Wednesday, April 22, 2020

US FDA uses guidance for Plasma Therapy for COVID 19

Novel Corona Virus Infection has literally halted the world, staying in house will ensure that people protect them selves from getting SARS-CoV-2 ( Novel Corona Virus 19 ) infection.

World is awaiting for a drug that can take care of this virus, and it will take time its own research and development, clinical investigation time period.

US FDA and Indian drug regulatory authority CDISCO have given clearance for using plasma of a recovered COVID 19 (Convalescent Plasma ) patient who is reticently recovered and is doing well, for treating a critically ill COVID19 patient.
This is because recovered patients plasma might have antibodies to fight against the viral infection.
Similar approach was used by a hospital for treatment of EBOLA patient who was a doctor who served in Libia during EBOLA out break.
Also five patients were treated in China with convelsant Plasma and all five were recovered from illness.

US FDA has come up with detail guidance document which might be very helpful to world for starting this novel therapy for COVID 19, even doctors in India may get helpful information about Plasma Therapy.
Here is the link for US FDA Guidance document Plasma Therapy for COVID19 Patients

Such therapies are easy to handle and execute in isolated one cases, but in this global out break a clear and crisp guidance issued by USFDA will be very helpful.
 This treatment in U S is required to be done through the process of Investigational New Drug Application.(INDA) regulatory pathway (21 CFR Part 312,305).
In USA hospitalized patients above age of 18 and who have following conditions are eligible for convalescent plasma with informed consent. Collection of plasma to be done by method of apheresis.

Apheresis is a medical technology in which the blood of a person is passed through an apparatus that separates out one particular constituent and returns the remainder to the circulation.

Plasma must be ABO compatible with the recipient’s red cells and about 200 ML to 250 ML of Plasma to be administered to patient rate of 100 to 250 mL/hr.
Pre medication required to be given to patient is Acetaminophen to take care of elevation in temperature and Diphenhydramine as antihistamine drug to control allergic reaction during infusion of Convalescent Plasma to COVID 19 Patient.

Severe COVID-19 is defined by one or more of the following:

Shortness of breath (dyspnea)
Respiratory frequency ≥ 30/min
Blood oxygen saturation ≤ 93%
Partial pressure of arterial oxygen to fraction of inspired oxygen ratio < 300 Lung infiltrates > 50% within 24 to 48 hours

Life-threatening COVID-19 is defined as one or more of the following:

Respiratory failure
Septic shock
Multiple organ dysfunction or failure.

All plasma products are required to be labeled in a manner to allow traceability for the
purpose of infectious disease testing, identification and if necessary recipient notification.

Donor plasma must be tested for presence of infectious disease transmitted through blood to blood contact.

Following is the requirement of blood Plasma to comply tests.

Negative Anti-HIV-1/2
• Negative Anti-HTLV-I/II
• Negative Anti-HCV
• Negative HBsAg
• Negative for anti-HBc
• Negative serologic test for syphilis
• Negative anti-T. cruzi or history of a negative test if a previous blood donor
• Negative testing for Babesia or a history of a negative test for Babesia, depending
upon geographic residency of the donor. (Note: This testing is required in
beginning May 4, 2020. Residents of endemic areas are tested with each
• Negative West Nile Virus (WNV) NAT
• Negative HCV NAT
• Negative HIV NAT
• Negative HBV NAT
• Negative Zika NAT

Risk Evaluation: 
Do not use FFP if there is evidence of container breakage or of thawing during storage. FFP must be thawed in a waterbath at 30-37C or in an FDA-cleared device. If a waterbath is used, thaw the component in a protective plastic overwrap using gentle agitation.
Transfusion-related acute lung injury (TRALI) may occur, but this risk will be minimized
by using male donated plasma or female donors who have not been pregnant or female
donors who have been tested since their most recent pregnancy and results interpreted as
negative for HLA antibodies.. TRALI is characterized by a clinical constellation of
symptoms including dyspnea, hypotension and fever. Although the precise pathogenesis
of TRALI remains unknown, it has been shown to be most often related to the transfusion
of anti-HLA and anti-neutrophil antibodies from plasma from multiparous women
(antibodies presumably generated during pregnancy) or donors who have received
multiple blood transfusions. The risk of TRALI is reported as 1 out of 5000

Each unit of plasma contains 200-400 mL of volume. Depending on the total volume
infused, there is the risk of volume overload in the recipient that could cause pulmonary
edema. Transfusion-associated circulatory overload (TACO) has been associated with
plasma infusion and may be clinically indistinguishable from TRALI even though the
physiologic mechanisms differ. TACO is hydrostatic not permeability edema and
more responsive to diuresis when it occurs. Subjects with preexisting conditions who
may not tolerate this volume of plasma will be excluded from this study, but this
condition could still occur in recipients.

There are case reports of pulmonary emboli occurring after administration of IVIG and
plasma therapy, though definitive studies assessing risk are lacking.
Pulmonary emboli have been shown to develop in approximately 10-15% of critically ill adults.
However, the potential risk of pulmonary embolism exists.

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