Haematology Flashcards
Blood production in foetus:
Just after conception
After 2 months
In adults
Yolk sac
Liver and spleen
Bone marrow
What % of the marrow is producing white cells
75%
Hormone that stimulate neutrophils, basophils and eosinophils
Granulocyte colony stimulating factors (G-CSF)
Produced by the endothelium and macrophages
Idiopathic thrombocytopenia purpura
Antibodies against glycoprotein IIb/IIIa complex or Ib-V-IX complex
Acute form:
Children following infection/vaccination
Self limiting over 1-2 weeks
Chronic:
Young middle aged women
Relapsing remitting
Evans syndrome
ITP in associated with autoimmune haemolytic anaemia
Platelet survival
RBC survival
Neutrophil survival
7 days
120 days
24 hours
Hb in pregnancy
Decreased
RBC increases but plasma increases more
Prevalence of anaemia in UK
4-5%
Methaemaglobin
Fe3+ is oxidised to Fe2+
Microcytic anaemia causes
Iron deficiency
Thalassaemia
Chronic bleeding
Normocytic anaemia
Chronic disease Haemolysis Acute blood loss Bone marrow infiltration Combined haematinic deficiency
Macrocytic anaemia causes
Haemolysis B12/folate deficiency (megaloblastic) Hypothyroidism Liver disease Alcohol excess Myelodysplasia
TIBC in:
Pregnancy
Anaemia of chronic disease
Iron deficiency anaemia
Increased
Decreased
Increased
RBC survival in anaemia of chronic disease
105 days
B12 source
Animal products
Folate source
Nuts vegetables cereals
Clinical features of b12 And folate deficiency
Glossitis
Jaundice
Neurological deficit - paresthesia and cognitive decline
Replacing B12 and folate
IM B12 then
Oral folate
Otherwise get subacute degeneration of the spinal cord
Hyposplenism blood film
Holly-Jowel bodies
Pappenheimer bodies
G6PDH
Inheritance
Enzyme cause of haemolytic anaemia
Mediterranean and middle eastern boys
Ciprofloxacin is a trigger
X-linked recessive
PK deficiency
Enzyme cause for haemolytic anaemia
Northern european children
Warm autoimmune haemolytic anaemia immunology
IgG mediated haemolysis occurring in spleen at body temperature.
Warm AIHA cause
SLE
Warm AIHA treatment
Steroids immunosuppression and splenectomy
Cold AIHA immunology
IgM and complement mediated haemolysis occurring at 4 degrees (e.g. In hands on cold day)
Responds less well to steroids`
Diagnosis of AIHA
Coombs’ test
Clinical features of haemolytic anaemia
Jaundice Anaemia Gallstones (if chronic) Haemoglobinuria (if intravascular) Splenomegaly (if extravascular)
Chromosomes of globin chain
A = 16 2 genes B = 11 1 gene Y = 11 2 genes D = 11 1 gene
Clinical features of beta thalassaemi major
Normal foetal life Anaemia in first few months Jaundice Medullary hyperplasia --> frontal bossing and hair on end appearance of cranium on xray Hepatosplenomegaly
Blood film of beta tahallasaemia major
Few RBC
Hypochromia
Target cells
Uncleared red cells
Barts syndrome
When all 4 of your alpha genes are mutated –> hydrops featalis and death as you cant make HbF
HbH disease
3/4 alpha genes are mutated
Commonly mistaken for iron deficiency anaemia as you get a microcytic hypochromia anaemia.
Dont give iron or you’ll make then worse. Usually live normal lives with the occasional transfusion
Inheritance pattern of thalassamieas and suckling disorders
AR
Prevalence of sickle cell anaemia
1 in 10,000
Specific mutation for HbS
6th amino acid of beta globin gene
Glutamic acid –> Valine
Rbc survival in sickle cell
<20 days
Sickle cell crises
- Thrombotic crisis - painful occlusion causing widespread infarction. Precipitated by dehydration, infection, deoxygenation. Acute chest syndrome can occur
- Sequestration crisis - spleen rapidly enlarges, pooling blood and causing anaemia but with high reticulocyte count
- Aplastic crisis - parvovirus infection leading to a sudden drop in Hb
- Haemolytic crisis - rare. Also causes sudden drop in Hb
Lab tests for sickle cell
High pressure liquid chromatography
Sickle cell solubility test ( goes cloudy in phosphate buffers)
First line treatment for neutropaenic sepsis
Tazocin
Definition of CLL
B cell >5x10’9 per litre for more than 3 months
If its raised but below the threshold its called a monoclonal B cell lymphocytosis
Smear cells
CLL
Flow Cytometry of CLL
T cell marker CD5
Survival of CLL
11 years
Pretty good considering diagnosis is around 72!
Somatic hypermutation, good or bad in CLL
Good
Un-somatically hypermutated CLL forms have a worse prognosis
Basal cell carcinoma is associated with which leukaemia
CLL
Presentation of CML
Early satiety (splenomegaly pushes on stomach)
Weight loss and sweats (hypermetabolic state)
SOB, priapism, eye problems (leucostasis)
Mainstay of management for myeloproliferative disorders
Track them Aspirin to reduce clotting Lifestyle factors to reduce clotting Hydroxycarbamide can be used as cytoreductive therapy In PRV --> venesection
Other treatment for JAK2 negative myelofibrosis
JAK2 inhibitors
Last line is transplant
Tear drop cells
Myelofibrosis
Chromosomal abnormality predisposing you to ALL/AML
Downs syndrome
Prognostic indicators for AML
Age (younger patients do better)
Genotype (FLT-3 neg/NPM-1 pos is better)
Cytogenetics - you know this
Treatment for very bad prognosis AML
BMT
Bone marrow histology for AML/ALL
Blasts must be >20% of nucleated cells for diagnosis
Clinical syndrome of ALL
Similar to AML: anaemia, thrombocytopenia, high blast
Dissimilar to AML: CNS symptoms, lymphadenopathy, bone pain.
Reasons for 20% mortality of BMT
Neutropenic sepsis
Graft versus host disease
Incidences of lymphomas
Hodgkin = bimodal Non-hodgkin = elderly
Ann Arbor staging
1 = 1 node 2 = 2 nodes same side of diaphragm 3 = 2 nodes different side of diaphragm 4 = involvement of major organs \+ A = no B symptoms B = B symptoms (drenching night sweats, fevers >38, weight loss >10% in 6 months)
Types of hodgkin lymphoma
Nodular sclerosing. 70%. F>M. Lacunar cells. Good prognosis.
Mixed cellularity. 20%. Many reed sternberg cells. Good prognosis.
Lymphocyte predominant. 5%. Best prognosis.
Lymphocyte depleted. <1%. Worst prognosis.
Burrkits lymphoma
High grade B cell neoplasm.
C-myc t(8.14) mutation
Starry sky appearance on microscopy
Common cause of tumour lysis syndrome
Two types:
Endemic - Africa, EBV, mandible
Sporadic - iléocaecal tumour
RF for hodgkin
EBV
Smoking
RF for non-hodkin
Autoimmune diseases
HIV/AIDS
HTLV1 infection
Smoking
Treatment of non-hodgkin
Low grade - nothing
High grade - RCHOP
1a –> 4 rounds every 3 weeks
Others –> 6-8 rounds every 3 weeks
RCHOP = rituximab, cyclophosphamide, hydroxydanunorubicin, oncovin, prednisolone.
Treatment of Hodgkin
ABVD +/- radiotherapy
Criteria for myeloma
> 30g/l paraproteinin blood
10% B cells in marrow
End organ damage CRABI
Monitoring for MGUS
Every 6 months
Monitoring for smouldering myeloma
Every 3 months
Treatment for myeloma
Chemo
Steroids
Thalidomide
Proteasome inhibitors
Whats in the blue blood test tube
Citrate to chelate all the calcium and prevent clotting in the tube
VWD inheritance
AD
Haemophilia inheritance
X-linked recessive
Management of haemophiliacs
Recombinant factor concentrate
Treatment of von willebrand disease
Tranexamic acid for mild bleeding
Desmopressin (DDAVP) raises levels of vWF by inducing releases f vWF from Weibel-
Palade bodies in endothelial cells
VWF/F8 concentrate if severe (v expensive)
Biliary obstruction leading to clotting problem?
Less bile and less vitamin K absorption so less 2 7 9 10
When to treat deranged PT aPTT platelet and fibrinogen levels in blood in someone with liver disease
Only if there are symptoms
What are thrombotic microangipathies
Thrombotic features + bleeding
DIC TTP HUS pre-eclampsia
Blood film in TTP
Thrombocytopenia and red cell fragments
Warfarin targets for first DVT
Recurrent DVT
- 5
3. 5
Length of warfarin treatment for
Provoked DVT
Unprovoked DVT
3months
6 months
What is factor V leiden
Prevalence
AD mutation in F5 gene making you 4x more likely to develop DVT
Activated protein C resistance
1 in 20
Peri-operative management of warfarin
Stop it 5 days before surgery
If INR <1.5 on the days, surgery can continue
Stratify into low, medium, high risk groups:
Low = no bridging therapy
High risk = prophylactic dose LMWH
Very high risk = treatment dose LMWH
Classic features of haemolytic transfusion reaction
Within minutes there is massive intravascualr haemolysis
Fever and tachycardia
Backache
Dark urine
–> DIC and renal failure
Management of acute haemolytic transfusion reaction
Termination of transfusion, generous fluid resuscitation and inform the lab
Allergic reaction to transfusion
Mild
Severe
Within minutes –> wheeze, urticaria, angiooedema etc
Simple urticaria = mild –> antihistamine and discontinue transfusion until symptoms have subsided and then can continue
Anything more = IM adrenaline, antihistamine, hydrocortisone
Over how long can you give red cells
FFP?
4 hours
30mins
Deferiprone
Iron chelation to prevent iron overload e.g. Haemophiliacs
