9. Haematology I: Clinical Aspects Of Haematological Disorders Flashcards

Question

Manifestations of iron deficiency clinical presentations

Answer 1

- Mild deficiency typically asymptomatic - Classic presentation includes: ~ Koilonychia ~ Angular cheilitis ~ Atrophic glossitis ~ Recurrent oral ulceration ~ Burning mouth ~ Oesophageal web (Plummer-Vinson / Patterson-Brown Kelly Syndrome)

Answer 2

- Identify cause - Red flags include men and post-menopausal women (may have unexplained blood loss which may be associated with a malignancy) - Investigations: ~Blood film ~ Iron studies - Treatment: ~ Address underlying cause ~ Oral supplementation (ferrous sulphate 200mg x3/day for 3 months) ~ Parenteral available (fever, arthropathy, anaphylaxis) ~ Blood transfusion (only in severe compromise)

Answer 3

- Anaemia's of chronic disease - Associated with: ~ Chronic inflammatory / connective tissue conditions (rheumatoid arthritis) ~ Chronic infections (tuberculosis) ~ Chronic renal disease (due to reduction in erythropoietin) ~ Malignancies (bone marrow infiltration)

Answer 4

this is where you have the large RBCs Divided into: 1. Megaloblastic erythropoiesis - abnormal red cell development due to disordered DNA synthesis 2. Normoblastic erythropoiesis – normal red cell maturation

Answer 5

folate deficiency

Answer 6

- Folate essential for DNA synthesis - Derived from many food sources (especially green leafy vegetables)

Answer 7

- Causes of deficiency: ~ Inadequate intake (elderly, alcoholism) ~ Malabsorption (Coeliac disease, Crohn’s disease, resection) ~ Increased requirement (pregnancy, haemolytic anaemias, myelofibrosis) ~ Increased loss (dialysis, liver disease, congestive heart failure) ~ Drugs (methotrexate, phenytoin, trimethoprim)

Answer 8

- Vitamin B12 required in number of enzymatic reactions - Found only in foods of animal origin - Deficiency impacts on DNA synthesis

Answer 9

Causes of deficiency: ~ Inadequate intake ~ Inadequate secretion of intrinsic factor (pernicious anaemia, gastrectomy) ~ Inadequate release from food (gastritis, PPI, EtOH abuse) ~ Diversion of dietary B12 (bacterial overgrowth, small intestinal strictures) ~ Malabsorption (Crohn’s disease, ileal resection)

Answer 10

FOLATE & VITAMIN B12 - Generic symptoms & signs of anaemia - Occasionally mild jaundice - Glossitis - Oral ulceration VITAMIN B12 - Peripheral neuropathy (loss of proprioception and vibration sense) (nerve related damage) (typically periphery = fingers + toes) - Demyelination with subacute combined degeneration of spinal cord (serious complication) - Dementia

Answer 11

- Identify cause - Investigations ~ Blood film ~ Serum folate and B12 (*low B12 can lead to low folate – always test together) - Treatment ~ Address underlying cause ~ Oral supplementation (never folate only if B12 level not known) ~ Parenteral vitamin B12 (IM) required in pernicious anaemia

Answer 12

- Alcohol excess - Liver dysfunction - Hypothyroidism - Drugs (methotrexate, azathioprine)

Answer 13

1. MEMBRANE DEFECTS 2. ENZYME DEFECTS 3. GLOBIN DEFECTS EXTRA INFO MEMBRANE DEFECTS - Number of proteins essential to maintain cell membrane integrity - Any mutation leads to increased fragility and haemolysis - Hereditary spherocytosis most common congenital ENZYME DEFECTS - Glucose-6-phosphate dehydrogenase (G6DP) deficiency - Involved in glucose metabolism - Deficiency results in increased sensitivity to oxidative stress

Answer 14

- immune and non-immune causes EXTRA INFO IMMUNE - occurs when IgG coated red cells interacting with marcophages resulting in phagocytosis - Include autoimmune processes with antibodies against red cells (including idiopathic or secondary to infections, drugs, SLE, haematological malignancies) - Alloimmune results from transfusion and production of antibodies to transfused red cell NON-IMMUNE - Include mechanical trauma (metallic valves), burns, infections (malaria) or drugs (dapsone)

Answer 15

- Vary greatly depending on cause - Common features include: ~ Pallor ~ Jaundice (due to elevated bilirubin) ~ Splenomegaly ~ Expansion of erythropoiesis leading to bone deformities (frontal bossing) and pathological fractures

Answer 16

- Normal Hb comprises of 2 alpha and 2 beta chains - Each globin group is associated with a haem group (protoporphyrin ring and iron) - Adult Hb composition ~ Hb A (α2β2) 97% ~ HbA2 (α2δ2) 1.8-3.6% ~ HbF (α2γ2) <1.5%

Answer 17

- Fundamental role of O2 transportation - Hb undergoes conformational change between O2 bound and unbound states - Altering affinity for O2 (loads O2 in high O2 tension environment and releases in low)

Answer 18

1 - Common genetic disorder with significant associated morbidity and mortality - Excess chains precipitate in precursor red cells leading to premature death - Precipitated chains also result in oxidative damage to the cell membrane leading to haemolysis 2 - 2 main groups depending on whether α or β chain defect ~ α-Thalassaemia ~ β-Thalassaemia 3 - Severity depends on degree of globin chain imbalance 4 - Diagnosis made on Hb electrophoresis (to identify various chains present in individual)

Answer 19

1. Most common SE Asia (Thailand, Indonesia) and W Africa 2. Prevalence 20-30% 3. 4 α-globlin genes on 2 chromosomes - depending on number of genes affected, affects the severity? a) α+-thalassaemia trait (deletion of 1 gene) – asymptomatic with normal Hb and reduced MCV b) α0-thalassaemia trait (deletion of 2 genes on 1 chromosome) – slight reduction Hb and reduced MCV c) Hb H disease (deletion of 3 genes) – chronic haemolytic anaemia however transfusion independent d) Hb Bart’s hydrops fetalis syndrome (deletion of all 4 genes) – intrauterine or neonatal death

Answer 20

1. ~1.5% world population are β-thalassaemia carriers 2. Southern Europe 10-30% especially Greece 3. - Usually due to mutation rather than deletion affecting β-gene a) Heterozygous β-thalassaemia (trait) – asymptomatic b) Homozygous β-thalassaemia – moderate to marked anaemia developing within 1st 2 years (may be transfusion dependent)

Answer 21

1. - depends on the degree of anaemia seen - based on minor or major presentation 2. - Thalassaemia minima ~ Presence of mutation without clinical consequence - Thalassaemia minor ~ Microcytosis and hypochromic red cells - Thalassaemia intermedia ~ Microcytic hypochromic anaemia ~ Extramedullary haematopoiesis with splenomegaly - Thalassaemia major ~ As above with severe anaemia and transfusion dependent

Answer 22

1 - Typically those of anaemia unless severe - If untreated leads to growth retardation, splenomegaly and bony deformities due to marrow expansion 2 ORAL - Enlargement of maxilla (chipmunk facies) - Migration and spacing of upper anterior teeth - Main concern = iron overload due to transfusion leading to iron accumulation in myocardium (cardiac failure), liver (cirrhosis), pancreas (DM) and salivary glands

Answer 23

1 Most common structural variant of Hb is HbS 2 - Due to mutation in β-globin gene - Interaction of sickle β-globin chains with normal α-globin chains = HbS - Results in deformation of cell into sickle shape 3 - Prevalence greatest in tropical Africa, Middle East and southern India - Areas in which falciparum malaria is endemic

Answer 24

- Occurs in Heterozygotes (20-40% HbS & remaining HbA) - Usually asymptomatic - Rarely experience spontaneous haematuria

Answer 25

- Homozygotes (100% HbS) - Clinical manifestations ~ Chronic haemolytic anaemia (60-90 g/L) ~ Hyposplenism (due to infarcts = increased risk of infection) ~ Splenic sequestration ~ Acute chest syndrome ~ CVA / TIA ~ Bone infarction and subsequent infections ~ Chronic leg ulcers ~ Haematuria and chronic renal disease Sickling ~ shortened erythrocyte survival ~ microcirculation obstruction

Answer 26

- Diagnosed with Hb electrophoresis - Transfusion when necessary - Pneumococcal, Hib (Haemophilus influenzae type b) and meningococcal vaccinations (increased susceptibility due to hyposplenism) - Prophylactic penicillin CRISES - Acute vaso-occlusive painful episodes - Precipitated by infection, dehydration, hypoxia - Oral and IV fluids - Analgesics (opiates)

Answer 27

BLOOD GROUP DIFFERENCES - due to the Variation in surface constituents of red cells can lead to immunological reaction between donor and recipient - 30 major blood group systems - Most important ABO and Rh systems - Compatibility or cross-matching essential

Answer 28

- H antigen is attached to cell membrane - Presence of A or B allele lead to H antigen modification whereas O encodes for no modification 6 possible genotypes ~ AA ~ AB ~ AO ~ BB ~ BO ~ OO 4 phenotypes ~ A (can receive A or O) ~ AB (can receive A, B or O) ~ B (can receive B or O) ~ O (can only receive O)

Answer 29

- More complex than ABO - Encoded by 2 genetic loci on one chromosome (RHD and RHCE) - D antigen in most clinically relevant - RhD-negative person at significant risk of developing anti-D antibodies after transfusion of RhD-positive blood - Main relevance is to pregnant RhD-negative mothers - Fetus may be RhD-postive and placental transfer may lead to an adverse reaction - Pregnant women have Rh status tested and antenatal anti-D prophylaxis given if necessary

Answer 30

- Immune-mediated transfusion reactions can be classified: ACUTE REACTIONS ~occur within 24 hours of transfusion and include acute haemolytic, febrile non-haemolytic, allergic, and transfusion-related acute lung injury DELAYED REACTIONS ~ occur days to weeks after the transfusion and include delayed haemolytic transfusion reactions, transfusion-associated graft-versus- host disease and post-transfusion purpura

Answer 31

10% mortality - Fever - Agitation / anxiety - Rigor - Rash - Flushing and sweating - Chest / abdominal pain - Profound hypotension - Bleeding - Diarrhoea

Answer 32

- Stop transfusion - Check patient identity against donor blood product unit - Replace giving set - Paracetamol - IV fluids - If suspect anaphylaxis IM Adr - Contact Haematology

Answer 33

- May present with oral features suggestive of anaemia - Alternatively anaemia may complicate treatment - Without a clear explanation it may be sensible to delay treatment

Answer 34

- Angular cheilitis - Glossitis - Oral ulceration - Peripheral neuropathies

Answer 35

- Oral pain possibly due to infarction - Osteomyelitis - Trigeminal neuropathy (due to osteomyelitis) - Hypomineralised dentition

Answer 36

- Dense lamina dura - Hypercementosis - Radio-opacities due to previous infarcts

Answer 37

BLEEDING - If bone marrow infiltration there may be failure of other cell lines including platelets with increased risk of bleeding - Liver disease may result in anaemia as well increased risk of bleeding due to impact on clotting factors synthesis ANAESTHESIA - Avoid prilocaine (methaemoglobinaemia) - Thalassaemia and sickle cell anaemia can complicate procedures performed under general anaesthesia

9. Haematology I: Clinical Aspects Of Haematological Disorders Flashcards

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