Blood Banks
Convalescent plasma, combating COVID-19
Further investigation is necessary to determine if convalescent plasma is safe and effective as a treatment for COVID-19, and whether it might shorten the duration of illness, reduce morbidity, or prevent death associated with COVID-19.
Increase in per capita income and changing lifestyles (especially food habits) have resulted into rise in prevalence of diabetes, heart attack/stroke, cancer, and other life-threatening diseases. Components in the blood are used to treat these blood-related diseases. Presently, when blood is donated, it is separated into three components – plasma, red blood cells, and platelets. Plasma is generally used to increase blood volume or it can be separated into individual plasma proteins such as fibrinogen, factor VIII, anti-thrombin III, and factor IX. Separation of plasma components is called plasma fractionation. Moreover, plasmapheresis therapy removes pathogenic factors from patient’s blood/plasma by extracorporeal circulation. These separators and fractionators have hollow fiber membrane, in which desired plasma component is separated.
Currently, there are no vaccines for SARS-CoV-2. But people who are recovering from the disease will have antibodies against the virus. So, what experts are doing is, they are taking some of the part of blood, which will have these antibodies, and give it to patients who are sick and hope that these anti-bodies will protect them. Now, this sounds good in theory, but doctors do not know how far it will work in reality.
Researchers in China have been experimenting with using blood plasma from patients, who have recovered from COVID-19, as a possible way to treat severely ill COVID-19 patients. In a new study published in the Proceedings of the National Academy of Science, clinicians reported that convalescent plasma therapy improved the outcomes of ten patients with severe cases of COVID-19.
Plasma therapy is a known concept, which has existed for more than 100 years. ICMR started the discussion for a trial on convalescent plasma on March 25, 2020.
At the moment, while researchers are exploring a number of experimental therapies and drugs, regulatory bodies have not approved any specific antiviral agent to treat COVID-19.
On May 1, 2020, USFDA has issued guidance to provide recommendations to healthcare providers and investigators on the administration and study of investigational convalescent plasma collected from individuals, who have recovered from COVID-19 (COVID-19 convalescent plasma) during the public health emergency.
The guidance provides recommendations on: pathways for use of investigational COVID-19 convalescent plasma; patient eligibility; collection of COVID-19 convalescent plasma, including donor eligibility and donor qualifications; labeling; and record keeping. Because COVID-19 convalescent plasma has not yet been approved for use by USFDA, it is regulated as an investigational product. A healthcare provider must participate in one of the pathways described below. USFDA does not collect COVID-19 convalescent plasma or provide COVID-19 convalescent plasma. Healthcare providers or acute care facilities should instead obtain COVID-19 convalescent plasma from a USFDA-registered blood establishment.
There is no scientific evidence that convalescent plasma works. Only randomized controlled trials can ascertain whether a particular drug works in a particular disease or not.
Currently, there are more than 20 clinical trials being conducted worldwide using convalescent plasma.
On May 7, 2020, the Indian Council of Medical Research (ICMR) has approved 21 institutions for participating in a randomized controlled study to assess the safety and efficacy of convalescent plasma to limit complications associated with COVID-19. The multi-center trials would be conducted on 452 patients across centers. ICMR’s project is called PLACID – Phase-II open-label randomized controlled trial to assess the safety and efficacy of convalescent plasma to limit COVID-19-associated complications in moderate disease. The study has received approval from the COVID-19 National Ethics Committee (CONEC) and the generic protocol was approved by the Drug Controller General of India.
Medical facilities, which have been given the approval to be a part of the trial, include Postgraduate Institute of Medical Education and Research, Chandigarh; Madras Medical College, Chennai; Smart NHL Municipal Medical College, Ahmedabad; BJ Medical College and Civil Hospital, Ahmedabad; Sawai Man Singh Medical College, Jaipur; Government Medical College, Nagpur; Gandhi Medical College, Telangana; and Gandhi Medical College, Bhopal.
About 90 hospitals, including seven in Delhi, are under consideration for participating in the clinical trials. Hospitals in the capital, which are awaiting approval, include AIIMS, Indraprastha Apollo, Batra Hospital and Medical Research Centre, Lady Hardinge Medical College, RML Hospital, Max Hospital-Saket, and Indian Red Cross Society.
As of May 27, 2020, the ICMR does not recommend this as a treatment option outside of clinical trials. The Union Health Ministry recently warned against its use, saying that plasma therapy for the treatment of coronavirus patients is at an experimental stage, and has the potential to cause life-threatening complications.
Going forward, further investigation is still necessary to determine if convalescent plasma is safe and effective as a treatment for COVID-19, and whether it might shorten the duration of illness, reduce morbidity, or prevent death associated with COVID-19.
Global market
The global apheresis market is projected to reach USD 2.7 billion by 2025 from USD 1.7 billion in 2019, at a CAGR of 8.1 percent, as per MarketsandMarkets. The rising prevalence of chronic diseases and the growing number of trauma and injury cases, the rising demand for blood components and growing concerns regarding blood safety, and the favorable reimbursement for apheresis procedures are the major factors driving the growth of this market.
The disposable segment is expected to grow at the highest CAGR, by products. This growth can be attributed to its recurrent use, increasing blood donations using apheresis devices, an increasing number of therapeutic apheresis procedures, and favorable reimbursement policies for apheresis procedures.
Based on application, the apheresis market is segmented into plasmapheresis, plateletpheresis, erythrocytapheresis, leukapheresis, and photopheresis. Photopheresis is expected to grow at the highest CAGR. The high growth of this segment can be attributed to the increasing prevalence of blood disorders, and the rising demand for photopheresis in organ transplant rejection treatment.
North America accounted for the largest share of the apheresis market in 2019, followed by Europe. The large share of this region can be attributed to easier accessibility to advanced blood collection technologies, the presence of established healthcare infrastructure, and the increasing presence of leading apheresis companies in the country.
The prominent players operating in global apheresis market include Terumo BCT, Fresenius SE & Co., Haemonetics Corporation, Asahi Kasei Medical, B. Braun Melsungen, Baxter International Inc., Cerus Corporation, Kaneka Corporation, Kawasumi Laboratories, Nikkiso Co. Ltd., Macopharma SA, Miltenyi Biotec, Otsuka Holdings Co., Medica S.p.A., Mallinckrodt plc, Medicap Clinic GmbH, Lmb Technologies GmbH, Bioelettronica, Infomed, Cytosorbents Corporation, and Toray Medical Co. Ltd.
Outlook
It is inevitable that completing any trials of therapy in a pandemic is a race against time during the pandemic. Although many measures are being put in place to control the epidemic, it is almost inevitable that the multiplication of the virus will increase, and it seems likely that there will be a long tail of cases and quite probably a resurgence of the infection in the coming months allowing completion of the trials and experts hope definition of possibly the first, but hopefully by no means the last, effective therapy for COVID-19.
In the year ahead, the data will be combined with the results of other clinical trials and also with the analysis of collection, use and outcome of convalescent plasma across the world to provide recommendations for the collection and use of convalescent plasma in this and future epidemics.
The use of convalescent plasma may be the first of many therapies and preventive measures for COVID-19, although at the present time with the first wave of the pandemic just past us, this seems almost too much to hope for. Vaccines are yet to be tested in earnest, but some scores of different vaccines are being developed and some have completed preliminary safety studies. While the success of any one immunotherapy or vaccines or drug is not guaranteed, one may be stepping slowly but surely along a path to the beginning of the end of this pandemic, and be better prepared for the next one.
Second Opinion
Dr Suman Hegde
Pathologist & Blood Bank Officer,
Manorama Diagnostic Centre
Plasma separators
The desirability of separating blood cells and plasma from each other for therapeutic and investigative purposes must have been recognized very early in the history of medicine. The success in this endeavour was largely confined to ex vivo separations until the need for large scale separations in donors and patients was appreciated by biomedical engineers and clinicians, which led to the present innovation of plasma separators.
One method of separating plasma is to collect whole blood initially in double/triple bags of 350 mL/450 mL capacity, centrifuge, separate plasma from RBCS and platelets, and transfer all of them separately in individual bags. The other method of obtaining plasma is by apheresis (plasmapheresis). Aphaeresis is a procedure where required single or more than one component are collected and the rest of the blood components are returned back to the donor. The working principle of apheresis equipment is either centrifugation (different specific gravity) or filtration (different size). The most commonly used equipment use the centrifugation principle. In this method, a fixed quantity of blood is collected in a bolus called extra corporeal volume (ECV) and the required component (like plasma) is separated, collected in collection bag, and the other component (e.g., red blood cells, leucocytes, and platelets) are returned back to the donor. Centrifugation apheresis equipment is classified as intermittent and continuous working. The intermittent equipment uses single-vein access for both collection and return. One cycle consists of one ECV whole blood collection in kit bowl, centrifugation of blood to separate components, collection of required component (plasma) in collection bag, and finally return of other constituents to the donor. The cycle is repeated till the therapeutic dose is attained. In the continuous-working equipment, two simultaneous phlebotomies are done – one for collection and the other for return. The collection, centrifugation, component collection, and return occur continuously and simultaneously. Each type has its own advantage and limitation. The ultimate goal of the procedure is not to overshoot ECV collection to more than 15 percent of the total blood volume. In the market, multi-component collection system (MCS+) is available that is portable, extremely user-friendly, and reliable with low failure/breakdown. Automated blood component separators with MCS 3P cell separators are available that provide buffy coat poor plasma and red cells. In the wake of Corona-19 pandemic, plasma therapy is under trial, and hence the plasma separators assume a lot of importance.
