Lack of oversight leaves COVID-19 patients scrambling for plasma

Donors give plasma at the Delhi Plasma Bank, for Covid-19 patients who will receive the trial antibody treatment, at the Institute of Liver and Biliary Sciences (ILBS) hospital in New Delhi. India's coronavirus epidemic became the third biggest in the world as infections surged after the nation eased containment measures to reverse an economic collapse that has left millions destitute. T. Narayan / Bloomberg / Getty Images
17 August, 2020

In mid-July, the family of a 74-year-old male COVID-19 patient at Patna’s All India Institute of Medical Sciences was in a bind. The patient was already critically ill and had been put on ventilator support. With his condition starting to further deteriorate, his doctors said that he needed convalescent plasma therapy urgently. The family first assumed that the hospital would organise this medically prescribed plasma. The patient’s son-in-law said in a phone call from Mumbai, “We first thought the blood bank will organise plasma themselves and we will have to pay for it.” They were in for a rude shock—the hospital expected them to find plasma themselves.

More and more, doctors across India have started to prescribe convalescent plasma therapy, commonly known as simply plasma therapy, for severely ill COVID-19 patients. Plasma is taken from a person who has recovered from a disease—a convalescent—because it contains antibodies to fight the disease. It is then injected into a patient still ill with the same disease whose own immune system may not be producing antibodies. Theoretically, it should jumpstart an antibody response in the patient. Even though it has been used as a medical intervention to treat other infectious diseases in the past, there is little scientific evidence to show that it helps COVID-19 patients. Results of most clinical trials for plasma therapy, including in India, have not yet been released, but a major trial in China showed plasma therapy had no significant effect on patients. 

But since the world has had just eight months of experience with this disease, doctors are deploying plasma and several other drugs as experimental tools to keep their patients alive. 

Dr RS Mishra, the director and senior consultant for internal medicine at Max Super Speciality Hospital in Delhi, said, “Our experience is that plasma therapy works if it is used at the right time. If it is used late when there are already antibodies in the system, the therapy will not work. If you give plasma after 15 to 16 days, the patient is already producing antibodies. Timing is very important.”

With only vague guidelines and little regulation, patients and their families are facing the added undue burden in the middle of a pandemic of trying to procure plasma. All patients who need plasma therapy have specific requirements. The Patna patient needed plasma from a donor who had recovered from COVID-19 at least 14 days earlier, and had his blood type, O positive. Neither his wife nor his daughter-in-law, who lived with the couple, could figure out where to source plasma. The family turned to relatives and friends in Mumbai to find plasma donors. This network of relatives and friends, the son-in-law said, called more than a hundred people. 

“We frantically posted in our friend groups on all social media, and contacted as many people as possible,” said the patient’s son-in-law. “We got two people who are complete strangers to us to donate plasma.” The family had a hard time roping in these two strangers, who felt that donating plasma could lower their own immunity. After many long conversations, the family persuaded them to part with some plasma, only to find that one was medically ineligible to donate.

Plasma therapy has historically been used as experimental therapy. Its potential was first identified in treating Spanish influenza, which tore across the world between 1918 and 1920. It then was tried as treatment for measles, mumps, chickenpox and various types of influenza. Recently, it was used to treat Ebola patients in West Africa, a disease for which, like COVID-19, there was no proven drug or vaccine. During the COVID-19 pandemic too, plasma therapy is being used on an experimental basis in many countries.  

The treatment found legitimacy in public imagination after Satyender Jain, Delhi’s health minister, recovered from COVID-19 after receiving plasma. Arvind Kejriwal, Delhi’s chief minister, then attributed a fall in the number of COVID-19 deaths in the city to the fact that its Lok Nayak Hospital started using plasma therapy. A few days later, the Delhi government started the country’s first plasma bank in the country at the Institute of Liver and Biliary Sciences, followed by a second one in Lok Nayak Hospital.

Plasma is a blood product and all blood products are essential medicines that can save millions of lives in both routine and emergency medical situations, especially during surgical interventions. These are especially important for people with blood-disorders like thalassaemia and sickle cell disease, who need regular blood transfusions to survive. Blood platelets are given to people with severe dengue fever whose platelets dip to dangerously low levels. Therefore, every country needs a system to ensure blood and blood products are available where they are needed. In India the National Blood Transfusion Council is the central body that develops policies and programmes for blood donation and banking. But the council and its guidelines have failed to curb unethical practices in blood donation. 

For example, replacement blood donation is widely practiced in India. Here, a patient needing blood is asked to find donors to replace the quantities of blood or blood product that he is using. 

This goes against the World Health Organisation’s recommendation that blood donation should be voluntary and non-remunerated. This means that a donor should not be forced or incentivised to donate. 

The WHO observes that replacement donation often has hidden payment systems or involves coercion, and increases the chances of transfusion-transmissible infections. While India’s National Blood Policy discourages replacement donation, there is no law that prevents the practice. As a result, replacement blood donation in India is as high as forty percent of all donated blood and only sixty percent is voluntary, according to Dr Sunil Gupta, the director of the National Blood Transfusion Council. This has led to hospitals absolving themselves of the responsibility of making sure that they have access to enough banked blood through voluntary donation. Crucially, it puts the entire responsibility of finding donors on patients and their families, putting them under severe stress. 

The problems of replacement blood donation are now being repeated with plasma donation for COVID-19. Even the establishment of dedicated plasma banks in some cities has not eased the pressure on patients. Plasma banks in Delhi, for instance, also seek replacement donations. In fact, on 11 August, the Delhi government ran a full- page newspaper advertisement promising free plasma to any COVID-19 patient who needs it but also requesting hospitals and patients to arrange replacement donors or sign an undertaking to provide such replacements at the earliest. The only relief here is that patients’ families can get a unit of plasma in exchange for a donor with any blood group, not necessarily the one that matches the patient.

I spoke to family members of 12 patients in Delhi, Hyderabad, Patna and Kanpur, and all of them were asked to find donors for the patients themselves or provide replacement plasma before receiving banked plasma. Most had  been asked to get more than one donor, even more so when the patient was given two or three units of plasma instead of the standard one unit.  All this for a therapy that is experimental and has not yet been proven to work against COVID-19.  

Gupta said that the National Blood Transfusion Council has little power to regulate processes involving blood donation. He said, for example, “It is the DCGI”—the Drugs Controller General of India, the government body that approves licences for drugs, vaccines and blood products —“which has the teeth to suspend the license of a blood bank. We can only advise them and request them to follow guidelines.”

India has always had a shortage of blood supply largely due to a poor culture of voluntary blood donation. This shortage of blood and plasma has been exacerbated in the pandemic, especially because of lockdowns in March and April. What makes it harder to find plasma are the multiple conditions for donation. The donor has to be a COVID-19 convalescent who has tested negative for at least two weeks, who is not underweight, who is not on certain kinds of medications, whose blood pressure is normal and who has not had cancer. Women who have ever been pregnant cannot donate plasma since they usually have potentially harmful antigens.  Besides, the plasma needs to have an adequate volume of COVID-19 antibodies, which all donors may not have. This has driven COVID-19 patients and their families to sheer desperation, even reportedly resorting to a black market and being duped by people posing as donors.   

After the COVID-19 pandemic began, the National Blood Transfusion Council issued two sets of guidelines related to safe blood donations but nothing in specific about convalescent plasma donation. The guidelines released on 25 June state that the council will issue guidelines for plasma therapy if efficacy of the treatment is established. 

The regulatory vacuum has left many patients scrambling for plasma. While a state government can organise convalescent plasma drives either by contacting COVID-19 recovered patients or counselling them as they recover, a patient’s family has no way to find a convalescent except asking family and friends. 

A lawyer in Gurgaon whose husband was critically ill with COVID-19 said that even her friends who had recovered from the disease were reluctant to donate plasma. “When I contacted them, some told me that if I do not get anyone else to donate, they will help,” she said. “That is why I choose to look for people who I had no connection with.” She found three donors, one through Dhoondh, a website that claims to connect COVID-19 patients with plasma donors. 

The family of a 57-year-old businessman with COVID-19 in Kanpur obtained a list of COVID-19 patients from a government hospital and called each person to find donors. “About ten to fifteen people in my family and friends’ circle started calling the people in the list,” the businessman’s brother-in-law said. “Some said they were too weak, or said they do not want to go to a laboratory. Some who were ready to help us would be dissuaded by their families.” The businessman succumbed to the disease on 3 August. Another patient’s relative told me he procured a list of COVID-19 patients from a government official. These under-the-radar practices violate COVID-19 patients’ privacy and the principles of confidentiality. 

In Hyderabad, the businessman Piyush Mehta said it took him about four days to arrange two donors for his 46-year-old sister. She was hooked to a ventilator and had already been administered the steroid dexamethasone—the only drug foundto have significant benefits for COVID-19 patients—and other experimental medicines such as remdesivir and tocilizumab. With no improvement in her condition, the doctors turned to plasma therapy. “We must have spoken to at least 4,000 people,” he said. His sister died in the first week of August. Mehta said, “I sometimes think about what went wrong in my sister’s case and feel that we got delayed in getting plasma.”

Often blood banks take at least a few hours to clear the formalities of testing and extracting plasma. Donors for the Patna patient had to wait two days for the blood bank to extract plasma as there was reportedly a massive shortage of staff. 

“One of the biggest issues ethically is that the medical fraternity is seeking donation for a therapy that has very little evidentiary value,” Dr Sanjay Nagral, a surgical gastroenterologist and member of the editorial board of Indian Journal of Medical Ethics, said.

Dr Meenu Bajpai, who is in charge of Department of Transfusion Medicine at Institute of Liver and Biliary Sciences, said that the institute gets between 25 and 30 donors everyday, of which at least half are replacement donors. “In the initial days of the pandemic, my team called over 900 recovered patients from a list of people who had been COVID-positive people in the city,” she continued. “Only 30 donors turned up, of whom 15 were eligible and finally donated. Some were extremely upset over the repeated calls they were getting for plasma donation.” 

Bajpai is of the opinion that it is difficult to manage the demand for plasma without some sort of replacement donation, though the response is getting better with the increased awareness. Delhi’s Lok Nayak Hospital, for instance, gets about five to ten voluntary walk-in plasma donors, said Dr Sunil Kumar, who handles the blood bank there.

Activists who work towards increasing voluntary blood donation in the country said that seeking replacement of convalescent plasma is unacceptable. “In short, the government and the hospitals are saying that they will not try a treatment unless you get a donor,” Vinay Shetty, the vice president of Think Foundation in Mumbai, a non-profit organisation that works to help thalassaemia patients get blood transfusions, said. “This coercion only fosters corruption.”

In some cases, state governments have introduced policies to invite plasma donors, though the ethics of such policies are suspect. In July, the Karnataka government announced an incentive of Rs 5,000 to anyone donating plasma, which is against Rule 122-P of the Drugs and Cosmetics Act, 1940, which explicitly prohibits collection of blood or blood products from a paid or professional donor. Since the beginning of the pandemic though, only 15 people have come forward in the state to donate plasma, of whom only nine were eligible. Dr R Sreelatha, a professor of immuno-hematology and blood transfusion at Bengaluru’s Victoria Hospital, said that the announcement was misguided. “I worry that the blood donation will not be considered voluntary because of the announcement,” she said. She added that despite the announcement, donors have not received remuneration and some donors had explicitly asked about it. 

Dr Gupta distanced the National Blood Transfusion Council from the Karnataka government’s policy, saying that since health is a state subject, the council did not have much role to play. Andhra Pradesh has also started a scheme to incentivise donors and Bihar is reportedly considering a similar policy. 

While Karnataka is paying donors, other states are charging patients for plasma. The Punjab government recently announced that it will charge a steep Rs 20,000 per unit of plasma for patients in private hospitals. This is even more than the cost at private hospitals in other parts of the country, which is about Rs 16,000 per unit. The National Blood Transfusion Board laid out in its guidelines in 2017 that the processing fee for collecting plasma can be up to Rs 500. This is for plasma obtained by separating it from donated blood. Doctors are using a different process to get plasma for COVID-19 called apheresis, where a donor’s blood is circulated through a machine that separates out plasma, and the rest of the blood is returned to the donor’s body. This is a costlier process because of the technology used. But in the absence of any guidelines or regulation both private hospitals and state government are free to decide the cost of plasma.  

These state-level policies expose the regulatory vacuum in convalescent plasma donation for COVID-19 patients, according to activists. Rajat Agarwal who runs Sankalp India Foundation that works towards voluntary blood donation in Bengaluru said that the government should counsel COVID-19 convalescents discharged from hospital to donate plasma and perhaps even set up a call centre to help coordinate plasma donations. Summarising both problem and solution in a single line, Patna patient’s son-in-law said, “The government should be arranging for plasma and should not be waiting for the patients’ relatives to organise it. Despite his family’s efforts and getting plasma therapy, the Patna patient died earlier this month.