Washed RBCs and Acute Hypotensive Transfusion Reactions
Washed RBCs and Acute Hypotensive Transfusion Reactions
Objectives: To examine whether a liver transplant patient, who was not taking an angiotensin-converting enzyme inhibitor and developed two episodes of hypotension with systolic pressure in the 50s within minutes of starting an RBC transfusion, may have had a disturbance in the production and metabolism of bradykinin and des-Arg-BK.
Methods: All patient information was obtained by reviewing the electronic medical record, the transfusion service database, and transfusion reaction investigation records.
Results: The blood pressure returned to normal once the transfusions were discontinued. In an effort to mitigate the acute hypotension, the blood products were washed. Subsequently, the patient received three additional packed RBC transfusions without further incidents of hypotension.
Conclusions: Our experience suggests that washing the products was an acceptable and effective preventative measure to avoid further acute hypotensive transfusion reactions in patients unable to metabolize these vasodilators present in the donor units.
Hypotension may be a manifestation of different types of transfusion reactions such as acute hemolysis, transfusion-related acute lung injury, bacterial contamination of platelets, anaphylaxis, and acute hypotension. In all but the latter type of reaction, other signs and symptoms are usually predominant and often precede the drop in blood pressure. Acute hypotensive transfusion reactions (AHTRs) are characterized by the early and abrupt onset of hypotension, which is often severe, with a drop of the systolic blood pressure below 80 mm Hg. While the hypotension may be isolated and is the predominant symptom, the patient may also experience lightheadedness, dizziness, and anxiety. Unlike the other reactions mentioned above, once the transfusion is stopped in an AHTR, the hypotension rapidly resolves without specific therapy. Although no particular treatment for AHTR exists, washing packed RBCs (PRBCs) has been suggested to prevent recurrence but without reported evidence of benefit. Implementing a kallikrein blockade may prevent these reactions; however, this approach is experimental.
Bradykinin (BK) has been considered a mediator of an AHTR, especially in those patients taking an angiotensin-converting enzyme (ACE) inhibitor or those who may have impaired alternate pathways of BK metabolism. BK is a vasoactive peptide that binds to receptors on the vascular endothelium and causes vasodilation. These native receptors are called B2 receptors, in distinction from cytokine-inducible B1 receptors. BK is produced from the activation of factor XII, which may be activated by interacting with the negatively charged surfaces of tubing, blood storage bags, dialysis membranes, or leukoreduction filters. Once activated, factor XIIa transforms prekallikrein into the active form, kallikrein. Kallikrein then converts high-molecular-weight kininogen into BK.
BK activity is normally limited to the site of formation because it is degraded rapidly by three main enzymes: kininase II ACE, aminopeptidase P (APP), and carboxypeptidase N. Each enzyme is responsible for BK degradation to varying degrees; ACE is responsible for 75%, APP for 20%, and carboxypeptidase N for the remainder. Carboxypeptidase N converts BK into its vasoactive metabolite, des-Arg-BK, which is subsequently inactivated by both ACE and APP. Thus, if an ACE inhibitor is present or there are dysfunctional polymorphisms of APP or ACE that render the enzymes less efficient at metabolizing des-Arg-BK, a larger amount of des-Arg-BK will be present. This increase may result in the development of hypotension, especially in those patients with comorbidities that upregulate the inducible B1 receptors.
Abstract and Introduction
Abstract
Objectives: To examine whether a liver transplant patient, who was not taking an angiotensin-converting enzyme inhibitor and developed two episodes of hypotension with systolic pressure in the 50s within minutes of starting an RBC transfusion, may have had a disturbance in the production and metabolism of bradykinin and des-Arg-BK.
Methods: All patient information was obtained by reviewing the electronic medical record, the transfusion service database, and transfusion reaction investigation records.
Results: The blood pressure returned to normal once the transfusions were discontinued. In an effort to mitigate the acute hypotension, the blood products were washed. Subsequently, the patient received three additional packed RBC transfusions without further incidents of hypotension.
Conclusions: Our experience suggests that washing the products was an acceptable and effective preventative measure to avoid further acute hypotensive transfusion reactions in patients unable to metabolize these vasodilators present in the donor units.
Introduction
Hypotension may be a manifestation of different types of transfusion reactions such as acute hemolysis, transfusion-related acute lung injury, bacterial contamination of platelets, anaphylaxis, and acute hypotension. In all but the latter type of reaction, other signs and symptoms are usually predominant and often precede the drop in blood pressure. Acute hypotensive transfusion reactions (AHTRs) are characterized by the early and abrupt onset of hypotension, which is often severe, with a drop of the systolic blood pressure below 80 mm Hg. While the hypotension may be isolated and is the predominant symptom, the patient may also experience lightheadedness, dizziness, and anxiety. Unlike the other reactions mentioned above, once the transfusion is stopped in an AHTR, the hypotension rapidly resolves without specific therapy. Although no particular treatment for AHTR exists, washing packed RBCs (PRBCs) has been suggested to prevent recurrence but without reported evidence of benefit. Implementing a kallikrein blockade may prevent these reactions; however, this approach is experimental.
Bradykinin (BK) has been considered a mediator of an AHTR, especially in those patients taking an angiotensin-converting enzyme (ACE) inhibitor or those who may have impaired alternate pathways of BK metabolism. BK is a vasoactive peptide that binds to receptors on the vascular endothelium and causes vasodilation. These native receptors are called B2 receptors, in distinction from cytokine-inducible B1 receptors. BK is produced from the activation of factor XII, which may be activated by interacting with the negatively charged surfaces of tubing, blood storage bags, dialysis membranes, or leukoreduction filters. Once activated, factor XIIa transforms prekallikrein into the active form, kallikrein. Kallikrein then converts high-molecular-weight kininogen into BK.
BK activity is normally limited to the site of formation because it is degraded rapidly by three main enzymes: kininase II ACE, aminopeptidase P (APP), and carboxypeptidase N. Each enzyme is responsible for BK degradation to varying degrees; ACE is responsible for 75%, APP for 20%, and carboxypeptidase N for the remainder. Carboxypeptidase N converts BK into its vasoactive metabolite, des-Arg-BK, which is subsequently inactivated by both ACE and APP. Thus, if an ACE inhibitor is present or there are dysfunctional polymorphisms of APP or ACE that render the enzymes less efficient at metabolizing des-Arg-BK, a larger amount of des-Arg-BK will be present. This increase may result in the development of hypotension, especially in those patients with comorbidities that upregulate the inducible B1 receptors.