An acute hemolytic transfusion reaction (AHTR), also called immediate hemolytic transfusion reaction, is a life-threatening reaction to receiving a

blood transfusion Blood transfusion is the process of transferring blood products into a person's circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used whole blood, but mo ...

. 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 The ABO blood group system is used to denote the presence of one, both, or neither of the A and B antigens on erythrocytes. For human blood transfusions, it is the most important of the 43 different blood type (or group) classification system ...

incompatibility, and is most severe when type A donor blood is given to a type O recipient.

Signs and symptoms

Early acute hemolytic transfusion reactions are typically characterized by fever, which may be accompanied by

rigors Chills is a feeling of coldness occurring during a high fever, but sometimes is also a common symptom which occurs alone in specific people. It occurs during fever due to the release of cytokines and prostaglandins as part of the inflammatory r ...

(chills). Mild cases are also typically characterized by abdominal, back, flank, or chest pain. More severe cases may be characterized by

shortness of breath Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing di ...

, low blood pressure, hemoglobinuria, and may progress to

shock Shock may refer to: Common uses Collective noun *Shock, a historic commercial term for a group of 60, see English numerals#Special names * Stook, or shock of grain, stacked sheaves Healthcare * Shock (circulatory), circulatory medical emerge ...

and

disseminated intravascular coagulation Disseminated intravascular coagulation (DIC) is a condition in which blood clots form throughout the body, blocking small blood vessels. Symptoms may include chest pain, shortness of breath, leg pain, problems speaking, or problems moving parts ...

. In anesthetized or unconscious patients,

hematuria Hematuria or haematuria is defined as the presence of blood or red blood cells in the urine. “Gross hematuria” occurs when urine appears red, brown, or tea-colored due to the presence of blood. Hematuria may also be subtle and only detectable w ...

(blood in the urine) may be the first sign of AHTR. Other symptoms include nausea, vomiting, and

wheezing A wheeze is a continuous, coarse, whistling sound produced in the respiratory airways during breathing. For wheezes to occur, some part of the respiratory tree must be narrowed or obstructed (for example narrowing of the lower respiratory tract ...

Causes

The most common cause of acute hemolytic transfusion reaction is

ABO incompatibility In ABO hemolytic disease of the newborn (also known as ABO HDN) 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 w ...

, 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. Rh, Kell, and

Duffy Duffy may refer to: People *Duffy (surname), people with the surname Duffy or Duffey * Duffy (nickname) *Duffy (singer) (born 1984), Welsh singer, born Aimee Ann Duffy Places *Duffy, Australian Capital Territory, a suburb of Canberra * Duffy, Ohi ...

antigen incompatibility have also been implicated in AHTR.

Mechanism

Antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of ...

against A and B blood groups (isohemagglutinins) present in the recipient's blood destroy the donor

red blood cell Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "hol ...

s. They also activate the

coagulation cascade Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It potentially results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The mechani ...

(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 Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in au ...

release from

white blood cell White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...

s. These inflammatory cytokines include IL-1, IL-6, IL-8, and TNF-alpha, which cause symptoms of low blood pressure, fever, chest pain, nausea, vomiting, and wheezing.

Diagnosis

The diagnosis of AHTR is made with microscopic examination of the recipient's blood and a

direct antiglobulin test A Coombs test, also known as antiglobulin test (AGT), is either of two blood tests used in immunohematology. They are the direct and indirect Coombs tests. The direct Coombs test detects antibodies that are stuck to the surface of the red blood c ...

. The donor and recipient blood can be re-tested with a type, crossmatch, and antibody screen to determine the cause of the reaction.

Treatment

Initial treatment for any type of transfusion reaction, including AHTR, is discontinuation of the transfusion.

Fluid replacement Fluid replacement or fluid resuscitation is the medical practice of replenishing bodily fluid lost through sweating, bleeding, fluid shifts or other pathologic processes. Fluids can be replaced with oral rehydration therapy (drinking), intravenous ...

and close monitoring of vital signs are important. People with AHTR are managed with

supportive care Symptomatic treatment, supportive care, supportive therapy, or palliative treatment is any medical therapy of a disease that only affects its symptoms, not the underlying cause. It is usually aimed at reducing the signs and symptoms for the comf ...

, which may include

diuretic A diuretic () is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. A diuretic tablet is sometimes colloquially called a water tablet. There are several categories of diuretics. All diuretics i ...

s, blood pressure support, and treatment of disseminated intravascular coagulation (with fresh frozen plasma,

cryoprecipitate Cryoprecipitate, also called cryo for short, is a frozen blood product prepared from blood plasma. To create cryoprecipitate, fresh frozen plasma thawed to 1–6 °C is then centrifuged and the precipitate is collected. The precipitate is re ...

, and

platelet transfusion Platelet transfusion, also known as platelet concentrate, is used to prevent or treat bleeding in people with either a low platelet count or poor platelet function. Often this occurs in people receiving cancer chemotherapy. Preventive transfus ...

Furosemide Furosemide is a loop diuretic medication used to treat fluid build-up due to heart failure, liver scarring, or kidney disease. It may also be used for the treatment of high blood pressure. It can be taken by injection into a vein or by mo ...

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 The renal cortex is the outer portion of the kidney between the renal capsule and the renal medulla. In the adult, it forms a continuous smooth outer zone with a number of projections (cortical columns) that extend down between the pyramids. It ...

Mannitol Mannitol is a type of sugar alcohol used as a sweetener and medication. It is used as a low calorie sweetener as it is poorly absorbed by the intestines. As a medication, it is used to decrease pressure in the eyes, as in glaucoma, and to lo ...

may also be used.

Dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 80% o ...

is used for blood pressure support because it causes

vasodilation Vasodilation is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. The process is the opposite of vasoconstrictio ...

(dilation of blood vessels) in the kidneys as well as increasing the

cardiac output In cardiac physiology, cardiac output (CO), also known as heart output and often denoted by the symbols Q, \dot Q, or \dot Q_ , edited by Catherine E. Williamson, Phillip Bennett is the volumetric flow rate of the heart's pumping output: th ...

(amount of blood pumped by the heart each minute).

Prognosis

The severity and prognosis of acute hemolytic transfusion depends on the rate of blood administration and the total volume of the transfusion. Approximately 2% of cases are fatal. Reactions that begin sooner are typically more severe.

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.

References

{{Transfusion medicine Transfusion reactions Complications of surgical and medical care Transfusion medicine