Haematology

Question 1

Haemostasis disorders: Thrombocytopaenia

Answer 1

This may be due to a failure of platelet production or increased destruction or sequestration of platelets, and abnormal platelet function.

Abnormal platelet function may cause bleeding despite a normal platelet count. Abnormal platelet function may occur with: drugs, e.g. aspirin, non-steroidal anti- inflammatory drugs, carbenicillin, and ticarcillin; uraemia; septicaemia; and von Willebrand’s disease.

Question 2

Haemostasis disorders: Blood vessel wall abnormalities

Answer 2

Blood vessel wall abnormalities
These are rare and may be due to scurvy, steroids, Cushing’s syndrome, or Henoch-Schonlein purpura.

Question 3

Haemophilia A

Answer 3

These are uncommon, the commonest being haemophilia A and von Willebrand’s disease.

Haemophilia A This is due to an inherited deficiency of Factor VIII. It is an X-linked recessive disorder affecting males and carried by females. Severity of the disease depends on the degree of factor VIII deficiency. The PT is normal but the APTT is prolonged.

Question 4

von Willebrand’s disease

Answer 4

This is due to deficiency of von Willebrand’s factor. It is transmitted as an autosomal dominant condition. Vascular endothelium releases decreased amounts of factor VIII. Although the platelet count is usually normal, platelet inter- action with the endothelium is defective because of deficiency of von Willebrand’s factor.

Question 5

Vitamin K deficiency

Answer 5

Vitamin K is present in green vegetables and is synthesised by intestinal bacteria. It is fat soluble and requires bile for its absorption. It is required for the formation of factors II, VII, IX, X. Vitamin K deficiency may occur in the surgical patient as the result of obstructive jaundice, antibiotic therapy which alters the normal intestinal flora, or prolonged parenteral nutrition without vitamin K supplements.

Question 6

Coagulation disorder: Liver disease

Answer 6

This is commonly associated with coagulation defects due to failure of clotting factor synthesis and the production of abnormal fibrinogen. Vitamin K will not help if there is hepatocellular fail- ure. In addition, there may be thrombocytopaenia due to hypersplenism.

Question 7

Disseminated intravascular coagulation (DIC)

Answer 7

This results from simultaneous activation of coagulation and fibrinolytic systems. Activation of the coagulation system leads to the formation of microthrombi in many organs, with the consumption of clotting factors and platelets, in turn leading to haemorrhage. DIC may arise as a result of the following disorders: septicaemia, malignancy, trauma, shock, liver disease, acute pancrea- titis, obstetric problems, e.g. toxaemia, amniotic fluid embolism. Clinically there is widespread haemorrhage. The presence of thrombocytopaenia, decreased fibrino- gen, and elevated fibrinogen degradation products con- firms the diagnosis.

Question 8

Natural anticoagulants: Antithrombin III

Answer 8

This is an inhibitor of thrombin, its action being potentiated by heparin. Congenital antithrombin III deficiency is inherited as an autosomal dominant. Heterozygotes may suffer from recurrent DVT, pulmonary embolism, and mesenteric thrombosis. Homozygotes present in childhood with severe arterial and venous thrombosis.

Question 9

Natural anticoagulants: Protein C and protein S

Answer 9

These are synthesised in the liver and are dependant on vitamin K. Protein C degrades factors Va and VIIIa and promotes fibrinolysis by inactivating plasminogen-activator inhibitor I.

Protein S is a cofactor for protein C and enhances its activity. Hereditary protein C deficiency may occur, patients being more susceptible to DVT, PE, superficial thrombophlebitis, and cerebral venous thrombosis.

Question 10

Anticoagulant drugs: Heparin

Answer 10

Heparin potentiates the action of antithrombin III. Standard unfractionated heparin is administered i.v. or s.c. and has a half life of about 1h. Low molecular weight heparin is used subcutaneously and has a longer biological half life. Intravenous heparin is used in patients with DVT or PE, and the dosage is monitored by performing the KCCT, which should be maintained at 2–2.5 times the normal value.

Subcutaneous heparin is given to reduce the risk of DVT or PE in patients undergoing major surgery or patients who are on prolonged bed rest, e.g. post-myocardial infarction or orthopaedic patients. Heparin does not cross the placenta and is, therefore, the drug of choice when anticoagulation is required during pregnancy. Bleeding due to overdose is managed by stopping the heparin and administering protamine sulphate intravenously. Side effects of heparin include thrombocytopaenia, hypersensitivity reactions, alopecia, and osteoporosis when used long term.

Question 11

Warfarin

Answer 11

Warfarin is a coumarin derivative which is administered orally. It is a vitamin K antagonist and in effect induces a state analogous to vitamin K deficiency. It interferes with the activity of factors II, VII, IX and X. It delays thrombin generation, thus preventing the formation of thrombi. It is usual to give a loading dose (10 mg) and to determine the INR (the prothrombin ratio standardised by correcting for the sensitivity of the thromboplastin used) about 15–18 h later. Subsequent doses are based on the INR.

Warfarin is usually administered for 3–6 months following DVT or PE. Lifelong warfarin is required for recurrent venous thromboembolic disease, some prosthetic heart valves, congenital deficiency of antithrombin III, deficiency of protein C or protein S,
patients with lupus anticoagulant, and valvular heart disease complicated by embolism or atrial fibrillation.

Bleeding is controlled by stopping warfarin and administering either fresh frozen plasma or vitamin K, depending upon the degree of urgency. If vitamin K is used there is a period of resistance to warfarin, and control may be difficult initially when the patient is restarted on warfarin. A number of drugs may interfere with the control of warfarin. These include antibiotics, laxatives (interfere with vitamin K absorption), phenylbutazone (interferes with binding of warfarin to albumin) and cimetidine (inhibits hepatic microsomal degradation). Warfarin crosses the placenta and is teratogenic. It should be avoided particularly in the first trimester of pregnancy.

Question 12

Transfusion: Whole blood

Answer 12

Nowadays whole blood is less readily available because of the demand for blood products. Most blood for transfusion is essentially red cells alone. Ideally, whole blood should be the product of choice for massive transfusion but in practice concentrated red cells with colloid or crystalloid is given usually following massive haemorrhage. Whole blood may be stored for up to 42 days. Granulocytes and platelets lose their function in a few days and clotting factors V and VIII are rapidly lost. In stored blood there is an increasing content of lactate, phosphate and potassium but this is usually clinically insignificant, except when massive blood transfusions are administered.

Question 13

Transfusion: Red cell concentrates

Answer 13

Red cell concentrates, or packed cells, consist of whole blood from which the majority of plasma has been removed. This type of blood is the treatment of choice for anaemia without hypovolaemia. The shelf life of red cell concentrates is 42 days at 4C. However, during storage changes take place in the constituents of the blood. These are as follows:

• increased lactate;
• increased potassium;
• increased phosphate;
• decrease in pH;
• haemolysis
• microaggregation of dead cells
• loss of granulocyte and platelet function
• loss of factor V and factor VIII

Question 14

Transfusion: Platelet concentrates

Answer 14

Platelet concentrates consist of platelets suspended in plasma. Their shelf-life is only three days at room temperature. The transfusion should be ABO compatible. Indications for platelet transfusion include:

• haemorrhage in the presence of thrombocytopenia
• thrombocytopenia prior to an invasive
procedure
• consumptive coagulopathy, e.g. DIC; and
• platelet counts of 50,000 109/L are adequate for
haemostasis.

Administration of platelet concentrate should occur four hours before any invasive procedure. Transfusion should be rapid via a short giving set with no filter. The usual adult dose is six units which should raise the platelet count by 40,000 109/L. Counts should be checked 10 mins to one hour post-transfusion. Failure of the count to rise may be due to platelet antibodies, post-transfusion purpura or DIC.

Question 15

Transfusion: Granulocytes

Answer 15

Granulocytes have a very short shelf-life (24 h at room temperature). Granulocyte transfusions are expensive. The effect of infusion is short-lived and often induces a pyrexial response. The role of granulocyte infusions remains controversial. Granulocyte-colony stimulat- ing factor (G-CSF) is now used to stimulate a bone marrow response.

Question 16

Transfusion: Fresh frozen plasma

Answer 16

Fresh frozen plasma (FFP) is plasma which is separated from fresh blood and frozen at 30C. It contains all the clotting factors. Shelf-life of FFP is one year at 30C. FFP should be used within one hour of thawing.

Indications for the use of FFP include:
• to replace clotting factors following major haemorrhage (due to poor clotting ability of stored blood);
• patients short of clotting factors (e.g. liver disease or for the rapid reversal of warfarin)
• DIC, when it should be given in conjunction with platelets and cryoprecipitate; and
• prophylaxis or treatment of haemorrhage in patients with specific clotting defects for which the specific factor is unavailable. Group compatible FFP should be used.

Question 17

Transfusion: Cryoprecipitate

Answer 17

Cryoprecipitate is a concentrate prepared by freeze- thawing of plasma from a single donor. It is rich in factor VIII, fibrinogen and von Willebrand’s factor. Indications for cryoprecipitate transfusion include:
• haemophilia;
• von Willebrand’s disease
• fibrinogen deficiency, e.g. DIC

Question 18

Factor VIII concentrate

Answer 18

This is used for treatment for haemophilia A.

Question 19

Complications of blood transfusion: Immediate

Answer 19

Haemolytic transfusion reactions
Immediate
This occurs with ABO incompatibility. Symptoms and signs include:
• pyrexia;
• dyspnoea;
• chest pain;
• severe loin pain;
• collapse;
• hypertension;
• haemoglobinuria;
• oliguria (often proceeding to acute renal failure); • jaundice; and
• DIC with spontaneous bruising and haemorrhage.

Question 20

Complications of blood transfusion: Delayed

Answer 20

This occurs with low-titre antibody too weak to detect in a cross match and unable to cause lysis at the time of transfusion. The reaction usually occurs 5–10 days post transfusion. Symptoms and signs include:
• pyrexia;
• anaemia;
• jaundice; and
• haemoglobinuria.

Question 21

Complications of blood transfusion: Reaction to white blood cells

Answer 21

Reaction to white blood cells usually results in a febrile reaction and is relatively common in patients who have had previous blood transfusions or pregnancy. Fever and flushing result soon after starting the transfusion. The reaction is due to recipient leucocyte antibodies. If a patient is known to have had a previous similar reaction, washed red cells should be given.

Question 22

Complications of blood transfusion: Infection

Answer 22

Infection is unlikely with the present testing in the UK but may be a problem where testing is not carried out. Causes of infection include:
• HIV;
• hepatitis B;
• hepatitis C;
• CMV;
• malaria;
• syphilis; and
• prion disease, e.g. Creutzfeldt-Jakob disease

Question 23

Complications of massive blood
transfusion

Answer 23

Complications of massive blood transfusion include:
• fluid overload;
• cardiac arrhythmias due to cold blood;
• citrate toxicity with resulting hypocalcaemia;
• hypothermia;
• hyperkalaemia;
• metabolic acidosis because of acidity of stored
blood;
• haemorrhage due to coagulopathy unless FFP and
platelets are administered simultaneously;
• DIC; and
• ARDS/TRALI (transfusion-related acute lung
injury).

Question 24

Autologous blood transfusion

Answer 24

Methods of reducing blood bank transfusion involve ‘recycling’ of patient’s own blood (autotransfusion). Some patients request this because they worry about getting infection from donated blood. Autotransfusion may be carried out in several ways.

1. Pre-donation. Blood is taken from the patient at weekly intervals prior to elective surgery. Up to 4 units may be taken over four weeks.
2. Normovolaemic haemodilution. Blood is collected immediately prior to surgery and replaced with colloid. Up to two litres can be removed safely from adults who are otherwise well. The blood
   is fresh, contains viable platelets and clotting
   factors.
3. Intra-operative blood salvage techniques. This
   is useful when massive bleeding occurs in an uncontaminated operative field, e.g. ruptured aortic aneurysm or liver trauma. It is unsuitable where contamination occurs, e.g. in abdominal surgery where the bowel is breached. Blood spilled at operation is collected by suction, processed and re-infused (using a ‘cell saver’). The blood is anticoagulated and returned to the patient via a fine filter.

Question 25

Lymphoid system:

Answer 25

Lymph nodes are discrete encapsulated structures, usually kidney-shaped, and range in diameter from a few millimetres to several centimetres. They are situ- ated along the course of lymphatic vessels and are numerous where these vessels converge, e.g. the root of the limbs, the neck, the pelvis and the mediastinum.

A lymph node has an outer capsule of connective tis- sue from which trabeculae pass into the deeper tissue (Fig. 10.4). Beneath the capsule is a space, the sub- capsular sinus into which the afferent lymphatics drain after penetrating the capsule. Lymph from the subcapsular sinus passes via the medullary cords to the hilum of the lymph node from which the efferent lymphatics drain. Both afferent and efferent vessels have valves which allow only forward flow. The node itself consists of an outer cortex and an inner medulla and contains lymphatic sinuses. There are three distinct microanatomical regions within a lymph node. These are:

1. the cortex: which contains either primary or secondary lymphoid follicles;
2. the paracortex: which is the T-cell-dependent region of the lymph node; and
3. the medulla: which contains the medullary cords and sinuses and also contains lymphocytes which are much less densely packed than in the cortex, together with macrophages, plasma cells and a small number of granulocytes.

Question 26

Lymphoid system: Cortex

Answer 26

The cortex consists of primary lymphoid follicles which are unstimulated follicles, spherical in shape, containing densely packed lymphocytes. Secondary follicles are present after lymphocytes have been stimu- lated antigenically. These follicles have an outer ring of small B lymphocytes surrounding the germinal centre, which contains largely dividing lymphoblasts, macro- phages and dendritic cells. Antigen is trapped upon the surface of the dendritic cells and presented to ‘virgin’ B lymphocytes in the presence of T helper cells, and these B cells subsequently undergo a series of morpho- logical and functional changes. The function of germinal centres is to generate immunoglobulin-secreting plasma cells in response to antigenic challenge.

Question 27

Lymphoid system: Paracortex

Answer 27

The paracortex is the T-cell-dependent region of the lymph node. When a T cell response occurs there is marked proliferation of cells in this area. The paracortex contains large number of T lymphocytes with a pre- dominance of helper/inducer cells. The cluster of differ- entiation (CD4) is expressed by helper/inducer T cells.

Question 28

Lymphoid system: Medulla

Answer 28

Lymph enters the marginal sinus of the node and drains to the hilum through the sinuses which converge into the medullary region. The sinuses are lined by macro- phages which phagocytose foreign or abnormal par- ticles from the lymph passing through the node, i.e. the filtering function. Between the sinuses in the medulla lie the medullary cords which contain numerous plasma cells and are one of the main sites of antibody secretion within the lymph node.

Question 29

Primary lymphoedema

Answer 29

This is a condition due to aplasia or hypoplasia of lymphatics. There are three types: congenital lym- phoedema or Milroy’s disease, which presents shortly after birth; lymphoedema praecox, which presents at puberty; and lymphoedema tarda, which presents around the age of 30.

Question 30

Secondary lymphoedema

Answer 30

Lymphoedema may be secondary to result of damage to lymphatic channels by infection, surgery, radiotherapy, malignant infiltration, or trauma. Blockage of inguinal lymphatics by filarial parasites frequently causes gross oedema of the legs and, in the male, the scrotum. The resulting deformity is called elephantiasis.

Blockage of the lymphatic drainage from the small intestine usually occurs because of tumour involve- ment causing malabsorption of fats and fat-soluble substances. Blockage of lymphatic drainage at the level of the thoracic duct causes chylous effusions in the pleural and peritoneal cavities. At paracentesis or thoracocentesis, the fluid is opalescent because of the presence of numerous tiny fat globules (chyle).

Question 31

Spleen

Answer 31

The spleen is an encapsulated, purplish, friable organ situated in the left hypochondrium. It forms the left lateral extremity of the lesser sac. It lies along the long axis of ribs 9, 10 and 11, from which the diaphragmatic surface of the spleen is separated by the diaphragm, lung, and pleura. It normally weighs approximately 150 g in the adult but atrophies in old age, when it may weigh only approximately 50 g.

The visceral surface of the spleen is related to the stomach anteriorly, left kidney posteriorly, and the splenic flexure of the colon near its inferior pole. The anterior border of the spleen is notched. The hilum of the spleen lies between the gastric and renal surfaces and contains the vessels and nerves entering or leaving the spleen, as well as the splenic group of lymph nodes and the tail of the pancreas. Passing to the spleen are the gastrosplenic ligament to the greater curvature of the stomach which carries the short gastric and left gastroepiploic vessels, and the lienorenal ligament which carries the splenic vessels and the tail of the pancreas.

Question 32

Spleen: Blood supply

Answer 32

The arterial blood supply is via the splenic artery, which is a branch of the coeliac axis. The splenic vein is joined by the superior mesenteric vein to form the portal vein. The splenic artery and vein, the lymph nodes, and the tail of the pancreas are enclosed in the lienorenal ligament.

Question 33

Spleen: Embryology

Answer 33

The spleen develops from several masses of mesenchyme in the dorsal mesogastrium. These masses coalesce and develop into lymphoid tissue and move to the left with the dorsal mesogastrium. By the end of the third month of gestation the spleen is formed.

The point at which the spleen remains attached to the dorsal mesogastrium becomes the gastrosplenic liga- ment. Congenital abnormalities in the form of acces- sory spleens or splenunculi are relatively common and occur in about 10% of the population.

They are usually rounded encapsulated structures up to several centimetres in size and are usually located in the region of the spleen. They are clinically important in that, if they are left behind following splenectomy for such conditions as congenital acholuric jaundice (heredi- tary spherocytosis) or idiopathic thromboctyopaenic purpura, they may result in persistent symptoms.

Question 34

Spleen: Structure
diagram

Answer 34

Deep to its peritoneal covering the spleen is enclosed in a thin connective tissue capsule. The connective tissue extends into the splenic pulp as trabeculae. These serve to support the pulp of the spleen and also transmit blood vessels into it. When a fresh spleen is cut across, two areas can be identified on the cut surface: firstly, islands of pale areas 1–2mm in diameter which are white and are known as the white pulp, and, secondly, a deep red background which is known as the red pulp.

The white pulp is composed of lymphatic nodules, mostly B lymphocytes. The red pulp acts as a filter, removing effete red cells and particulate matter, and thus contains a large amount of red blood cells.

The splenic artery enters the spleen at the hilum, branches and follows the trabeculae of the fibrous capsule into the spleen. The branches leave the trabecu- lae as central arteries and arterioles and become ensheathed in lymphoid cells. Localised extensions of the lymphatic sheath form lymphatic nodules, each having an eccentrically placed arteriole which is a branch of the ensheathed artery.

Question 35

Spleen: White pulp

Answer 35

The white pulp consists of ensheathed arteries and lymphoid nodules. The lymphocytes within the white pulp show distinct microarchitectural segregation of different functional subsets.

T lymphocytes are located in the immediate vicinity of the central artery, while the nodules contain mostly B lymphocytes. Activated lymphocytes migrate to the periphery of the nodule, to the marginal zone between red and white pulp, and differentiate into plasma cells capable of producing antibodies. The plasma cells circulate in the red pulp and enter the sinusoids.

Question 36

Spleen: Red pulp

Answer 36

Most of the spleen is occupied by the red pulp, which consists of cords of cells separated by sinusoids. The red pulp has a dual circulation with a closed circula- tion via sinusoidal pathways and an open circulation through the splenic pulp cords.

These cords contain a large number of red cells which give the spleen its characteristic appearance. They also contain lymphocytes, granulocytes, platelets and macrophages. In the red pulp, macrophages phagocytose senes- cent red cells and particulate matter.

The red pulp is drained by sinusoids, i.e. narrow channels with a discontinuous endothelial cell lining, cells being able to pass between the space between endothelial cells. The spaces between the endothelial cells allow normal pliable and deformable cells to pass.

Red cells, plasma cells, granulocytes and platelets leave the spleen by passing through the spaces into the sinusoids.

Defective or effete cells are trapped as they attempt to enter the sinusoids through the spaces and are destroyed by adjacent macrophages. The open circulation, where the cells percolate slowly through the cords, leaves cells in prolonged contact with rows of macrophages before they enter the splenic sinusoids. Any abnormal cells are rapidly phagocytosed. The sinusoids join together as venules which leave the spleen as the trabecular veins eventually forming the splenic vein.

Question 37

Spleen: Filtering function

Answer 37

1. Removal of old or abnormal red cells.
2. Removal of abnormal white cells, normal
   and abnormal platelets and cellular debris. In splenectomised individuals, cells with inclusion bodies, e.g. Howell-Jolly bodies, are seen.
3. Normally any intracytoplasmic inclusions, such as Howell-Jolly bodies, are removed by macrophages in the pulp cords (a process known as ‘pitting’). In the absence of a functioning spleen there are characteristic changes in red cell morphology. Howell-Jolly bodies, which are remnants of nuclear material from developing erythrocytes, occur.

Question 38

Spleen: Immunological function

Answer 38

1. Opsonisation. While opsonised bacteria can be removed from the circulation by the entire reticuloendothelial system, the spleen is well suited to removing poorly opsonised or encapsulated pathogens.
2. Antibody synthesis. This occurs chiefly within the white pulp. Blood-borne antigens stimulate B cells which proliferate and differentiate to form plasma cells which produce large amounts of antibodies (immunoglobulins).
3. Protection from infection. Splenectomy leaves some patients more prone to infection

Question 39

Hypersplenism

Answer 39

This is a term applied to splenomegaly associated with the following:
1. any combination of anaemia, leucopaenia, or thrombocytopaenia;
2. compensatory bone marrow hyperplasia; and
3. improvement after splenectomy.
There is an exaggerated destruction or sequestration of circulating blood elements, which can affect red cells, white cells and platelets. The condition may be either primary or secondary.

Question 40

Primary hypersplenism

Answer 40

This is essentially a diagnosis of exclusion where all causes of secondary hypersplenism have been excluded. It is a rare condition of unknown aeti- ology, mainly affecting women. There may be massive splenomegaly and an accompanying pancytopaenia, especially leucopaenia. There may be recurring fevers and infection. Splenectomy results in a good haematological response, although some patients may remain leucopaenic. Secondary splenomegaly may also be associated with hypersplenism.

Question 41

Splenomegaly

Answer 41

The causes of splenomegaly are numerous but may be grouped together under the following headings:
1. congestion
2. infection
3. haematological disorders
4. immune disorders
5. storage disorders
6. amyloid

Question 42

Splenomegaly: Congestion

Answer 42

Conditions leading to elevation of splenic venous pressure are capable of causing splenomegaly. Causes may be prehepatic, hepatic, or posthepatic. Prehepatic causes include thrombosis of the extra hepatic portion of the portal vein or splenic vein thrombosis. Hepatic causes include longstanding portal hypertension associ- ated with cirrhosis. Posthepatic causes are usually asso- ciated with a raised pressure in the inferior vena cava, which is transmitted to the spleen via the portal system. There is usually coexisting ascites and hepatomegaly. Decompensated right-sided heart failure and pulmon- ary or tricuspid valve disease are the usual causes.

Question 43

Splenomegaly: Infection

Answer 43

The spleen may enlarge in several infectious diseases but particularly in chronic malaria, typhoid and some viral diseases, particularly infectious mononucleosis.

Question 44

Splenomegaly: Haematological disorders

Answer 44

Splenomegaly may occur in haemolytic anaemias, hereditary spherocytosis, idiopathic thrombocy- topaenic purpura, and polycythaemia rubra vera. Splenic infiltration is a common feature of a variety of haematological neoplasms, including leukaemias, myeloproliferative disorders, Hodgkin’s disease and non-Hodgkin’s lymphoma. In chronic myeloid leukae- mia and myeloproliferative syndromes, splenomegaly may be massive and the spleen may be palpable in the right iliac fossa.

Question 45

Splenomegaly: Immunological disorders

Answer 45

A variety of immunological disorders may lead to splenomegaly, chiefly rheumatoid arthritis and sys- temic lupus erythematosus.

Question 46

Splenomegaly: Storage disorders

Answer 46

Several storage disorders may cause splenomegaly. These include Niemann-Pick disease, Gaucher’s dis- ease and the mucopolysaccharidoses.

Question 47

Splenomegaly: Amyloidosis

Answer 47

In systemic amyloidosis, amyloid is deposited in a wide variety of organs and virtually no organ is exempt. Clinical features suggesting amyloidosis include gen- eralised diffuse organ enlargement, e.g. hepatomegaly or splenomegaly, and evidence of organ dysfunction, e.g. cardiac failure or renal failure.

Question 48

Splenectomy: Haematological effects

Answer 48

Loss of splenic tissue reduces the capacity of the spleen to remove immature or abnormal red cells from the circulation. The red cell count does not change, but red cells with cytoplasmic inclusions, e.g. Howell- Jolly bodies, may appear. Target cells, reticulocytes and siderocytes appear within a few days of operation. Granulocytosis occurs immediately after splenectomy but is replaced in a few weeks by lymphocytosis and monocytosis. The platelet count is usually increased and may stay at levels of 400,000–500,000 109/L for over a year. Occasionally there may be a thrombocy- tosis in excess of 1000 109/L. This is not an indica- tion for anticoagulation, but antiplatelet agents such as aspirin may help prevent thrombosis.

Question 49

Postsplenectomy sepsis

Answer 49

Individuals are susceptible to fulminant bacteraemia after splenectomy. The risk is greatest in young children, especially in the first two years after surgery, accounting for 80% of all cases. The risk is also greater when splenectomy is undertaken for disorders of the reticulo-endothelial system rather than for trauma.

In general, the younger the patient undergoing splenectomy and the more severe the underlying condition, the greater is the risk of developing overwhelming post- splenectomy sepsis. There is a small but significant risk of infection even in otherwise healthy adults following splenectomy. The risk is much higher in the first two years than in subsequent years. Lethal sepsis is more common in children and indeed is very rare in adults.

Streptococcus pneumoniae, Haemophilus influenzae and meningococci are the most common pathogens. There is a distinct clinical syndrome starting with mild non-specific symptoms followed by a high pyrexia and septicaemic shock which may ultimately be fatal. The risk of fatal sepsis is less after splenectomy for trauma. This may be due to splenosis, i.e. multiple small implants of splenic tissue which result from dissem- ination and autotransplantation of splenic fragments following splenic rupture. Presumably this results in areas of splenic tissue which function well enough to protect against septicaemia.

Question 50

Splenectomy vaccination

Answer 50

Prophylactic vaccinations should be given against pneumococcal septicaemia. For planned procedures a polyvalent pneumococcal vaccine should be given prior to splenectomy. Evidence exists that splenic func- tion may be important in the immune response to the vaccine. Antipneumococcal IgM titres are lower when patients are vaccinated after splenectomy. The vaccine is only effective against 80% of pneumococcal organisms; therefore, it is recommended that prophylactic penicil- lin be given for two years after splenectomy, when the risk of sepsis is at its greatest. Antibiotic prophylaxis
is essential in children under two years of age. Some authorities believe that antibiotic prophylaxis should be continued for life. Vaccination against H. influenzae type b (HiB) and meningococci A and C should also be given

Question 51

Thymus structure and function

Answer 51

The thymus develops from the third and fourth pha- ryngeal pouches and descends into the anterior super- ior mediastinum. It is an encapsulated structure, the capsule extending into the thymus as trabeculae divid- ing into a number of lobules. Each lobule has a cor- tex and medulla. The cortex contains densely packed lymphocytes which stain darkly. The medulla contains a few lymphocytes, macrophages but chiefly epithelial cells. The medulla also contains thymic (Hassall’s) corpuscles, which are epithelial cells arranged concentrically, the centre of which may be keratinised. Their function is unknown. It is relatively largest at birth in comparison to body weight. It is absolutely at its largest at puberty but thereafter declines in size such that in the elderly it is atrophied and composed largely of fat. It lies behind the manubrium sterni, anterior to the large veins draining its venous blood into the left brachiocephalic vein. It extends slightly into the neck and also along the surface of the pericardium and may abut on the pleura. Its arterial blood supply is derived from the internal mammary artery or the pericardio- phrenic arteries. Occasionally the lower parathyroids may be related to the thymus, both structures develop- ing from the third pharyngeal pouch.

Question 52

Thymus disorders

Answer 52

Agenesis may occur, resulting in immunodeficiency syndromes. Histological abnormalities of the thymus such as lymphoid hyperplasia or tumours may be seen in association with certain autoimmune diseases such as myasthenia gravis, systemic lupus erythematosus, dermatomyositis, and aplastic anaemia.

Question 53

Thymic tumours

Answer 53

Thymoma is a rare tumour of the epithelial elements of the thymus. Many are asymptomatic and are detected on chest x-ray performed for other reasons. Some are detected when myasthenia gravis develops. Others may present with signs of local disease such as cough, dyspnoea, stridor, or superior vena caval obstruction. The majority of thymomas are benign and well encapsulated. Malignant tumours are locally invasive, spreading
by direct invasion of adjacent structures. Distant spread is exceedingly rare.
Other tumours of the thymus include Hodgkin’s disease, non-Hodgkin’s lymphoma, teratoma, thymol- ipoma and, rarely, thymic carcinoid.