Haematology Flashcards
1
Q
Causes of macrocytic anaemia
A
Aplastic anaemia Myelodysplastic syndrome Acute leukaemia (>20% blast cells) Megaloblastic anaemia - Vit B12 deficiency - Folate deficiency Chronic liver disease Drugs Hypothyroidism
2
Q
Causes of aplastic anaemia
A
Idiopathic Cytotoxic drugs and radiation (cancer treatment) Drug reaction: - anticonvulsants - antibiotics - NSAIDs - Anti-thyroids - Gold Toxins Viral (EBV, HIV) Immune disorders (SLE, graft v host) Miscellaneous - Pregnancy - anorexia nervosa - paroxysmal nocturnal haemoglobinuria
3
Q
Diagnostic criteria for aplastic anaemia
A
Hypocellular bone marrow with no abnormal cells or fibrosis \+ 2 of the following: - Hb below 100 - PLT below 50 - ANC below 1.5
4
Q
Risks of blood transfusion
A
High-moderate (1/100-1000): urticaria, fluid overload, cardiac failure
Low (1/1000-100,000): delayed haemolysis, TRALI, non-fatal acute haemolytic reaction (e.g. wrong blood)
Rare (less than 1/100000): fatal acute haemolytic reaciton, sepsis, HIV, Hep C, HTLV, malaria, syphilis
5
Q
What is aplastic anaemia
A
Failure of bone marrow to produce enough blood cells due to reduced haematopoietic precursors due to replacement of stem cells in the marrow with fat. Leads to pancytopaenia
6
Q
Causes of normocytic anaemia
A
Chronic inflammatory disease Endocrine: - Hypopituitarism - Hypothyroidism - Hypoadrenalism Aplastic anaemia Haemolytic anaemia Acute blood loss
7
Q
What is myelodysplastic syndrome
A
Group of haematopoietic disorders characterised by a hyper- or hypocellular marrow with impaired morphology and maturation + peripheral blood cytopaenias due to imeffective haematopoiesis - may involve all 3 lineages in myeloid haematopoiesis (RBC, PLT, PMN)
Blast cell count less than 20%
8
Q
Presentation of myelodysplastic syndrome
A
B symptoms: weight loss, malaise Anaemia symptoms Thrombocytopaenia symptoms Neutropaenia symptoms Symptoms of marrow failure (hyperviscosity - clots, bone pain, organ/skin infiltration, gout)
9
Q
CBE and marrow results in myelodysplastic syndrome
A
Peripheral cytopaenias, increased MCV, dimorphic RBCs, oval shaped RBCs, hypersegmented nuclei of PMNs, hypogranular PLT
Marrow: hypercellular (usually) with dyserythropoiesis
10
Q
Management of myelodysplastic sydnrome
A
Supportive: treat infections, transfuse PLT or RBC as needed, recombinant EPO
Cytotoxic chemo in patients with increasing myeloblasts or progression to AML
11
Q
What is polycythaemia vera
A
It is the most common chronic myeloproliferative disorder (though still rare) characterised by predominantly raised RBCs, in addition to increased production of platelets and neutrophils.
12
Q
Prognosis and complications of polycythaemia rubra vera
A
Untreated: 6-18m survival Treated: >10y Shorter life span than general public Complications: - thrombosis - haematological malignancy (AML, MDS) - non-haem malignancy - haemorrhage - post-PV myelofibrosis
13
Q
Presentation of polycythaemia vera
A
Hyperviscosity: headache, dizziness, vertigo/tinnitus, vision disturbances, angina, intermittent claudication, major thrombotic events
H2/Cytokine prodn: peptic ulcer - abdo pain, aquagenic pruritus (40%)
Erythromelalgia (burning hands/feet + erythema/pallor/cyanosis c palpable pulses)
Early satiety (splenomegaly)
Weight loss/malaise
14
Q
Clinical findings of polycythaemia vera
A
Hepatomegaly Splenomegaly Facial plethora Hypertension Arthritis and gouty tophi
15
Q
Genetic mutation associated with polycythaemia rubra vera
A
JAK2
16
Q
Criteria for diagnosis of polycythaemia vera
A
All of CA OR CA1+CA2+2 of CB: Criteria A: 1. Raised total RBC mass 2. Arterial O2 >92% (not secondary to hypoxia) 3. Splenomegaly
Criteria B:
- thrombocytosis
- leukocytosis
- raised ALP
- raised Vit B
17
Q
History of lymphoma
A
LN enlargement - most commonly cervical nodes B symptoms (night sweats, malaise, weight loss) Systemic sx (pruritus, fatigue, anorexia, alcohol-induced pain at site of node) Involvement of other organs - cough/SOB, PUD/abdo pain
18
Q
Most common lymphomas
A
Hodgkin 3/100,000, NHL 15/100,000
HL: nodular sclerosing (70%), mixed cellularity (15%), lymphocyte-rich (5%)
NHL: 85% are B cell, 15% T-cell
DLBCL (30%), Follicular (20%), Marginal Zone [MALT] (5-10%), Mantle Cell (5%), Burkitt Cell (1-2%)
19
Q
Histological marker of Hodgkin’s lymphoma (vs NHL)
A
Reed-Sternberg cells (“Owl-eyes” - 2 mirror image large nuclei with eosinophilic nucleolus)
20
Q
What is Waldeyer’s ring
A
Pharyngeal/tonsillar lymphoid ring
21
Q
International prognostic index for Non-hodgkins Lymphoma
A
Age >60 Stage III or IV disease Raised Serum LDH ECOG status >1 extranodal site (FLIPI [follicular]: +Hb level) (MIPI [mantle cell]: + WCC)
22
Q
Red flags of CLL - need to refer to haem urgently
5
A
- Rapidly rising WCC
- Rapidly progressing lymphadenopathy or splenomegaly
- Progressive anaemia or thrombocytopaenia
- Recurrent life-threatening sepsis
- Worsening constitutional symtpoms
23
Q
What is the inheritance pattern of Glucose-6-phosphate dehydrogenase deficiency (G6PD)
A
X-linked
24
Q
What is the role of glucose-6-phosphate dehydrogenase
A
Reduces NAPD to NAPDH which protects the cell from oxidative damage. Particularly effects RBCs because they lack other enzymes to produce NAPDH
25
What are Howell-Jolly bodies, how do you recognise them and what is the cause?
Remnants of the RBC nucleus. Dark round dots in the RBC cytoplasm visible without any staining. Caused by reduced splenic function
26
What are Heinz bodies, how do you recognise them and what is the cause?
Accumulations of denatured globin chains within the RBC, can be seen only on staining with Cresyl blue (used for reticulocyte counting)
Caused by oxidative stress, e.g. G6PD deficiency
27
Diagnostic criteria for multiple myeloma
```
CRAB
Calcium raised
Renal insufficiency (raised creatinine)
Anaemia
Bone lesions/osteoporosis
```
28
Classic triad of multiple myeloma
Marrow plasmacytosis
Lytic bone lesions
Serum/urine M component
29
Aims for treatment in polycythemia rubra vera
PCV below 45%
| Hb below 140
30
Cell markers for T cells
T helper cells: CD4
| Cytotoxic T cells: CD8
31
What is produced by Th1 cells?
IL2 and gamma IFN
32
What is produced by Th2 cells
IL4, 5, and 10
33
Cause of pernicious anaemia
Autoimmune Disease
Anti-intrinsic factor antibodies
and
Anti parietal cell antibodies
34
Definition of sideroblastic anaemia
A group of inherited or acquired anaemias caused by dysfunctional metabolism of iron by the mitochondria in erythroblasts
35
Inheritance pattern of familial sideroblastic anaemia
X-linked
36
Causes for acquired sideroblastic anaemia
```
Myelodysplasia
Myeloprolferative disorders
Myeloid leukaemias
Drugs (e.g. isoniazid)
Alcohol abuse
Lead
RA
Carcinoma
```
37
Sideroblastic anaemia on blood film
Excess ring sideroblasts (ring of iron granules around nucleus due to accumulation of iron in cell)
38
Definition of sickle cell anaemia
A haemolytic anaemia caused by disorder of haemoglobin resulting from a single-base mutation: deoxygenated HbS is insoluble, thus inflexible cells - irreversible sickling due to dehydration = reduced red cell survival
39
Clinical features of sickle cell anaemia
HbS releases O2 more readily to tissues, thus patients feel well despite being anaemic
```
Vaso-occlusive crises:
- dactylitis (child)
- acute pain in hands and feet
- attacks of severe bone pain (e.g. AVN)
Haemolytic anaemia
- usually stable in 60-80 range
```
40
Cause of vaso-occlusive complications in sickle cell anaemia
Insoluble, rigid cells - impaired passage through microcirculation - obstruction of small vessels - tissue infarction
41
Long term complications of sickle cell anaemia
```
Reduced growth and development
- low weight and height in childhood
- regain height by adulthood
- delayed sexual maturation
Bones:
- AVN
- compression of vertebrae
- shortening of bones
- osteomyelitis
Infections (esp. bones, lung, kidney)
Resp
- pulm HTN
- Acute chest syndrome
Leg ulcers
Cardiac
- cardiomegaly
- arrhythmias
- iron overload cardiomyopathy
- MI
Neuro:
- TIA, CVA
- seizures
- cerebral haemorrhage
Cholelithiasis
Chronic hepatomegaly and liver dysfn
Chronic tubule-interstitial nephritis
Priapism
Retinopathy
Pregnancy issues
- abortion
- IUGR
- PET
- IUFD
```
42
Diagnosis of sickle cell aneamia
High reticulocyte count
Sickle cells on blood film
Hb electrophoresis: No HbA, 80-95%HbS, 2-20% HbF
Electrophoresis required for diagnosis
43
Management of sickle cell anaemia
Hydroxyurea (increases HbF concentrations)
Inhaled NO (red. platelet function, vascular adhesion of RBCs, inc. vasodilation)
Blood transfusions (only if symptomatic e.g. CHF, TIA, aplastic crises)
Bone marrow transplantation (children under 16 with severe complications e.g. CVA, recurrent chest syndrome)
44
Definition of anaemia of chronic disease
Anaemia caused by the insufficient release of iron from bone marrow cells to developing erythrocytes in the context of chronic inflammation
45
Pathophysiology of anaemia of chronic disease
High levels of hepcidin expression during chronic inflammation - destroys ferroportin - reduced iron efflux from exporting tissues into plasma - reduced iron mobilisation and absorption from gut
reduced release of iron from BM to developing RBCs
46
Biochemical investigations in anaemia of chronic disease
MCV: low normal, normal or low
Iron studies: low serum Fe, reduced total iron binding capacity, normal or increased ferritin
Bone marrow biopsy: stainable iron, iron not seen in developing erythroblasts
47
Management of anaemia of chronic disease
```
Symptomatic
Recombinant EPO (in setting of renal disease, sometimes in setting of inflammatory disease e.g. RA, IBD)
```
48
Definition of megaloblastic anaemia
A macrocytic anaemia resulting from inhibition of DNA synthesis during erythropoiesis
49
Causes of megaloblastic anaemia
VitB12 deficiency:
- vegans
- stomach pathology
- small bowel pathology
- abnormal utilisation (NO)
Folic acid deficiency
- nutritional (e.g. alcohol abuse, GI disease)
- Antifolate drugs (AEDs, MTX)
Excess utilisation
- Physiological (pregnancy, lactation, prematurity)
- Pathological (malignancy, inflammatory disease, haemodialysis, haematologic disease)
- Malabsorption
Congenital enzyme deficiencies in DNA synthesis
Drugs interfering with DNA synthesis (hydroxyurea)
50
Peripheral blood smear in megaloblastic anaemia
Megaloblasts (large oval cells with large immature nuclei, chromatin finely dispersed and opened stippled appearance)
Polymorphs (hypersegmented 6+ lobes)
Giant metamyelocytes (2x normal size of cells, twisted nuclei)
51
Management of megaloblastic anaemia
Transfusion not indicated
B12def:
- oral vit B12 2mg/day
- expect clinical improvement within 48h
- reticulocytosis starting after 2-3 days
- improvement of polyneuropathy over 6-12m
Folate def:
- 5mg folic acid/day
52
markers of haemolysis
```
Inc red cell production:
- reticulocytosis
- erythroid hyperplasia of marrow
Inc. red cell breakdown:
- inc. LDH
- inc. urobilinogen
- inc. plasma Hb
- Haemosiderinuria
- red. haptoglobulins
- +ve Schumm's test (methaemalbumin)
- inc K+
```
53
Definition and types of myeloproliferative neoplasms
A group of disorders characterised by cellular proliferation of 1 or more haematologic cell lines in the peripheral blood, distinct from acute leukaemia
Polycythaemia vera
Essential thrombocythaemia
Primary myelofibrosis
Chronic myelogenous leukaemia
54
Causes of secondary polycythaemia vera
EPO-ing
COPD/chronic hypoxic lung disease
high altitude`
55
Management of polycythaemia vera
Phlebotomy
Maintenance therapy with myelosuppressive agents
- hydroxyurea, IFN a or anagrelide
- ruxolitinib (JAK1/2 inhibitor)
Prevent complications:
- daily aspirin
- allopurinol if hyperuricaemia becomes symptomatic
56
Definition of essential thrombocytosis
A clonal disorder of unknown aetiology involving a multi-potent haematopietic progenitor cell manifested clinically by overproduction of platelets without a definable cause
57
Mutations associated with essentical thrombocytosis
JAK2 (signalling proteins in cell)
MPL (receptor protein)
Increase activity of TPO
58
Clinical features of essential thrombocytosis
Most often incidental finding of raised PLT on routine CBE
Haemorrhagic tendencies:
- easy bruising
Thrombotic tendencies:
- microvascular occlusions - erythromelalgia, occular migraine, TIAs
Mild splenomegaly on physical examination
59
Bone marrow findings in essential thrombocytosis
Hypercellular marrow
Megakaryocyte hyperplasia and hypertrophy
Normal marrow reticulin - if increased, consider another diagnosis
60
Complications of essential thrombocytosis
Intravascular stasis and thrombosis
| Haemorrhage secondary to acquired Von Willebrand deficiency
61
Management of essential thrombocytosis
Patient-based, not PLT-based
Migraine-related symptoms only respond to lowering PLT
Erythromelalgia responds to COX-1 inhibitors (aspirin, ibuprofen)
No therapy required in asymptomatic patient without CVS risk factors
Platelet reduction due to refractory symptoms on salicylates:
- IFNa
- Anagrelide
- Hydroxyurea
Evolution to leukaemia is more likely to occur due to management (hydroxurea) than from the disease itself
62
Definition of primary myelofibrosis
Clonal disorder of a multipotent haematopoietic progenitor cell characterised by marrox fibrosis, extramedullary haematopoiesis and splenomegaly
63
Clinical features of primary myelofibrosis
Often asymptomatic, incidental discovery of splenomegaly or abnormal CBE
```
Night sweats
Fatigue
Weight loss
Splenomegaly
+/- hepatomegaly
No lymphadenopaty
depending on degree of extremedullary haematopoiesis:
- ascites
- intracranial HTN
- intestinal or ureteral obstruction
- pericardial tamponade
- spinal cord compression
- skin nodules
```
64
Peripheral blood film and biochem in myelofibrosis
Features of extramedullary haematopoiesis:
- teardrop-shaped RBCs
- nucleated RBCs, myelocytes and promyelocytes
+/- myeloblasts
Inc. LD
Inc. ALP
Bone marrow usually inaspirable due to fibrosis
65
Management of myelofibrosis
No specific treatment
Allogenic bone marrow transplant is only curative treatment (consider in younger patients)
Splenectomy may be necessary if impairs feeding
Allopurinol to control hyperuricaemia
Hydroxyurea to control organomegaly
Glucocorticoids to control constitutional symptoms and AI complications
Transfusion for severe anaemia
66
Complications of myelofibrosis
Increasing marrow failure
Shorter survival than patients with PV or ET
10% spontaneously transform to aggressive acute leukaemia
67
Definition of CML
A myeloproliferative disease characterised by infiltration of the blood, bone marrow, and other tissues by neoplastic cells of granulocytic cell line
68
Epidemiology of CML
20% of all adult leukaemias
85% diagnosed in chronic phase
Middle aged individuals (45-55y)
5 year survival 90% with imatinib
69
Mutation associated with good prognosis in CML
Philadelphia chromosome
| BCR-ABL1 relocation mutation from long arm of 22 to chromosome 9
70
Phases of CML
1. Chronic:
- insidious onset
- fatigue, malaise, anorexia, weight loss
- symptoms of anaemia
- symptoms of splenomegaly (early satiety, LUQ pain or mass)
- vasoocclusive disease
2. Accelerated and 3. Blastic:
- unexplained fever
- sig. weight loss
- bone and joint pain
- bleeding
- thrombosis
- infections
Splenomegaly
Hepatomegaly
Lymphadenopathy a poor prognostic indicator in late disease
71
Confirming CML
CBE: inc. WCC, inc. PLT, normocytic normochromic anaemia, low leukocyte alkaline phosphatase
Film: circulating immature cells
Biopsy: hypercellular, inc Myeloid:erythroid ratio
Chromosomal studies: philadelphia chromosome (FISH)
72
Management of CML
IMATINIB 400mg daily
- competitive inhibition at ATP-binding site of Abl-knase - inhibits tyrosine phosphorylation of proteins involved in BCR-Abl signal transduction - prevents activation of downstream pathway in cellular proliferation
S/E: fluid retention, nausea, muscle cramps, diarrhoea, skin rashes, myelosuppression
```
Second line (in addition to imatinib)
- Allo-HSCT
- nilotinib, dasatinib
Chemotherapy
- reserved for rapid lowering of WCC initially
- hydroxyurea
```
73
definition of AML
A rapidly progressing excess of myelocytes in the blood due to an uncontrolled proliferation of leukaemic stem cells in the bone marrow. It is characterised by an excess of immature precursor cells in both the blood and the bone marrow
74
Epidemiology of AML
most common in infants less than 1y and people over 60y
Untreated survival is less than 3m
Accounts for 70% of acute luekaemias
3/100,000
75
What is a granulocytic sarcoma
AML as a discrete lump
Biopsy reveals many blastic neutrophils
Leukaemic cells are not in circulation, but accumulated in specific sites
Same treatment as for AML
76
Clinical features of AML
```
Bone marrow failure:
- anaemia
- neutropenia (infection)
- thrombocytopaenia (haemorrhage)
Increased WCC:
- hyperviscosity
- organ infiltration
- bone pain
- gout/hyperuricaemia
Constitutional symptoms
DIC
gum infiltration
```
77
Peripheral blood smear in AML
```
Granules
Auer rods (linear red composigion of crystallised granules)
```
78
APML blood smear
Multitude/bundle of auer rods (faggot bundles
79
APML
Type of AML with high cure rates BUT high mortality in early stages - must treat very early
Associated with significant DIC
80
CLL staging
Rai Staging system:
0: low risk - lymphocytosis ONLY
1: intermediate risk: lymphocytosis + lymphadenopathy
2: intermediate risk: lymphocytosis + hepatomegaly or splenomegaly
3: high risk: lymphocytosis + anaemia, normal platelets
4. High risk: lymphocytosis + thrombocytopaenia
Binet staging:
According to number of lymphoid tissues involved
A: less than 3 areas of enlarged lymphoid tissue
B: 3 or more areas of enlarged lymphoid tissue
C: Patients with anaemia or thrombocytopaenia regardless of lymphadenopathy
81
Definition of lymphoma
Abnormal proliferation of the lymphoid system, occurring at any site where lymphoid tissue is found, classified as Hodgkin's or non-Hodgkin's based on histological appearance
82
Epidemiology of Hodgkin's lymphoma
Peak incidence in 20s
Male:female almost equal
3/100,000
83
Prognostic factors for Hodgkin's lymphoma
Hasenclever score: based on
- serum albumin
- Hb
- age
- sex
- stage
- leukocytosis
- lymphopaenia
84
Diagnostic investigations in multiple myeloma
```
Urinalysis
-high protein, little albumin
- urinary light chains
- Bence jones proteins (light chains/paraproteins)
Biochemistry:
- reduced anion gap
- high Ca
- inc. BUN
- inc. Cr
- inc. uric acid
SERUM PROTEIN ELECTROPHORESIS: IgG, paraproteins
CBE: normocytic anaemia
Marrow biopsy: Plasmacytosis (over 10%)
Chest and bone XR: lytic lesions, diffuse osteopaenia
Immunoelectrophoresis: M spikes
Serum beta crosslaps: marker of bone breakdown (target in therapy less than 400)
```
85
Management of multiple myeloma
Initial management:
- manage anaemia (t/f), renal failure (hydrate, dialysis), infections (ABx)
- bony lesions: analgesia, radiation, vertebroplasty, bisphosphonates
Autologous stem cell transplant
High dose CTx
86
Definition of hereditary haemochromatosis
An inherited disorder of iron metabolism, most commonly due to a mutation in the HFE gene
87
Clinical features of haemochromatosis
```
Mostly asymptomatic
Nonspecific symptoms:
- weakness
- fatigue
- lethargy
- weight loss
Specific, organ related:
- abdominal pain
- arthralgias
- chronic liver disease stigmata
```
88
Complications of haemochromatosis
Deposition in a number of different organs:
- Liver: cirrhosis, HCC
- Heart: CHF, cardiac arrhythmias
- Endocrine: hypogonadism, DM, thyroid dysfunction
- Joints: arthroplasty
89
Laboratory findings in disseminated intravascular coagulation
```
Thrombocytopaenia
Prolonged PT, APTT and TT
Increased fibrin degradation products
Reduced fibrinogen level
Fragmented RBCs
```
90
serotonin release assay is testing for
heparin induced thrombocytopaenia
