What Is Intravenous Immunoglobulin Used For?

Intravenous Immunoglobulin (IVIG) is made up of pooled plasma of more than 1,000 donors. It's used for a variety of conditions.

Intravenous immunoglobulin (IVIG) therapy is a treatment for people with weakened immune systems. Intravenous immunoglobulins are antibodies prepared from pooled plasma of over 1,000 healthy blood donors. The pooled plasma samples are purified before administration.

Humans have five primary types of immunoglobulins, IgG, IgM, IgA, IgD and IgE, each of which performs a different function in the immune system. Intravenous immunoglobulin products typically consist of 95% IgG antibodies and traces of IgM and IgA. These three antibodies are called natural antibodies because they are naturally present in blood, without immunization or antigen exposure.

Intravenous immunoglobulins are used in two opposing ways:

• To suppress inflammatory response in people
  • With autoimmune disorders
  • Who undergo solid organ transplants to prevent graft-versus-host disease (the transplant patient’s immune system attacks the transplanted organ)
  • Who undergo bone marrow transplants to prevent graft-versus-host disease (the new immune cells from the transplanted bone marrow attack the transplant patient’s own body)
• To provide supplemental antibodies and boost immunity against common infections in people with
  • Primary immunodeficiency caused by hereditary or genetic conditions
  • Secondary immunodeficiency caused by diseases and infections such as HIV

Intravenous immunoglobulin works in multiple ways. IVIG suppresses the immune system’s inflammatory response by

• Blocking Fc receptors, the areas on the membranes of immune cells, which activate upon molecular coupling with antigens. This is one mechanism by which immune cells “recognize” antigens.
• Modulating the activation of the complement immune system, which consists of proteins in plasma that are activated by pathogens.
• Suppressing antibodies which are antigen-specific antibodies.
• Suppressing proteins that cause inflammation, such as cytokines and chemokines released by immune cells.

The natural IgG antibodies in IVIG can 

• Prevent infection by binding to pathogens
• Help in removal of dying cells and altered cells such as tumors
• Induce growth of myelin, which is a sheath around nerves that enables normal transmission of nerve signals
• Inhibit growth of autoreactive B cells, which attack native tissue

Intravenous immunoglobulin is used to treat several autoimmune and infectious diseases, as well as against conditions with no known cause. The FDA-approved uses of IVIG are for the following conditions:

• Common variable immunodeficiency (CVID): A group of approximately 150 primary immunodeficiencies (PIDs) that have a common set of features with different underlying causes
• Chronic inflammatory demyelinating polyneuropathy: A nerve disorder that causes weakness and loss of sensation in the legs and arms The only approved drug for this condition is Gamunex
• Primary immunodeficiency disorders associated with defects in humoral (antibody-mediated) immunity
• Immune-mediated thrombocytopenia: An autoimmune blood disorder in which the immune system attacks platelets
• Kawasaki disease: A condition that causes inflammation of blood vessels, often affecting children under five
• Chronic B-cell lymphocytic leukemia
• Pediatric HIV type 1 infection
• Multifocal motor neuropathy: An immune-mediated disorder that causes muscle weakness and atrophy

Intravenous immunoglobulin is prepared from pooled plasma of thousands of healthy donors. The higher the number of donors, the wider the array of antibodies. The Immunoglobulins are extracted from the plasma and further purified to isolate immunoglobulin G and remove other plasma proteins and any pathogens present.

Intravenous immunoglobulin administration is usually performed at an infusion center, especially when it is initiated. Subsequent IVIG infusions may be performed at home by an experienced infusion nurse. IVIG infusions are usually given every three or four weeks.

Patients receiving IVIG therapy are monitored and undergo regular tests that include:

• Liver function tests
• Kidney function tests
• CBC count with differential
• Hepatitis screening for possible transmission from IVIG
• Immunoglobulin levels
• Rheumatoid and cryoglobulin levels

The minimum standards for IVIG preparations as published by the World Health Organization are:

• IVIG should be extracted from a minimum of 1000 donors
• It should contain as few IgA molecules as possible
• It should be free of preservatives or stabilizers that may accumulate in the body
• The IgG molecules should be as little biochemically modified as possible

The FDA-approved human IVIG preparations are:

• Gammagard Liquid: Approved for
  • Primary humoral immunodeficiency
  • Multifocal motor neuropathy
• Gammagard S/D: Approved for
  • Primary humoral immunodeficiency
  • B-cell chronic lymphocytic leukemia
  • Immune thrombocytopenic purpura
  • Kawasaki syndrome
• Gammaplex: Approved for
  • Primary humoral immunodeficiency
  • Immune thrombocytopenic purpura
• Bivigam: Approved for
  • Primary humoral immunodeficiency
• Carimune NF: Approved for
  • Primary humoral immunodeficiency
  • Immune thrombocytopenic purpura
• Privigen: Approved for
  • Primary humoral immunodeficiency
  • Immune thrombocytopenic purpura
• Gamunex-C: Approved for
  • Primary humoral immunodeficiency
  • Immune thrombocytopenic purpura
  • Chronic inflammatory demyelinating polyneuropathy
• Flebogamma DIF 5% and 10%: Approved for
  • Primary humoral immunodeficiency
• Octagam: Approved for
  • Primary humoral immunodeficiency
• Asceniv: Approved for
  • Primary humoral immunodeficiency for adults and adolescents
• Panzyga: Approved for
  • Primary humoral immunodeficiency for 2 years and older
  • Chronic immune thrombocytopenic purpura for adults

Some of the other IVIG products marketed in the United States include:

• Gammar-P IV 
• Iveegam
• Polygam S/D
• Sandoglobulin
• Venoglobulin-I
• Venoglobulin-S
• Gamimune-N

Adverse effects are reported to occur in 5% to 15% of all IVIG infusions and in 20% to 50% of patients undergoing IVIG therapy. Most side effects are mild and transient, and if they occur during an infusion, the infusion is slowed or stopped.

Common side-effects include:

• Headache
• Flushing
• Chills
• Muscle pain (myalgia)
• Wheezing
• Rapid heart rate (tachycardia)
• Lower back pain
• Nausea
• Low blood pressure (hypotension)

Other risks and complications as reported from studies include:

• Severe allergic (anaphylactic) reactions from IgA in patients who have IgA deficiency
• Pompholyx eczema, a type of eczema that causes fluid-filled blisters in palms and feet
• Acute renal failure (uncommon, but irreversible)
• Blood clots (thrombosis), transient serum sickness and transient neutropenia (rare)
• Thromboembolism, especially in patients with underlying conditions, leading to 
  • mini-strokes (transient ischemic attack)
  • heart attack (myocardial infarction)
• Human parvovirus B19 and hepatitis C infections
• Severe cutaneous vasculitis (inflammation of blood vessels in the skin) in a patient with type II mixed cryoglobulinemia, a condition in which cold-sensitive abnormal proteins in blood clump together
• Aseptic meningitis which cause:
  • Fever
  • Neck stiffness
  • Headache
  • Confusion
  • Nausea
  • Vomiting
• Abnormality of blood such as:
  • Hyperproteinemia (excess protein in blood)
  • Increased serum viscosity
  • Pseudohyponatremia (low sodium in blood)
• Unsuitable for patients sensitive to thimerosal, a mercury containing compound which may be used as a preservative in IVIG
• Eczematous dermatitis and alopecia
• Kidney damage