Anaemia - normocytic + macrocytic Flashcards
What is aplastic anaemia?
BM stops making cells leading to pancytopenia
What are the causes of aplastic anaemia?
- autoimmune - paroxysmal nocturnal haemoglobinuria
- drugs - chloramphenicol + NSAIDS + TOXINS
- viruses - HEPATITIS
- irradiation
- congenital - fanconi anaemia
What tests would u do for aplastic anaemia? what may u find
- FBC
2. hypo cellular marrow w no abnormal cell
How may someone present w aplastic anaemia?
Hx of recurrent infection
Fatigue
Pallor
Hx of bleeding or easy bruising
What is involved in treatment of aplastic anaemia?
Supportive if asymptomatic
Immunosuppression - lymphocyte Ig, antithymocyte globulin, methylpred, ciclosporin
Severe - allogeneic marrow transplant HLA matched
How would u differentiate between IDA and AOCD?
TIBC is high in IDA
Ferritin is low in IDA and high in AOCD
What is the most common cause of anaemia in renal failure?
reduced erythropoietin levels
at what GFR does anaemia become apparent in CKD?
<35
What are complications of anaemia of chronic disease?
worsening of pre-existing heart failure due to increased CO necessitated by anaemia
What causes hypochromic cells?
reduced Hb in the cell leading to reduced mean corpuscular Hb conc (MCHC)
when should you suspect marrow failure in normocytic anaemia?
if WCC or platelets decreased
What can the causes of macrocytic anaemia be divided into?
- Megaloblastic - vit B12 deficiency + folate deficiency
- Normoblastic:
- alcohol
- liver disease
- hypothyroidism
- reticulocytosis e.g. haemolysis
- myelodysplasia
- cytotoxics
What are megaloblasts?
cell in which nuclear maturation is delayed compared with the cytoplasm
What is the function of vitamin B12
synthesises thymidine so DNA - maturation of rbc in BM
synthesis of myelin
What are the causes of vitamin B12 deficiency?
- Diet
- Malabsorption - lack of IF (pernicious anaemia) or terminal ileal resection, Crohns, post gastrectomy
- Congenital metabolic errors
What foods is vitamin B12 found in?
meat fish dairy
How and where is vitamin B12 absorbed?
binds to intrinsic factor (parietal cells in stomach produce) and absorbed in terminal ileum
What are the general features of vitamin B12 deficiency?
- Sx of anaemia
- Lemon tinge to skin due to combination of pallor and mild jaundice (haemolysis)
- Glossitis - beefy red sore tongue
- Angular cheilosis
What neurological sx does B12 deficiency cause?
paraesthesia, peripheral neuropathy
neuropsychiatric - irritability depression, psychosis
What is the management of symptomatic vitamin B12 deficiency?
If severe - IM cyanocobalamin or hydroxocobalamin (these are both vit B12 injections) + folic acid
What is the management of asymptomatic b12 deficiency?
- Dietary supplementation + multivits
what is pernicious anaemia?
autoimmune condition in which atrophic gastritis leads to lack of IF secretion from parietal cells in the stomach
In what groups of ppl is pernicious anaemia more common?
females
>40yrs
blood group A
what other conditions is pernicious anaemia associated w?
thyroid disease
vitiligo
Addisons
what are the features of pernicious anaemia?
lethargy weakness SOB paraesthesia mild jaundice, diarrhoea, sore tongue
What is the treatment of pernicious anaemia?
If due to malabsorption - vit B12 injections - hydroxocobalamin
If due to diet - oral B12 after initial IM course
What are the causes of folate deficiency?
- Poor intake - found in green leafy veg, legumes and fruit nd fortified cereals etc
- Malabsorption - tropical sprue, coeliac, intestinal resection
- Increased demand - pregnancy, increase cell turnover
- Increased loss - chronic dialysis, chronic haemolytic disease
- Alcoholism
- Drugs
What drugs cause folate deficiency/
sulfasalazine trimethoprim methotrexate pyrimethamine anticonvulsants - phenytoin
What is usually seen on blood film in b12 and folate deficiency?
microcytic anaemia and hyperhsegmented neutrophils
Where is folate usually absorbed?
duodenum/proximal jejunum
What is folate also known as?
vitamin B9
What are normal body stores of folate and how long do they last?
10-12mg lasting 4 months
What is the main difference between vitamin B12 deficiency and folate deficiency?
folate deficiency isn’t associated w neurological sx
Why should you not give folate treatment until you’ve excluded vitamin B12 deficiency?
can worsen neuropathy - can precipitate/worsen subacute combined degeneration of the spinal cord
What are the signs and sx of folate deficiency?
- May be asymptomatic
- Anaemia sx - pallor, fatigue, SOB, anorexia, headache
- Glossitis
What are causes of increased cell turnover?
haemolysis
malignancy
inflammatory disease
renal dialysis
What is the treatment of folate deficiency?
Rx underlying cause
Folic acid tablets daily for 4ms
PLUS B12 supplement
What is the function of folate?
essential for DNA synthesis fetal development (neural tube defects)
How does folate deficiency cause anaemia?
impairment of DNA synthesis -> delayed nuclear maturation -> large rbcs + decreased rbc production in BM
What is haemolysis?
premature breakdown of rbc’s
Where can haemolysis occur in the body?
- Intravascular
2. Extravascular -reticuloendothelial system i.e. macrophages of liver, spleen + BM
Why does haemolysis not always result in anaemia?
compensatory increase in red cell production by BM
Why may haemolysis cause a macrocytic anaemia?
Reticulocytes are released prematurely which are larger than mature cells
What are the causes of haemolytic anaemia?
- RBC membrane defects - hereditary spherocytosis
- Enzyme defects - G6PD deficiency
- Haemoglobinopathies - thalassaemia, sickle cell disease
- Autoimmune haemolytic anaemia
What are the features of haemolytic anaemia?
High serum unconjugated bilirubin high urinary urobilinogen high faecal stercobilinogen splenomegaly BM expansion Reticulocytosis
What is the pattern of inheritance of hereditary spherocytosis? (HS)
autosomal dominant
Explain the pathophysiology behind HS
Deficiency in the structural protein spectrin
Cells are spherocytic - more rigid and less deformable
Unable to pass through splenic microcirculation and trapped in the spleen -> shortened lifespan + destroyed via extravascular haemolysis
How does HS present?
Jaundice at birth
Splenomegaly
Failure to thrive
Chronic - formation of gallstones
What investigations would u do for HS?
- Blood film - spherocytes and reticulocytes
- FBC - anaemia + increased reticulocytes + MCHC
- Raised serum bilirubin + urinary urobilinogen
- Negative Coombs test
What other condition is associated w spherocytes?
autoimmune haemolytic anaemia
What is the treatment of HS?
Folate replacement
Splenectomy
What is the inheritance pattern of G6PDD? who does it affect most?
x linked - males
africans, mediterranean, Middle East and SE asia
Explain the pathophysiology of G6PDD, give the function of G6PD
↓ G6PD -> ↓ glutathione → increased red cell susceptibility to oxidative stress
Where is the gene for G6PD?
chromosome Xq28
How do patients w G6PD usually present?
Usually asymptomatic unless they get an oxidative crisis due to reduction in glutathione production
Chronic haemolytic anaemia - gallstones
Neonatal jaundice
What are the causes of an oxidative crisis in G6PDD?
- acute drug induced:
- aspirin
- antimalarials
- abx (sulphonamides, nitrofurantoin, chloramphenicol)
- dapsone
- quinidine - Ingesting fava beans
How would someone present in an attack w G6PDD?
rapid anaemia
jaundice
What investigations would you do in G6PDD?
- Film - bite and blister cells
2. G6PD levels - low, may be normal after attack
What is the treatment of G6PDD?
- Stop cause
- Blood transfusion
- avoid henna use!
What is the pattern of inheritance in sickle cell anaemia? (SCA)
Autosomal recessive
What is the pathology underlying SCA?
Synthesis of abnormal Hb chain - HbS
Who is more commonly affected in SCA?
African
What is the chance of being. a carrier (heterozygous) of SCA?
50%
Explain the pathophysiology of SCA
AA substitution in gene coding for beta chain (valine replaces glutamine) -> production of HbS rather than HbA
HbS polymerises when deoxygenated, rbcs deform -> sickle cells, fragile and haemolyse + block small vessels
What is sickle cell trait? What is a benefit of having it?
those who are heterozygous for sickle cell (HbAS) - no disability
+ve - protects from falciparum malaria
What things can precipitate sickling?
infection dehydration cold acidosis hypoxia
What does sickling result in?
shortened rbc survival -> haemolysis
impaired passage of cells through the microcirculation leading to obstruction of small vessels and tissue infarction and this impaired pain
How does a person w sickle cell trait tend to present?
sx free w no disability
When will a person w sickle cell trait present w symptoms?
hypoxia e.g. unpressurised aircraft, anaesthesia
What crises can occur as a result of SCA/
- Vaso-occlusive ‘painful’ crisis
- Aplastic crisis
- Acute chest syndrome
- Aplastic crisis
How do vaso-occlusive crises present in children?
acute pain in the hand and feet -> dactylitis due to vaso-occlusion of the small vessels and avascular necrosis of the bone marrow
How can vaso-occlusive crises present in adults?
pain in the long bones e.g. femur, spine, ribs and pelvis due to avascular necrosis of theBM
How can vaso-occlusive crises present neurologically?
CNS infarcts -> stroke seizures or cognitive defects
What is acute chest syndrome?
vaso-occlusive crisis of the pulmonary vasculature
what causes acute chest syndrome?
infection (clam, mycoplasma, strep pneumoniae)
fat embolism from necrotic BM
pulmonary infarction - due to sequestration in the pulmonary vasculature
How does acute chest syndrome present?
SOB
chest pain
hypoxia
What causes pulmonary hypertension in SCA? what is the definition?
Mean pulmonary artery pressure >25mmHg
Damage from repeated chest crises and repeated thromboembolism and intravascular haemolysis
What causes aplastic crises in SCA? how does it do this? What is the rx?
parvovirus B19
invades proliferating erythroid progenitors -> rapid fall in Hb w no reticulocytes in the peripheral blood due to failure of erythropoeisis in the BM,
Rx: transfusion
What are sequestration crises? why does it affect children more?
splenic sequestration leads to acute painful splenomegaly w acute fall in Hb, affects children more as spleen is atrophic in adults
What is the treatment of sequestration crises?
urgent transfusion
What are the long term effects of SCA on bones?
Bones are common sites for vaso-occlusive crises resulting in chronic infarcts
Avascular necrosis of the hips and shoulders, vertebrae compression, shortening of bones in hands and feet
Osteomyelitis due to staph. aureus, staph pneumonia and salmonella
What are the long term cardiac complications of SCA>
Cardiomegaly
arrhythmias
iron overload cardiomyopathy
MI
What are the long term neurological complications of SCA?
TIA
fits
cerebral infarction
coma
What are the long term hepatic complications of SCA?
chronic hepatomegaly and liver dysfunction due t trapping of liver cells
What are the long term renal complications from SCA/?
chronic tubulointerstitial nephritis
what are the long term eye complications of SCA?
retinopathy
vitreous haemorrhage
retinal detachments
What investigations would you do for SCA?
- FBC - Hb 60-80, raised reticulocytes
- Blood film - sickle cells
- Sickle solubility test - +ve
- Hb electrophoresis - 80-95% HbS, absent HbA
How is SCA screened for in the newborn?
neonatal blood spot screening “Guthrie” test at 5-9 days of life
What test is diagnostic for SCA?
Hb electrophoresis
What is the treatment of ongoing chronic sickle cell disease?
- Analgesia
- Hydroxycarbamide to help w disease severity
- Prophylaxis + prompt rx of infections
- FOLIC ACID to all haemolytic pts
- BM transplant
What is the rx of a vaso-occlusive crisis?
- Analgesia
- antihistamine as opioids cause pruritus
- rx precipitating cause eg. correct acidosis, warm pt
What is the rx of acute chest syndrome?
- O2 + incentive spirometry
- Analgesia
- Antihistamine
- Broad spec abx
- transfusion
When are blood transfusions indicated in the rx of SCA?
ACS Acute anaemia due to acute splenic sequestration Aplastic crisis Stroke HF
How can autoimmune haemolytic anaemia (AIHA) be divided?
- Warm
- Cold
depends on what temperature the abs best cause haemolysis
What is AIHA?
abs are directed against rbcs causing extravascular haemolytic and spherocytosis
What is warm AIHA?
ab (usually IgG) causes haemolysis best at body temp,
What are the causes of warm AIHA?
autoimmune disease: e.g. systemic lupus erythematosus*
neoplasia: e.g. lymphoma, CLL
drugs: e.g. methyldopa
What is cold AIHA? what is the usual ab? How does it present?
ab - IgM
Haemolysis usually at 4C
More commonly intravascular
Sx of raynauds and acrocyanosis
What usually causes cold AIHA
infection - mycoplasma, EBV
What is rx of warm AIHA
Steroids
immunosuppressants
+/-splenectomy
