From the Guidelines
Febrile nonhemolytic transfusion reactions (FNHTRs) are primarily caused by the interaction between recipient antibodies and donor white blood cells or the presence of inflammatory cytokines in stored blood products, as supported by the most recent guidelines from the Association of Anaesthetists 1. The pathophysiology of FNHTRs involves two main mechanisms:
- Recipient antibodies against donor leukocyte antigens (particularly HLA antigens) trigger the release of pyrogens
- Pro-inflammatory cytokines such as IL-1, IL-6, and TNF-α accumulate in stored blood components during storage, as noted in the guidelines 1. These cytokines are released from white blood cells and platelets as they degrade over time in the blood bag. When transfused, these substances activate the recipient's immune system, stimulating the hypothalamic thermoregulatory center to increase body temperature. Leukoreduction of blood products before storage significantly reduces the incidence of FNHTRs by removing the white blood cells responsible for cytokine production and antigenic stimulation, as recommended by recent studies 1. While generally not life-threatening, these reactions can cause significant discomfort and may necessitate interruption of the transfusion. Management typically includes antipyretics like acetaminophen for symptomatic relief, though premedication is not routinely recommended for all transfusions, as advised by the Association of Anaesthetists guidelines 1. Key considerations in managing FNHTRs include:
- Assessing the need for transfusion
- Body weight dosing of RBCs
- Slow transfusion
- Close monitoring of vital signs and fluid balance
- Prophylactic diuretic prescribing, as outlined in the guidelines 1.
From the Research
Pathophysiology of Febrile Nonhemolytic Transfusion Reaction
The pathophysiology of febrile nonhemolytic transfusion reaction (FNHTR) is complex and involves both immune and non-immune pathways 2. The immune pathway is associated with antibodies against human leukocyte antigen (HLA) produced in transfused patients, while the non-immune pathway is associated with cytokines released from blood products during storage.
Risk Factors
Several risk factors have been identified for the development of FNHTR, including:
- Women with a reproductive history and those patients with multiple blood transfusions 2
- Primary hematologic disease, malignant disease, and transfusion with over 6 units of leukocyte-depleted packed red blood cells 2
- The use of platelets and red blood cells (RBCs) as blood products 3
Diagnosis
FNHTR can be diagnosed by the presence of fever symptoms (body temperature ≥38 ℃, or an increase of body temperature of more than 1 ℃ compared with that before blood transfusion) during or within 4 hours after transfusion, or the presence of chills, shakes, headache, and nausea, among other symptoms 2, 3.
Prevention and Treatment
Several strategies have been proposed to prevent and treat FNHTR, including:
- Leukoreduction, which can reduce the incidence of FNHTR significantly 2, 4
- Premedication with acetaminophen and diphenhydramine, although the benefit of this practice is not supported by research 4, 5
- Removal of leukocyte components from blood products 6
- Reduction of the platelet storage period to 3 days 6
Burden of FNHTR
FNHTR can have a significant burden on patients and hospitals, including: