Anaemia Flashcards
What are the 6 types of anaemia?
- anaemia of chronic disease (ACD)
- aplastic anaemia (ApA)
- haemolytic anaemia (HmA)
- iron deficiency anaemia (IDA)
- pernicious anaemia (PA)
- sideroblastic anaemia (SdbA)
What causes ACD?
- malignancy
- chronic infection (TB)
- CTDs (RA)
How do chronic diseases cause anaemia?
IL-1, IL-6
- hepcidin release from liver inhibits Fe absorption (ferroportin activity)
What is ferroportin?
Fe export channel
- gut enterocytes
- reticuloendothelial cells (macrophages)
What cells are seen on a blood film in ACD?
Initially: normochromic, normocytic
Develops to: hypochromic, microcytic
(low TIBC, high ferritin)
What is aplastic anaemia?
Pancytopenia + hypocellular marrow
(no abnormal cells)
What bloods are diagnostic of an aplastic anaemia?
- anaemia (Hb<10)
- thrombocytopenia (platelets<50)
- neutropenia (absolute<1.5)
Name the common acquired causes of aplastic anaemia?
- drugs (NSAIDs, chloramphenicol)
- infection (hepatitis)
- paroxysmal nocturnal haemoglobinuria (PNH)
Name the common inherited causes of aplastic anaemia?
Fanconi’s anaemia (AR)
Dyskeratosis congenita (XL)
How does aplastic anaemia typically present?
Pancytopenic features:
- fatigue, pallor
- infection
- easy bruising/bleeding
Risk:
- drug exposure (6/12)
- occ exposure
- recent infection
- comorbidities
What is Fanconi’s anaemia?
Aplastic anaemia +
- pigmentation abnormalities
- hearing defects
- renal/ genital abnormalities
- solid tumours
- short stature
How do patients with dyskeratosis congenita present?
Aplastic anaemia +
- nail malformations
- oral leukoplakia
- reticulated skin rash
How is haemolytic anaemia classified?
Intravascular
Extravascular
AI (Coombs+)
Non-AI (Coombs -)
How does haemolytic anaemia present on biochemistry?
- low Hb
- high UCB, LDH, urinary UBG
- reticulocytosis
Intravascular haemolysis releases Hb into the circulation. How does the body deal with this excess Hb?
Combination
- haptoglobin
- albumin (methaemalbuminaemia)
Excretion
- urine (haemoglobinuria, haemosiderinuria)
Storage
- haemosiderin (tubular epithelial cells)
What are the causes of intravascular haemolytic anaemia?
- intrinsic cellular injury (G6PD)
- compliment-mediated lysis (AI, PNH, acute transfusion reactions)
- mechanical injury (microangiopathy & cardiac valves)
- autoimmune
What are the features of a Glucose-6-phosphate deficiency anaemia? (G6PD)
- XLR
- presents neonatally with jaundice
- presents later with episodic intravascular haemolysis (exposure to oxidative stressors)
What triggers G6PD?
- intercurrent illness/infection
- fava beans
- henna
- meds: primaquine, sulfa-drugs, nitrofurantoin, dapasone, NSAIDs/aspirin
How is a G6PD investigated?
Blood film
- Heinz bodies
- bite cells
Diagnostic test
- G6PD enzyme assay
How is G6PD managed?
- avoid precipitants
- transfusions (rare)
How does extravascular haemolytic anaemia present?
- hepatomegaly
- splenomegaly
(Reticuloendothelial system)
What are the causes of extravascular haemolytic anaemia?
- abnormal RBCs (SCA, hereditary spherocytosis)
- cells marked by abds for splenic phagocytosis
What is hereditary spherocytosis?
AD
- mutations in RBC membrane proteins
- membrane sections removed by spleen
- reduced SA:vol
= spherical distortion > haemolysis
What is the classic presentation of hereditary spherocytosis?
- neonatal jaundice/anaemia
- splenomegaly
Management of hereditary spherocytosis?
Conservative
- folate supplements
Severe disease
- splenectomy (<5) curative
What is the test for AIHA ?
Direct Coombs test
- Abd against autoabd
- cross-link & agglutinate
What are the two types of Coombs+ AIHA?
Warm & cold AIHA
What is warm AIHA?
IgG-mediated
- spleen tags cells for splenic phagocytosis
What is cold AIHA?
IgM-mediated
- IgM fixes complements, causing direct INTRAvascular haemolysis (cold agglutinins)
What are the causes of warm AIHA?
- idiopathic
- lymphoproliferative neoplasms (CLL, lymphoma)
- drugs (methyldopa)
- SLE
What are the causes of cold AIHA?
- idiopathic
- infection post-2/3w (EBV, mycoplasma)
What disorders present as Coombs- haemolytic anaemias?
- microangiopathy
- PNH
- physical lysis of RBCs (malaria)
- haemolytic uraemic syndrome (E.coli)
- infection causing DIC (fulminant meningococcemia)
What is microangiopathic haemolytic anaemia?
A type of intravascular Coombs- haemolytic anaemia
- physical lysis of RBCs by deposited fibrin strands
- schistocytes on film
Cause:
- isolated
- associated with thrombotic microangiopathy syndromes (DIC, haemolytic uraemic syndrome, thrombotic thrombocytopenia purpura)
What is PNH?
Paroxysmal nocturnal haemoglobinuria
- abnormal surface glycoprotein expressed on subclone of RBC marks for complement-mediated lysis
How does PNH present?
- young adult
- nocturnal intravascular haemolysis
- other stem cell defects
- increased clotting risk
What test is diagnostic of PNH?
Flow cytometry
In what circumstances would physical lysis of RBCs occur?
- falciparum malaria
- babesiosis
- prosthetic valves
What is pernicious anaemia?
Vitamin B12 deficiency causing anaemia
(2ry to AI impairment of IF production)
What causes a Vitamin B12 deficiency?
Gastric
- pernicious anaemia
- chronic severe atrophic gastritis
Pancreatic insufficiency
Small bowel
- bacterial overgrowth
- resection of terminal ileum
- Crohn’s
TB
Metformin
ZES
What does pernicious anaemia present as on biochemistry?
- macrocytic anaemia
- high MCH (normal conc)
- low serum B12, folate
- low reticulocyte count
- large, oval-shaped RBCs
- IF abd/parietal cell abd
(Hyperchlorhydria - gastric body atrophy)
How is pernicious anaemia managed?
Lifelong replacement (cobalamin)
- monitor for early diagnosis of IDA
- advise about GI complications (gastric cancer, carcinoids)
What is sideroblastic anaemia?
Microcytic anaemia due to ineffective erythropoiesis (increased Fe absorption in marrow)
How does sideroblastic anaemia appear on film?
- sideroblastic inclusions in RC cytoplasm
- haemosiderosis of liver, heart, endocrine organs
How does sideroblastic anaemia present clinically?
- microcytic anaemia refractory to intensive Fe Tx
- high serum ferritin & Fe
What are the causes of sideroblastic anaemia?
Congenital (XL, AR, AD)
Acquired
- drugs/toxins (alcohol, Pb, isoniazid)
- myelodysplastic syndromes
