Week 1 - I - Approach to anaemia - Haemolysis/haemorrhage,Maturation abnormality/Hypoproliferative state (Normo/Micro/Macrocytic) Flashcards
What is anaemia defined as?
Anaemia is defined as a reduction in Hb concentration (either due to a decreased red cell mass or increased plasma volume) This decreases the blood ability to carry oxygen
What is the Hb level for anaemia in males and females?
In males anaemia is a Hb concentration below 135g/L
In females anaemia is a Hb concentration below 115g/L
Approach to anaemia * history/examination/clinical context- main tool! * full blood count indices * reticulocyte count * blood film features * haematinics (ferritin/B12/folate) * bone marrow * Specialised tests (hb electrophoresis etc) What are the different classifcations for the cause of anaemia? (come under headings - production or destruction)
Decreased production * Hypoproliferative mechanism - decreased erythropoeisis or * Maturation abnormality - erythropoeisis present but ineffective Cytoplasmic defect - impaired haemaglobinastion Nuclear defect - impaired cell division Increased destruction/loss * Haemolysis * Haemorrhage
As stated maturation can be due to impaired haemoglobin formation or due to ineffective red blood cell maturation via cell division causing the anaemia Which type is micro and which causes macrocytic anaemias? How would the colour of the red cells be described in these anaemias?
Microcytic anaemias (hypochromic) - due tocytoplasmic defects - impaired haemaglobinisation (haem or globin problems) Macrocytic anaemias (normochromic) - due to nuclear defects - imparied cell division (problems that affect the normal division of the red cells)
What count is a marker of red cell destruction? When does this count increase? What stains can be used to check the reticulocyte count?
Reticulocyte count Increases in response to haemolysis &haemorrhage as the bone marrow tries to compensate Also increases in repsonse to treatment of iron deficiency anaemia Can use new methylene blue and brilliant cresyl blue dye (these stain the ribosomal RNA)
If there is a reticulocytosis then red cell production is increased So if anaemic. either blood being lost or increased red cell turnover (haemolysis)? If bleeding, red cells are gone, if haemolysing then increased products of red cell destruction are seen What increased products would be seen? (Whether extra or intravascular) What signs would be seen?
Would see an increase in serum unconjugated bilirubin Would see an increase in urine urinobilogen Signs - anaemia+jaundice due to excess red cell destruction breakdown components and also splenomgealy as the macrophages of the spleen are working hard to deal with the increased blood products
What breaks down haem to what? WHat breaks down this product to bilirubin? What does bilirubin bind to to be conjugated where? What conjugates the bilirubin?
Porphyrin ring - broken down by haem oxygenase to biliverdin broken down by biliverdin reductase to unconjugated bilirubin Unconjugated bilirubin binds to albumin to be transported to the liver where it is conjugated by glucoronic acid
Classification of the anaemia by red cell size and haemoglobinisation What are the classifications of size and how is this assessed? How is the classification of haemaglobinsation assessed?
Size - calculated by assessing the mean cell (corpuscular) volume (MCV) * Microcytic * Normocytic * Macrocytic Haemaglobinsation - assessed by blood film or mean cell haemaglobin from anaylser * Hypochromic * Normochromic
What is the commonest cause of hypochromic microcytic anaemia? What are other causes?
Commonest cause = iron deficiency anaemia Other causes Anaemia of chronic disease Thalaseemia Sideroblastic anaemia - ALA synthase defect (porphyri maturation abnormality) Find The Small Cell
What is the main causes of macrocytic anaemia? Name some other causes
B12/folate deficiency Cytotoxic drugs Bone marrow disorders (myleoma, myelodysplasia, aplastic anaemia, reticulocytosis, cold agglutins)
How can reticulocytosis cause macrocytic anaemia? What is cold agglutins also known as? What mediates it? What can cause it? What can diagnose it? What can treat it?
Increased reticulocytes can be interpreted as red cells by the analyser - this makes it seem like there is an increase in red cell MCV when there is an increase in reticulocytes Cold aggltuins - cold autoimmune haemolytic anaemia Mediated by IgM and becomes apparent when it is cold - temps of 4degress (Mostly idopathic, can be caused by mycoplasma and EBV infections) Diagnose using Direct Coombs test - will see spherocytes and reticulocytosis on blood - Treat by avoiding the cold
What are three causes of macrocytosis in the absence of anaemia?
Alcohol Hypothyroidism Liver disease
Normochromic normocytic anaemia It is mostly due a hypoproliferative state Why may renal failure cause this type of anaemia?
The kidneys normally sense low levels of oxygen the blood and the intersitial fibroblasts of the kidney release EPO which acts on the bone marrow to stimulate erythropoiesis - in renal failure, EPO is not produced
Anaemia of chronic disease can cause a hypochromic microcytic anaemia or a normochromic normocytic anaemia * A multifactorial pathophysiology with inflammation a central process * Common - second only to iron deficiency as cause for anaemia worldwide Cytokine production due to inflammation drives the process What are the three main mechanism due to cytokine production that cause anaemia? What is the main cytokine?
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Iron deficiency anaemia vs anaemia of chronic disease Serum iron? Transferrin (total iron binding capcity)? % transferrin saturation? Ferritin? MCV?
Iron deficiency anaemia Serum iron - reduced Transferrin - increased %transferrin sats- reduced Ferritin - reduced MCV- reduced/normal
Anaemia chronic disease Serum iron - reduced Transferrin - reduced %transferrin sats- reduced Ferrtin - increased MCV - normal/reduced
Describe the blood results? What could be possible causes?
Hypochromic microcytic anaemia Iron deficiency Anaemia of chronic disease Sideroblastic anaemia Thalassemia
Describe the results? State potential causes?
Normocytic normochromic anaemia Hyproproliferative disorder * Could be due to renal anaemia * Anaemia of chronic disease * Marrow failure * Acute blood loss * Pregnancy
Describe the results? State possible causes
Normochromic macrocytic anaemia This however could be due to the massive increase in reticulocytes Retiulocytes usually increase due to haemorrhage or haemolysis If haemolysis Could be due to sickle cell disease, ABO-incompatibilty, G6PDD, hereditaty spherocytosis, autoimmune haemolytic anaemia - etc etc
