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Hemolytic Transfusion Reaction
Hemolysis Transfusion

The hemolytic transfusion reaction is a potentially severe adverse reaction to blood transfusion that may be divided into acute episodes, occurring during the first 24 hours after blood administration and delayed ones, that are often less serious. AB0 incompatibilities cause severe distress, whereas non-AB0 incompatibility leads to milder discomfort. Symptoms occasionally resolve by themselves, but advanced cases require immediate treatment.

Presentation

Any individual that has a history of blood transfusion or pregnancy is a potential candidate for a hemolytic transfusion reaction after blood administration. Initial signs may be nonspecific. An acute episode presents with pulmonary findings such as wheezing tachypnea or dyspnea, cardiovascular abnormalities like tachycardia and hypotension, renal anomalies like anuria or a change of urine color to reddish due to hemoglobinuria and systemic symptoms, such as high fever, chills, headaches, flushing or paleness, loss of consciousness and anxiety [1] [2] [3]. The involvement of digestive system may cause jaundice, nausea, and vomiting. The patient may complain of a chest, back or abdominal pain. If disseminated intravascular coagulation sets in, a bleeding tendency is described later during the course of the disease.

A delayed hemolytic transfusion reaction is often less severe, consisting only of anemia signs and fever, the latter present one week after the incompatible blood transfusion. In other cases, the disease has no specific symptoms and is incidentally discovered during laboratory investigations [4]. Severe complaints usually arise after hemolyzed blood administration.

The magnitude of the hemolytic reaction depends on the volume of incompatible blood that was administered. Even 1 ml of blood can cause a reaction, but complaints usually appear after 5 to 20 ml are administered. If the clinical status declines, the physician should investigate the presence of acute renal failure, disseminated intravascular coagulation, and shock.

Workup

The hemolytic transfusion reaction is accompanied by hemolysis, therefore the physician should order tests that highlight its presence [5]. The first step is to retype patient and donor blood and inspect patient urine and blood. Pink, red, brown or yellow color of plasma suggests hemolysis and hemoglobinemia, while red urine after centrifugation signifies hemoglobinuria. The Coombs test must follow. The direct test will be found positive. If the polyspecific direct antiglobulin test is positive, monospecific tests and antibody elution tests should be performed in order to identify the antibody involved. The antiglobulin exam becomes positive several days after the transfusion in case a delayed hemolytic reaction is present, therefore a sample of the transfused blood must be kept in the laboratory for at least 10 days [6]. The patient's hemoglobin value will diminish again 1 or 2 weeks after the transfusion of incompatible blood. At that time, increased reticulocyte levels and spherocytes may also be noticed.

Other examinations that prove hemolysis are the reduction of the plasma haptoglobin and hemopexin concentration, as well as an increase in the lactate dehydrogenase and bilirubin levels. Unfortunately, none of these markers are specific for hemolysis, but their combined presence is a strong indicator of the condition. Additional recommended tests include the prothrombin time, activated partial thromboplastin time, D- dimers, platelet count and fibrinogen levels, that help diagnose disseminated intravascular coagulation. The renal function must be closely monitored.

If no incompatibilities are demonstrated, but the patient has the complaints described above, the blood bag must be tested for hemolysis, since the administration of hemolyzed blood may induce these symptoms. Other hemolysis causes should also be searched for in case no explanation is found by conventional methods [7] [8].

Treatment

The primary step in treating HTR is to stop the transfusion as soon as a reaction is suspected. Supportive care is crucial and may include intravenous fluids to maintain blood pressure and kidney function, medications to manage symptoms like fever and pain, and, in severe cases, dialysis to support kidney function. Identifying and addressing the underlying cause of the reaction, such as mismatched blood types, is essential to prevent further complications.

Prognosis

The prognosis for patients with HTR depends on the severity of the reaction and how quickly it is recognized and treated. Mild reactions often resolve with supportive care, while severe reactions can lead to significant complications, including kidney failure and, in rare cases, death. Prompt recognition and treatment are key to improving outcomes.

Etiology

HTR is primarily caused by the immune system's response to foreign antigens on transfused red blood cells. This can occur if the blood types of the donor and recipient are not compatible. The most common cause of acute HTR is ABO incompatibility, where the recipient's antibodies attack the donor's red blood cells. Delayed reactions are often due to antibodies formed from previous transfusions or pregnancies.

Epidemiology

HTR is a relatively rare complication of blood transfusion, thanks to rigorous blood typing and crossmatching procedures. Acute HTR occurs in approximately 1 in 25,000 transfusions, while delayed reactions are more common but often go unrecognized due to their milder symptoms. The risk of HTR is higher in patients with a history of multiple transfusions or pregnancies.

Pathophysiology

In HTR, the recipient's immune system recognizes the transfused red blood cells as foreign and mounts an immune response. This involves the production of antibodies that bind to antigens on the donor red blood cells, leading to their destruction. The breakdown of red blood cells releases hemoglobin into the bloodstream, which can cause kidney damage and other complications.

Prevention

Preventing HTR involves careful blood typing and crossmatching before transfusion to ensure compatibility between donor and recipient blood. This includes checking for ABO and Rh compatibility and screening for other antibodies that may cause a reaction. In patients with a history of transfusion reactions, additional precautions, such as using leukocyte-reduced blood products, may be necessary.

Summary

Hemolytic Transfusion Reaction is a potentially serious complication of blood transfusion caused by the immune system's response to incompatible red blood cells. It can present with a range of symptoms, from mild to life-threatening, and requires prompt recognition and treatment. Prevention through careful blood matching is key to reducing the risk of HTR.

Patient Information

If you or a loved one is receiving a blood transfusion, it's important to be aware of the signs of a Hemolytic Transfusion Reaction. Symptoms like fever, chills, back pain, or dark urine during or after a transfusion should be reported to medical staff immediately. While HTR is rare, understanding the risks and ensuring proper blood matching can help prevent complications.

References

  1. Yeh SP, Chang CW, Chen JC, et al. A well-designed online transfusion reaction reporting system improves the estimation of transfusion reaction incidence and quality of care in transfusion practice. Am J Clin Pathol. 2011;136(6):842-7.
  2. Fastman BR, Kaplan HS. Errors in transfusion medicine: have we learned our lesson?. Mt Sinai J Med. 2011;78(6):854-64.
  3. Squires JE. Risks of transfusion. South Med J. 2011;104(11):762-9.
  4. Vamvakas EC, Pineda AA, Reisner R, et al. The differentiation of delayed hemolytic and delayed serologic transfusion reactions: incidence and predictors of hemolysis. Transfusion. 1995;35:26–32.
  5. Beauregard P, Blajchman MA. Hemolytic and pseudo-hemolytic transfusion reactions: an overview of the hemolytic transfusion reactions and the clinical conditions that mimic them. Transfus Med Rev. 1994; 8(3):184-99.
  6. Flegel WA, Kubanek B, Northoff H. Abklärung einer Transfusionsreaktion. Dtsch Ärztebl. 1990;87:B–860–864.
  7. Strobel E, Nathrath M, Peters J, et al. Akute intravasale Hämolyse bei Clostridium-perfringens-Sepsis. Dtsch Med Wochenschr. 1994;119:375–9.
  8. Strobel E. Diagnostic importance and difficulties in testing of T-antigen activation. Infus Ther Transfus Med. 2002;29:249–52.
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