anaemia Flashcards
What is high unconjugated bilirubin usually due to?
Pre-hepatic causes because bilirubin is metabolised in the liver.
High in haemolysis (breakdown of RBC)
What are spherocytes and their features?
Round RBC lacking central pallor (very pigmented centre). Have shorter life span
What is hereditary spherocytosis and what does it cause? What is it due to?
Inherited defect in RBC membrane so it cant hold normal shape & becomes rounded.
Disruption of vertical linkages usually ankyrin/spectrin
Why do we see polychromatic macrocytes & reticulocytes in spherocytosis?
Bone marrow trying to produce more of these cells to compensate for reduced Hb
What do you do for the mild phenotype of hereditary spherocytosis and the severe type?
Mild phenotype give folic acid + annual assessment. Severe phenotype give splenectomy to increase red blood life span
What does hereditary spherocytosis predispose to and why? What can this cause?
Predisposes to gallstones due to high bilirubin. Can get obstructed common bile duct and pigment stones leading to high conjugated bilirubin later on
What is difference between haemolysis and haemolytic anaemia?
Haemolysis is pathological process where RBC have shortened life. Haemolytic anaemia is when haemolysis leads to anaemia
What is the key diagnostic for hereditary spherocytosis?
Family history
What does a slightly increased MCV indicated vs a significantly elevated MCV?
Slightly elevated MCV - megaloblasts or reticulocytes. Significantly elevated MCV- megaloblasts
When do you get reduced haptoglobins?
In haemolysis. Means that blood cells are getting destroyed more quickly
What is the direct antiglobulin test DAT and when is it used?
DAT test detects antibody bound to RBC, to see cause of haemolysis
what does positive direct antiglobulin test DAT point to?
auto-immune haemolytic anaemia AIHA
What is auto-immune haemolytic anaemia (DAT positive)? What is it associated with?
AIHA is idiopathic. Associated with disorders of the immune system eg SLE, underlying lymphoid cancers (lymphoma)
What can inherited defects of RBC cause?
Membrane defect, abnormal haemoglobin (sickle cell, thalassaemia), defect in glycolytic pathway (eg pyruvate kinase deficiency), defect in enzyme of pentose shunt (GDPD deficiency)
What does the glycolytic pathway do?
Provides energy for the cell
What does the pentose shunt do and what enzyme does it use?
Protects from oxidant damage using enzyme G6PD (glucose-6-phosphate dehydrogenase)
What are irregularly contracted cells?
RBC with irregular borders lacking central pallor. Oxidant damage
What are hemighost cells and what do they show?
RBC pushed to one side and other side pale, intravascular haemolysis
What are ghost cells & what do they mean?
Very faint RBC cant see much Hb. Intravascular haemolysis
What are heinz bodies? How do you see them? What do they mean?
- Blister/dot RBC.
- there is special test for heinz bodies but can see on normal film too
- Precipitated oxidised haemoglobin (show oxidant damage)
What are features of oxidant damage?
Irregularly contracted cells, heinz bodies, hemighost/ghost cells
How do you confirm G6PD deficiency?
assay
What do you advise people with G6PD deficiency to do?
Avoid oxidant drugs, don’t eat broad beans (fava beans), avoid napthalene, be aware haemolysis can result from infection
What would you see in iron studies of iron deficiency?
Low Hb, low MCV, low MCHC. Low ferritin, high transferrin. Cells smaller with increased central pallor
What questions should you ask someone with iron deficiency anaemia?
Diet (vegetarian), GI symptoms (dysphagia, pain, bowel habits, haematemesis, PR bleeding, malaena), menstrual history/post-menopausal bleeding, weight loss, meds (aspirin, NSAIDs)
What are clinical signs of iron deficiency anaemia?
Koilonychia, glossitis, angular stomatitis. Tired/lethargy/breathlessness/ankle swelling
What are investigations to do for cause of iron deficiency anaemia?
Blood in stool (faeceal immunochemical test FIT), for GI causes OGD, duodenal biopsy, colonsocopy, coeliac antibody testing
What are causes of iron deficiency anaemia?
- increased blood loss: hoockworm, menstrual, GI.
- insufficient intake: dietary, malabsorption (coeliac, H.pylori gastritis)
- increased requirements: pregnancy, infancy
What is ferritin & transferrin like in iron deficiency? In anaemia of chronic disease?
ferritin low in iron def but transferrin high to compensate. Anaemia of chronic disease ferritin high but transferrin low.
Can ferritin be normal in iron def & anaemia of chronic disease?
yes
What does excess iron do? What is haemostasis of iron?
Excess iron toxic to organs (heart, liver) and it is not excreted so absorption tightly regulated (1-2mg of iron a day from diet).
-Absorption carefully regulated by hepcidin (storage of iron)
When does hepcidin increase and what does this cause?
Hepcidin increases in inflammation pushing ferritin levels up (stored iron) and decreasing release from storage/absorption
When does EPO decrease and what does this cause?
EPO decreases in inflammation due to pro-inflammatory cytokines (IL-1, TNFα, IL-6).
Decreased iron absorption, transport and availability
What are common causes of anaemia of chronic disease?
Infections TB and HIV, RA, other autoimmune disorders, malignancy
What are presentations of megaloblastic anaemia?
Tired, feels like walking on cotton wool, pale/yellow skin, areas of depigmentation
What would be seen in megaloblastic anaemia blood panel?
Hb low, MCV high, white cells & platelets low, reticulocytes normal, bilirubin high, hyper-segmented neutrophils (more than 6), poikilocytosis
In megaloblastic anaemia what does the bone marrow show?
Megaloblastic features, megaloblasts very large with nucleocytoplasmic dissociation. Impaired DNA synthesis, nuclear maturation and cell division
What is vitamin B12 needed for?
DNA synthesis and integrity of nervous system
What is folic acid needed for?
DNA synthesis and homocysteine metabolism
What can megaloblastic anaemia be secondary to?
Agents / mutations that impair DNA synthesis eg. Drugs (azathioprine cytotoxic chemotherapy), folate antagonists (methotrexate), BM cancer (myelodysplastic syndrome)
What is megaloblastic anaemia associated with?
Megaloblastic morphological changes in bone marrow due to asynchronous nucleocytoplasic maturation
What are causes of vitamin B12 deficiency?
diet (vegan), gastric (gastrectomy or autoimmune eg. Pernicious anaemia). Terminal ileum (resection or inflammation in chrohns)
What are causes of folic acid deficiency?
Diet, proximal jejunum (coeliac), increased demand in haemolysis, pregnancy
What neurological disorders can vitamin B12 and folic acid cause respectively?
Vitamin B12 - dementia and SACD (sub-acute combined degeneration) of spinal cord.
Folic acid - developmental neural tube defects
What are common causes of microcytic anaemia?
Iron deficiency, anaemia chronic disease, defect in globin synthesis (a-chain -> a-thalassaemia, Β chain β-thalassaemia)
What is different in iron deficiency anaemia and in thalassaemia?
MCHC low in iron deficiency, maintained in thalassaemia. RBC low in iron deficiency, high in thalassaemia.
Hb electrophoresis normal in iron deficiency, HbA2 raised in b-thalassaemia but normal in a-thalassaemia.,
What are causes of normocytic anaemia?
Recent blood loss (GI, trauma), failed RBC production (bone marrow suppression in chemo, infiltration in leukaemia, early stages iron deficiency), pooling RBC in spleen (hypersplenism in liver cirrhosis, splenic sequestration in sickle cell anaemia)
What are causes of macrocytic anaemia?
Vit B12 def, folate def, haemolytic anaemia (reticulocyte increased), drugs interfering with DNA synthesis, liver disease, ethanol toxicity
What are causes of haemolytic anaemia?
Hereditary spherocytosis, autoimmune haemolytic anaemia, sickle cell anaemia, G6PD deficiency
