Haematology Flashcards
Iron Deficiency Anaemia
Causes
- excessive blood loss ( young F: Menorrhagia, Adult M& PostMeno F: GI bleeding ?cancer)
- inadequate dietary intake (vegan, vegetarian)
- poor intestinal absorption (coeliac disease)
- increased iron requirements. (Children rapid growth, pregnancy
Features
- Fatigue
- SOB
- pallor & palpitations
- hair loss
- atrophic glossitis (tongue)
- nail changes: spoon shaped (Koilonychia)
- angular stomatitis
Ix
- Good history (look for signs of cancer)
- hypochromic microcytic anaemia
- Total iron-binding capacity (TIBC)/transferrin will be high. (due to low iron stores)
- anisopoikilocytosis (diff shapes of RBCs)
Management
- malignancy has been excluded
- Oral ferrous sulfate: patients should continue taking iron for 3 months after the iron deficiency has been corrected in order to replenish iron stores.
- Iron-rich diet: this includes dark-green leafy vegetables, meat, iron-fortified bread
Side fx of Iron tabs: nausea, abdominal pain, constipation, diarrhoea
What type of anaemia is: Anaemia of Chronic Disease
normocytic anaemia
Others include
- chronic kidney disease
- aplastic anaemia
- haemolytic anaemia
- acute blood loss
anemia that is found in people with certain long-term (chronic) medical conditions that involve inflammation
Sideroblastic Anaemia
microcytic
- Red cells fail to completely form haem
- Leading to deposits of iron in the mitochondria that form a ring around the nucleus called a ring sideroblast
Ix
- full blood count
- hypochromic microcytic anaemia (more so in congenital)
- iron studies
- high ferritin
- high iron
- high transferrin saturation
- blood film: basophilic stippling of red blood cells
- bone marrow: Prussian blue staining will show ringed sideroblasts
Management
- Management
- supportive
- treat any underlying cause
- pyridoxine may help
Congenital or Acquired
Acquired causes
* myelodysplasia
* alcohol
* lead
* anti-TB medications
macrocytic
Vit B12 Deficiency
Cobalamin deficiency
Background
- Used in the body for red blood cell development and also maintenance of the nervous system
- absorbed after binding to intrinsic factor in terminal ileum
Causes
- pernicious anaemia: most common cause
- post gastrectomy or resection in crohns
- vegan diet or a poor diet
- Metformin
Signs and Ix
- macrocytic anaemia
- sore tongue and mouth
- Distal parasthesia
Management
- 1 mg of IM hydroxocobalamin 3 times each week for 2 weeks then x1 every 3m
- Treat B12 before treatinf B9
macrocytic
Vit B9 Deficiency
Folate Deficiency
- Green, leafy vegetables are a good source of folic acid.
Causes
- phenytoin
- methotrexate
- pregnancy
- alcohol excess
Management
- all women should take 400mcg of folic acid until the 12th week of pregnancy
- women at higher risk of conceiving a child with a NTD should take 5mg of folic acid from before conception until the 12th week of pregnancy
High risk = prev history of neural tube defect (NTD) in either partner family, mother on antieplileptics, mother obese
Autosomal Recessive
Sickle Cell Anaemia
heterozygous condition offers some protection against malaria.
Heterozygotes dont show symptoms unless crisis
Homozygotes show symptoms after 4-6m, abnormal HbSS molecules take over from fetal haemoglobin.
- synthesis of an abnormal haemoglobin chain termed HbS forming crescent shaped RBCs
Types
- normal haemoglobin: HbAA
- sickle cell trait: HbAS
- homozygous sickle cell disease: HbSS.
- milder form of sickle cell disease (HbSC) - C is deformed Hb
Ix & mngement
- definitive diagnosis of sickle cell disease is by haemoglobin electrophoresries
- hydroxyurea - prophylaxis
- Pneumococcal vaxx every 5 years
Sickle Cell crisis
- Thrombotic, ‘vaso-occlusive’, ‘painful crises’ - caused by infection, Dehydration, high altitudes, Diagnosed clinically
- Acute chest syndrome - dyspnoea, chest pain, pulmonary infiltrates on chest x-ray, low pO2
- Aplastic crises - infection with parvovirus, sudden fall in haemoglobin + reticulocytes
- Sequestration crises - sickling in organs like spleen, increased reticulocyte count
Management Crisis
- analgesia e.g. opiates
- rehydrate
- oxygen
- consider antibiotics if evidence of infection
- blood transfusion
Thalassaemia
Alpha, Beta Major, Beta minor, Intermedia
Thalassaemia is caused by a genetic defect in the protein chains that make up haemoglobin. Normal haemoglobin consists of two alpha-globin and two beta-globin chains.
Types
- Alpha: 2 separate alpha-globulin genes are located on each chromosome 16
- Beta Major: absence of beta globulin chains
- Beta Minor: one abnormal and one normal gene.
- Beta Intermedia: two abnormal copies of the beta-globin gene.
Features
- Fatigue
- Pallor
- Jaundice
- Gallstones
- Splenomegaly
- Poor growth and development
Ix
- Microcytic anaemia (Low MCV)
- Haemoglobin electrophoresis is used to diagnose globin abnormalities.
- DNA testing can be used to look for the genetic abnormality.
- All pregnant women offered screening
- B Major: HbA2 & HbF raised
- B Minor: microcytosis is characteristically disproportionate to the anaemia
Management
- B Major: repeated transfusion + iron chelation therapy (desferrioxamine)
- Alpha: monitor,Blood transfusions, maybe bone marrow
- B minor: Monitoring
- Intermedia: Monitoring but may need transfusion
G6PD Deficiency
- Heinz bodies on blood films. Bite and blister cells may also be seen
- G6PD enzyme assay - diagnostic
levels should be checked around 3 months after an acute episode of hemolysis
Hereditary Spherocytosis
most common hereditary haemolytic anaemia in people of northern European descent
Presentation
- failure to thrive
- jaundice, gallstones
- splenomegaly
- aplastic crisis precipitated by parvovirus infection
Ix
- Clinical diagnosis with bloods
Management
- treatment is generally supportive
- transfusion if necessary
longer term treatment: - folate replacement
- splenectomy
Multiple Myeloma
CRAB
haematological malignancy characterised by plasma cell proliferation
- Genetic mutations -> B-lymphocytes differentiate into mature plasma cells.
- Median age 70
Features
- C: Hypercalcaemia
- R: Renal Failure (light chain deposition within the renal tubules)
- A: Anaemia
- B: Bleeding (thrombocytopenia), Bony Pain
- I: Infections
Ix
- Anaemia + renal failure on U&E
- peripheral blood film: rouleaux formation
- Diagnostic: Bone marrow aspiration: plasma cells is significantly raised
- whole-body MRI: For bony leisions
Management
Chemo
* Bortezomib (a proteasome inhibitor)
* Thalidomide
* Dexamethasone
RF:
- Older age
- Male
- Black ethnic origin
- Family history
- Obesity
MGUS
Monoclonal gammopathy of undetermined significance
Around 10% of patients eventually develop myeloma at 10 years, with 50% at 15 years
- Causes a paraproteinaemia* and is often mistaken for myeloma.
Feautures
* Asymptomatic
* Demyelinating neuropathy in some
* Increased risk of Infection
MGUS VS Myeloma
- normal immune function
- normal beta-2 microglobulin levels
- lower level of paraproteinaemia than myeloma (e.g. < 30g/l IgG, or < 20g/l IgA)
- stable level of paraproteinaemia
- no clinical features of myeloma (e.g. lytic lesions on x-rays or renal disease)
*Excessive amounts of paraproteins in the blood. Paraproteins are immunoglobulin proteins that are produced by a clone of plasma cells in the bone marrow.
rapidly progressing cancer of the myeloid cell line
Acute Myeloid Leukaemia
most prevalent acute leukaemia in adult population
can be the result of a transformation from a myeloproliferative disorder, such as polycythaemia ruby vera or myelofibrosis.
Feautures
- Fatigue
- Fever
- Pallor due to anaemia
- Petechiae or bruising due to thrombocytopenia
- Abnormal bleeding
- Lymphadenopathy
Ix
- blood film and bone marrow biopsy - Blast cells & Auer rods
Management
- chemo
Acute Lymphocytic Leukemia
most common in children
affects one of the lymphocyte precursor cells, causing acute proliferation of a single type of lymphocyte, usually B-lymphocytes. Excessive accumulation of these cells replaces the other cell types in the bone marrow, leading to pancytopenia.
common with Down’s syndrome.
Poor Prognosis
- age < 2 years or > 10 years
- WBC > 20 * 109/l at diagnosis
- T or B cell surface markers
- non-Caucasian
- male sex
Chronic Myeloid Leukemia
CML has three phases, including a long chronic phase, and is associated with the Philadelphia chromosome
- Philadelphia chromosome - BCR ABL1
- an increase in granulocytes at different stages of maturation +/- thrombocytosis
- management: IMATINIB - inhibitor of the tyrosine kinase
Chronic phase
Accelerated phase
Blast phase
Chronic Lymphocytic Leukemia
Most common form in adults
Leukaemia is cancer of a particular line of stem cells in the bone marrow, causing unregulated production of a specific type of blood cell.
- where there is slow proliferation of a single type of well-differentiated lymphocyte, usually B-lymphocytes. It usually affects adults over 60 years of age.
- warm autoimmune haemolytic anaemia
- blood film: **smudge cells **(also known as smear cells)
- Ritcher’s transformation occurs when leukaemia cells enter the lymph node and change into a high-grade, fast-growing non-Hodgkin’s lymphoma. Patients often become unwell very suddenly.
Hodgkin’s Lymphoma
- Malignant proliferation of lymphocytes accumulating in lymph nodes
Features
- Painless Lymphadenopathy
- B symptoms ( Weight loss, Pruitis, Night sweats, fever)
Ix
- Normocytic anaemia
- Raised Eosinophils
- Lymph node biopsy: Reed Sternberg cells
Management
- ABVD ( doxorubicin, bleomycin, vinblastine, and dacarbazine)
- Or BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone)
Having B Symptoms is poor prognosis
Non-Hodgkin Lymphoma
More common than Hodgkins
- Malignant proliferation of lymphocytes accumulating in lymph nodes
- can affect B or T cells
- RF: elderly, previous infection of EBV or Hiv, SLE
Features
- Painless Lymphadenopathy
- B symptoms ( Weight loss, Pruitis, Night sweats, fever)
Ix
- Biopsy mainstay example: Burkitt’s Lymphoma: Starry Sky appearance
Management
- Rituximab
- CHOP
Pancytopenia
AKA Aplastic Anaemia
Pancytopenia is a medical condition characterized by a deficiency of all three major types of blood cells: red blood cells (erythrocytes), white blood cells (leukocytes), and platelets (thrombocytes). It can result from various underlying causes, including bone marrow disorders, nutritional deficiencies, autoimmune diseases, infections, medications, and certain cancers.
Features
- normochromic, normocytic anaemia
- leukopenia, with lymphocytes relatively spared
- thrombocytopenia
- may be the presenting feature acute lymphoblastic or myeloid leukaemia
- a minority of patients later develop paroxysmal nocturnal haemoglobinuria or myelodysplasia
Causes
- idiopathic
- congenital: Fanconi anaemia, dyskeratosis congenita
- drugs: cytotoxics, chloramphenicol, sulphonamides, phenytoin, gold
- toxins: benzene
- infections: parvovirus, hepatitis
- radiation
Polycythemia Vera
myeloproliferative disorder caused by clonal proliferation of a marrow stem cell leading to an increase in red cell volume, often accompanied by overproduction of neutrophils and platelets.
Features
- pruritus, typically after a hot bath
- splenomegaly
- hypertension
- hyperviscosity
Ix
- JAK2 gene in 95%
- full blood count/film: raised haematocrit; neutrophils, basophils, platelets
Management
- aspirin: reduces the risk of thrombotic events
- venesection: first-line treatment to keep the haemoglobin in the normal range
- chemotherapy
Secondary Causes
- COPD
- altitude
- obstructive sleep apnoea
- excessive erythropoietin: cerebellar haemangioma, hypernephroma, hepatoma, uterine fibroids*
Thrombocytopenia
Immune Thrombocytopenic purpura
Immune (or idiopathic) thrombocytopenic purpura (ITP) is an immune-mediated reduction in the platelet count.
- Antibodies are directed against the glycoprotein IIb/IIIa or Ib-V-IX complex.
- Elderly females most affected
- petechiae, purpura, bleeding (e.g. epistaxis)
- full blood count: isolated thrombocytopenia
- Management: Oral Prednislone
*
Evan’s syndrome
ITP in association with autoimmune haemolytic anaemia (AIHA)
Thrombotic Thrombocytopenic purpura
- abnormally large and sticky multimers of von Willebrand’s factor cause platelets to clump within vessels
- a deficiency of ADAMTS13
Features
- fever
- fluctuating neuro signs (microemboli)
- microangiopathic haemolytic anaemia
- thrombocytopenia
- renal failure
Causes
- post-infection e.g. urinary, gastrointestinal
- pregnancy
- drugs: ciclosporin, oral contraceptive pill, penicillin, clopidogrel, aciclovir
- tumours
- SLE
- HIV
Autosomal dominant
Von Willebrand Disease
most common inherited bleeding disorder
Role of von Willebrand factor
- large glycoprotein which forms massive multimers up to 1,000,000 Da in size
- promotes platelet adhesion to damaged endothelium
- carrier molecule for factor VIII
Ix
- prolonged bleeding time
- APTT may be prolonged
- factor VIII levels may be moderately reduced
Management
- tranexamic acid for mild bleeding
- desmopressin (DDAVP): raises levels of vWF by inducing release of vWF from Weibel-Palade bodies in endothelial cells
- factor VIII concentrate
Haemophilia A
Haemophilia is an X-linked recessive disorder of coagulation. Up to 30% of patients have no family history of the condition.
- Haemophilia A is due to a deficiency of factor VIII (8)
- haemoarthroses (blood in Joints)
- haematomas
- prolonged bleeding after surgery or trauma
- Prolonged APTT
- Diagnosis is based on bleeding scores, coagulation factor assays and genetic testing.
Management
- The affected clotting factor (VIII) can be given by intravenous infusion, either regularly or in response to bleeding.
- Up to 10-15% of patients with haemophilia A develop antibodies to factor VIII treatment.
