Haematology Flashcards
What is sickle cell
Haemaglobinopathy caused by inappropriate exchange of valine for glutamic acid on BETA globin chain
HbS forms if homozygous = aa,SS
What type of inheritance is sickle cell, alpha and beta thalassaemia
Autosomal recessive
Consequences of sickle cell
- Painful venoocclusion
- Haemolysis - anaemia, jaundice, pigmented gallstones
- Splenic atrophy, infection
- Priapism
- Acute sickle chest syndrome
How is sickle managed
- Folic acid supplementation
- Infection prophylaxis
- Blood transfusion
- Hydrozycarbamide or hydroxyurea to inc HbF in crises
What is sickle trait
HbAS so they make some HbA and HbS because one b chain normal
protect against malaria, asymptomatic
Risks assd with being sickle trait
- pregnancy
- can sickle under stress
- splenic infarction
- renal disease
- vte risk
What is alpha thalassaemia
Lack of alpha chain -> excess b and g production = abnormal hb produced
HbH = bbbb
HbBarts = GGGG
What is beta thalassaemia and types
BTM = B0B0 absent alleles for beta BTI = B0B+ one absent one mutated BTT = BB0 one normal one absent
all of them -> relative alpha xs = unstable = extravascular haemolytic anaemia
Chelation drugs
Deferiprone = neutropenia risk Deferasirox = renal + liver tox Desferrioxamine
Differences in MCV, chromicity, and epidemiology of sickle and thalassaemia
Sickle is normocytic and normochromic - Thalassaemia is microcytic and hypochromic - Sickle = black and asian Thalassaemia = mediteranean
Causes of microcytic anaemia MCV <80
TAILS Thalassaemia AofCD IDA Lead poisoning Sideroblastic
Causes of IDA
- Poor diet
- Poor absorption (coeliac, Crohns)
- Inc demand (preg)
- Iron loss
- Bleeding due to cancer
- Ulcers
- IBD
- Gastritis
- Menorrhagia
Features of IDA on blood film
Microcytic, hypochromic cells
Pencil shaped
Target cells
Presentation of lead poisoning + tx
Abdo signs + neuropathy + anaemia + blue gum line
Tx - dimercaprol
Causes of normocytic anaemia
BABS
- blood loss
- A of cd
- BM failure - aplastic, chemo
- Sickle + other haemolytic anemias
Causes of macrocytic anaemia
- Megaloblastic (b12, folate)
- Alcohol, liver disease
- Drugs eg antiepileptics, hydroxycarbamide
- Myelodysplasia
Causes of folate deficiency
+ sign on blood smear
- Poor diet
- Malabsorption (coeliac, crohns, drugs eg cholestyramine)
- Inc requirement
(pregnancy, haemolysis, inflammation, homocystinuria) - Inc loss
(dialysis, drugs eg methotrexate)
Hypersegmented nuclei of neutrophils > 5
Causes of B12 deficiency
- Poor intake
- Pernicious anaemia (AI destruction of gastric pariteal cells releasing IF)
- Malabsorption (crohns, terminal ileum, drugs eg metformin)
- Nitrous oxide
What is the significance of G6PD deficiency? What are the triggers and genetics
G6PD protects against oxidative stress on RBCs so deficiency assd with haemolytic anaemia
It is X linked autosomal dominant, women carriers may have malaria protection
TRIGGERS:
Fava(broad) beans
Infection
Drugs (aspirin, malaria meds)
Blood smear findings of G6PD deficiency
Heinz bodies
Bite cells
What is the genetic inheritance of PK
Autosomal recessive
What is the most common cause of inherited haemolytic anaemia in west
Hereditary Spherocytosis
What is the inheritance of HS
Autosomal dominant
What is hereditary spherocytosis
beta spectrin or alpha ankyrin deficiency = spherical rbc = haemolytic anaemia
What is warm AI haemolytic anaemia and causes
igG against rbc = extravascular destruction
CAUSES:
1. idiopathic
2. secondary to conditions eg SLE, HIV,, CLL + B lymphoma etc
3. Secondary to drugs eg anti malarial, penicillin, dopa
How is warm haemolytic anaemia dx and which leukaemia is it assd with
DAT (coombs) +
CLL
What is cold haemolytic anaemia
igM that binds weakly to rbc at cooler temperatures
What is MAHA
Microangiopathic haemolytic anaemia = pathological changes to blood in small vessels usually secondary to TTP
Schistocytes + anaemia
Signs and symptoms of PCV
Fullness = headache, blurred vision, splenomegaly
+
aquagenic pruritis
plethora
Tx of PCV
Venesection
cytoreduction + aspirin (like ET)
How does ET present
asymptomatic but may
erythromelalgia
acroparasthesia
bleeding
How is ET treated
depends on risk
cytoreduction + aspirin
cytoreduction = hyroxycarbamide, anagrelide 2nd
What is APML
- genetics
- smear
- tx
defect in promyelocyte -> myelocyte = no neutrophils
Genetic: 15,17
Smear: auer
Tx: tretinoin + arsenic trioxide based therapy
Genetic basis of CML and which organs are enlarged
Tx
9,22 Ph
spleen only
imatinib
Symptoms of MM and what do we look for in dx
CRABI C- hypercalcaemia R- renal failure A - anaemia B - bone pain I - infections
M protein , bence jones protein i nurine
Presentation of hodgkin lymphoma
Painless lymphadenopathy or pain precipitated by alcohol
B symptoms
What disease causes bulky lymphadenopathy
Diffuse large B cell lymphoma
What is the most common low grade NHL and genetics of it
follicular
14,18 translocation
Describe clotting mechanism
- BV damaged
- Collagen exposed to blood so vwF binds
- vwF binds to platelets via gp1b
- platelets accumulate via gp2b/3a
- Bv wall releases tissue factor
- Bv constricts
5+6 stimulate clotting cascade - intrinsic pathway (starts with 12) requires 8 to convert 9a -> 10
- extrinsic pathway (starts with 7 -> 7a which -> 10)
- Common final pathway
10 -> 10a
10a requries 5 to convert prothrombin to thrombin
thrombin converts fibrinogen to fibrin
fibrin + primary clot = stable
Describe anticoagulation pathway
- thrombin goes to distal site and binds to thrombomodulin
- this complex activates protein c
- c binds to s
- c/s complex cleaves factors 5 and 8
- plasminogen converts to plasmin which breaks down clot
Which parts of clotting are vit k dependent
2,7,9,10
protein C - so warfarin can cause paradoxical thrombosis at first
What is vw disease
genetics
common defect assd
abnormality in quantity (t1) or quality (t2) of vWF
Autosomal dominant
TTP = AI to ADAMST13 which cleaves xs vwF so xs vWF = microthrombi
Name 4 types of platelet disease and what is prolonged
- Gray platelet syndrome = no alpha granules
- Storage pool disease = no beta granules
- Bernard Soullier = absent gp1b
- Glanzmanns = absent gp2b/3a
bleeding time prolonged if platelet dysfunction
what is the most common inherited RF for VTE and the genetics
factor 5 leiden mutation
means resistance to c/s cleaving
= prothrombotic
autosomal dominant
What is absent in haemophilia A
factor 8
ACE910 emicizumab
Inheritance of haemophilias
X linked recessive
What is absent in haemophilia B
factor 9
Universal rbc donor
O rhd-
Universal rbc recipient
AB rh +
What antibodies are involved in transfusion reactions
igM
What transfusion product presents biggest risk of infection
platelets (temp stored 22, shelf life 7 days)
Indications for RBC transfusion
Hb <70g/L stable
Hb < 80g/L CVD
Indications for platelet transfusion
significant bleed
platelet dysfunction
prior to invasive
prophylactic eg recurrent intracranial bleed
Indications for FFP
Major haemorrhage
PT INR ration >1.5 + bleed or pre procedure
PT INR ratio > 2 + liver disease + pre procedure
Indications for cryoprecipitate
PURPOSE TO INC fibrinogen Major haemorrhage + <1.5g/l <1 + pre-procedure CLD DIC
3 most serious transfusion
ABO incompatibility
Anaphylaxis (esp pxs who have igA deficiency)
Bacterial
3 most common transfusion reactions
TACO
NHFTR
Allergic
Signs of ABO incompatible haemolytic reaction
fever, abdo pain, hypotensive
Signs of TACO
pulmonary odema, hypertension
caused by high flow or HF existing
What are B symptoms
Fatigue Weight Loss Night sweats Fever Pruritis
