Haemolytic transfusion reactions T80.9

The first human-to-human blood transfusion was performed in 1825 by James Blundell between a postpartum hemorrhaging woman and the child's father, which is why Blundell is called the "father of modern blood transfusion" (Türkmen- Uthayanan 2022).

It was not until 1901 that Karl Landsteiner discovered the AB0 blood groups and only 3 years later he discovered the antibodies that we now call anti-A and anti-B (Owen 2000).

Hemolytic transfusion reaction (HTR) is an unexpected reaction to the transfusion of labile blood products (Schoenenberger 2009). This results in an immunological antibody reaction(hemolysis) to incompatible erythrocytes of the donor (Schaps 2008).

Hemolytic transfusion reaction (HTR) is one of the transfusion-related adverse events (TRAE). (Jhaveri 2022).

HTR is differentiated between a:

- Immediate Hemolytic Reaction (AHTR).

In the majority of cases, this is caused by a mix-up between the blood unit and the recipient with regard to the AB=- system (Herold 2022).

- Delayed hemolytic reaction (DHTR)

Delayed reaction occurs in patients who have sensitivity to red cell alloantigens (Kasper 2015).

The reaction itself occurs one to several weeks after transfusion. This occurs due to a large spectrum of antibodies, but their AK titers are already below the detection limit at the time of transfusion (Herold 2022).

Cause of HTR can be:

- Preforming erythrocytic antibodies in the immediate reaction.

- In principle any antibody in the delayed form (Herold 2022)

Hemolytic immediate reaction

In an immediate hemolytic reaction, activation of the complement system occurs during or immediately after transfusion (Herold 2022).

In the case that serologically incompatible blood products - in the vast majority AB0 incompatibility - are administered, an accelerated degradation of erythrocytes occurs in the recipient. This hemolysis is triggered by:

- Antibodies of the recipient against the transfused erythrocytes, so-called "major incompatibility" (Schoenenberger 2009). In this case, the isoagglutinins anti-A and anti-B of the IgM type rapidly form antigen antibody complexes with the transfused erythrocytes. The cell decay activates a tissue factor. This causes hemolysis and can thereby trigger acute disseminated intravascular coagulation (DIC) (Rump 2003).

- Antibodies in the plasma to be transfused against antigens of the recipient's erythrocytes, so-called "minor incompatibility" (Schoenenberger 2009).

Delayed hemolytic reaction

In this case, IgG antibodies are formed in the recipient. These lead to destruction of the erythrocytes. It is possible that the delayed HTR is only triggered during phagocytosis of the antibody-loaded erythrocytes (Rump 2003).

Basically, it should be noted that anesthetized patients show significantly fewer symptoms. In them, the following changes may indicate HTR:

- hypotension

- bleeding tendency

- Tachycardia (Rump 2003)

Immediate hemolytic reaction (AHTR)

Reactions can occur after a transfusion of 5 ml of incompatible blood. Severe reactions are usually seen after transfusions of > 200 ml (Herold 2022). The following symptoms have been described in the event of an immediate reaction:

- chills

- fever

- sweating

- dyspnea

- drop in blood pressure

- Nausea and vomiting

- Headache and backache (Herold 2022)

- Skin erythema (Schoenenberger 2009)

- urticaria

- pruritus

- Icterus (appearing only after hours [Schoenenberger 2009])

- Hemoglobinuria (Herold 2022)

Indications of a severe complication are:

- oliguria

- anuria

- pulmonary edema

- Circulatory shock (Schoenenberger 2009)

Delayed hemolytic reaction (DHTR)

- Hb drop

- Mild icterus

- Fever (Herold 2022)

- Hemoglobinuria (Rump 2003).

The diagnosis of HTR is made by history, clinical symptoms, and serologic diagnosis (Herold 2022).

Emergency history

What blood product transfused where and when?

Previous transfusions that have taken place?

History of known reactions to transfusion?

Known allergies?

In women, question about possible pregnancy, miscarriages or haemolyticus neonatorum (Schoenenberger 2009).

Inspection

Particular attention should be paid to:

Urticaria, exanthema, cyanosis, neck vein congestion, cold extremities (Schoenenberger 2009).

Chest X-ray

Chest X-ray may reveal transfusion-associated pulmonary insufficiency or pulmonary edema (Schoenenberger 2009).

- Free hemoglobin detectable in urine and plasma already at the first micturition (Schoenenberger 2009)

- due to intravascular hemolysis caused by complement activation there is an increase of

- LDH

- Indirect bilirubin

- Decrease of

- haptoglobin

- Hemopexin (only when haptoglobin is no longer measurable)

- Absence of increase in

- erythrocytes

- Hemoglobin

- Hematocrit (Herold 2022)

- Blood cultures

- ABG

- Coagulation status (Schoenenberger 2009)

In particular, the following should be monitored in the presence of HTR:

- Prothrombin time (PTZ)

- fibrinogen

- Activated partial thromboplastin time (aPTT)

- Platelet count (Kasper 2015)

Hemolytic immediate reaction:

The preformed erythrocytic AK causing an immediate reaction can be detected by an indirect Coombs test. This antibody screening test is therefore mandatory for blood grouping and must be repeated at regular intervals if transfusion is required (Herold 2022).

Delayed hemolytic reaction:

These antibodies cannot be detected by an antibody screening test because immunization took place some time ago or the antibody titer is now below the detection limit. In principle, any antibody can cause this reaction, primarily AK against Duffy, Kell and Kidd antigens (Herold 2022).

The direct Coombs test is positive in the majority of those affected (Rump 2003).

Non-hemolytic transfusion reactions such as.

- Fever due to pyrogens in the blood unit

- Septic reaction due to contamination of the container with bacteria

- Transfusion-associated acute lung insufficiency (TRALI) with dyspnea and pulmonary edema

- Allergic transfusion reaction with formation of antibodies against HLA antigens of the leukocytes or against components of the plasma (Herold 2022)

Hemolytic immediate reaction

Complications of an immediate reaction may include:

- Acute renal failure due to the immune complexes that led to the lysis of the erythrocytes (Kasper 2015).

- DIC (disseminated intravascular coagulation)

- Shock (Herold 2022)

- Circulatory arrest (Rump 2003).

Delayed hemolytic reaction

Complications of delayed hemolytic reaction may include:

- Renal failure, although rarely occurring (Rump 2003).

Immediate hemolytic reaction

- Stop transfusion immediately if HTR is present.

- Venous access should be maintained for further therapeutic measures

- The C5 antibody eculizumab should be administered as soon as possible as a therapeutic trial in AB0 incompatible transfusion, as it leads to terminal complement blockade

- Vital signs monitoring (Herold 2022).

- Anti-allergic therapy with H1 antihistamines such as clemastine 2 mg i. v.

- If SIRS (systemic inflammatory response syndrome) is present, additionally hydrocortisone 100 mg i. v. (Schoenenberger 2009)

- Dialysis, in case of acute renal failure.

- Induction of anesthesia, since both hemolytic TR and nonhemolytic TR are easier in the anesthetized state (Herold 2022)

- Administration of furosemide or mannitol (Kasper 2015) together with sodium bicarbonate i. v. to increase diuresis ( > 100 ml / h [Schoenenberger 2009]).

The cannula itself should be sterilely clamped and sent together with patient blood samples and the transfusion reaction protocol for serological diagnosis (Herold 2022).

Delayed hemolytic reaction

As a rule, no specific therapy is required in this case (Kasper 2015). In severe courses, an intensive medical approach should be taken as in acute HTR (Rump 2003).

Immediate hemolytic reaction

There are approximately 90% of all deaths in HTR due to an immediate reaction. In up to 70% of deaths, AB0 incompatibility is present (Herold 2022).

One in 250,000 transfused patients dies in the USA (in Germany the figures are likely to be similar) as a result of AB0 compatibility and about 40% of deaths following red blood cell transfusion die after an acute HTR (Rump 2003).

In a nearly 3 ½ year study by Caspari et al. in 2001, it was shown that 13 of 30 patients suffering from HTR did not have a bedside AB0 test performed beforehand, and it was performed incorrectly in 14 of 30 patients (Rump 2003).

Delayed hemolytic reaction

Approximately 10% of all fatal HTRs are caused by a delayed reaction (Rump 2003).

Hemolytic immediate reaction

To prevent an immediate reaction, it is recommended:

- Correct determination of blood group

- Antibody screening test before providing a transfusion

- Ensure proper storage of the container

- The major test is obligatory, the minor test optional.

- Pay attention to the expiry date and the integrity of the container

- Perform the so-called "bedside test" immediately before the transfusion (also when transfusing autologous blood). This test is required by law.

- Do not release the blood unit for transfusion until the result of the crossmatch test is negative.

- Do not perform any infusions or injections together with the transfusion (only exception: isotonic saline solution).

- Establish a transfusion protocol (Herold 2022).

Delayed hemolytic reaction

Prevention of delayed reaction has proven to be difficult. In this case, documentation of all antibodies in the emergency card and attention to anamnestic information are important (Herold 2022).

An immediate hemolytic reaction (AHTR) is preventable in principle (Rump 2003).

Unexpected transfusion reactions must be reported immediately to the person responsible for transfusion at the respective institution, to the manufacturer of the blood products and, if necessary, to the public prosecutor's office (Rump 2003).

If further transfusions are medically necessary after a transfusion reaction, a transfusion specialist should first be consulted to coordinate the further procedure (Schoenenberger 2009).

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