Transfusion Science and Immunohaematology Comprehensive Review

Comprehensive vocabulary flashcards covering the full transfusion science syllabus across blood groups (ABO, Rh, Kell, Kidd, Duffy, MNSs), laboratory serology, pretransfusion standards, component processing, adverse transfusion reactions, and haemolytic disease of the newborn.

James Blundell

The English obstetrician regarded as the 'father of modern blood transfusion,' who performed the first documented transfusion of human blood on 22nd December 1818 and emphasized that transfusion should be reserved only for the desperately ill.

Blood Group (ISBT Definition)

One or more red blood cell surface antigens controlled by an allelic gene whose DNA sequence has been identified, whose chromosomal location is mapped and distinct from all other blood group systems, and whose corresponding human alloantibody has been characterized.

Zeta ($\zeta$) Potential

The electrical charge measured at the slipping plane of the cation cloud surrounding red blood cells, quantified at $-18\,\text{mV}$ in isotonic saline, which produces electrostatic repulsion that maintains a distance of approximately $20\,\text{nm}$ between erythrocytes.

Naturally Occurring Antibodies

Antibodies present in plasma without prior exposure to foreign red blood cells, synthesized in response to environmental or gut bacterial antigens sharing identical carbohydrate epitopes; they are predominantly of the IgM class, react optimally at $4\,^\circ\text{C}$, and activate complement.

Immune Antibodies

Antibodies produced only following deliberate or accidental exposure to foreign red cell antigens via pregnancy, blood transfusion, or therapeutic immunization; they are predominantly monomeric IgG, react optimally at $37\,^\circ\text{C}$, and act as 'incomplete' agglutinins in saline.

Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC)

An extravascular haemolytic mechanism wherein IgG-sensitized red blood cells bind to splenic and hepatic reticuloendothelial macrophages via cell-surface Fc receptors, leading to phagocytosis and destruction.

IgM Antibody Structure

A pentameric immunoglobulin molecule measuring approximately $30\,\text{nm}$ across with a molecular weight capable of directly bridging the $20\,\text{nm}$ intercellular gap between erythrocytes in saline to cause direct agglutination.

Type 2 Precursor Substance

The oligosaccharide core structure anchored to the red blood cell membrane consisting of glucose, D-galactose, and N-acetylglucosamine (GlcNAc), terminating in a D-galactose residue linked via a $\beta\text{-1,4}$ bond.

H Antigen

The foundational ABO antigen synthesized by the action of $\alpha\text{-2-L-fucosyltransferase}$ (encoded by the $FUT1$ gene on chromosome 19), which transfers an L-fucose residue to the terminal D-galactose of the Type 2 precursor substance.

A Antigen

The ABO carbohydrate antigen produced by $\alpha\text{-3-N-acetylgalactosaminyltransferase}$ (encoded on chromosome 9q34), which adds N-acetyl-D-galactosamine (GalNAc) to the terminal D-galactose of the H antigen structure.

B Antigen

The ABO carbohydrate antigen produced by $\alpha\text{-3-D-galactosyltransferase}$ (encoded on chromosome 9q34), which transfers a D-galactose residue to the terminal D-galactose of the H antigen structure.

Forward Grouping

The front-typing serological procedure that tests patient red blood cells against known monoclonal commercial anti-A and anti-B reagents to determine the presence of ABO antigens on the erythrocyte surface.

Reverse Grouping

The back-typing serological confirmation procedure testing patient plasma or serum against known reagent red blood cells ($A_1$ and $B$ cells) to identify expected reciprocal ABO antibodies.

Dosage Effect

A serological phenomenon where an antibody reacts with significantly greater avidity and agglutination strength against red cells exhibiting homozygous ('double dose') antigen expression compared to cells with heterozygous ('single dose') expression.

Antithetical Antigens

Pairs of alternative red cell surface antigens encoded by allelic genes located at the same genetic locus that segregate reciprocally, such as C and c, E and e, K and k, or $Jk^a$ and $Jk^b$.

RhCE Protein

A 417-amino acid multipass transmembrane erythrocyte protein carrying C or c specificity depending on a Ser/Pro polymorphism at residue $103$, and E or e specificity determined by a Pro/Ala polymorphism at residue $226$.

Partial D

An altered RhD protein phenotype resulting from genetic exchange between $RHD$ and $RHCE$, producing a mosaic D molecule lacking specific extracellular epitopes; affected individuals can form alloanti-D if exposed to complete D-positive red blood cells.

Weak D

A quantitative reduction in the number of complete, structurally intact RhD antigen molecules per erythrocyte, managed clinically as RhD-positive in recipients and donors.

Fisher-Race and Wiener Nomenclature Equivalents

The parallel Rh naming system where $DCe$ equals $R_1$, $DcE$ equals $R_2$, $Dce$ equals $R_0$, $dce$ equals $r$, $dCe$ equals $r'$, and $dcE$ equals $r''$.

Kell System Antigen K (KEL1)

A potent, highly immunogenic red cell glycoprotein antigen present in approximately $9\%$ of the population, which is resistant to proteolytic enzyme degradation (ficin, papain) but destroyed by sulfhydryl reducing agents such as DTT and AET.

Kidd Blood Group System (ISBT 009)

A red cell antigen system consisting of $Jk^a$ and $Jk^b$ urea transporter proteins; its antibodies are characteristically labile, demonstrate striking dosage, decline rapidly in vivo below detectable thresholds, and frequently cause delayed haemolytic transfusion reactions.

Duffy Null Phenotype: $Fy(a-b-)$

The complete absence of $Fy^a$ and $Fy^b$ antigens on erythrocytes due to a promoter mutation in the ACKR1 gene, found in $68\%$ of African Americans and up to $100\%$ of indigenous West and Central African populations, conferring natural resistance to Plasmodium vivax merozoite invasion.

Anti-Human Globulin (AHG) Test

A testing method described by Coombs, Mourant, and Race in 1945 that employs animal-derived antibodies directed against human IgG and/or complement fragment $C3d$ to bridge non-agglutinating antibodies bound to red blood cells.

Direct Antiglobulin Test (DAT)

A diagnostic serological procedure performed on washed patient red blood cells to detect in vivo coating of erythrocytes with IgG antibodies and/or complement components ($C3d$).

Indirect Antiglobulin Test (IAT)

A two-stage in vitro assay wherein reagent or donor red cells are incubated with patient plasma at $37\,^\circ\text{C}$, washed thoroughly to remove unbound globulins, and exposed to AHG reagent to detect clinically significant red cell antibodies.

AHG Control Cells (Check Cells)

Pre-sensitized, IgG-coated red blood cells added to all negative AHG tube tests to verify that active anti-human globulin reagent was added, was not neutralized by residual unbound globulin from inadequate washing, and that the negative result is valid.

Low Ionic Strength Saline (LISS)

A potentiating medium containing $0.2\%$ saline and glycine that reduces the ionic cloud surrounding red blood cells, enhancing the rate of antibody uptake during sensitization and allowing incubation time to be shortened from $60\,\text{minutes}$ to $5\text{--}10\,\text{minutes}$.

Polyethylene Glycol (PEG)

A linear, water-soluble macromolecular additive that concentrates antibody molecules through the steric exclusion of water, markedly accelerating antigen-antibody complex formation during IAT incubation.

Prozone Effect

A serological false-negative or falsely weak agglutination reaction caused by a vast excess of antibody relative to available antigen binding sites, preventing adequate lattice cross-linking.

Column Agglutination Technology (CAT) Grading

A microtyping gel card system grading haemagglutination from $0$ to $4+$, where $4+$ represents a distinct red cell band trapped at the top of the gel matrix and $0$ represents an unagglutinated red cell pellet at the bottom of the microtube.

Patient Identification Requirements (ANZSBT 1.4)

The mandatory baseline requiring three unique identifiers for pathology requests, compatibility reports, and laboratory records (full name, date of birth, and unique record number MRN/NHI), and at least two unique identifiers legibly marked on the specimen tube.

Pretransfusion Sample Validity Period (ANZSBT 2.2.6)

The defined duration for which a pretransfusion testing sample remains valid for issuing red cells: strictly $72\,\text{hours}$ from collection if the patient was transfused or pregnant in the preceding $3\,\text{months}$ (or history is unknown), and up to $3\,\text{months}$ if there has been no transfusion or pregnancy in the preceding $3\,\text{months}$.

Pretransfusion Specimen Retention (ANZSBT 1.6.3.3)

The regulatory standard mandating that patient red cells and serum/plasma from pretransfusion specimens be retained at $2\text{--}8\,^\circ\text{C}$ for up to $7\,\text{days}$ following transfusion to permit investigation of potential adverse transfusion reactions.

The '2+2' Rule

The statistical requirement in red cell antibody identification panel analysis mandating that an antibody candidate react with at least 2 panel cells carrying the antigen, and fail to react with at least 2 panel cells lacking the antigen, achieving a $p\text{-value} \le 0.05$.

Maximum Surgical Blood Order Schedule (MSBOS)

A hospital guide defining standard preoperative blood ordering and crossmatch requirements based on historical surgical consumption; procedures with a crossmatch-to-transfusion (C:T) ratio $> 1.8$ are designated as suitable for 'Group and Screen' (G&S) only.

Electronic Crossmatch (eXM)

The computer-verified automated release of compatible red blood cells without physical serological crossmatching, permitted only when validated software verifies two identical ABO/Rh typings, a negative antibody screen, and no history of clinically significant red cell antibodies.

Emergency Uncrossmatched Blood Protocol (ANZSBT 4.1.4)

The urgent release protocol specifying that females of childbearing potential ($\le 50\,\text{years}$) and paediatric males ($\le 18\,\text{years}$) receive Group O RhD-negative (preferentially K-negative) uncrossmatched red cells, whereas females $> 50\,\text{years}$ and adult males $> 18\,\text{years}$ receive Group O RhD-positive red cells.

Leukocyte Depletion (Leucodepletion)

The routine filtration of whole blood, red cells, or platelets during manufacturing to reduce residual donor white blood cells to below standard limits, substantially decreasing the risk of febrile non-haemolytic transfusion reactions, HLA alloimmunization, and cytomegalovirus transmission.

SAGM Additive Solution

A red blood cell preservative solution composed of Saline, Adenine (to maintain ATP levels), Glucose (to sustain glycolysis), and Mannitol (to prevent red cell lysis), granting packed red cells a refrigerated storage life of $42\,\text{days}$ at $2\text{--}6\,^\circ\text{C}$.

Apheresis

An automated blood collection technology wherein anticoagulated whole blood is continuously separated into components via in-line centrifugation, target fractions (such as platelets or plasma) are retained, and non-target components are returned to the donor.

Fresh Frozen Plasma (FFP)

The fluid portion of whole blood or apheresis plasma frozen to $-25\,^\circ\text{C}$ or below, containing all normal coagulation factors including labile Factors V and VIII, indicated for multiple factor deficiencies and coagulopathies where specific factor concentrates are unavailable.

Cryoprecipitate

The cold-insoluble plasma fraction harvested after thawing FFP at $2\text{--}6\,^\circ\text{C}$, enriched in Fibrinogen, Factor VIII, von Willebrand Factor, Factor XIII, and Fibronectin, indicated primarily for acquired hypofibrinogenaemia or dysfibrinogenaemia.

Blood Component Gamma Irradiation

The treatment of cellular blood components (red blood cells and platelets) with $25\text{--}50\,\text{Gy}$ of ionizing gamma radiation to inactivate donor T-lymphocytes and prevent Transfusion-Associated Graft-versus-Host Disease in susceptible recipients.

Haemolytic Disease of the Fetus and Newborn (HDFN)

A fetomaternal alloimmune disorder occurring when maternal IgG antibodies cross the placenta into fetal circulation, binding to paternal-inherited red cell antigens and triggering immune-mediated hemolysis, severe fetal anemia, and newborn hyperbilirubinemia.

Kernicterus

A devastating neurological condition resulting from neurotoxic unconjugated bilirubin crossing the immature blood-brain barrier of the neonate and depositing in the basal ganglia and brainstem nuclei.

Hydrops Fetalis

A severe manifestation of intrauterine fetal anemia characterized by gross generalized fetal edema, ascites, pleural effusions, and high-output cardiac failure.

Middle Cerebral Artery (MCA) Doppler Ultrasound

A non-invasive antenatal ultrasound assessment that measures peak systolic velocity in the fetal middle cerebral artery, where elevated blood velocity corresponds with reduced blood viscosity caused by fetal anemia.

Kleihauer-Betke Test (Acid Elution Test)

A quantitative microscopic technique for measuring fetomaternal haemorrhage based on the principle that adult haemoglobin ($HbA$) is eluted from maternal RBCs in an acid buffer leaving 'ghost' cells, whereas fetal haemoglobin ($HbF$) is acid-resistant and stains darkly.

Prophylactic Rh(D) Immunoglobulin (Rh(D)Ig)

Hyperimmune polyclonal anti-D extracted from sensitized donor plasma, administered to non-sensitized RhD-negative women at $28$ and $34\,\text{weeks}$ of gestation, post-delivery of an RhD-positive infant, and following sensitizing events, to destroy fetal RhD+ cells and prevent maternal alloimmunization.

Phototherapy for HDN

A non-invasive treatment exposing the hyperbilirubinemic neonate to blue-green light ($\lambda = 460\,\text{nm}$) to convert unconjugated bilirubin into water-soluble photoisomers that can be excreted in bile and urine without hepatic conjugation.

Anti-Kell HDFN Pathophysiology

A unique form of HDFN where maternal anti-K targets early erythroid progenitors expressing the Kell glycoprotein, causing suppression of fetal erythropoiesis in the liver rather than marked peripheral haemolysis.

Acute Haemolytic Transfusion Reaction (AHTR)

A hyperacute, life-threatening transfusion complication usually triggered by ABO-incompatible red blood cells interacting with recipient isohemagglutinins, causing intravascular hemolysis, complement-mediated shock, and DIC.

Delayed Haemolytic Transfusion Reaction (DHTR)

An extravascular haemolytic reaction occurring $> 24\,\text{hours}$ (often $5\text{--}14\,\text{days}$) post-transfusion, occurring when an anamnestic IgG antibody (most commonly anti-$Jk^a$, Rh, Kell, or Duffy) clears transfused antigen-positive red blood cells.

Transfusion-Related Acute Lung Injury (TRALI)

A life-threatening complication characterized by acute non-cardiogenic pulmonary edema, hypoxemia, and bilateral pulmonary infiltrates developing within $6\,\text{hours}$ of transfusion, triggered by donor anti-HLA or anti-HNA antibodies activating recipient pulmonary neutrophils.

Transfusion-Associated Circulatory Overload (TACO)

A cardiogenic form of acute pulmonary edema occurring within $1\text{--}2\,\text{hours}$ of transfusion due to excessive infusion rate or volume, presenting with dyspnoea, cyanosis, severe hypertension, peripheral edema, and elevated Brain Natriuretic Peptide (BNP).

Febrile Non-Haemolytic Transfusion Reaction (FNHTR)

A benign adverse reaction characterized by an unexpected fever rise ($\ge 1\,^\circ\text{C}$) accompanied by chills, caused by leukocyte-derived cytokines accumulating in the stored unit or recipient antibodies reacting against donor white cells.

Transfusion-Associated Graft-versus-Host Disease (TA-GvHD)

A lethal immunological complication occurring when transfused, immunocompetent donor T-lymphocytes engraft and attack recipient tissues sharing common HLA haplotypes, leading to profound pancytopenia and bone marrow aplasia.