Complications after blood transfusion

The most frequent transfusion complications are reactions with chills and febrile non-hemolytic reactions. The most serious complication is the acute hemolytic reaction caused by ABO incompatible transfusion, and acute transfusion-associated lung damage, which is accompanied by a high percentage of deaths.

Important is the early recognition of transfusion complications and notification of this blood bank. The most common symptoms are chills, fever, shortness of breath, dizziness, rash, itching and pain. If these symptoms occur (except for localized rash and itching), transfusion should be stopped immediately, and intravenous infusion should be continued with saline solution of sodium chloride. The remaining component of blood and a sample of the recipient's blood with an anticoagulant should be sent to the blood bank for the necessary studies. Further transfusions should be deferred until the cause of the reaction is clarified, in case transfusion is necessary, the erythrocyte mass of the O-Rh-negative group is used.

Hemolysis of the erythrocytes of the donor or recipient during or after transfusion may be caused by ABO / Rh incompatibility, plasma antibodies, hemolyzed or brittle red blood cells (for example, from blood overheating, contact with hypotonic solutions). The most frequent and severe is hemolysis, when incompatible donor erythrocytes are hemolysed by the recipient's plasma antibodies. The hemolytic reaction can be acute (within 24 hours) or delayed (from 1 to 14 days).

Acute hemolytic transfusion reaction (OGTR)

About 20 people die each year from acute hemolytic transfusion reactions in the United States. An acute hemolytic transfusion reaction is usually the result of interaction of plasma recipient antibodies with donor erythrocyte antigens. ABO incompatibility is the most common cause of acute hemolytic transfusion reaction. Antibodies to other group antigens (except ABO) can also cause an acute hemolytic transfusion reaction. The most common cause of an acute hemolytic transfusion reaction is not a laboratory error in the selection of blood, but an incorrect labeling or entanglement of the blood product just before transfusion.

Hemolysis is intravascular, causes hemoglobinuria with acute renal insufficiency of various degrees and possible development of disseminated intravascular coagulation (DVS). The severity of an acute hemolytic transfusion reaction depends on the degree of incompatibility, the amount of transfused blood, the rate of administration and preservation of kidney, liver and heart function. The acute phase usually develops within 1 hour from the onset of transfusion, but may manifest later during or immediately after transfusion. The beginning is usually sudden. The patient may complain of discomfort or anxiety. Dyspnoea, fever, chills, hyperemia of the face and severe pain in the lumbar region may occur. Perhaps the development of shock, which manifests a weak frequent pulse, cold sticky skin, lower blood pressure, nausea and vomiting. The consequence of hemolysis is jaundice.

If the acute hemolytic transfusion reaction develops under general anesthesia, only hypotension, uncontrolled hemorrhage from the incision and mucosa, caused by the development of ICE, dark urine caused by hemoglobinuria may be present from the symptoms.

If there is a suspicion of an acute hemolytic transfusion reaction, one of the first steps is to check the labeling data of the transfusion medium and the patient's personal data. The diagnosis is confirmed by the determination of hemoglobin in urine, serum LDH, bilirubin and haptoglobin. Intravascular hemolysis produces free hemoglobin in blood plasma and urine; the level of haptoglobin is very low. Hyperbilirubinemia may develop later.

After the completion of the acute phase, the prognosis depends on the degree of renal failure. The presence of diuresis and a decrease in the level of urea usually heralds a recovery. The outcome in chronic kidney failure is rare. Long oliguria and shock are poor prognostic signs.

If suspected of an acute hemolytic transfusion reaction, transfusion should be stopped and maintenance therapy initiated. The purpose of the initial treatment is to maintain blood pressure and renal blood flow, using intravenous infusions of 0.9% sodium chloride solution with furosemide. It is necessary to achieve a volume of diuresis of 100 ml / h for 24 hours. The initial dose of furosemide is 40-80 mg (1-2 mg / kg in children) with an increase in dose to support diuresis 100 ml / h on the first day.

Antihypertensive drugs are administered with caution. Pressor drugs that reduce renal blood flow (for example, adrenaline, norepinephrine, high doses of dopamine) are contraindicated. If prescribing prescription drugs is necessary, dopamine is used in a dose of 2-5 μg / (kg-min).

An emergency examination of the patient by a nephrologist is necessary, especially in the absence of diuresis within 2-3 hours after the initiation of therapy, which may indicate the development of acute tubular necrosis. In such cases, hydration and diuretics can be contraindicated and dialysis is necessary.

[1], [2], [3], [4]

Delayed hemolytic transfusion reaction

Sometimes a patient sensitized to erythrocyte antigens has a very low level of antibodies and a negative pre-transfusion examination. After the transfusion of the red blood cells carrying this antigen, a primary or anamnestic response can develop that causes a delayed hemolytic transfusion reaction that does not have such a dramatic manifestation as an acute hemolytic transfusion reaction. It can be asymptomatic or cause a slight increase in temperature. Severe symptoms are rare. Usually, the transfused erythrocytes (having an antigen) are destroyed, which leads to a decrease in hematocrit, a slight increase in the concentration of LDH and bilirubin. Due to the fact that the delayed hemolytic transfusion reaction usually proceeds easily and is self-limiting, it is often not detected and clinically manifested by an unexplained decrease in hemoglobin concentration. Treatment of pronounced reactions is similar to treatment of an acute hemolytic transfusion reaction.

[5], [6], [7], [8], [9]

Febrile nonhemolytic transfusion reactions

Febrile reactions can develop in the absence of hemolysis. One possible reason for the febrile response is antibodies directed against leukocyte antigens of the HLA system for all other compatible parameters of the donor blood. This cause is most typical in patients receiving frequent blood transfusion. The second possible cause is cytokines released from leukocytes during storage, especially in thromboconcentrate.

Clinically, the febrile response is manifested by an increase in body temperature of more than 1 ° C, chills, sometimes headache and back pain. Often simultaneously develop symptoms of an allergic reaction. Since fever and chills also accompany severe hemolytic transfusion reactions, all patients with febrile reactions should be examined as described above.

Most febrile reactions are successfully treated with acetaminophen and, if necessary, with diphenhydramine. Patients can be assigned acetaminophen before other transfusions. If the patient had more than one febrile reaction, special anti-leukocyte filters could be used before the next transfusion. Many clinics use pre-prepared blood components with a low white blood cell count.

[10], [11], [12], [13], [14], [15], [16]

Allergic reactions

An allergic reaction to an unknown component of the donor blood is a frequent occurrence and is caused by allergens of the donor plasma or, more rarely, by the antibodies of the al-ferrified donor. These reactions usually proceed easily, with the manifestation of hives, swelling, sometimes dizziness and headache during or immediately after transfusion. Often the body temperature rises. Less common is shortness of breath, noisy breathing and urinary and fecal incontinence, which indicates a generalized spasm of smooth muscles. Occasionally, anaphylaxis occurs, especially in recipients with IgA deficiency.

In patients with an allergy or a post-transfusion allergic reaction in history, prophylactic administration of antihistamines may be used before the onset of transfusion (eg, diphenhydramine 50 mg orally or intravenously). Note: medications never mix with blood. At the onset of an allergic reaction, transfusion stops. With the help of antihistamines (for example, diphenhydramine 50 mg intravenously) it is usually possible to control mild urticaria and itching, and transfusion can be resumed. However, with moderately expressed reactions (generalized urticaria or easily expressed bronchospasm), administration of hydrocortisone (100-200 mg intravenously) is required, and in case of severe anaphylactic reaction, additional adrenaline injection of 0.5 ml in a 1: 1000 subcutaneous dilution is required, as well as a study of the cause of the reaction together with a blood bank. In the future, transfusions are not carried out until a full explanation of the causes. Patients with severe IgA deficiency require transfusions of washed red blood cells, washed-out platelets and plasma from lgA-deficient donors.

[17], [18], [19],

Overload volume

High osmotic pressure of blood products, especially whole blood, increases the volume of intravascular fluid, which can lead to volume overload, especially in patients that are sensitive to this factor (for example, with cardiac or renal failure). To such patients, transfusions of whole blood are contraindicated. Erythrocyte mass should be transfused slowly. The patient should be under observation, and if there are signs of heart failure (dyspnea, wheezing), transfusion should be stopped and treatment of heart failure started.

Usually, diuretics are prescribed (furosemide 20-40 mg intravenously.If necessary transfusions of large volumes of plasma, for example, with an overdose of warfarin, furosemide can be used simultaneously with the onset of blood transfusion.In patients who have a high risk of volume overload (with cardiac or renal insufficiency), preventive treatment diuretics (furosemide 20-40 mg intravenously).

Acute lung damage

Transfusion-associated acute lung injury is a rare complication and is due to anti-HLA or anti-granulocyte antibodies in the donor plasma that agglutinate and degranulate the recipient's granulocytes in the lungs. An acute respiratory syndrome develops, and on the roentgenogram of the lungs, characteristic signs of non-cardiogenic pulmonary edema are revealed. After ABO incompatibility, this complication is the second most frequent cause of death associated with blood transfusion. The frequency of this pathology is 1: 5000-10 000, but mild or moderate acute lung lesions usually go unnoticed. Conducting maintenance therapy usually leads to recovery without long-term consequences. The appointment of diuretics should be avoided. Cases of acute lung involvement are recorded.

[20], [21], [22], [23], [24], [25]

Increased affinity for oxygen

In blood stored for more than 7 days, the content of erythrocyte 2,3-diphosphoglycerate (DPG) decreases, which leads to an increase in affinity for O ₂ and makes it difficult to release it into tissues. There is unconvincing evidence that the deficiency of 2,3-DPG is clinically significant, except for the cases of replacement transfusion produced in children in patients with sickle cell disease with acute coronary syndrome and stroke in some patients with severe heart failure. After transfusion of erythrocytic mass, regeneration of 2,3-DPG occurs within 12-24 hours.

Graft-versus-host disease (GVHD)

Transfusion-associated "graft versus host disease" is usually caused by transfusions of blood products containing immunocompetent lymphocytes to patients with immunodeficiency. Donor lymphocytes attack host tissues. Graft versus host disease is sometimes found in patients with normal immunity if they receive blood from donors that are homozygous for the HLA-haplotype (usually close relatives) for whom the patient is heterozygous. Symptoms and signs include fever, skin rash, nausea, watery with a trace of blood, diarrhea, lymphadenopathy, pancytopenia due to bone marrow aplasia. There may also be jaundice and increased activity of liver enzymes. The disease "graft versus host" manifests itself within 4-30 days after transfusions and is diagnosed on the basis of clinical signs and biopsy of the skin and bone marrow. Lethality in the disease "transplant against the host" exceeds 90%, since there is no specific treatment.

Preliminary irradiation of all transfused blood products prevents the development of the "graft versus host disease" (damaging the DNA of donor lymphocytes). This is done in recipients with immunodeficiency status (hereditary immunodeficiency syndromes, hematological diseases, hematopoietic stem cell transplantation, neonates), and also if the donor is a first-degree relative or transfusion of HLA-compatible components other than hematopoietic stem cells.

Complications of massive transfusions

Massive transfusions are transfusions in excess of or equivalent to one volume of blood taken within 24 hours (eg 10 doses for an adult patient of 70 kg). When a patient receives canned blood in such a large volume, the patient's own blood can make up only about 1/3 of the original volume.

In situations not complicated by prolonged hypotension or DIC, the most common complication of massive transfusions is dilution thrombocytopenia. Platelets in the stored blood are not fully functional. The content of clotting factors (other than factor VIII) usually remains sufficient. There may be a microvascular type of bleeding (bleeding from cutaneous cuts, trauma). Transfusion of 5-8 doses (1 dose / 10 kg) of thromboconcentrate is usually sufficient to correct this type of bleeding in adult patients. It may be necessary to additionally introduce fresh-frozen plasma and cryoprecipitate.

Hypothermia caused by rapid transfusion of large amounts of cold blood can cause arrhythmia or acute heart failure. The development of hypothermia can be prevented by using equipment to carefully warm the blood. The use of other methods of warming (for example, a microwave oven) is contraindicated because of the potential for damage to erythrocytes and hemolysis.

Citrate and potassium toxicity, as a rule, does not develop even with massive transfusions, but this kind of toxicity can be intensified in the presence of hypothermia. In patients with a deficiency of liver function, metabolism of citrate may be impaired. Hypocalcemia occurs, but rarely needs treatment (intravenously, 10 ml of a 10% solution of gluconate Ca) is injected no faster than 10 minutes. In patients with kidney failure, potassium levels may rise if blood is transfused with a shelf life of more than 1 week (in blood stored for less than 1 week, potassium accumulates usually only slightly). Mechanical hemolysis during transfusion can lead to increased levels of potassium. Hypokalemia can occur 24 hours after the transfusion of old red blood cells (more than 3 weeks of storage), which accumulate potassium.

[26], [27], [28], [29], [30]

Infectious complications

Bacterial contamination of packets with erythrocytes is rare and possibly due to non-compliance with asepsis rules in the collection of blood or transitory asymptomatic donor bacteremia. Cooling the erythrocyte mass usually limits bacterial growth, with the exception of cryophilic organisms such as Yersinia sp, which can produce a dangerous level of endotoxin. All doses of the erythrocyte mass should be inspected daily for possible bacterial growth, as indicated by a discoloration of the preparation. Since the platelet concentrate is stored at room temperature, it has an increased risk of bacterial growth and endotoxin production in cases of contamination. To minimize bacterial growth, the shelf life is limited to five days. The risk of bacterial contamination of platelets is 1: 2500. Therefore, thromboconcentrate is routinely tested for the presence of bacteria.

Occasionally syphilis is transmitted through fresh blood or platelets. Storage of blood for more than 96 hours at 4-10 ° C destroys spirochetes. Although federal regulations require serological testing for donated blood syphilis, infected donors are seronegative in the early stages of the disease. Recipients of infected blood can develop a characteristic secondary rash.

Hepatitis can occur after transfusion of any component of the blood. The risk decreases after viral inactivation when the serum albumin and plasma proteins are heated and when recombinant coagulation factor concentrates are used. Testing for hepatitis is required for all donor blood. The risk of hepatitis B is 1: 200 000, hepatitis C 1: 1.5 million. Due to the short-term viremic phase and concomitant clinical manifestations that prevent blood shedding, hepatitis A (infectious hepatitis) is not a frequent cause of transfusion-associated hepatitis.

HIV infection in the United States is almost entirely HIV-1, although there are cases of HIV-2. Testing for the presence of antibodies to both viruses is mandatory. DNA testing for the HIV-1 antigen is also required, as is HIV-1 p24 antigen. In addition, blood donors are questioned about lifestyle, on the basis of which they can be classified as a high-risk group of HIV infection. HIV-0 is not identified among blood donors. Estimated risk of HIV transmission during transfusion is 1: 2 million.

Cytomegalovirus (CMV) can be transmitted through leukocytes of transfused blood. The virus is not transmitted through fresh frozen plasma. Since the virus does not cause disease in recipients with normal immunity, routine testing of antibodies in the donor blood is not required. However, CMV can cause severe or fatal disease in immunosuppressive patients who should receive CMV negative blood products from donors that do not have antibodies to CMV, or it is necessary to remove leukocytes from the blood with filters.

Human Type I T-cell lymphotropic virus (HTLV-I) can cause T-cell lymphoma / leukemia in adults, HTLV-1-associated myelopathy, tropical spastic paraparesis, the cause of post-transfusion seroconversion in some patients. All blood donors are tested for antibodies to HTLV-I and HTLV-II. The estimated risk of a false-negative result in the testing of donor blood is 1: 641,000.

There were no reports of transfusion of Creutzfeldt-Jakob disease, current practice hinders the delivery of blood to persons receiving human growth hormone, a dural trench or family members with patients with Creutzfeldt-Jakob disease. A new version of the Creutzfeldt-Jakob disease (a disease of cow rabies) is not transmitted through blood transfusion. However, donors who have spent considerable time in the UK and parts of Europe are suspended from donating blood.

Malaria is easily transmitted through infected blood. Many donors do not suspect that they have malaria, which can be latent and capable of transmission for 10-15 years. The storage of blood does not prevent the transmission of the pathogen of malaria. Possible donors need to be interviewed about malaria, as well as about visiting regions where infection may occur. Donors who endured malaria or are immigrants or citizens from endemic countries are denied blood donation within 3 years, persons traveling in endemic countries are denied blood donation within 1 year. Babesiosis is rarely transmitted by transfusion.