What Tests Are Done on Donated Blood? FDA's 5-Layer Safety System

How the US Blood Supply Is Protected

The United States blood supply is protected through a multi-layered system that goes far beyond a single test. The FDA oversees blood collection, testing, and distribution — and has established five distinct safeguards that work together to reduce the risk of transfusion-transmitted infections.

Testing standards in the US are determined by a combination of tradition, scientific evidence, cost considerations, and local conditions — with the FDA setting the floor that all blood banks must meet.

The FDA’s 5-Layer Blood Safety System

No single safeguard can catch every risk. The FDA’s system is designed so that multiple independent layers must each fail before a contaminated unit reaches a patient.

Layer 1: Donor Screening

Before a single drop of blood is collected, donors complete a detailed health and lifestyle questionnaire. The answers determine whether the donor is eligible to give on that day or must be deferred — temporarily or permanently.

Questions cover:

• Recent illnesses, surgeries, or medical treatments
• Travel to malaria-endemic or variant CJD (mad cow) affected regions
• Intravenous drug use, sexual history, and HIV/STD risk factors
• Recent tattoos, piercings, or acupuncture
• Prior blood transfusions or organ transplants
• Medications currently being taken

Donors who answer “yes” to disqualifying questions are deferred. This happens before any blood is drawn.

An important limitation: In the United States, donor screening relies on an honor system. The donor must be truthful for screening to work. Cases have been documented where donors continued giving despite knowing they were ineligible.

Layer 2: Blood Testing

After collection, every donated unit is sent to a certified laboratory for mandatory testing. This is the most technically rigorous layer. No blood can be released for transfusion until all required tests are complete and results reviewed.

See the full list of tests in the section below.

Layer 3: Donor Deferral Lists

Blood banks maintain databases of donors who have been permanently or temporarily deferred. Before a donation is accepted, the donor’s identity is checked against these registries.

Known limitation: Deferral registries are not nationally coordinated in the US. A deferred donor in one state can potentially donate at a blood center in another state that hasn’t received their deferral record.

Layer 4: Quarantine

Each collected blood unit is held in quarantine — it cannot be distributed or used — until all FDA-required testing has been completed and results reviewed. Units with any reactive test result are destroyed; they never enter the supply.

Layer 5: Investigation and Reporting

When safety failures occur, they must be investigated and reported. Licensed blood establishments are required to:

• Report manufacturing errors, accidents, and deviations to the FDA
• Investigate any report of transfusion-transmitted disease
• Trace donor units when recipients report adverse outcomes
• Notify recipients if a previously donated unit is found to have come from a donor later found to be infected

Mandatory Blood Tests: Complete List

Every unit of donated blood collected in the United States must be tested for the following before it can be used in transfusion:

Blood Group Testing

Transfusing incompatible blood is one of the most dangerous errors in medicine — immediate hemolytic reactions can be fatal. Blood group testing is foundational to safe transfusion.

Infectious Disease Screening

Specialized Tests for Specific Recipients

What Is Nucleic Acid Testing (NAT)?

Traditional antibody tests detect the immune system’s response to a virus — not the virus itself. This creates a problem: there is always a gap between when someone becomes infected and when their body produces detectable antibodies. This gap is the “window period.”

Nucleic Acid Amplification Testing (NAT) changes this. Instead of looking for antibodies, NAT directly detects viral genetic material (RNA or DNA) in the blood. This dramatically shortens the window period:

NAT testing for HIV and HCV became standard in US blood banking around 1999–2002 after studies demonstrated its ability to close these detection gaps.

What Happens When a Unit Tests Reactive?

If any test returns a reactive (positive) result, a strict protocol is followed:

1. The unit is immediately quarantined — it will not be distributed
2. Confirmatory testing is performed (Western blot for HIV, RIBA for HCV, etc.)
3. The unit is destroyed if confirmed positive
4. The donor is notified and counseled
5. The donor is placed on the national deferral registry — all future donations are blocked
6. Prior donations are traced — if the same donor gave blood previously, those units are recalled and recipients may be notified

What the Tests Don’t Catch

No testing system screens for everything. Gaps in current blood safety testing include:

Bacterial contamination — The most common cause of fatal transfusion reactions in the US. Bacteria can be introduced during collection and multiply during storage, especially in platelets stored at room temperature. Bacterial screening is performed on platelets in many blood centers but is not universally mandated.

Emerging pathogens — New infectious agents can appear before tests are developed. West Nile Virus, Zika virus, and babesiosis are examples of pathogens that required new testing to be developed after they were recognized as transfusion risks.

Variant CJD (vCJD) — The human form of mad cow disease. No currently available blood test can detect prion diseases in blood. Donors who lived in the UK during certain periods are permanently deferred as a precautionary measure.

Chagas Disease — Trypanosoma cruzi screening has been implemented at many blood centers following increased immigration from endemic regions, but coverage is not universal.

Window Period donations — Even with NAT, a small window remains. Donors who are very recently infected may not yet have detectable levels of viral nucleic acid.

Historical Context: How Blood Safety Has Improved

Before routine testing existed, the US blood supply transmitted disease at catastrophic rates:

• Approximately 10,000 hemophiliacs and 12,000 other patients contracted HIV through blood products in the early 1980s
• An estimated 300,000 people acquired hepatitis C from blood transfusions before HCV screening began in 1990
• Hepatitis B transmission was endemic before HBsAg testing was implemented

The implementation of systematic testing — combined with improved donor screening, deferred donor registries, and NAT — has reduced these risks by orders of magnitude.

Today the US blood supply is described by the FDA as “safer than it has ever been.” But the goal of zero transmission risk has not yet been achieved, and vigilance remains essential.

For an overview of how blood tests work and what they measure, see our understanding blood tests guide. For full reference ranges of common blood markers, visit our blood test normal ranges chart.