L06 - Classification and Lab Dx of Anemia Flashcards
Define Anaemia? Is it a disease?
Clinical condition: haemoglobin (Hb) 血紅素 concentration in red blood cell falls below the reference interval*
Specific for age, sex, race, altitude
Not a disease, But a manifestation/sign of the underlying disease
What are the 2 determinants of Hb conc.? What variation of these determinants = anemia?
Hb (gram) ÷ Volume of blood (dL / L)
1) Reduced mass of Hb/ normal plasma volume
2) Normal mass of Hb/ Reduced plasma volume
Factors that influence normal Hb concentration?
- Age: newborn = 19g/dL, Child = 10g/dL, Adult = 15g/dL
- Sex: lower Hb conc. in female
- Race
- Altitude: Higher alt = higher Hb conc.
Principle mechanism of anemia?
upset of the dynamic balance between normal red cell production and loss
Describe breakdown of RBC?
In tissue macrophages:
1) Heme > Iron and Biliverdin > Transferrin-Iron and Bilirubin into blood stream
2) Globulin > Amino acids
Unconjugated bilirubin > transformed into bilirubin glucuronides by liver to be excreted > excreted as stercobilinogen in feces or urobilinogen in urine
Breakdown products recycled or excreted
Classify anemia under 4 pathological classes?
- Production defect – bone marrow failure
- Destruction – haemolysis, blood loss
- Sequestration – hypersplenism
- Dilution – increase in plasma volume relative to red cell mass
Subclassification of anaemia caused by production defect?
1) Inadequate red cell production - upstream stem cell failure or stimulation failure or failure of maturation
2) Ineffective red cell production - Failure of maturation
List causes of inadequate RBC production.
a) Bone marrow defect:
i) Haematopoietic stem cells (e.g. aplastic anaemia)
ii) Production site defect (e.g. marrow infiltrative lesions)
b) Lack of humoural stimulation / erythropoietin (e.g. chronic renal failure)
c) Iron metabolism problem:
i) Iron deficiency anaemia
ii) Inability to use iron (sideroblastic anaemia)
List causes of ineffective RBC production.
A) Vit B12 metabolism problem
i) dietary B12 deficiency
ii) Inability to use Vitamin B12 (e.g. congenital transcobalamin II deficiency)
B) Involving globin metabolism: quantitative abnormality (Thalassaemia)
C) Myelodysplastic syndrome: common myeloid progenitor mutation with premature apoptosis
C) Megaloblastic anaemia: impaired nucleotide synthesis with abnormal maturation
Normal life span of RBC? Factors that influence life span?
Normal lifespan of red cells = 100-120 days – depends on:
- Membrane integrity
- Normal Haemoglobin structure
- Adequate supply of ATP (glycolysis and unloading)
- Adequate supply of reducing power (oxidative damadge)
What are the different root causes of increased red cell destruction?
Haemolysis:
1) Intrinsic/ intracorpuscular defect
2) Extrinsic/ extracorpuscular defect: Immune/ Non-immune haemolysis
3) Interaction between intra- and extracorpuscular factors
List some Intrinsic/ intracorpuscular defect of RBC?
– Red cell membrane defect
– Red cell enzyme defect (G6PD)
– Haemoglobin defect
List some Extrinsic/ extracorpuscular, Immune haemolysis defect of RBC?
Immune haemolysis (antibody-mediated):
1) Alloimmune (e.g. haemolytic transfusion reaction, haemolytic disease of the newborn)
2) Autoimmune (autoimmune haemolytic anaemia)
3) Drug-induced immune haemolysis
List some Extrinsic/ extracorpuscular, Non- immune haemolysis defect of RBC?
1) Mechanical damage (e.g. microangiopathic haemolytic anaemia, artificial heart valves)
2) Toxin
3) Infection (e.g. malaria – blackwater fever)
4) Burn
List one haemolytic disease due to Interaction between intracorpuscular and extracorpuscular factors ?
paroxysmal nocturnal haemoglobinuria
List some causes of RBC sequestration?
hypersplenism/splenomegaly from trapping / pooling of red cells, white cells, platelets:
1) Portal hypertension (e.g. due to liver cirrhosis, Hep B)
2) Haematological diseases (e.g. sickle cell anemia)
3) Uncommon: Chronic infections, Storage diseases
List some causes of Haemodilution?
- Pregnancy
- Fluid resuscitation after acute blood loss
Both increase plasma volume
Clinical features of anaemia?
Low Hb concentration → impaired O2 transport → tissue hypoxaemia → body compensation / decompensation
• Pallor
• Fatigue (tissue hypoxia)
Cardiopulmonary compensation:
• Palpitation
• Shortness of breath
Central and periphery pallor are both accurate in accessing the lack of O2 transport in anaemia. T or F?
False
Periphery = subject to temp change, not accurate
Central = accurate
What does the severity of anemic symptoms/ symptomatology depend on?
1) Extent to which haemoglobin concentration is lowered
2) Rate / rapidity of onset (e.g. acute =no time to compensate)
3) Adequacy of cardiopulmonary compensation (e.g. elderly = more severe)
Initial investigations techniques used to help guide Dx of anaemia?
1) Complete blood count (CBC):
- Cell count, Hb conc., Red cell indicies, Reticulocyte count, White cell and platelets
2) Examination of peripheral blood smear
> > Provide useful information on possible differential diagnosis, pathogenic mechanism for anaemia
List the variation in the size, shape and colour of blood cells seen under peripheral blood smear?
- Size: normocytic, microcytic, macrocytic, dimorphic (2 red cell populations)
- Variation in size = anisocytosis
- Colour (chromia): normochromic, hypochromic, polychromatic (indicates reticulocytosis)
- Variation in shape = poikilocytosis
List the RBC indicies obtained in CBC?
- Haemoglobin (HGB)
- Mean cell volume (MCV)
- MCH (follows MCV normally)
- Red cell distribution width (RDW)
- Mean cell haemoglobin concentration (MCHC)
Which RBC indicies is the most useful for DDx of anaemia after HGB?
Mean cell volume (MCV)
How to guide the DDx of anaemia based on MCV?
Classify into Microcytic, Normocytic, Macrocytic
List causes of Microcytic anaemia?
Iron deficiency
Thalassaemia
Anaemia of chronic disease
List causes of Normacytic anaemia?
- Renal failure
Anaemia of chronic disease:
- Haemolysis
- Aplastic anaemia/ BM defects
- Myelodysplasia
List causes of Macrocytic anaemia?
- Megaloblastic anaemia
Anaemia of chronic disease:
- Severe haemolysis
- Aplastic anaemia/ BM defect
- Myelodysplasia
Define RDW and its use in DDx of anaemia?
Reflects differences in red cell sizes
Useful to differentiate between thalassaemia trait and iron deficiency anaemia (both microcytic anaemia)
Explain how to use RDW to DDx anaemia?
Microcytic:
• normal RDW, High RBC = thalassaemic trait (genetic defect)
• high RDW, Low RBC = acquired iron deficiency, severe thalassaemia (intermedia or major)
Derive MCHC and its use to DDx anaemia?
Derived from Hb, MCV and red cell count
MCHC = Hb / (MCV x RBC)
High value = sensitive indicator of spherocytosis (membranopathy causing loss of central pallor and SA:vol ratio) /agglutination
Fast way to analyze PBS result
Appearance of reticulocytes in PBS?
- Large, light-blue staining cells (due to RNA, no nucleus)
* Polychromasia
How is reticulocyte count used to guide DDx of anaemia?
Reticulocytosis indicates marrow compensation to hypoxemia, which requires:
- Functioning marrow
- Adequate erythropoietin
- Adequate raw materials (Fe, vitamin B12, folate, normal hemoglobin)
Aplastic anaemia can lead to reticulocytosis. T or F?
False
Apalstic anaemia = BM defect
Impossible to make normal marrow compensation to increase reticulocyte count
How is WBC count used to guide DDx of anaemia?
- Isolated anaemia = limited defect
- Pancytopenia = generalized defect, more suggestive of BM disorder
Appearance of RBC in PBS?
- Biconcave disc with central pallor (pallor too big = hypochromia; too small = hyperchromia)
Diameter of pallor should not exceed 1/3 of total RBC diameter
- Normal, consistent size and shape
Give examples and underlying causes of haemotological disease that give rise to abnormal shape RBC. SSS TEAC
Sickle cell anemia
Spherocyte (immune-mediated hemolysis, congenital red cell membrane defects)
Schistocyte (microangiopathic hemolytic anemia)
Target (beta thalassemia trait, liver disease)
Elliptocyte (iron deficiency anemia)
Acanthocyte (severe liver disease)
Crenated (liver / renal failure)
Give examples and underlying causes of haemotological disease that give rise to abnormal disposition of RBC.
Rouleaux (stacks / aggregations: increased serum proteins (e.g. globulin), plasma cell myeloma)
Agglutination (e.g. Ab against RBC)
Give examples and underlying causes of haemotological disease that give rise to abnormal Inclusion bodies of RBC.
HbH inclusion bodies = a-thalassemia
Howell-Jolly body = hypersplenism, asplenism, severe hemolytic anemias e.g. sickle cell anemia
Pappenheimer body (iron granules) = Sideroblastic anaemia, Thalassemia, Hemolytic anaemia, Post-splenectomy
Basophilic stippling = lead poisoning to bone marrow, megaloblastic anemia
Organism (e.g. malarial parasite)
Morphology of RBC from PBS and CBC are enough for DDx of anaemia. T or F?
False
Red cell morphology should not be examined out of clinical context
> > Clinical history, physical examination findings, morphology of other cell lines and other available investigation results need to be taken into account
Apart from CBC and PBS, what other investigations are valuable in guiding DDx of anaemia?
1) Iron profile (inadequate RBC production)
2) Total active Vit B12 level (Ineffective RBC production)
3) Markers of haemolysis: LDH, reti count, urine hemosiderin, bilirubin
4) Direct anti-globulin test (DAT)
5) Renal function test (EPO, inadequate stimulation)
6) Hb pattern study
