Haematology Flashcards
1
Q
What happens in antiphospholipid syndrome?
A
APL antibodies against plasma proteins bound to phospholipids
Second event needed for syndrome to develop
Complement activation by APL
2
Q
Symptoms and signs of antiphospholipid syndrome?
A
Recurrent miscarriages
Arterial and venous thrombosis
Livedo reticularis - mottled reticulated vascular pattern
3
Q
Investigations for antiphospholipid syndrome?
A
- Anticardiolipin antibodies - ELISA
- Lupus anticoagulant assay
• Bloods - low platelets, high APTT
4
Q
What does aplastic anaemia involve?
A
Diminished haematopoietic precursors in bone marrow
Deficiency of all blood cell elements (pancytopaenia)
5
Q
Onset of aplastic anaemia?
A
Rapid-onset (days) or slow-onset (months)
6
Q
Investigations for aplastic anaemia?
A
- Bloods - pancytopaenia, normal MCV, ABSENT RETICULOCYTES
- Bone Marrow Trephine biopsy - HYPOCELLULAR (not abnormal)
• Check chromosomal breakage in lymphocytes for Fanconi’s anaemia
7
Q
What are the 2 forms of disseminated intravascular coagulation?
A
Acute overt form - bleeding/endothelial damage => explosive thrombin generation - depletion of platelets + clotting factors
Chronic non-overt form - same, but time for compensatory mechanisms => hypercoagulable states and thrombosis
8
Q
In whom does DIC usually occur?
A
- Gram-negative sepsis
- Obstetric - missed micarriage, pre-eclampsia etc.
- Malignancy
9
Q
Signs of acute and chronic DIC?
A
Acute
• Petechiae, purpura
• Epistaxis
• Oliguria - renal failure
Chronic
• Deep vein and arterial thrombosis or embolism
• Superficial venous thrombosis
10
Q
Investigations for DIC?
A
- Bloods - low platelets, low Hb, high APTT, LOW FIBRINOGEN, high D-dimer
- Peripheral blood film - schistocyctes
11
Q
What is haemolytic anaemia?
A
Shortened erythrocyte life span - premature breakdown (< 120 days)
12
Q
Most common inherited haemolytic anaemia in northern europe?
A
Hereditary spherocytosis
13
Q
Presentation of haemolytic anaemia (4)
A
- Jaundice
- Anaemia
- Haematuria
- Hepatosplenomegaly
14
Q
Investigations for haemolytic anaemia?
• Including what Direct Coomb’s test, osmotic fragility, Ham’s test is?
A
- FBC - high reticulocytes, high MCV, low haptoglobin
- Blood film - many abnormal cells
- Urine - high urobilinogen, haemosiderin
- Direct Coombs’ test - autoimmune
- Osmotic fragility/spectrin mutation - membrane abnormalities
- Ham’s test - lysis in paroxysmal nocturnal haemoglobinuria
15
Q
Which 2 disorders have similar characterisations of haemolysis and thrombocytopaenia?
A
Haemolytic uraemic syndrome and Thrombotic Thrombocytopaenic purpura
16
Q
What do HUS and TTP have in common and difference?
A
In common: triad
• Microangiopathic haemolytic anaemia (MAHA)
• Acute renal failure
• Thrombocytopaenia
TTP also has:
• Fever
• Fluctuating CNS signs
17
Q
What are the 2 forms of HUS?
A
D- = no prodromal illness
D+ = diarrhoea-associated form
18
Q
Outline cause of HUS?
A
- Endothelial injury
- Small vessel thrombosis
- Fibrinoid necrosis in glomerular-afferent arteriole (vulnerable)
- Renal ischaemia and acute renal failure
19
Q
Infective cause of HUS?
A
E. coli
20
Q
Who does D+ HUS and TTP mainly affect?
A
D+ HUS - young children
TTP - adult females
21
Q
Outline cause of TTP?
A
- Multimers of vWF clumping
* Deficiency of metalloprotease (ADAMST13) which normally cleaves this
22
Q
What is immune thrombocytic purpura (ITP)?
A
Syndrome characterised by immune destruction of platelets
23
Q
2 types of ITP and when are they seen?
A
- Acute - after viral infections in children
* Chronic - female adults
24
Q
Why should you do a blood film in ITP?
A
Excluse pseudothrombocytopaenia - platelets clumping together to give falsely low counts
25
Cause of haemophilia and the 3 types?
Inherited deficiency of clotting factor
A - most common, factor 8
B - factor 9
C - rare, factor 11
A+B X-linked recessive so mainly seen in males, C common in Ashkenazi Jews
26
Features of haemophilia?
Generally deep bleeds
• Haemarthroses
• Muscle haematomas
• Female carriers may be asymptomatic (X-linked recessive), but may bleed lots after trauma
27
Investigations for haemophilia?
* High APTT
| * Coagulation factor assays
28
Difference between ALL, AML, CLL, CML
ALL - proliferation of lymphoblasts (early lymphocytes)
AML - proliferation of myeloblasts (early innate cells)
CLL - proliferation of well-differentiated lymphocytes (almost always B cells)
CML - proliferation of granulocutes at different stages of differentiation (neutrophils, eosinophils, basophils) in bone marrow and blood
(Philadelphia chromosome)
29
Which cancer does CLL overlap with?
Non-hodgkin's lymphoma
30
Who gets ALL, AML, CLL, CML?
ALL - young children (second peak in elderly)
AML - most common acute leukaemia in adults, increases with age
CLL - > 50 yrs, males
CML - increases with age, males
31
Presentation of ALL, AML, CLL, CML?
ALL - anaemia, neutropaenia, thrombocytopaenia, bone pain, hepatosplenomegaly, testicular swelling
AML - anaemia, neutropaenia, thrombocytopaenia, bone pain, hepatosplenomegaly, gum hypertrophy
CLL - bleeding, infections, lymphadenopathy (autoimmune anaemia is a complication)
CML - splenomegaly, anaemia, sweating
32
Investigations for ALL, AML, CLL, CML?
ALL
• FBC - normochromic normocytic anaemia, high WCC
• Blood film - abdundant lymphoblasts
• Bone marrow aspirate - hypercellular
AML
• FBC - variable WCC
• Blood film - abdudant myeloblasts, Auer rods
• Bone marrow aspirate - hypercellular
CLL
• FBC - high lymphocytes, later autoimmune haemolysis
• Blood film - smudge/smear cells
• Bone marrow aspirate - lymphocytic replacement of normal marrow
CML
• FBC - high WCC, high myeloid cells
• Blood film - numerous granulocytic cells at different stages of differentiation
• Bone marrow aspirate - hypercellular
33
What is lymphoma and what is the difference between Hodgkin's and Non-Hodgkin's lymphoma?
Lymphoma - proliferation of lymphocytes in lymph nodes
Hodgkin's - histopathological presence of Reed-Sternberg cells (binucleate lymphocytes - usually B)
Non-Hodgkin's - diverse group, mostly diffuse large B-cell lymphoma
34
Cause and incidence of H and N-H lymphoma?
H - unknown cause (EBV genome?), peak in 20s and over 50, males
N-H - immunodeficiency, introduction of foreign genes by oncogenic viruses e.g. EBV,
35
Presentation of H and N-H lymphoma?
```
H
• Enlarged, non-tender, rubbery superficial lymph nodes
• Painful after alcohol
• Continuous spread
• Node size fluctuates
• Hepatosplenomegaly
• Pel-Ebstein fever (cyclical)
```
N-H
• Enlarged, non-tender, rubbery superficial lymph nodes
• Non-continuous spread
• Mass on jaw (Burkitt's)
• Extranodal disease (1) Gastric (2) skin e.g. mycosis fungoides
36
Diagnostic, staging and prognostic investigations for lymphoma?
* Diagnostic - excisional node biopsy
* Staging - CT chest, abdo, pelvis, Ann-Arbor system
* Prognostic - ESR, LDH (cell turnover)
37
What is multiple myeloma?
Malignancy characterised by proliferation of plasma cells
• Characterised by bone lesions
• Production of monoclonal immunoglobulins (usually IgG or IgA) causing dysfunction in many organs
38
Who is usally affected by multiple myeloma?
* 70yrs
| * Afro-Caribbean > White > Asians
39
Presentation of multiple myeloma?
```
CRABBI
• Calcium- hypercalcaemia
• Renal damage - dehydration
• Anaemia
• Bleeding - thrombocytopaenia
• Bone pain (especially back) - infiltration and increased osteoclast activity, lytic lesions and increased risk of fragility fractures
• Infection
```
40
Investigation for multiple myeloma?
* Bloods - normochromic normocytic anaemia and thrombocytopaenia, raised urea and creatinine, raised calcium
* Blood film - rouleaux formation with bluish background (high protein)
* BENCE-JONES PROTEIN in urine
* Bone marrow aspiration and trephine biopsy - diagnostic
41
Most common form of anaemia worldwide?
Iron deficiency anaemia
42
Causes of microcytic, normocytic and macrocytic anaemia?
```
Microcytic
• Iron deficiency
• ACD
• Thalassaemia
• Sideroblastic anaemia (haem synthesis abnormality)
• Lead poisoning
```
```
Normocytic
• Decreased production (ACD, aplastic)
• Sickle cell
• Haemolysis
• Uncompensated increase in plasma volume e.g. pregnancy
• Vitamin B2 and 6 deficiency
```
```
Macrocytic
Megaloblastic:
• Vitamin B12 or folate deficiency (problem with DNA synthesis)
• Drugs
Non-megaloblastic:
• Alcohol excess
• Liver disease
• Multiple myeloma
• Hypothyroidism
• Haemolysis - left shift
```
43
Investigations for microcytic and macrocytic (megaloblastic) anaemia?
```
Microcytic
• Anisocytosis
• Poikilocytosis
• Lead - basophilic stippling
• Hb electrophoresis for thalassaemia
```
Macrocytic megaloblastic
• Pancytopaenia
• Hypersegmented neutrophil nuclei
44
What is myelodysplasia?
Series of haematological conditions characterised by chronic cytopaenia:
• anaemia
• neutropaenia
• thrombocytopaenia
and abnormal cellular maturation
45
Cause of myelodysplasia? (3)
* Primary - intrinsic bone marrow problem
* Chemotherapy or radiotherapy
* Chromosomal abnormalities
46
Signs of myelodysplasia?
* Cytopaenia
* Gum hypertrophy
* Lymphadenopathy
* NO splenomegaly (except CML)
47
What can myelodysplasia progress to?
AML
48
What is myelofibrosis?
* Progressive bone marrow fibrosis
| * Extramedullary haematopoiesis and splenomegaly
49
What happens in myelofibrosis?
* Increased number of abnormal megakaryocytes
* Stromal proliferation
* Release cytokines that stimulate fibroblast proliferation and collagen deposition in bone marrow
50
What do 30% of patients with myelofibrosis have a history of?
Polycythaemia rubra vera or essential thrombocythaemia (overproduction of platelets by bone marrow)
51
What is seen on blood film, bone marrow aspirate and biopsy of myelofibrosis?
* Blood film - poikilocyte 'tear drop' red cells
* Bone marrow aspirate - usually unsuccessful due to fibrosis
* Biopsy - fibrotic hypercellular marrow, with dense reticulin fibres on silver staining
52
What is polycythaemia and what 2 groups can it be classified into?
Increase in [Hb] above normal for person's age and sex
• Absolute (true) : rubra vera or secondary - increased red cell mass
• Relative - normal red cell mass, low plasma volume
53
What causes polycythaemia rubra vera?
Clonal proliferation of myeloid cells - mutations in JAK2 tyrosine kinase involved
54
What causes secondary polycythaemia?
Appropriate increase in erythropoietin
• Chronic hypoxia
Inappropriate increase in erythropoietin
• Renal
• Hepatocellular carcinoma
• Erythropoietin abuse by athletes
55
What can cause relative polycythaemia?
* Dehydration
| * Gaisbock's syndrome - young male smokers with HTN
56
Symptoms and signs of polycythaemia?
* Pruritis after hot bath
* Headaches
* Gout
* DVT, stroke, dizziness
* Choreiform movements
* Splenomegaly
* Scratch marks from itching
* Plethoric complextion (red, ruddy)
* Conjunctival suffusion (redness)
57
Investigations for polycythaemia (including rubra vera vs secondary)?
Needed for diagnosis
• FBC - high Hb, high Hct, low MCV
Isotope dilution techniques
• Confirmation of plasma volume and red cell mass (absolute vs relative)
Rubra vera
• Low serum EPO
• JAK2 mutation
• Biopsy - erythroid hyperplasia and raised megakaryocytes
Secondary
• High serum EPO
58
Sickle cell disease is a chronic condition with sickling of red blood cells caused by inheritance of...
haemoglobin S
59
What is the difference between sickle cell anaemia, trait and disease in terms of genes?
* Anaemia - homozygous HbS
* Trait - carriers (heterozygous) HbS
* Disease - heterozygous for HbS and HbC/beta-thalassaemia
60
How does the abnormal formation of haemoglobin S occur?
Autosomal recessive
Point mutation in beta-globin gene - substitution of glutamic acid by valine in position 6
(deoxygenation of HbS causes sickling)
61
What 4 factors precipitate sickling?
* Infection
* Dehydration
* Hypoxia
* Acidosis
62
Symptoms of sickle cell?
Symptoms secondary to vaso-occlusion
• Splenic atrophy or infarction (autosplenectomy) - increased risk of infection with encapsulated organisms
• Abdo pain
• Dactylitis in children, painful ribs/spine/pelvis/long bones in adults
• Proliferative retinopathy
• Breathlessness
• Painful erection (priapism)
63
Signs of sickle cell?
* Joint or muscle tenderness due to avascular necrosis
* Short digits due to infarction in small bones
* Cotton wool spots
* Splenomegaly
* Anaemia signs
64
Investigations for sickle cell?
* Bloods - low Hb, high reticulocytes (haemolytic crises), low reticulocytes (aplastic crises)
* Blood film - sickle cells, target cells, Howell-Jolly bodies
* Sickle solubility test - increased turbidity (doesn't distinguish between AS and SS)
* DIAGNOSTIC - ELECTROPHORESIS (confirms HbSS)
65
What is an aplastic and sequestration crisis?
Aplastic crisis - sudden reduction in marrow production due to parvovirus B19
Sequestration crisis - pooling of blood in spleen (and liver, lungs, corpora cavernosa). Mainly affects children as spleen becomes atrophic in adults.
66
Crisis management of sickle cell?
* Analgesia (IV opiates)
* Rehydrate
* Oxygen
* Antibiotics if infection
* Blood transfusion
67
Long-term sickle cell management?
* Hydroxyurea - increases HbF, prevents painful episodes
* Pneumococcal polysaccharide vaccine every 5 years
(folic acid, repeated red cell transfusions, advice, bone marrow transplant)
68
What happens in thalassaemia?
* Underproduction or no production of one globin chain
| * Unmatched globins precipitate, damaging RBC membranes - haemolysis in bone marrow
69
Outline the 3 types of beta thalassaemia
* Trait/minor - heterozygous
* Intermedia - mild homozygous, or heterozygous with another haemoglobinopathy e.g. HbC
* Major - homozygous, little or no beta-chain synthesis
70
Presentation of 3 types of beta thalassaemia?
* Trait/minor - asymptomatic, may be mild anaemia, may worsen in pregnancy
* Intermedia - moderate anaemia, may be splenomegaly
* Major - presents within first year, mild jaundice, frontal bossing, 'hair on end' sign on skull x-ray due to increased marrow activity
71
Investigations for thalassaemia?
* FBC - microcytic anaemia
* Blood film - hypochromic, target cells, nucleated red cells, high reticulocytes
* Hb electrophoresis - absent or reduced HbA, high HbF
* Bone marrow - hypercellular
* Skull X-ray - hair on end in major
72
What is the main characterisation of von Willebrand disease?
Mucocutaenous bleeding (mouth, epistaxis, menorrhagia)
73
Outline the 3 types of vWD
Type 1 - not enough vWF (but it works well)
Type 2 - abnormal vWF (but there is enough)
Type 3 - no vWF
74
Investigations for vWD?
* Prolonged bleeding time but platelets are normal
* Prolonged APTT
* Reduced Factor VIII
* Defective platelet aggregation with ristocetin
75
Difference between warm and cold autoimmune haemolytic anaemia?
Warm
• IgG
• Extravascular haemolysis
• Can be caused by drugs
```
Cold
• IgM
• Intravascular haemolysis
• Mediated by complement
• Can be caused by infections
```
