Phase 2 Jamie McConnell and Erin Whyte The Peer Teaching Society is not liable for false or misleading information… Haematology

Phase 2

Jamie McConnell and Erin Whyte

The Peer Teaching Society is not liable for false or misleading information…

Haematology

• Anaemias• Leukaemias• Lymphomas• Myeloma


aims


Anaemia• What does anaemia mean?

• A reduction in the concentration of haemoglobin in the blood.


Anaemia• What are the symptoms of anaemia?

• Pallor (subconjunctival)• Fatigue• Tachycardia• Breathless• Koilonychia

• 65 y/o man presents with a 2 month history of fatigue and weight loss. FBC shows he has a haemoglobin of 60g/l (normal 130-180g/l)

• What does this tell you?


Case 1

• Anaemia ?cause

• Haematologically, what other information would you like to know?


Case 1

• Haematinics: folate, B12 and ferritin.

• Our patient has a normal folate and B12, but ferritin is low at 7mcg/l.

• What is the diagnosis and most likely cause?


Case 1

• Iron deficiency anaemia secondary to colon carcinoma

• What does iron deficiency anaemia look like on a blood film?


Case 1


Case 1

NormalAnaemic

• Iron deficiency anaemia is a hypochromic, microcytic anaemia.

• This is due to reduced iron content - haemoglobin gives RBCs their colour and volume

• Reduction in iron → reduction in haemoglobin


Case 1

• 21 y/o lady presents with fatigue. • Hb 47g/l• What other information would you like?• Haematinics! B12 & folate normal, ferritin low• Diagnosis and most likely cause?• Iron deficiency anaemia 2ndary to

menorrhagia.


Case 2

• 34 y/o lady presents with 3 months of fatigue. She has a history of coeliac disease. Hb is low…

• Haematinics! B12 and ferritin are normal, folate is low.

• Diagnosis and most likely cause?• Folate deficiency 2ndary to malabsorption due

to coeliac disease.


Case 3


Case 4• 34 y/o lady presents with 3 months of fatigue.

She has a history of hypothyroidism. Hb is low…• Haematinics! Folate and ferritin are normal,

B12 is low.• Diagnosis?• Pernicious anaemia

• Autoimmune destruction of parietal cells in the stomach

• Parietal cells produce intrinsic factor which is required for absorption of B12 in terminal ileum

• ↓ parietal cells → ↓ intrinsic factor → ↓B12


Pernicious Anaemia

• What do RBCs in folate and B12 deficiency look like on a blood film?

• Macrocytic

• B12 and folate are involved in DNA synthesis


B12 and folate

• Replace what’s missing:– Iron (e.g. oral ferrous sulphate)– B12 (im hydroxocobalamin)– Folate (oral folic acid)


Management

• 47 y/o woman with 7 year history of RA is found to have a mild anaemia on FBC.

• What is the diagnosis?• Anaemia of chronic disease• What would you expect to see on blood film?• Normochromic, normocytic


Case 5

• Patient on dialysis is anaemic.

• What is the pathophysiology?• Inadequate erythropoietin production by failing

kidneys• What would you see on a blood film?• Normochromic normocytic


Case 6

• 12 month old Italian boy presents with failure to thrive. He has mild jaundice and lacks energy. On examination he has splenomegaly and subconjunctival palor.

• What is the probable diagnosis?• B Thalassaemia major


Case 7


Thalassaemia

• 2 main types of haemoglobin

• HbA (adult haemoglobin A2B2)• HbF (Foetal haemoglobin (A2G2)


Thalassaemia

• Alpha-thalassaemia is dysfunction of alpha chain.• 4 genes control production of alpha chain. • being a carrier of 1 or 2 dysfunctional genes produces

a mild anaemia which would probably go unnoticed.• Carriers of 3 dysfunctional genes develop a severe

haemolytic anaemia• Having 4 dysfunctional genes is incompatible with life


Thalassaemia

• In B thalassaemia there are no problems initially as foetal heamoglobin compensates

• As you grow up, your requirement for adult haemoglobin increases resulting in an increasingly severe anaemia


Thalassaemia


Thalassaemia

• 2 genes produce b chains. • Being a carrier of one dysfunctional gene produces

"thalassaemia trait" which is a mild, haemolytic anaemia

• Being a carrier of 2 dysfunctional genes is B-thalassaemia major - severe haemolytic anaemia.

• Why do you get jaundice and frontal bossing?


Thalassaemia

• Jaundice is a result of haemolysis (haem - biliverdin - bilirubin)

• Frontal bossing is due to extramedullary haemopoiesis

• How would you treat this?


Thalassaemia

• Blood transfusion• Risks of transfusion?• Haemochromatosis• How would you prevent that?• Chelation


Thalassaemia

• 7 y/o boy from Ghana presents with acutely painful left hip. He is slightly anaemic.

• Likely diagnosis?• Sickle cell• What would you see on his blood film?• Sickle cells• How is this condition inherited?• Autosomal recessive


Case 8


Any questions about anaemia?

• What are the symptoms of bone marrow failure?

• Anaemia (low RBC)• Immunocompromised (remember SPUR -

severe, persistent, unusual and recurrent infections)

• Bleeding, bruising, petechiae (low PLT)


Bone Marrow Failure

• Neoplasm of the bone marrow• 2 broad types: acute and chronic• Further split into lymphoid or myeloid


Leukaemia


• Presentation of acute leukaemia?– Bone marrow failure– Systemically unwell (usual cancer stuff)– Rapidly progressive - death in weeks/months

if untreated


Leukaemia

• Peak age 4y• Associated with Philadelphia chromosome in adults• FBC (↓RBC, ↓PLT)• Primitive white cells (lymphoblasts)• Bone marrow aspiration• Rx chemo, bone marrow transplant• Children have very good prognosis (>80% cure),

adults less good (30-40%)


Acute lymphoblastic leukaemia

• Peak age 70• Associated with skin and gum infiltration• Investigations as for ALL (myeloblasts)• Auer rods in cytoplasm of blasts pathognomic

of AML• Rx with chemo, bone marrow transplant• Prognosis poor (12% 5y survival) - remember

this is disease of elderly


Acute Myeloid Leukaemia

• Incidence increases with age, M>F 2:1• Family history of ALL, CLL• Malignant illness of B cells (lymphocytes)• 50% are diagnosed incidentally• Systemic symptoms, bone marrow failure,

lymphadenopathy and hepatosplenomegaly are late


Chronic lymphocytic leukaemia

• What would you see on FBC?• Lots of lymphocytes• As these B cells will not mature in plasma cells, may

have hypogammaglobulinaemia• Usually chronic, incurable condition which patients

die with rather than from• Treat if symptomatic with chemo, bone marrow

transplant in the young• Prognosis: Stage A >10y, stage C<5y


Chronic lymphocytic leukaemia

• Most common in middle age - ionising radiation• Associated with philadelphia chromosome• Clonal disorder arising from myeloid stem cell• Presents with systemic symptoms, abdominal

pain (splenomegaly), anaemia• Chronic phase → acute phase


Chronic Myeloid Leukaemia

• FBC - leukocytosis, slightly low Hb, PLT normal or high

• Bone marrow aspirate hypercellular• Treatment with imatinib, bone marrow transplant in

young or resistant• Chronic phase responds to chemo, acute phase is

more resistant and usually rapidly fatal• Prognosis 60% 5y overall • 90% of those with chronic phase survive 5y


CML

• Neoplasm of the "lymphoid system"• Symptoms: lymphadenopathy (neck), pain with

alcohol, general cancery things, can obstruct SVC• Peaks in young adults and elderly• Reed Sternberg cells• Associated with EBV• Staged by Ann Arbor system• Treat with chemo, PBSC transplant


Lymphoma - Hodgkins

• 80% B-cell, 20% T-cell• Symptoms: similar to Hodgkin's but get bone

marrow infiltration earlier• Incidence increasing (AIDS)• Associated with RA, SLE, Sjogrens• Low grade: manage with chemo, unlikely to cure,

median survival 3-10 years• High grade: aggressive, e.g. Burkitt's lymphoma

(EBV), 30% curable


Lymphoma - Non-Hodgkin's


Myeloma

A malignancy of plasma cells in the bone marrow


Myeloma - pathophysiology

• Clone of cancerous plasma cell forms filling the bone marrow producing a single (monoclonal) immunoglobulin (M band/paraprotein)• Normal immunoglobulin production suppressed - immunoparesis•Bence-Jones protein deposition in kidneys• Anaemia - due to tumour infiltration - anaemia of chronic disease


Typically 60-70 years oldAfrican AmericansMen>Women (slightly!)

Myeloma - the patient

Confusion - due to hyperviscosity syndrome, hypercalcaemia or infection (e.g. UTI, septicaemia)

Renal Failure - producing malaise, anorexia, confusion. Due to hypercalcaemia, Ig deposition (Bence-Jones), septicaemia, drugs (e.g. NSAIDs)

Osteoporotic fractures and bone pain. Particularly to hips, ribs, skull and to back (height may decrease by 8-10cm).

Tired, breathless and fatigue due to anaemia and cachexia of chronic disease


Myeloma - clinical presentation

• Bacterial infection - hypogammaglobulinaemia• Bone pain and fractures - resulting from lysis and resorption of cortical bone• Hypercalcaemia (nausea, thirst, polyuria, constipation, confusion)• Anaemia • Renal impairment - normal immunoglobulin = 1:1 ratio of heavy:light chains, in myeloma excess light chain (Bence-Jones protein) - deposition in kidney and impair function


Myeloma - diagnosis• Monoclonal immunoglobulin band seen on protein electrophoresis• Bone marrow aspirate - excess plasma cells• Lytic lesions on X-rays of long bones, skull, spine

Also may have abnormal -• FBC - low Hb• Renal function - high creatinine• Albumin - low if chronically unwell• Cultures for bacteria - urine, blood




Myeloma - management

• Depends on age of patient, co-morbidities etc.• Chemotherapy - common induction thalidomide-dexamethasone (initial disease control)• High dose treatment + autologous peripheral blood stem cell support increases response rate and remission in younger patients• Bone marrow transplant in some (young patients) - cure around 25%• Supportive care including bisphosphonates• Life expectancy 4-5 years (slowly increasing)

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Phase 2 Jamie McConnell and Erin Whyte The Peer Teaching Society is not liable for false or misleading information… Haematology