Immunoglobulins - Normal and Specific

Human immunoglobulins can be given by IV or IM injection to confer passive (temporary) immunity.¹ They provide immediate protection. The effects last weeks. They tend to be large volume injections and should be given by deep IM injection into the thigh or buttock, and in children should be divided and given in different sites. They are derived from plasma of non-UK blood donors (to avoid nCJD) and are safe from hepatitis B and C, HIV and syphilis (and can be tested for CMV and malaria if necessary).

There are 2 types of immunoglobulins

• Normal (non-specific) - from unselected donors
• Hyperimmune (specific) - from selected donors

• Malaise, chills, fever
• Headache, nausea, facial flushing
• Anaphylaxis (rarely)

HNIG is made from the plasma of about 1000 donors. This provides antibodies against hepatitis A, rubella, measles and other viruses prevalent in the general population. It is most effective within 3 days of contact (but has some effect up to 6 days); protection is immediate and lasts several weeks. They block the immune response to live vaccines (except yellow fever) for 3 months, and live vaccines should ideally be given at least 3 weeks before or 3 months after an injection of HNIG, although this can be ignored if there is insufficient time, e.g. for travellers. It is contraindicated in those with class specific antibody to IgA.

HNIG is used for:

• Hepatitis A contact in immuno-compromised patients, preferably given within 72 hours, together with HAV vaccine (in a different site) because there may be a poor antibody response to the vaccine alone. HAV vaccine protects normal individuals if given within a week of contact (possibly even up to the day of travel).²
• Rubella contact in non-immune pregnant women where termination is unacceptable - it does not prevent infection but reduces symptoms and the risks to the fetus. Give as soon as possible after exposure. Serological follow-up is essential. MMR and anti-D may be given in the postpartum period (separate syringes and into different limbs). Measure rubella antibodies after 8 weeks and vaccinate if necessary. However, rubella vaccine is not effective for post exposure prophylaxis.
• Measles contact, within 72 hours of exposure (some effect if given within 6 days) if:
  • Immuno-compromised
  • Non-immune pregnant women (but no evidence it prevents fetal loss)
  • Infant under 9 months - if mother not immune
  • Infant 6-8 months - if mother immune (because under 6 months the child is protected by maternal antibodies and after 9 months MMR can be given for prophylaxis following exposure to measles)
• Mumps contact - neither HNIG nor MMR offer protection

Intravenous human normal immunoglobulins allow large amounts to be given, for broad -spectrum passive protection for premature babies, congenital hypogammaglobulinaemia, immunoglobulin deficiencies, autoimmune disorders, e.g. thrombocytopenic purpura (where temporary rapid rise in platelets needed, such as, pregnancy or pre-operatively). Kawasaki syndrome, following bone-marrow transplantation, children with HIV, Guillain-Barre Syndrome, and myasthenia gravis (unlicensed use) when it can induce remission in severe relapse.

These solutions are made from plasma containing high levels of certain antibodies.


1. Anti-D (Rh₀) immunoglobulin, (see separate article on anti-D) 500 units, can be given at 28 weeks, 34 weeks and at birth to rhesus-negative mothers to block fetal RhD-cells from stimulating antibodies (which could cause haemolytic disease of the newborn in future babies). Anti-D is given within 72 hours of abortion, miscarriage or birth, and after any potentially sensitising situations, e.g. amniocentesis, antepartum haemorrhage and abdominal trauma. Anti-D can be safely repeated as many times as needed during one pregnancy.³
2. Hepatitis B immunoglobulin (see separate article on hep B immunisation) is used after needle-stick or sexual exposure and in infants born to infected mothers (persistent carrier with detectable hepatitis e antigen or its antibody or in recent infection). It should also be given in hepatitis B mothers when the birth weight of the baby is <1500g.² The sexual contacts of acute hepatitis B sufferers and chronic hepatitis B sufferers (newly diagnosed) should also receive specific immunoglobulin if unprotected sexual contact occurred in the last seven days. It should be given preferably within 12 hours and not later than 1 week after exposure. Hepatitis B vaccine should also be given.
3. Zoster immunoglobulin is given to the non-immune exposed to chickenpox or shingles if at risk of severe infection:
   • Immuno-compromised individuals
   • High dose steroids therapy (adult who has received 40 mg daily for more than a week in the previous 3 months, or a child who has received a daily dose of 2 mg/kg for more than a week, or 1 mg/kg for more than a month, in previous 3 months)
   • Non-immune pregnant women (to protect the fetus)
   • Neonates of women who develop chickenpox 7 days before/after delivery
   • Significant exposure to the virus
4. Rabies immune globulin is indicated for an unimmunised person exposed to a bite from an animal from a high risk country; as much as possible is injected into or around the cleansed wound (after washing with soapy water). Rabies vaccine should also be given.
5. Tetanus immunoglobulin (together with metronidazole and wound cleansing) is given for tetanus-prone wounds, in the non-immune or those not up-to-date with boosters. Tetanus vaccine should also be given. IV Immunoglobulins are also given for treatment of tetanus).
6. Cytomegalovirus immune globulin (on a named-patient basis) for patients receiving immunosuppressive treatment.

• Aplastic anaemia - IV anti-lymphocytic globulin (50% respond)
• Diphtheria anti-toxin - (from horses) for suspected diphtheria, adverse reactions are common. Diphtheria anti-toxin does not provide any benefit when used prophylactically.
• Botulism anti-toxin for suspected botulism, again adverse reactions are common.

Immunoglobulins are available from NHS microbiology laboratories, and in Scotland from the Blood Transfusion Service - they are prepared by Bio Products Limited (BPL), and are issued by the Health Protection Agency.