Haematology Flashcards

1
Q

What is Microcytic anaemia

A

This is anaemia associated with an MCV of <80fL

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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

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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
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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)

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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

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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
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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
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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

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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

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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

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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

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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

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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
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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
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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
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16
Q

How is Thalassemia treated

A

Blood transfusions to keep Hb>10

Iron chelators to prevent iron overload

Bone marrow transplant - Curative

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17
Q

What is Macrocytic anaemia

A

This is anaemia associated with an MCV of >96fL

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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

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19
Q

What causes of a megaloblastic Macrocytic anaemia

A

Vitamin B12 deficiency
Folate deficiency

Drugs: Methotrexate, Hydroxyurea, Azathioprine, Zidovudine

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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
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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
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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

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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

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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

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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
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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 ```
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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
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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
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Who is usually affected by CLL
Adult males
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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 ``` Symmetrical painless lymphadenopathy Hepatosplenomegaly Pallor Cardiac murmur Purpura Easy bruising or bleeding ```
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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
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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
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Who is usually affected by ALL
Children Bimodal - Second peak in elderly
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What are the signs and symptoms of ALL
``` 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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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
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What is Multiple myeloma
Haematological malignancy characterised by proliferation of plasma cells resulting in bone lesions and the production of monoclonal immunoglobulin
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What are risk factors for Multiple myeloma
Possible viral trigger Chromosomal aberrations are frequent Associated with ionising radiation, agricultural work or occupational chemical exposures
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Who is usually affected by Multiple myeloma
Afro-caribbean>White>Asians | Peak incidence at 70 years old
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What are signs and symptoms of Multiple myeloma
Bone pain - Back and ribs Infections - Often recurrent ``` 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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How is Multiple myeloma diagnosed
``` 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
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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
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Who is usually affected by Hodgkin's lymphoma
Males | Bimodal - 20-30 and >50
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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 ``` Pruritus - Skin excoriations Cough Dyspnoea Splenomegaly Signs of intrathoracic disease (Pleural effusion, SVC obstruction) ```
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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
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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
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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
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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 ```
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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