Haem Flashcards
Erythroderma (chronic inflammatory skin condition with scaling in >50% of total body) is associated with which cutaneous malignancy
T-cell lymphoma
Treatment of hypercalcaemia (i.e. due to mets/multiple myeloma)
IV saline (first-line for dehydration) Then afterwards give IV bisphosphonates
12 year patient - easy bruising, nose bleeds, small ecchymoses on skin. Last week he reported a mild fever and sore throat. Nose bleeds are not prolonged and soon stop after pressure is applied. Blood test = mild thrombocytopenia.
Immune thrombocytopenic purpura
Abs from the spleen against Ags e.g. GlpIIb/IIIa. Acutely follows a viral infection in children, and usually self limited.
A 78 year old woman with widespread itching O/E: hepatosplenomegaly. The patient appears plethoric with no lymphadenopathy.
Polycthaemia rubra vera
A 78 year old woman attends complaining of recent onset of tiredness. She is pale, has hepatosplenomegaly and generalised painless lymphadenopathy in the neck, axillae and groin. Coombs’ (DAT) test is positive
CLL, generally older adults and asymptomatic. Peripheral blood smear shows smear cells and is associated with warm type AIHA = pallor and fatigue (and positive Coombs DAT test). Lymphocytosis will be seen.
A 27 year old Afro-Caribbean man presents with fever, weight loss and an intractable itch. His spleen is just palpable and he has two 3cm nodes in his right neck. Hb is low.
Hodgkin’s lymphoma
Reed-Sternberg cells
Hodgkin’s lymphoma
Non-tender firm rubbery lymphadenopathy in cervical, axillary and inguinal regions
More painful on drinking alcohol
Ann-Arbor staging
Non-hodgkin’s lymphoma
B cell (85%) - burkitt's caused by EBV T cell (15%) NK cell
Enlarged rubbery, non-tender lymph nodes, blood film shows smear cells, lymphocytes with no blast cells
CLL
A 65 year old male undergoing chemotherapy for acute myeloid leukaemia starts to deteriorate on the ward. He complains of a tingling sensation in his fingers and around his lips. He also complains of muscle weakness and appears confused. His biochemistry reveals that he is hyperkalaemic, hyperphosphataemic, hyperuricaemic and hypocalcaemic. His creatinine is elevated to 300umol/L. What is the diagnosis?
Tumour lysis syndrome occurs in patients undergoing chemotherapy for lymphoproliferative malignancies. Lysis of tumour cells leads to the release of large amounts of potassium, phosphate and uric acid into the circulation. Excess phosphate binds to calcium, leading to hypocalcaemia and its clinical features. Patients are also at risk of developing AKI due to the deposition of uric acid and calcium phosphate crystals in renal tubules.
Philadelphia Chr (Abelson-BCR gene), sweats, massive splenomegaly, increased WCC
CML
Bruising, pale, usually children btw 2-4 years old, blast cells seen on blood film
ALL
Auer rods and blast cells seen on blood film, splenomegaly, SOB, bone pain
AML
Hereditary haemochromatosis (increased iron absorption) liver model and crypt cell model
Liver model: decreased expression of hepcidin hormone
Crypt cell model: impaired uptake of transferrin-bound iron into crypt cells
Hereditary haemochromatosis (increased iron absorption) signs and symptoms
Skin - slate grey pigmentation from increased melanin deposits
Liver - hepatomegaly
Heart - HF, arrhythmias
Hypogonadism
Bloods: high iron, ferritin, low TIBC and transferrin sats
Jaundice and increased unconjugated bilirubin suggests
Haemolytic anaemia
Sideroblastic anaemia blood film
Dimorphic blood film
Hypochromic microcytic cells
Basophilic stippling on blood film suggests
lead poisoning
Megaloblastic macrocytic anaemia causes
B12/folate def
Anti-folate drugs e.g. methotrexate, phenytoin, azathioprine
Large erythrocytes
Hypersegmented neutrophils nuclei (>5lobes) on blood film suggests
Megaloblastic macrocytic anaemia
Pernicious anaemia Rx
IM hydroxycoalbumin
Folate deficiency Rx
Oral folic acid
n.b. treat underlying vit B12 def first because folic acid can worsen vit B12 def neuro complications
High MCV
Normal RCDW
cause is likely to be…
Alcohol
Liver disease
Marrow problem (chemo or aplastic anaemia)
Increased RCDW is due to
Mixed anaemias
Microcyte and macrocyte prsence at the same time e.g. iron and folate deficiencies
Myelodysplasia (chronic cytopenia) presents with BM failure. What investigations would you do and what would the findings be?
Blood - FBC shows pancytopenia
Blood film - low granulocytes
Bone marrow trephine biopsy - hypercellular and ringed sideroblasts (haemosiderin deposits)
N.b. there is NO splenomegaly
Myelofibrosis (progressive marrow fibrosis) = abnormal megakaryocytes secreting platelet growth factor. What investigations would you do and what would be the findings?
Blood - FBC shows pancytopenia
Blood films - tear drop pilokilocyte RBCs
Bone marrow trephine biopsy - aspiration is unsuccessful = dry tap. Trephine biopsy shows fibrotic hypercellular marrow.
O/E - massive splenomegaly
von Willebrand’s disease definition
Abnormalities in expression or function of vWF
Autosomal dominant - type 1
Acquired forms possible
F>M
vWF signs and symptoms
Easy bruising
Bleeding after minor trauma
Mucocutanenous bleeding (menorrhagia, epistaxis)
Internal bleeding/into joints
Anaemia
Signs of liver disease
Increases APTT and bleeding time. Low factor 8 + vWF
vWF functions
- Brings platelets in contact with exposed subendothelium (acts as adhesive bridge)
- Makes platelets bind together
- Binds to factor 8 and prevents it degradation
Causes of DIC (widespread activation of coagulation)
Infection: sepsis
Malignancy: acute leukaemias, chronically lung breast and GI cancers
Obstetric: pre-eclampsia, miscarriages
Trauma
Low platelets High PT and APTT Low fibrinogen High fibrin degradation products Schistocytes
What is diagnosis?
DIC
Acute: petechiae, purpura, ecchymosis, mucosal bleeds, haemorrhage, end organ damage
Chronic: DVT/ thrombi
A child is 2 weeks post-viral infection has acute sudden self-limiting purpura with epistaxis. What is the likely diagnosis?
Immune thromobocytopenic purpura
- anti-platelet Abs
- causes thrombocytopenia
- bruising, mucosal bleeds, petechiae, menorrhagia
Bone marrow failure symptoms and signs
present in leukaemias
Anaemia - lethargy, dyspnoea, pallor
Bleeding - thrombocytopenia
Recurrent infections
Cardiac flow murmur
Organ/tissue infiltration symptoms and signs
present in leukaemias
Skin rashes Tender bones Lymphadenopathy CNS - headache, N+V Hepatosplenomegaly Gum hypertrophy + bleeds
Myelodysplasia definition
Chronic cytopenia (anaemia, neutropenia, thrombocytopenia) and abnormal cellular maturation
30% transform to AML
Myelofibrosis definition
Disorder of haematopoietic stem cells (megakaryocyte hyperplasia) leading to progressing bone marrow fibrosis and myeloid metaplasia
Associated with extramedullary haematopoiesis and massive hepatosplenomegaly
Myelofibrosis risk factors
Polycthaemia rubric vera (30%)
Essential thrombocytopenia
Types of polycthaemia (distinguish between relative and absolute)
Relative - low plasma volume, normal RBC mass. Acute causes = dehydration. Chronic = obesity, HTN, alcohol, smoking.
Absolute - high RBC mass
Absolute polycthaemia (high RBC mass) can be primary or secondary. Define these
Primary - polycthaemia rubric vera. Malignant proliferation. JAK2 tyrosine kinase mutation.
Secondary - due to chronic hypoxia (appropriate high erythropoietin) and inappropriate high erythropoietin (e.g. renal/HCC)
A man aged 50 presents with headache, dizziness, dyspnoea, itchy after a hot bath and visual disturbance/blurriness. O/E: facial plethora, splenomegaly. What is the likely diagnosis?
Polycthaemia
Sickle cell crisis types
Vaso-occlusive crisis - infarction. Severe pain triggered by cold, dehydration, infection, hypoxia. i.e. bone pain, abdo pain, splenic atrophy/infarction, stroke
Aplastic - parovirus B19, sudden low BM production, 2 weeks, self-limiting, low reticulocytes
Sequestration crisis - RBC pools in organs e.g. spleen (splenomegaly), high reticulocytes, severe anaemia, shock. mainly in children.
Sickle solubility test will confirm …
Sickle cell disease
Increases turbidity of solution
N.b. does not distinguish between HbSS and HbAS (carrier) - do Hb electrophoresis
Sickle cell anaemia
Acute crisis and chronic Rx
Acute - O2, IV fluids, analgesia (IV opiates), Abx ±transfusion
Chronic - infection prophylaxis (IV penicillin etc). Folic acid (pregnancy or severe haemolysis). Hydroxyurea to increase HbF and reduce crisis risk. RBC transfusions
Surgical: BM transplant
Advice: avoid triggers
a-thalassaemia
Decreased a-globin chain synthesis
Chr has 4 a-globin genes.
Types of a-thal?
Hb Barts - 4 gene deletion. Intrauterine death
3 gene deletion - microcytic hypochromic anaemia. Splenomegaly.
1-2 gene deletion - microcytic hypochromic RBCs. No anaemia.
b-thalassaemia
Decreased b-globin genes on Chr11
Types of b-thal?
B-thal major - homozygous. Severe anaemia and failure to thrive at age 1
B-thal intermedia - mild defect in b-chain synthesis. Microcytic anaemia, low a-chain synthesis or increased gamma chains
B-thal trait - heterozygous, asymptomatic, mild microcytic anaemia
A child (presenting ~3-6months old) has recurrent infections. They are noted to have pallor, malaise, dyspnoea and mild jaundice. Frontal bossing and hepatosplenomegaly are present. What is the likely diagnosis?
B-thalassaemia major
Failure to thrive
Marrow hyperplasia due to extra-medullary haematopoiesis
Hepatosplenomegaly due to RBC pooling and haematopoiesis.
n.b. b-thal intermedia may present similarly
Howell Jolly bodies are found in a patient with coeliac disease. What do they show
HJBs are found in hyposplenism.
Coeliac disease is associated with hyposplenism in 15%. Hyposplenism is also caused by sickle cell disease, radiation of spleen e.g. in Hodgkin’s lymphoma and splenectomy.
A 45yr old man presents with fever, wt loss, tiredness and gout. O/E: splenomegaly. WCC is raised and Philadelphia Chr is detected. What is the likely diagnosis?
CML - high WCC, Philadelphia Chr, massive splenomegaly.
N.b. hyperuricaemia occurs with leukaemias hence gout
Myelofibrosis bone marrow aspirate or biopsy results
Aspiration = unsuccessful (‘dry tap’)
Trephine biopsy = fibrotic hypercellular marrow with dense reticulin fibres on silver staining
Criteria for severe aplastic anaemia
<25% normal cells
or <50% normal cells + <30% haemopoietic cells and two of the following:
low neutrophils
low platelets
low reticulocytes
