Haem Flashcards
A / b thalassaemia chromosomes
A - 16
B - 11
Homozygous a-thal presentation?
stillborn
Thalassaemia blood film?
Hypochromic, microcytic anaemia
On blood film: Mexican hat cells ? Sickle cells? schistocytes? Abnormal cells? spherocytes? (x2) elliptocytes? Heinz-bodies / blister cells?
Mexican hat cells - A-thal
Sickle cells - sickle
schistocytes - microangiopathic haemolysis
Abnormal cells - malignancy
spherocytes - hereditary spherocytosis / autoimmune haemolytic anaemia
elliptocytes - hereditary elliptocytosis
Heinz-bodies / blister cells - G6PD
How to make diagnosis of thalassaemia?
Hb electrophoresis
[a2 >3.5%)
Why skeletal survey in thalassaemia
for bone deformities - duh
Target Hb in thalassaemia? why?
Should be >95
suppress extramedullary haemopoiesis
Why is vit c (ascorbic acid) used in thalassamia
increase urinary iron excretion
Common surg for thalassaemia? Cure?
splenectomy (wait until >5)
bone marrow transplant
Key organs in iron overload
Pituitary - Hypogonads, low PTH/Thyroid, risk of diabetes
Heart - Dysrhythmias, eventual reduced LVF
bones - osteoperosis, short stature, bony overgrowth
Liver - cirrhosis + HCC
Bar B12 deficiency when else might you use b12
cyanide poisoning [displaces cyanide]
What causes an actue haemolytic reaction in transfusion
ABO incompatibility
3 ways transfusion of PRC causes clotting abnormalities
Dilution - should always give platelets after 4uPRC
Reduced Calcium (binded by citrate in PRCs)
Hypothermia - often thawed from frozen
Issue of rhesus D in pregnancy
Rh-ve mother with Rh+ve baby
-> Mother develops Anti-D antibiodies
Next pregnancy if baby is Rh+ve, Anti-D antibodies will attack baby causing haemolytic disease of newborn
Who gets given anti-D immunoglobulin
All mothers who have not been sensitised by 28 weeks (Rh Negative and no anti-d antibodies)
Rh -ve and PV bleeding after 12 weeks
Antibodies/antigens in blood groups
A - antigen A, Anti-b antibody
B antigen B, Anti-A antibiody
AB - Antigen A and B, No antibodies
O - no antigens , A and B antibodies
Anaemia, raised LDH. Dark brown urine with blood on dipstick but no red cells in there? Gene? What else is usually present in this illness? Rx?
Paroxysmal nocturnal haemoglobinuria
[Red cells haemolysed in cirulation -> Hb passed in urine (causing positive dipstick) but not red cells
Mutation of PIGA gene -> complement issues]
Think Peega gene
Usually get thrombotic events Eg DVT and pancytopenia
Eculizumab (disease specific) - inhibits complement C5
[pEE = Eculiz]
What causes the haemolysis in paroxysmal noctural haemaglobinuria
Complement attacks red cells due to lack of regulatory factors
Triad of paroxysmal nocturnal haemobloginuria
Haemolytic anaemia
pancytopenia
large vessle thrombosis
When do you get myoglobinuria
Rhabdo
When is coombs test positive
Warm autoimmune haemolytic anaemia
Haemoglobinuria in kids in winter?
Paroxysmal cold haemaglobinuria
Haemolysis on bloods
anaemia raised LDH Reticulocytes raised bilrubin LOW haptoglobin
Differentiate paroxysmal nocturnal haemaglobinuria and autoimmune haemolytic anaemia
Coombs test - positive in AHA
Pt with PNH with big neuro signs - whats happened?
Saggital vein thrombosis
Gold standard diagnosis in PNH
Flow cytometry for CD55 and CD59 [Absence diagnostic]
Fluorescent aerolysin test [most sensitive test]
PNH with marrow dysfunction Rx
ciclosporin and antithymocyte globulin
Allogenic BMT
Name a couple congenital / acquired prothombotic states
Congenital
Factor V leiden - most common
Prothombin (factor II) gene mutation
Protein C/S/antithrombin deficiency
Acquired Lupus antivcoagulant/antiphospholipid antibodies Polycythemia hormonal therapy (oestrogen containing) Pregnancy/nephrotic/malignancy
What does vit K affect?
Protein C (dependent on Vit K for synthesis)
[CalvinKlein]
When do you get warfarin induced skin necrosis
Protein C deficiency
Which of the hodgkins lymphomas has the best overall prognosis
Lymphocyte predominant
[Love lymphocytes]
What differentiates hodgkins and non-hodgkins
presence of reed-sternberg cells (in hodgkins)
[Giant abnormal lymphocytes - often binucleated]
Infection which seems to increase risk of NHL
EBV
Staging of lymphomas
Ann-arbour
1 - 1 lymph node
2 - 2 nodal areas on one side of diaphragm
3 - Lymph nodes on both sides of diaphragm
4 - Involvement of extra nodal tissues such as bone marrow or liver
Usual Rx of lymphoma
Chemo
[Can use autologous transplant - Stem cells from self]
patients on warfarin with life threatening bleeding need
prothrombin complex concentrate
When are platelets indicated
Bleeding with platelet count <50
Red cells demonstrating speherocytes? What causes the Jaundice, spenomegaly and anaemia? What else seen on blood film? Management?
Hereditory spherocytosis
Get spherical RBCs which are fragile and get stuck in microcirculation of spleen and removed
Red cells demonstrate osmotic fragility. Reticulocytes,
Splenectomy
What is coombs test also called? What is it?
Direct antiglobulin test
Tests for red cell / platelet antibodies
Post splenectomy what prophylaxis do you need
Pneumococcal - benpen / amox
Anaemia. Bone marrow biopsy shoes reduced haematopoetic cells, with a mainly fatty marrow and NO abnormal infiltrates. What is this? Rx
Aplastic anaemia
ATG (Anti Thymocyte Globulin)
BMT - If HLA matched sibling
If <50 first line in BMT,
If >50 first line in immunosuppressive
Aplastic anaemia
Hearing loss, pigmentation abnormalities, urogenital abnormalities?
Inheritance?
faconi anaemia
Recessive or x linked
-> aplastic anaemia
What is leukoplakia?
Abnormalities with nails, skin rashes and leukoplakia? Risk developing?
White spots in mouth
Dyskeratosis congenita
-> aplastic anaemia
Exocrine pancreatic dysfunction
aplastic anaemia
Skeletal abnormaities
MDS
Schwachman-diamond syndrome
What is the basic mechanism of all aplastic anaemia
Deficiency of haematopoetic CD34+ stem cells
Danazol / oxymetholone used in?
Aplastic anaemias (3rd line)
What are target cells? what conditions
Red cells with central staining
Seen in liver disease/ thalassaemia /hyposplenism
When should someone get cryo
Active bleeding, low fibrinogen
Treat immune TTP with?
Steroids / plasma exchange
DONT give platelets unless life threatening bleeding
Lenalidomide used in?
low risk MDS for Rx of transfusion dependent anaemia
What does MDS transform into ?
AML
First line investigation of likely low grade CLL?
High grade / rapidly progressing?
Low - peripheral blood flow cytometry and immunotyping
[Positve for CD5, CD19, CD20, CD23]
High - lymph node biopsy
What does a blood film show in CLL? descrived as dark staining with scant cytoplasm
Lymphocytosis
Smudge/smear cells
Usual Rx Of CLL?
can watch and wait if slow
Chemo usually first line - 25-50% remission with 1st line Rx
Which mutation has poor prognosis in CLL? What does this mean?
TP53
[17p(del) also bad]
Should be referred for stem cell transplant following if they achieve remission following medical therapy
What is richter transformation
transformation of B cell chronic lymphocytic leukemia (CLL) or hairy cell leukemia into a fast-growing diffuse large B cell lymphoma, a variety of non-Hodgkin lymphoma which is refractory to treatment and carries a bad prognosis
Poor prognostic factors for CLL - get a couple and try recognise a couple more
Which gene? Which chromosome?
Level in blood of?
Impaired renal function Male sex Some genes - Eg TP53 beta-2-microglobulin (B2M) > 3.5mg/l 17p(del) on chromosome typing elvetated thymadine kinase (>10 U/l)
Plasmodium malaria treatment started
-> Acutely unwell with significant intravascular haemolysis and renal shutdown
What is this condition?
Black water fever
Intra vs extravascular haemolysis
Intra - destroyed in the blood vessel
->More acute
[(G6PD) deficiency or certain immune-mediated processes]
Extra - destroyed by spleen / liver
->more chronic
[RBC membrane disorders such as hereditary spherocytosis]
What are shistocytes? What does this indicate? Why do you get low platelets? Important 3 syndromes associated with this?
Sheared erythrocytes
Microangiopathic haemolytic anaemia
Thrombocytopenia from platelet aggregation and micro thrombi
TTP and HUS / HELLP
Microangiopathic haemolytic anaemia (MAHA)+ thrombocytopenia is what until proven othewise? Ix for this?
Other causes of MAHA
TTP
ADAMSTS13 assay <5% + IgG
HUS Prosthetic heart valves SLE infection HELLP syndrome
2 bugs that cause HUS
E coli -0157
Pneumococcus
Basic pathophysiology of MAHA
Intravascular haemolysis caused by turbulence of blood flow due to a trigger
-Platelet microthombi in organs shred erythrocytes
How does MAHA vary from DIC
In MAHA consumption of clotting factors is not always a feature
-> PT/APTT may remain normal
[DIC may be a trigger for MAHA]
What does ADAMS13 do in TTP?
Cleaving protein for von willebrand factor
-> Deficiency causes inappropriate clumping of platelets as they stick to the unusually large vwf. RBCs then get smashed on these clumps
Symptoms of TTP
ALL DUE TO MICROTHROMBI
Fever Confusion Altered neurology Jaundice Renal impairment
[don’t always get neurology and renal impairment]
TTP management? Drug to prevent relapses?
plasma exchange
[Caplacizumab can be used to help prevent relapses - helps to cleave VWF)
HELLP syndrome - 2 key management parts
Magnesium
Deliver bab
DVT treatment length? Drug of choice if renal impairment?
3 months provoked
6 months unprovoked
LMWH - can use unfractionated heparin if sever renal impairment
What does having low protein C/S levels cause ? 2 other causes?
thombosis - not haemorrhage
Factor V leiden
Antiphospholipid syndrome
What would a derranged APTT mean you should look into? How is it different to PT
Assay of clotting factors [VIII, IX, XI, XII]
As it measures the intrinsic system
PT measures extrinsic
Both measure final common pathway
What does thrombin time measure? When is it prolonged
Final part of common pathway
Lack of fibrinogen to convert to fibrin
or inhibitors Eg Heparin of this conversion
Which factor is part of extrinsic? Which other thing
Factor VII
tissue thromboplastin
What would a normal fibrinogen level with prolonged thrombin time mean? Who gets this
Dysfibrinogenaemia
Usually found in liver disease
Diagnosis of myeloma made by? Pneumonic for presentation
serum electrophoresis
or urinary bence-jones protein
CRAB Calcium raised Renal impairment Anaemia Bone lytic leisions
Which types of myloma M-protein are common
IgG and IgA (IgE and IgM are rare)
What type of cell in myeloma
Plasma (B cell) -secretes monoclonal Ig
Why do you get renal issues in myeloma
Hypercalcaemia from bone lysis
Bense-jones protein clogging
2 tests for staging of myeloma
Serum beta2-microglobulin
serum albumin
Myleloma is can be treated with Chemo + steroids.
Rx avoided if pain from leisions?
Rx of bone lesions?
2 other key parts of pharmacological management ?
DONT give NSAIDS - renal impairment
bisphosphonates
Thromboprophylaxis
Pneumoccal + seasonal influenza vaccines
Anaemia + gallstones =
hereditary spherocytosis
Which bilirubin is high in hereditary spherocytosis
Unconjugated
unconjugated found in blood which is then conjugated by liver to be excreted
Bar splenectomy what other prophylactic surgery common in herediatory spherocytosis
Cholescystectomy - high incidence gallstones
How long after stopping warfarin do you need to wait to do a thombophilia screen
At least 3 weeks
What are cold agglutinins? Which disease
Antibodies which bind to haemoglobin in cold temperature
Lymphoproliferative diseases -> Eg Non-Hodgkins
[They are not present in hodgkins]
Most common cell type for NHL
B cells (85%) T cells or natural killer cells
How to confirm diagnosis of NHL
Needle core biopsy
reed sternberg cells are absent
Most common type of lymphoma? Most common low grade
Diffuse large B cell
Follicular
1 virus and 1 bacteria linked to lymphoma
Ebstein Barr (HIV, HepB/C) H pylori
Vaccines in Lymphoma
Mengingococcus type C
H influenzae type B
Chemo is mainstay of treatment in lymphoma. What is the treatment of CNS primary ?
High dose MTX + steroids
Microcytic anaemia
Raised ferritin
Increased iron and abnormal erythropoeisis on BMT
Heritability in question
Sideroblastic anaemia
Worst prognosis for hodgkins types on biopsy
Lymphocyte depleted
CLL first line Ix
Blood smear with immunophenotyping
teenager with painless lymphadenopathies
HODGKINS
Polycythemia is characterised by…? Most common mutation and what does this cause? What is low and why?
Increased red cells, platelets, leukocytes
Splenomegaly
JAK2 -> activates pathways which stimulate EPO receptors -> Erythrocyte formation (will therefore have low EPO levels due to negative feedback)
What does Polycythemia cause? Symptoms with these?
Expansion of Red/White cells which leads to increased viscosity of blood
- Headaches + hypertension + visual distubance
- erythromelalgia (burning cyanosis in hands/feet) - Itching in warm water
Increased RBC turnover -> gout
Increased prothrombotic factors -> thrombosis Eg MI/Stroke/PE
Splenomegaly
hypercellularity for age with trilineage growth Seen on bone marrow biopsy
polycythemia
Polycythemia and deranged LFTs. Key worry?
Budd-chiari syndrome
Polycythemia 2 parts of usual Rx? What if high risk / worsening Sx?
Low dose apsirin
Phlebotomy - aim to keep haematocrit <45%
Hydroxyurea
Ruxolitinib is used in polycythemaia with severe symptoms which haven’t responded to treatment / post PV myleofibrosis . How does it work? How to to spot it?
JAK1/2 inhibitor
RUxolitinib in polucythemia RUba vera
what kills people with polycythemia? Most common complications
CV complications
Transition to myelofibrosis [AML less common but also possible]
Bleeding and thrombus are the most common
Marker to assess prognosis of myeloma
serum B2-microglobin
[and albumin - use these to calculate the ISS international scoring system]
Best investigation for chronic myeloid leukaemia
BCR-ABL analysis on peripheral blood
[DON’T Need marrow aspirate]
Most common cause of death in CLL
Infections [due to a reduction in immunoglobulin production ]
Copperhead snake venom assay used for?
used to detect protein C deficiency
C for C
What is shown in clotting study of DIC? Key blood test which will be raised
Low platelets
Prolonged PT / APTT
Low fibrinogen + high fibrin degredation products - prolonged thromin time
D dimer
Howell-jolly bodies are due to? most common cause?
Hyposplenism (due to infarction from sickle cells)
Sickle cell
[Amyloid, IBD, Coeliac, cirrhosis, SLE, spherocytosis, sickle cell, sarcoid, splenic thrombosis, rhem A]
ABCCSSSSSSSSR
Which infection in sickle cell leads to
Aplastic crisis?
Asplenia?
Parovirus B19 - Aplastic crisis
Encapsulated organisms - asplenia
[Haemophilus influenzae type B
Streptococcus pneumoniae
Neisseria meningitides
Group B streptococcus
Salmonella typhi]
How to confirm sickle cell homo/heterozygous
Hb electrophoresis
Sickle cell vaccines? What do they get life long (x2)?
to prevent painful crises/ acute chest syndrome?
If all this doesn’t work and young?
penumococcal / influenza / hepB Vaccines
Penicillin lifelong
Folic acid - for anaemia
Hydroxycarbamide to prevent painful chest / acute crisises
Stem cell transplant
Most common inherited bleeding disorder ? What drug should everyone be trialled on?
Von willebrand
Desmopressin (releases vWF and Factor III) from endothelial stores
Weird thing sickle cell can cause in kidneys
Nephrogenic DI
Management of anaemia in CKD dialysis
IV iron (not oral - don’s absorb it well in end stage CKD)
once iron stores increased ferritin >100
->EPO
[ Pts with CKD usually have iron deficiency due to blood loss in dialysis / frequent blood samples +/- malnutrition… (can give oral iron if not on dialysis -> IV)
They will often be deficient in EPO too but need iron replaced first ]
Most common long term risk of radiotherapy
secondary Ca
Thombocytopenia, recurrent thrombosis =
Antiphospholipid syndrome
Differentiate antiphosopholipid syndrome and Factor V leiden
Phospholipid = livedo reticularis (mottling - netlike pattern of reddish-blue skin discolouration - usually on legs)
Thrombocytopenia and prolonged APTT
[None of the above in factor V leiden]
Most common inherited bleeding disorder? Most common inherited thrombosis disorder?
von willebrand
Factor V leiden
Prev hodgkins treated with chemo / radio 10 years ago. Now symptoms of anaemia and thrombocytopenia. What has happened ?
Developed AML secondary to chemo / radio
Blood film shows what percent myeloblasts in AML
> 20%
Main assessment for prognostication in AML
through cytogenic analysis of the bone marrow
3 congenital disorders with high risk AML
Downs
Faconni
Neurofibromatosis
What do myeloblasts become in normal people
Red blood cells, neutrophils, platelets
[The big 3 really]
Seen on blood film AML
Blast cells
Auer rods
cytogenetics are used for AML prognositcation. How do you classify sub types
Immunophenotyping and molecular studies
Chemo is mainstay of AML. What other drugs are used usually as supportive Rx ?
hydroxycarbamide, allopurinol, rasburicase
How would with a-thalassaemia present in adult in question
Mild anaemia + mild low MCV and MCH.
Normal iron / ferritin (probs a bit raised)
Asymtomatic or mild symptoms when preg
Probs Mediterranean or south asian.
Major trauma Eg fracture femur. Then get dyspnea and confusion 24 hrs later. What has happened? What rash do you get?
Fat embolism
Multiple petechiae in axilla and skin folds upper body
Asymptomatic
Then start new drug -> intravascular haemolysis.
Diagnosis? Inheritance
Blood film shows? Other test?
G6PD - x linked recessive
Heinz bodies, blister cells, bite cells
quantitative spectrophotometric analysis
Bar drugs name a couple other triggers for G6PD haemolysis
FAVA BEANS [Hep A/B CMV Pneumonia typhoid ] Basically infections
NADP is involved in the production of glutathione (protects cells from oxidative damage) what is required for its formation? How do you test for NADPH formation?
G6PD
Rapid fluorescent spot test
Resected ileum now anaemic. What is most likely deficiency
B12 - absorbed terminal ileum
[Dude Is Just Feeling Ill Bro]
Important first step in sickle cell acute pain joint
Oxygen - pain is due to veno occlusive state and tissue hypoxia
Acute breathlessness 15 mins into a transfusion, with diffuse bilateral infiltrates on CXR
Transfusion related lung injury
NOT Anaphylaxis / ABO incompatibility
What drug do you give before starting chemo
rasburicase
-> reduce urate nephropathy
Von willebrand disease. What drug needs to be ok’d by haematologist before using
NSAID
VW disease if going for operation? Key risk? What else can they get if bleeding risk high?
desmopressin (synthetic ADH -> fluid retention and risk of pulmonary oedema)
tranexamic acid
vWF contatining concentrate (given 8 hours pre op) eg haemate p
Aminocarproic acid
Which finding exam is specific to iron deficiency anaemia
Koilonychia
Spoon shaped nails
Infections people with coeliac suseptible to?
Encapsulated Eg pneumococcus / menigococcus
Hyposplenism
what else is seen on blood film in megaloblastic anaemia
Hypersegmented neutrophils
Haemophilia Coag screen
PT - normal
APTT - Prolonged
Bleeding time - normal
vwf - normal
Factor 7 deficiency on coag
Prolonged PT
Example of substrate with vWF in
haemate P
Factor VIII and vWF
Which of B12 and folate rely on the other
Need B12 for folate metabolism
Therefore Low b12 -> low folate
[B comes before F]
Eg in Terminal ileum disease
B12 deficiency what do you see on bloods
-Macrocytic anaemia
-Low folate
-Raised LDH and bilirubin (due to inneffective erythropoeis and haemolysis)
HbA2 and HbF levels
Differentiate a and b thalassaemia traits on bloods ? B intermedia?
A - HbA2 <4%
HbF <1%
B - HbA2 >4%
HbF >1%
B intemedia HbF 5-50%
Who gets CMV negative blood
Preganant people who are CMV negative
Who gets irradiated blood? why ?
Blood cancer - reduce the risk of GVHD from donor lymphocytes in blood
Why improved absorbtion of iron with vit C
chelates it from ferric to ferrous form
Essential thrombocythemia Ix?
Rx of low risk ? high risk?
Blood smear
Bloods (thrombocytosis / iron pannel)
Antiplatelets
High risk add in:
-Hydroxycarbamide + anticoag
CML Rx drug
May be fine
BCR-ABL Tyrosine kinase inhibitor
Eg Imatinib
Philidelphia chromosome positive Rx
haematopoeitic stem cell transplant
Reasons to regect a blood donor
Weight?
Tattoo?
Travel?
Blood test?
<50kg
Peircing / tatoo <4months
Travel to endemic area <6months
Anaemia
Acute chest in sickle cell due to
Pulmonary infarction
Which common Abx is high risk for G6PD? Other drugs?
Nitrofuratoin
Antimalarials
Dapsone
Rasburicase
sulphonomides (eg co-trimoxazole)
Which common Abx is high risk for G6PD? Other drugs?
Nitrofuratoin
Antimalarials
Dapsone
Rasburicase
sulphonomides (eg co-trimoxazole)
Anaemia, thrombocytopenia, rasied WCC + DIC =?
Acute promyelocytic leukaemia
2 core features of MAHA ? If renal impairment and preceeding diarrhoeal illness?
Anaemia, thrombocytopenia
TTP -> Plasma exchange
DVT -> stroke what do you need to do to work out diagnosis?
ECHO
clot though patent foramen ovale
Hypereosinophilic syndrome Rx
Steroids
[after excluding parasites and a Marrow issue]
Bleeding on warfarin life threatening 2 things
Vit K 5mg
Prothrombin complex concentrate
[FFP no longer recommended for warfarin]
Anaemia, thrombocytopenia, spenomegally, multiple enlarged lymph nodes, headaches and weight loss. Raised IgM? Why headaches?
Non-hodgkin Lymphoma - Eg Waldenstroms macroglobulinaemia
Headaches due to hyperviscositiy -(lymphoma secreting IgM)
There is no Hyperviscosity in hodgkins
How does desmo help with clotting
-> Release of factor VIII and VWF
Mediastinal / cervical lympadenopathy in young person with weight loss
Hodkins
Mediastinal / cervical lympadenopathy in young person with weight loss
Hodkins
What are reed-sternberg cells
Giant binucleated lymphocytes
ITP + Haemolytic anaema? Rx?
Evans syndrome
steroids
Single Neck lump with B symptoms. Best diagnositic test?
Excision biopsy
Skin lesions, lymphadenopathy, hypercalcaemia. What virus?
Human t-cell lymphatrophic virus -1
Rheum A, splenomegally and neutropenia
Felty syndrome
Rheum A, splenomegally and neutropenia
Felty syndrome
HIV with low cd4. Neck lump
high grade NHL
AML prognostication
Bone marrow karyotyping
[%blasts has no prognotic value]
Reversal of altepase? Which is more important
tranexamic acid - most important as inhibits plasmin
FFP
Itching in Polycythemia rx?
Aspirin
[then clopidogrel + antihistamines]
Haemophillia vaccination?
Hep B
Vasopressin can be used in what haemohillia
Mild type A
[ineffective in Heam B]
Few weeks post BMT. widespread rash, profuse diarrhoea
Acute GVHD
New Elevated TT and very high APTT with normal reptilase time. What needs to be considered
Heparin in sample (Eg from lines in ICU)
Mechanism of action. Key drug in Overdose.
LMWH?
DOACs?
Dabigatran?
Activates antithrombin III (which then inhibits to Xa)
-Protamine
Xa inhibitors
-Andexanet (if apix / rivarox)
ApiXAban XA, andeXAnet
Direct thrombin inhibitor
-idarucizumab
D for D
phenytoin key worry
Pancytopenia
Which leukaemia has philidephpia commonly
CML
Anaemia, raised platelets, granulocytosis, hepatomegally?
What is granulocytosis
CML
raised neutrophils, eosinophils and basophils
How differentiate aML and CML if not given marrow
AML - low platelets and blasts on blood
CML - high platelets and increased counts of mature cells
Both will have anaemia
What causes Secondary polycythaemia
Hypoxia, testosterone or elevated EPO
CLL andd then worsening anemia and raised bilirubin 1st line Ix?
Direct antiglobulin test
[CLL associated with autoimmune haemolytic anaemia]
1st line Rx in warm AIHA? Also what extra Ix?
Steroids +/- Rituximab
Also need to screen fro DVT
Cold AIHA rx if Hb <70? Immediate vs longer? If all else fails?
Transfusion + plasma pheresis
Rituximab + bendamustine
Finally bortezomib
Which blood cancer linked to autoimmune haemolytic anaemia - especially if new symptoms of anaemia in question
CLL
Which genetic abnormality bad in AML?
Chromosome 7 abnormalities
Which genetic abnormality bad in AML? Good prognosis (and most common)?
Chromosome 7 abnormalities
t (8:21) - good prognosis and most common
>60 also carries poor prognosis
Most common genetic change in acute promyelotic leukaemia?
t (15:17)
Carries a good prognosiss
Key drug for aplastic anaemia?
What if they are old and cant hack it?
ATG (Anti thymocyte globulin )
Danazol / oxymethalone
Women should get danazol as less masculinising side effects
How to differentiate mycosis fungities from cutaneous B cell lymphoma
immunophenotyping
Differentiate mycosis fungitides and sezary syndrome
Sezary syndrome has high levels of circulating atypical lymphocytes with cerebreform nuclei
(sezary cells)
Differentiate mycosis fungitides and sezary syndrome
Sezary syndrome has high levels of circulating atypical lymphocytes with cerebreform nuclei
(sezary cells)
GVHD is due to?
Treansfusion related lung injury is due to?
Donor T lymphocytes
Donor antibodies (anti-HLA)
Pancytopenia in a young person + DIC
Acute Promyelotic Leukaemia
Classically associated with DIC
Pink/red stained cytoplasmic inclusion bodies in myeloid cells is describing
auer rods
(AML)
First line CML
Imatinib
Tyrosine kinase inhibitor
Evidence of polycythemia .
Blood gas shows PO2 of 6 but SpO2 of 98% what is the cause
Increased affinity haemoglobin
Ie Hb has increased affinity to O2 -> doesn’t release it to cells which drives hypoxia -> polycythemia
Weird false positive test in antiphospholipid
VDRL
Antibodies bind to test
Antiphopholipid syndrome - which part of coag screen is always normal
PT
First line Ix in sickle cell who has significant acute anaemia
Reticulocyte count - allows to work out if it is:
Haemolysis with normal marrow - raised reticulocytes
Aplastic anaemia with non functioning marrow -low reticulocytes
Parovirus is commoncause of aplastic anaemia but NOT the first line Ix
Raised levels of what type of Hb increase risk of thalassaemia in offspring
HbF
Old. Anaemia with riased bilirubin. Marrow shows iron accumulation around neucli around growing erythrocytes
Lead poisoning
if sideroblastic anaemia they would have presented younger
Consider this if people living in OLD house [may still have lead pipes]
Drug Rx of APML - How does it work
ATRA (all-trans-retinoic acid)
Promotes differentiation of APML cells into mature cells
And apoptosis of bad cells
Hairy cell leukaemia which genetic change is implicated
Mutation of BRAF
What is used to replace fibrinogen in DIC
Cryo
What is hydroxycarbamide mechanism? When might it be used?
Hydroxyurea?
Hydroxycarbamide decreases the production of deoxyribonucleotides [via inhibitoon of ribonucleotide reductase
Sickle ell / thalassaemia - increases HbF production
Myeloproliferative disorders Eg Polycythemia, essential thrombocytopenia
CML - though now mostly imatinib
Hydroxycarbamide (sometimes used) as much cheaper than imatinib
Hydroxyurea is the same thing
First line Rx for DVT
Apix / rivarox
LWMH if CI’d
What symtoms during a blood transfusion would make you think acute haemolytic reaction rather than non-haemolytic febrile reaction
Back/ abdo pain
Evidence of CV collapse Eg hypotension /tachy
What symtoms during a blood transfusion would make you think acute haemolytic reaction rather than non-haemolytic febrile reaction
Back/ abdo pain
Evidence of CV collapse Eg hypotension /tachy
What symtoms during a blood transfusion would make you think acute haemolytic reaction rather than non-haemolytic febrile reaction
Back/ abdo pain
Evidence of CV collapse Eg hypotension /tachy
Microcytic anaemia but normal ferritin first line Ix?
Hb electrophoresis
[dont need endoscopy as ferritin normal = not iron deficiency]
Importnant immediate blood test in AML likely new diagnosis?
Clotting screen - rule out DIC
(may have APML)
Key things to exclude before diagnosis of essential thrombocythemia
Inflammatory process -
Anaemia
Spenectomy
Infection
Only 50% are JAK2 positive
Differentiate IDA and thalassaemia
Hb A2 levels
What happens in HIT ? When does it develop
Heparin binds to PF-4 on platelets
some people have IgG against this
Whn IgG binds -> platelet activation
->clots + thrombocytopenia
Usually after 1 week [Takes a week for IgG to form]
May develop in 1 day if previously treated with heparin and already have IgG
Gold standard Ix for HIT
Serotonin release assay
Mild splenomegally, mild raised WCC (neutrophils), Thrombocytosis, normal Hb? Common Rx
Essential thrombocythemia
Hydroxycarbamide + aspirin
WCC usually much higher in CML and likely to be anaemic
Heparin vs LMWH
Rate of HIT?
Less in LMWH
Haemophilia B - rx of acutely swelling knee joint post sport?
Factor 9
Need to stop bleeding as risk of long term joint damage
Presents in preg with microcytic anaemia. HbA2 is 4.5% HbF <1
B thalassaemia trait
If HbA2 is > 4% it is B thal
ALL good prognosis vs bad prognosis mutation
Good - t (12:21)
Bad - t (9:22) - Philadelphia
Tired all the time, weakness. Anaemia with raised MCV. Not megaloblastic anaemia on marrow. What is Dx?
Hypothyroid
Anaemic, thrombocytopenia and acute bleed Rx?
IV Ig
Platelets not used in ITP
ITP what is the antibody to?
GP2b/3a receptor
ITP vs TTP
Cause?
Levels of what in blood?
PT/APTT?
Rx?
Mab?
Who gets a splenectomy?
ITP - IgG to GP2a/3b
watch and wait if Asx -> steroids
IV Ig if severe
Rituximab
May need splenectomy
TTP - Deficiency of ADAMSTS13
-schistocytes, raised bilirubin, raised LDH
Plasmapheresis
PT and APTT normal in both
Rasburicase mechanism
Uric acid oxidation
Longstanding polycythemia - now anaemia and thrombocytopenia. What has happened
Progressed to myelofibrosis
DVTs and pancytopenia. Haemosiderin in urinalysis. Key iX? What is the significance of haemosiderin in urine?
Blood immunophenotyping (for CD55 and 59)
Chronic intravascular haemolysis -> Hb released + absorbed by proximal tubule of kidney cells.
These slough off with haemosiderin (storage of iron)
This person has PNH
Target for immunotherapy in lymphoma? Eg of drug?
CD20 (B-cell lymphoma)
Rituximab
Raised bilirubin, spherocytes, splenomegaly, anaemia = Dx?
Hereditary spherocytosis
Can do an osmotic fragility test if required for confirmation but this is reserved for cases where the diagnosis is uncertain.
Known CLL with hb 50. Given blood transfusion and fludarabine. 4 days later SOB + patchy shadowing on CXR. What has happened?
PCP
Fludarabine depletes T-cells
[Transfusion GVHD wouldn’t present with specific respiratory Sx and XR changes. It would be more systemic with haemolysis and liver dysfunction]
Nasal bleeding, headaches and papilloedema with distended retinal veins. Anaemia=? Dx?
Waldenstrom macroglobulinaemia
Needs serum electrophoresis (IgM)
Woman with low factor 8. How to differentiate Haem A carrier and Von willebrand?
Bleeding time
Normal in Haem a
Longer in VWF
History of brusing / bleeding with thrombocytopenia and mild anaemia =
ITP
G6PD -> haemolysis
What does G6P usually do?
formation of NADPH (protects RBCs from oxidative stress)
Low levels of NADPH in G6PD
Lytic lesions on MRI appear?
High intensity on t2
[low instensity on t1]
Without bleeding when would you use IV Ig in ITP rather than steroids?
If diabetic - risk worsening BM with high dose steroids
No bleeding - when platelets if febrile ?afebrile?
<20 if febrile
<10 if afebrile
Which infection classically -> cold haemolytic anaemia ? Rx if severe?
Mycoplasma
Plasmapheresis
[CMV/EBV too]
Warfarin OD on clotting study
PT prolonged +++
APTT prolonged ++
Normal fibbrinogen
2 causes of massive splenomegaly in older person? Differentiate the 2
Myelofibrosis
mild raised WCC
Teardrop cells characteristic
CML
Super high WCC
Plasmodium vivax use what antigen to get into cells
Duffy
Nephrotic syndrome lose what
Protein S
Antithrombin
[Not protein C]
Takes Dapsone now ++ SOB. Headaches and dark blood when sampling Suspect? what occurs here?
Methaemaglobulinaemia
Oxidation of Fe2+ to Fe3+
[Fe2+ is the usual form and can carry oxygen, Fe3+ is inactive]
Methaemaglobulinaemia most common mutation? Most common acquired form?
How does this affect Rx?
Cytochrome b5 reductase deficiency
If acquired its G6PD
Methylene blue [reduces ferric iron to ferrous iron (Fe3+ ->Fe2+) ]+ O2
Ascorbic acid if G6PD as methylene blue is contraindicated
When steroids for gestational thrombocytopenia
<30 in last 2 weeks of pregnancy
3 years post renal Tx with mild anaemia, thrombocytopenia and lymphadeopathy =
lymphoma
When pneumococcal vaccine in splenectory routine vs emergency operation?
1 month before procedure
2 weeks after if the procedure is done as an emergency
Hodgkins. Chemo and blood transfusions. Now Diarrhoea, Derranged LFTs and maculopapular rash
Transfusion-related GVHD
Which Ca gets cold agglutins? Infection?
Non hodgkins
Mycoplasma, EBV
Why do you get clots with protein C deficiency?
What usually activates protein C ?
Reduced degradation of factor Va and VIIIa
Thrombin activates protein C
[Vitamine K dependent]
Lymphadenopathy. Marrow demonstrates lymphoblasts. Test for certain diagnosis?
Blood immunophenotyping
prev DVT in preg. Now pregnant again - what needs to happen?
LMWH throughout
Bar immunocompromised who gets kaposi’s sarcoma
Old men
Burkitt’s lymphoma gene/ chromosome
C-myc
Chrom 8
CLL, Haemolytic anaemia - first line rx is steroids then what?
fluaranine + rituxumab
splenectomy
Best test for invasive aspergilliosis
Galactomannan
Genetics of follicular and mantle cell lymphoma
Follicular t (14:18)
Mantle cell t (11:14)
Lymphocyte count of 5
blood film large cells without a nucleus and large cytoplasm + broad-based projections ?
Hairy cell leukaemia
Myelofibrosis most common presentation
Faatigue
What has occured if haem A pt bleeding gets less controlled despite lots of no change to their usual factor 8 prophylactic infusions?
Developed factor 8 inhibitors (20% develop this)
Most common symptom in Waldenstrom’s
generalised weakness
Myelofibrosis characteristic blood picture
Leukoerythroblastic with tear drop cells
Most common complication of HITT
DVT
[Arterial do occur but much less common]
What is it called when no sample on bone marrow aspirate? What next?
Dry tap
need bone marrow biopsy
AML now presents with a stroke. what is cause?
Hyperleukocytosis
