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Definition

Acute hemolytic transfusion reactions can involve destruction of red blood cells within 24 hours of transfusion, and more often within several hours of transfusion. The hemolysis can involve the donor red blood cells (RBCs) or the recipient RBCs. Hemolysis can be intravascular or extravascular. Delayed hemolytic transfusion reactions occur within 5 days of the transfusion.

Risk factors

 Incompatible blood types, especially in a horse that has been previously transfused or exposed to a different blood type (e.g. broodmare) and has developed alloantibodies

 Crossmatch‐incompatible blood

 Improper storage of blood products (non‐immune reaction)

Pathogenesis

Acute hemolytic reactions typically occur when there is major incompatibility (donor RBCs and recipient plasma), resulting in rapid destruction of the transfused RBCs. Hemolysis of recipient red blood cells can occur if there are RBC antibodies in the donor plasma. Delayed hemolytic reactions occur >24 hours after transfusion, likely due to RBC antibody production shortly after transfusion. Clinical signs of acute hemolysis include hemoglobinemia, hemoglobinuria, and anemia. In severe cases, shock and cardiovascular collapse may occur. Clinical signs with delayed hemolytic reaction are similar to those with acute hemolysis, although usually less severe. Acute renal failure may occur secondary to pigment nephropathy.

Acute hemolytic transfusion reactions occur in approximately 1 out of 76,000 transfusions in humans [2]. In a retrospective study of blood transfusions in canine patients, there was a complication rate of approximately 25%, with hemolysis in 6% [3].

Prevention

Ideally, all blood donors should be tested for RBC antibodies, and blood typing should be used to find the optimal blood donor. Blood typing is not practical in an emergency situation, and due to the large number of blood types, an ideal donor may not be available. While anti‐Aa antibodies are thought to be the most immunogenic, anti‐Ca antibodies appear to be the most common in horses [4]. There is a stall‐side test available (Alvedia, Limonest, France) to detect Ca‐positive horses, but Aa and Qa tests are not available. A complete crossmatch is recommended to determine donor‐recipient incompatibility.

In an emergency, most horses can safely be given a blood transfusion without crossmatch, since they are unlikely to have preexisting RBC antibodies. A crossmatch is strongly recommended for horses that have previously been exposed to red blood cells either through blood transfusion or transplacental exposure. The major crossmatch detects incompatibility between the donor RBCs (RBC antigens) and the recipient plasma (RBC antibodies). The minor crossmatch detects incompatibility between the recipient RBCs and the donor plasma. Crossmatch can be performed by traditional tube incubation and microscopic evaluation to assess for agglutination. Ideally, complement should be added to assess for hemolysis. Recently, a microgel assay and modified rapid gel assay have been evaluated for use in horses [5]. Crossmatch incompatibility is associated with decreased RBC survival time as well as increased risk of febrile reaction [6].

If there is a history of transfusion reaction or if a crossmatch‐compatible donor cannot be identified, autologous transfusion options, such as preoperative autologous donation or cell salvage, should be considered (see Chapter 7: Complications Associsted with Hemorrhage).

Diagnosis and monitoring

Whole blood and packed RBC transfusions should be monitored very closely during the first 10–20 minutes, checking temperature, heart rate, and respirations. The transfusion should be slowed or stopped if there are any signs of allergic reaction such as muscle fasciculations, sweating, or urticaria. Signs of acute hemolytic reaction include a sudden decrease in packed cell volume (PCV), hemoglobinuria, hemoglobinemia, and systemic inflammatory response syndrome. Delayed hemolytic reactions result in an unexpected decrease in PCV more than 24 hours after transfusion.

Treatment

Stop the transfusion if it is still in progress. Note the adverse reaction in the medical record and discontinue any orders for further blood transfusion from that donor [7]. Signs of shock or hypotension should be treated with IV fluids. Crystalloid fluids should be continued to maintain renal perfusion and reduce the risk of pigment nephropathy. If there is minor incompatibility (donor plasma and recipient RBCs), the red blood cells can be washed to remove the plasma fraction and blood transfusion may continue with careful monitoring. If the patient remains anemic and requires additional blood transfusion, crossmatch is strongly recommended with new donors.

Expected outcome

The expectations after blood transfusion are for improved oxygenation of tissues. A decrease in heart rate, decrease in lactate, and increase in PCV are reasonable expectations after transfusion, but the rise in PCV is not predictable. In a retrospective report of horses receiving blood transfusions, heart rate and respiratory rate improved significantly after transfusion, but PCV did not increase significantly in horses with hemorrhagic anemia receiving blood transfusions [1]. It is likely that these horses were transfused during or soon after the episode of hemorrhage, so the pre‐transfusion PCV may have been relatively high due to splenic contraction and incomplete volume resuscitation.

Acute hemolytic reactions can be severe and may lead to organ failure and death. If recognized early, outcome can be good, especially if a compatible donor is identified. Horses may develop RBC antibodies after transfusion, without any clinical signs. These horses may develop acute hemolysis with subsequent transfusions, and broodmares may have RBC antibodies in their colostrum, leading to neonatal isoerythrolysis in the foal [8].