Security measures, risks and circulatory, immunological and infectious accidents
Security measures: Law of 1 July 1998 so-called “safety”:
The organization of blood transfusion was amended by the Act of 1 July 1998 on the strengthening of disease surveillance and control of the safety of products intended for humans. This law transfers part of the French Blood Agency activities (AFS) to the French Agency for Safety of Health Products, and plans before 31 December 1999, the creation of a French Blood Establishment. The current situation is mainly the result of the Law of 4 January 1993, the various decrees and orders, as well as the implementation of “good practices”. The regulations governing the activities of blood transfusion are very numerous and had as main purpose transfusion safety.
1- Products derived from blood:
The blood products were divided into two classes: labile blood products and blood products. The legislation applies to blood products is the same as that which applies to medicines, and this in the whole of Europe. Blood components have a definition specified in the Gazette and shall, before being used in therapy, the authorization of a special committee of the French Blood Agency. Security measures are multiple, some apply to all blood products as donor selection or biological selection, others are specific as viral inactivation or the respect of immunological compatibility.The packed red cells, platelet concentrates and plasma are blood components. The red cells are now all leukodepleted, but they can include special mentions: phenotyped, irradiated, frozen, washed. Platelet concentrates can be obtained by fractionation of whole blood (standard platelet concentrate) or by apheresis (apheresis platelets).Plasma is fresh frozen, it is secured by quarantine and are indications now limited to complex disorders of hemostasis.The list of blood products is longer, it includes albumin, factor VIII, factor IX, the complex II, VII, IX, X, fibrinogen, antithrombin III, alpha 1-antitrypsin, immunoglobulins the biological glue …
2- General measures:
These measures apply for the basic blood product with minimal risk of communicable disease.
• Selection of donors: the donor’s health is an essential element of security, and quality of medical care is key to the detection of risk. Epidemiological data has outlined so-called population groups “at risk” to the extent that their living conditions expose them to infectious agents transmissible by transfusion. This is the case of subjects living in malarious areas or regions where certain infections are endemic. Some subjects may be exposed to risks by their behavior (substance abuse, sexual promiscuity, tattoo), for treatment received (transfusion) by an infectious contagion.
• biological selection: it will allow to spread the gifts in which we detect an infectious agent, or serological indicator of a possible infection. We will see later that despite progress in laboratory tests, the extension of the number of infectious agents sought, there remains a risk, is linked to the onset of the marker (window period), is related to the reliability of the test (<106).
• Leukoreduction: To reduce the risk of transmitting viruses or bacteria intraleucocytaire, leukocyte depletion or depletion of leukocytes of blood products became mandatory. This technique does not eliminate all leukocytes, but significantly reduces the number and, therefore, reduces the risk of transmission of infectious agents intraleucocytaires.
• The blood product quality control applied to all products, and these must comply with the standard set by the regulatory authorities.
• Distribution of blood products: prescription of blood products should be standardized order specifying the data of the patient’s marital status, the nature and amount of product required, indicating the name and the quality of prescribing.The issuance will take into account the immunological data of the recipient and the prescribed product. The product distribution will be nominal.
• Haemovigilance: any incident or accident transfusion must be notified (plug transfusion incident) to be transmitted to the French Blood Agency. This system, virtually in real time, to experience system failures and take corrective measures.
• Authorization and Inspection: to carry on business, a transfusion institution must have received approval from the French Blood Agency. It has a staff of inspectors who check the operation of blood establishments is in compliance with various laws or regulations.
3- Specific measures:
Some blood products or blood derivatives can undergo without damage treatments to inactivate infectious agents, despite the selection of measures, could be contained in blood products. Many techniques are currently being tested for blood components, but others are applied routinely for many years and more recently. The pasteurization type of heating is used for decades for albumin, and more recently for the a1-antitrypsin or antithrombin III. The alcohol precipitation, the treatment pH acid and / or pepsin, are often used for the preparation of immunoglobulins. The solvent detergent treatment and immuno-purification are techniques used for the purification of factor VIII. The ultraviolet irradiation with or without added photosensitizer is experimental, but the results can hope for development. All these measures and quality control effectiveness are yet to reduce the risk of transmission of infectious agents, but their performance depends largely on the quality and training of personnel. We will see that many accidents associated with transfusions are often secondary to human error.
Risks and circulatory events:
Abnormalities in blood volume and oxygenation are both transfusion indications and risk of accidents.
The hypovolemia and inadequate correction of anemia are causes ischemia that can be coronary or cerebral. The desire to want to avoid exposing a patient to the risk of communicable disease, in some cases led to insufficiently transfuse a patient. Poorly corrected anemia, especially when the hematocrit is less than 28% in a subject over 60 years, causes coronary suffering.
Too rapid transfusion of blood products in patients with heart failure may be the cause of an acute pulmonary edema, which should be prevented by a suitable infusion rate and when indicated by the administration of diuretics. In the particular case of sickle cell anemia, transfusion sometimes requires the pathological blood subtraction to allow transfusion. exsanguino- transfusion of partial programs can reduce the risk of stroke in sickle cell disease.
Such accidents should not be, because every transfusion tubing is fitted with a filter that stops the micro-emboli that may have formed in the blood bag. In addition, the systematic removal of leukocytes should eliminate the risk of infusing originally microcaillots thrombophlebitis, pulmonary embolism or even eliminating transfusion before leukocyte and platelet aggregates.
4- cardiocirculatory disorders:
Abnormal heart rhythm induced by the rapid infusion of citrate are known for a long time without one yet knows with certainty today whether the effect is due to a chelating effect of citrate, a direct toxicity. They usually corrected by reducing the flow and (or) calcium gluconate administration.
The immunological risk is between 1/6 and 1/12 000 000 transfusions.
1- ABO incompatibility:
The risk of ABO incompatibility are known since the beginning of the century, the way to avoid them is also well known, but accidents persist and can cause death of patients. They are always the result of successive failures, each step in the chain have not been respected. The final check at the time of transfusion have been failing in over half the cases, prescription errors and destination are the two most common causes. The establishment of reliable tests at the ultimate control should at least partly compensate for the lack of compliance with procedures. Transfusion ABO incompatibility situation can be asymptomatic clinically and not be detected by the absence of increases in hemoglobin in the recipient following transfusion. In over 25% of cases, the patient shivering and fever. ABO incompatibility can be very serious and cause a collapse, intravascular coagulation, anuria, death.
2- Accident due to alloantibodies:
Unlike the ABO accident that can occur in a blank about transfusion history or pregnancy, accidents due to the presence of alloantibodies occur most frequently in patients who had opportunities to become immunized, especially if their erythrocyte phenotype predisposes them to meet an immunogenic antigen of high frequency (Rh, K …). As in the case of the OBA, about 10% of incompatibilities have no clinical translations, but only organic. The chills-hyperthermia association is common, but serious clinical picture combining collapse, anuria and death, unfortunately, is not unique.In the vast majority of cases, the incompatibility accidents should not occur if the procedures were properly followed.The prescription must be adjusted taking into account the history of the subject; checking his blood and the search for irregular antibodies are systematic. The distribution must be customized, systematic ultimate control and well done, careful monitoring and extended transfusion enough for this type of accident disappears risk for transfusion.
1- viral hazards:
If the case of blood contaminated with HIV (HIV) is still subject to legal proceedings, the transmission of other viruses, particularly the hepatitis C virus (HCV) is still a major concern. Statistics show that the risk of transmission of known viruses is steadily decreasing, but the fear persists in the assumption of the transmission of a previously unknown pathogen. HTLV-I and II (human T leukemia virus) are the most common viruses in the Caribbean area and Japan than in our regions: the risk of transmission is low (1 to 8 million). The theoretical and identified risk of HIV through transfusion is now low, on the order of 1 to 1.2 million. The risk of transmission of hepatitis B or C is 4 times higher (1 280 000, 1 200 000) and is perceived to interest hepatitis B vaccination. CMV is very common in the French population (60%), but results in a benign except in immunocompromised. Leucodepletion significantly reduces the risk of cytomegalovirus transmission because it is essentially intraleucocytaire. Parvovirus B19 causes a mild illness (mononucleosis) in the majority of cases, it can induce more severe diseases in pregnant women and especially in immunocompromised (PRCA). The virus called hepatitis G does not appear linked to a well-identified liver disease, but could be a co-infection of virus. The herpes virus-type (HHV6, HHV7, HHV-8) are transmissible by transfusion and may be responsible for different diseases, but today it is not possible to establish a clear link between a transmission by transfusion and disease secondary to transfusion. TTV or transfusion Transmitted virus is one of the last candidates, but the exact risk of this virus and its transmission still needs to be evaluated.
2- unconventional transmissible agents:
Creutzfeldt-Jakob disease is a rare disease and its transmission by transfusion is hypothetical. The variant which have been observed several cases in England and which is related to the presence of prions may pose a risk of transmission to the extent that prions may be present in lymphocytes.
Malaria is a very prevalent disease in the world. Its incidence is between 300 and 500 million hits a year. Imported malaria has more than doubled in the last 12 years to more than 5000 cases. Indigenous malaria cases account for less than 7 cases per year. The measure for the temporary exclusion of subjects who stayed in endemic areas is surely an effective measure when combined with a systematic search of parasites in donors have been at risk. The surveillance network did not report transmission by transfusion, which does not completely rule out the risk, but suggests that, if it exists, it should be low.
The bacterial contamination of blood component can have three origins: the collection, the donor blood, the pocket.The contamination of the bag can result in serious accidents in series due to a lack of sterilization or the presence of bacterial endotoxin resistant to sterilization processes. Systematic checks of manufacturing processes explain the rarity of such accidents, and blood safety limits the possibility of mass accidents. Sources of contamination are most frequently due to insufficient disinfection of the skin, or to the presence of bacteria in the donor blood. Bacterial growth is slow to 4 ° C, this means that the more often the product in question is the platelet concentrate kept it at 20 ° C. Two types of germs are usually involved: staphylococci and gram-negative bacilli in particular Yersinia enterocolitica or Escherichia coli. As an experiment, simple techniques were tested to detect possible bacterial contamination but are not widespread. Proper aseptic, excluding febrile donor, “good practices” of preparation, storage and transportation compliant, filtration, are elements that reduce the risk. Monitoring the first 10 minutes of the transfusion can detect the symptoms (fever, headache, digestive disorders), stop the transfusion and to bacteriological research in the recipient and the blood components.
Blood products or blood-derived drugs and their specific risks:
1- stable blood products:
The blood products having the status of drugs, they are subject to the same rules as those applied to the pharmaceutical industry, and are distributed through pharmacies. Stable products are derived from plasma obtained from whole blood by centrifugation or collected by plasmapheresis. Derivatives most widely used plasma are albumin and Factor VIII. Their indications are smaller because they are competing with crystalloid and genetic constructs.Factor IX, immunoglobulins keep their indications next to new products such as a1-antitrypsin, antithrombin III, C1 inhibitor esterase biological glue. Plasma-derived stable products were fractionated by precipitation, today are used in chromatography, affinity chromatography, filtration and ultrafiltration. As for labile products, donor screening and biological selection are important steps for security, but today many producers use more direct viral research techniques (PCR) and it is likely that these have a technical development in both the selection and the quality control.Specific treatments are applied in order to inactivate certain viruses such as solvent detergent treatment, pasteurization, immunopurification.
2- Risk stable products:
The inactivation by solvent detergent eliminates enveloped viruses, but has no effect on the virus of hepatitis A or parvovirus B19. Pasteurization is performed at a temperature too low to get rid of the infectivity of all transmissible agents. There is therefore a theoretical possibility of transmission by albumin without epidemiological data and vigilance were not able yet clearly identify the risks associated with albumin. Antihemophilic factor VIII may induce the appearance of antibodies anti-factor VIII inhibitor coagulant activity. The recombinant factor VIII seems very immunogenic in a recent study without a comparison of immunogenicity of immunopurified factor VIII and recombinant factor VIII can be made. The development of factor IX in hemophilia B is rarer; by cons, there seems thrombogenic greater risk especially at high doses. Multipurpose or specific immunoglobulins are widely prescribed and few immediate side effects have been described. Intravenous immunoglobulin used in the treatment of immune thrombocytopenic purpura cause moderate hemolysis but which significantly lowers the hemoglobin. Disease transmission with immunoglobulins is a controversial subject and reported cases may be due to a failure in the manufacturing process. Finally, it is classic but probably exceptional observed that subjects with IgA deficiency have an anaphylactic shock when immunoglobulin administration. Security measures are numerous, scalable, more accurate and more rigorous procedures, but zero risk does not exist. However, the study of accidents shows that many failures are due to human error in one or often several stages of the transfusion chain. The adaptation of the system, the application of rapid and effective remedies can not be conceived without a continuity from donor to recipient, any anomaly in the recipient before to analyze all stages to the donor. This back and forth of information is an essential element of the system and the quality of staff training and motivation in a series from the generosity of the donor to the welfare of the patient.
Highlights to include:
• The risks associated with transfusion of blood products or blood derivatives led to develop other therapeutic solutions.
• Thus autologous transfusion is used whenever possible in planned surgery, that hemodilution is applied more widely, as erythropoiesis stimulating cytokines or thrombopoiesis saw their broad scope and experienced acceleration in their development. Meanwhile, products of genetic recombination have invaded the market especially for the treatment of hemophilia A.
• The risks are now better valued and are far more limited due to the implementation of legislative security measures, regulations, the establishment of “best practices” of quality assurance, and the principle of caution.
• We will consider successively the major principles regarding security measures, blood products and the risks and accidents that may be associated with their use, either because of non-compliance with procedures or technical limitations.
Strong Points to remember:
• The safety measures are intended to: prevent the risk, limit risk, correct the failures, improve products and human practice.
• Measures to reduce the risk of blood transfusion are:
– Careful selection of donors by qualified doctors; – A more efficient biological qualification;
– Preparation of standardized blood products;
– Transportation, conservation, distribution of blood products in accordance with good practice;
– A medical prescription, a customized distribution;
– A systematic and careful ultimate control, monitoring of transfusion;
– A blood safety, a collection and analysis of incidents.
– An initial qualification and continuous training of staff.