Adverse Reaction Reporting and IMMP
Reporting Adverse Reactions to Manufactured Blood Products
Most patients receiving manufactured blood products (albumin, normal immune and hyperimmune globulin and coagulation factor concentrates) do not experience adverse effects. Others may have mild to severe effects, immediately or delayed for 48 hours. Reporting adverse effects enables the identification of unusual or unpredictable reactions, risk factors (such as concomitant medication or underlying disease) and batch problems. Reporting can also lead to an improvement in the quality of the blood collection process and the manufacture of blood products.
Reactions obvious or obscure,
immediate or delayed
Specific database for adverse reactions to blood products
Reporting improves quality of manufacturing & collection
Isolated reports can form a deluge
Reports increase knowledge
Most manufactured blood products available in New Zealand are made by CSL (Bioplasma) Ltd in Australia. Because of shortages of supply of products made from New Zealand donor plasma, some manufactured blood products (e.g. RhoGam) are manufactured by other overseas companies.
Manufactured blood products are albumin, normal immune and hyperimmune globulins and coagulation factor concentrates (such as Factors VIII and IX).
Because of their source, blood products are more immunogenic than most synthetic agents and hence carry a greater risk of immunological reactions. As well, blood products are frequently given to critically ill patients on concomitant medication. However, most patients do not adversely react when receiving blood products. Others may have mild to severe effects, experienced immediately or delayed after 48 hours.
Reactions obvious or obscure, immediate or delayed
Adverse reactions to manufactured blood products are often similar to those seen when cellular products or plasma components are transfused.
Some reactions are obvious (e.g. fever, urticaria) while others, such as failure of the product to give the expected response (e.g. adequate rise in Factor VIII levels after appropriate dosage) are less obvious but are of equal importance to an overt adverse reaction.
A slightly higher frequency of minor adverse reactions may be seen if the patient is monitored very closely while being transfused. Reactions may not manifest until 48 hours or more after the transfusion. In one case, about 5 years ago, a patient transfused IV immunoglobulin for an immunoglobulin deficiency became anaemic 48 hours later and tested positive to anti-human globulin (Coombs test). Investigations revealed a significant level of Anti-D in the IV immunoglobulin. The batch was withdrawn and new standards developed to prevent this type of event re-occurring.
Reporting system
The following chart shows the system of reporting adverse reactions to blood products:
Adverse reactions should be reported using an Adverse Reactions to Fractionated Blood Form (Microsoft Word document 45KB) (which can also be obtained from local blood banks or blood centres). The completed form is sent to the manager/medical director of the local blood bank or blood centre, who forwards it to the national co-ordinator in Auckland. Copies of the form are sent to CSL Australia Ltd and the Centre for Adverse Reactions Monitoring (CARM) in Dunedin.
If necessary, more information is requested from the reporting doctor to assist in determining causality. When a reply is received from CSL Australia Ltd, a causality assessment is sent to the doctor and CARM.
Significant adverse reaction reports are reviewed by the Medicines Adverse Reactions Committee (MARC) which recommends a course of action to the Minister of Health. Alternatively, if prompt action is required, Medsafe may proceed without the intervention of MARC.
Specific database for adverse reactions to blood products
At CARM information is entered into the national database for monitoring adverse reactions to blood products.
The blood products database enables the identification of -
- unusual or unpredictable adverse reactions;
- risk factors such as concomitant medication, underlying diseases and rate of administration; and
- batch problems.
Reporting improves quality of manufacturing & collection
Reporting adverse reactions to manufactured blood products is one form of quality control. Some of the impetus for the continual improvement in blood products seen in recent years has come from reports of adverse reactions to specific products.
In New Zealand the same batch of any product is usually available nationwide, and feedback is necessary for the manufacturer to improve either its manufacturing processes or quality control. For example, isolated reports of inadequate vacuum in some bottles of Factor VIII concentrate resulted in changes to the manufacturing process of the product. Reporting of what appeared to be a minor defect resulted in improved quality of the product.
Each time an adverse reaction is reported, the manufacturer checks the production record of the product deemed at fault to see if there were borderline results. Sometimes stored samples of the product are retested to see if there is a change in the composition with storage.
In addition, the blood centres collecting donations may have to change criteria for the collection, separation and storage of plasma from which the product is made.
Isolated reports can form a deluge
Since manufactured blood products are distributed nationwide, the national blood services co-ordinator in Auckland, the product manufacturer and CARM determine if there is a trend in the reporting that may require product recall. What may be an isolated event to one doctor may be part of a deluge to the co-ordinator. A few years ago apparently isolated anecdotal reports of hypotensive reactions to Stable Plasma Protein Solution (SPPS) from various hospitals accumulated into 26 reports, resulting in the withdrawal of SPPS from the market.
Reports increase knowledge
The receipt of reports of adverse reactions also allows a profile of the product to be built. This useful information cycles back to doctors via package inserts or published articles on specific adverse effects.
Form for reporting adverse reactions to fractionated blood products (Microsoft Word document 45KB)