In Focus

Delayed adverse reaction in blood donors

A call for timely inclusion

Sadhana Mangwana

Sri Balaji Action Medical Institute, Paschim Vihar, New Delhi, India

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Blood donor safety is of paramount importance, and all blood centres and establishments must ensure its protection through strict adherence to donor selection guidelines, well-defined standard operating procedures (SOPs), adequately trained personnel, and appropriate infrastructure. A robust quality framework not only safeguards donors but also reinforces public trust in the blood transfusion system.

Nevertheless, despite stringent screening and preventive measures, ADRs may occasionally occur during or after the donation process. The majority of these reactions arise within the first 30 minutes of initiation of donation and are typically mild and self-limiting, responding well to simple supportive interventions.

ADRs can be classified as immediate and delayed reactions. Immediate ADRs occurs on-site (on the collection facility) before donor has left the facility and delayed ADRs can be off-site (outside the collection facility) after donor has left the donation site1. Immediate reactions are well documented in the literature while delayed ADRs are under reported due to many reasons, yet they significantly impact donor retention and return rates. Incidence of delayed ADRs is reported varying from 6.31%, 11.2%, to 13.69%2-4. Delayed ADRs are more common than immediate ADRs in some studies (13.7% vs 2.9%)4.

Delayed ADRS often manifest as –

  • Localized Reactions: Bruises, hematomas, and painful arms are the most common. Bruising reported in various studies is varying from 1.3% to 30.9% (2-5) while hematomas were reported in 0.3% to 1.22%, (2, 4). Incidence of painful arm varies from 0.7% to 26.2% (2, 3). In one study 1.02% donors reported allergic reactions or itching at phlebotomy site 4.
  • Systemic Reactions: Fatigue or generalized weakness, delayed vasovagal reactions (VVR), dizziness, headache, nausea, diarrhoea, and rarely, rash or fever. Generalised weakness is reported in 3.4%, to 18.9% donors2-4. Incidence of fever was found higher in first time donors than repeat donors (5.5% Vs 3.6%)4.
  • Serious Complications: Grade 3 and above, although rare; some delayed reactions can include injury due to fall (when VVR occurs off-site), severe hematoma, anaphylaxis, air embolism or very rarely, death. SHOT 2024 data reports 42 cases of Severe adverse donor reactions in 20246.
  • Pathophysiology:DARs stem from physiological stress of phlebotomy, including hypovolemia, vasovagal activation, or localized trauma.
  • Hematomas/Bruises: Venipuncture leakage is a common complication. Large leaks (>5 cm) indicate poor technique or fragile veins and can persist for 7–14 days. Haemorrhage formation is generally mild and donors typically do not report to blood establishments.
  • Fatigue/Weakness: Higher risk in low-Estimated Blood Volume (EBV) donors is linked to acute blood volume loss of 450–500 mL. This risk peaks at 24 hours and resolves within 3–7 days.
  • Arm Pain/Swelling: Nerve irritation or infiltration can cause severe cases to mimic compartment syndrome, a rare condition requiring urgent assessment.
  • Delayed VVRs: Syncope or presyncope can occur from 6 to 48 hours after an episode of orthostatic intolerance. Off-site occurrences increase the risk of falls. High-Risk Categories:
  • First-time donors are more prone to delayed ADRs (16.1%) compared to repeat donors (12.5%)4.
  • Females have higher susceptibility to both immediate and delayed VVRs due to lower body weight.
  • Younger donors (18–24 years) often have lower body weight and lower estimated blood volume (EBV).
  • Occupation: Manual/farm workers have reported higher incidence of delayed ADRs3.
  • Procedural factors: Such as First-time phlebotomists, high-gauge needles, or rapid collection exacerbate issues also come under expanded risk stratification along with comorbities like dehydration or manual labour amplifying off-site severity, especially injury potential, like falls.

Reason for underreporting

Various factors may influence a donor’s decision not to report adverse events. These include limited awareness or understanding of potential complications, normalization or trivialization of symptoms, apprehension regarding temporary or permanent deferral, and social or cultural influences. Such underreporting can delay timely intervention and may adversely affect donor safety and retention.

Structured Follow-up Protocols for increase reporting

A systematic follow-up framework strengthens haemovigilance and promotes donor safety. Increased reporting can be best achieved through a structured surveillance model.

  • 24-Hour Surveillance: Telephonic contact at 24 hours is recommended for donors who experienced vasovagal reactions (VVRs) or significant fatigue, allowing early identification of persistent symptoms. A follow-up calls to assess dizziness, weakness, syncope, or venepuncture-site concerns can also be useful.
  • 7–14 Day Assessment: An additional follow-up between 7 and 14 days is particularly useful for assessing delayed complications such as bruising or localized pain. Evaluate persistent bruising, swelling, or pain, and classify severity (e.g., Grade 1: mild and self-limiting; Grade 3: requiring hospitalization or specialist intervention). Day-7 calls serve a dual purpose: early detection of evolving issues and provision of reassurance, thereby enhancing donor satisfaction and retention.
  • Emergency Escalation: Donors reporting progressive swelling, increasing pain or symptoms persisting beyond 48 hours should be advised immediate medical evaluation to exclude complications such as infection or thrombophlebitis. Re-donation may be deferred for 4–12 weeks, depending on the severity and clinical resolution of the reaction.

Prevention Strategies for delayed reactions

Preventive measures should be integrated across all phases of the donation process:

  • Pre-donation: Careful screening of high-risk donors, adherence to EBV-based eligibility criteria, and ensuring adequate pre-donation hydration.
  • Intra-donation: Ongoing staff training in optimal vein selection, gentle needle handling, and consideration of slower flow rates in at-risk donors. Vigilant observation during collection remains critical.
  • Post-donation: Provision of written instructions, educational pamphlets, or digital self-reporting platforms to facilitate early communication of symptoms. DARs are known to significantly reduce return rates; therefore, proactive reassurance, empathetic communication, and timely follow-up are essential to sustain donor loyalty and maintain a stable donor base.

References

1. International Society of Blood Transfusion. Standard for surveillance of complications related to blood donation [Internet]. 2019

2. Jain R, Gupta A, Bava D, Patil V, Sinha P, Garg S, et al. Time-deferred consequences: A deep dive into delayed adverse reactions among whole blood donors. Asian Journal of Transfusion Science. 2025 Jul 1; 19(2):217-23.

3. Kaur S, Mittal K, Kaur R, Kaur G, Kaur P, Sood T. Reporting of delayed adverse donor reactions in whole blood donors: Just the tip of an iceberg!. Transfusion Clinique et Biologique. 2022 May 1; 29(2):141-6.

4. Gupta AM, Bajpai M. Delayed adverse reactions in whole blood donors: Importance of active surveillance in identifying the missing gaps in the donor safety. Indian Journal of Medical Research. 2023 Jan 1; 157(1):30-6.

5. Kumar R, Kaur P, Verma K, Rajeev K, Bhaskar B, Kumar S. Delayed adverse reaction in donors after whole blood donation: Is it a matter of concern?. Transfusion Clinique et Biologique. 2023 May 1; 30(2):232-7.

6. SHOT 2024 report. https://www.shotuk.org/shot-reports/annual-shot-report-2024/

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