IVIG Intragram P use in NZ

Submitted by Christopher Corkery, NZ Blood Service Nurse Specialist, Waikato. Originally printed in December 2005 IVNNZ Inc. Newsletter

What is IntragamP?

Intravenous Immunoglobulin (IVIG), otherwise known as Intragam®P in New Zealand, is made from plasma donated by New Zealand donors for use by New Zealand patients. The plasma collected in New Zealand is sent to CSL in Australia for processing and returned to New Zealand. Plasma from other countries is not used to make the New Zealand product. The manufacturing procedure involves pasteurisation (heating at 60ºC for 10 hours) and incubation at a low pH. These processes are designed to recover as much IgG as possible and reduce the viral load of enveloped viruses (e.g HIV, HBV, HCV) and the non-enveloped virus Hepatitis A1.

 The result is a product that is a sterile preservative free solution containing human protein, at least 90% of which, is IgG. There are trace amounts of IgA and IgM. Put simply, we are harvesting antibodies from New Zealand donors for patients who are immune deficient or have an immune component to their disease.

Indications

The use of Intragam®P as a replacement therapy in patients with primary and secondary immune deficiency is well established. Intragam®P is also widely employed as first line or adjuvant therapy, or as an alternative to plasmapheresis, in a variety of diseases attributed to an immune aetiology2. As a result it is currently the most widely used plasma product in the world2. The use of IVIG in immunomodulatory settings (e.g. Guillian-Barre Syndrome, Chronic Inflammatory Demyelinating Polyneuropathy) is supported by lower levels of evidence than its use in replacement therapy2. Lower levels of evidence is accepted because of the rarity of some disorders that make it difficult to perform double blind studies.

 Intragam®P is licensed in New Zealand for use as replacement IgG therapy in primary immunodeficiency; myeloma and chronic lymphocytic leukaemia with severe secondary hypogammaglobulinaemia and recurrent infections. It is also licensed for use in congenital or acquired immune deficiency syndrome with recurrent infections, as well as therapy in idiopathic thrombocytopenic purpura (ITP), allogeneic bone marrow transplantation and Kawasaki disease1.

 An audit undertaken by the NZBS over a 6 month period showed that in NZ, primary antibody deficiency, CIDP, ITP and Guillain-Barre Syndrome accounted for 59% of all patients and 61% of all Intragamâ P used over 6 months3.

 Nursing Implications

Administration

As Intragam®P is a medicine, like all blood products, nurses need to be aware of their responsibilities when administering it. Similar considerations to that of red cells and plasma products are required.

Consent: The patient needs to provide informed consent before a transfusion proceeds. Every DHB within New Zealand have their own policies regarding consent and these should be adhered to. Generally, it requires medical staff to obtain consent but there may be exceptions in some DHBs which allow nursing staff to obtain informed consent. NZBS provides a patient information leaflet discussing the risks associated with Intragam®P to make consenting easier.

The patient needs to provide informed consent before a transfusion proceeds. Every DHB within New Zealand have their own policies regarding consent and these should be adhered to. Generally, it requires medical staff to obtain consent but there may be exceptions in some DHBs which allow nursing staff to obtain informed consent. NZBS provides a patient information leaflet discussing the risks associated with IntragamP to make consenting easier.

 

1. Observations: Baseline observations are required as with other blood products and this is regardless of how frequent patients have a symptom free infusion of Intragam®P. Other records required are the weight of the patient (as dose is weight dependent) and the patient should have at least one Group and Screen performed before the start of their therapy. The recommendation from the manufacturer is that patients who are grouped A or AB should be monitored closely for haemolysis post Intragam®P especially if receiving high doses (>0.4gm/kg). The NZBS audit found that only 38% of high dose recipients had a group and screen test.

 

Baseline observations are required as with other blood products and this is regardless of how frequent patients have a symptom free infusion of IntragamP. Other records required are the weight of the patient (as dose is weight dependent) and the patient should have at least one Group and Screen performed before the start of their therapy. The recommendation from the manufacturer is that patients who are grouped A or AB should be monitored closely for haemolysis post IntragamP especially if receiving high doses (>0.4gm/kg). The NZBS audit found that only 38% of high dose recipients had a group and screen test

 

2. Ordering from Blood Bank: When requesting Intragam®P, written information should be sent to the blood bank which include the details of the patient in a similar way to when red cells are requested. Blood bank will then issue the product for that patient. It is important to realise that if a department is transfusing multiple units of Intragam®P to multiple patients (as in a busy day stay unit) that the right bottles are going to the intended patient.

 

When requesting IntragamP, written information should be sent to the blood bank which include the details of the patient in a similar way to when red cells are requested. Blood bank will then issue the product for that patient. It is important to realise that if a department is transfusing multiple units of IntragamP to multiple patients (as in a busy day stay unit) that the right bottles are going to the intended patient.

 

3. Clerical Check: Ensure the clerical details on the compatibility label are correct and where possible confirm these with the patient. For any discrepancy please contact your blood bank.
Ensure the clerical details on the compatibility label are correct and where possible confirm these with the patient. For any discrepancy please contact your blood bank.

 

4. Administration: On commencement of the transfusion the rate of infusion should begin at a rate of 1ml/minute. Depending upon the condition of the patient this rate can be increased by 1ml/minute at 15 minute intervals to a maximum of 4ml/minute. Paediatric units should have a protocol that explains the procedure for patients under 40kg or under 12 years of age. A too rapid infusion can cause flushing, headaches, changes in pulse and blood pressure.
On commencement of the transfusion the rate of infusion should begin at a rate of 1ml/minute. Depending upon the condition of the patient this rate can be increased by 1ml/minute at 15 minute intervals to a maximum of 4ml/minute. Paediatric units should have a protocol that explains the procedure for patients under 40kg or under 12 years of age. A too rapid infusion can cause flushing, headaches, changes in pulse and blood pressure.

 

5. Adverse Reactions: The nurse should be aware that allergic and anaphylactic reactions can occur at any time during the transfusion. Patients may react to new batches or to batches that they have received problem free in the past. Also, patients who are elderly or have renal impairment are prone to hyperviscosity due to the amount of protein in Intragam®P.
The nurse should be aware that allergic and anaphylactic reactions can occur at any time during the transfusion. Patients may react to new batches or to batches that they have received problem free in the past. Also, patients who are elderly or have renal impairment are prone to hyperviscosity due to the amount of protein in IntragamP.

 

6. Completion: At the completion of the transfusion, the compatibility label must be placed in the clinical notes of the patient as this is part of the audit trail which assists in the tracing blood products from recipient to donor. The nurse should also make a comment in the clinical notes regarding the transfusion.
At the completion of the transfusion, the compatibility label must be placed in the clinical notes of the patient as this is part of the audit trail which assists in the tracing blood products from recipient to donor. The nurse should also make a comment in the clinical notes regarding the transfusion.

 

Adverse Reactions

All adverse reactions, regardless of severity or intervention, should be reported to the blood bank using the NZBS adverse reaction form. This information is then passed on to CSL (Intragam®P manufacturer) who collates information nationally to ensure identification of any national trend in reports. Adverse reactions are often rate and volume related, so, often all that is required is to slow the infusion down to relieve such symptoms as:  headache, flushing, nausea, vomiting, pallor, hot sensations, itching, non-urticarial skin rash .

For more serious reactions such as: hypotension, angioedema, bronchospasm, urticaria, abdominal pain, chest tightness, renal impairment  and aseptic meningitis, then the transfusion should be stopped immediately and treatment for the symptoms commenced. Discussions with the patient's Consultant, or with a Haematologist or Transfusion Medicine Specialist should follow regarding further treatment.

Case Study 1

Rebecca is a 35 year old teacher who is active in several sporting codes and is involved as a volunteer in her son's soccer club. Rebecca also has 1 teenage daughter. Rebecca describes herself as being happy and healthy. However as a child, life was often plagued by serious chest infections resulting in multiple hospital admissions every year particularly in the winter months, but often at other times of the year as well. Rebecca has always been a non-smoker. Although her health improved a little when as a teenager she moved to a coastal town, she still required frequent antibiotics for chest infections. Rebecca's new GP decided to investigate her immune status and discovered that her IgG levels were well below normal. After consultation with an immunologist, Rebecca was diagnosed with hypogammaglobulinaemia and started on monthly courses of Intragam®P. Since commencement of treatment she hasn't required any further hospitalisations and now is prone only to the usual colds that other people receive.

Case Study 2

Edith is a 74 year old grandmother who was admitted into the cardiac care unit for investigations of chest pain and shortness of breath. Edith was previously fit and independent and enjoyed an active life. Edith's condition in the following days did not improve and investigations were inconclusive but eventually she was diagnosed as having a viral myocarditis. Several case studies citing IVIG to treat viral myocarditis appears in the literature and with the consent of the patient a trial of Intragam®P was commenced. The patient's blood group was A positive. The incorrect dose of IVIG was charted and in one day the patient received 4 days worth of Intragam®P. The patient initially had increased shortness of breath and headaches. The infusions were slowed but with no reduction in symptoms the transfusion was stopped. Following discussions with NZBS staff, the error was noted and further Intragam®P was withheld. Laboratory investigations showed a viscosity level of 5 with elevated levels of protein. The patient's renal function results indicated impairment and the patient now had extensive oedema and increased shortness of breath. Also the patient's Hb now dropped to below 100 and results showed haemolysis as a result of the transfusion of blood group antibodies present in the IntragamP. The patient's condition deteriorated and was admitted to ITU for closer monitoring. Over the next few days the patient slowly improved and eventually made a full recovery.

The first case study demonstrates that Intragam®P can be very useful in the treatment of certain immune deficiency disorders. Immune disorders were in the past often under diagnosed but this is now changing and hopefully people like Rebecca will get treatment sooner. The second study is an example where the product is used in an unfamiliar setting. Special consent was obtained from the patient, but then the dose was incorrect. Neither medical nor nursing staff checked the appropriate dosing, despite the patient's age, illness and blood group making her susceptible to a serious adverse reaction. If you are unfamiliar with a medication ensure that you get good advice before you administer it.

Conclusion

The widespread off-label use of IVIG has become an urgent problem in some countries and the relative ease of IVIG therapy is a factor in influencing its choice ahead of other established options2. In New Zealand, the national average increase of IVIG usage is around 8% pa over the last 8 years4. This rate of increase is an important consideration to the blood service as Intragam®P has now become one of the main drivers for recruiting donors, particularly plasma donors. If you have any concerns about patients who are receiving Intragam®P or about its administration please contact the Haematologist, Blood Bank or Transfusion Nurse Specialist in your area.

References

1. New Zealand Blood Service. Intragamâ P datasheet. 2004. www.nzblood.co.nz
2. Knezevic-Maramica I , Kruskall MS. Intravenous immune globulins: an update for clinicians. Transfusion 2003;43:1460-1480.
3. New Zealand Blood Service. "Intragam®P audit within 8 centres in New Zealand." Unpublished report. 2005
4. New Zealand Blood Service. Demand Management Project. Unpublished reports.