Overview

Immunoglobulins (also known as antibodies) are glycoproteins (a type of protein produced by our body) which help us fight foreign substances like bacteria, fungi, and protozoa. These glycoproteins are derived from a specialised type of white blood cell called plasma cells (also known as effector B cells). 

Intravenous immunoglobulins (IVIG) are immunoglobulins given through the veins to treat certain conditions, such as primary immunodeficiency, Kawasaki disease, and chronic inflammatory demyelinating polyneuropathy. The goal of this particular treatment is to bring the immune system back to a healthy and balanced state.^1,2,3

In this article, we will review IVIG in the following aspects: indications, contraindications, manufacturing, administration, side effects, and cost and accessibility. 

Indications

The use of IVIG varies worldwide. IVIG has emerged as a promising treatment for a range of diseases, including:

• Chronic lymphocytic leukaemia
• Chronic inflammatory demyelinating polyneuropathy (CIDP) 
• Multifocal motor neuropathy
• Kawasaki disease
• Chronic B-cell lymphocytic leukaemia
• Primary immunodeficiency disorders associated with defects in humoral immunity
• Immune-mediated thrombocytopenia
• Paediatric HIV type 1 infection
• Common variable immunodeficiency (CVID) 

IVIG has off-label applications for a lot of diseases. The best approach depends on the specific details of a patient’s condition. Consulting a healthcare provider is essential to determine if this is right for the patient.⁴

Contraindications

IVIG is contraindicated in certain patients. The most common contraindications are:

• Some cases of renal failure
• Sugar-based IVIG for diabetics
• Post transplantation patients
• High sodium IVIG should be used with caution for patients with cardiac conditions 
• History of anaphylaxis with IVIG use
• MMR (Measles, Mumps, Rubella) vaccine should not be administered as it can render the vaccine inactive^2,3 

Manufacturing

Intravenous immunoglobulins contain a specific type of antibody: IgG. IVIG is created from a collection of plasma (a part of the blood) donated by 1000-10000 individuals. A process called cold alcohol fractionation is used to concentrate and isolate immunoglobulins. After that further purification techniques are performed. Specific treatments are provided to the solution to kill any pathogens present.⁴

According to the World Health Organisation (WHO), these are the minimum standards required for IVIG manufacturing:⁴

• For broader protection and fewer risks, IVIG should be sourced from at least 1000 individuals.
• IgA antibodies should be minimal.
• To minimise potential long-term accumulation (in the body) and associated risks, the formulation should be devoid of preservatives and stabilisers.
• Unmodified IgG should be prioritised for potent opsonisation and complement-fixing functions. These special proteins need to be in their natural form to work best at helping the immune system fight off infections.

IVIG administration

IVIG is usually given at a hospital or a doctor’s office but it can be given at home by experienced medical staff. IVIG is normally stored in the refrigerator, once it comes to room temperature, it is administered through the veins by an experienced healthcare provider. This helps reduce side effects. It is a slow infusion which can take up to several hours depending on the underlying disease and the body weight. Patients are advised to be well hydrated before the infusion to minimise side effects, especially in cases where blood clotting is a risk or if there is a kidney-related pathology. The dosage varies from person to person and is calculated by the healthcare provider based on the patient’s needs. Results can be seen after a few days to a few weeks.^4,5

Important tests are taken into consideration before IVIG infusion to ensure patient safety, they are:

• A well-documented history is taken with special attention to a history of kidney or liver disease and a history of blood transfusion reactions 
• A physical examination is done accordingly
• Complete blood count (CBC) with differential count
• Liver function test
• Kidney function test
• Hepatitis screening
• Immunoglobulin levels
• Rheumatoid and cryoglobulin levels

Side effects

Unwanted effects are seen in around 20-50% of the individuals who have IVIG therapy. It varies for different diseases and various dosages.  To reduce your risk of having side effects from the treatment, your healthcare provider may slow down the transfusion rate, lower the dosage, or halt treatment and replace it with an alternative IVIG preparation. 

The most common side effects normally occur after 30 min to 1 hour of IVIG administration. They can be improved using antihistamines, steroids and painkillers. Common side effects of IVIG therapy are generally mild and may include:^2,3 

• Nausea 
• Pain at the site of infusion
• Headache
• Flushing
• Chills
• Sweating
• Hypotension (reduced blood pressure)
• Myalgia (muscle pain) 
• Wheezing
• Tachycardia (raised heart rate)
• Lower back pain
• Fluid overload
• Breathlessness
• Stomach pain^4,5

Serious reactions are rare and occur mostly in geriatric patients who already have comorbidities.  They may include:^4,5

• Anaphylaxis (a severe allergic reaction)
• Eczema (a skin condition)
• Acute renal failure (kidney damage)
• Thrombosis (blood clots)
• Disseminated intravascular coagulation (blood clots throughout the body)
• Transient serum sickness (an allergic reaction)
• Transient neutropenia (reduced neutrophils, a type of white blood cells important for immunity)
• Transient ischaemic attacks (a condition caused due to blood clots, similar to a stroke but less severe)
• Infectious disease transmission
• Severe cutaneous vasculitis (inflammation of the skin and blood vessels)
• Acute myocardial infarction (heart attack)
• Aseptic meningitis (a non-communicable form of meningitis)
• Post-infusion hyperproteinemia (increased protein in the blood)
• Increased serum viscosity (thicker blood)
• Pseudohyponatremia (similar to reduced sodium in the body)
• Alopecia (hair loss)^2,4,5,

Summary

Intravenous immunoglobulin (IVIG) is a treatment involving the administration of antibodies through the veins to address various conditions such as primary immunodeficiency, Kawasaki disease, and chronic inflammatory demyelinating polyneuropathy. These antibodies, produced by plasma cells, aim to restore a balanced and healthy immune system. This article provides a comprehensive review of IVIG, covering aspects such as indications (including off-label applications), contraindications (e.g., renal failure and allergies), manufacturing (involving cold alcohol fractionation and stringent quality standards), administration (typically performed in a medical setting with careful consideration of patient history and tests), and side effects (ranging from common, manageable symptoms like nausea and headache to rare, severe reactions like anaphylaxis and kidney damage). The dosage varies based on individual needs, and results can be observed within days to weeks after administration. Overall, IVIG is a promising therapeutic option, but its use requires careful medical consideration and monitoring.

FAQs

Should you get a vaccine after IVIG treatment?

Some vaccines don’t work as efficiently after IVIG therapy. The patient must consult their healthcare provider before getting a vaccine as it can be rendered ineffective after IVIG use for a certain period of time (weeks to months). 

As a patient what can I do for a better outcome?

Keep your medical records safe, including your IVIG product number and date. This can help your healthcare provider provide you with the same brand to avoid unnecessary change as this one works for you. Also, keep track of your side effects and inform your medical practitioner if any alarming symptoms occur. A prompt follow-up when advised is recommended as well. 

How long is an IVIG infusion?

It depends on the dosage, disease and body weight. Normally it lasts from 1-6 hrs.