Haematology Flashcards
Non-haemolytic febrile reaction
- temp increase by 1-2, or >38
- ABs reacting to WBC fragments/cytokines in blood product
Px
- fever, chills
Mx
- slow / stop transfusion
- paracetamol
- monitor
Blood product transfusion reactions
Acute reactions
- Immunological – acute haemolytic, non-haemolytic febrile, allergic / anaphylaxis
- Infective
- Transfusion-related acute lung injury (TRALI)
- Transfusion-associated circulatory overload (TACO)
- Hyperkalaemia, iron overload, clotting
- hypotension in isolation
- transfusion associated dyspnoea
Delayed reactions
- Delayed haemolytic transfusion reaction
- Post transfusion purpura
- Transfusion associated graft vs host disease
Minor allergic reaction
- ?from foreign plasma proteins, hypersensitivity reaction
Px - pruritis
- urticaria
Mx - stop transfusion
- antihistamine
- monitor
- continue once sx resolve
Anaphylaxis
Px
- hypotension, SOB, wheeze, angioedema
Mx
- stop the transfusion
- IM adrenaline
- A-E, O2, fluids, antihistamine, corticosteroids, bronchodilators, ITU review
Acute haemolytic reaction
- ABO-incompatible blood -> massive intravascular haemolysis
Px
- begin in minutes
- fever
- abdo/chest pain
- hypotension
- UO falls
Mx
- stop transfusion
- check pt identity, name on blood product
- Send bloods - DAT, G/S, crossmatch
- fluid resus
- discuss with haem / ITU - maybe steroids +/- IV Ig
Cx
- DIC
- renal failure
Transfusion-associated circulatory overload (TACO)
- excessive rate of transfusion, eg pre-existing HF
- immediately, can be <24hrs
Px - pulm oedema
- ?hypertension
Mx - Slow / stop transfusion
- Consider furosemide, O2
Transfusion-related acute lung injury (TRALI)
- non-cardiogenic pulmonary oedema - increased vascular permeability from host neutrophils
- hypoxia / ARDS <6hrs post-transfusion
Px - hypoxia
- fever
- hypotension
Ix - CXR - pulm infiltrates
Mx - stop transfusion
- O2, supportive
Delayed haemolytic transfusion reaction
- fever, failure to respond to transfusion, unexplained bilirubin rise
- Dx on lab tests
Post-transfusion purpura
- immune mediated - 5-12d after transfusion
- platelet drop
Indications for blood transfusion
- acute bleeding, haemodynamically unstable
- Hb <70, stable
- Hb <80, ACS
- chronic transfusion-dependent anaemia
- radiotherapy (aim Hb>100)
- exchange transfusion
Anticoagulants reversal
dabigatran - idarucizumab
heparin - protamine sulfate
apixaban/rivaroxaban - andexanet alfa
edoxaban - ?andexanet alfa
warfarin - vit K, FFP, PCC
anaemia - definition
- low Hb conc
- Men Hb 130-180, women Hb 120-165
- MCV 80-100
causes of microcytic anaemia?
MCV<80 - microcytic
- iron deficiency
- anaemia of chronic disease
- thalassaemia
- congenital sideroblastic anaemia
- lead poisoning
causes of normocytic anaemia?
MCV80-100 - normocytic
- acute blood loss
- anaemia of chronic disease
- combined haematinic deficiency - iron + B12
- aplastic anaemia
- pregnancy
- haemolytic anaemia
- hypothyroidism
causes of macrocytic anaemia?
MCV>100 - macrocytic
- B12/folate deficiency - megaloblastic - pernicious anaemia
- alcohol excess / liver disease
- hypothyroid
- bone marrow failure / infiltration
- drugs - azathioprine, methotrexae
- reticulocytosis - rapid turnover, eg haemolytic anaemia
- myelodysplasia
what is haemolytic anaemia?
- abnormal breakdown of RBCs
- see reticulocytosis, increased bilirubin, LDH
Anaemia general Px
- fatigue, SOB, faint, dizzy
- palpitations, headaches, tinnitus, anorexia
- angina, HF
- conjunctival pallor, pale skin
- hyperdynamic circulation - tachycardia, flow murmurs, cardiac enlargement
Anaemia general Ix
- FBC - Hb, MCV
- reticulocyte count
- blood film
- renal profile
- LFTs
- ferritin, B12, folate
- TFTs
- IF ABs
- Coeliac ABs
- HB electrophoresis
- DAT
- colonoscopy + OGD
- bone marrow biopsy
iron deficiency anaemia
- low Hb due to low iron
- iron absorbed in duodenum/jejunum - needed for haem formation
causes of iron deficiency anaemia?
- low iron diet - vegans, lack of green leafy veg
- blood loss - menorrhagia, GI bleed, hookworm
- malabsorption - coeliac, Crohn’s
- higher iron demand - pregnancy, growing children
- PPIs
- paeds - excessive cow’s milk intake, CMPA
iron deficiency anaemia px
- anaemia - fatigue, SOB, pallor, dizzy/faint, palpitations, headaches
- brittle hair, nails
- atrophic glossitis
- koilonychia
- angular stomatitis / cheilitis
- pica
iron deficiency anaemia Ix
- FBC, blood film - hypochromic, microcytic anaemia, anisocytosis, poikilocytosis
- iron studies - low serum ferritin, high TIBC / transferrin
- reduced reticulocyte count
- colonoscopy + OGD
iron deficiency anaemia Mx
- oral iron - ferrous sulfate / fumarate
- iron-rich diet
- iron infusions - IV CosmoFer
- blood transfusion
Sideroblastic anaemia - Px, Ix and Mx
- RBCs fail to completely form haem
- congenital / acquired
Px
- anaemia sx
Ix
- FBC - hypochromic, microcytic anaemia
- blood film - basophilic stippling of RBCs
- iron studies - high ferritin/iron/transferrin saturation
- bone marrow - Prussian blue staining – ringed sideroblasts
Mx
- tx cause, supportive
- pyridoxine (vit B6)
- transfusions
anaemia of chronic disease - Px, Ix and Mx
- anaemia secondary to chronic disease
- poor use of iron / decreased RBC survival / decreased EPO
Causes - Crohn’s, RA, TB, malignancy, CKD, SLE
Px
- anaemia sx
Ix
- FBC, blood film - microcytic/normocytic, hypochromic
- iron studies - low serum iron/TIBC/transferrin sat, increased/normal serum ferritin
Mx
- tx cause
- recombinant EPO
- ?IV iron
aplastic anaemia - causes, Px, Ix and Mx
- bone marrow failure - pancytopenia
Causes
- Fanconi, acquired, chemo, infections (EBV, HIV, TB, hepatitis), pregnancy, radiation
Px
- anaemia sx
- infections, bruising, bleeding
Ix
- FBC - normochromic, normocytic anaemia, low WCC, low platelets
- low reticulocyte count
- bone marrow biopsy - hypocellular marrow, increased fat spaces
Mx
- remove cause
- blood / platelet transfusion
- bone marrow transplant
- immunosuppression
B12 deficiency
- needed for RBC production / DNA synthesis
- megaloblastic / macrocytic anaemia
- absorbed in terminal ileum bound to IF (produced by parietal cells in stomach)
- also important for myelination of nerves
causes of B12 deficiency
- pernicious anaemia - associated with thyroid, T1DM, Addison’s, RA, vitiligo
- low dietary intake - vegans
- alcoholism, malnutrition
- atrophic gastritis
- gastrectomy
- Coeliac’s, Crohns
- drugs - colchicine, AEDs, PPIs, metformin
B12 deficiency Px
- anaemia sx
- glossitis
- angular stomatitis
- mild jaundice
- neuro sx - peripheral neuropathy, subacute combined degeneration of spinal cord, neuropsych
B12 deficiency Ix
- FBC, blood film - macrocytic anaemia, hypersegmented polymorphs, low WCC/platelets
- Auto-ABs - IF ABs, parietal cell ABs
- serum B12 low
- Schilling test not done
- LDH - increased
B12 deficiency Mx
Initial
- IM hydroxocobalamin - 3x weekly for 2wks
Maintenance
- pernicious - 2-3monthly injections
- diet - oral cyanocobalamin / 2x yearly injections
- do not give folic acid at same time - wait for B12 to resolve
folate deficiency
- (Vit B9) - absorbed in jejunum, found in green veggies
causes of folate deficiency
- poor folate diet - poverty, alcoholics, elderly
- malabsorption - Crohn’s, Coeliac, alcoholism
- pregnancy
- anti-folate drugs - methotrexate, trimethoprim, AEDs
folate deficiency Px
- anaemia sx
- no neuropathy
folate deficiency Ix
- FBC, blood film - macrocytic anaemia, hypersegmented polymorphs
- increased LDH
- low reticulocyte count
folate deficiency Mx
- tx cause
- folic acid
Haemolytic anaemia
- premature breakdown of RBCs - intra/extravascular
Haemolytic anaemia causes
Hereditary
- membrane - hereditary spherocytosis / elliptocytosis
- enzymes - G6PD deficiency, pyruvate kinase deficiency
- haemoglobinopathies - sickle cell, thalassaemia
Acquired - immune (Coombs+)
- autoimmune - warm/cold
- alloimmune - transfusion, haemolytic disease of newborn
- Drug - methyldopa, penicillin
Acquired - non-immune (Coombs-)
- microangiopathic haemolytic anaemia - TTP, HUS, DIC, malignancy, pre-eclampsia
- prosthetic heart valves
- paroxysmal nocturnal haemoglobinuria
- infections - malaria
Haemolytic anaemia causes by site
Intravascular
- Mismatched blood transfusion
- G6PD deficiency (bit of both)
- RBC fragmentation – heart valves, TTP, DIC, HUS
- Paroxysmal nocturnal haemoglobinuria
- Cold autoimmune haemolytic anaemia
Extravascular
- SCA, thalassaemia
- Hereditary spherocytosis
- Haemolytic disease of newborn
- Warm autoimmune haemolytic anaemia
Haemolytic anaemia general Px
- anaemia sx
- splenomegaly
- jaundice
Haemolytic anaemia general Ix
- FBC, blood film - normocytic anaemia, schistocytes
- Direct Coombs test (DAT) - positive in AIHA
Autoimmune haemolytic anaemia (AIHA) - Ix and Mx
- body creates ABs against RBCs -> haemolysis
- warm / cold types
Ix
- FBC - anaemia
- increased reticulocytes
- low haptoglobin
- raised LDH + indirect bilirubin
- blood film - spherocytes, reticulocytes
- positive DAT (Coombs)
Mx
- blood transfusions
- prednisolone
- rituximab
- splenectomy
Hereditary spherocytosis - Px, Ix and Mx
- autosomal dominant - defect in RBC cytoskeleton -> fragile RBCs break down in spleen
Px
- failure to thrive
- anaemia
- jaundice
- gallstones
- splenomegaly
- aplastic crisis (parvovirus)
Ix
- FBC - raised MCHC, raised reticulocytes
- Blood film - spherocytes
- EMA binding test
Mx
- acute - blood transfusions, supportive
- long-term - folate, splenectomy, cholecystectomy
Hereditary elliptocytosis
- as spherocytosis but RBCs ellipse-shaped
- autosomal dominant
- Px / Mx the same
G6PD deficiency - Px, Ix and mx
- x-linked recessive - defect in gene for G6PD -> RBCs susceptible to oxidative stress
- triggers - infections, fava beans, meds
Px
- jaundice
- gallstones
- anaemia
- splenomegaly
Ix
- FBC
- blood film - Heinz bodies, bite+blister cells
- G6PD enzyme assay - dx
Mx
- remove trigger
- supportive
- transfusions
what is haemolytic disease of the newborn?
- If fetus is RhD+ (has RhD antigens on RBCs), and mother is RhD-, then during sensitisation event, mother can be exposed to fetal RhD, produce anti-D ABs against RhD
- In future, these ABs can cross placenta, cause haemolysis, destroying fetal RBCs
- To prevent sensitisation – give anti-D – Ig against RhD antigens that may have come from fetal blood into maternal bloodstream
Microangiopathic haemolytic anaemia (MAHA)
- destruction of RBCs as they travel through circulation
- abnormal activation of clotting cascade - thrombi obstruct vessels, churn RBCs -> haemolysis
- HUS, DIC, TTP, SLE, cancer
- schistocytes on blood film
Prosthetic valve haemolysis
- turbulent flow around valve -> shearing of RBCs
Mx - monitor
- oral iron / folic acid
- blood transfusions
- revision surgery
fanconi anaemia
- autosomal recessive cause of aplastic anaemia
- bone marrow failure, increased AML risk, neuro sx, short stature, thumb / radius abnormalities, café au lait spots
Sickle cell anaemia (SCA)
- autosomal recessive - production of abnormal Hb leading to vaso-occlusive crises (disorder of quality)
sickle cell pathophysiology
- HbS produced rather than HbA - which polymerises when deoxygenated - RBCs deform, produce fragile sickle cells -> intravascular haemolysis, obstruction, infarction
- HbSS/HbAS - anaemia / trait
Triggers
- spontaneous
- dehydration, infection, stress, cold weather, high altitude
sickle cell crises
Vaso-occlusive crisis - RBCs clog capillaries -> distal ischaemia
Acute chest syndrome - lung vessels blocked
Splenic sequestration crisis - RBCs block flow through spleen
Aplastic crisis - cessation of RBC formation - parvovirus B19 trigger - anaemia
sickle cell Px
- anaemia
- jaundice
- infection, fever etc
- vaso-occlusive crisis - pain/swelling in hands, feet (also chest, back, elsewhere)
- acute chest syndrome - fever, SOB, chest pain, cough, hypoxia
- aplastic crisis - anaemia
- splenic sequestration crisis - painful splenomegaly, blood pooling -> anaemia, shock
sickle cell Ix
- newborn blood spot screening
- test pregnant women at risk of being carrier
- FBC - low Hb, increased reticulocytes, increased bilirubin
- Blood film - sickle cells
- Hb electrophoresis - definitive
- CXR - pulm infiltrates (acute chest syndrome)
sickle cell Mx
- avoid triggers, dehydration
- pneumococcal vaccine (and others)
- pen V abx prophylaxis
- hydroxycarbamide
- crizanlizumab
- blood transfusions
- bone marrow transplant
sickle cell crises management
- low threshold to admit
- abx for infections
- keep warm, hydrate, IV fluids, analgesia, O2
- blood transfusion
- exchange transfusion
- splenectomy
- acute chest syndrome - incentive spirometry, resp support
sicke cell complications
- anaemia
- infections
- CKD
- sickle cell crises
- stroke
- avascular necrosis
- hypoxia -> fibrosis -> pulm HTN
- gallstones
- priapism
- splenic infarction, hyposplenism etc
what is thalassaemia
- autosomal recessive genetic defect in Hb protein chains -> underproduction of one globin chain
- reduced production + premature destruction of RBCs - disorder of quantity
thalassaemia pathophysiology
- HbA - 2 alpha, 2 beta chains
- lack of production of a/b chain
- reduced RBC production, fragile RBCs break down
thalassaemia Px
- Microcytic anaemia
- Fatigue
- Pallor
- Jaundice
- Gallstones
- Splenomegaly
- Poor growth + development
alpha thalassaemia
- Defect on gene for alpha-globin, 2 separate genes on each c16 (4 total)
1 deletion
- blood picture normal
2 deletions
- asym, mild microcytic anaemia
3 deletions
- Hb H disease
- severe haemolytic anaemia, splenomegaly
4 deletions
- alpha thalassaemia major - no a-chain, stillborn infant
beta thalassaemia
- defect in b-globin gene c11
- Homozygous B-thalassaemia -> little/no B chain production -> excess A-chain production -> A-chains combining with whatever B, delta, gamma chains available -> increased production of HbA2 and HbF -> ineffective erythropoiesis and haemolysis
- either abnormal gene / deletion of gene
B-thalassaemia minor / trait
- asym, heterozygous carrier
- mild/absent anaemia
- monitor only
B-thalassaemia intermedia
- 2 defective genes - 2 abnormal / 1 abnormal + 1 deletion
- moderate anaemia
- splenomegaly
- transfusions, iron chelation
B-thalassaemia major
- homozygous - 2 deletion genes
- severe anaemia, failure to thrive
- bony abnormalities - frontal bossing, enlarged maxilla, depressed nasal bridge, protruding upper teeth, prominent frontal/parietal bones
- HSM