2 Classification
Based on the urgency of the occurrence of adverse transfusion reactions and clinical manifestations, adverse transfusion reactions are classified into two types: acute transfusion reactions and delayed transfusion reactions.
Acute transfusion reactions
are transfusion adverse reactions that occur during or within 24 hours after blood transfusion.
(I) Pathogenesis
Based on the pathogenesis, it is divided into two types: immune transfusion reaction and non-immune transfusion reaction.
1. Immune transfusion reactions are caused by antigen-antibody incompatibility between the blood groups of the donor and the recipient. These include: acute hemolytic reaction due to ABO blood group incompatibility,
Rh blood group incompatibility, etc.; febrile non-hemolytic reaction due to leukocyte antibody; IgA antibody-mediated anaphylactic shock reaction; transfusion-associated lung injury due to input of blood with anti-recipient leukocyte or platelet antibodies; urticaria, etc.
2. Non-immune transfusion reactions are caused by certain non-blood group antigen-antibody reactions. These include: hyperthermia, even infectious shock due to blood product contamination; acute congestive heart failure due to circulatory overload; hemolytic reaction occurring due to destruction of blood cells by physicochemical factors; air embolism and sodium citrate intoxication due to the input of large amounts of stored blood [2].
(2) Clinical manifestations and management
According to their clinical manifestations and severity, acute transfusion reactions are categorized into three types: mild, moderately severe and life-threatening reactions.
1. Mild reaction is a mild hypersensitivity reaction caused by a certain protein in the input plasma, and histamine is released excessively in the local skin.
Clinical manifestationsPatients develop a localized skin reaction within minutes of transfusion, most commonly a rash and urticaria, often accompanied by itching of the skin.
Treatment ①Slow down the rate of blood transfusion. ② Administer antihistamine drugs (e.g. chlorpheniramine 0.1mg/kg intramuscularly). If the symptoms are relieved within 30 minutes after the above treatment, the transfusion can be continued at the normal rate; if there is no clinical improvement or there is deterioration within 30 minutes, it will be treated as a moderately severe reaction.
Prevention Antihistamines are usually given prophylactically 30 minutes before transfusion, such as chlorpheniramine 0.1 mg/kg, intramuscularly or intravenously, or isoprinosine 50 mg,orally [3].
2. Moderate-to-severe reaction It is caused by the release of cytokines from stock blood components and/or the reaction of leukocytes in the transfused blood with antibodies in the patient's serum resulting in the release of pyrogens. It is also known as a non-hemolytic febrile reaction. The incidence is about 1 to 2% in patients requiring regular blood transfusions.
Clinical manifestationsPatients usually develop fever, chills, flushing, urticaria, intense itching of the skin, irritability, rapid heartbeat, and may experience mild dyspnea and headache within 30 to 60 minutes of transfusion of blood products.
Treatment ①Stop the transfusion immediately, replace the transfusion apparatus, and keep the venous access open with saline; ②Inform the patient's attending physician and the blood bank; ③Send the transfusion apparatus and the remaining blood, the fresh urine sample, and the blood sample (one anticoagulated, one non-anticoagulated) collected from the other arm to the blood bank and the testing department for analysis. ④ Intramuscular injection of antihistamines (e.g., chlorpheniramine 0.1 mg/kg or other drugs equivalent). Oral (acetaminophen 10mg/kg) or anally inserted antipyretic drugs (e.g. indomethacin suppository 50-100mg). ⑤ If symptoms of allergic reactions, such as bronchospasm and asthma, are present, sedate corticosteroids. ⑥ Generally, if the symptoms improve after 15 minutes of the above treatment, the blood can be replaced by a bag of blood to be re-infused slowly and closely observed; if there is no clinical improvement or a tendency to deteriorate within 15 minutes, the patient will be treated according to the life-threatening reaction.
Prevention For patients with repeated regular transfusions, or those who have had more than two transfusion-related non-hemolytic febrile reactions, the rate of transfusion should be slowed down (3 to 4 hours per unit of red blood cells, platelet concentrates for 2 hours per bag) and antipyretic drugs can be given prophylactically for 60 minutes prior to the transfusion, but the use of aspirin should be avoided if thrombocytopenia is present. If conditions permit, leukocyte removal or filtered red cells and platelets may be used.
3. Life-threatening reactions include acute intravascular hemolysis, bacterial contamination and septic shock, fluid overload, anaphylaxis, and transfusion-related lung injury.
(1) Acute intravascular hemolysis: it is caused by transfusion of red blood cells of incompatible blood groups. Antibodies in the patient's plasma react hemolytically with the transfused heterotypic blood erythrocytes. It is mainly seen in ABO blood group incompatibility, and other blood group incompatibility also occurs, such as Rh blood group. Even a small amount of heterotypic blood (5-10 ml) transfusion can cause severe hemolysis [4].
Clinical manifestations fever, chills, increased heart rate, hypotensive shock, shortness of breath or respiratory distress, headache, irritability and anxiety, low back pain, oliguria, hemoglobinuria, and even disseminated intravascular coagulation (DIC) can occur. Symptoms of acute intravascular hemolysis can appear within minutes of the start of the transfusion if the patient is conscious, whereas in patients who are unconscious or under anesthesia, hypotension and more than one bleed due to DIC may be the only manifestations of acute hemolysis.
Treatment ①Stop the blood transfusion immediately, change the transfusion equipment, and keep the venous pathway open with saline. ②Keep the airway open, and give high concentration mask oxygen. ③Circulatory support: Infuse saline 20～30mg/kg to maintain blood volume and systolic blood pressure; if necessary, use cardiotonic agents and antihypertensive agents to support blood circulation, such as epinephrine, dopamine and dobutamine. ④Prevent renal failure, use diuretics, such as tachycardia 1-2mg/kg, while maintaining stable blood volume and blood pressure. ⑤Monitor coagulation status, prevent and correct DIC. ⑥Verify blood labels and send samples for testing: send transfusion equipment and remaining blood, fresh urine samples, and blood samples (one anticoagulated, one not) from the other arm to the blood bank and testing department. Verify crossmatching and blood grouping, monitor renal function and routine blood changes, check direct anti-human globulin test, blood gas analysis, urinary occult blood, hemoglobinuria and bilirubin levels. (7) If symptoms of allergic reactions, such as bronchospasm and asthma, occur, sedate corticosteroids.
Prevention: (1) correctly fill out the transfusion application form; (2) cross-matching; (3) labeling management system, correctly labeled blood samples and blood products; (4) before the start of transfusion, strictly carry out the "three checks and seven pairs"; (5) for the patients who have had an unexplained transfusion of intravascular hemolysis, the antibodies to rare blood group antigens should be screened for, such as Kidd, Kell and Duffy system antigens.
(2) Bacterial contamination and septic shock
According to statistics, the probability of bacterial contamination of red blood cells and platelets is 0.4% to 2%. Contamination may occur if the donor is in a state of bacteremia when donating blood. And blood contamination can occur when blood is collected and processed improperly; when plastic blood collection bags are defectively manufactured or damaged; and when plasma is thawed or cold precipitated in a contaminated water bath. Pseudomonas aeruginosa is a typical contaminating bacterium in the latter three cases, and can grow at low temperatures (2-6°C) and multiply rapidly as the temperature rises.
Clinical manifestations usually occur rapidly after the start of infusion, or may be delayed for several hours. Presentation is characterized by sudden onset of high fever and chills and hypotension.
Treatment ①Stop the transfusion immediately when symptoms are found, make bacterial culture and drug sensitivity of the transfusion equipment and the remaining blood, and make smear staining examination of the transfused blood. ②Apply broad-spectrum antibiotics. ②Apply broad-spectrum antibiotics. ③If shock occurs, actively treat with anti-shock therapy.
(3) Fluid overload: too fast blood transfusion can lead to fluid overload, triggering acute heart failure and pulmonary edema. It mostly occurs in patients with severe chronic anemia and patients with basic cardiovascular diseases.
Clinical manifestations of chest tightness, palpitations, dyspnea, inability to lie down, and wet rhonchi in the lungs.
Treatment slow down the rate of blood and fluid transfusion, control the total volume of fluid intake, maintain the balance of in and out, and use cardiotonic agents if necessary [5].
Prevention of elderly patients, patients with long-term chronic anemia, and patients with underlying cardiovascular disease should slow down the rate of blood transfusion.
(4) Anaphylaxis: transfusion-related anaphylaxis is relatively rare. Typically, large amounts of fresh frozen plasma are used during plasma exchange, and cytokines in the plasma may be responsible for the development of anaphylaxis. Rarer causes include recipients with IgA defects, and the importation of any blood product can lead to severe anaphylactic reactions in patients.
Clinical manifestations often develop minutes after the start of the transfusion. Typical manifestations are cardiac failure with accelerated heart rate, hypotension, shock, dyspnea, respiratory distress, and patients are often agitated. If not treated in time, fatal consequences occur quickly.
The treatment is the same as acute intravascular hemolysis. For IgA antibody-positive patients, IgA-negative blood products should be transfused.
(5) Transfusion related acute lung injury (TRALI): usually due to the donor plasma contains antibodies against the recipient's leukocytes, and almost always occurs when the donor is a transsexual woman who has had multiple births.
The clinical picture usually begins 1 to 4 hours after the start of the transfusion, with rapid respiratory failure and diffuse shadowing on lung X-ray.
TreatmentThere is no specific method of treatment, and the main respiratory support therapy.
PreventionTry not to use blood products supplied by multiple births to transient mothers.
(C) Investigation procedures for acute transfusion reaction
When acute transfusion reaction first occurs, the signs and symptoms are often not obvious, and it is difficult to diagnose and classify the transfusion reaction, except for mild urticaria and non-hemolytic febrile reaction, all other acute transfusion reactions are potentially fatal, so it is very important to closely observe and analyze the condition. According to WHO regulations on clinical blood use, the procedure for investigating acute transfusion reactions is as follows:
1. All transfusion reactions except mild reactions must be reported immediately to the patient's attending physician and the blood bank that supplied the blood must be notified.
2. Document in the patient's medical record file the type of transfusion reaction, how long after the transfusion the transfusion reaction occurred, and the volume, type, and blood bag number of the blood product transfused.
3. Collect specimens for testing: blood specimen 1 (blood sample taken from the other arm) for complete blood count, coagulation studies, direct anti-human globulin test, urea, creatinine, electrolytes; blood specimen 2 for blood culture; transfused blood and transfusion set with residual red blood cells and plasma; and the first urine sample after the reaction.
4. Fill out a report on transfusion reactions.
5. After completing the initial cause analysis, send the following specimens for testing: blood samples taken from the other arm at 12 and 24 hours post-transfusion (1 non-anticoagulated and 1 EDTA-anticoagulated.). ; a 24-hour urine sample from the patient.
6. The findings of the investigation and analysis were recorded in the patient's medical record file for further analysis in the future [6].
Delayed transfusion reactions
These are transfusion-related adverse reactions that occur days, weeks, or months after transfusion. They can be divided into two basic categories: transfusion-transmitted diseases and other delayed transfusion reactions.
(I) Transfusion-transmissible diseases
are caused by the presence of infectious agents in the blood of the blood donor, leading to the development of corresponding infectious diseases in the recipient. Blood donors may contain infectious agents in their blood, and thus any transfusion of blood or blood products carries the risk of transmitting disease. Strictly speaking, bacterial contamination (from the donor's skin and blood) would also be classified as a transfusion-transmitted disease, and it is rare for blood products to become bacterially contaminated during preparation, or for bacterial infections to come from an infected donor. Common transfusion-transmitted diseases include HIV-1 and HIV-2 infections, HTLV-I and HTLV-II infections, viral hepatitis B and C, syphilis, malaria, cytomegalovirus infections, EBV infections, human microvirus B19, and Toxoplasma gondii infections. Infected patients may persist for a long time without any associated manifestations.
1. Common transfusion transmitted diseases include:
(1) Acquired Immuno-deficiency Syndrome (AIDS): AIDS is caused by infection with human immunodeficiency virus (HIV), a lethal infectious disease HIV mainly destroys the human body's immune system so that the body gradually loses its immunity. HIV mainly destroys the body's immune system so that the body gradually loses its ability to defend itself against various pathogens from the outside world, so it is very easy to get infected with infectious diseases and tumors that are not easy for healthy people to suffer from, and eventually leads to death.
HIV exists in both plasma and cells, so transfusion of whole blood, component blood, plasma and its products can transmit HIV. among the transfusion transmitted diseases, AIDS is the most harmful. With the rapid spread of AIDS in the world and our country has entered the period of rapid growth of AIDS, it poses a serious threat to the safety of blood transfusion.
(2) Hepatitis B: Hepatitis B is an infectious disease caused by Hepatitis B Virus (HBV), mainly inflammatory lesions of the liver. It mainly affects children and young adults, and blood contact is the main means of transmission. China is a high prevalence area of hepatitis B, and the positive rate of HBV antigen in blood test of the general population accounts for about 12% of the total population, and it is an infectious disease that accounts for the highest proportion of blood-borne diseases in China, and it is the most widely prevalent and very serious in terms of harm. acute hepatitis can occur after infection by HBV through the bloodstream and is subsequently relieved or transformed into chronic hepatitis. The long-term consequence is the development of cirrhosis and primary liver cancer.
Patients with long-term blood transfusions should be vaccinated against hepatitis B.
(3) Hepatitis C: Hepatitis C is caused by hepatitis C virus (HCV). The clinical manifestations of hepatitis C are similar to those of hepatitis B, but the clinical course is often characterized by asymptomatic infections and chronic infections, which are more likely to evolve into chronic hepatitis, cirrhosis and liver cancer.
(4) Syphilis: the pathogen of syphilis is the syphilis spirochete. Direct sexual contact is the most important mode of transmission of syphilis. Second-stage syphilis is the syphilis spirochete from the lymph nodes into the bloodstream in the body a large number of dissemination, the third stage of syphilis invasion of the skin mucous membranes, the skeletal system, the nervous system and the cardiovascular system, leading to serious consequences. Another part of the untreated syphilis patients or the treatment of drug dosage is insufficient, the treatment is not complete, the patient does not have obvious symptoms, but the blood test can be found when the syphilis seropositivity, for hidden syphilis or latent syphilis.
Because the syphilis spirochete is very sensitive to low temperature, the donor's blood is stored at 2℃～6℃ for 72h before being sent for clinical use, which can effectively avoid the infection of missed positive syphilis and ensure the safety of clinical blood.
While syphilis-positive does not indicate HIV infection, it does indicate a high risk of exposure to HIV and other sexually transmitted diseases, and therefore, syphilis-positive donors are not qualified blood donors.
(5) Cytomegalovirus (CMV) infection: CMV infection is distributed worldwide, and humans are the only host for CMV. The rate of CMV antibody positivity in developing country populations can be as high as 90% or more. Cytomegalovirus can cause cytomegalovirus inclusion body disease, which mainly occurs in infants and young children, and adult CMV infection and immune function are closely related. The main clinical manifestations are: ① congenital infection: pregnant women infected with CMV within 3 months of gestation, the fetus may show recessive infection, but also lethal, miscarriage, preterm delivery and congenital anomalies. ② Neonatal infection: Pneumonia, hepatitis, swollen lymph nodes and rash within 3 months of birth. ③ Infection in children and adults. Most are occult infections. A few develop mononucleosis, pneumonia, hepatitis and myocarditis. ④ CMV infection in patients with immunodeficiency and organ transplantation can manifest systemic infection of various organs, with severe condition and high mortality rate.
CMV virus is mainly present in leukocytes, thus transfusion of leukocyte-denuded blood components, fresh frozen plasma, and cold precipitates can prevent the transmission of CMV.High-risk groups should be transfused with CMV-negative or leukocyte-denuded blood components [7].
(6) Malaria: Malaria is a disease caused by the mosquito-borne Plasmodium. It is mainly found in tropical and subtropical territories. The incubation period of malaria (from mosquito bite to onset of illness) is about seven to thirty days, and in some cases up to ten months. The most serious consequence of malaria is that it affects the central nervous system, causing confusion, cramps, blood and kidney problems, and death within 24 hours. In non-endemic areas, transfusion-transmitted malaria is extremely rare and is related to the type and number of Plasmodium parasites imported.
All blood components can carry Plasmodium, which can survive for years in frozen cells.
No one who has recently traveled to an infected area or has been infected with malaria is a qualified blood donor.
(7) Human T-lymphotropic virus types I and II (HTLV-Ⅰ/Ⅱ): also known as adult T-cell lymphoma/leukemia virus, is a retrovirus infecting humans by cell-mediated transmission. HTLV-Ⅰ infects mainly CD4+ T-lymphocytes in vivo, and is transmitted mainly through breastfeeding, sexual transmission, blood transfusion, and intravenous drug use*** with injection needles. HTLV-Ⅰ infection is mainly endemic in southern Japan, the Caribbean, central and western Africa, central and southern America, Papua New Guinea and Australia. The prevalence of HTLV infection in China is mainly in the southeastern coastal area, and the anti-HTLV-Ⅰpositive rate is 0.024%.
Adult T-cell leukemia and/or lymphoma (ATL) may occur in some patients infected with HTLV-Ⅰ/Ⅱ, and may also cause HTLV-Ⅰassociated myelopathy (HAM)/tropical spastic paraparesis (TSP).
HTLV-I/II infects only lymphocytes and is not present in plasma, and plasma products with the white blood cells removed do not transmit HTLV. HTLV is no longer transmissible when blood products are stored for more than 14 days.
Since the infection rate of HTLV-Ⅰ/Ⅱ is very low in China and mainly limited to the southeast coastal area, it is suggested that the screening of blood donors can be started in the HTLV-endemic areas of China, and the rest of the areas where the infection rate of HTLV is very low can be tested only once at the time of the initial blood donation.
(8) Other rare transfusion-transmitted diseases: including human short-stage virus B19 infection, EBV infection, trypanosomiasis, brucellosis, toxoplasmosis, infectious mononucleosis, and Lyme disease. There are reports that Creutzfeldt-Jakob disease may also be transmitted by blood transfusion.
2. Screening and prevention of transfusion transmitted diseases
Screening of blood donors' blood is an important part of prevention of transfusion transmitted diseases. China's "Blood Transfusion Technical Operating Procedures" stipulates that the blood collection and supply system should be tested for five items: ALT, HBsAg, anti-HCV, syphilis and anti-HIV
Despite rigorous testing, transfusion-transmitted diseases are still present for the following reasons:
(1) "Window period ": in syphilis, hepatitis, AIDS and other infectious diseases in the early stages of infection, although there has been pathogen infection, but the body has not yet formed antibodies, at this time the test is negative.
(2) the limitations of the current means of detection: in the, antibody detection, but can use genetic diagnostic techniques (PCR methods) on the "window period" of the pathogen DNA or RNA detection, improve the detection rate. Because of the PCR method of experimental technology requirements, high cost, difficult to popularize, can not be included in the scope of routine testing.
(3) The error of the detection method itself can cause missed detection: due to the error of the experiment itself, it can cause false-negative results.
(4) caused by the donor's own situation: due to the poor immunity of some donors, even if they are infected with certain pathogens, the body will not produce antibodies in a short period of time, or it takes a long time to produce antibodies, thus causing the problem of blood transfusion infection.
In order to ensure the health and safety of blood recipients, it is necessary to take strong measures to improve the quality of blood, actively carry out non-remunerated blood donation, strictly screen blood donors, carry out component transfusion, self-transfusion, and strengthen the overall quality management of blood in order to ensure the safety of blood transfusion.
(2) Other delayed transfusion reactions
Mainly including delayed hemolytic reaction; post-transfusion purpura; transfusion-associated graft-versus-host disease (TA-GVHD); and iron overload after multiple transfusions.
1. Delayed hemolytic reaction
Pregnant or multiple transfusion patients whose red blood cells have been sensitized have reduced levels of erythrocyte blood group antibodies in their bodies so that pre-transfusion monitoring fails to detect them. When the input of red blood cells with related antigens, the patient's body once again immune response, antibody levels rise, so that the red blood cells with related antigens in the transfusion within 5 to 10 days after the destruction. It is usually extravascular hemolysis.
Clinical manifestations include fever, jaundice, hemolytic anemia, and occasionally hemoglobinuria.
Treatment generally does not require special treatment. If shock, DIC, renal failure occurs, it is treated according to the corresponding rules. Monitor the anti-human globulin test, bilirubin level and perform blood group re-testing.
2. Post-transfusion purpura
It is a post-transfusion alloimmune reaction, which can be caused by destruction of platelets by HLA alloimmune reaction or HPA (human platelet antigen) alloimmune reaction, which is rare but potentially fatal.
Clinical manifestations are most often seen in female patients, acute thrombocytopenia occurs 5-10 days after transfusion of red blood cells or platelets, PLT<100×10/L. Purpura and hemorrhage of the skin and mucous membranes appear,.
Treatment generally platelets higher than 50×10/L do not need special treatment. If lower than 20 × 10 / L or obvious bleeding manifestations can take the following treatments: ① give high-dose adrenocorticotropic hormone, such as prednisone 1mg / kg. ② intravenous application of high-dose gammaglobulin (0.4 / kg) for 5 days. ③ Plasma replacement. ④ If platelets are too low, bleeding is obvious, or important organs are bleeding, platelet transfusion with antibodies compatible with the patient can be used. Generally speaking, the transfusion of those with incompatible antibodies is ineffective.
3. Transfusion associated graft versus host disease (TA-GVHD)
It is a lethal complication of blood transfusion. It usually occurs 10 to 12 days after blood transfusion. It used to occur commonly in immunodeficient patients such as bone marrow transplantation. However, in recent years the occurrence of TA-GVHD in non-immunodeficient recipients has been recognized, and it is triggered mostly by related blood donors. Among them, the predicted risk of combined TA-GVHD from transfusions between first-degree relatives (parents and children) is higher than that from transfusions between non-relatives, and second-generation blood relatives, such as (maternal) grandparents and (paternal) grandchildren, are at greater risk than first-generation blood relatives, so that the American Association of Blood Banks (AABB) recommends that radiation be performed on all blood relatives. The onset of the disease is primarily related to the leukocyte antigen (HLA) haplotype gene of the donor-recipient.
Clinical manifestations fever, rash, diarrhea (may be loose, watery or bloody stools, diarrhea is often accompanied by abdominal pain), liver damage (discomfort or pain in the liver area． Hepatomegaly, gangrene, ALT, AST, LDH, etc. are increased to different degrees) and reduction of blood tertiary system. The prognosis of this disease is very poor.
Treatment of the current high-dose epinephrine, anti-thymocyte globulin and other immunosuppressive drugs can not reduce mortality. Mostly supportive symptomatic treatment is given, emphasizing prevention.
Prevention Blood products can be irradiated by gamma radiation and then transfused to reduce lymphocyte proliferation and prevent the occurrence of GVHD. Leukocyte filters can also be used to remove leukocytes.
4. Iron overload
Each unit of blood contains about 200mg to 250mg of iron, long-term blood transfusion patients probably after 10-20 transfusions of patients with iron overload, usually after 1 year of blood transfusion or after 50 transfusions of red blood cells need to start iron removal therapy.
Clinical manifestations of iron overload caused by long-term blood transfusion, manifested in parenchymal tissues (such as liver, heart) fibrosis and functional impairment, known as secondary hemochromatosis, if only the tissue ferritin deposits, ferritin deposits. The tissues involved are liver, heart, skin, pancreas and other endocrine glands, leading to cirrhosis, liver fibrosis, liver cancer, heart failure, diabetes, infertility and growth inhibition.
Treatment The use of iron-binding factors, such as desferrioxamine, 20-60 mg/kg/d, and deferiprone (Deferiprone), 75 mg/kg/d, to keep serum ferritin below the level of 1,000 μg/L, can be effective in decreasing the accumulation of iron in the body and in reversing cardiac and hepatic disease. For those with severe iron overload, deferoxamine can be combined and used. Desferrioxamine is advantageous in removing iron deposited in the liver, while deferiprone is more effective in removing iron deposited in the heart. Deferoxamine has ocular, ototoxic and osteotoxic side effects, but they are generally tolerated. Deferiprone has mainly granulocyte deficiency side effects.
Clinicians should have a full understanding of the adverse effects of blood transfusion, and should make the decision to transfuse blood on the basis of a full assessment of the risks and benefits of blood transfusion to the patient, as well as have the knowledge and skills to identify and deal with possible adverse effects and complications of blood transfusion, actively avoid, timely and correctly deal with adverse effects of transfusion, and to ensure the safety of clinical blood transfusion.