Haematology 1 Flashcards
What is anaemia?
Decreased Hb in the blood such that there is inadequate oxygen delivery to tissues
Hb <135g/L in men
Hb <115g/L in women
What are the symptoms of anaemia?
non-specific: fatigue, weakness, headaches
CV: dyspnoea on exertion, angina, intermittent claudication, palpitations
What are the signs of anaemia?
pallor
tachycardia
systolic flow murmur
cardiac failure
What are the specific signs for certain types of anaemia?
kolionychia: spoon shaped nails in IDA
jaundice: in haemolytic anaemia
leg ulcers: often seen in sickle cell disease
bone marrow expansion: leading to abnormal facial structure or pathological fracture
What is MCV?
size of each red blood cell
What is MCH?
amount of haemoglobin each red blood cell
What is classed as low MCV?
<80fL (microcytic anaemia)
What are the causes of low MCV?
T – Thalassaemia A – Anaemia of chronic disease I – Iron deficiency anaemia L – Lead poisoning S – Sideroblastic anaemia
What are the causes of normocytic anaemia (normal MCV)
acute blood loss
anaemia of chronic disease
renal anaemia
haemolytic anaemia: can be macrocytic due to reticulocytosis
marrow failure
pregnancy
connective tissue disease
dimorphic blood film: combined microcytic / microcytic processes
A – Acute blood loss A – Anaemia of Chronic Disease A – Aplastic Anaemia H – Haemolytic Anaemia H – Hypothyroidism
What are the causes of macrocytic anaemia >96fL
B12 deficiency Folate deficiency: coeliac disease alcohol excess (or severe liver disease) myelodysplastic syndromes Severe hypothyroidism (myxoedema, can be normocytic)
What clinical signs can be looked for with anaemia?
kolionychia
angular stomatitis
brittle nails / hair
What further tests can be done to confirm anaemia?
Iron studies: serum iron, ferritin, total iron binding capacity, serum soluble transferrin receptors
Blood film: microcytic anaemia = hypo chromic (pale on blood film)
Film may show sideroblasts / signs of thalassemia
Why is the body limited in taking up iron?
iron more readily taken up in the gut as ferrous iron (Fe2+) which is less abundant than the insoluble ferric Fe3+ iron
IDA develops when there is inadequate iron for haemoglobin synthesis
What are the causes of IDA?
Blood loss: hookworm is the most common cause worldwide
Heavy menstruation GI bleeds Decreased absorption e.g. in coeliacs, patients on antacids increased demand; growth / pregnancy Inadequate intake
How is IDA diagnosed?
Blood film: microcytic, hypochromic cells with poikilocytosis and anisocytosis (pale and small and funny shaped)
serum iron: decreased
total iron binding capacity: increased
serum ferritin: decreased
represents amount of stored iron
Soluble transferrin receptor: increased - MOST SPECIFIC TEST
What are the findings for anaemia of chronic disease?
microcytic or normocytic
serum iron will be decreased
TIBC will be decreased and STR will be normal
Ferritin will be raised
FERRITIN Represents increased stored iron, BUT it is an acute phase reactant and raises in infection or malignancy
What are the further investigations for anaemia?
If menorrhagia hx - start oral iron
?coeliac
Non-obvious cause of bleeding, refer for GI investigation
OGD and colonoscopy
stool microscopy
What is the management of IDA?
Address underlying cause: menorrhagia
Oral ferrous sulphate: 200mg t.d.s and commence before awaiting ix results
Advise increased dietary intake of dark green vegetables, fortified bread/cereals, lean red meat and prunes or raising
How should patents who do not tolerate ferrous sulphate be handled?
Switch to ferrous gluconate,
What are teh common side effects of iron supplements?
GI related: cramping, bloating, nausea, vomiting, constipation, black stools
adverse effects can be decreased if taken with meals, offering laxatives for constipation or dose reduction
How should iron supplements be monitored?
monitor for improvements in symptoms and blood parameters after 1 month; there should be a Hb increase of 20g/L in this time period
Treatment should continue for 3 months after blood parameters return to normal to replenish supplies
Describe the rule of 10s in anaemia?
The maximum rise in Hb concentration in one week is 10g/L
if more than 10g/L decline is seen over a week then blood is being lost
When transfusing, one bag will raise the Hb concentration by 10g/L
What is Plummer-Vinson syndrome?
Rare disease characterised by dysphagia, odynophagia, IDA, glossitis, chelitis and oesophageal webs
What is the management of Plummer-Vinson syndrome?
Iron supplementation and mechanical widening of the oesophagus generally provides an excellent outcome
What is thalassemia?
Genetic disorder of Hb synthesis, common in the Middle/Far East
caused by deficient alpha or beta chain synthesis, thus resulting in alpha or Beta thalassemia
What are the traits of B-thalassemia minor?
Carrier state: asymptomatic and gives mild microcytic anaemia that may worsen in pregnancy.
Often confused with IDA
HbA2 is raised, with slightly raised HbF also
What is the cause of B-thalassemia major?
Abnormality in both globin genes,
What is the presentation of B-thalassemia
presents within the first year with severe anaemia, hepatosplenomegaly and FTT
extra-medullary haematopoiesis results in facial deformities
survival is possible due to HbF
What does the blood film for B-thalassemia show?
Hypochromic, microcytic cells, also target cells ad nucleated RBCs
What is the management of B-thalassemia?
Lifelong blood transfusion
What is alpha thalassemia?
alpha chains are coded for by 4 genes
Deletion of all 4 alpha-globing genes, leading to HbBarts
Physiologically useless and leads to death in utero
What does deletion of 3 genes lead to? (alpha)
2 genes?
1 gene?
3 genes - moderate microcytic anaemia with features of haemolysis
2: asymptomatic carrier state with reduced MCV
1: clinically normal
What is sideroblastic anaemia?
bone marrow produces ringed sideroblasts rather than erythrocytes, which can be seen in the bone marrow
Can be a congenital disorder, or more commonly acquired in myelodysplastic syndrome
How should macrocytic anaemia be investigated
Blood film: hypersegmented neutrophils in B12/folate deficiency, may reveal other clues e.g. target cells in liver disease
LFTs/TFTs: thyroid or hepatic cause
Serum B12/folate levels: serum folate reflects recent intake so many labs do red cell folate
If B12 low: Anti-parietal cell Ab, anti-IF ab
Schilling test
Bone marrow biopsy: megaloblasts suggests B12/folate deficiency, also seen in myelodysplasia
What is schilling’s test?
distinguishes between pernicious anaemia and small bowel disease (radio labelled B12 given with and then without IF), amount of labelled B12 excreted in urine then detected
What is deoxyuridine suppression test used for?
Differentiate B12 folate deficiency in vitro after bone marrow biopsy
How do B12 and folate deficiency lead to megaloblastic anaemia?
B12 acts as a co-enzyme for the conversion of folate (B9) to activated folate
activated folate is required for DNA synthesis and thus if there is a deficiency in either B12 or folate, DNA synthesis malfunctions
In this case, the DNA fails to ‘stop’ erythrocyte development, leading to very large cells - which eventually are trapped and destroyed in the reticulo-endothelial system
Where do humans get B12 from?
Animal sources e.g. meat, fish, eggs and milk
Where is B12 stored?
LIVER, excreted in bile but around 70% is reabsorbed
Free vitamin B12 binds to R proteins in the upper GI tract, but these complexes are degraded by pancreatic proteases
What is IF secreted by?
Gastric parietal cells
What is the function of IF?
Binds free B12 with far less affinity than R proteins, but the IF-B12 complex is highly resistant to protease degradation.
Receptors for the IF-B12 complex are present on the brush border of the terminal ileum where B12 is absorbed
Why is IF important?
Necessary for B12 ingestion
lack of = pernicious anaemia
How are patients with pernicious anaemia managed?
IM b12 or high dose PO supplementation
What are the causes of B12 deficiency?
Chronic low dietary intake: vegans
Impaired binding in the stomach: pernicious anaemia, congenital absence of IF, gastrectomy
Small bowel disease: resection, Chron’s, backwash ileitis in UC, bacterial overgrowth
What is pernicious anaemia?
Autoimmune disease resulting in severe B12 deficiency
3 autoantibodies that may contribute towards disease: autoantibodies against parietal cells Blocking antibodies (prevent IF-B12 binding) Binding antibodies (prevent IF binding to ileal receptors)
What is subacute combined degeneration of the cord?
Simultaneous posterior column (LMN) and CST (UMN) loss due to B12 deficiency and gives a combination of UMN and LMN signs
What is the presentation of subacute combined degeneration of the cord?
Peripheral neuropathy and on examination there is a classical triad of extensor plantars, brisk knee jerk but absent ankle jerks
Tone and power usually normal, gait may be ataxic
How does folate occur in nature?
dihydrofolate, tetraydrofolate
found in green vegetables or offal however cooking causes a loss of up to 90%
Where are dhf and thf converted to folate?
upper GIT and folate is absorbed in the jejunum
What are the causes of folate deficiency?
Poor nutritional intake: poor diet, alcohol excess, anorexia
Malabsorption: coeliac disease
Anti-folate drugs: trimethoprim, methotrexate, anti-convulsants
Excess physiological use: pregnancy, lactation, prematurity
Excess pathological use: excess erythrocyte production (e.g. in haemolysis, malignancy, inflammatory diseases
What is the treatment of folate deficiency?
Folic acid 5mg/day PO for 4 months, always with combined B12 unless the patient is known to have a normal B12 level
(folate can precipitate subacute combined degeneration of the cord)
What questions should be asked for normocytic anaemia?
A – Acute blood loss A – Anaemia of Chronic Disease A – Aplastic Anaemia H – Haemolytic Anaemia H – Hypothyroidism
is there acute blood loss?
Is there underlying chronic disease
is it haemolytic
are other cell lines affected i.e. bone marrow failures
What is anaemia of chronic disease?
normochromic or hypochromic, rarely severe
seen in chronic infection, malignancy, CKD and rheumatoid disorders
What are the lab findings of anaemia of chronic disease?
Predominant WBC production in the bone marrow
low serum iron, raised ferritin, low TIBC, normal STR
what are the lab findings of bone marrow failure?
HB, reticulocytes, WBC and platelets all equally low
Alterations in the blood film
?abnormal blasts in the marrow
What are the causes of bone marrow failure?
Aplastic anaemia; idiopathic or due to drugs haematological malignancies metastatic disease myelofibrosis myelodysplasia parvovirus
What is haemolysis?
breakdown of RBC before the end of their normal lifespan (120 days)
The haemolysis can be intravascular or extravascular (reticuloedothelial system of the liver, spleen and bone marrow)
May be asymptomatic but haemolytic anaemia then develops if the bone marrow does not sufficiently compensate
What are the inherited causes of haemolytic anaemia
Hereditary Spherocytosis Hereditary Elliptocytosis Thalassaemia Sickle Cell Anaemia G6PD Deficiency
What are the acquired causes of haemolysis?
Autoimmune haemolytic anaemia Alloimmune haemolytic anaemia (transfusions reactions and haemolytic disease of newborn) Paroxysmal nocturnal haemoglobinuria Microangiopathic haemolytic anaemia Prosthetic valve related haemolysis
What investigations should be done for haemolysis?
Increased Red cell breakdown signs:
Anaemia with raised MCV
Raised bilirubin: unconjugated, pre-hepatic
Raised serum LDH: released from RBCs
Increased RBC production: reticulocyte count >2% or 100 x 10^9
Blood film
What blood film clues are there for haemolysis?
Hypochromic, microcytic cells: thalassemia
Sickle cells: sickle cell anaemia
Spherocytes: hereditary spherocytosis, or autoimmune haemolytic anaemia
eliptocyctes: hereditary eliptocytosis
Heinz bodies / ‘bite’ cells: G6PD deficiency
Schistocytes: microangiopathic haemolytic anaemia
What further tests can be done for haemolysis?
Full blood count shows a normocytic anaemia
Blood film shows schistocytes (fragments of red blood cells)
Direct Coombs test is positive in autoimmune haemolytic anaemia
Name the most common haemoglobinopathies
Thalassemia
sickle cell disease
What is sickle cell anaemia?
autosomal recessive disorder causing production of abnormal b-globulin chains due to a single amino acid substitution (glu6val)
resulting in production of HbS rather than HbA
In which patients is sickle cella anaemia more common?
African
What are the two genotypes for sickle cell anaemia?
HBSS: sickle-cell anaemia phenotype
HbAS: sickle cell trait - HbAS confers protection from falciparum malaria
Rarely symptomatic BUT vaso-occlusive events may occur in hypoxia (when flying or under anaesthesia)
Describe the pathogenesis of sickle cell anaemia
HbS polymerises when deoxygenated causing RBCs to form ‘sickle cells’
the sickle cells are fragile and haemolyse and also block small vessels
How is diagnosis of sickle cell anaemia done?
Guthrie screening card
sickle cells are seen on the blood film
Hb electrophoresis can confirm the diagnosis and also distinguish variants
What are the symptoms of sickle cell anaemia?
Often presents in the first few months of life - anaemia developing as HbF levels fall
acute haemolytic crises occurring causing bone infarcts and painful dactylitis in the fingers and toes
What happens if haemolytic crises goes untreated?
repeated splenic infarction leading to hyposplenism, repeated renal infarction causing CKD and CVA
What are the complications of SCA?
Anaemia Increased risk of infection Stroke Avascular necrosis in large joints such as the hip Pulmonary hypertension Painful and persistent penile erection (priapism) Chronic kidney disease Sickle cell crises Acute chest syndrome
What is the chronic treatment of SCA?
lifelong folate supplementation
pneumococcal vaccination and prophylactic penicillin due to hyposplenism
Hydroxycarbamide can help by increasing HbF production and is advised if there are frequent crises
Regular lifelong transfusions (2-4 weekly) with iron chelators to prevent overload
Bone marrow transplantation is curative: but limited by availability of matched donors
What are the causes of SCA vaso-occlusive crises
sickle shaped blood cells clog capillaries causing distal ischaemia
Micro-vascular occlusion, often affecting the bone marrow causing severe pain
What triggers a crisis?
cold, infection, dehydration, hypoxia
What is the presentation of a vaso-occlusive crisis?
pain in body
mesenteric ischaemia mimicking the acute abdomen, cerebral infarction, priapism
What is an aplastic crisis caused by?
temporary loss of the creation of new blood cells. This is most commonly triggered by infection with parvovirus B19
What is a sequestration crisis?
Pooling of blood in the spleen +/- liver, with organomegaly, severe anaemia and shock
urgent transfusions are required
What is the management of a sickle cell crisis?
A-E resuscitation, high flow oxygen and IV fluids
Strong analgesia within 30 mins
FBC, reticulocytes, cross match blood
Secret for infection: blood cultures, MSU, CXR and treat early
prophylactic enoxaparin. give fully cross-matched blood transfusion if Hb or reticulocytes fall sharply
Exchange transfusion if rapidly deteriorating
What is the cause of G6PD deficiency?
defect in the red blood cell enzyme G6PD
X linked inheritance
What are the symptoms of G6PD deficiency?
Mostly asymptomatic, jaundice (usually in the neonatal period), gallstones, anaemia, splenomegaly and Heinz bodies on blood film
susceptible to oxidative crisis due to reduced glutathione production.
These attacks cause rapid anaemia and jaundice with ‘bite cells’ and ‘blister cells’ seen on the blood film
What are the precipitants of attack from G6PD?
drugs: aspirin, primaquine, sulphonamides
broad bean consumption
illness
How is diagnosis of G6PD crisis done?
Enzyme assay 3 months after initial crisis
delay as young RBCs may have enough enzyme, and appaear normal.
treatment = precipitant avoidance, plus transfusion if severe
What is the cause of PK (pyruvate kinase deficiency)?
Autosomal recessive condition - with reduced ATP production, shortening the RBC lifespan
What is the production of PK deficiency?
Neonatal jaundice, and later chronic jaundice with hepatosplenomegaly
diagnosis = with enzyme assay
often well tolerated, so no specific therapy is needed, although splenectomies may help
What is hereditary spherocytosis?
autosomal dominant condition. It causes sphere shaped red blood cells that are fragile and easily break down when passing through the spleen.
What is hereditary eliptocytosis?
Hereditary elliptocytosis is very similar to hereditary spherocytosis except that the red blood cells are ellipse shaped. It is also autosomal dominant. Presentation and management are the same.
What is the management of hereditary spherocytosis / eliptocytosis =?
Folate
Splenectomy is curative, but reserved for severe dissed
What is autoimmune haemolytic anaemia?
antibodies are created against the patient’s red blood cells. These antibodies lead to destruction of the red blood cells. There are two types based on the temperature at which the auto-antibodies function to cause the destruction of red blood cells.
What are the classifications of AHA?
Warm AHA: IgG mediated, haemolysis occurs at 37 degrees (normal temperature)
Treated with steroids or immunosuppressants +/- splenectomy
Cold AHA: IgM mediated,
At lower temperatures (e.g. less than 10ºC) the antibodies against red blood cells attach themselves to the red blood cells and cause them to clump together. This is called agglutination. This agglutination results in the destruction of the red blood
often associated with Raynaud’s
Treated with cold avoidance +/- chlorambucil
What is drug induced haemolysis?
penicillin based drugs can cause formation of RBC antibodies, whereas drugs such as quinine cause production of immune complexes
Of the extrinsic causes of haemolysis, which are immune mediated?
Non-immune mediated?
Immune mediated: AHA, Drug induced
Non-immune mediated: Infection, Microangiopathic anaemia
Alloimmune reactions (transplant, transfusion or rhesus reaction) - immuned mediated but Coomb’s negative
What infections cause acute haemolysis?
Malaria and other intracellular parasites
What is microangiopathic anaemia caused by?
Microangiopathic haemolytic anaemia (MAHA) is where the small blood vessels have structural abnormalities that cause haemolysis of the blood cells travelling through them. Imagine a mesh inside the small blood vessels shredding the red blood cells. This is usually secondary to an underlying condition:
Haemolytic Uraemic Syndrome (HUS)
Disseminated Intravascular Coagulation (DIC)
Thrombotic Thrombocytopenia Purpura (TTP)
Systemic Lupus Erythematosus (SLE)
Cancer
What is the most common abnormality seen in pre-op patients?
Anaemia:
<60g/L will require transfusion
<100g/L may require transfusion depending on cardiac risk and anticipated blood loss
What are the cells included in a WBC differential?
Neutrophils Lymphocytes Eosinophils Monocytes Basophils
What to neutrophils do?
Ingest and kill bacterial, fungi and cellular debris
What do lymphocytes do?
Produce antibodies for cell mediated immunity
What do eosinophils do?
Role in allergic reactions, and defence of parasitic infection
What do monocytes do?
precursor of tissue macrophages
What do basophils do?
Release histamine in inflammatory reactions
What is leucocytosis?
Increase in the number of white blood cells in the blood
What are the differentials for neutrophilia?
Bacterial infection Inflammatory reaction Disseminated malignancy Stress e.g. surgery or burns Myeloproliferative conditions Corticosteroid therapy
What are the differentials for neutropenia?
Viral infections Severe sepsis Neutrophil antibodies e.g. SLE Bone marrow failure Hypersplenism e.g. Felty's Cytotoxic drugs
What is agranulocytosis?
Complete absence of circulating neutrophils
Side effect of carbimazole (exam q)
What are the differentials for lymphocytosis?
viral infections
Chronic infections (TB, hepatitis)
Myeloproliferative conditions
What are the differentials for lymphopenia?
Bone marrow failure Corticosteroid failure SLE Uraemia HIV infection Cytotoxic drugs
What is a leukaemia?
Malignant proliferation of blood forming cells.
Either acute or chronic
either myeloid or lymphoid
hamopoetic stem cell –> myeloid or lymphoid progenitor.
Then, What do MYELOID progenitor cells divide to form?
erythrocytes
mast cells
megakaryocytes
myeloblasts
which go on to form monocytes, basophils, neutrophils and eosinophils
What do LYMPHOID progenitor cells divide to form?
NK cells, T and B lymphocytes
Name the three myeloproliferative conditions
due to uncontrolled proliferation of a single type of stem cell: considered a type of bone marrow cancer
Myelofibrosis
Essential thrombocythaemia
Polycythaemia vera - considered pre-leukaemic
What is ALL?
Malignancy of lymphoid cells of either B or T cell lineages, leading to uncontrolled proliferation of immature blast cells. Excessive proliferation of these cells causes them to replace the other cell types being created in the bone marrow, leading to a pancytopenia
Leads to eventual bone marrow failure and tissue infiltration
What is the most common malignancy in childhood?
ALL - more common in certain genetic syndromes e.g. Down’s
What are the good and poor prognostic factors in ALL?
Prognosis is good in children below 10 - with cure rates of >80%
Poor prognosis is suggested by older age of presentation, male sex, B cell disease and presence of the Philedelphia chromosome (9:22 translocation)
What is AML?
Malignancy of Blast cells from the marrow myeloid elements
How does AML occur?
Can arise de novo or on a background of a myeloproliferative condition, previous chemotherapy, ionising radiation or genetic syndromes
What is the general age of presentation of AML?
65 years old
Incidence increases with age
What Is the prognosis for AML?
Rapidly progressive - only 20% 3-year survival after chemotherapy
What are the symptoms of acute leukaemia?
GENERALLY B-symptoms, bone pain etc
B-symptoms: Fatigue, weight loss, night sweats, fevers, pruritus
Bone pain
Symptoms related to bone marrow failure:
Anaemia: SOB, weakness
Leukopenia: recurrent infections
Thrombocytopenia: bleeding and bruising - more common in AML
Hepato/splenomegaly
Why do you get leukopenia symptoms when the presentation = leucocytosis?
Cells = immature and non-functioning blast cells
thus symptoms of leucopenia are seen
What are the investigations for acute leukaemias?
FBC
Blood film: blasts diagnostic, with lineage identified morphologically and confirmed with immunotyping
CXR: T cell ALL classically shows mediastinal widening
Bone marrow aspiration: to confirm diagnosis and confirm lineage
PET scanning: check for metastatic disease
U&Es, LFTs, cardiac function testing ECG/echo are then essential for planning therapy
What are the supportive care steps in managing leukaemias?
Nurse with full barrier nursing
Hickman line - venous access
high calorie diet
frequent blood and platelet transfusions required
Allopurinol to prevent tumour lysis syndrome due to chemotherapy
What antibiotics are given in management of acute leukaemia and why?
If temperature >38 degrees on two occasions greater than an hour apart, assume sepsis and start broad spectrum Abx until afebrile for 72 hours
Often a cephalosporin plus gentamicin
What is the management of ALL?
High dose chemotherapy to induce remission
Consolidation with high/medium dose ‘blocks’ over many weeks
2 years of maintenance therapy
Consider a marrow transplant if poor prognosis or relapse
Transplant necessary to cure those with philedelphia chromosome
What is the management of AML?
Intensive chemotherapy
In disease with poor prognosis, allogenic marrow transplant from HLA-matched siblings is indicated after first-round therapy
This then allows further high dose chemotherapy
In intermediate prognosis disease, autologous marrow transplants may be used (cells grown from own bone marrow)
Further chemotherapy must be at lower doses
When does each leukaemia onset?
ALL CeLLmates have CoMmon AMbitions
Under 5 and over 45 – acute lymphoblastic leukaemia (ALL)
Over 55 – chronic lymphocytic leukaemia (CeLLmates)
Over 65 – chronic myeloid leukaemia (CoMmon)
Over 75 – acute myeloid leukaemia (AMbitions)
What % of people with CML have the philedelphia chromosome?
95% - better prognosis than those without
What are the symptoms of CML?
Insidious B symptoms
Others = gout due to purine breakdown and abdominal discomfort due to scenic enlargement
Splenomegaly, Hepatomegaly and signs of anaemia/thrombocytopenia
What Ix are done for CML?
FBC: WCC very high, raised across the whole spectrum of myeloid cells
Bone marrow biopsy: hyper cellular
CT/PET
Cytogenic analysis of blood/marrow for the Philedelphia chromosome
What is the management of CML?
Imatinib chemotherapy has response rates >90% and is first line
Stem cell transplantation is teh only treatment that may achieve remission, but carries significant mortality / morbidity
What are the three phases of CML?
chronic phase, the accelerated phase and the blast phase.
The chronic phase - 5 years, is often asymptomatic and patients are diagnosed incidentally with a raised white cell count.
The accelerated phase occurs where the abnormal blast cells take up a high proportion of the cells in the bone marrow and blood (10-20%).
Patients become more symptomatic, develop anaemia and thrombocytopenia and become immunocompromised.
The blast phase - even higher proportion of blast cells and blood (>30%). This phase has severe symptoms and pancytopenia. It is often fatal.
Which is the most common leukaemia for all ages?
Chronic lymphocytic leukaemia - twice as common in males
Median age of presentation: 70 years
Describe how CLL occurs?
Accumlation of mature B cells that have escaped apoptosis and this increasing mass of immune-competent cells leads to bone marrow failure
What are the symptoms of CLL?
Often none: surprise finding on a routine FBC
Patient may be anaemic or infection prone or if severe there can be B symptoms
On examination there are enlarged non-tender lymph nodes and hepatosplenomegaly
What investigations are done for CLL?
FBC: markedly raised lymphocytes, may be a sign of bone marrow failure
Autoimmune haemolysis develops later
Blood film: predominant smudge cells (small mature lymphocytes)
What is the management of CLL?
Without tx, 1/3 never progress, 1/3 eventually progress and 1/3 actively progress from diagnosis
Treatment is only indicated if symptomatic, or there are cytogenic markers of poor prognosis
Tx = chemotherapy or radiotherapy o relive hepatosplenomegaly
What is the prognosis of CLL?
Stage 0: lymphocytosis alone; >13 years mean survival
Stage 1: lymphocytosis and lymphadenopathy, 8 years
Stage 2: lymphocytosis and hepato-splenomegaly: 5 years
Stage 3: lymphocytosis and anaemia: 2 years
Stage 4: lymphocytosis and thrombocytopenia, 1 year
What is the cause of death in CLL?
Usually due to an infection, or transformation to an aggressive lymphoma (Richter’s syndrome)
What is myeloma?
Myeloma is a cancer of the plasma cells. These are a type of B lymphocyte that produce antibodies. Cancer in a specific type of plasma cell results in large quantities of a single type of antibody being produced.
How does myeloma occur?
Normally, many different plasma cells produce a range of immunoglobulins i.e. they are polyclonal
In myeloma, a single clone of plasma cells produce a single immunoglobulin which can be seen as a monoclonal band, or paraprotein, on serum/urine electrophoresis
What are the clinical features of myeloma?
CRAB: calcium, renal, anaemia, bone C – Calcium (elevated) R – Renal failure A – Anaemia (normocytic, normochromic) from replacement of bone marrow. B – Bone lesions/pain
Osteolytic bone lesions due to osteoclast activation
Backache
pathological fractures
hypercalcaemia (bones, stones, moans and groans)
Bone marrow failure:
infection
symptoms of anaemia
bleeding
Renal impairment:
Seen in 20% at diagnosis, due to light chain deposition
