Haematology Flashcards
What is the Hb threshold for anaemia in men? (with units)
135 g/L
What is the Hb threshold for anaemia in women? (with units)
115g/L
What conditions are microcytic anaemias associated with?
FAST:
Fe-deficiency anaemia
Anaemia of chronic disease
Sideroblastic anaemia
Thalassaemia
What conditions are normocytic anaemia associated with?
HABHARP
Hypothyroidism Acute blood loss Bone marrow failure Haemolysis Anaemia of chronic disease Renal Failure Pregnancy
What conditions are macrocytic anaemia associated with?
HABARM
Hypothyroidism Antifolate drugs (e.g. phenytoin) B12 or folate deficiency Alcohol excess or liver disease Reticulocytosis Myelodysplastic syndromes
What symptoms may somebody with anaemia complain of?
Fatigue Faintness Headache Tinnitus Dyspnoea Palpitations Anorexia
What signs are associated with Iron-deficiency anaemia?
Koilonychia Brittle hair and nails Angular cheilosis Atrophic glossitis Post-cricoid webs (Plummer-Vinson syndrome)
How can you categorise the causes of iron-deficiency anaemia?
Decreased intake Decreased absorption Increased utilisation Blood loss Intravascular haemolysis
Causes of iron-defiency
Prematurity, infants/children/elderly (decreased intake)
Coeliac, post-gastric surgery (decreased absorption)
Pregnancy, infants/children during growth (increased utilisation)
Gastrointestinal loss (blood loss)
Haemolytic anaemia (intravascular haemolysis)
What conditions are microcytic anaemias associated with?
FAST:
Fe-deficiency anaemia
Anaemia of chronic disease
Sideroblastic anaemia
Thalassaemia
What conditions are normocytic anaemia associated with?
HABHARP
Hypothyroidism Acute blood loss Bone marrow failure Haemolysis Anaemia of chronic disease Renal Failure Pregnancy
What conditions are macrocytic anaemia associated with?
HABARM
Hypothyroidism Antifolate drugs (e.g. phenytoin) B12 or folate deficiency Alcohol excess or liver disease Reticulocytosis Myelodysplastic syndromes
What symptoms may somebody with anaemia complain of?
Fatigue Faintness Headache Tinnitus Dyspnoea Palpitations Anorexia
What signs are associated with Iron-deficiency anaemia?
Koilonychia Brittle hair and nails Angular cheilosis Atrophic glossitis Post-cricoid webs (Plummer-Vinson syndrome)
BLOOD FILM: Microcytic Hypochromic Anisocytosis Poikilocytosis (shape) Pencil cells
Iron-deficiency anaemia
How can you categorise the causes of iron-deficiency anaemia?
Decreased intake Decreased absorption Increased utilisation Blood loss Intravascular haemolysis
Causes of iron-defiency
Prematurity, infants/children/elderly (decreased intake)
Coeliac, post-gastric surgery (decreased absorption)
Pregnancy, infants/children during growth (increased utilisation)
Gastrointestinal loss (blood loss)
Haemolytic anaemia (intravascular haemolysis)
What happens to ferritin in anaemia of chronic disease?
It is raised
What causes anaemia of chronic disease in renal failure?
EPO deficiency
Which cytokine is raised in anaemia of chronic disease and what effect does this have on the body?
IL-6 is raised
leads to increased hepcidin production and release from the liver … leads to reduced ferroportin (therefore less iron access in the circulation)
What would you look for when diagnosing sideroblastic anaemia?
Ringed sideroblasts
Causes of sideroblastic anaemia?
myelodysplastic disorders myeloproliferative disease post-chemotherapy irradiation alcohol excess lead excess anti-TB drugs
One way of treating sideroblastic anaemia?
Pyridoxine (vitamin B6 which promotes RBC production)
Iron: low
TIBC: raised
Ferritin: low
Iron deficiency
Iron: low
TIBC: low
Ferritin: raised
Anaemia of chronic disease
Iron: raised
TIBC: low
Ferritin: raised
Chronic haemolysis
Iron: raised
TIBC: low/normal
Ferritin: raised
Haemochromatosis
Iron: normal
TIBC: raised
Ferritin: normal
Pregnancy
Iron: raised
TIBC: normal
Ferritin: raised
Sideroblastic anaemia
What might you see on a megaloblastic blood film?
Hypersegmented polymorphs
Leucopenia
Macrocytosis
Thrombocytopenia
What are two causes of vitamin B12 deficiency?
Dietary (e.g. vegan)
Malabsorption:
1) STOMACH: Lack of intrinsic factor produced by gastric parietal cells leads to pernicious anaemia OR post-gastrectomy
2) Terminal ileum due to ileal resection, Crohn’s, bacterial overgrowth, tropical sprue, tapeworms
What test might you perform for pernicious anaemia?
Parietal cell antibodies
Intrinsic factor antibodies
Schilling test
How do you treat vitamin B12 deficiency?
IM hydroxycobalamin
What dietary sources contain folate?
Green veg
Nuts
Yeast
Liver
Causes of folate deficiency? and how do you treat?
Dietary
Increased demand: Pregnancy or increased cell turnover (e.g. haemolysis, malignancy, inflammatory disease, renal dialysis)
Malabsorption, e.g. coeliac, tropical sprue
Drugs: alcohol, anti-epileptics, methotrexate, trimethoprim
Give oral folic acid
What cluster of lab findings might make you suspect a haemolytic anaemia?
Increased bilirubin (unconjugated)
Increased urobilinogen
Increased LDH
Reticulocytosis (increased MCV and polychromasia)
What signs and symptoms might indicate a haemolytic anaemia specifically?
All those associated with anaemia plus
Dark red urine (haemogloburinia)
Jaundice
In terms of haemolytic anaemia what does ‘intrinsic’ and ‘extrinsic’ mean?
Intrinsic: factors related to the RBC
Extrinsic: factors outside of the RBC
What intrinsic causes of haemolytic anaemia are there? and give two examples of each.
Membrane defect: hereditary spherocytosis; hereditary elliptocytosis.
Enzyme defect: G6PD deficiency; Pyruvate kinase deficiency
Haemoglobinopathies: Sickle Cell Disease; Thalassaemias
What extrinsic causes or haemolytic anaemias are there and give examples of each.
Immune: Autoimmune (hot/cold); Alloimmune (haemolytic transfusion reactions).
Non-immune: Mechanical (metal heart valves, trauma); Paroxysmal nocturnal haemoglobinuria; Infections/Drugs
What is heparin’s mechanism of action?
Potentiates antithrombin III which then inactivates thrombin and other clotting factors (e.g. 10a)
What is the antidote for heparin?
Protamine sulfate
What are the clinical side-effects of heparin use? What might you see on lab results?
Heparin-induced-thrombocytopenia
Alopecia (rare!)
Osteoporosis (rare!)
Lab results:
elevated aminotransferase
hyperkalaemia
What is warfarin’s mechanism of action and what factors/proteins does this affect?
Vitamin K antagonist
Inhibition of factors 2, 7, 9 and 10
Inhibition of proteins C, S and Z
How might you reverse warfarin overdose?
IV vitamin K
Prothrombin complex concentrates (FII, VII, IX, X and Protein C and S)
In general what does a high INR put you at risk of? and a low INR?
High INR: High risk of bleeding
Low INR: High risk of clot formation
Who are more likely to develop ALL: children or adults?
Children
What are the clinical features of ALL?
Bone Marrow Failure:
Anaemia
Thrombocytopenia (bleeding)
Neutropenia (infections)
Lymphadenopathy Organ involvement (hepatomegaly, splenomegaly, CNS)
What are you looking for in the blood of an ALL patient?
High WCC
Blast cells, lymphoblasts
What is the aim of ‘remission induction’ chemotherapy? What agents are usually used?
Kill most tumour cells and get patient into remission (less than 5% of leukemic blasts in bone marrow, normal blood cells in blood and absence of other signs/symptoms).
Agents: Steroid (dexamethasone/prednisolone) Vincristine Asparaginase (better for paeds) Daunorubicin (better in adults)
What is the aim of ‘consolidation’ chemotherapy?
High dose multi-drug chemotherapy
Can target the CNS too
What is the aim of ‘maintenance’ chemotherapy?
Kill off any remaining tumour cells that were not killed by the remission induction/consolidation phases, otherwise the patient may relapse.
Auer rods are associated with which condition?
Acute Myeloid Leukaemia
What investigation can you perform to distinguish AML from ALL?
Myeloperoxidase and Sudan black stains
What signs/symptoms can be found in chronic myeloid leukaemia?
Fever
Bone pain
Splenomegaly
You perform a blood count in a patient you suspect has CML. What are you looking for?
Elevated granulocytes: eosinophils; basophils; mast cells; neutrophils.
What is the Philadelphia chromosome? What does it give rise to?
Abnormal chromosome 22. The result of a chromosomal translocation (9;22)
Philadelphia chromosome results in the BCR-ABL fusion gene.
What are the three phases in CML and what order do they typically occur in?
- Chronic Phase
- Accelerated Phase
- Blast Crisis
What is the first phase of CML? What signs and symptoms may the patient present with? What is the treatment in the first phase?
Chronic Phase.
Asymptomatic/mild symptoms Fatigue Left side pain joint/hip pain Abdominal fullness
Treatment:
Imatinib (a BCR-ABL tyrosine kinase inhibitor)
or, if resistant to imatinib, can use dasatinib/nilotinib.
What is the second phase of CML? What signs/symptoms/lab findings might there be?
Accelerated phase
Incrasing splenomegaly Unresponsive to therapy 10-19% myeloblasts in blood/bone marrow >20% basophils in the BM/blood Platelets really high, or really low.
What is the third and final phase of CML? What signs/symptoms/lab findings might there be?
Blast crisis.
> 20% myeloblasts/lymphoblasts in the blood/BM
Development of a chloroma (solid focus of leukaemia outside of the bone marrow)
What condition is Binet Staging used in? How many stages are there and what are the features of each stage?
Chronic Lymphocytic Leukaemia
3 stages: A, B and C.
A: Less than 3 groups of enlarged lymph nodes and a raised WCC
B: Greater than 3 groups of enlarged lymph nodes and a raised WCC
C: Enlarged lymph nodes or spleen, raised WCC, low RBC/platelets.
What condition is Rai Staging used in?
Chronic Lymphocytic Leukaemia
Name some agents used in the treatment of chronic lymphocytic leukaemia.
Chlorambucil (nitrogen mustard alkylating agent)
Fludarabine (purine analog that interferes with DNA synthesis)
Alemtuzumab (monoclonal antibody, anti-CD52)
Who is affected more in Hodgkin’s lymphoma … Males or Females?
Males.
What age of incidence does Hodgkin’s lymphoma tend to have?
bimodal age incidence.
20-29 year olds
Greater than 60 year olds
EBV is associated with what haematological condition?
Hodgkin’s lymphoma
A patient presents to you complaining of a fever that gets worse and then eases off over a period of one or two weeks. What clinical sign is this and what condition is it associated with? How can you treat it?
Pel-Ebstein fever (1-2week, cyclical)
Associated with Hodgkin’s lymphoma (can get it in other conditions but then it isn’t called Pel-Ebstein)
Treat it with NSAIDs or treat the underlying Hodgkin’s.
What effect might alcohol have on a patient with Hodgkin’s lymphoma?
Sudden development of pain in affected node after consuming alcohol.
Describe a fibrin ring granuloma and what conditions it may appear in.
A central lipid vacuole surrounded by a dense fibrin ring and epithelioid macrophages.
You might see it in Q Fever, Hodgkin’s lymphoma and infectious mononucleosis.
Over a game of jenga your friend asks you what cells are binucleated with prominent nucleoli and a CD30+, CD15+ immunophenotype? What condition are they associated with?
Reed-Sternberg Cells
Associated with Hodgkin’s lymphoma.
Describe the different components of the Ann Arbor staging classification.
Stage 1: involvement of a single lymph node region … or single extralymphatic site
Stage 2: involvement of two or more LN regions on the SAME SIDE of the diaphragm … or one LN region and a contiguous extralymphatic site
Stage 3: LN regions on both sides of the diaphragm.
Stage 4: disseminated involvement of one or more extralymphatic organs.
‘A’=lack of systemic symptoms
‘B’=presence of systemic symptoms
‘S’=splenic involvement
‘X’=bulky disease
What four agents are used in the treatment of Hodgkin’s lymphoma?
Adriamycin
Bleomycin
Vinblastine
Dacarbazine
What risks are associated with allogeneic stem cell transplant versus autologous?
Allogeneic: Graft versus Host Disease risk, opportunistic infections, infertility, secondary malignancies.
Patient with lymphoma, they drink alcohol, they don’t get pain. Do they have Hodgkin’s or non-Hodgkin’s?
Hodgkin’s
What is Richter’s transformation?
B-cell CLL and hairy cell leukaemias convert into a diffuse large B-cell lymphoma.
Mantle cell lymphoma is due to what chromosomal abnormality and what does this result in?
t(11:14) translocation … over-expression of cyclin D1
What organism is MALT lymphoma associated with?
H. Pylori
What happens in Sjogren’s syndrome?
WCC destruction of exocrine glands like salivary and lacrimal.
What are the three types of Burkitt’s lymphoma?
Endemic
Sporadic
Immuno-deficiency
What is sideroblastic anaemia?
BM produces ringed sideroblasts instead of healthy red cells.
Unable to incorporate iron into the haemoglobin.
What are the clinical features of Multiple Myeloma?
CRAB
Calcium high - thirst, moans, groans, stones, bones
Renal failure (plus amyloidosis and nephrotic syndrome)
Anaemia (+panytopenia)
Bones - pain, osteoporosis, osteolytic lesions, fractures
+hyperviscosity syndrome
The Durie-Salmon staging system is used in what condition?
Multiple Myeloma
The presence of Bence-Jones protein in the urine is indicative of what conditions?
Multiple Myeloma
Woldenstrom’s macroglobunlinaemia
What investigations do you want to perform in a multiple myeloma patient?
Serum electrophoresis - see a dense narrow band
Blood film - can see rouleaux
Urinalysis
Blood test - ESR will be high
What are the three management categories in multiple myeloma?
Supportive for CRAB symptoms
Chemotherapy combinations
Steroids (dex or pred)
Patients with monoclonal gammaglobinopathy of Unknown Significance are at increased risk of developing what condition?
Multiple Myeloma
What are the three features of smouldering myeloma?
Greater than 30 g/L paraprotein
Less than 10% plasma cells in BM
No CRAB symptoms
What antibody is attributed to Waldenstrom’s Macroglobulinaemia?
IgM
What stain is useful in diagnosing amyloidosis?
Congro-Red stain will appear apple-green under polarized light on microscopy.
In what patient population is Fanconi Anaemia more frequently found in?
Ashkenazi Jewish
Afrikaners in S.A.
What age does Fanconi Anaemia usually present at?
5-10 years
What are signs/symptoms of Fanconi Anaemia?
‘FANCONIS’
Facial microcephaly Abnormal testis n kidneys Neutropenia Cafe au lait Ocular abnormality No thumbs n radius Increased risk of AML Skin abnormality
What condition are people with Fanconi’s at greater risk of progressing to?
Acute Myelogenous Leukaemia
What triad of physical clinical features are characterisitic of Dyskeratosis Congenita?
Skin Pigementation
Nail dystrophy
Oral Leukoplakia
What type of inheritance pattern does Dyskeratosis Congenita have?
X-linked
What type of inheritance pattern does Schwachman-Diamond Syndrome have?
Autosomal recessive
What signs/symptoms does Schwachman-Diamond usually exhibit?
SCHwachman
Short stature
Cells of the blood (neutropenia)
Hepatic impairment
Pancreatic dysfunction
People with Schwachman-Diamond Syndrome are at greater risk of progressing to what condition?
Acute Myelogenous Leukaemia
When does Diamond-Blackfan Syndrome usually develop?
Neonatal/1year
What do you expect the MCV to be in Diamon-Blackfan?
Normal or micro
What signs/symptoms do you expect to see in Diamond-Blackfan Syndrome?
Craniofacial malformations
Thumb/upper limb abnormalities
Urogenital malformations
Cleft palate
The Philadelphia Chromosome is associated with what condition?
Chronic Myeloid Leukaemia (CML)
What are common symptoms of Polycythaemia Rubra Vera?
PRV
Pruritis
Ringing in ears
Visual blurriness
What is a Pseudo Polycythaemia?
Red cell mass is normal but plasma volume is reduced
What can cause a pseudopolycythaemia?
‘Fire’
Burns, Cigarette Smoking
‘Water’
Dehydration, vomiting, diarrhoea
What might you see on blood results in a patient with polycythaemia rubra vera? and in a secondary PRV?
Raised Hb
Raised hct
Raised platelets
Raised WCCs
secondary: only raised red cells
What happens to the bone in myelofibrosis?
Fibrosis of the bone marrow
Signs/Symptoms of myelofibrosis?
Hepatomegaly Splenomegaly Weight Loss Fever Bone Pain
What type of cells are in the bone marrow and what do they do in Essential Thrombocythaemia?
Megakaryocytes dominate in the BM. They produce a lot of platelets.
What are people with essential thrombocythaemia at increased risk of?
venous/arterial thrombosis
haemorrhages
Which Ig can cross the placenta?
IgG
At how many weeks do we usually administer antiD Ig to pregnant women?
28 and 34 weeks
What are some sensitising events during pregnancy that we should be aware of with regards to rhesus status?
Abortion Miscarriage Abdominal trauma External cephalic version amniocentesis
What are some acute (
FITATAT
Febrile non-haemolytic
Infection (bacterial)
Transfusion associated circulatory overload (TACO)
Allergic/anaphylaxis
Transfusion related Acute Lung Injury (TRALI)
Acute haemolytic
Transfusion associated dyspnoea (TAD)
What are some delayed (>24 hours) adverse reactions to blood transfusion?
Antibody formation Delayed haemolytic Infection (viral, malaria) TA-GvHD Post transfusion purpura
