Haematology Flashcards
Discuss the differences between megaloblastic and normo / non-megaloblastic subsets of macrocytic anaemia.
Megaloblastic refers to increased MCV as a result of impaired DNA synthesis, usually as a result of B12 or folate deficiencies
Non-megaloblastic still has increased MCV but does not affect DNA synthesis, not typically related to B12 or folate.
Which 2 biochemical tests are useful to differentiate between megaloblastic and non-megaloblastic macrocytic anaemias?
serum homocysteine
methylmalonic acid
Both are normal in non-megaloblastic anaemia.
Give causes of megaloblastic vs non-megaloblastic macrocytic anaemia.
Megaloblastic;
Folate deficiency (more common); methotrexate, poor diet, increased demand e.g. pregnancy, cancer, haemolytic anaemia. Shows as increased homocysteine, normal methylmalonic acid.
B12 deficiency, less common; pernicious anaemia most common. Others include pancreatic insufficiency, dietary insufficiency e.g. vegan diet and damage to terminal ileum.
Non;
alcohol excess + liver disease
hypothyroidism
reticulocytosis
drugs e.g. flurouracil
pregnancy
Describe the pathophysiology of pernicious anaemia.
B12 requires intrinsic factor to be absorbed. Gastric parietal cells secrete this.
Autoimmune destruction of parietal cells leads to pernicious anaemia. Main cause of B12 deficiency (macrocytic megaloblastic anaemia).
What is the clinical difference between B12 and folate deficiencies?
Neurological symptoms occur in B12 deficiency, due to the increased methylmalonic acid. They can be severe. Known as subacute combined degeneration of the spinal cord.
Symptoms include:
Loss of sensation
Loss of mental and physical drive
Symmetrical neuropathy in legs > arms, typically presenting as ataxia or parasthesia
Optic neuropathy
Urinary / fecal incontinence
Muscle weakness
Psychiatric disturbances i.e. severe dementia
UMN signs in legs but absent reflexes
https://gpnotebook.com/pages/neurology/subacute-combined-degeneration-of-the-spinal-cord/clinical-features
Which tracts of the spinal cord are affected in SCDSC?
Posterior dorsal columns (ataxic gait). Ascending pathways, also known as the gracilis / cuneate fasciculi, and carry fine and discriminative touch and proprioception
Corticospinal tract; descending pyramidal tract supplying the musculature of the body.
Important to note that the clinical picture is complicated by the early development of coexisting peripheral nerve damage.
What is the treatment for B12 deficiency / SCDSC?
Hydroxycobalamin IM
1mg repeated 5 times at intervals of 2-3 days, then maintenance doses every 3 months.
You suspect a DVT. What medications should you commence as interim before a definitive diagnosis is made?
DOAC e.g. apixaban, rivaroxaban
In suspected DVT a two-level Wells score is carried out. What score would prompt further investigation, and what would this be?
2 points or more indicates DVT likely:
A proximal leg vein US scan should be carried out within 4 hours.
If positive, diagnose DVT and start / continue anticoagulation treatment. If not available within 4 hours, start anticoag and wait until results of US scan.
If negative, arrange a D-Dimer test.
If scan negative but D-Dimer positive stop interim anticoag and repeat US 6-8 days later.
1 point or less = unlikely;
D-dimer within 4 hours; if positive do US within 4 hours.
What are contraindications to DOAC use in DVT?
Severe renal impairment; LMWH, UFH or LMWH followed by VKA (warfarin).
Antiphospholipid syndrome; LMWH followed by a VKA.
What is Burkitt’s lymphoma? (types, genetics, management and complications)
High grade B-cell neoplasm (NHL).
2 forms:
Endemic; ‘African’ FORM, typically involves the maxilla or mandible. EBV strongly associated.
Sporadic e.g. ileocaecal tumours. More common in patients with HIV. EBV weakly associated.
c-myc gene translocation t(8:14)
Mx = chemo
Cx = tumour lysis syndrome. Rasburicase is given before chemo to try and reduce this complication.
Describe the biochemical abnormalities that can result from tumour lysis syndrome.
Hyperkalaemia
Hyperphosphataemia
Hypocalcaemia
Hyperuricaemia
… acute renal failure
What is the pathophysiology behind an acute haemolytic transfusion reaction? + symptoms
ABO-incompatible blood e.g. secondary to human error.
Antibodies in the patient’s plasma react to antigens on the donor red blood cells, causing haemolysis.
Fever, abdominal pain, hypotension.
What are the typical features of TACO during a blood product transfusion + underlying pathophysiology + management.
Pulmonary oedema and hypertension.
Excessive rate of transfusion +/- underlying heart failure.
Slow or stop the transfusion. Could consider IV loop diuretic.
What are the clinical features associated with TRALI?
Pulmonary oedema
Hypotension
Fever
Non-cardiogenic pulmonary oedema thought to be caused by increased vascular permeability caused by host neutrophils that become activated by substances in donated blood.
What is the mnemonic for multiple myeloma’s clinical features?
Calcium; osteoclastic action causing bone resorption (IL-1, TNF released by tumour cells). Sx include constipation, nausea, anorexia and confusion.
Renal; monoclonal production of Ig results in light chain deposition within renal tubules (dehydration and increasing thirst)
Anaemia; bone marrow crowding suppresses erythropoeisis
Bleeding; bone marrow crowding results in thrombocytopenia and puts patients at risk of bleeding
Bones; marrow infiltration by plasma cells, and cytokine mediated osteoclast overactivity causes lytic bone lesions
Infection; reduced production of normal Ig
What is the underling pathophysiology of ITP in adults? + treatment
Antibodies directed against glycoprotein IIb/IIIa or Ib-V-IX complex.
Treatment is oral prednisolone first line.
Pooled IVIg may also be used; it raises the platelet count quicker than steroids so may be used if active bleeding or an urgent invasive procedure is required.
What is Evan’s syndrome?
ITP in association with AIHA
What does the presence of schistocytes (‘helmet cells’) on a blood film indicate?
Intravascular haemolysis
Mechanical heart valve
DIC
What do lead poisoning, thalassaemia, sideroblastic anaemia and MDS all have in common?
Basophilic stippling on a blood film
G6PD is an inherited haemolytic anaemia an the most common RBC enzyme defect, more common in Mediterranean and African descent. What is the inheritance mechanism of G6PD deficiency, and what things can precipitate a crisis?
X-linked recessive
Antimalarials e.g. primaquine
Ciprofloxacin
Sulfonamides, sulfasalazine, sulfonylureas
Infection
Fava / broad beans
Briefly describe the pathophysiology of G6PD deficiency.
Reduced G6PD => reduced NADPH => reduced glutathione => increased red cell susceptibility to oxidative stress
Give clinical features of G6PD deficiency.
Neonatal jaundice
Intravascular haemolysis
Gallstones
+/- splenomegaly
Heinz bodies on blood film
What is first line treatment for CML?
Imatinib (TKI)
Has very high response rate in chronic phase of CML.
What is polycythaemia vera, and what is the management?
Polycythaemia vera is a myeloproliferative disorder. It is due to clonal proliferation of marrow stem cells, leading to increased red cell volume, + neutrophilia and thrombophilia. Peaks in the 60s, and features would include hyperviscosity, pruritis and splenomegaly.
Aspirin reduces risk of thrombotic events.
Venesection keeps Hb in normal range.
?Chemo e.g. hydroxyurea, but this may increase risk of secondary leukaemia.
What is the prognosis for polycythaemia vera?
Thrombotic events are a signficant cause of morbidity and mortality.
5-15% will progress to myelofibrosis.
5-15% will progress to acute leukaemia, and the risk is increased in chemotherapy treatment.
What are the potential complications in CLL?
Anaemia
Richter transformation into high grade lymphoma
Warm AIHA
Hypogammaglobulinaemia leading to recurrent infections
What rises paradoxically in antiphospholipid syndrome?
APTT
APS is an acquired disorder that predisposes to both arterial and venous thromboses, but an ex-vivo reaction of the lupus anticoagulant autoantibodies with phospholipids involved in the coagulation cascade cause an APTT rise.
