The haematological system and skin - Anaemia and red cell metabolism and transfusion Flashcards
Which groups are most vulnerable of Iron deficiency?
Women of child-bearing: because of menstrual blood losses and pregnancies
Children: Because of increased requirements for iron to meet growth (muscles, tissues, and commencement of period in girls)
a) Symptoms
b) Signs
a)
- Tiredness
- Weakness
- Pale skin
- Fast or irregular heartbeat
- SOB
- Chest pain
- Dizziness
- Cognitive problems
- Numbness or coldness in extremities
- Headache
- Restless legs syndrome
- Failure to thrive in infant
- Growth retardation in children
b)
- Bounding pulse
- Postural hypotension
- Tachycardia
- Conjunctival pallor
- Shock
Sources of iron in the diet
- Cereals
- Meat
- Vegetables
- Dairy
- Eggs
- Fish
- Chocolate
- Beverages
- Alcoholic beverages
- Soups, sauces, pickles
Risk factors of iron deficiency anaemia
- H.pylori infection
- Long-terms use of PPIs
- Blood loss: high menstrual losses, frequent blood donation
- Pregnancy
Explain dietary factors that explain iron deficiency in industrialised countries
- Low bioavailability
- Sedentary lifestyles
- Low micronutrient density (Highly processed foods contain more fat and sugar (‘empty calories’) than unprocessed foods)
How much red or processed meat is recommended by the UK government?
The UK government recommends no more than 70g of red or processed meat
Describe the function of Vitamin B12
- Development, myelination, function of CNS
- RBC formation, DNA synthesis
Describe the causes of B12 deficiency
Primary cause - impaired absorption of vitamin B12 (pernicious anaemia) resulting from a lack of intrinsic factor
Other causes of vitamin B12 deficiency include:
- Inadequate dietary intake of vitamin B12 e.g., vegan diet
- Gastric-related causes e.g., gastrectomy, gastric resection, atrophy gastritis, H.pylori infection
- Long-term use of drugs that affect gastric production (e.g., H2 receptor antagonists, PPIs) can worsen deficiency because gastric acid is needed to release B12 bound to proteins in food
- Intestinal causes e.g., malabsorption, ileal resection, Crohn’s disease affecting the ileum, chronic tropical sprue, HIV, and radiotherapy
- Drugs e.g., colchicine, neomycin, metformin, anticonvulsants
Consequences of vitamin B12 deficiency
- Neural tube defects
- Stroke
- Dementia
- The brain is particularly; in children, inadequate B12 stunts brain and intellectual development
Dietary sources of B12
Products of animal origin
- Meat (especially liver)
- Poultry
- Fish
- Milk and dairy products
- Eggs
Fortified breakfast cereals
Fermented food e.g., sauerkraut
Describe the NICE guidelines for treatment of B12 deficiency
Advise people to eat foods rich in vitamin B12.
Foods which have been fortified with vitamin B12 (E.g., some soy products, breakfast cereals and breads) are good alternative sources to meat, eggs, and dairy products
Describe the role of folate and folic acid
- RBC formation
- Cell growth and function
- Works with B6 and B12 to control elevated blood homocysteine
Good dietary sources of folate
- Liver
- Yeast extract
- Green leafy vegetables
- Legumes (beans, lentils)
- Orange juice
- Fortified cereals
At risk groups of folate deficiency
Children 11-18 years old
Women of child-bearing age
Describe a strategy made in the UK to deal with flic acid deficiency
in sept 2021, folic acid fortification of flour made mandatory in the UK to prevent spinal conditions in babies
What is is the controversy over safety of folic acid
There is a risk that if folic acid is given to people with undiagnosed deficiency of Vitamin B12 it may lead to neurological damage
This is because folic acid will correct the anaemia of Vitamin B12 deficiency and so delay diagnosis but will not prevent progression to neurological damage
Describe the NICE guidelines for treatment of folate deficiency
Give dietary advice: good sources of folate are broccoli, Brussel sprouts, asparagus, peas, chickpeas, and brown rice
Prescribe oral folic acid 5mg daily
Check vitamin B12 levels in all people before starting folic acid, as treatment can improve well-being such that it can mask underlying B12 deficiency and allow neurological disease to develop
In most people, treatment will be required for 4 months. However, folic acid need to be take for longer (sometimes for life), if the underlying cause of deficiency is persistent
Vulnerable groups in nutritional anaemia
- Infants and children (iron deficiency)
- Vegans (iron and B12 deficiency)
- Pregnant women (iron and folate deficiency)
- Elderly (iron, folate and B12 deficiency)
- Low income
- Ethnic minorities
Why may iron and B12 deficiency occur in children?
- Prolonged breast or bottle feeding may lead to iron/ B12 deficiency
- If weaning foods have a low iron/B12 content
- Vegan children
State the factors that make elderly patient at high risk of anaemia
- Higher risk of nutritional deficiencies
- Impaired absorption (particularly vitamin B12)
- Dental problems - restricted food choice
- Poor quality meals in institutions
- Lower socioeconomic status
- Less mobile - restricted shopping
- Mental problems - dementia, depression
- Lower physical activity requires lower energy intake
Causes of iron deficiency
Inadequate diet
Increased requirements
- Pregnancy
- Growth
Malabsorption
Blood loss
- Menstrual
- GI
- Urinary
- Lung
Laboratory findings of iron deficiency anaemia
- Microcytic hypochromic anaemia
- Serum ferritin reduced, serum iron low, raised transferrin and reduced saturation of iron building capacity
- Raised platelet count
- Blood film appearances: hypochromic/microcytic cells, anisocytosis/poikilocytosis, target cells and ‘pencil’ cells
- Bone marrow (not need for diagnosis): erythroblasts show ragged irregular cytoplasm; absence of iron from stores and erythroblast
Gi investigations in iron-deficiency anaemia
Faecal haemoglobin (FIT) - sensitive test for blood in stools
GI causes of iron deficiency anaemia
- Hookworm infections
- Oesophago-gastric cancer
- Coeliac disease
- Crohn’s disease
- Gastritis
- Peptic ulceration
- Oesophagitis
- Gastrectomy
- NSAID enteritis
- Meckel’s diverticulum
- Colon cancer - Especially right sided
- Large polyps
- Colitis
- Angiodysplasia
- Diverticular bleeding
- Haemorrhoids
Describe the main treatment of iron deficiency anaemia
Oral iron - ferrous sulphate for 3 months before meals 3x daily
Name 3 other preparations of iron replacement therapy
- Ferrous gluconate
- Sodium ironedate
- Ferric maltol
a) Side effects of iron replacement therapy e.g., ferrous sulphate
b) What should you do if patient experiences these symptoms?
a) Abdominal pain, diarrhoea or constipation
b) Lower dose or a different preparation
When should you consider parenteral iron over oral iron?
If absorption impaired
Macrocytic anaemia - megaloblastic causes
- B12 deficiency
- Folate deficiency
- Combine deficiency
- Abnormal folate metabolism: methotrexate
- Abnormal DNA synthesis: Orotic aciduira, azathioprine, Zidovudine
- Myelodysplasia
Macrocytic anaemia - non-megaloblastic causes
- Just macrocytosis
- Pregnancy
- Liver disease
- Alcoholism
- Reticulocytotic
- Hypothyroidism
- Drugs
- Marrow infiltration
- Sideroblastic anaemia
- Cold agglutinins
Causes of folate deficiency
Diet
- Anorexia
- Children
- Elderly
- Alcoholics
Increased utilisation
- Physiological: Pregnancy and growth
- Pathological: Haemolysis, cancers, inflammation
Malabsorption
- Diffuse small bowel disease
Urinary loss
- Haemodialysis
Drugs
- Phenytoin
- Primidone
- Sulfasalazine and related
- Methotrexate
Describe the treatment of folate deficiency
5mg oral folic acid daily for 4 months or continuously
Which patients should you provide folic acid as prophylaxis
- Pregnancy and preconception
- Haemolysis
- Methotrexate therapy
a) What is pernicious anaemia
b) What is the management?
a) Lack of intrinsic factor production leads to less absorption of vitamin B12 and so causes vitamin B12 deficiency
b) IM Vitamin B12 (cobalamin) replacement
Haemolytic anaemia
a) Symptoms
b) Signs
a)
- Fatigue
- Weakness
- Paraesthesia
- Dyspnoea
- GI symptoms (e.g., nausea, dyspepsia)
- Weight loss
b)
- Jaundice
- Drak urine
- Abdominal pain
- Atrophic glossitis
- Pallor
- Fever
- Splenomegaly
Investigations/Laboratory findings in haemolytic haemolysis
RBC - anaemia (normocytic or macrocytic)
Reticulocyte count - raised
Blood film - typical morphologies of associated with haemolysis which includes spherocytes, schistocytes, sickle cells
LDH - raised
LFTs (bilirubin) - raised
Serum haptoglobin - low
Inherited causes of haemolytic anaemia
Membrane defects
- Hereditary spherocytosis
Elliptocytosis
Enzyme defects
- G6PD deficiency
- Pyruvate kinase deficiency
Haemoglobinopathy
- Sickle cell disease
- Thalassaemia
Acquired causes of haemolytic anaemia
a) Immune mediated
b) Non-immune mediated
a)
Alloimune haemolysis
- Haemolytic disease of newborn
- Haemolytic transfusion reaction
AIHA
- Warm AIHA
- Cold AIHA
b)
- Mechanical trauma
- Microangiopathic haemolytic anaemia (MAHA): HUS, TTP, DIC
- Infections
- Renal disease
- Drugs and chemicals
- Hypersplenism
Name membrane defects that cause haemolytic anaemia
Hereditary spherocytosis
Hereditary elliptocytosis
Hereditary stomatocytosis
Pathophysiology of inherited membrane defects e.g., hereditary spherocytosis
RBC cannot maintain biconcave shape
In these conditions RBC is more easily damaged and removed by macrophages (so shorter half life of RBC)
Inheritance of hereditary sperocytosis
Autosomal dominant
Clinical features of inherited RBC membrane defects
- Cause of prolonged neonatal jaundice
- Mild anaemia presenting at any age
- Jaundice fluctuant
- Gallstones
- Aplastic crises precipitated by parovirus
Investigations for inherited RBC membrane defects
- Family history
- Blood film
- Haemolysis screen: FBC, reticulocytosis, LDH, billirubin
Laboratory findings of inherited RBC membrane defects
- Anaemia (usually mild)
- Reticulocytosis
- Bilirubin raised
- LDH raised
- Blood film shows abnormally shaped RBC
- Direct Coombs test negative
Treatment of inherited RBC defects
Folic acid
Splenectomy (in severe cases of HS)
Cholecystectomy (+ splenectomy) - pigment gallstones may cause cholecystitis
Inheritance of G6PD deficiency
X-linked recessive
Epidemiology of G6PD deficiency
Common in black (Africa), Mediterranean, Middle Eastern and oriental population
Usually seen in areas with a high prevalence of malaria
Predominantly male
Pathophysiology of G6PD deficiency
G6PD produces NADPH which is required for (reduced glutathione) regeneration
Glutathione rapidly inactivates oxidants that can damage RBC
When patients with G6PD are exposed to a variety of oxidants, they are rapidly depleted of glutathione
This leads to oxidation of numerous proteins in RBC that alters and renders them susceptible to break down (haemolysis) by macrophages
Role of G6PD
To prevent oxidative stress in RBC
This is by producing NADPH which is required for (reduced) glutathione regeneration.
Glutathione inactivates oxidants that can
damage RBC
Precipitants of G6PD deficiency
Drugs
- Antibiotics: nitrofurantoin, fluoroquinolone, sulphonamides
- Antimalarials: primaquine, chloroquine (possible), quinine (possible)
- Other: Dapsone, Methylene blue, Sulfonylureas, Rasburicase
Food
- Fava beans
Infections
Moth balls
Clinical features of G6PD deficiency
a) Symptom
b) Signs
a)
- Lethargy
- Dizziness
- SOB
- Jaundice
- Dark urine
- Abdominal/back pain
b)
- Pallor (anaemia)
- Jaundice
- Splenomegaly
Diagnosis of G6PD deficiency
Assessment of G6PD enzyme activity
Who do you test for G6PD deficiency?
Patients with unexplained haemolytic anaemia
Babies with neonatal jaundice
Patients on medications that is down to precipitate haemolysis in G6PD deficiency
Laboratory features of G6PD deficiency
FBC - anaemia and macrocytosis
Blood film - Heinz bodies, may show fragments due to haemolysis
Reticulocyte count - raised
LFTs (bilirubin) - raised
Haptolglobin - reduced
Coombs test - negative
Management of G6PD deficiency
- Avoidance of precipitants of oxidative injury
- Treat infection if present
- Transfuse RBC if necessary (in severe anaemia)
- Folic supplementation (in severe anaemia)
Thalassaemia - definition
Reduced/no alpha or beta chains produced
Alpha thalassaemia - definition
Reduced/no alpha chains produced
Beta thalassaemia - definition
Reduced/no beta chains produced
Thalassaemia major - definition
No alpha/beta chains
Thalassaemia strain - definition
Reduce alpha/beta chains person is asymptomatic
Beta thalassemia clinical features
Severe anaemia from 3-6 months
Failure to thrive, intercurrent infection, pallor, mild jaundice
Liver and spleen enlargement
Skeletal changes
- Thalassaemic facies
- Osteoporosis/osteopenia
- Body habits changes: typically, short limbs (due to early fusion of epihyses)
- Skull (frontal bossing), pelvis, ribs, and spinal changes may be seen
- Bony pain
Disorders associated with iron overload
- Growth impairment
- Hepatic impairment
- Cardiac failure
- Cardiac arrhythmias
- Joint symptoms
- Hyper-pigmented appearance
- Endocrine disorders: hypogonadism and hypothyroidism and diabetes mellitus
Other abnormalities
- Pulmonary: obstructive and restrictive defects
- Thrombosis
- Leg ulcers
Alpha thalassaemia major: Haemoglobin Barts definition
Four alpha genes are inactive
Alpha thalassaemia major: Haemoglobin Barts - consequence
Four alpha genes are inactive, which is incompatible with extrauterine life
Leads to hydros fetalis (Fatal in utero due to severe anaemia, high-out cardiac failure and generalised oedema)
Alpha thalassaemia major: Haemoglobin H (HBH) - definition
Deletion or functional inactivity of 3/4 alpha genes
Alpha thalassaemia major: Haemoglobin H (HBH) - clinical features
Variable phenotype from mild affected to requiring life-long blood transfusions
Bone deformities and features of iron overload do not usually occur
Pallor
Ananemia
Jaundice
Gallstone disease
Extramedullary haematopoiesis: hepatosplenomegaly, skeletal changes
Osteopenia/osteoporosis
Aplastic/hyoplastic crisis
Leg ulcers
Thalassaemia trait - clinical features
Mild microcytic anaemia
Asymptomatic
Thalassaemia - screening protocals
Screening for thalassaemia is offered to all pregnant women within the uK
Advise to parents who have alpha thalassaemia with 2/4 genes deleted?
There is a risk of conceiving a foetus with no alpha genes leading to hydrops fetalis
Thalassaemia laboratory findings
FBC - anaemia, low mCV
Blood film - hypochromic, microcytic
LFTS (unconjugated bilirubin) - raised
Haemolysis screen - LDH raised, haptoglobin reduced, Coombs test negative
Hb electrophoresis / Hyper performance liquid chromatography - absence HbA (beta thalassaemia major) / increased HbA2 (beta thalassaemia trait)
Genetic analysis - for alpha that
Diagnostic testing for beta thalassaemia
Hb electrophoresis
Diagnostic testing for alpha thalassaemia
Genetic analysis
Diagnostic findings of beta thalassaemia major in Hb electrophoresis
Absence HbA
Diagnostic findings of beta thalassaemia trait in Hb electrophoresis
Increased HbA
Management of thalassaemia major
Lifelong transfusions (every 3-4 weeks)
Splenectomy
Allogenic bone marrow transplantation
Treat iron overload with iron chelation
Beta thalassaemia: treat osteoporosis with bisphosphonates and Vitamin D and calcium
Management of thalassaemia treatment
Asymptomatic - do not need treatment
Avoid iron unless iron deficient
Genetic counselling
Genetic inheritance of sickle cell disease
Autosomal recessive
Sickle cell disease - pathophysiology
Point mutations leads to single amino acid substitution of valine to glutamate at position 6 in beta chain. This forms HbS
HbS forms crystals when exposed to low oxygen levels - causes ‘sickling’ of RBC
This damages RBC leading to chronic haemolysis
Clustering results in blood vessel occlusion
Give 3 types of crises in sickle cells disease
Vaso occlusion
Visceral sequestration
Aplastic crisis
Vaso-occlusion in sickle cell disease - pathophysiology
Due to shape and stickiness, sickle cells can occlude capillaries and cause infarction of tissue supplied by that blood vessel
Vaso-occlusion in sickle cell disease - consequences
Acute painful episodes
Acute chest syndrome
Renal infarction
Bone infarction or dactylitis
Myocardial infarction
Stroke
Venous thromboembolism
Priapism (persistent, painful erection)
Visceral sequestration in sickle cell disease - pathophysiology
Caused by sickling with pooling of red cells in the liver, spleen or lung
Aplastic crisis in sickle cell disease - pathophysiology
Occurs following infection by B19 Parovirus
This causes temporary arrest for erythropoiesis (virus prevents RBC production)
In health individuals there is no consequence as lifespan of RBC is 120 days
Due to reduced red cell survival in sickle cell 910-20 days) this can rapidly cause severe anaemia (requiring blood transfusion)
Sickle cell disease - clinical features
Anaemia
Increased susceptibility to infections
Vaso-occlusive phenomenon
Acute painful episodes
Acute chest syndrome: fever, chest pain, hyperaemia, wheezing, cough, respiratory distress
Chronic complications
- Neurological: stroke and seizure disorders
- Blood: chronic anaemia
- Bone: osteoporosis and avascular necrosis
- Cardiac: cardiomyopathy and heart failure
- Pulmonary: pulmonary hypertension
- Kidneys: CKD
- Liver: liver damage from iron overload, gallstones
- Others: chronic pain, delayed puberty, leg ulcers and retinal disease
Acute chest syndrome in sickle cell disease - definition
New radiodensity on chest imaging accompanied by fever and/or respiratory symptoms.
Acute chest syndrome in sickle cell disease - clinical features
fever, chest pain, hyperaemia, wheezing, cough, respiratory distress
Sickle cell disease: chronic complications
Neurological: stroke and seizure disorders
Blood: chronic anaemia
Bone: osteoporosis and avascular necrosis
Cardiac: cardiomyopathy and heart failure
Pulmonary: pulmonary hypertension
Kidneys: CKD
Liver: liver damage from iron overload, gallstones
Others: chronic pain, delayed puberty, leg ulcers and retinal disease
Sickle cell disease - laboratory features
FBC: mild anemia
Haemolysis screening: raised LDH, raised bilirubin, low haptoglobin
Blood film - sickle cells and Howell-jolly bodies (hyposplenism)
Sickle solubility screen - positive
Hb electrophoresis/Hyper performance liquid chromatography - HbS, no HbA, variable amounts of HbF
Describe findings of sickle solubility screen in sickle cell diseases
Sickle solubility screen - positive
HbS less soluble when reduced
Sickle cell disease - Hb electrophoresis/Hyper performance liquid chromatography
Shows hbS, no HbA, variable amounts of HbF
Sickle cell disease - screening protocols
Newborn screening - involves a blood spot sample (typically heel prick) that is taken on day 5 of life
Sickle cell disease - prophylactic management
Prophylactic
- Patient education
- Avoid precipitating factors
- Folic acid
- Pneumococcal vaccine; regular oral penicillin
- Stroke prevention: transcranial doppler ultrasound is perfumed annually between 2-16 years of age to determine risk of stroke
Crises
- Analgesia (opiates), rest, rehydration, oxygen +/- antibitocis
Blood transfusion
Exchange transfusion
Oral hydroxycarbamide
Crizanlizumab
Stem cell transplantation
Joint replacement surgery for avascular necrosis
Iron chelation - prevent iron overload
Sickle cell trait - clinical features
No/mild anaemia
Sickle cell trait - management
Genetic counselling
Advice that acre should be taken during anaesthesia and high altitudes (hypoxia can rarely cause sickling)
Warm autoimmune haemolytic anaemia - definition
Antibodies (IgG) attack RBC at 37 degrees degrees
Cold autoimmune haemolytic anaemia
Antibodies (IgM) attack RBC below 37 degrees celsius
Warm autoimmune haemolytic anaemia - antibody associated
IgG
Cold autoimmune haemolytic anaemia - antibody associated
IgM
Warm auto immune haemolytic anaemia - Causes
Idiopathic
Secondary
- Autoimmune conditions e.g., SLE
- Disordered immune system e.g., CLL, low grade lymphoma
- Drugs e.g., penicillin, methldopa
Cold haemolytic anaemia - causes
Idiopathic
Secondary
- Lymphoma
- Infections: mycoplasma pneumonia, EBV
- Paroxysmal cold haemoglobinuria
Autoimmune haemolytic anaemia - laboratory findings
FBC: anaemia
Reticulocytes: raised
LDH: raised
LFTs (unconjugated bilirubin): raised
Blood film: spherocytes in warm haemolytic anaemia; schistocytes and agglutination in cold AIHA
Direct antiglobulin test (DAT)/Coombs: positive
Autoimmune haemolytic anaemia - blood film findings
Spherocytes in warm haemolytic anaemia;
Schistocytes and agglutination in cold AIHA
Warm autoimmune haemolytic anaemia - management
- Remove or treat underlying cause
- Corticosteroids e.g., prednisolone emg/kg orally with subsequent gradual reduction
- Other immunosuppressive drugs e.g., rituximab, azathioprine, ciclosporin, cyclophosphamide, mycophenolate
- Blood transfusion if necessary
- Consider splenectomy if steroid and immunosuppressive drug therapy fails
- Folic acid
Cold autoimmune haemolytic anaemia - management
- Keep the patient warm
- Consider immunosuppression: corticosteroids, rituximab
- Consider plasma exchange to lower antibody tire
- Folic acid
Thrombotic thrombocytopenia purpura - pathophysiology
There is a deficiency of ADAMTS13 (metalloprotease enzyme) which normally breaks down large multimers of vWF
Abnormally large and sticky multimers of vWF causes platelets to clump within vessels leading to shearing of RBCs in vessels
Thrombotic thrombocytopenia purpura - Investigations
FBC
Blood film
Reticulocyte count
LFTs: Unconjugated bilirubin
LDH
DAT (Coombs)
Virology screen
ADAMTS13 assay
Thrombotic thrombocytopenia purpura - treatment
- Plasma exchange using fresh from plasma
- Antiplatelet drugs
- Corticosteroids
- Splenectomy
- Rituximab
Thrombotic thrombocytopenia purpura - clinical features (classic pentad)
Pentad of:
- Thrombocytopenia
- Neurological impairment
- Fever
- Renal impairment
- Microangiopathic haemolytic anaemia
Disseminated intravascular coagulation - pathophysiology
Occurs when the balance between the formation of new clots (coagulation) and the breakdown of clots (fibrinolysis) is tipped in favour of coagulation.
It causes widespread clot formation and tissue ischaemia whilst also using up platelets and clotting factors, leading to excess bleeding.
Disseminated intravascular coagulation - clinical features
- Purpura
- Ecchymoses
- GI bleeding
- Bleeding from IV sites and venepuncture may occur
- Impaired renal function
- ARDS
- Adrenal necrosis
- Shock
- Thromboembolism
Disseminated intravascular coagulation - laboratory features
- Thrombocytopenia
- raised D-dimer
- low platelets
- low fibrinogen
Disseminated intravascular coagulation - management
- Treat underlying cause
- Fresh frozen plasma
- Platelet concentrated and cryoprecipitate if bleeding is dominant
- Anticoagulant therapy if thrombosis is dominant
Haemolytic uremic syndrome - main cause
Occurs in children and 90% of cases in children are caused by E-coli which produces a shiga-like toxin
Haemolytic uremic syndrome - clinical features (classic triad)
AKI
Microangiopathic haemolytic anaemia
Thrombocytopenia
Haemolysis - Infectious cause
Malaria
Haemolysis - chemical and physical agent cause
Drugs - e.g., dapsone
Cooper
Lead
Burns
Snake and spider bites
Paroxysmal nocturnal haemoglobinuria (PNH) - pathophysiology
Acquired defect of marrow stem cells that leads to defect in anchorage of surface proteins because of absence of GPI (glycosylphosphatidylinositol)
GPI prevents lysis of RBC therefore in PNH, RBC is rendered sensitive to lysis by complement
Paroxysmal nocturnal haemoglobinuria (PNH) - Clinical features
- Patients present early adulthood with nocturnal episodes of intravascular haemolysis
- Dark urine
- Increased risk of clot formation, particularly at unusual sites e.g., hepatic veins
Paroxysmal nocturnal haemoglobinuria (PNH) - management
- Eculizumab - reduce haemolysis, thrombosis, and improve life expectancy
- Transfusion of leucodepelted RBC may be necessary
- Warfarin may be needed to prevent thrombosis
- Allogenic stem cell transplant (severe cases)
Microcytic anaemia - causes
Thalassaemia
Anaemia of chronic disease
Iron-deficiency anaemia
Lead positioning
Sideroblastic anaemia
Normocytic anaemia - causes
Anaemia of chronic disease
Acute blood loss
Chronic renal failure
Mixed B12/folate and iron deficiency
Bone marrow disorders
Macrocytic anaemia - causes
B12/folate deficiency
Liver disease
Drugs inc. alcohol
Reticulocytosis (haemolysis)
Hypothyroidism
Myelodysplasia
Pregnancy
Sideroblasic anaemia - pathophysiology
Occurs due to ineffective erythropoiesis, resulting in increased iron absorption and deposition within the bone marrow
Sideroblastic anaemia - clinical/laboratory features
Microcytic anaemia refractory to intensive iron therapy
Atypically high serum ferritin and iron
Acute haemolytic transfusion - commonest cause, clinical features and management
Commonest cause - ABO incompatibility
Clinical features - fever, hypotension, anxiety, red-coloured urine. DIC
Management - stop transfusion, supportive care e.g., blood pressure support, hydration combined with diuretics to increase urine output
Delayed transfusion reaction (more than 24 hours post transfusion)
- Delayed haemolytic transfusion reaction
- Transfusion associated graft v host disease
- Post transfusion pupura
Febrile non haemolytic transfusion reaction: clinical features and management
Clinical features
- At the end of transfusion or up to 2 hours afterwards
- Fever
Management
- Stop transfusion
- Treat fever with antipyretic
Allergic reaction (anaphylaxis) transfusion reaction - clinical features and management
Clinical features
- Itchy rash
- Angioedema
- Shortness of breath
- Vomiting
- Light headedness
- Hypotension
Management
- Stop transfusion
- Administer adrenaline
Bacterial contamination transfusion reaction - clinical features and management
Clinical features
- Rapid severe pyrexia
Management
- Stop transfusion
- Oxygen
- Diuretics
Transfusion associated circulatory overload (TACO) - Clinical features and management
Clinical feature
- With 12 Horus of transfusion
- Bipedal oedema
- Bibasal crackles on auscultations
Management
- Stop transfusion
- Oxygen
- Diuretics
Transfusion related acute lung injury (TRALI) - Clinical features and management
Clinical features
- Occurs within 6 hours of transfusion
- Respiratory symptoms: dyspnoea, cough, ARDs
Management
- Stop transfusion
- Respiratory support
- Supportive care and monitoring
- Inform blood bank and haematology
Transfusion related acute lung injury (TRALI) - CXR changes
“white out”
Delayed haemolytic transfusion reaction - laboratory findings, clinical features and management
Laboratory findings
- Low Hb
- High bilirubin
Clinical features
- Within 1-4 days of transfusion
- Fever
- Jaundice
Hameglobinuria
Management
- Stop transfusion
- IVIg and steroids
Transfusion associated graft v host disease - clinical features and management
Clinical features
- Within 1-2 weeks of transfusion
- Flue like illness
- Rapidly develops into multi organ failure
Management
- Supportive
- Immunosuppressants
Post transfusion purpura - cause, clinical features and management
Causes
- Occurs when the body produces alloantibodies to the introduced platelets antigens
Clinical features
- 5-9 days post transfusion
- Thrombocytopenia
- Purpura
Management
- Usually self limited
- IV Ig
Acute transfusion reaction (up to 24 hours post transfusion) - types
- Febrile non haemolytic transfusion reaction
- Allergic reaction (anaphylaxis)
- Acute haemolytic transfusion reaction
- Transfusion associated circulatory overload (TACO)
- Transfusion related acute lung injury (TRALI)
How is the risk of transfusion associated graft vs host disease prevented?
Irradiated blood/blood product
Indications of irradiated blood/blood products - lifelong and temporary
Lifelong
- Hodgekin’s disease
- Fludarabine, Bendamustine or Alemtuzumab
- Congenital immunodeficiency state
Temporary
- Stem cell harvest
- Autologous transplant
- Allogenic transplant
- Intra uterine transfusion
Tropical infections commonly causing splenomegaly
Malaria
Leishmaniasis
Schistosomiasis
Trypanosomiasis
Leishmaniasis - laboratory findings
Hyergammaglobulinaemia
Normochromic anaemia
Raised ESR
Bone marrow aspirate shows macrophages containing Leishman-Donovan bodies
Leishmaniasis - management
Pentavalent antimonial compounds or with amphotericin B (AmBisone)
Lymphatic filariasis - causative organism
Filarial worm - Wuchereria Bancrofti
Lymphatic filariasis - clinical features
Fever
Pain
Acute inflammation
Lymphatic filariasis - management
Diethylcarbamazine (unlicensed)
Chemotherapy
Trypanosomiasis - transmission
The parsites (Trypanosome brucei gambiense and Brucei rhodesiense) transmitted by tsetse fly
Trypanosomiasis - clinical features
Fever
Lymphadenopathy
Anaemia
Splenomegaly
Progressive parasitaemia
- Drowsiness
- Meningoencephalititis
Complications - haemolytic anaemia, thrombocytopenia and DIC
Trypanosomiasis - diagnosis
Pentamidine (antimicrobial) and Suramin
