Haematology Flashcards
What is Microcytic anaemia
This is anaemia associated with an MCV of <80fL
What are the causes of a Microcytic anaemia
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
What are the signs and symptoms of a Microcytic anaemia
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
How is Iron deficiency anaemia diagnosed
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)
How is Iron deficiency anaemia treated
Treat underlying causes
Oral iron supplements
IM/IV iron if intolerant or poorly responsive to oral iron
What are causes of Anaemia of chronic disease
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
How is Anaemia of chronic disease diagnosed
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
Outline Sideroblastic anaemia
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
Outline Lead poisoning
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
What is Thalassemia
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
What are the 2 different types of Thalassemia
Alpha-Thalassemia - Reduced synthesis of alpha chain
Beta-Thalassemia - Reduced synthesis of beta chain
Outline the different types of Alpha-thalassemia
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
Outline the different types of Beta-thalassemia
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
What are signs and symptoms of Thalassemia
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
What are the investigative findings in Thalassemia
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
How is Thalassemia treated
Blood transfusions to keep Hb>10
Iron chelators to prevent iron overload
Bone marrow transplant - Curative
What is Macrocytic anaemia
This is anaemia associated with an MCV of >96fL
What are the 2 types of Macrocytic anaemia
Megaloblastic = Developing RBCs in bone marrow with delayed nuclear maturation relative to their cytoplasm - Defective DNA synthesis
Normoblastic
What causes of a megaloblastic Macrocytic anaemia
Vitamin B12 deficiency
Folate deficiency
Drugs: Methotrexate, Hydroxyurea, Azathioprine, Zidovudine
What causes of a normoblastic Macrocytic anaemia
- 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
What are the signs and symptoms of Macrocytic anaemia
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
How is Macrocytic anaemia diagnosed
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
How is a Macrocytic anaemia treated
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
What are complications of Macrocytic anaemia
Pernicious anaemia gives and increased risk of gastric cancer
In pregnancy a folate deficiency increases risk of neural tube defects
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
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
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
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
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
What is Normocytic anaemia
This is anaemia associated with a normal MCV
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
What are the signs and symptoms of Normocytic anaemia
Typical signs and symptoms of anaemia
How is Normocytic anaemia
FBC - Low Hb, Normal MCV
Check history for haemorrhage
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
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
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
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
What is Sickle cell disease
A Chronic condition with sickling of red cells caused by inheritance of HbS
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
What are factors that precipitate sickling in Sickle cell disease
Infection
Dehydration
Hypoxia
Acidosis
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
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
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
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
What is Antiphospholipid syndrome
This is the association of AP antibodies with a variety of clinical features characterised by thromboses and pregnancy related morbidity
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
What are the Antiphospholipid antibodies
Anti-cardiolipin
Anti-B2-glycoprotein 1
Lupus anticoagulant - Strong association with SLE
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
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
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
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)
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
How is Aplastic anaemia diagnosed
FBC: Low Hb, platelets, WCC, Normal MCV, Low or absent reticulocytes
Bone marrow biopsy and cytogenetic analyses - Hypocellularity
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
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
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
How is DIC diagnosed
FBC - Low Platelets, High PT and APTT, Low fibrinogen, High -dimers
Peripheral blood film
- Schistocytes
What is Haemolytic anaemia
This is premature erythrocyte breakdown causing shortened erythrocyte life span with anaemia
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
What are the signs and symptoms of Haemolytic anaemia
Jaundice
Haematuria
Anaemia - Pallor
Hepatosplenomegaly
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
What are Haemolytic uraemic syndrome (HUS) and Thrombotic thrombocytopenic purpura (TTP)
HUS is a triad of symptoms:
- Microangiopathic haemolytic anaemia
- Acute renal failure
- 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-)
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
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
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
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
What is Haemophilia
Bleeding disorder resulting from an inherited deficiency of a clotting factor
X-Linked recessive inheritance
What are the different types of Haemophilia
A - Factor 8 - Most common
B - Factor 9
C - Factor 11 - Very rare - Ashkenazi Jews
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
How is Haemophilia diagnosed
Clotting screen - High aPTT
Mixing study - aPTT corrected
Coagulation factor assays - Low Factor 8, 9 or 11
What is Immune thrombocytopenic purpura (ITP)
Syndrome characterised by immune destruction of platelets resulting in bruising or bleeding tendency
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
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
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
What is Von Willebrand’s disease
Genetic bleeding disorder which may present with mucocutaneous bleeding increased bleeding after trauma and easy bruising
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
What are the causes of Von Willebrand’s disease
Usually autosomal dominant
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
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
What is Myelofibrosis
Disorder of haematopoietic stem cells characterised by progressive bone marrow fibrosis associated with extra medullary haematopoiesis and splenomegaly
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
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
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
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)
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
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)
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
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
Who is usually affected by CML
Adults aged 40-60
Males
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
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
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
Who is usually affected by AML
Most common acute leukaemia in adults
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
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
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
Who is usually affected by CLL
Adult males
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
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
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
Who is usually affected by ALL
Children
Bimodal - Second peak in elderly
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
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
What is Multiple myeloma
Haematological malignancy characterised by proliferation of plasma cells resulting in bone lesions and the production of monoclonal immunoglobulin
What are risk factors for Multiple myeloma
Possible viral trigger
Chromosomal aberrations are frequent
Associated with ionising radiation, agricultural work or occupational chemical exposures
Who is usually affected by Multiple myeloma
Afro-caribbean>White>Asians
Peak incidence at 70 years old
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
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
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
Who is usually affected by Hodgkin’s lymphoma
Males
Bimodal - 20-30 and >50
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)
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
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
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
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
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
