Haematology Flashcards
What is flow cytometry?
Tests for types of proteins on surface of the cell, size + complexity ie type of cell
What’s the difference between serum and plasma
Plasma = coag factors and protein rich
Serum = no coag factors and proteins (clot using them up)
What does haematocrit refer to
The % of RBC’s column over total
Causes of low reticulocyte count
Iron def
Marrow diseases
Lack of erythropoietin
Decreased O2 consumption
Ineffective erythropoeisis
Chronic inflam or malig disease
Causes of neutropenia
> increased destruction = hyperspace sim, immune mediated destruction
decreased production = bone marrow failure (aplastic anaemia, chemo, acute leukaemia), specific neutrophil dysfunction (congenital/ drug induced)
Causes of neutrophil leukocytosis
> bacterial infection
tissue necrosis
pregnancy
acute haemorrhage
drugs
asplenia
What is a leukaemoid reaction
When mature and immature leukocytes are found in the peripheral blood in response to a severe infection
Causes of leukoerythroblastic blood film (nuclei in RBC’s)
> acute/chronic myeloid leukaemia
severe megaloblastic anaemia
myeloma/lymphoma
Severe haemolysis
primary myelofibrosis
Causes of eosinophilia NB
> allergic disease
parasitic disease
recovery from acute infection
certain skin diseases eg psoriasis
drug sensitivity
metastatic malignancy
What’s the difference between chronic and acute leukaemia
Acute - immature cells proliferate (aggressive)
Chronic - mature cells don’t die
What pattern of bleeding does thrombocytopenia give you
Mucocutaeous bleed (gums, nose etc)
Joint/muscle bleed = coag factor deficiency
Causes of deranged platelet counts
Thrombocytopenia
> decreased production
>increased destruction
>hypersplenism
>dilutional
Thrombocytosis
>reactive (acute haemorrhage, chronic infections, post splenectomy
>endogenous (myeloproliferative disorders)
Indications for bone marrow aspiration NB
> unexplained cytopenias
lymphoma staging
suspecting infiltration by TB or malignancy
leukaemia follow ups
Risk factors for thrombosis
Increased age
Pregnancy
Surgery
Arterial thrombosis risk factors
- male
- hyperlipidaemia
- family history
- diabetes
-hypertension - gout
- smoking
- polycytaemia
- lupus
Venous thrombosis risk factors
VIRCHOWS TRIAD
- age
- obesity
- lupus
- immobility
- lupus
- trauma
- surgery
- hormone replacement therapy
- previous thrombosis
What’s ironic about antiphospholipid syndrome
High PTT when tested in the lab, but the patient thrombosis
What are the symptoms of paroxysmal nocturnal haemaglobinuria
> dark urine in the morning from haemolysis
fatigue, dizziness, blood clots
can lead to aplastic anaemia
What tests would you run for a thrombophilia screen?
> FBC (platelets), diff and smear (fragments)
Clotting profile
Vit K
aPTT and PT (lupus antibody)
ESR (inflammation)
APS = antiphospholipid screen
thrombin time
Fribrinogen
antithrombin, protein C and s
PNH screen (paroxysmal nocturnal haemaglobinuria)
How long do you treat a patient who has clotted?
Provoked =3 months
Unprovoked = lifelong
Who do you test and who do you not test for thrombophilia?
TEST
>VTE in unusual location, unprovoked
>DVT/PE high risk of recurrence
CONSIDER
>VTE pt request
>family of strong thrombophilia in index pt
>arterial thrombosis in young, unexplained
NO TEST
>pregnancy loss (UNLESS >2 MISCARRIAGES >15 WEEKS →antiphospholipid)
What are the strong thrombophilia?
APLS
Protein C def
Protein S def
Antithrombin def
What do you do before you test for thrombophilia?
Wells score probability of having a PE or DVT
> 4 = high probability
What’s the difference between therapeutic and prophylactic anticoagulant treatment?
Therapeutic dose is higher
How do you treat thrombophilia?
Initiate LMWH parenteral and VitKA (warfarin) = bridging therapy
Warfarin also inhibits natural anticoagulants
When INR>2 then you can stop LMWH
What is a complication of not using bridging therapy?
Warfarin induced Skin necrosis
High INR indicates
Longer time to clot (pt bleeds)
What are the advantages of direct oral inhibitors?
Fixed dose
Few drug/food interactions
No monitoring
No need for bridging
What are disadvantages of direct oral inhibitors?
No reversal agents
Can’t miss a dose as short acting
Hepatic and renal effects
Less experience
What are the advantages of warfarin?
Long acting
Reversible
Long experience
Monitoring encourages compliance
Safe in renal failure
Disadvantages of warfarin
Monitoring frequency
Food and drug interactions
Variable dose
Narrow therapeutic range
Slow onset
What is heparin induced coagulopathy and treatment
Heparin binds to platelet factor and forms complex (removes platelets from plasma)
Antibodies attack complex and activate platelets to form throng = thrombocytopenia with clots
If this happens, stop heparin and find alternative.
Indications for ordering haemostasis tests?
> to ID pts who are acutely bleeding who have a correctable bleeding tendency
to ID pts with acute clots who have a correctable clotting tendency
monitoring anticoagulant medication
prognostication of liver failure pts
screening for DIC
Why do you need to fill the citrate tube to the top?
So that the ratio of plasma to anticoagulant is 1:9
What are the conventional tests for haemostasis?
Platelet count
PTT
PT/INR
Fibronogen
D-dimer
What may cause pseudothrombocytopenia?
Platelet trapping clots in tube from not mixing properly
EDTA dependent agglutinates
Causes of thrombocytosis? NB
Reactive: infection, post-surgery, post-splenectomy,malignancy, acute blood loss
Myeloproliferative
Causes of thrombocytopenia?
Decreased production: bone marrow disease, nutritional deficiencies
Increased destruction: autoimmune disease, DIC, medications, alcohol, HIV
Hypersplenism
Isolated increased PT/INR indicates…
VII deficiency
Increased INR + other coagulation abnormalities could be …
Vit K deficiency
Vit K antagonist
Malabsorption
Liver disease
Dilutional coagulopathy
High conc unfractionated heparin
How to prepare sample for PT measurement
> centrifuge
discard RBC’s
add calcium, thromboplastin (phospholipid and tissue factor)
fibrin clot
How to conduct aPTT test in lab?
> centrifuge
remove RBC’s
add calcium, partial thromboplastin (phospholipid with no tissue factor) and silica =activating agent
fibrin clot
Causes for isolated elevated aPTT
Factor XII, XI, IX and VII deficiency
Contact factor deficiency
Acquired clotting factor inhibitors
Prolonged aPTT and PT
Vit K deficiency
Liver disease due to malabsorption, decreased synthesis of clotting factors,
DIC
Multiple clotting factor deficiencies
Direct thrombin inhibitors
Dilutional coagulopathy
Causes of increased PTT +- increased PT
UFH
Antiphospholipid antibodies
Acquired clotting factor inhibitors
What causes high fibrin levels?
Acute phase reactant
Pregnancy
What causes low fibrin levels?
Liver failure (synthesised in the liver)
DIC
What is mixing studies and how does it help?
Take pt plasma and normal pt plasma and mix them. If clotting corrects then factor deficiency. If it doesn’t correct then there is a factor inhibitor.
Helps decide treatment
What is D-dimer?
A fibrin degradation product.
Causes of high D-dimer
PE
DVT
Arterial clot
Severe sepsis
Malignancy
Recent surgery or trauma
Liver disease
Pregnancy
DIC
Reasons for an artefactual abnormal result?
Pts haematocrit
Pt fasting state
Time between sample collection and test
Concentrate of citrate in tube
Define blood transfusion
Safe transfer of blood components from a donor to a recepient
What is acute normovolaemic haemodilution?
Remove blood from pt once under anaesthesia and replace with acellular fluid. Return as detected by intracellular loss.
How is platelet rich plasma formed?
4 huffy coat units and 1 plasma unit
Pre-transfusion tests of recipient?
Crosshatch
ABO and are blood ground
Antibody screen
Red cell concentrate indications
Acute blood loss
Anaemia symptomatic
Obs haemorrhage
Surgery
Platelet transfusion indications
Bone marrow failure
Massive transfusion
Acute DIC
Congenital disorders of platelets
Contraindications of platelet transfusion
Immune thrombocytopenia unless bleeding
Thrombotic thrombocytopenia purpura
Heparin induced thrombocytopenia
FFP indications
Replacement of inherited single factor deficiencies
Multiple coag deficiency
Thrombotic thrombocytopenia purpura
Reversal of warfarin if active bleeding
Vit K deficiency
Haemolytic disease of the newborn
What is leukodepletion?
Removal of majority of WBC’s from transfused blood products
Indications for leukodepletion
Pts on chronic transfusion regimens
Risk of CMV infection (intracellular)
Organ and stem cell transplant patients
Infant <1y
Pts undergoing cardiac surgery
What is gamma-irradiation
Kills off T lymphocytes to prevent graft vs host disease
Indications for gamma irradiation
Transfusion from relatives
HLA matched platelets
Intrauterine transfusions
Exchange transfusion
Congenital immunodeficiency states
Post allogenic transplants
Hodgkin lymphoma
Pts treated with purine analogue
Early complications of blood transfusions
Haemolytic reaction
Anaphylaxis
bacterial contamination
Allergic reaction
Febrile non-haemolytic transfusion
Electrolyte imbalances
Transfusion related acute lung injury
Late complications of blood transfusion
Graft vs host disease
Purpura
Alloimmunisation
Transmission of infection
Clinical features of haemolytic anaemia
Anaemia
Jaundice
Splenomegaly
Ankle ulcers(sickle cell)
Pigment gallstones
Bone expansion in children due to marrow expansion
Lab features of haemolytic anaemia
→/↑ Hb
↑ unconjugated bilirubin
↓ Haptoglobin
↑ LDH
↑reticulocytes
Increased urin + plasma Hb
How can you measure lifespan of RBC’s
Radioactive chromium labelling
Causes of intravascular haemolysis
Mismatched blood transfusion
Red cell fragmentation syndromes
Autoimmune haemolytic anaemia
Drug/infection induced
G6PD deficiency
Hereditary spherocytosis
Abnormal RBC membrane proteins = lipid bilateral unsupported = dehydration and K loss
Clinical features of hereditary spherocytosis
Increased haemolysis during infection
Splenomegaly, mild anaemia, mild jaundice,gallstones, iron overload, lower leg ulcers
Lab features hereditary spherocytosis
Hb varies
MCHC increased
Microspherocytes
Polychronasia
Osmotic fragility
Treatment of hereditary spherocytosis
Folic acid
Blood transfusion
Splenectomy
Cholecystectomy
G6PD enzyme deficiency clinical picture
Haemolysis 1-3 days after drug exposure
Dark urine, backache
Neonatal jaundice
Heinz bodies appear and Hb decreases rapidly
Lab features G6DP deficiency
Polychromatic
Acute ingravascular haemolysis
Heinz bodies on supravital staining
Management of G6DP deficiency
Stop offending drug
Treat infection
Transfuse red cells
Consider splenectomy
What is thalassaemia
Reduced synthesis of alpha or beta glob in chain subunit of Hb
Clinical features of thalassaemia
Anaemia
Failure to thrive, inter current infection, mild jaundice
Iron overload
Lab findings thalassaemia
Hypochromic microcytic anaemia
Raised RCC
Hyper cellular bone marrow
Management of thalassaemia
Keep Hb >9-10
Iron chelation therapy
Immunise for hep B
Splenectomy
Bone marrow transplant
What is iron stored as in the body?
Haemosiderin and ferritin
Iron deficiency vs iron deficiency anaemia
In the latter, there is depletion of the iron stores in the presence of anaemia
What is functional iron deficiency?
Insufficient mobilisation of iron for the purpose of erythropoiesis.
Iron restricted erthropoiesis
Reduced iron supply for the purpose of erythropoiesis, regardless of the level of iron stores.
Symptoms of iron deficiency anaemia
Pallor
Fatigue
Dizziness
Headache
Dyspnoea
Dry and damaged hair
Cardiac murmur
Tachycardia
Dry and rough skin
Lab features of iron deficiency anaemia
Microcytic hypochromic RBC’s
Reticulocytopenia
Pencil shaped poikilocytes
Target cells
What does S-ferritin levels tell us
Decreased in iron and Vit C deficiency
Increased in chronic disease from haemolysis after organ damage and inflammation
What does s-transferrin receptor levels tell us
Increased in iron deficiency anaemia (but not in chronic disease)
Influenced by change in rate of erythropoiesis
How does reticulocyte haemaglobin content help us?
Decreased in iron deficiency anaemia <27,2
But also in thalassaemia
Causes of iron tx failure
Non compliance
Continuing haemorrhage
Mixed deficiency
Another cause
Malabsorption
Wrong diagnosis
Expected response to iron supplements
Increase in Hb by 2g/dl every 3 weeks
What is iron refractive iron deficiency anaemia
Inherited disorder of both absorption and utilisation of iron
Partially responsive to parenteral, nonresponsive to oral
Causes for macrocytosis
Pregnancy
Reticulocytosis
Alcohol
Smoking
Liver disease
Myxoedema
Myeloma
Cytotoxic drugs
What are the effects of VitB12 deficiency and folate deficiency?
Megaloblastic anaemia
Macrocytosis of epithelial cell
Neuropathy
Sterility
Decreased osteoblast activity
Neural tube defects in fetus
Causes of ViB12 deficiency
Malabsorption
>pernicious anaemia
>gastrectomy
Abuse of nitric oxide
Inherited metabolic
>impaired ability to transport VitB12
Dietary deficiency
Pathophysiology of pernicious anaemia
Autoimmune gastritis = gastric atrophy = reduced acid and intrinsic factor
Clinical features of pernicious anaemia
Gradual onset with features of anaemia
Mild jaundice
Glossitis
Angular stomatitis
Purpura
Reversible melanin pigmentation
Progressive neuropathy
Lab findings of pernicious anaemia
Low reticulocyte count
Oval macrocytes
Hypersegmented neutrophils
Decreased leukocyte and platelet count
Treatment for Vit B12 deficiency
IM hydroxocobalamin 1000micrograms
6 doses over 2-3 weeks and then 1 dose every 3 months
Treatment for folate deficiency
5mg oral folic acid daily for 4 months (if chronic condition = lifelong tx)
