Hypercoagulability in COVID19 Patients pt. 2

Clinical observation and management of COVID-19 patients.

Li T, Lu H, Zhang W

DOI: 10.1080/22221751.2020.1741327

Disclaimer: This is a summary of the highlights of this article, I do not own any or endorse any of the findings within this article. This is for educational purposes only and a full link for further review is included.

Key Highlights:

• 3 leading infectious disease experts in China shared their bedside observations in the management of COVID19 patients

  • Prof. Taisheng Li: sent to Wuhan to provide frontline medical care

    • Observed significant abnormalities of coagulation function

    • Proposes early IVIG and low molecular weight heparin anticoagulation therapy are very important

• Prof. Hongzhou Lu: leader in China to try various anti-viral drugs

  • Concern on the quality of ongoing clinical trials due to small size, repetitive nature

  • Important to have quick publication of clinical trial results

• Prof. Wenhong Zhang: responsible for Shanghai’s overall clinical management of COVID cases

  • Introduces team approach to manage COVID patients

  • For severe or critically ill, add:

    • respiratory supportive treatment

    • timely multi organ evaluation and treatment

Key Points:

Professor Taisheng Li Observations (sent to Wuhan from Beijing to be frontline)

• Based on his observations in treating severe and critically ill patients in ICU: proposes that IVIG and LMWH anticoagulation therapy are very important.

• Clinical Course:

  • Virus enters the body and causes viremia.

    • Main clinical presentation: fever, pharyngalgia, fatigue, diarrhea, other non-specific symptoms

    • Incubation: typically 1-14 days (3-7 days is most common)

      • Peripheral blood leukocytes and lymphocytes may be normal or slightly low at this time

• Virus spreads to bloodstream and mainly to the lungs, GI tract, and heart.

  • The virus is thought to be concentrated in tissues expressing ACE2

  • This phase occurs around 7-14 days after symptom onset which is when the virus causes a 2nd attack.

    • This is thought to be the main cause of symptom aggravation.

    • Pulmonary lesions get worse and chest CT scans show imaging changes consist with COVID19

    • Laboratory findings:

      • Peripheral blood lymphocytes decrease significantly –> involving both T and B lymphocytes.

      • Inflammatory factors in peripheral blood are increased.

Abnormal Coagulation Status:

• Patients develop a hypercoagulable state and D-Dimer based coagulation appear abnormal.

• Management strategies:

• Use of IVIG will provide patients with effective clinical benefits and inhibit formation of inflammatory factors storm (“cytokine storm”).

• Use of LMWH may also alleviate the hyper coagulable state

• During development of SOB and when the chest imaging worsened:

• D-dimer increased from mild to significant

• Prolonged PT

• Gradual increase of fibrinogen and platelets

• Some non-survivors were seen to have suffered from ischemic changes:

• Ecchymosis of fingers and toes at the same time that the organ functions of the heart and kidney worsened.

• This is consistent with the diagnosis of the hypercoagulable phase of DIC.

• It is believed that COVID19 can activate coagulation cascade through various mechanisms.

• Early anticoagulation may block clotting formation and reduce micro thrombus and potentially reduce the risk of major organ damages.

Professor Hongzhou Lu’s Observations (leader in China to try various anti-viral drugs to treat COVID19)

• Considering clinical and epidemiological characteristics of COVID, need effective medications to improve prognosis and stem virus spread.

• Trials are subject to all kinds of practical limitations: majority of trials are small in scale and repetitive in nature.

• World Health Organization (WHO): shown deep concern over quality of these clinical trials and has provided guidance

• Research design: testing drugs are selected mainly based on past experience of these drugs treating other related diseases.

  • Effective and relatively safe medications can be coordinated to the large-scale and multi-center clinical trials to avoid a bulk of repetitive trials

  • Another reality situation is that the National COVID Treatment Guideline has been updated multiple times to include possibly effective drugs and experts offering new medical suggestions.

    • Medical workers in the trials usually take consideration of national guidelines so the intervention group might be covered by a variety of anti-viral meds since its difficult to leave a control group blank.

    • Specific effects of testing medication can’t be verified.

    • Even though current clinical studies aren’t as rigorous as the traditional clinical trials – they help draw initial results

    • Its important to motivate quick publication of clinical trial results.

Professor Wenhong Zhang’s Observations (leader in China to try various anti-viral drugs to treat COVID19)

• In Shanghai there are more than 330 lab-confirmed adult cases of COVID and most (>90%) are mild-moderate and more than 90% of these have been cured

• Since no specific drugs have shown any effectiveness in clearing the virus – the disease severity rate objectively reflected the natural history of the virus.

• All critically ill patients received invasive mechanical ventilation and 6 patients received extracorporeal membrane oxygenation (ECMO).

  • In addition to the involvement of the lungs, critically ill patients had systemic involvement of multiple organs like the heart/kidney/coagulation system in early disease course.

  • Sometimes at the time of initial hospital admission, there was multi-system involvement.

    • Therefore, its important to have timely multi organ evaluation + treatment in addition to have respiratory supportive treatment.

• Every critically ill patient in Shanghai is managed by a team of:

  • Pulmonologist

  • Infectious disease expert

  • Critical care specialist

  • ECMO specialist (if necessary)

• Mild patients are more alike but severe cases are severe in their own way.

  • Might be multiple pathophysiological mechanisms in these critically ill patients.

• Early and effective treatment of mild cases is critical.

  • Once the disease course progressed to critically illness state (requiring mechanical ventilation) –> the prognosis of the patients became significantly worse.

  • Treatments that can prevent mild state from progressing can significantly improve the overall prognosis of the clinical courses.

• Effective treatments include:

  • Intermittent short term hemofiltration

  • Low-dose glucocorticoid therapy

    • Controversial but based on their experiences, stably mild patients can self-manage infection effectively and corticosteroids would not be recommended due to potential risks

    • If patients have overly exuberant inflammatory response or at a high risk of ARDS: might be helpful to have an early-start of corticosteroid

    • Use of corticosteroids as rescue treatment is doubtful.