Evaluation of Donors with
Abnormal Test Results

Information on this page is provided to assist physicians in managing patients who come to them with an abnormal test result found during a recent blood donation. As discussed below, the vast majority of abnormal results in healthy donors are likely false-positive and have no implications for their health. To protect blood recipients, however, we must discard their blood and disqualify them from future donation.

Background - Blood Donor Testing Process

Donated blood is subjected to a battery of very sensitive tests to screen for blood-borne infectious agents. A "non-reactive" (negative) result qualifies the blood for release, provided that all other tests and screening procedures are negative. If one of these screening tests is abnormal ("reactive"), it is repeated in duplicate. If 2 of the 3 tests are abnormal, the result is termed "repeat reactive" (= positive), and the blood donation is discarded.

The abnormal serum sample is sent to our National Confirmatory Testing Lab for another more specific confirmatory/supplemental test. Results of these tests, usually available in 7-10 working days, are either positive, negative, or indeterminate. A positive result means the screening test result has been confirmed as positive. A negative result means the screening test result was false positive; to protect recipients we take a very conservative approach, and disqualify these donors. An indeterminate result, one that is not clearly negative or positive, usually means one of two possibilities:

• The donor is not infected but has something in his/her sera that triggered a reactive result in the screening test and an abnormality in the confirmatory/supplemental test. (most common)
• The donor has been recently infected with the agent, but has not yet developed the criteria/bands required to qualify as a positive result. (rare)
  
  Because blood donors are generally healthy individuals who have been screened for disease by a battery of health history questions, an indeterminate result usually is not a sign of infection. This has been confirmed for agents such as HIV, by a number of large studies using viral culture, nucleic acid testing and clinical followup. However, in order to protect blood recipients, persons with indeterminate (or negative) confirmatory/supplemental results are currently disqualified from further donation.

Blood donors with abnormal test results that might disqualify them from further donation are notified by mail and provided with the test results, along with a Fact Sheet explaining the significance of the results. Those with test abnormalities of medical significance are encouraged to consult with their physician. (Donors with confirmed positive test results for HIV are informed of this only during personal interview, by a blood center physician or trained donor counselor.)

Hepatitis

• Antibody to hepatitis C

  A positive supplemental result indicates past exposure to hepatitis C virus (HCV), usually though blood contact from sharing needles for illicit drug use, accidental exposure in a medical situation, or blood transfusion before 1990. Although some of these individuals no longer have the virus, the majority do (as indicated by PCR tests for viral RNA) and are at risk of chronic hepatitis; of these about 10-15 percent develop cirrhosis. Such persons should be evaluated by a physician knowledgeable in hepatitis, in order to decide whether special treatment is needed.
  
  A negative supplemental result means the first screening test was a false positive. About 1 in 500 donors show such results, which are not associated with any known disease.
  
  An indeterminate supplemental result. Although a small number of these persons may have been infected with HCV, most have not, and are perfectly healthy. Because we cannot be certain, we must disqualify these donors. A PCR test for viral RNA often helps in further assessment.

• Antibody to hepatitis B core antigen

  A positive test result usually means past infection with hepatitis B virus. In about 1 in 4 cases it could be a transient "false positive". For this reason we wait until a second donation tests positive before disqualifying these donors. Most persons with isolated positive results (i.e., in the face of negative results for hepatitis B surface antigen) are not infectious. However, since some persons may harbor low levels of virus not detectable by our tests for hepatitis B surface antigen we cannot currently accept blood with these results. This policy may change after introduction of genome amplification tests for hepatitis B.

• Hepatitis B surface antigen

  A positive confirmatory (neutralizating) test result means the person is a carrier of hepatitis B.
  
  A negative unconfirmatory (non-neutralizing) result means the screening result was "false positive". Although this is not a sign of disease, we are unable to accept these donors at present. This policy may change after implementation of newer tests.

• Elevated ALT (SGPT) level

  Although this test has little value now that sensitive viral tests for hepatitis B and C are in place, some manufacturers of plasma derivatives (albumin, clotting factor concentrates, immune globulin, etc.) will not accept plasma from donors with ALT levels above 120 u/L. Most donors with elevated ALT and normal viral markers have some benign and transient cause, such as recent viral illness, medication, being overweight, recent vigorous exertion, or overindulgence in alcohol.

HIV (AIDS)

• Antibody to HIV-1/2

  The test used in blood banks, an enzyme immunoassay (EIA) screens for both HIV-1 and HIV-2, in contrast to the anti-HIV-1 EIA test used in most diagnostic laboratories. Therefore it is not unusual for a person to have a positive screening result from a blood donation, and then a negative result in a test run by a diagnostic laboratory.
  
  A negative confirmatory (Western blot) result means the screening (enzyme immunoassay) result was false positive. About 1 in 3,000 healthy donors have such results. Although in most cases there is no known cause, a recent report showed a transient false-positive HIV screening result after acute cytomegalovirus (CMV) infection.
  
  An indeterminate Western blot is usually not of any medical significance (see Background - above). Studies have shown such results in 10-15 percent of healthy EIA-negative donors.
  
  A positive Western blot means the person is a carrier of HIV. Rarely, persons without risk behavior for HIV may show a false positive Western blot. In this case, further testing such as PCR is needed.

• HIV antigen

  This test was implemented in early 1996, to enable earlier detection of HIV. It is estimated that the average "window period" (time between onset of infectivity and detection by tests) was reduced from 22 days (for antibody test alone) to 16 days (for both tests).
  
  A positive screening result requires confirmatory testing with a neutralization test.
  
  A positiveneutralization result means recent infection with HIV, and may be seen before antibody is demonstrable. In over 30 million donations tested since 1996, only three have been positive for antigen in the face of a negative antibody result.
  
  If the neutralization test is negative, the HIV antigen result must be reported as "indeterminate" because the FDA has insufficient data to be certain that HIV is not present. In donors like this without risk behavior further studies including PCR have not shown any evidence of HIV. The test abnormality is not associated with any known disease, and may be persistent. Persons with persistently abnormal screening results or indeterminate neutralization results are currently disqualified as donors.

Antibody to HTLV-I/II (human T-lymphotropic viruses, types I and II)

A negative supplemental (Western blot) result means the screening result was a "false positive". Transient results like this can be caused by many factors, such as influenza vaccine, some bacterial infections, autoimmune disorders and multiple pregnancies.

An indeterminate supplemental result. Although a small number of these persons may have been infected with HTLV-I or HTLV-II, most have not, and are perfectly healthy. Because we cannot be certain, we must disqualify these donors.

A positive supplemental result means infection with either HTLV-I or HTLV-II. Research tests may help in distinguishing the two.

• HTLV-I is endemic in certain countries such as southern Japan (and migrants to Hawaii), the Carribean, and parts of South America and Africa. It is transmitted by blood, sexual contact and from mother to infant during childbirth. Most persons carry the virus for many years without showing signs of disease. About 2-4 percent may develop either adult T-cell leukemia-lymphoma or a neurologic condition known as HTLV-associated myelopathy (HAM) or tropical spastic paresis (TSP).
• HTLV-II occurs predominately in persons who have shared needles for self-injected illicit drug use. Transmitted like HIV and HTLV-I, it occurs with increased frequency in some populations such as certain North American-Indian tribes in New Mexico and Panama, where its epidemiology is unclear. A small number of carriers may develop minor neurologic symptoms due to spinal involvement.