Friday, April 10, 2020



Dr K K Aggarwal
President Confederation of Medical Associations of Asia and Oceania

401: tPA for COVID ARDS
Fact: A team of physician-scientists at Harvard Medical School and Beth Israel Deaconess Medical Center is now enrolling patients in a clinical trial to evaluate a common anticlotting drug for the treatment of COVID-19-positive patients with ARDS. The newly launched trial follows a special report the team published in the Journal of Trauma and Acute Care Surgery suggesting that the use of tPA (tissue plasminogen activator) could reduce deaths among patients with ARDS as a complication of COVID-19.
A clinical observation made about a subset of patients with COVID-19 induced ARDS made the idea seem newly relevant.
We’re hearing anecdotally that a subset of patients with COVID-19 induced ARDS are clotting abnormally around their catheters and IV lines, said senior author, Michael Yaffe, HMS instructor in surgery at Beth Israel Deaconess. “We suspect these patients with aggressive clotting will show the most benefit from tPA treatment, and this new clinical trial will reveal whether that’s the case.

402: Free tests in India

Fact: The Supreme Court on Wednesday ordered the central government to issue directions to approved private laboratories to conduct Covid-19 tests free of cost. The two-judge bench of Justices Ashok Bhushan and Ravindra S Bhat was hearing a PIL. The court further held that the tests must be carried out in labs accredited by the NABL.

403: Mask compulsory

Fact: In India Delhi and Uttar Pradesh joined Madhya Pradesh, Odisha and Nagaland to make it mandatory to cover the face while in public, either with a mask or a cloth. The municipal corporation of Mumbai, union territory of Ladakh and Chandigarh also issued similar orders. UP also sealed 15 districts, including Noida and Ghaziabad in the National Capital Region, till April 15.

403: Plasma treatment in India

Fact: Kerala on Wednesday received approval for its protocol on experimental treatment using convalescent plasma therapy from the Indian Council for Medical Research. The treatment involves transfusing the blood plasma of a recovered patient, replete with antibodies that helped her fight the virus, to another patient.

404: New York the epicentre

Fact: New York State, the epicenter of the U.S. outbreak, has now confirmed more than 149,000 cases — a higher number than any country outside the United States, including Italy and Spain, the two other countries the pandemic has hit hardest. The death toll hit another daily high but the rate of hospitalizations was flattening.

405: Is X ray indicated in asymptomatic cases

A multinational consensus statement on the role of chest imaging in the management of patients with COVID-19 was jointly published in the journals Radiology and Chest, endorsed by the Radiological Society of North America and the American College of Chest Physicians.
The statement represents the collective opinions and perspectives of thoracic radiology, pulmonology, intensive care, emergency medicine, laboratory medicine and infection control experts practicing in 10 countries, representative of the highest burden of COVID-19 worldwide.
The consensus statement suggests that imaging is not routinely indicated in asymptomatic individuals or patients with suspected COVID-19 and mild clinical symptoms. Use of chest imaging is indicated in patients with COVID-19 who have worsening respiratory status.
Imaging is also indicated for patients with moderate to severe features of COVID-19 regardless of COVID-19 test results.
406: When to go for chest CT

The panel also found that CT is appropriate in patients with functional impairment and/or hypoxemia after recovery from COVID-19. When there is known community transmission, evidence of COVID-19 has been incidentally found on CT scans. In these cases, patients should have COVID-19 testing using reverse-transcription polymerase chain reaction.

407: What is new ICMR testing policy

The Indian Council of Medical Research (ICMR) revised its strategy to fight the spread of coronavirus on Thursday, saying all symptomatic ILI (fever, cough, sore throat, runny nose) patients will now be tested for COVID-19 infection.

Now All symptomatic ILI patients will be tested for rRT-PCR within 7 days of illness and After 7 days of illness Antibody test will be conducted.

408:  what is the percentage positive rate of covid in SARI in India

For five weeks between, February 15 and April 2, ICMR tested 5,911 SARI (Severe Acute Respiratory Illnesses) patients for Covid-19. Of these cases, 104 tested positive (1.8 per cent of those who were tested) and these were from 52 districts in 20 states and union territories.

At least 40 cases (39.2 per cent of those tested positive) didn't have any foreign travel history or any connection with a foreign traveller. These cases were reported from 36 Indian districts in 15 states.
In 15 Indian States, more than one per cent of SARI patients were Covid-19 positive.

Gujarat: 792 SARI patients tested, 13 cases (1.6%) found to be positive for Covid-19

Tamil Nadu: 577 SARI patients tested, 5 cases (0.9%) found to be positive for Covid-19

Maharashtra: 553 SARI patients tested, 21 cases (3.8%) found to be positive for Covid-19

Kerala: 502 SARI patients tested, 1 case (0.2% ) found to be positive for Covid-19

ICMR's overall conclusion on the basis of this report stated, "Covid-19 containment activities need to be targeted in districts reporting Covid-19 cases among SARI patients. Intensifying surveillance for Covid-19 among SARI patients may be an efficient tool to effectively use resources towards containment and mitigation efforts."

409:  COVID and thrombosis more evidences

Systemic clotting problems emerging in severe and critically-ill COVID-19 patients. Disseminated intravascular coagulation has been noted by Chinese physicians on the initial front of the pandemic. Autopsies showing clots in "not only the lungs but also including the heart, the liver, and the kidney," were described on a webinar co-sponsored by the Chinese Cardiovascular Association and American College of Cardiology in March.

410: What is the role of D Dimer and FDP
Elevated D-dimer, a fibrin degradation product indicating thrombosis, at admission has also been linked to substantially higher odds of death in hospital among COVID-19 patients in Wuhan, China.

411: In which parts thrombosis is seen

COVID-19 disease is much associated with thrombosis: large vessel clots, DVT/PE [deep vein thrombosis/pulmonary embolism], maybe arterial events, and potentially small vessel disease, microvascular thrombosis.

412: Can prophylactic anticoagulation prevent

Hospitalized patients often develop blood clots despite being on prophylactic anticoagulation.

413: Whether everybody with COVID-19 in the hospital should be on blood thinners

Fact: The answer is probably yes.

414: Should they be on higher than usual prophylactic doses?

And the answer is possibly yes.

415: Is there a micro vascular thrombosis
Now, full-dose anticoagulation is being considered even if patients don't have documented blood clots, he said, "because it may be microvascular thrombosis in the lung, in the kidneys that lead to pulmonary failure and renal failure and eventually death."

416: What are the guidelines
The International Society on Thrombosis and Haemostasis recently recommended that all hospitalized COVID-19 patients, even those not in the ICU, should get prophylactic-dose low molecular weight heparin (LMWH), unless they have contraindications (active bleeding and platelet count <25×109/L).

417: What are British recommendations
Recommendations from Britain also call for VTE prophylaxis for all high-risk patients as well as considering PE for patients with sudden onset of oxygenation deterioration, respiratory distress, and reduced blood pressure. It suggested LMWH rather than oral anticoagulants, including switching patients who normally take a direct oral anticoagulant (DOAC) or vitamin K antagonist.

418: What are threshold values upon which to start systemic anticoagulation
Fact: Around a D-dimer >1,500 ng/mL and fibrinogen >800 mg/mL, noted Jason Katz, MD, director of cardiovascular critical care at Duke University Health System in Durham, North Carolina.

419: What about heparin
Long chain (unfractionated) heparin would theoretically be preferable among anticoagulants because of their anti-inflammatory effects. While LMWH has less of an anti-inflammatory effect and DOACs have little. And inflammation plays a big role in COVID-19. IV unfractionated heparin also has an advantage in that it can be stopped quickly if bleeding occurs.

420: Is it practical to give twice LMWH

Practical matters may dominate. In New York City, Montefiore and many other hospitals have chosen DOACs.

They don't want the nurses to go into the patients' room to give the unfractionated heparin two or three times a day or to adjust the IV unfractionated heparin. It's much easier to just give an oral anticoagulant with a huge number of patients."

421: What about antiphospholipid autoimmune responses

Three ICU patients with COVID-19 in China showed antiphospholipid autoimmune responses, reported Yongzhe Li, MD, of Peking Union Medical College Hospital in Beijing, and colleagues in a letter to the New England Journal of Medicine published Wednesday. All three tested positive for anticardiolipin IgA and anti-β2-glycoprotein I IgA and IgG.

The presence of these antibodies may rarely lead to thrombotic events that are difficult to differentiate from other causes of multifocal thrombosis in critically patients, such as disseminated intravascular coagulation, heparin-induced thrombocytopenia, and thrombotic microangiopathy.

D-dimer was over 21 mg/L in the first patient, who "had evidence of ischemia in the lower limbs bilaterally as well as in digits two and three of the left hand. Computed tomographic imaging of the brain showed bilateral cerebral infarcts in multiple vascular territories." Lab results also showed leukocytosis, thrombocytopenia, an elevated prothrombin time and partial thromboplastin time, and elevated levels of fibrinogen.

D-dimer was around 3 mg/L in the other two patients, both had multiple cerebral infarctions in the right frontal lobe and other locations in the brain on imaging, and other findings were similar as well.

Lupus anticoagulant was not detected in any of them.

422: How sensitive is  antiphospholipid autoimmune responses
However, Moll cautioned against drawing any causal conclusions, as antiphospholipid antibodies are well known to be transiently positive at the time of acute infectious illness. Also, antiphospholipid antibody titers and lab assay used were not reported.

423: What is the mechanism of microvascular thrombosis

The SARS-CoV-2 virus that causes COVID-19 disease enters cells via the angiotensin converting enzyme 2 (ACE2) receptors. When the virus binds to these cells, it may damage the blood vessel, especially the microcirculation of the small blood vessels, and thus spur platelet aggregation.

424: Is their any autopsy confirmation

Autopsies have also shown inflammatory changes in the heart with fine interstitial mononuclear inflammatory infiltrates, but no viral inclusions in the heart. Other potential mechanisms for the cardiac damage are hypoxia-induced myocardial injury, cardiac microvascular damage, and systemic inflammatory response syndrome.

425: Is thrombosis the major reason for multiorgan failure

If the thrombosis is the major reason for multiorgan failure, then the anticoagulation is really important.

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