What Are the Criteria for Hypotensive Transfusion Reaction?

Accounting for about 3% of reported transfusion reactions, a hypotensive transfusion reaction (HTR) is a distinct type of adverse event characterized by a rapid, isolated drop in blood pressure. Unlike other reactions, HTR is defined by specific blood pressure changes, occurring during or shortly after the transfusion, and requires the exclusion of other potential causes.

Quick Summary

A hypotensive transfusion reaction (HTR) is defined by a significant drop in blood pressure during or shortly after transfusion, resolving upon cessation, and after excluding other causes.

Key Points

• Diagnostic Thresholds: In adults, a drop of $\ge 30$ mmHg in systolic blood pressure, resulting in an SBP of $\le 80$ mmHg, defines hypotension for a suspected HTR.

• Timing is Crucial: The reaction typically occurs early, often within 15 minutes of the transfusion's start, and must be during or within one hour of its completion.

• Diagnosis of Exclusion: To diagnose HTR, other causes of hypotension like anaphylaxis, sepsis, and acute hemolysis must be ruled out.

• ACE Inhibitor Interaction: A major risk factor is the concomitant use of ACE inhibitors, which prevents the breakdown of the vasodilator peptide bradykinin, causing severe hypotension.

• Rapid Resolution: A hallmark of HTR is the rapid resolution of hypotension once the blood product infusion is stopped.

• Preventive Strategies: Prevention includes temporarily stopping ACE inhibitors for elective procedures or using washed blood products for high-risk patients.

• Bradykinin Mechanism: HTR is mediated by an accumulation of bradykinin, which is generated during blood product processing and typically degraded by ACE.

Defining the Hypotensive Transfusion Reaction

The diagnostic criteria for a hypotensive transfusion reaction (HTR) are precise and hinge on specific measurements of blood pressure drop, the timing of the event, and the exclusion of alternative diagnoses. The National Healthcare Safety Network (NHSN) has established clear surveillance protocols for defining hypotension based on patient age.

Key Diagnostic Criteria

• Timing of Onset: A decrease in blood pressure must occur during or within one hour after the cessation of a blood transfusion. Many cases present very rapidly, often within the first 15 minutes.
• Specific Blood Pressure Thresholds: The definition varies slightly by age group:
  • Adults (≥18 years old): A systolic blood pressure (SBP) drop of at least 30 mmHg, with a resulting SBP of 80 mmHg or less.
  • Children and Adolescents (1 to <18 years old): A greater than 25% drop in SBP from the patient's baseline.
  • Neonates and Infants (<1 year or <12 kg): A greater than 25% drop from the patient's baseline mean blood pressure.
• Exclusion of Other Reactions: The diagnosis of a primary HTR is one of exclusion. This means that other adverse transfusion reactions that can cause hypotension must be ruled out. These include anaphylaxis, septic reactions, and acute hemolytic reactions, which typically present with other distinct symptoms.
• Rapid Resolution: The blood pressure must rapidly return to normal once the transfusion is stopped.

Pathophysiology: The Bradykinin Connection

Unlike immune-mediated reactions, the primary mechanism of HTR involves the vasoactive peptide, bradykinin. The pathophysiology is a cascade of events:

• Bradykinin Generation: During the processing of blood products, Factor XII can be activated by negatively charged surfaces, such as the filters used for leukoreduction and plastic tubing. This activation triggers a cascade that results in the generation of bradykinin within the transfused component.
• Bradykinin Vasodilation: The accumulated bradykinin is then introduced into the patient's circulation, causing vasodilation and a rapid drop in blood pressure.
• Impaired Degradation: Normally, the body's angiotensin-converting enzyme (ACE) rapidly inactivates bradykinin. However, in patients taking ACE inhibitors, this enzyme's function is blocked, preventing the breakdown of the excess bradykinin and leading to pronounced hypotension.

Risk Factors for Developing HTR

While HTR is relatively rare, certain factors can increase a patient's risk. Awareness of these factors is crucial for prevention and early intervention.

• Use of Angiotensin-Converting Enzyme (ACE) Inhibitors: This is the most strongly associated risk factor. Patients on medications like lisinopril or enalapril are at a significantly higher risk due to their impaired ability to break down bradykinin.
• Leukoreduced Blood Products: The leukoreduction filters, particularly older bedside versions, use negatively charged surfaces that activate the contact system, leading to bradykinin generation. While prestorage leukoreduction has become standard, the risk can still exist.
• Underlying Medical Conditions: Patients with conditions that upregulate bradykinin receptors (like some inflammatory states or liver disease) or those undergoing cardiac surgery where ACE activity is bypassed may also be predisposed.

Distinguishing HTR from Other Reactions

Since hypotension can be a sign of multiple types of adverse transfusion reactions, differential diagnosis is a critical step. A primary HTR is identified only after excluding these other, often more severe, possibilities.

Feature	Hypotensive Transfusion Reaction (HTR)	Acute Hemolytic Transfusion Reaction (AHTR)	Anaphylactic Transfusion Reaction	Transfusion-Related Acute Lung Injury (TRALI)
Onset	Early and abrupt (often within 15 min)	Early, but hypotension can appear later	Acute onset, typically early	Delayed (1-6 hours after start)
Key Symptoms	Isolated hypotension is predominant	Fever, chills, back pain, hemoglobinuria	Hypotension, urticaria, pruritus, dyspnea, edema	Hypoxemia, severe dyspnea, pulmonary edema
Resolution	Rapidly resolves upon cessation of transfusion	Does not resolve by stopping transfusion alone	Requires epinephrine and other treatments	Does not resolve by stopping transfusion alone
Mechanism	Bradykinin accumulation and impaired breakdown	Antibody-mediated hemolysis of red blood cells	Pre-existing IgA deficiency or other allergens	Donor antibodies activating recipient neutrophils

Management and Prevention

The management of a suspected HTR begins with immediate action, followed by a thorough investigation to confirm the diagnosis and prevent future episodes.

Acute Management Steps

1. Stop the Transfusion: Immediately clamp the infusion line and disconnect the blood product.
2. Maintain IV Access: Keep the intravenous line open with a normal saline infusion.
3. Supportive Care: A fluid bolus may be administered to address the hypotension. In severe, persistent cases, vasopressors may be needed, although they are not always effective with bradykinin-mediated vasodilation.
4. Investigate: Follow the standard protocol for suspected transfusion reactions, including a clerical check and sending the blood product and patient samples back to the blood bank for testing. This is vital for confirming the diagnosis of exclusion.

Preventive Measures for At-Risk Patients

• Consider a Different Antihypertensive: For patients on an ACE inhibitor who require future transfusions, consider switching to an alternative class of medication, such as an angiotensin receptor blocker (ARB), before transfusion.
• Use Washed Cellular Components: Washing blood products removes residual plasma and any accumulated bradykinin, which can prevent recurrence.
• Ensure Prestorage Leukoreduction: The risk is significantly reduced when blood products are leukoreduced by the blood bank prior to storage, rather than at the bedside.

Conclusion

Properly identifying a hypotensive transfusion reaction relies on strict adherence to specific criteria that quantify the blood pressure drop and timing. Crucially, the diagnosis can only be confirmed by excluding other, more common transfusion-related causes of hypotension. Awareness of the underlying bradykinin-mediated mechanism and key risk factors, particularly the use of ACE inhibitors, is essential for both swift management and effective prevention. By following established protocols, healthcare providers can ensure patient safety and effectively manage this distinct, yet often overlooked, adverse event. For more detailed information on transfusion reactions, please consult authoritative medical guidelines and literature, such as resources from the New England Journal of Medicine.

Frequently Asked Questions

What is the primary cause of a hypotensive transfusion reaction?

The primary cause is the accumulation of bradykinin, a potent vasodilator peptide, in the transfused blood product. This is exacerbated in patients taking ACE inhibitors, as the enzyme responsible for breaking down bradykinin is blocked.

How quickly does an HTR typically resolve?

Hypotension from an HTR typically resolves quickly and spontaneously once the blood transfusion is stopped, often within minutes.

Which patients are at greatest risk for HTR?

Patients taking ACE inhibitors are at the highest risk. Other risk factors include receiving leukoreduced blood products (due to filter activation) and certain underlying conditions that affect bradykinin metabolism.

What is the first step in managing a suspected HTR?

The first and most critical step is to immediately stop the transfusion. The intravenous line should be kept open with normal saline while the reaction is investigated.

How can HTR be distinguished from an acute hemolytic reaction (AHTR)?

HTR is primarily characterized by isolated hypotension that resolves with cessation of transfusion. AHTR also involves hypotension but is accompanied by other symptoms like fever, chills, and back pain, and does not resolve by simply stopping the transfusion.

Is it safe to re-transfuse the same blood product after an HTR?

No, the patient should not be re-challenged with the same blood product. A new unit of blood, potentially a washed product, should be used for subsequent transfusions.

What preventive measures can be taken for a patient at risk for HTR?

For elective transfusions, an ACE inhibitor may be temporarily withheld. The use of washed blood components can also prevent a reaction by removing residual bradykinin.