Blood Transfusion

The Blood Safety and Quality Regulations (BSQR)

Set standards of quality and safety for the collection, testing, processing, storage and distribution of human blood and blood components

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SABRE – Serious Adverse Blood Reactions and Events

SAE Serious Adverse Event Any untoward occurrence associated with the collection, testing, processing, storage and distribution, of blood or blood components that might lead to death or life-threatening, disabling or incapacitating conditions for patients or which results in, or prolongs, hospitalisation or morbidity.’

SAR Serious Adverse Reaction: ‘An unintended response in a donor or in a patient that is associated with the collection, or transfusion of blood or blood components that is fatal, life-threatening, disabling or incapacitating, or which results in or prolongs hospitalisation or morbidity’

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Competent Authorities

The Medicines and Healthcare- Products Regulatory Agency (MHRA) monitor compliance with the regulations and carry out inspections of blood establishments.

The MHRA has the authority to prosecute individuals and organisations and close establishments

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Blood Components

JPAC: Joint UKBTS/NIBSC Professional Advisory Committee undertakes regular review of the Guidelines in the light of developments in the field, both scientific, ethical and regulatory.

The overall aim is to ensure as far as possible the safety of blood transfusion in the UK.

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Safety of Donor

  • Weight < 50Kg
  • Under 17/over 65
  • Minimum donation interval 16 weeks
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Red cell transfusion

To increase the oxygen delivering capacity of the blood when acute or chronic anaemia contributes to inadequate oxygen delivery to tissues.

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Platelet transfusions

The prevention and treatment of haemorrhage in patients with thrombocytopenia or platelet function defects.

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Fresh frozen plasma

Replacement of coagulation factors in a few specific situations and for treatment of thrombotic thrombocytopenia.

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Human plasma derivatives

Human IgG from a large pool of unselected.  Human IgG from donors with high levels of specific antibodies.

Human albumin - Restoration and maintenance of circulating the blood volume where volume deficiency has been demonstrated and use of a colloid is appropriate.

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Blood groups

Red cell groups and antibodies. Each  blood group system is a series of red cell antigens determined by a single genetic locus. 

Other antigen systems:

       HPA Platelets

       HNA Granulocytes

       HLA Lymphocytes      

Some Common Blood Group Systems and Antigens:

       ABO:  A, B (O)  

       Rh:  D, E, e, C , c   

       Kell:  K, k, (Kpa/Kpb Jsa/Jsb)

       MNS:  S, s, M, N   

       Fy (Duffy):   Fya, Fyb  

       Jk (Kidd): Jka, Jkb    

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Red Cell Membrane

Red blood cells are deformable, flexible, are able to adhere to other cells, and are able to interface with immune cells.

Half of the membrane mass in human and most mammalian red blood cells are proteins. The other half are lipids, namely phospholipids and cholesterol.

 

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The ABO Blood group System

A and B antigens are indirect gene products, the direct products are transferase enzymes. ABO locus is on chromosome 9, the expression also requires H (FUT1) gene on chromosome 19.

Acquired B Antigen

Occurs in:

·       Rectal and bowel carcinomas

·       Perforation/ulceration

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The Oh Phenotype

Rare individuals are phenotypically hh.  Naturally occuring anti-H which makes them incompatible with all ABO groups except Oh.

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Rh Blood Group System

The RH locus is found on chromosome 1. 

RhD Neg in Caucasians is a gene deletion, in other populations, some  individuals typing as RhD Neg are found to have single point mutations, partial deletions or recombinations

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Rhnull

Rare individuals fail to produce not only RhD but also RhCE proteins. Two types: amorph type is homozygous for a silent allele at the RH locus; regulator type is homozygous for an autosomal suppressor gene X°r

Involved in ion transport. 

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Kell System

The Kell antigen system is a group of antigens on the human red blood cell surface which are important determinants of blood type and are targets for autoimmune or alloimmune diseases.

 Expression depends on production of Kx protein by genes at XK locus on X chromosome. Kell protein is complexed by a disulphide bridge to Kx.

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FY System

  • FY locus is on chromosome 1
  • Fya and Fyb antigens are co-dominant, they differ by 1 residue at position 44,glycine in Fya, asparagine in Fyb.
  • Fy glycoprotein is expressed on vascular endothelial cells and Purkinje cells in the cerebellum
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The Fy(a-b-) Phenotype

This occurs in populations where malaria is endemic.

An alternative gene at the FY locus, Fy, occurs.

The Fy gene is identical to the Fyb gene in its structural region but has a mutation in the promoter region.

Fy glycoprotein is not produced on red cells when an individual is homozygous for this gene.

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The JK System

  • JK locus (now HUT11) on chromosome 18
  • Codominant alleles Jka and Jkb, differ by single amino acid substitution
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MNS System

       GYPA and GYPB are closely linked genes on chromosome 4, coding for glycophorin A and B respectively.

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Red Cell Antibodies

•Immune -  made following transfusion or during pregnancy

•Antibodies are made to red antigens that the recipient lack 

•Antibody can be IgM or IgG or occasionally mixture of both

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Intravascular haemolytic transfusion reaction

A hemolytic transfusion reaction is a serious complication that can occur after a blood transfusion. The reaction occurs when the red blood cells that were given during the transfusion are destroyed by the person's immune system.

 Haemoglobin is released into the circulation. C3a and C5a are potent anaphylotoxins -  proinflammatory effects.

Patient (if conscious) experiences fever, chills, rigors, tight chest, pain at infusion site, joint pain, lower back pain, hemoglobinuria. 

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Extravascular haemolytic transfusion reaction

       IgG binds to (sensitises) the red cell

       Macrophages bind via Fc receptor sites (affinity of binding greatest for IgG1 and IgG3)

       Cells phagocytosed or lysed

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Haemolytic Disease of the New-born/Fetus

Hemolytic disease of the newborn, also known ashemolytic disease of the fetus and newbornHDN, HDFN, or erythroblastosis fetalis, is an alloimmune condition that develops in a peripartum fetus, when the IgG molecules (one of the five main types of antibodies) produced by the mother pass through the placenta.

Is a condition in which the lifespan of the infant’s red cells is shortened by the action of specific antibodies derived from the mother by placental transfer; the disease begins in intrauterine life and may result in significant mortality and morbidity.

 

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Red Cell Matching for Transfusion

  • ABO and Rh D matched (‘electronic issue’)
  • K neg and full Rh phenotype match (C,c, E and e antigens) for transfusion dependant patient
  •  Individuals with antibody to  high frequency antigens e.g. anti-k (Cellano), cause acute problems –donor panel/frozen cell
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Pregnancy: prevention and management of HDN

  •  Purpose: To identify fetuses at risk of HDN predict the severity of the HDN  and to plan treatment.

Rh D negative pregnancies

Anti-D immunoglobulin is administered i.m. at 30 weeks gestation.

blood test used to measure the amount of fetal hemoglobin transferred from a fetus to a mother's bloodstream. It is usually performed on Rh-negative mothers to determine the required dose of Rho(D) immune globulin (RhIg) to inhibit formation of Rh antibodies in the mother and prevent Rh disease in future Rh-positive children

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Pregnancy complicated by blood group antibodies

Phototherapy is treatment with a special type of light (not sunlight). It's sometimes used to treat newborn jaundice by lowering the bilirubin levels in your baby's blood through a process called photo-oxidation.This makes it easier for your baby's liver to break down and remove the bilirubin from their blood.

Exchange transfusion is a potentially life-saving procedure that is done to counteract the effects of serious jaundice or changes in the blood due to diseases such as sickle cell anemia. The procedure involves slowly removing the person'sblood and replacing it with fresh donor blood or plasma.

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Platelet-Specific Antibodies and NAIT

Neonatal alloimmune thrombocytopenia, (NAIT) is caused by maternal antibodies raised against alloantigens carried on fetal platelets. Although many cases are mild, NAIT is a significant cause of morbidity and mortality in newborns

        Maternal antibodies to HPA-1a and HPA-5b

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Febrile non-haemolytic transfusion reaction

  • Rise in temp of 1°C or more, flushing, tachycardia, rigors
  • Occurs 30mins to 2 hr after start of infusion
  • Caused by HLA and/or neutrophil antibodies, antigen-antibody-complement complexes cause release of’pyrogens’ e.g. IL-1
  • Can be caused by platelet infusion due to cytokines released during storage
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Allergic Reactions

Mild allergic, local cutaneous reaction, urticaria, wheezing,  IgE 

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Bacterial Contamination

  • Main source are platelets (pooling/storage at 22°C
  •  Donor bacteraemia, skin, pack contamination
  • Organisms in red cells include Yersinia enterocolitica, Pseudomonas fluorescens
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Post-Transfusion Purpura

  • Severe thrombocytopenia and bleeding occur 5 – 12 days after transfusion of red cells, rapid onset, Platelets fall to <10x.
  • HPA-1a neg patient has previously made anti-HPA-1a, other platelet antibody specificities occasionally cause PTP.
  • HPA-1a positive platelets in the red cell unit stimulate secondary immune response
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