Acute hemolytic transfusion reaction

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An acute hemolytic transfusion reaction (AHTR), also called immediate hemolytic transfusion reaction, is a life-threatening reaction to receiving a blood transfusion. AHTRs occur within 24 hours of the transfusion and can be triggered by a few milliliters of blood. The reaction is triggered by host antibodies destroying donor red blood cells. AHTR typically occurs when there is an ABO blood group incompatibility, and is most severe when type A donor blood is given to a type O recipient. [1] [2] [3]

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Signs and symptoms

Early acute hemolytic transfusion reactions are typically characterized by fever, which may be accompanied by rigors (chills). Mild cases are also typically characterized by abdominal, back, flank, or chest pain. More severe cases may be characterized by shortness of breath, low blood pressure, hemoglobinuria, and may progress to shock and disseminated intravascular coagulation. In anesthetized or unconscious patients, hematuria (blood in the urine) may be the first sign of AHTR. Other symptoms include nausea, vomiting, and wheezing. [4]

Causes

The most common cause of acute hemolytic transfusion reaction is ABO incompatibility, which is typically due to human error that results in a recipient receiving the incorrect blood product. Rarely, other blood type incompatibilities can cause AHTR, the most common of which is Kidd antigen incompatibility. [4] Rh, Kell, and Duffy antigen incompatibility have also been implicated in AHTR. [5]

Mechanism

Acute hemolytic transfusion reactions result when antibodies against A and/or B antigens (isohemagglutinins) present in the recipient's blood destroy the respective donor red blood cells. [4] [5] This is mediated through the antibodies IgM (and to a lesser extent IgG) which cause activation of the complement cascade, with complement C5-C9 forming the membrane attack complex which leads to pore formation and red blood cell lysis. [6] The lysed red blood cells release free hemoglobin into the bloodstream, overwhelming hemoglobin binding proteins such as albumin, haptoglobin, and hemopexin, with the excess free hemoglobin leading to renal vasoconstriction (via nitric oxide scavenging), which then leads to acute tubular necrosis and acute kidney injury. [6]

The antibodies also activate the coagulation cascade (blood clotting system) via factor XII, which can lead to disseminated intravascular coagulation and kidney damage. Isohemagglutinins also activate the complement cascade via C3a and C5a, which then promote inflammatory cytokine release from white blood cells. C3a and C5a also activate mast cells which release serotonin and histamine, which along with fragments of red blood cells that were destroyed, further stimulate the release of inflammatory cytokines. [6] These inflammatory cytokines include IL-1, IL-6, IL-8, and TNF-alpha, which cause increased capillary permeability and vasodilation leading to symptoms of low blood pressure, fever, chest pain, nausea, vomiting, and wheezing. [4] [6]

Diagnosis

The diagnosis of AHTR is made with microscopic examination of the recipient's blood and a direct antiglobulin test (direct Coombs test) which detects IgG antibodies or complement bound to red blood cells and is usually diagnostic of acute hemolytic transfusion reactions. [6] The donor and recipient blood can be re-tested with a type, crossmatch, and antibody screen to determine the cause of the reaction. [4] The donor blood should be examined for any labelling error or other possible errors from the blood bank, which may help prevent other mislabeled blood products from being distributed. [6] Testing the donor blood using a gram stain and blood culture can also help to rule out an infectious cause of the symptoms (such as the donor receiving infected blood). [6] Testing for urine or plasma free hemoglobin may also assist in the diagnosis. [6]

Treatment

Initial treatment for any type of transfusion reaction, including AHTR, is discontinuation of the transfusion. Fluid replacement and close monitoring of vital signs are important. People with AHTR are managed with supportive care, which may include diuretics, blood pressure support, and treatment of disseminated intravascular coagulation (with fresh frozen plasma, cryoprecipitate, and platelet transfusion). [6] The use of steroids, intravenous immune-globulins (IVIG) or plasma exchange is not supported by evidence. [6] Furosemide is the diuretic of choice in treatment of AHTR with decreased urine output, because it increases the amount of blood that reaches the renal cortex. [4] Mannitol may also be used. [5] Dopamine is used for blood pressure support because it causes vasodilation (dilation of blood vessels) in the kidneys as well as increasing the cardiac output (amount of blood pumped by the heart each minute). [4]

Prognosis

The severity and prognosis of acute hemolytic transfusion depends on the rate of blood administration and the total volume of the transfusion. The levels of anti-A and anti-B antibodies in the recipients blood may also predict the prognosis, with higher levels of antibodies thought to portend a more severe course. [6] Approximately 2% of cases are fatal. Reactions that begin sooner are typically more severe. [4]

Epidemiology

Acute hemolytic transfusion reaction is estimated to occur in 1 in 38,000 to 1 in 70,000 transfusions. An estimated 41% of ABO-incompatible transfusions result in AHTR. [4]

Related Research Articles

<span class="mw-page-title-main">Blood type</span> Classification of blood based on antibodies and antigens on red blood cell surfaces

A blood type is a classification of blood, based on the presence and absence of antibodies and inherited antigenic substances on the surface of red blood cells (RBCs). These antigens may be proteins, carbohydrates, glycoproteins, or glycolipids, depending on the blood group system. Some of these antigens are also present on the surface of other types of cells of various tissues. Several of these red blood cell surface antigens can stem from one allele and collectively form a blood group system.

Humoral immunity is the aspect of immunity that is mediated by macromolecules – including secreted antibodies, complement proteins, and certain antimicrobial peptides – located in extracellular fluids. Humoral immunity is named so because it involves substances found in the humors, or body fluids. It contrasts with cell-mediated immunity. Humoral immunity is also referred to as antibody-mediated immunity.

<span class="mw-page-title-main">Hemolytic anemia</span> Medical condition

Hemolytic anemia or haemolytic anaemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells (RBCs), either in the blood vessels or elsewhere in the human body (extravascular). This most commonly occurs within the spleen, but also can occur in the reticuloendothelial system or mechanically. Hemolytic anemia accounts for 5% of all existing anemias. It has numerous possible consequences, ranging from general symptoms to life-threatening systemic effects. The general classification of hemolytic anemia is either intrinsic or extrinsic. Treatment depends on the type and cause of the hemolytic anemia.

<span class="mw-page-title-main">Hemolytic disease of the newborn</span> Fetal and neonatal alloimmune blood condition

Hemolytic disease of the newborn, also known as hemolytic disease of the fetus and newborn, HDN, HDFN, or erythroblastosis fetalis, is an alloimmune condition that develops in a fetus at or around birth, when the IgG molecules produced by the mother pass through the placenta. Among these antibodies are some which attack antigens on the red blood cells in the fetal circulation, breaking down and destroying the cells. The fetus can develop reticulocytosis and anemia. The intensity of this fetal disease ranges from mild to very severe, and fetal death from heart failure can occur. When the disease is moderate or severe, many erythroblasts are present in the fetal blood, earning these forms of the disease the name erythroblastosis fetalis.

The direct and indirect Coombs tests, also known as antiglobulin test (AGT), are blood tests used in immunohematology. The direct Coombs test detects antibodies that are stuck to the surface of the red blood cells. Since these antibodies sometimes destroy red blood cells they can cause anemia; this test can help clarify the condition. The indirect Coombs test detects antibodies that are floating freely in the blood. These antibodies could act against certain red blood cells; the test can be carried out to diagnose reactions to a blood transfusion.

Alloimmunity is an immune response to nonself antigens from members of the same species, which are called alloantigens or isoantigens. Two major types of alloantigens are blood group antigens and histocompatibility antigens. In alloimmunity, the body creates antibodies against the alloantigens, attacking transfused blood, allotransplanted tissue, and even the fetus in some cases. Alloimmune (isoimmune) response results in graft rejection, which is manifested as deterioration or complete loss of graft function. In contrast, autoimmunity is an immune response to the self's own antigens. Alloimmunization (isoimmunization) is the process of becoming alloimmune, that is, developing the relevant antibodies for the first time.

<span class="mw-page-title-main">Agglutination (biology)</span> Type of antibody response

Agglutination is the clumping of particles. The word agglutination comes from the Latin agglutinare.

Autoimmune hemolytic anemia (AIHA) occurs when antibodies directed against the person's own red blood cells (RBCs) cause them to burst (lyse), leading to an insufficient number of oxygen-carrying red blood cells in the circulation. The lifetime of the RBCs is reduced from the normal 100–120 days to just a few days in serious cases. The intracellular components of the RBCs are released into the circulating blood and into tissues, leading to some of the characteristic symptoms of this condition. The antibodies are usually directed against high-incidence antigens, therefore they also commonly act on allogenic RBCs. AIHA is a relatively rare condition, with an incidence of 5–10 cases per 1 million persons per year in the warm-antibody type and 0.45 to 1.9 cases per 1 million persons per year in the cold antibody type. Autoimmune hemolysis might be a precursor of later onset systemic lupus erythematosus.

Paroxysmal cold hemoglobinuria (PCH) or Donath–Landsteiner hemolytic anemia (DLHA) is an autoimmune hemolytic anemia featured by complement-mediated intravascular hemolysis after cold exposure. It can present as an acute non-recurrent postinfectious event in children, or chronic relapsing episodes in adults with hematological malignancies or tertiary syphilis. Described by Julius Donath (1870–1950) and Karl Landsteiner (1868–1943) in 1904, PCH is one of the first clinical entities recognized as an autoimmune disorder.

In ABO hemolytic disease of the newborn maternal IgG antibodies with specificity for the ABO blood group system pass through the placenta to the fetal circulation where they can cause hemolysis of fetal red blood cells which can lead to fetal anemia and HDN. In contrast to Rh disease, about half of the cases of ABO HDN occur in a firstborn baby and ABO HDN does not become more severe after further pregnancies.

The Kidd antigen system are proteins found in the Kidd's blood group, which act as antigens, i.e., they have the ability to produce antibodies under certain circumstances. The Jk antigen is found on a protein responsible for urea transport in the red blood cells and the kidney. They are important in transfusion medicine. People with two Jk(a) antigens, for instance, may form antibodies against donated blood containing two Jk(b) antigens. This can lead to hemolytic anemia, in which the body destroys the transfused blood, leading to low red blood cell counts. Another disease associated with the Jk antigen is hemolytic disease of the newborn, in which a pregnant woman's body creates antibodies against the blood of her fetus, leading to destruction of the fetal blood cells. Hemolytic disease of the newborn associated with Jk antibodies is typically mild, though fatal cases have been reported.

<span class="mw-page-title-main">Packed red blood cells</span> Red blood cells separated for blood transfusion

Packed red blood cells, also known as packed cells, are red blood cells that have been separated for blood transfusion. The packed cells are typically used in anemia that is either causing symptoms or when the hemoglobin is less than usually 70–80 g/L. In adults, one unit brings up hemoglobin levels by about 10 g/L. Repeated transfusions may be required in people receiving cancer chemotherapy or who have hemoglobin disorders. Cross-matching is typically required before the blood is given. It is given by injection into a vein.

Type II hypersensitivity, in the Gell and Coombs classification of allergic reactions, is an antibody mediated process in which IgG and IgM antibodies are directed against antigens on cells or extracellular material. This subsequently leads to cell lysis, tissue damage or loss of function through mechanisms such as

  1. complement activation via the classical complement pathway
  2. Antibody-dependent cellular cytotoxicity or
  3. anti-receptor activity.

Hematologic diseases are disorders which primarily affect the blood and blood-forming organs. Hematologic diseases include rare genetic disorders, anemia, HIV, sickle cell disease and complications from chemotherapy or transfusions.

This page is currently under construction.

The Vel blood group is a human blood group that has been implicated in hemolytic transfusion reactions. The blood group consists of a single antigen, the high-frequency Vel antigen, which is expressed on the surface of red blood cells. Individuals are typed as Vel-positive or Vel-negative depending on the presence of this antigen. The expression of the antigen in Vel-positive individuals is highly variable and can range from strong to weak. Individuals with the rare Vel-negative blood type develop anti-Vel antibodies when exposed to Vel-positive blood, which can cause transfusion reactions on subsequent exposures.

The Junior blood group system is a human blood group defined by the presence or absence of the Jr(a) antigen, a high-frequency antigen that is found on the red blood cells of most individuals. People with the rare Jr(a) negative blood type can develop anti-Jr(a) antibodies, which may cause transfusion reactions and hemolytic disease of the newborn on subsequent exposures. Jr(a) negative blood is most common in people of Japanese heritage.

<span class="mw-page-title-main">Blood compatibility testing</span> Testing to identify incompatibilities between blood types

Blood compatibility testing is conducted in a medical laboratory to identify potential incompatibilities between blood group systems in blood transfusion. It is also used to diagnose and prevent some complications of pregnancy that can occur when the baby has a different blood group from the mother. Blood compatibility testing includes blood typing, which detects the antigens on red blood cells that determine a person's blood type; testing for unexpected antibodies against blood group antigens ; and, in the case of blood transfusions, mixing the recipient's plasma with the donor's red blood cells to detect incompatibilities (crossmatching). Routine blood typing involves determining the ABO and RhD type, and involves both identification of ABO antigens on red blood cells and identification of ABO antibodies in the plasma. Other blood group antigens may be tested for in specific clinical situations.

The Sid blood group system is a human blood group defined by the presence or absence of the Sd(a) antigen on a person's red blood cells. About 96% of people are positive for the Sd(a) antigen, which is inherited as a dominant trait. Among Sd(a) positive individuals, the expression of the antigen ranges from extremely weak to extremely strong. Very strong expression of the antigen is referred to as a Sd(a++) phenotype. In addition to being expressed on red blood cells, Sd(a) is secreted in bodily fluids such as saliva and breast milk, and is found in the highest concentrations in urine. Urine testing is considered the most reliable method for determining a person's Sid blood type.

<span class="mw-page-title-main">Monocyte monolayer assay</span> Laboratory test for clinically significant alloantibodies

The monocyte monolayer assay (MMA) is used to determine the clinical significance of alloantibodies produced by blood transfusion recipients. The assay is used to assess the potential for intravascular hemolysis when incompatible cellular blood products are transfused to the anemic patient. When donor cells possess substances that are not produced by the recipient, the recipient's immune system produces antibodies against the substance; these are called alloantibodies. Specific white blood cells, called monocytes, are tasked with ingesting foreign material and become activated during certain inflammatory events. These activated monocytes come in contact with antibody-sensitized red blood cells (RBC) and may or may not exhibit phagocytosis (ingestion) and destroy the donor red blood cells. If monocytes destroy the RBC, the antibody attached to those RBC is considered clinically significant.

References

  1. ↑ Covin RB, Evans KS, Olshock R, Thompson HW (2020). "Acute hemolytic transfusion reaction caused by anti-Coa". Immunohematology. 17 (2): 45–9. doi: 10.21307/immunohematology-2019-543 . PMID   15373591. S2CID   235243237.
  2. ↑ Hoffbrand, A. V.; P.A.H. Moss; J.E. Pettit (2006). Essential Haematology: 5th Edition. Blackwell Publishing. ISBN   1-4051-3649-9.
  3. ↑ Molthan L, Matulewicz TJ, Bansal-Carver B, Benz EJ (1984). "An immediate hemolytic transfusion reaction due to anti-C and a delayed hemolytic transfusion reaction due to anti-Ce+e: hemoglobinemia, hemoglobinuria and transient impaired renal function". Vox Sang. 47 (5): 348–53. doi:10.1111/j.1423-0410.1984.tb04138.x. PMID   6438912. S2CID   41434530.
  4. 1 2 3 4 5 6 7 8 9 Caligiuri, Michael; Levi, Marcel M.; Kaushansky, Kenneth; Lichtman, Marshall A.; Prchal, Josef; Burns, Linda J.; Press, Oliver W. (2015-12-23). Williams Hematology, 9E. McGraw-Hill Education. ISBN   9780071833004.
  5. 1 2 3 Jameson, J. Larry; Kasper, Dennis L.; Longo, Dan L.; Fauci, Anthony S.; Hauser, Stephen L.; Loscalzo, Joseph (2018-08-13). Harrison's principles of internal medicine (20th ed.). New York. ISBN   9781259644030. OCLC   1029074059.{{cite book}}: CS1 maint: location missing publisher (link)
  6. 1 2 3 4 5 6 7 8 9 10 11 Panch, Sandhya R.; Montemayor-Garcia, Celina; Klein, Harvey G. (11 July 2019). "Hemolytic Transfusion Reactions". New England Journal of Medicine. 381 (2): 150–162. doi:10.1056/NEJMra1802338. PMID   31291517. S2CID   261097623.
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