THE SPLEENThe spleen is the largest lymphoid organ in the body and issituated in the left hypochondrium. There are two anatomicalcomponents:■ the red pulp, consisting of sinuses lined by endothelialmacrophages and cords (spaces)■ the white pulp, which has a structure similar to lymphoidfollicles.Blood enters via the splenic artery and is delivered to the redand white pulp. During the flow the blood is ‘skimmed’, withleucocytes and plasma preferentially passing to white pulp.Some red cells pass rapidly through into the venous systemwhile others are held up in the red pulp.

FunctionsSequestration and phagocytosis. Normal red cells, whichare flexible, pass through the red pulp into the venous systemwithout difficulty. Old or abnormal cells are damaged by thehypoxia, low glucose and low pH found in the sinuses of thered pulp and are therefore removed by phagocytosis alongwith other circulating foreign matter. Howell–Jolly and Heinzbodies and sideroblastic granules have their particlesremoved by ‘pitting’ and are then returned to the circulation.IgG-coated red cells are removed through their Fc receptorsby macrophages.

Extramedullary haemopoiesis. Pluripotential stem cells arepresent in the spleen and proliferate during severe haematologicalstress, such as in haemolytic anaemia or thalassaemiamajor. Immunological function. About 25% of the body’s T lymphocytesand 15% of B lymphocytes are present in the spleen.The spleen shares the function of production of antibodieswith other lymphoid tissues.Blood pooling. Up to one-third of the platelets are sequestratedin the spleen and can be rapidly mobilized. Enlargedspleens pool a significant percentage (up to 40%) of the redcell mass.

SPLENOMEGALYCausesA clinically palpable spleen can have many causes.■ Infection:(a) acute, e.g. septic shock, infective endocarditis,typhoid, infectious mononucleosis(b) chronic, e.g. tuberculosis and brucellosis(c) parasitic, e.g. malaria, kala-azar andschistosomiasis.■ Inflammation: rheumatoid arthritis, sarcoidosis, SLE.■ Haematological: haemolytic anaemia,haemoglobinopathies and the leukaemias, lymphomasand myeloproliferative disorders.■ Portal hypertension: liver disease.■ Miscellaneous: storage diseases, amyloid, primary andsecondary neoplasias, tropical splenomegalyMassive splenomegaly. This is seen in myelofibrosis, chronicmyeloid leukaemia, chronic malaria, kala-azar or, rarely,Gaucher’s disease.

HypersplenismThis can result from splenomegaly due to any cause.

It is commonly seen with splenomegaly due to haematologicaldisorders, portal hypertension, rheumatoid arthritis

)Felty’s syndrome (and lymphoma. Hypersplenismproduces:

■pancytopenia ■haemolysis due to sequestration and destruction of red

cells in the spleen ■increased plasma volume.

Treatment. This is often dependent on the underlying cause,but splenectomy is sometimes required for severe anaemiaor thrombocytopenia

Splenectomy

Splenectomy is performed mainly for:

■trauma

■immune thrombocytopenic purpura

■haemolytic anaemias

■hypersplenism.

Problems after splenectomyAn immediate problem is an increased platelet count (usually

600–1000 × 109/L) for 2–3 weeks. Thrombo-embolic phenomenamay occur. In the longer term there is an increasedrisk of overwhelming infections, particularly pneumococcalinfections.

Prophylaxis against infection after

splenectomy or splenic dysfunction

Vaccinate 2–3 weeks before elective splenectomy. ■A 23-valent unconjugated pneumococcal

polysaccharidevaccine repeated every 5 years

■Meningococcal group C conjugate vaccine ■Annual influenza vaccine

■Haemophilus influenzae type b (Hib) vaccine ■Long-term penicillin V 500 mg 12-hourly (if

sensitive, useerythromycin(

■Meningococcal polysaccharide vaccine (ACWY) fortravellers to Africa/Saudi Arabia, e.g. during Hajj andUmrah pilgrimages

Prophylaxis against infection after

splenectomy or splenic dysfunction

All patients should be educated about the risk of infection

and the importance of its early recognition and treatment.

They should be given an information leaflet and should carry

a card or bracelet to alert health professionals to their risk of

overwhelming infection

Postsplenectomy haematological features■ Thrombocytosis persists in about 30% of cases.■ The WBC count is usually normal but there may be amild lymphocytosis and monocytosis.■ Abnormalities in red cell morphology are the mostprominent changes and include Howell–Jolly bodies(contain basophilic nuclear remnants), Pappenheimerbodies (contain sideroblastic granules), target cells andirregular contracted red cells. Pitted red cellscan be counted.

Splenic atrophyThis is seen in sickle cell disease due to infarction. It is alsoseen in coeliac disease, in dermatitis herpetiformis, andoccasionally in ulcerative colitis and essential thrombocythaemia.

Postsplenectomy haematological features areseen.

BLOOD TRANSFUSION

The cells and proteins in the blood express antigens whichare controlled by polymorphic genes; that is, a specificantigen may be present in some individuals but not in others.A blood transfusion may immunize the recipient againstdonor antigens that the recipient lacks (alloimmunization),and repeated transfusions increase the risk of the occurrence of

alloimmunization. Similarly, the transplacental passage offetal blood cells during pregnancy may alloimmunize themother against fetal antigens inherited from the father. Antibodiesstimulated by blood transfusion or pregnancy, suchas Rh antibodies, are termed immune antibodies and areusually IgG, in contrast to naturally occurring antibodies,such as ABO antibodies, which are made in response toenvironmental antigens present in food and bacteria andwhich are usually IgM.

BLOOD GROUPSThe blood groups are determined by antigens on the surfaceof red cells; more than 280 blood groups are recognized. TheABO and Rh systems are the two major blood groups, butincompatibilities involving many other blood groups (e.g.

Kell, Duffy, Kidd) may cause haemolytic transfusion reactionsand/or haemolytic disease of the newborn (HDN).

ABO systemThis blood group system involves naturally occurring IgManti-A and anti-B antibodies which are capable of producingrapid and severe intravascular haemolysis of incompatiblered cells.

The ABO system is under the control of a pair of allelicgenes, H and h, and also three allelic genes, A, B and O,

producing the genotypes and phenotypes .The A, B and H antigens are very similar in structure;

differences in the terminal sugars determine their specificity.The H gene codes for enzyme H, which attaches fucose tothe basic glycoprotein backbone to form H substance, which

is the precursor for A and B antigens.(

The A and B genes control specific enzymes responsiblefor the addition to H substance of N-acetylgalactosamine forGroup A and d-galactose for Group B. The O gene is amorphicand does not transform H substance and therefore O isnot antigenic. The A, B and H antigens are present on mostbody cells. These antigens are also found in soluble form intissue fluids such as saliva and gastric juice in the 80% ofthe population who possess secretor genes

The ABO system: antigensand antibodiesPhenotype Genotype Antigens Antibodies Frequency

UK)%( O OO None Anti-A andanti-B43A AA or AO A Anti-B 45B BB or BO B Anti-A 9AB AB A and B None 3

Rh systemThere is a high frequency of development of IgG RhD antibodiesin RhD-negative individuals after exposure to RhD positivered cells. The antibodies formed cause HDN andhaemolytic transfusion reactions.This system is coded by allelic genes, C and c, E and e,D and no D, which is signified as d; they are inherited astriplets on each chromosome 1, one from each pair of genes

)i.e. CDE/cde .(RhD-negative individuals have no D protein inthe red cell membrane which explains why it is so immunogenic.In Caucasians, the RhD-negative phenotype almostalways results from a complete deletion of the RhD gene; inblack Africans, it can also result from an inactive gene containingstop codons in the reading frame.

PROCEDURE FOR BLOOD TRANSFUSIONThe safety of blood transfusion depends on meticulousattention to detail at each stage leading to and during thetransfusion. Avoidance of simple errors involving patient andblood sample identification at the time of collection of thesample for compatibility testing and at the time of transfusionwould avoid most serious haemolytic transfusion reactions,

almost all of which involve the ABO system

Pretransfusion compatibility testingBlood groupingThe ABO and RhD groups of the patient are determined.Antibody screeningThe patient’s serum or plasma is screened for atypical antibodiesthat may cause a significant reduction in the survivalof the transfused red cells. The patient’s serum or plasma istested against

red cells from at least two group O donors,expressing a wide range of red cell antigens, for detection ofIgM red cell alloantibodies (using a direct agglutination testof cells suspended in saline) and IgG antibodies (using anindirect antiglobulin test. About 10% of patientshave a positive antibody screening result; in which case,further testing is carried out using a comprehensive panel oftyped red cells to determine the blood group specificity ofthe antibody (clinically significant red cell antibodies aredetected in about 20% of patients with positive antibodyscreens).

Selection of donor blood andcrossmatchingDonor blood of the same ABO and RhD group as the patientis selected. Matching for additional blood groups is carriedout for patients with clinically significant red cell antibodiesfor patients who are likely to be multitransfusedand at high risk of developing antibodies, e.g. sickle celldisease, and many centres routinely provide c-negative andKell-negative blood for women of child-bearing age to minimizethe risk of alloimmunization and subsequent HDN

COMPLICATIONS OF BLOODTRANSFUSIONImmunologicalAlloimmunization andincompatibilityRed cellsImmediate haemolytic transfusion reactions.

Delayed haemolytictransfusion reactions.

Leucocytes and plateletsNon-haemolytic (febrile)transfusion reactions

Post-transfusion purpuraPoor survival oftransfused plateletsand granulocytesGraft-versus-host diseaseLung injury (TRALI)Plasma proteinsUrticarial andanaphylactic reactions

Transmission of infectionViruses

–HAV, HBV, HCV –HIV, HHV8

–CMV, EBV, HTLV-1, WNVParasites

–malaria, trypanosomiasis,toxoplasmosisBacteriaPrion – CJDCirculatory failure due tovolume overloadIron overload due to multipletransfusionsMassive transfusion ofstored blood may causebleeding reactions andelectrolyte changesPhysical damage due tofreezing or heatingThrombophlebitisAir emboiism

Incompatibility

This may result in poor survival of transfused cells, such as

red cells and platelets, and also in the harmful effects of

antigen–antibody reaction

1 .Red cellsHaemolytic transfusion reactionsImmediate reaction. This is the most serious complication ofblood transfusion and is usually due to ABO incompatibility.There is complement activation by the antigen–antibodyreaction, usually caused by IgM antibodies, leading to rigors,lumbar pain, dyspnoea, hypotension, haemoglobinuria andrenal failure. The initial symptoms may occur a few minutesafter starting the transfusion. Activation of coagulation alsooccurs and bleeding due to disseminated intravascular coagulation

)DIC (is a bad prognostic sign. Emergency treatmentfor shock .is needed to maintain the blood pressureand renal function.

DiagnosisThis is confirmed by finding evidence of haemolysis (e.g.

haemoglobinuria), and incompatibility between donor andrecipient. All documentation should be checked to detecterrors such as:

■failure to check the identity of the patient when takingthe sample for compatibility testing (i.e. sample from thewrong patient(

■mislabelling the blood sample with the wrong patient’sname

■simple labelling or handling errors in the laboratory ■errors in the collection of blood, leading to delivery of

the wrong blood to the ward/theatre ■failure to perform proper identity checks before the

blood is transfused (i.e. blood transfused to the wrongpatient.(

InvestigationsTo confirm where the error occurred, blood grouping shouldbe carried out on:

■the patient’s original sample (used for the compatibilitytesting(

■a new sample taken from the patient after the reaction ■the donor units.

At the first suspicion of any serious transfusion reaction, thetransfusion should always be stopped and the donor unitsreturned to the blood transfusion laboratory with a new bloodsample from the patient to exclude a haemolytic transfusionreaction.

Delayed reaction. This occurs in patients alloimmunized byprevious transfusions or pregnancies. The antibody level istoo low to be detected by pretransfusion compatibilitytesting, but a secondary immune response occurs aftertransfusion, resulting in destruction of the transfused cells,usually by IgG antibodies.

Haemolysis is usually extravascular as the antibodies areIgG, and the patient may develop anaemia and jaundiceabout a week after the transfusion, although most of these episodes are clinically silent. The blood film shows spherocytosisand reticulocytosis. The direct antiglobulin testis positive and detection of the antibody is usuallystraightforward.

2 .Leucocytes and plateletsNon-haemolytic (febrile) transfusion reactionsFebrile reactions are a common complication of blood transfusionin patients who have previously been transfused orpregnant. The usual causes are the presence of leucocyteantibodies in an alloimmunized recipient acting against donorleucocytes in red cell concentrates leading to release ofpyrogens, or the release of cytokines from donor leucocytesin platelet concentrates. Typical signs are flushing and tachycardia,fever (> 38°C), chills and rigors. Aspirin may be usedto reduce the fever, although it should not be used in patientswith thrombocytopenia. The introduction of leucocyte depletedblood in the UK, to minimize the risk of transmissionof variant Creutzfeldt–Jakob disease (vCJD) by blood transfusion

,has reduced the incidence of febrilereactions.

Potent leucocyte antibodies in the plasma of donors, whoare usually multiparous women, may cause severe pulmonaryreactions (called transfusion-related acute lung injury orTRALI) characterized by dyspnoea, fever, cough, and shadowingin the perihilar and lower lung fields on the chest X-ray.Prompt respiratory support is essential; mechanical ventilationis frequently necessary. It usually resolves within 48–96hours, but the mortality is approximately 20% in the 185cases