dear Rabiul,

Would an AT1 antagonist help with vasodilation in these patients thereby preventing ischemic strokes in these patients?

Also, an ACEI could help prevent the binding of spike s1 protein to its binding domain on ACE2. Could that help prevent the virus from entering the lung epithelial cells?

Thank you!

Balamane

Thank you Dr. Rabiul Alam

Regarding parthenogenesis; there are many factors e.g. inflammation, direct endothelial injury, complement activation, and other possibilities that published recently as theories.

Regarding anticoagulants; as you mentioned some experts advised to start prophylactic Enoxaparin but I believe we need to start even therapeutic Enoxaparin (1mg/kg BID) specially for very sick patients in ICU if there is no contraindications because autopsy of the lungs for many COVID-19 patients showed micro-thrombosis.

Dear Saad Balamane , thanks for your interesting points. The benefits of ACEI/ARB are observed in COVID-19 patients with hypertension. This is associated with a lower risk of all-cause mortality compared with ACEI/ARB non-users. But we don't know yet about its usage and haven't used ACEI as an adjunct to prevent ischemic stroke as you mentioned. You may please go through:

Preprint COVID-19 and erythrocytes aggregates: An intensivist's exper...

Article Association of Inpatient Use of Angiotensin-Converting Enzym...

Article Coronavirus Disease 2019 (COVID-19): Do Angiotensin-Converti...

Dear Rabiul,

Thanks so much for answering my question! I will have a look at the papers you attached here.

Kind regards,

Balamane

Dear Abdul Hadi Al-Qahtani , yes I agree with your view of using enoxaparin, but it should be, of course, case-specific where there is a definite indication. We may sometimes ignore a simple issue that hypoxia due to alveolar infiltration of CoV aggravates RBC production and haemoconcentration which has substantial contributions to the thromboembolic phenomenon. So, we have to prevent hypoxia and must achieve the goal of SpO2 >92% by high flow oxygen & prone ventilation. Awake patients are to be encouraged for prone & lateral position, postural drainage, breath-holding exercise, incentive spirometry. Enteral N-acetyl cysteine and nebulization with bronchodilator & steroid are works worthy. Thanks.

Preprint COVID-19 and erythrocytes aggregates: An intensivist's exper...

To shed light - coronaviruses use heparan sulfate for entry to the endothelial cells. Thus hypothetically and attractively, blockage/saturation of the endothelial glycocalyx with heparin may ameliorate endothelial cell infection, endotelitis and generalized thrombosis.

Preprint The 2019 coronavirus (SARS-CoV-2) surface protein (Spike) S1...

Hello. Several medicine centers recommend in thromboprophylaxis give more than traditional enoxaparin 40 mg daily. They recommend the strict dose of 1 mg/kg/day

Raul Gonzalez Fregoso Hard to say, especially when dealing with subsets of patients with obesity, kidney failure of various degree, infected, heavily inflamed with hypercoagulable state etc. However, if no apparent bleeding risk (HAS BLED OF VALUE?) - I would go for 1 mg/kg or more.

Yes of course. In the extremes and, in my opinion, I would prefer to control a hemorrhage instead of PTE. Best regards

following

COVID19 is this a critical condition? Always microcirculatory disorders and sludge syndrome? Does latent thrombohemorrhagic syndrome take place?

A number of changes in circulating prothrombotic factors have been reported or proposed in patients with severe COVID-19 :

•Elevated factor VIII

•Elevated fibrinogen

•Circulating prothrombotic microparticles

•Neutrophil extracellular traps (NETs)

Very elevated levels of D-dimer have been observed that correlate with illness severity; D-dimer is a degradation product of cross-linked fibrin indicating augmented thrombin generation and fibrin dissolution by plasmin. However, high D-dimer levels are common in acutely ill individuals with a number of infectious and inflammatory diseases.

Venous thromboembolism (VTE) prophylaxis is appropriate in all hospitalized medical, surgical, and obstetric patients with COVID-19 , unless there is a contraindication to anticoagulation (eg, active bleeding or serious bleeding in the prior 24 to 48 hours) or to the use of heparin (eg, history of heparin-induced thrombocytopenia [HIT], in which case an alternative agent such as fondaparinux may be used)

Enoxaparin – For patients with creatinine clearance (CrCl) >30 mL/min, 40 mg once daily; for CrCl 15 to 30 mL/min, 30 mg once daily.

•Dalteparin – 5000 units once daily.

•Nadroparin – For patients ≤70 kg, 3800 or 4000 anti-factor Xa units once daily; for patients >70 kg, 5700 units once daily. In some cases, doses up to 50 anti-factor Xa units/kg every 12 hours are used.

•Tinzaparin – 4500 anti-factor Xa units once daily.

Dear Gamal,

Thank you so much for your detailed answer!

Kind regards,

Balamane

SARS-CoV-2 enter host cells via ACE2 receptors, which are situated in blood vessels too, so this results in inflammation, which damages the endothelial lining of blood vessels that in turn trigger the coagulation cascade, causing coagulation.

Please have a look at this article in NEJM

Article Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogen...