Haematology Flashcards
(116 cards)
1
Q
What is Microcytic anaemia
A
This is anaemia associated with an MCV of <80fL
2
Q
What are the causes of a Microcytic anaemia
A
Iron deficiency - Most common
- Blood loss - e.g. GI
- Reduced absorption - Small bowel disease
- Increased demands - Growth, pregnancy
- Reduced intake - Vegans
Anaemia of chronic disease - Microcytic anaemia associated with chronic disease
Thalassemia
Sideroblastic anaemia - Abnormality of haem synthesis
Lead poisoning
3
Q
What are the signs and symptoms of a Microcytic anaemia
A
Asymptomatic
Fatigue
Faitness
Dyspnoea
Angina pectoris, intermittent claudication if coexistent arterial disease
Pale skin Pale mucous membranes Tachycardia Koilonychia (Spoon shaped) Cardiac failure Glossitis Angular stomatitis
4
Q
How is Iron deficiency anaemia diagnosed
A
FBC: Low Hb, Low MCV
Serum iron: Low
Ferritin: Low
Transferrin: High
Transferring saturation: Low
Blood film:
- Microcytic
- Hypochromic
- Anisocytosis (variations in size) - Poikilocytosis (variations in shape)
Cause: OGD + Colonoscopy if: - Male - Post-menopausal women - Women with minimal menstrual loss
IgA-TTG - For coeliac (Malabsorption)
5
Q
How is Iron deficiency anaemia treated
A
Treat underlying causes
Oral iron supplements
IM/IV iron if intolerant or poorly responsive to oral iron
6
Q
What are causes of Anaemia of chronic disease
A
Chronic inflammatory disease - RA
Chronic infection - TB
Chronic malignancy
Due to cytokine release:
- Blocking erythropoietin production
- Blocking iron flow out of cells
- Increasing iron stores intracellularly
- Increasing red cell turnover
7
Q
How is Anaemia of chronic disease diagnosed
A
CRP/ESR - Raised
FBC - Low Hb, Low or Normal MCV
Iron studies: Serum iron: Low Ferritin: High or Normal (Acute phase protein) Transferrin: Normal or Low Transferrin saturation: Normal
8
Q
Outline Sideroblastic anaemia
A
This is a microcytic anaemia due to a problem with them synthesis
The blood film will be dimorphic and show hypochromic microcytic cells and there will be ring sideroblasts in the bone marrow
To manage it one would five Pyridoxine if it is an inherited form and if all else fails blood transfusions with chelation should be considered
9
Q
Outline Lead poisoning
A
Lead poisoning will lead to:
Anorexia, N+V, Abdominal pain, constipation and peripheral nerve lesions
Signs: Blue gumline Peripheral verne lesions (Wrist or foot drop) Encephalopathy Convulsions Reduced consciousness
Finding:
Basophilic stippling
Management:
Dimercaprol
D-penicillinamine
10
Q
What is Thalassemia
A
A group of genetic disorders characterised by reduced global chain synthesis - Autosomal recessive
5% of the world thought to be carriers - Greek, Turkish, Cypriot, South East Asain and Chinese
11
Q
What are the 2 different types of Thalassemia
A
Alpha-Thalassemia - Reduced synthesis of alpha chain
Beta-Thalassemia - Reduced synthesis of beta chain
12
Q
Outline the different types of Alpha-thalassemia
A
The are 4 alpha-globin genes on the chromosome
4 deletions = Haemoglobin Barts Hydrops Fetalis (interuterine death)
3 deletions = Haemoglobin H
- Microcytic Hypochromic anaemia
- Target cells and Heinz bodies.
- Hepatosplenomegaly - Lifelong transfusions
2 deletions = Alpha 0 thalassemia
- Microcytic Hypochromic RBCs - No anaemia
1 deletion = Alpha+ thalassemia
- Microcytic Hypochromic RBCs - No anaemia
13
Q
Outline the different types of Beta-thalassemia
A
Major (Homozygous)
- Presents at 2-3 months with profound anaemia failure to thrive and recurrent infections.
- Bony abnormalities due to bone marrow hypertrophy
- Extramedullary hematopoiesis causes hepatosplenomegaly
Intermedia (Homozygous beta and alpha thalassemias)
- Moderate anaemia that doesn’t require transfusion.
- Splenomegaly
- Gallstones
- Bone deformities
- Recurrent leg ulcers
Minor/Trait (Heterozygous)
- Asymptomatic carrier
- Mild or absent anaemia can be confused with IDA
14
Q
What are signs and symptoms of Thalassemia
A
Beta - Anaemia, presenting in first few months of life. Failure to thrive. Prone to infection
Beta thalassemia major/Intermedia Pallor Malaise Dyspnoea Mild jaundice Frontal bossin Thalassaemia facies Hepatosplenomegaly
15
Q
What are the investigative findings in Thalassemia
A
FBC - Low Hb, MCV, MCH
Iron studies:
All normal
Blood film:
- Hypochromic microcytic anaemia
- Target cells
- Nucleated red cells
- Reticulocytosis
Hb electrophoresis: - Alpha: Low or normal HbA2 - Beta: High HbA2 and HbF Major: No/Minimal HbA Intermedia: Decreased HbA Trait: Mostly HbA
16
Q
How is Thalassemia treated
A
Blood transfusions to keep Hb>10
Iron chelators to prevent iron overload
Bone marrow transplant - Curative
17
Q
What is Macrocytic anaemia
A
This is anaemia associated with an MCV of >96fL
18
Q
What are the 2 types of Macrocytic anaemia
A
Megaloblastic = Developing RBCs in bone marrow with delayed nuclear maturation relative to their cytoplasm - Defective DNA synthesis
Normoblastic
19
Q
What causes of a megaloblastic Macrocytic anaemia
A
Vitamin B12 deficiency
Folate deficiency
Drugs: Methotrexate, Hydroxyurea, Azathioprine, Zidovudine
20
Q
What causes of a normoblastic Macrocytic anaemia
A
- Pregnancy
- Alcohol excess + Liver disease
- Reticulocytosis (Haemolytic processes) - Red cell immature form
- Hypothyroidism
- Haematological disorders (Aplastic anaemia)
- Drugs (Hydroxycarbamide, Tyrosin kinase inhibitors)
- Multiple myeloma + Myelodysplasia
21
Q
What are the signs and symptoms of Macrocytic anaemia
A
Asymptomatic
Fatigue
Faitness
Dyspnoea
Angina pectoris, intermittent claudication if coexistent arterial disease
Pale skin Pale mucous membranes Tachycardia Koilonychia (Spoon shaped) Cardiac failure Glossitis Angular stomatitis
22
Q
How is Macrocytic anaemia diagnosed
A
FBC - Low Hb, High MCV
- Pancytopenia - Megaloblastic anaemia
- Different degrees off cytopenia - Myelodysplasia
- Exclude reticulocytosis
LFT - High bilirubin - Due to ineffective erythropoiesis or haemolysis
B12
Folate
TFT
Anti-parietal cell and Anti-intrinsic factor antibodies
Blood film:
Megaloblastic anaemia:
- Megaloblasts
- Hypersegmented neutrophil nuclei
Schilling test - Method testing for pernicious anaemia - B12 will only be absorbed when given with intrinsic factor
23
Q
How is a Macrocytic anaemia treated
A
Pernicious anaemia - IM hydroxycobalamin for life
Folate deficiency - Oral folic acid
If B12 deficiency is present it must be treated before the folic acid deficiency
24
Q
What are complications of Macrocytic anaemia
A
Pernicious anaemia gives and increased risk of gastric cancer
In pregnancy a folate deficiency increases risk of neural tube defects
25
What are causes of vitamin B12 deficiency
Low intake - Vegans (B12 is found in meat and animals protein foods)
Impaired absorption
- Stomach (Pernicious anaemia, gastrectomy etc.)
- Small bowel (Crohn's disease, coeliac disease, tropical sprue)
B12 is absorbed in the terminal ileum and requires Intrinsic factor which is produced by gastric parietal cells
Pernicious anaemia is an autoimmune condition involving gastritis, atrophy of all layers of the body and fungus of the stomach and loss of normal gastric glands, parietal and chief cells - 80% of megaloblastic anaemia due to impaired vitamin B12 absorption
Drugs: Colchicine, metformine
26
What are the signs and symptoms of B12 deficiency
Normal symptoms and signs of anaemia
+
Jaundice
Neurological symptoms: Paraesthesia, Numbness, Cognitive changes, Visual disturbances
Neuropsychiatric signs: Irritability, dementia, depression
Neurological signs: Subacute combined degeneration of the spinal cord, peripheral neuropathy
27
How is a B12 deficiency diagnosed
FBC & Blood film
- Hypersegmented neutrophils
- Oval macrocytes
- Circulating megaloblasts
- Low reticulocytes
Pernicious anaemia tests
- Anti-Intrinsic factor antibodies
- Anti-parietal cell antibodies
- Schiling test
Serum B12 - Is not completely accurate
Plasma total homocysteine - Elevated
Plasma methylmalonic acid - Elevated
Holotranscobalamin - Low
28
What are causes of folate deficiency
- Poor intake (Main cause) - Elderly, poverty, alcohol excess, eating disorders
- Malabsorption - Crohn's disease, coeliac disease, tropical sprue
- Drugs (Methotrexate, phenytoin)
Excess utilisation:
- Physiological: Pregnancy, adolescent, prematurity
- Pathological: Haemolytic anaemia, malignancy, inflammatory diseases
Folate is found in leafy greens
29
How is a folate deficiency diagnosed
FBC & Blood film:
- Hypersegmented neutrophils
- Oval macrocytes
- Circulating megaloblasts
- Low reticulocytes
Serum folate: Low
RBC folate: Low - Diagnostic
Investigate malabsorptive causes if needed
30
What is Normocytic anaemia
This is anaemia associated with a normal MCV
31
What are causes of a Normocytic anaemia
Decreased production of normal-sized blood cells (Anaemia of chronic disease, aplastic anaemia)
Increased production of HbS (Sickle cell disease)
Increased destruction of red blood cells (Haemolysis, Acute blood loss)
Uncompensated increase in plasma volume (Pregnancy, fluid overload)
Marrow infiltration/fibrosis
Endocrine disease
32
What are the signs and symptoms of Normocytic anaemia
Typical signs and symptoms of anaemia
33
How is Normocytic anaemia
FBC - Low Hb, Normal MCV
| Check history for haemorrhage
34
What is Polycythaemia
An increase in Hb Concentration above the upper limit of normal for a person's age and sex
Relative - Normal red cell mass but low plasma volume
Absolute/True - Increased red cell mass
35
What are the causes of Polycythaemia
Polycythaemia Rubra Vera
- Myeloproliferative disorder
- JAK2 tyrosine kinase are involved
Secondary polycythaemia
Appropriate increase in erythropoietin
- Due to chronic hypoxia (Chronic lung disease, living at high altitude)
Inappropriate increase in erythropoietin
- Renal (Carcinoma, cysts, hydronephrosis)
- Inapproriate blood transfusion
- Secondary ploycythaemia may be due to erythropoietin abuse by athletes
- HCC
- Fibroids
- Cerebellar haemangioblastoma
Relative polycythaemia
- Dehydration
- Gaisbock's syndrome - Occurs in young male smokers with HTN, which results in a decrease in plasma volume and an apparent increase in red cell count
36
What are signs and symptoms of Polycythaemia
Frequently asymptomatic
- Features of thrombosis
- Features of haemorrhage
- Headache
- Pruritus
- Erythromelalgia
- Redness of fingers, palms, toes, heels
- Facial redness
- Splenomegaly (75%)
- Plethoric complexion
- Scratch marks from itching
- Conjunctival suffusion
- Retinal venous engorgement
- HTN
37
How is Polycythaemia diagnosed
FBC - High Hb, High Ht, Low MCV
Isotope dilution techniques:
- Allows confirmation of plasma volume and red cell mass
- Distinguishes between relative and absolute polycythaemia
```
Polycythaemia Rubra Vera:
High WCC
High Platelets
Low serum EPO
JAK2 mutation
Bone marrow trephine and biopsy shows erythroid hyperplasia
```
Secondary Polycythaemia:
- High serum EPO
- Exclude chronic Lung disease/hypoxia
- Check for EPO-secreting tumours
38
What is Sickle cell disease
A Chronic condition with sickling of red cells caused by inheritance of HbS
39
What are the different types of Sickle cell disease
Sickle cell anaemia = Homozygous HbS
Sickle cell trait = Carrier of one copy of HbS
Sickle cell disease = Includes compound heterozygosity for HbS and:
- HbC (Glutamic acid replaced by lysine)
- Beta-thalassemia
Present after 4 months
40
What are factors that precipitate sickling in Sickle cell disease
Infection
Dehydration
Hypoxia
Acidosis
41
What are the signs and symptoms of Sickle cell disease
Vaso-occlusion
- Autosplenectomy
- Abdominal pain
- Bones - Dactylitis
- Myalgia and arthralgia
- Fits and strokes
- Visual loss
- Joint and muscle tenderness
- Short digits
- Cotton will spots due to retinal ischaemia
Sequestration crisis
- Liver -> Exacerbation of anaemia
- Lungs -> Acute chest syndrome (SOB, Cough, Pain, Fever)
- Corpora cavernosa - Persistent painful erection - Priapism
- Impotence
- Organomegaly
42
How is Sickle cell anaemia diagnosed
FBC - Low Hb, High platelets, High WCC
Reticulocytes: High in haemolytic crisis, Low in aplastic crisis
Peripheral blood smear: Presence of nucleated red blood cells, sickle-shaped cells and Howell-Jolly bodies
Anisocytosis
Diagnostic: Hb Electrophoresis or DNA-based assay
43
How is Sickle cell disease treated
Acute - Painful crisis
- Oxygen
- IV Fluids
- Strong analgesia (IV opiates)
- Antibiotics
Infection Prophylaxis
- Penicillin V
- Regular vaccinations (particularly against capsulated bacteria e.g. pneumococcus)
Folic Acid
- If severe haemolysis or in pregnancy
Hydroxyurea/Hydroxycarbamide
- Increases HbF levels
- Reduces the frequency and duration of sickle cell crisis
Red Cell Transfusion
- For SEVERE anaemia
- Repeated transfusions (with iron chelators) may be required in patients suffering from repeated crises
Advice
- Avoid precipitating factors, good hygiene and nutrition, genetic counselling, prenatal screening
Surgical
- Bone marrow transplantation
- Joint replacement in cases with avascular necrosis
44
What are the possible complication of Sickle cell disease
Aplastic crisis - Infection with Parovirus B19 can lead to temporary cessation of erythropoiesis (Which can cause red cell count to plummet)
```
Haemolytic crisis
Pigment gallstones
Cholecystitis
Renal papillary necrosis
Leg ulcers
Cardiomyopathy
```
45
What is Antiphospholipid syndrome
This is the association of AP antibodies with a variety of clinical features characterised by thromboses and pregnancy related morbidity
46
What are the criteria for pregnancy related morbidity in Antiphospholipid syndrome
- 3 miscarriages before 10 weeks
- 1 miscarriage after 10 weeks
- Premature birth of a morphologically normal neonate before 34 weeks because of Eclampsia, Severe Pre-eclampsia or placental insufficiency
47
What are the Antiphospholipid antibodies
Anti-cardiolipin
Anti-B2-glycoprotein 1
Lupus anticoagulant - Strong association with SLE
48
What are signs and symptoms of Antiphospholipid syndrome
```
Recurrent miscarriages
History of thromboses
Headaches (migraine)
Chorea
Epilepsy
```
Livedo reticularis (Mottled reticulated vascular pattern that appears as a lace-like purplish decolouration of the skin)
Signs of SLE
Signs of Valvular heart disease
49
How is Antiphospholipid syndrome diagnosed
Lupus anticoagulant +ve twice 12 weeks apart
Anti-cardiolipin elevated twice 12 weeks apart
Anti-B2-glycoprotein elevated twice 12 weeks apart
High SLE antibodies (ANA, Anti-dsDNA, Anti-S)
FBC - Low platelets
U&C - Elevated if nephaopathy
Clotting screen - High APTT
50
what is Aplastic anaemia
This is diminished haematopoietic precursors in the bone marrow and deficiency of all blood cell elements (pancytopenia)
At least 2 of Hb, Platelets or Neutrophils
51
What are causes of Aplastic anaemia
Idiopathic (>40%)
- May be due to destruction or suppression of stem cells via autoimmune mechanisms
Acquired
- Drugs (e.g. chloramphenicol, sulphonamides, methotrexate)
- Chemicals (e.g. benzene, DDT) - Radiation
- Viral infection (e.g. parvovirus B19)
- Paroxysmal nocturnal haemoglobinuria (PNH)
Inherited
- Fanconi's anaemia
- Dyskeratosis congenita (a rare, progressive bone marrow failure syndrome)
52
What are signs and symptoms of Aplastic anaemia
There can be slow-onset or rapid-onset
Anaemia symptoms: Tiredness, lethargy, dyspnoea, pallor
Thrombocytopenia symptoms: Easy bruising, bleeding gums, epistaxis, petechiae
Leukopaenia symptoms: Increased frequency and severity of infections, Multiple bacterial and fungal infections
53
How is Aplastic anaemia diagnosed
FBC: Low Hb, platelets, WCC, Normal MCV, Low or absent reticulocytes
Bone marrow biopsy and cytogenetic analyses - Hypocellularity
54
What is Disseminated intravascular coagulation (DIC)
Acquired syndrome where there is activation of coagulation pathways that leads to intravascular thrombi and a decrease in platelets and coagulation factors. This leads to vascular obstruction and ischaemia leading to multi-organ failure
Generalised bleeding in at least 3 unrelated sites should lead to a high suspicion of DIC
55
What are causes of DIC
Acute overt = Bleeding and depletion of platelets and clotting factors
Chronic non-overt: VTE is accompanied by generalised activation of the coagulation system
- Sepsis
- Malignancies - AML (Acute), Lung, GI, breast (Chronic)
- Obstetric disorders
- Sever organ destruction or failure
- Vascular disorders
- Severe trauma or surgery
- Severe toxic immunological reactions
56
What are the signs and symptoms of DIC
```
Presence of underlying disorder
Hypotension and/or Tachycardia
Delirium and/or coma
Petechiae and/or Purpura fulminans
Oliguria and/or haematuria
Gangrene and/or aural cyanosis
Ecchymosis and/or oozing
```
57
How is DIC diagnosed
FBC - Low Platelets, High PT and APTT, Low fibrinogen, High -dimers
Peripheral blood film
- Schistocytes
58
What is Haemolytic anaemia
This is premature erythrocyte breakdown causing shortened erythrocyte life span with anaemia
59
What are causes of Haemolytic anaemia
Inherited:
- Membrane defects: Hereditary spherocytosis, Elliptocytosis
- Metabolic defects: G6PD deficiency, pyruvate kinase deficiency
- Haemoglobinopathies: Sickle cell disease, Thalassemia
Acquired:
- Autoimmune - Antibodies attach to erythrocytes causing intravascular and extravascular haemolysis
- Isoimmune: Transfusion reaction, Haemolytic disease of newborn
- Drugs: Penicillin, Quinine, Caused by the formation of drug-antibody-erythrocyte complex
- Trauma: Microangiopathic haemolytic anaemia (caused by RBC fragmentation in abnormal microcirculation) - Haemolytic uraemia syndrome, DIC, Malignant HTN.
- Infection: Malaria, Sepsis
- Paroxysmal nocturnal haemoglobinuria
60
What are the signs and symptoms of Haemolytic anaemia
Jaundice
Haematuria
Anaemia - Pallor
Hepatosplenomegaly
61
How is Haemolytic anaemia diagnosed
FBC - Low Hb, High reticulocytes, High MCV, High UCB
Blood film
- Leucoerythroblastic picture
- Macrocytosis
- Nucleated erythrocytes or reticulocytes
- Polychromasia
```
Potential:
Spherocytes
Elliptocytes
Sickle cells
Schistocytes
Malarial parasites
```
Urinalysis:
- High URB
- Haemoglobinuria
- Haemosiderinuria
Direct Coombs Test - Tests for autoimmune haemolytic anaemia
Ham's test - Lysis of erythrocytes in acidified serum in PNH
62
What are Haemolytic uraemic syndrome (HUS) and Thrombotic thrombocytopenic purpura (TTP)
HUS is a triad of symptoms:
1. Microangiopathic haemolytic anaemia
2. Acute renal failure
3. Thrombocytopenia
TTP is HUS with 2 additions symptoms:
- Fever
- Fluctuating CNS signs
```
There are 2 types of HUS:
Diarrhoea associated (D+) and no-prodomal illness identified (D-)
```
63
What are the aetiology/risk factors for HUS and TTP
Infection - E. coli O157H7
- Shigella
- Neuraminidase-producing infections
- HIV
Drugs
- COCP
- Ciclosporin
- Mitomicin
- 5-fluorouracil
Others:
- Malignant HTN
- Malignancy
- Pregnancy
- SLE
- Scleroderma
64
Who is likely to be affected by HUS and TTP
D+ HUS often affects children
It is the most common cause of AKI in children
TTP mainly affect adult females
65
What are the signs and symptoms of HUS and TTP
HUS
- Mainly affecting children
- Watery diarrhoea (Especially blood stained)
- Abdominal pain
- Absence of fever
- Oliguria or anuria
- Haematuria
- Pallor
- HTN
```
TTP - Affects older patients (Pregnant, Black, Female)
Above
+ Fever
+ CNS signs
- Weakness
- Reduced vision
- Fits
- Reduced consciousness
```
66
How are HUS and TTP diagnosed
HUS
FBC: Low Hb, Low Platelets,
Peripheral smear: Thrombotic microangiopathy (Schistocytes)
Reticulocyte: Elevated
Serum creatinine: Elevated
LDH: Elevated
Stool culture (Sorbitol) - E. coli O157:H7
```
TTP
FBC: Low Hb, Low WCC, Low Platelets
Peripheral smear: Thrombotic microangiopathy (Schistocytes)
Reticulocyte: Elevated
Serum creatinine: Elevated
LDH: Elevated
Indirect bilirubin: Elevated
Pregnancy test
```
67
What is Haemophilia
Bleeding disorder resulting from an inherited deficiency of a clotting factor
X-Linked recessive inheritance
68
What are the different types of Haemophilia
A - Factor 8 - Most common
B - Factor 9
C - Factor 11 - Very rare - Ashkenazi Jews
69
What are the signs and symptoms of Haemophilia
- Symptoms usually begin in early childhood
- Swollen painful joints occurring spontaneously or with minimal trauma (haemarthroses)
- Painful bleeding into muscles
- Haematuria
- Excessive bruising or bleeding after surgery or trauma
- FEMALE carriers are usually asymptomatic, but may experience excessive bleeding after trauma
- Generally speaking, bleeding in haemophilia is DEEP (into muscles and joints)
- Multiple bruises
- Muscles haematomas
- Haemarthroses
- Joint deformity
- Nerve palsies (Compression)
- Signs of Iron deficiency anaemia
70
How is Haemophilia diagnosed
Clotting screen - High aPTT
Mixing study - aPTT corrected
Coagulation factor assays - Low Factor 8, 9 or 11
71
What is Immune thrombocytopenic purpura (ITP)
Syndrome characterised by immune destruction of platelets resulting in bruising or bleeding tendency
72
What are causes of ITP
Often idiopathic
Acute ITP is often seen after viral infection in children
Chronic ITP is more common in adults (Women)
ITP may be associated with:
- Infections (Malaria, EBV, HIV)
- Autoimmune disease (SLE, thyroid disease)
- Malignancies
- Drugs (Quinine)
Autoantibodies are generated which bind to platelet membrane proteins resulting in thrombocytopenia
73
What are signs and symptoms of ITP
```
Easy bleeding
Mucosal bleeding
Menorrhagia
Epistaxis
Visible petechiae and bruising
Signs of other illness would suggest that there is an underlying cause
```
74
How is ITP investigated
Diagnosis of exclusion:
Exclude:
Myelodysplasia
Acute leukaemia
Marrow infiltration
Bloods:
FBC - Low platelets
Clotting screen - Normal PT, aPTT, Fibrinogen
Blood film:
Rule out Pseudothrombocytpoenia which is caused by platelets clumping together and giving falsely low counts
Bone marrow
75
What is Von Willebrand’s disease
Genetic bleeding disorder which may present with mucocutaneous bleeding increased bleeding after trauma and easy bruising
76
What are the different types of Von Willebrand's disease
Type 1 - vWF works well but there isn't enough of it
Type 2 - There are normal levels of vWF but it is abnormal and doesn't function correctly
Type 3 - There is no vWF
77
What are the causes of Von Willebrand’s disease
Usually autosomal dominant
78
What are the signs and symptoms of Von Willebrand's disease
```
Easy bruising
Epistaxis - Hard to stop
Menorrhagia
Blood in stools
Haematuria
```
Just lots of prolonged bleeding
79
How is Von Willebrand's disease diagnosed
```
aPTT - Prolonged
Factor VIII - Low
Bleeding time - High
vWF - Low/Normal
Ristocetin cofactor - reduced platelet aggregation by vWF in the presence of ristocetin
```
80
What is Myelofibrosis
Disorder of haematopoietic stem cells characterised by progressive bone marrow fibrosis associated with extra medullary haematopoiesis and splenomegaly
81
What causes Myelofibrosis
Sometime causes there to be an increase in abnormal megakaryoctyes with stroll proliferation secondary to growth factors released by megakaryoctes
30% of patients have a previous history of polycythaemia ruby vera or essential thrombocythaemia
82
What are the signs and symptoms of Myelofibrosis
Common:
- Weight loss
- Anorexia
- Fever
- Night sweats
- Pruritus
- LUQ pain
Uncommon:
- Indigestion
- Bleeding
- Bone pain
- Gout
Splenohepatomegaly
83
How is Myelofibrosis diagnosed
FBC - Low Hb, Low WCC and Platelets in later stages
Peripheral smear: Nucleated red cells, teardrop cells (Poikilocyte), leukoerythroblastic changes
Bone marrow biopsy: Fibrosis (fibroblasts, collagen, and reticulin)
Abdominal CT scan: Enlarged spleen, perisplenic fluid collection if splenic infarction has occurred
84
What is Myelodysplasia
A serious of haematological conditions characterised by chronic cytopenia and abnormal cellular maturation
```
5 types:
- Refractory anaemia (RA)
- RA with ringed sideroblasts (RARS)
- RA with excess blasts (RAEB)
- Chronic myelomonocyticleukaemia
(CMML)
RAEB in transformation (RAEB-‐t)
```
85
What are the causes of Myelodysplasia
It can be primary but it may also arise in patients who have received chemotherapy or radiotherapy for previous malignancies
Patients may have chromosomal abnormalities
86
What are the signs and symptoms of Myelodysplasia
May be asymptomatic and diagnosed on routine blood counts
Anaemia - Fatigue, dizziness, pallor
Neutropenia - Recurrent infections
Thrombocytopenia - Easy bruising, epistaxis, purpura, petechiae
Gum hypertrophy
Lymphadenopathy
Spleen not enlarged (Except in CMML)
87
How is Myelodysplasia diagnosed
FBC: Pancytopenia
Peripheral blood film:
- Irregular or macrocytic RBCs
- Dysplastic granulocytes
- Platelets may be large and hypogranular
Bone marrow aspiration:
- Usually hyper cellular
- Dysplastic changes
- Ringed sideroblasts
Cytogenetics:
May be abnormal
88
What is Chronic myeloid leukaemia (CML)
Malignant clonal disease characterised by uncontrolled proliferation of mature and maturing granulocytes with fairly normal differentiation
95% have chromosomal translocation between ch9 and 22 forming the Philadelphia chromosome (BCR-ABL)
3 phases:
Chronic (4-6yrs)
Accelerated (3-9months)
Acute blast phase
89
Who is usually affected by CML
Adults aged 40-60
| Males
90
What are the signs and symptoms of CML
Asymptomatic 50% diagnosed routine blood count
```
Weight loss
Malaise
Sweating
Lethargy
Easy bruising
Epistaxis
Splenomegaly - 90%
Gout
Hyperviscosity - Priapism, Headaches, Visual disturbances
```
91
How is CML diagnosed
FBC: High WCC, Hb Low/Normal, Platelets
Blood film: Neutrophilia, Full spectrum of development stages, number of blasts depends on stage of disease
Bone marrow Aspirate or biopsy: Hypercellular with raised myeloid precursors
Cytogenics: FISH or PCR - Philadelphia chromosome
92
What is Acute myeloid leukaemia (AML)
Malignancy of primitive myeloid linage white blood cells (Myeloblasts) with proliferation in the bone marrow and blood
Classfied using the FAB (French-American-British) system into 8 morphological variants
Replacement of normal marrow and bone marrow failure
93
Who is usually affected by AML
Most common acute leukaemia in adults
94
What are the signs and symptoms of AML
```
Anaemia - Lethargy, SOB, pallor
Bleeding, ecchymosis - due to thrombocytopenia
Recurrent infections
Gum swelling
CNS involvement
Cardiac murmur
```
95
How is AML diagnosed
FBC: High WCC, Low Platelets
Blood film: Myeloblasts, auer rods
Bone marrow Aspirate or biopsy: Hypercellular with >20% blasts
Cytogenics
Immunocytochemistry
96
What is Chronic lymphocytic leukaemia (CLL)
Malignant monoclonal expansion of B lymphocytes that are morphologically normal but are immature and non-reactive
There is an overlap between CLL and non-Hodgkin's lymphoma
Chromosomal changes include:
- Trisomy 12
- 11q and 13q deletions
97
Who is usually affected by CLL
Adult males
98
What are the signs and symptoms of CLL
50% are asymptomatic and diagnosis is made during a routine blood test
Symptoms and signs of anaemia
Recurrent infections
Constitutional symptoms
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Symmetrical painless lymphadenopathy
Hepatosplenomegaly
Pallor
Cardiac murmur
Purpura
Easy bruising or bleeding
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99
How is CLL diagnosed
FBC: High WCC, Hb Normal/Low, Platelets Normal/Low
Blood film: Lymphocytosis, smear cells/smudge cells
Bone marrow Aspirate or biopsy: Heavy infiltration with lymphocytes
Cytogenics (For prognostication)
Immunocytochemistry
100
What is Acute lymphoblastic leukaemia (ALL)
Malignancy of the bone marrow and blood characterised by the proliferation of lymphoblasts
Replacement of marrow leading to bone marrow failure
RFs:
Environmental: Radiation, viruses
Genetic: Down's syndrome, NF type 1, Fanconi's anaemia, Xeroderma pigmentosum
101
Who is usually affected by ALL
Children
Bimodal - Second peak in elderly
102
What are the signs and symptoms of ALL
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Constitutional symptoms
Anaemia - Fatigue, SOB, pallor
Bleeding
Recurrent infection
CNS disturbances
Bony tenderness
Gingival hyperplasia
Hepatosplenomegaly
Lymphadenopathy
Retinal haemorrhage + Papilloedema
Infiltration of anterior chamber of the eye
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103
How is ALL diagnosed
FBC - Low Hb, Platelets, High WCC
High LDH
Clotting screen
Blood film:
Abundant Lymphoblasts
Bone marrow Aspirate or biopsy: Hypercellular with >20% blasts
Cytogenics
Immunocytochemistry
104
What is Multiple myeloma
Haematological malignancy characterised by proliferation of plasma cells resulting in bone lesions and the production of monoclonal immunoglobulin
105
What are risk factors for Multiple myeloma
Possible viral trigger
Chromosomal aberrations are frequent
Associated with ionising radiation, agricultural work or occupational chemical exposures
106
Who is usually affected by Multiple myeloma
Afro-caribbean>White>Asians
| Peak incidence at 70 years old
107
What are signs and symptoms of Multiple myeloma
Bone pain - Back and ribs
Infections - Often recurrent
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Fatigue
Polydypsia
Polyuria
Nausea
Constipation
Mental changes - Hypercalcaemia
```
Hyper-viscosity: Bleeding, Headaches, Visual disturbances
```
Palow
Cardiac flow murmur
Signs of HF
Dehydration
Purpura
Hepatosplenomegaly
Macroglossia
Carpal tunnel syndrome
Peripheral neuropathies
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108
How is Multiple myeloma diagnosed
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FBC: Low Hb
High ESR
High CRP
U&Es - High creatinine, high Ca
Normal ALP
```
Rouleaux formation with bluish background (Suggesting high protein)
Serum or urine electrophoresis: - Serum paraprotein
- Bence-Jones protein (Monoclonal immunoglobulin light chain that's found in the urine and suggests Multiple myeloma)
Bone marrow aspirate and biopsy: High plasma cells >20%
Chest, pelvic and vertebral X-ray
- Osteolytic lesions without surrounding sclerosis
- Pathological fractures
109
What is Hodgkin's lymphoma
Neoplasms of the lymphoid cells originating in the lymph nodes or other lymphoid tissue.
Hodgkins (15% of lymphomas) is diagnosed histopathologically by the presence of Reed-Sternberg cells (binucleate lymphocytes)
EBV genome detected in 50% of Hodgkin's lymphomas
110
Who is usually affected by Hodgkin's lymphoma
Males
| Bimodal - 20-30 and >50
111
What are the signs and symptoms of Hodgkin's lymphoma
Painless enlarging mass - Most commonly in the neck can be in axilla or groin
Mass may be painful after alcohol ingestion
Fever
Night sweats
Weight loss 10% body mass in past 6 months
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Pruritus - Skin excoriations
Cough
Dyspnoea
Splenomegaly
Signs of intrathoracic disease (Pleural effusion, SVC obstruction)
```
112
How is Hodgkin's lymphoma diagnosed
FBC - Low Hb, High WCC, High Neutrophils and eosinophils, Lymphopaenia in advanced disease
Lymph node biopsy - Reed-Sternberg cell
Bone marrow aspirate and biopsy:
Hodgkin's cells
Imaging -
CXR - Mediastinal mass
CT - May show enlarged lymph nodes and other sites of disease
PET - Involved sites appear fluorodeoxyglucose (FDG)-avid (bright) with PET imaging
Ann Arbor staging
- I = single lymph node region
- II = 2+ lymph node regions on one side of the diaphragm
- III = lymph node regions on both sides of the diaphragm
- IV = extranodal involvement
- A = absence of B symptoms
- B = presence of B symptoms
- E = localised extranodal extension
- S = involvement of spleen
113
What is Non-Hodgkin's lymphoma
Neoplasms of the lymphoid cells originating in the lymph nodes or other lymphoid tissue.
Non-Hodgkin's lymphomas are a diverse group consisting of:
- 85% B cell
- 15% T cell and NK cell
Stable
Indolent disease
Aggressive disease
114
What are the causes of Non-Hodgkin's lymphoma
Multiple genetic lesions
Oncogenic viruses: EBV and Burkitt's lymphoma
```
Radiotherapy
Immunosuppressive agents
Chemotherapy
HIV, HBV, HCV
Connective tissue disease (SLE)
```
Increasing age + males
115
What are the signs and symptoms of Non-Hodgkin's lymphoma
Painless enlarging mass - Most commonly in the neck can be in axilla or groin
Fever
Night sweats
Weight loss 10% body mass in past 6 months
Symptoms of Hypercalcaemia
Extranodal disease more common in NHL than HL
```
Skin rashes
Headache
Sore throat
Hepatosplenomegaly
Testicular swelling
Infections
Purpura
```
116
How is Non-Hodgkin's lymphoma diagnosed
```
FBC
Low Hb, Platelets and Neutrophils
High ESR and CRP
Hypercalcaemia
HIV, HBV, HCV serology
```
Blood film: Lymphoma cells may be visible in some patients
Bone marrow aspirate and biopsy: Positive
Lymph node biopsy - Positive
Imaging -
CXR - Mediastinal mass
CT - May show enlarged lymph nodes and other sites of disease
PET - Involved sites appear fluorodeoxyglucose (FDG)-avid (bright) with PET imaging
Ann Arbor staging
- I = single lymph node region
- II = 2+ lymph node regions on one side of the diaphragm
- III = lymph node regions on both sides of the diaphragm
- IV = extranodal involvement
- A = absence of B symptoms
- B = presence of B symptoms
- E = localised extranodal extension
- S = involvement of spleen
