Friday, February 23, 2024

Plasma Therapy: Not a Magic Cure

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While the therapy has been touted as a remedy for corona, there can be transfusion reactions or the disease worsening. This includes acute lung injury or acute respiratory distress

By Dr KK Aggarwal

A 47-year-old woman, who was the first Covid-19 patient to receive plasma therapy at Sassoon General Hospital in Pune, tested negative for the disease. ICMR has now given permission to many government and private hospitals to use plasma therapy for off-label use in Covid-19 conditions.

Convalescent plasma refers to the plasma component of blood from an individual who has recovered from corona. It is experimental for Covid-19 patients and involves intravenous transfusion of plasma from a recovered patient to a critically ill patient early in the illness. It is a readymade antibody transfer to provide passive immunity (through neutralising antibodies or possibly other immune mediators directed against the infectious pathogen) until the individual can develop an active immune response, with the hope that clinical outcomes can be improved.

Imagine a house being attacked by thieves. The thieves are equivalent to viruses. In this case, corona viruses. The first response of those in the house will be to call a PCR van, which can be compared to the PCR test. The PCR van will file an FIR and leave the place, informing the local police to act. The local police in the case of the coronavirus, takes a week to reach. During this period, the house inmates themselves will try to fight the thieves using their personal security and that is called inmate passive immunity.

In case we find that our personal security is not able to fight the thieves, we are at liberty to hire personal security from anyone who has faced similar viruses in the past. Hiring that personal security from a person who has recovered from a virus is called plasma therapy. It will, therefore, only work till the local police or IgG and IgM antibodies arrive.

Convalescent plasma is not routinely available, nor is it a licensed FDA or Drug Controller General product. Instead, it has been made available for specific agents at times of disease epidemics or pandemics. Once an epidemic has subsided, convalescent plasma is likely to become unavailable.

The criteria for optimal preparation of plasma (or hyperimmune globulin) include a high titer of neutralising antibodies. Donors should be negative RT PCR; the blood group should match; male donors or female donors who have been pregnant, should have negative testing for anti-HLA antibodies; evidence for efficacy and lack of harm and informed consent with discussion of the risks and benefits of therapy told to them.

Two weeks after a person has been declared antigen negative, he can donate 400-500 ml of plasma and the same can be used for 2-3 patients. A donor can donate again after an interval and ultimately be able to help 8-10 patients. Related products include convalescent serum (contains antibodies but not clotting factors) and hyperimmune globulin (a manufactured concentrated product containing a high titre of antibodies).

Convalescent plasma (or hyperimmune globulin) could, in theory, be used to improve the clinical course of the disease in affected individuals or to reduce the risk of developing disease (eg, post-exposure prophylaxis). However, the risk of transfusion reactions or disease worsening must be considered in the risk-benefit analysis. Monoclonal antibodies with neutralising potential are other options. Plasma can be obtained via apheresis or whole blood donation. Apheresis is preferred because this optimises the yield (two to four units of plasma can be obtained per apheresis donation).

So how does plasma therapy work for other viral infections? In SARS-CoV (2003 SARS epidemic), there was reduced mortality (of the order of seven to 23 percent lower mortality). There was reduced stay in hospital, especially when convalescent plasma was administered within two weeks of the onset of symptoms. No major complications were reported.

In the case of MERS-CoV (2012 outbreak), no clinical studies were identified, although animal models suggested there might be a benefit. In the case of the H1N1-pdm09 (2009 pandemic), a study reported an 80 percent reduction in mortality, especially with early treatment. There was a reduced stay in the ICU. No major complications were reported. In H5N1 (avian influenza), non-significant benefits were found. In the H1N1 (1918-19 flu epidemic), there was reduced mortality (approximately 20 percent reduction), according to another meta-analysis. These studies used convalescent blood rather than plasma; chills, fever, and sweats were reported following the infusions.

A patient with type A blood can accept plasma from donors who are type A (identical) or type AB (compatible); a patient with type B blood can accept plasma from donors who are type B (identical) or type AB (compatible); a patient with type O blood can accept plasma from donors who are type O (identical) or types A, B, or AB (compatible) and a patient with type AB blood can only accept plasma from donors who are type AB (identical).

Plasma is derived from the human blood and therefore carries an infectious risk. The risk of most transfusion-transmitted infections is approximately equivalent for a transfusion of a unit of plasma as it is for a unit of red blood cells, with the exception of a lower risk of transmitting intracellular viruses. Plasma is basically a cellular blood component.

But plasma can lead to adverse reactions in some cases. Infusion of large amounts of plasma or other blood products may cause volume overload and precipitate pulmonary edema, especially in older adults, small children, and those with pre-existing cardiac disease. This can be avoided by reducing the rate of infusion to 1 mL/kg per hour in susceptible patients. Infusion of plasma is also associated with allergic reactions, fever and chills. These should be treated symptomatically.

Anaphylactic reactions following transfusion of plasma may occur in patients with IgA deficiency and antibodies to IgA. Transfusion-related acute lung injury (TRALI) is a rare, but potentially fatal, complication of blood product transfusion. It is characterised by new acute respiratory distress (eg, hypoxemia, infiltrates on chest radiography) within six hours of transfusion. As one of the mechanisms of TRALI is transfusion of donor antibodies directed against recipient HLA or neutrophil antigens, a worldwide approach to TRALI prevention involves preparing plasma components for transfusion from either male donors or female donors who have been screened and found not to have antibodies to HLA class I or class II antigens.

Because of these safety concerns, plasma therapy is not indicated in asymptomatic and mild cases. 

—The writer is President, Confederation of Medical Associations in Asia and Oceania, and former National President, IMA

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