Normocytic Anaemia Flashcards
Give 3 causes of normocytic anaemia.
- Acute blood loss / bleeding
- Anaemia of chronic disease (80% is normocytic)
- Hypothyroidism
- Haemolytic anaemia
- Bone marrow failure; - renal failure (decreased erythropoietin)
- Pregnancy
Define haemolytic anaemia.
Where there is destruction of RBCs (haemolysis) leading to anaemia.
Can either be caused by inherited conditions or acquired conditions.
Name 3 categories of inherited causes of haemolytic anaemia.
- Enzymopathies (Enzyme defects)
- Membranopathies (Membrane defects)
- Haemoglobinopathies (Abnormal Hb production)
Give 2 examples of enzymopathies for haemolytic anaemia.
- G6PD Deficiency
- Pyruvate kinase deficiency
Give 2 examples of membranopathies for haemolytic anaemia.
- Hereditary Spherocytosis
- Hereditary Elliptocytosis
Give 2 examples of haemoglobinopathies for haemolytic anaemia.
- Thalassaemia
- Sickle Cell Anaemia
Give 5 examples of acquired conditions that cause haemolytic anaemia.
- Autoimmune haemolytic anaemia
- Alloimmune haemolytic anaemia (transfusions reactions and haemolytic disease of newborn)
- Paroxysmal nocturnal haemoglobinuria
- Microangiopathic haemolytic anaemia
- Prosthetic valve related haemolysis
Give the 3 main signs + symptoms for haemolytic anaemia.
- Pallor due to Anaemia -> due to the reduction in circulating RBCs
- Splenomegaly -> as the spleen becomes filled with destroyed RBCs
- Jaundice -> as bilirubin is released during the destruction of RBCs
What is sickle cell disease?
A haemoglobin disorder of quality. HbS polymerises -> sickle shaped RBC.
What is the advantage of being a carrier of sickle cell disease?
Carriage offers protection against falciparum malaria.
What gene causes sickle cell disease and on which chromosome?
An abnormal gene for β-globin on CH 11
Describe the difference between sickle cell trait and sickle cell disease.
2 abnormal copies = homozygous HbSS = sickle cell disease.
1 abnormal gene = heterozygous HbAS = sickle cell trait (carrier) = usually asymptomatic.
Why is sickle cell not diagnosed until 6 months after birth?
Not diagnosed until 6 months after birth because:
= HbF is not affected by sickle cell anaemia as it is made up of 2 alpha and 2 gamma chains.
Why does sickle cell anaemia not present until after 6 months of age?
HbF is not affected by sickle cell anaemia as it is made up of 2 alpha and 2 gamma chains.
What is the risk factor for sickle cell anaemia?
Family history
Describe the inheritance pattern of sickle cell disease.
Autosomal recessive. Sickle cell disease is homozygous SS.
What is the pathogenesis of sickle cell anaemia?
HbS polymerizes if hypoxia/acidosis causing RBCs to sickle - rigid, fragile cells that occlude small vessels and have short lifespan (haemolyse).
If both parents are carriers of the sickle trait, what is the chance that their first child will have sickle cell disease?
Their offspring have a 1/4 chance of being affected with a sickle cell disease. (50% chance of being a carrier).
How long do sickle cells last for?
5-10 days - this explains why sickle cell disease is described as haemolytic.
What is the significance of parvovirus for someone with sickle cell disease?
Parvovirus is a common infection in children. It leads to decreased RBC production and can cause a dramatic drop in Hb in patients who already have a reduced RBC lifespan. This can be dangerous for someone with sickle cell.
What factors can precipitate a sickle cell crisis?
CHIDS:
Cold
Hypoxia (including extreme exercise)
Infection
Dehydration
Stress
Give 4 acute complications of sickle cell disease.
- Very painful crisis.
- Stroke in children.
- Cognitive impairment.
- Infections.
Give 4 complications for chronic sickle cell anaemia/disease.
o Renal impairment.
o Pulmonary hypertension.
o Joint damage, bone problems, leg ulcers.
o Poor growth.
o Gallstones.
o Lung fibrosis.
o Neurological complications – TIA, fits, coma, cerebral infarction.
o Cardiac – cardiomegaly, MI, arrythmias, Fe-overload cardiomyopathy
Give the 4 different types of crisis that can happen in sickle cell anaemia.
- Splenic sequestration crisis (acute)
- Aplastic / Bone Marrow crisis
- Haemolytic crisis
- Vaso-occlusive crisis
What is splenic sequestration?
A type of sickle-cell crisis:
- Vaso-occlusion produces acute painful enlargement of spleen.
- Pooling of RBCs in spleen = hypovolaemia = circulatory collapse and death.
- Immediate transfusion needed.
Describe vaso-occlusive crises seen in sickle-cell anaemia.
Severe pain due to effect on marrow of microvascular occlusion. Acutely painful hands and feet.
Specific signs + symtoms:
Dactylitis
Visual floaters
Chest/abdominal pain (mesenteric ischaemia)
Chronic renal failure.
Avascular necrosis femoral head/bone infarcts.
General signs + symptoms:
Parent with sickle cell anaemia/trait
Symptoms of anaemia + haemolysis = jaundice, pallor, lethargy, tachycardia.
For sickle cell crisis, what syndrome can be caused?
Acute Chest Syndrome (ACS).
Describe ACS.
A vaso-occlusive crisis of the pulmonary vasculature.
What can ACS be caused by? Give 3 examples.
- Infection (due to Chlamydia, mycoplasma and Streptococcus pneumoniae)
- Fat embolism from necrotic bone marrow
- Pulmonary infarction due to sequestration of sickle cells (where sickle cells get trapped in the pulmonary vasculature)
For ACS, what are the 2 most common causes of death?
- Pulmonary hypertension
- Chronic lung disease
What symptoms can ACS result in? Name 3.
SOB, chest pain, hypoxia
What test is diagnostic for sickle cell anaemia?
Hb electrophoresis
What are the investigations for sickle cell anaemia?
- FBC
- Low Hb -> in the range of 60-80 g/L
- Raised reticulocyte count - Blood film
- Sickle cells and target cells (pale centre)
- Howell-Jolly bodies - Sickle solubility test
- Positive result = HbSS/HbAS instead of HbA - Hb electrophoresis = DIAGNOSTIC!!!
- Distinguishes HbSS and HbAS
What is seen after doing a blood film for sickle cell anaemia?
- Howell-Jolly bodies
- Sickle cells
What drug can be used to prevent painful crises in people with sickle cell anaemia?
Hydroxycarbamide.
Give the management for acute sickle cell anaemia.
Acute painful attacks:
1. IV fluids
2. Analgesia – morphine, codeine, paracetamol and NSAIDs
3. Oxygen and antibiotics, if required
Give the management for sickle cell anaemia.
- Blood transfusion given for:
*Acute chest syndrome, Acute anaemia due to acute splenic sequestration, Aplastic crisis, Stroke, Heart failure
(Note: increased risk of iron overload)
- Oral HYDROXYCARBAMIDE:
- Increases HbF concentrations and to try prevent painful crises
- Need monthly blood tests - Regular vaccinations e.g. pneumococcal vaccine
- Penicillin prophylactically = lifelong phenoxymethylpenicillin
→ risk of infection - Stem cell / bone marrow transplant → curative
What can be given orally to increase HbF and for the prevention painful crises in sickle cell anaemia?
Oral Hydroxycarbamide
Describe the inheritance pattern for membranopathies.
Autosomal dominant.
Name 2 common membranopathies.
- Spherocytosis.
- Elliptocytosis.
Briefly describe the physiology of membranopathies.
Deficiency of red cell membrane proteins caused by genetic lesions
Give 3 clinical features of a patient with a membranopathy.
- Jaundice.
- Anaemia.
- Splenomegaly.
Define Hereditary Spherocytosis / Hereditary Elliptocytosis.
HS: autosomal dominant genetic condition that causes sphere-shaped RBCs that are fragile; the most common inherited haemolytic anaemia in northern Europeans.
HE: autosomal dominant genetic condition that causes the RBCs to be ellipse-shaped
Give 4 symptoms of Hereditary Spherocytosis / Hereditary Elliptocytosis.
- Jaundice at birth
- Gallstones – due to chronic haemolysis
- Leg ulcers
- Splenomegaly
Which 2 conditions can stop the course of HS/HE?
- Aplastic anaemia (sudden stop in RBC production) e.g. after infections, particularly with erythrovirus (parvovirus) OR
- Megaloblastic anaemia (result of folate depletion) caused by the hyperactivity of the BM
Outline the investigations for HS/HE.
- Blood film:
- Shows spherocytes (spherical RBCs)
- Raised reticulocytes (due to rapid RBC turnover) - FBC:
- Anaemia (Hb low)
- MCHC (mean corpuscular haemoglobin concentration) raised - Haemolysis:
- Serum bilirubin and urinary urobilinogen is RAISED - Direct antiglobulin (Coombs’) test:
- This is NEGATIVE, virtually ruling out an autoimmune haemolytic anaemia, in which spherocytes are also commonly present
What is the management for HS/HE?
- Folate supplementation
- Splenectomy
- Removal of the gallbladder (cholecystectomy)
What is glucose-6-phosphate dehydrogenase (G6PD) deficiency?
X linked recessive haemolytic condition caused by mutation in the G6PD gene leading to G6PD enzyme deficiency.
Common in parts where malaria is common as it’s protective!
What does G6PD do?
Catalyses step 1 of pentose phosphate pathway (similar glycolysis), which generates NADPH (important for red cells to protect from oxidative stress) - protects RBC membrane from damage.
Why does a deficiency in glucose-6-phosphate dehydrogenase lead to shortened red cell lifespan?
G6PD protects cells against oxidative damage.
Give 5 causes for G6PD deficiency syndrome.
- Infections
- Medications e.g. antimalarials (e.g. primaquine, quinine & chloroquine), antibacterials (e.g. most sulphonamides, ciprofloxacin), sulfonylureas, sulfasalazine
- Fava beans (broad beans)
- Red wine
- Soy
- Metabolic acidosis
Which disease does G6PD deficiency syndrome protect?
Common in parts where malaria is common as it’s protective!
Who does G6PD deficiency syndrom eaffect more? Male or females?
Males
Give 3 signs of G6PD deficiency.
Crises characterised by:
- Haemolysis.
- Jaundice - specifically neonatal jaundice!
- Anaemia.
Give 4 symptoms during G6PD deficiency syndrome during attacks.
- Jaundice (usually in the neonatal period)
- Gallstones
- Anaemia
- Splenomegaly
- Dark urine (suggests intravascular haemolysis)
Give some precipitants of G6PD deficiency crises
Henna.
Favism (ingesting fava/broad beans).
Drugs (cephalosporins), infections.
Name the 3 tests to do to investigate possible G6PD deficiency syndrome.
- Blood film
- FBC
- G6PD enzyme assay
What is seen in a blood film during attacks?
o Heinz bodies present
o Bite cells present
o Reticulocytosis
Management of G6PD deficiency at acute haemolysis
- Maintain fluid intake
- Folic acid 5mg orally
- Blood transfusion if severe anaemia (<7g/dL)
- Renal support if renal impairment
Describe the management for G6PD deficiency syndrome.
- Stop offending drugs and or fava beans
- Blood transfusion may be lifesaving
- Splenectomy is not usually helpful
Give 2 complications for G6PD deficiency syndrome.
Gallstones.
Kidney damage.
What is malaria?
Parasitic infection caused by protozoa of genus plasmodium
How is malaria transmitted?
Protozoa that is transmitted by bite of infected female Anopheles mosquito
What is the most dangerous cause of malaria?
Plasmodium falciparum → 75% of UK cases
Give the 4 causes of malaria (the 4 species).
4 species of Plasmodium:
1. P vivax
2. P ovale
3. P malariae
4. P falciparum
Give 3 signs for malaria.
- Pallor (anaemia)
- Jaundice (unconjugated bilirubin from RBC destruction)
- Hepatosplenomegaly (compensation for anaemia)
Give 3 symptoms for malaria.
- Fever, sweats, rigors (in spikes)
- Fatigue (anaemia)
- Headaches
- Myalgia / Malaise
- Vomiting
- Diarrhoea
Give 3 features of Vivax/ovale malaria
Anaemia, tender hepatosplenomegaly, mild illness
Which species cause anaemia and milder form of malaria??
- P vivax
- P ovale
Give 3 features of Malariae malaria
Relatively mild, more chronic, glomeulonephritis/nephrotic syndrome
Give 3 features of Falciparum malaria
Anaemia, jaundice, hepatosplenomegaly, cerebral malaria (fits, confusion, coma), metabolic acidosis, pulmonary oedema, hypoglycaemia, diarrhoea, DIC
Which species causes the more chronic form of malaria?
P Malariae
Give 5 symptoms for malaria caused by P falciparum.
- Anaemia
- Jaundice
- Hepatosplenomegaly
- Cerebral malaria (fits, confusion, coma)
- Metabolic acidosis
- Pulmonary oedema
- Hypoglycaemia
- Diarrhoea
- DIC
What are the investigations for malaria diagnosis?
- Giemsa-stained Thick and thin blood smears
- Thick = diagnoses malaria
- Thin = quantifies % of infected RBCs, identifies species
- Rapid diagnostic tests (RDTs)
- FBC
- Clotting profile
Describe the management of malaria.
Before treating, take into account:
- Whether they’ve taken any prophylaxis - which type? Likely their malaria is resistant, so don’t treat them with this!
- Examples of prophylaxis: mefloquine, atovaquant, proguanil, chloroquine, doxycycline.
P. Falciparum malaria:
- Uncomplicated = oral riamet or quinine ± doxycycline.
- Complicated = IV artesunate or quinine.
Non P. Falciparum malaria:
- Oral chloroquine.
Give 3 prevention methods for malaria.
- Full body clothing
- Mosquito repellent
- Mosquito nets
- Indoor insecticide sprays
- Clean water
- Antimalarials (malarone, mefloquine, doxycycline)
What drugs can be used as prophylaxis for malaria?
Mefloquine, atovaquant, proguanil, chloroquine, doxycycline.
Give 3 complications for malaria.
- Cerebral malaria
- Bilious malaria
- AKI
- Pulmonary oedema
- DIC
- Severe haemolytic anaemia
- Multi-organ failure and death
What is autoimmune haemolytic anaemia (AIHA)?
Occurs when antibodies are created against the patient’s RBCs. These antibodies lead to destruction of RBCs.
What are the 4 main types of AIHA?
- Warm antibody haemolytic anaemia
- Cold antibody haemolytic anaemia (cold agglutinin disease)
- Paroxysmal cold haemoglobinuria
- Mixed AIHA (MAIHA)
Give 2 symptoms specific for Cold agglutination disease.
- Acrocyanosis.
- Raynaud phenomenon with a rare complication of gangrene.
Give 3 symptoms for Paroxysmal cold haemoglobinuria.
- Red urine in the morning containing haemoglobin and haemosiderin.
- Anaemic due to the haemolysis
- Predisposed to thrombosis (e.g. DVT, PE and hepatic vein thrombosis)
- Predisposed to smooth muscle dystonia (e.g. oesophageal spasm and erectile dysfunction)
What are the 2 main categories of immune-mediated haemolytic anaemia? How do you treat each?
Warm = IgG mediated, Rx is steroids
Cold = IgM mediated, Rx keep warm.
Investigations for AIHA.
- Bedside investigation: Urinalysis
- High urinary urobilinogen
- High unconjugated bilirubin
- Low conjugated bilirubin - FBC
- Normocytic anaemia
- High serum lactate dehydrogenase (LDH)
- Reticulocytosis - increased reticulocytes - Blood film
- Schistocytes (fragments of red blood cells) - Direct Coombs test
- Is negative if it is not autoimmune
- Is positive in autoimmune haemolytic anaemia
Because of the jaundice, what markers will be elevated in the blood for haemolytic anaemia?
- High serum unconjugated bilirubin
- High urinary urobilinogen
- High faecal stercobilinogen
What would a FBC show for haemolytic anaemia?
- Normocytic anaemia
- Reticulocytosis
- High serum LDH
Management for AIHA.
o Blood transfusions
o Prednisolone (steroids)
o Rituximab (a monoclonal antibody against B cells)
o Splenectomy
What is aplastic anaemia?
Non-haemolytic anaemia due to BM failure
I.E. BM stops making all cells
What is the triad for aplastic anaemia?
- Pancytopenia
- Hypoplastic BM
- No abnormal cells
Give some causes of aplastic anaemia.
Major associations = pregnancy, coeliac, SLE
Acquired causes:
- Idiopathic (50%)
- Drug/toxin exposure (Chemothepray drugs, NSAIDs, antibiotics like chloramphenicol, gold)
- Post viral (e.g. Epstein-Barr virus, HIV, Hepatitis and TB)
Inherited causes:
- Fanconi anaemia (AR)
- Shwachman-Diamond syndrome (AR)
Briefly describe the pathophysiology of aplastic anaemia.
- A stem cell disorder in which the cells of the BM that develop into mature blood cells are damaged, leading to low numbers of RBCs, WBCs, and/or platelets.
- Characterised by pancytopenia → anaemia, leukopenia and thrombocytopenia.
- Due to a reduction in the number of pluripotent stem cells, together with a fault in those remaining or an immune reaction against them, so that they are unable to repopulate the BM
Give the 3 general signs of aplastic anaemia.
Presents with neutropenia (infections), anaemia symptoms and thrombocytopaenia (bleeding and bruising)
Give 2 specific signs/features of aplastic anaemia.
- Bruising with minimal trauma.
- Blood blisters in mouth.
What tests would you perform in aplastic anaemia?
What would it show?
- Blood count:
- Pancytopenia with low reticulocyte count - Bone marrow examination:
- Hypocellular marrow with increased fat spaces
- No abnormal cell population
How would you treat aplastic anaemia?
If asymptomatic - give neutropenic regimen.
If severe - matched related allogenic marrow transplant (can be curative) + RBC and Platelet transfusion + Antibiotics
- Treatment of cause
- Broad-spectrum antibiotics parenterally urgently to any patient with severe neutropenia with a fever
- Give red cell transfusion and platelets
- Bone marrow transplant
o From HLA identical sibling or donor treatment of choice in those under 40
o Blood and platelet transfusion used cautiously in patients, who are candidates for bone marrow transplant to avoid sensitisation - Immunosuppressive therapy with ANTITHYMOCYTE GLOBULIN (ATG) and CICLOSPORIN in those:
o Over 40
o Below 40 with severe disease, who do not have a HLA identical sibling donor
o Those who are transfusion dependent
Define anaemia of chronic disease.
Anaemia that is secondary to a chronic disease, can think of it as if the body is sick, then the bone marrow will be too, resulting in anaemia
Give 3 examples of chronic diseases for anaemia of chronic disease.
o Tuberculosis
o Crohn’s
o Rheumatoid arthritis
o SLE
o Malignant disease
Give 3 symptoms for anaemia of chronic disease.
- Fatigue, headaches and faintness
- Dyspnoea and breathlessness
- Angina (if there is pre-existing coronary disease)
- Anorexia
- Intermittent claudication
- Palpitations
Briefly describe the pathophysiology for anaemia of chronic disease.
Anaemia + evidence of immune system activation.
Release of pro-inflammatory cytokines by infection, neoplasm, autoimmune and trauma. cascade leads to fall in serum iron and decreased RBC survival.
What investigations would you do for anaemia of chronic disease?
Iron studies:
1. Serum iron and Total iron-binding capacity (TIBC) are low
2. Serum ferritin is normal or raised due to the inflammation
3. Serum soluble transferrin receptor level is normal
- Blood count & film
* RBC: Normocytic + normochromic / microcytic + hypochromic
(pale as in RA and Crohn’s)
* Reticulocyte count is low
Give the management for anemia of chronic disease.
- Treat underlying chronic cause
- Give EPO medication (Erythropoiesis stimulating medication – I.E. Erythropoietin) is effective in raising the Hb level and is used in anaemia of renal disease and inflammatory disease e.g. rheumatoid arthritis and inflammatory bowel disease
