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Adverse Events Related to Blood Transfusion

Okweny David

Senior Laboratory Technologist

0766933766

18^Th July 2024

Republic of Uganda

MINISTRY OF HEALTH

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Presentation outline

Introduction

Understanding Adverse events

Identifying Types and Causes

Investigative approaches &

Discussions

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Session Aim

By the end of this session, participants should be able to;
Define Adverse Events
Identify Types and Causes of Adverse Events
Apply Investigative Approaches
Share experiences; Transfusion services in your respective Health facilities “a resource-constrained setting”

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Introduction

Blood transfusion has been a cornerstone of life support since discovery of ABO classification in the 20^Th C but sometimes carries risks
Defn: Transfusion reactions are adverse events that can occur during or after transfusion of blood or its components. (Popovsky et al,2011).
Understanding these reactions is crucial for

ensuring patient safety and providing timely and effective treatment.

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Introduction ctd..

The severity of transfusion reactions can range from mild to life-threatening, highlighting the importance of identifying and managing them promptly.
It is our duty to understand the transfusion aspects, do it with the best practice, and strive to reduce these events and manage their consequences if they happen

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�Causes of transfusion reactions�

1. Clerical errors: Pt ID, Inadequate labeling, order entry, Wrong blood issued

2. Technical errors: Error in blood grouping & xmatching, Incorrect interpretation of test results

Transfusion Protocol Deviations e.g, Failure to Verify Patient Information

Others : Handling and Storage Errors

Blood contamination during phlebotomy/ processing if no closed system
Blood infusion through a small bore needle
Concomitant adm of bld & drugs thru common set
Miscommunication of critical information between laboratory staff and clinical teams

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Causes of TRs, ctd..

Direct Reasons

Failure to follow SOPs.
Improperly trained staff.
Poor documentation.
Lack of stringent supervision.
Transfusion outside regular working hours

Lack of structured hemovigilance system.
Absence of functional HTC.
Fragmented transfusion service on a national level.
Inefficient QS.

Indirect Reasons

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Classification of Adverse Transfusion Reactions varies..

WBC Ags/ CK CK present in the blood

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WHEN DO TRANSFUSION �REACTONS TYPICALLY HAPPEN? VS FREQUENCY

Graphic design by Kimberly E. Crookston. March/April 2015

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IMMUNOLOGIC ATR

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�Consequences of Complement Activation��

Immediate Effects:

Rapid destruction of transfused RBCs lead to reduced red sell mass
Release of hemoglobin into the bloodstream which is extremely toxic and harms several body organs specially kidneys.
In severe hemolytic reactions, permanent damage to kidneys can happen, or even multi-organ failure leading to death.

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Prolonged=Prothrombin Time (PT), Activated Partial Thromboplastin Time (aPTT), Thrombin Time (TT), with Fibrinogen Level:

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Febrile Non-Hemolytic Transfusion Reaction (FNHTR)

Rise in Temp >1⁰C
Fever without hemolysis
Occurs in 1%PRBCs and 20%plts
Risks: Generally mild, but may cause discomfort

Causes:

Cytokines in transfused blood, Fever Induction: Cytokines like IL-1 and TNF-α act on the hypothalamus,
Allo antibodies directed against HLA

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Allergic Blood Transfusion Reaction

Allergic reactions to blood transfusions are adverse responses to blood or blood products.
Caused by an allergic response to components like plasma proteins (immunoglobulin A (IgA) or albumin) or white blood cells in the donated blood.
Varies in severity from mild to life-threatening.

Pathophysiology:

Immune Response:Antigen-Antibody Interaction:

Foreign proteins in donor blood (e.g., plasma proteins) act as antigens.
Recipient's immune system recognizes these proteins as foreign.
IgE antibodies bind to these antigens.
Mast Cell and Basophil Activation:

IgE-antigen complexes bind to receptors on mast cells and basophils.
Trigger release of histamines and other mediators.

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Transfusion-Related Acute Lung Injury (TRALI)

TRALI is a serious complication of BT characterized by acute lung injury or within 6 hours of transfusion.

A leading cause of transfusion-related mortality.

Caused by donor antibodies

Investigations

Laboratory Tests: Blood gases PaO2, PaCO2, complete blood count.
Imaging: Chest X-ray to detect pulmonary infiltrates.
Serological Tests: Donor and recipient antibody testing.

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Key Features:

Arterial Blood Gas (ABG) Analysis; PaO2 (Partial Pressure of Oxygen), PaCO2 (Partial Pressure of Carbon Dioxide)
Acute lung injury during or within 6 hours of transfusion.
Hypoxemia (PaO2/FiO2 ratio ≤ 300 mm Hg). Severe Hypoxemia: P/F ratio below 100.
Bilateral infiltrates on chest X-ray.
No evidence of circulatory overload (to rule out TACO).

TRALI Diagnostic Criteria

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Transfusion-Associated Circulatory Overload (TACO)

NON IMMUNOLOGIC ATR

Occurs when the volume of the transfused component causes hypervolemia (volume overload) or exceeds the capacity of the circulatory system..
Caused by rapid infusion of Blood or its product
Onset during or shortly after transfusion
Dyspnea, edema, and hypertension

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Clinical Assessment

History and physical examination

Laboratory Tests

BNP (B-type natriuretic peptide) levels
Arterial blood gases

Imaging

Chest X-ray showing pulmonary edema

TACO Diagnostic Criteria

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Destruction of red blood cells (RBCs)

Release of hemoglobin into the bloodstream Types of Hemolysis

Physical Hemolysis

Mechanical damage to RBCs

Chemical Hemolysis

Destruction of RBCs by chemical agents, antibiotics

Osmotic Stress
Hypotonic solutions causing cell swelling and rupture
Thermal Injury
High temperatures denaturing cell membranes

Physical Hemolysis &Chemical Hemolysis

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Hemoglobin levels, reticulocyte count, LDH a marker for tissue damage ,

Peripheral Blood Smear

Presence of schistocytes, spherocytes

Coombs Test

Differentiating immune vs. non-immune hemolysis

Serum Markers

Elevated bilirubin, free hemoglobin

Laboratory Tests for Hemolysis

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Delayed Transfusion Reactions

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�Delayed Hemolytic Transfusion Reaction (DHTR)

Immune-mediated destruction of transfused red blood cells

Occurs days to weeks after transfusion

Causes and Risk Factors

Previous Sensitization (Prior transfusions, pregnancy, transplantation)
Alloantibodies

Common antibodies: anti-Kidd, anti-Duffy, anti-Rh

Immunologic

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Delayed Transfusion Reactions

Laboratory Findings

Hemolytic Markers

Decreased hemoglobin levels
Elevated bilirubin
Increased lactate dehydrogenase (LDH)
Decreased haptoglobin

Direct Antiglobulin Test (DAT)

Positive for IgG or complement

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�Transfusion-Transmitted Infections (TTIs)�

Viral Infections; HIV, hepatitis B and C, cytomegalovirus, HTLV.
Bacterial Infections; Syphilis
Parasitic Infections; Malaria, Trypanosomiasis, Chagas diseas …

NB: The reasons for not routinely testing for some in all blood donations are:1. High seroprevalence e.g CMV =50-80%

2. Limited disease burden:

3. Cost and resource considerations:

UBTS: Focus on higher-risk pathogens e.g HIV and hepatitis.

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Graft-Versus-Host Disease (GVHD), �Iron Overload, Hypothermia, and Hypocalcemia

Occurs after a stem cell transplant. It happens when the donor's iT cells, attack the recipient's tissues. This can lead to various symptoms and affect different organs.

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WHAT DO I DO WHEN I SUSPECT �A TRANSFUSION REACTION?

Stop the transfusion immediately and keep the line open.
Perform a clerical check of blood component labeling and patient identification
Notify the clinical team including Lab
Complete a transfusion reaction evaluation request form
Send the blood bag, infusion set, and anything else connected to it except the needle, as well as a newly drawn blood specimen, to the laboratory (EDTA tube).
Examine the urine for free hemoglobin.

Katz EA et al 2012, UBTS-HQS-RCD-01-02

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STEPS LABORATORY INVESTIGATION OF A SUSPECTED TRANSFUSION REACTION

On post transfusion sample;

confirmation of the patient’s blood type to rule-out a clerical error.
Look for free hemoglobin in serum and urine
DAT may be negative at first but becomes Ve+ soon after.
pretransfusion blood specimen stored in the blood bank is evaluated for comparison
e blood bag is examined for possible hemolysis from contamination or mishandling before the transfusion.
Reapeat x-match to verify serological compatibility
Blood cultures should be taken, and broad-spectrum antimicrobials commenced.

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�Samples to be Collected�

1.Blood Samples

Blood samples are collected from the patient before, during, and after the transfusion. The samples are analyzed in the laboratory to monitor the patient's response to the transfusion.

2.Urine Samples

Urine samples are collected to check for signs of hemolysis

3.Tissue Samples

In cases of suspected acute hemolytic transfusion reaction, tissue samples may be collected from the patient.

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Challenges

Improper xmatch (most referrals have automated machines which they do not use).
Lack of monitoring pts undergoing BT
Under reporting of transfusion rxns
Failure to maintain closed system when aliquoting blood
Non aseptic use of transfer bags
Use of IV fluid giving set for BT

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Way forward

Do proper xmatch
Maintain closed system
Monitor pts undergoing BT
Implement hemovigilance system to improve reporting and investigation of tx rxns
Observe strict SOPs for BT
Make use of the BT clinical guidelines

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Conclusion:

Blood transfusion reactions can be diverse in their presentation and underlying causes.
Prompt recognition and appropriate lab investigations are critical for effective management and improving patient outcomes.
Implementing preventive strategies like leukoreduction and careful monitoring can significantly reduce the incidence of adverse reactions.

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Conclusion: TRANSFUSION REACTION RECOGNITION AT THE BEDSIDE

. Signs and symptoms help the clinical team differentiate a normal patient response

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References

Popovsky MA . Transfusion Reactions. 4th ed. Bethesda, MD : AABB Press ; 2012 .
Katz EA . Blood transfusion: friend or foe . AACN Adv Crit Care. 2009 ; 20 ( 2 ): 155-163 .
Allain, J. P., Stramer, S. L., Carneiro-Proietti, A. B. F., Martins, M. L., Da Silva, S. L., Ribeiro, M., ... & Reesink, H. W. (2009). Transfusion-transmitted infectious diseases. Biologicals, 37(2), 71-77.
Sahu, S., & Verma, A. (2014). Adverse events related to blood transfusion. Indian journal of anaesthesia, 58(5), 543-551.
Tinegate, H., Birchall, J., Gray, A., Haggas, R., Massey, E., Norfolk, D., ... & Allard, S. (2012). Guideline on the investigation and management of acute transfusion reactions Prepared by the BCSH Blood Transfusion Task Force. British journal of haematology, 159(2), 143-153.
Ackfeld, T., Schmutz, T., Guechi, Y., & Le Terrier, C. (2022). Blood transfusion reactions—a comprehensive review of the literature including a swiss perspective. Journal of Clinical Medicine, 11(10), 2859.
Dhabangi, A., Musisi, E., & Kyeyune, D. (2020). Improving blood transfusion safety in resource-poor countries: A case study of using leucocyte reduced blood in Uganda. African Health Sciences, 20(2), 977-983.