Haematology Flashcards
What cells do NHL arise from
B cells (85%)
T cells
Natural killer cells
How is NHL differentiated from HL
Absence of Reed-Sternberg cells at biopsy
Which type of lymphoma is more common
NHL
Most common Sx of NHL
Asymmetric painless lymphadenopathy
Features of Waldenstroms macroglobinaemia (low grade B cell neoplasm)
Raised plasma viscosity
Raised total protein
Assosiated IgM paraprotein
Can lead to hyperviscosity syndrome
How to distingush between Haemophilia A carrier and Von Willebrands in a lady
NORMAL BLEEDING TIME in Haemophilia A
Glucose 6 dehydrogenase (G6PD) deficiency predisposes patients to haemolysis when exposed to what?
Dapsone
Primaquine
Aspirin
Quinolones
Nitrofurantoin
Fava beans
Ingestion of napthalene (found in mothballs)
Hep A and B
CMV
Pneumonia
Typhoid
WHat is acquired haemolytic anaemia is a recognised complication of what?
Methyldopa
Penicillin
Quinine
Quinidine
What can myelofibrosis change into?
AML
Features of idiopathic myelofibrosis
Extensive bone marrow scelrosis - excessive fibroblast proliferation and collagen deposit in the bone marrow
Leukoerythoblastic picture
Splenomegaly
Tear droped shaped red blood cells
What is paroxysmal nocturnal haemoglobuinuria (PNH)?
Rare type of acquried haemolysis caused by intrinsic red cell abnormalities
Classic triad of paroxysmal nocturnal haemoglobuniruia
Haemolytic anaemia
Pancytopenia
Large vessel thrombosis
Genetics of PNH
Lack of complement regulatory GPI and anchored proteins (C55 and CD59) due to a a haematopoietic stem cell fault of the PIGA gene, on chromosome X
gold standard for diagnosis of PNH
Flow cytometry or fluorescent aerolysin (blood immunophenotyping)
First line Tx of PNH
Eculizumab (monoclonal Ab) for lifelong Tx
Stem cell transplant
What is shown in the urinalysis of PNH
Haemoseridin
Causes of thrombocytosis
Autonomous / primary
Secondary
- Anaemia
- Infection
- Non infectious inflammation (malignancy, rheumatological conditions, reactions to meds)
- post splenectomy
What are the most common subtypes of cutaneous T cell lymphomas
Sezary syndrome
Mycosis fungoides
WHat part of the coagulation cascade is PT in
ExtrinsicW
What part of the coagulation cascade is APTT in
Instrinsic
What is DIC
Characteristed by innapropriate systemic activation of the coagulation cascade, leading to small and medium vessel thrombosis and subsequent organ dysfunction
This can lead to major haemorrhage due to exhaustion of clotting factors and platelets
What is DIC caused by
As a complication of an underlying pathology, rather than being a primary event itself
Common causes of DIC
Sepsis
Malignancy
Incompatible blood transfusion
Obstetric emergencies
Liver failure
Widespread tissue damage from severe burns / trauma
Bloods findings in DIC
Prolonged APTT
Prolonged PT/INR
Prolonged thrombin time
Low fibrinogen
High fibrin degredation products
Low platelets
Raised d dimer
Treatment of DIC
FFP
Cyroprecipitate
Factor concentrates
What is the most common form of inherited haemolytic anaemia
Hereditary spherocytosis
Lab features of hereditary spherocytosis
Prescence of spherocytes on blood smear
Negative direct anti-globulin tests
Elevated reticulocytes
Pathology of hereditary spherocytosis
Inherited defect in structural proteins in red blood cell membranes
Abnormalities result in changes in red cell shape due to defects in skeletal proteins
Become spherical - flexibility decreases and they are removed to the spleen due to frailty
Increased red cell destruction causes hyperbilirubinaemia, elevated reticulocyte count and splenomegaly
Inheritance of G6PD
X linked recessive
Presentation of G6PD
Usually asymptomatic until a trigger causes haemolysis
Diagnosis of G6PD
Measuring G6PD activity
What is seen in the bloods during an attack of a patient with G6PD
Raised reticulocytes
Increased unconjugated bilirubin
Increased LDH
Low haptoglobin
Heinz bodies
Bite cells
Blister cells
CML causes what in the blood
Increase in neutrophils and myelocytes
What should be done if you have developed an above the knee DVT in pregnancy
LMWH for subsequent pregnancies
Ingestion of what aids iron absorption?
Vitamin C
What is aplastic anaemia
Pancytopenia with hypocellular bone marrow in the abscence of abnormal infiltrate (dysplasia, blasts) or marrow fibrosis
Presentation of asplastic anaemi
Neutropenia
- recurrent infections
anaemia
thrombocytopenia
- bleeding/bruising
Persistent warts
Bone marrow biopsy of aplastic anaemia
Hypocellular bone marrow
Treatment of aplastic anaemia
Immunosuppressants
Haematopoieitic stem cell transplantation
Most common congential cause of aplastic anaemia
Fanconi anaemia
Pathology of aplastic anaemia
Deficiency in haematopoeitic CD34+ stem cells
Presentation of fanconis anaemia
Hearing loss
Pigmentation abnormalities
Urogenital abnormalities
Splenomegaly - which produces this - myelofibrosis or myelodysplasia?
Myelofibrosis
The two major causes of gross splenomegaly
CML
Myelofibrosis
WCC in CML
often > 100 x109
Blood film of myelofibrosis
Leucoerythroblastic blood picture
Teardrop cells
Genetics of von willebrand disease
Mutation in the von willebrand gene
Screening tests for von willebrands disease
vWF antigen (diagnostic if <0.3)
vWF activity (functional assays)
Factor VIII activity
Blood tests of von willebrands disease
Normal FBC
Normal platelets / mild thrombocytopenia
Normal or mildly prolonged APTT
Normal PT
Treatment of type I + II vwd
Desmopressin (DDAVP)
Antifibrinolytics can be used in addition therapeutically or prophylactically
Treatment of type III vwd
vWF-containing concentrates
for elective surgery =- need vwF concentrate at least 8 hours pre procedure
Bleeding time in haemophilia A and B
NORMAL
Features of waldenstorms macroglobuniaemia
Monoclonal IgM peak
Lymphadenopathy
Hepatosplenomegaly
Hyperviscotiy
What is waldenstorms macroglobuniaemia
A low grad lymphoma
What indicates a poor prognosis in ALL
Prescence of philadelphia chromosome
Definitive diagnosis of ALL
20% or more of lymphoblasts in the bone marrow
What is shown in a peripheral blood smear for ALL
Peripheral blasts cells
The combination of anaemia and jaundice should indicate what until proven otherwise?
Haemolytic anaemia
A reticulocytosis indicates what?
Bone marrow is workign
WHat does anaemia in the prescence of reticulocytes indicate?
Blood cells are being lost/destroyed outside of the bone marrow
i.e. bleeding or haemolysis
If red cells show osmotic fragility, what does this indicate
Hereditary spherocytosis
When is it common to see a prolonged PT
Patients in liver disease
leading to failure of synthesis of vitamin K dependent clotting factors
Blood features of anti-phospholipid antibody syndrome
Thrombocytopenia
Positive VDRL test
Positive anti-cardiolipin Abs
Prolonged APTT
Normal PT
What is the most common cause of aplastic crisis in patients with sickle cell disease
Human parovirus B19
Definitive cure for sickle cell disease
Stem cell transplanation (reserved for patients < 17 who have severe disease non responsive to medical therapy)
WHat can sickle cell crisis be triggered by
Infection
Stress
Trauma
Pregnancy
Surgery
Cold weather
Alcohol
Hypoxia
Dehydration
Acidosis
Inheritance of sickle cell disease
AR
What should patients with sickle cell disease be started on for lifelong
Penicillin as prophylactic Abx
What may be used to prevent acute painful crisis and acute chest Synrome
Hyroxycarbamide
Where is the gene deletion with alpha thalassaemia
chromosome 16
where is the gene mutation with beta thalassaemia
chromosome 11
What do the thalassaemias result in
Haemolysis
Blood film of alpha thalassaemia
Mexican hat cells
Blood film of sickle cell anaemia
Sickle cells
Blood film of G6DH deficiency
Heinz bodies
Blister cells
Blood film of microangiopathic haemolysis
Schistocytes
Blood tests of thalassaemias
Microcytic anaemia
May be assosiated raised WCC
Reduced platelets
Serum iron and ferritin elevated
What is polycythaemia vera characterised by
Eyrthrocytosis
Thrombocytosis
Leuckocytosis
Splenomegaly
Risks of PV
Thrombosis
Haemorrhage
Transformation to acute leukaemia
Myelofibrosis
Diagnosis of PV
Increased Hb or haematocrit AND
JACK2 mutation AND
Bone marrow biopsy - hypercellularity for age with trilineage growth
Treatment of PV
Phlebotomy
Low dose aspirin
Cytoreductive therapy
Presentation of PV
HTN
Headache
Erythromelalgia (burning cyanosis in hands/feet)
Transient visual disturbance
Features of thrombosis
Gouty arhtiris (increased RBC turnover)
Bleeding
Aquagenic pruritis (itching worse with warm water)
Facial plethora
Splenomegaly
Bloods of PV
High Hb
High hct
High WCC
High Platelets
Low MCV
Decreased EPO levels
JAK2 mutation
Treatment of PV
Low dose aspirin
Phlebotomy
Management of CV risk factors
Some patients - cytoreductive therapy (hyroxyrua)
Scoring system of multiple myeloma uses what
serum B2 microglobulin
Albumin
Top two most common malignancies seen after transplant
- Skin malignancy
- Lymphoma
Why are patients with CLL immunodeficienct
Immunoglobulin deficiency
What does hepatosplenomegaly in haematology conditions indicate?
Lymphoproliferative disorder
Whats hypochromia
Reduction in amount of Hb in each RBC
WHat is usually found in the peripheral blood if you have thalassaemia
Nucleated red blood cells
Why do we give irridated blood
To prevent transfusion assosiated graft vs host disease
What reverses alteplase/thrombolysis drugs
Tranexamic acid
What reverses warfarin
Prothrombin complex
Vitamin K
What reverses heparin
Protamine sulphate
The combination of iron deficiency and hyposplenism would suggest what
Coeliac disease
Haptoglobin levels in haemolysis
Reduced
What antigen is involved in the entry of plasmodium vivax into cells
Duffy
What organisms are patients with sickle cell disease at risk of and why
Because of their splenic state
Strep pneumonia
Haemophilus influenzae
Neiserria meningitis
Inheritance of haemophilia B
X linked recessive
Presentation of essential thrombocytosis
Asymptomatic
Thrombosis
Bleeding
Genetic mutations of essential thrombocytosis
JAK2
CALR
MPL
Essential thrombocytosis has a risk of progressing into what
AML
Peripheral blood smear of essential thrombocytosis
immature precursor cells
Large platelets
Howell jolley bodies (splenectomy or hyposplenism)
WHat drug should you not give to patients with acquired VWD
Aspirin
CML vs myelofibrosis
CML - very high WCC
Myelofibrosis - often pancytopenia
Types of myeloproliferative disorders
Polycythaemic vera (proliferating RBCs)
CML (proliterating WCCs)
Essential thrombocythaemia (platelets)
Myelofibrosis (fibroblasts)
Syndrome assosiated with PV
Budd chairi syndrome
Treatment of CML
BCR-ABL tyrosine kinase inhibitor
Myelofibrosis blood film
Leukoerythroblastic blood picture
Tear drop poikilocytosis
Bone marrow biopsy of myelofibrosis
Patchy reticular fibrosis
Small areas of haemapoieitc cells
Another name for coombs test
Anti-globulin test
What is CLL assosiated with
Autoimmune haemolytic anaemia
What is the method of action of desmopressin in VWD
Realeases stored VW factor and factor VIII
Genetics of burkiits lymphoma
c-Myc
What kind of lymphoma is burkitts lymphoma
NHL
WHat is prolonged in anti-phospholipid syndrome
APTT
Cause of haemolysis in G6PD deficieency
Reduced levels of NADPH
What are thrombophilias
A group of disorders that cause abnormality of blood coagulation, leading to an increased risk of thrombosis
What is the most common cause of inherited thrombophilia in caucasions
Factor V Leiden
Causes of inherited thrombophilias
Factor V Leiden
Prothrombin (factor II) gene mutation
Protein C, protein S, anti-thrombin III deficiency
Features of an adult T cell leukaemia/lymphoma
Skin lesions
Lymphadenopathy
Hypercalcaemia
Assosiation of adult T cell leukaemia/lymphoma
HTVL-1 (virus)
What is an appropriate treatment to prevent urate nephropathy in patients starting on chemotherapy
IV rasburicase
What is a key initial therapy of acute promyelocytic leukaemia with DIC? (APML)
all-trans retinoic acid (ATRA)
How long is the time period for acute graft vs host disease can occur post transplant?
100 days
Skin rash in acute graft vs host disease
Widespread macular rash
Starts on the palms and soles
How does rasburicase work to reduce the risk of tumour lysis syndrome
Uric acid oxidation
Presentation of methaemoglobinaemia
Cyanosis not matching their level of clinical presentation
Symptoms related to low O2 levels
Chocolate coloured blood
Hypoxia that does not improve with supplemental oxygen
Pathology of methaemoglobinaemia
RBCs have excessive methaemoglobin, this cannot bind oxygen and is unable to deliver oxygen to tissues
Causes of methaemoglobinaemia
Acquired
- toxins
- drugs
Congenital
- cytochrome b5 reductase deficiency
Gold standard investigation for methaemoglobinaemia
MetHb levels in the blood
Treatment of methaemoglobinaemia
Supportive oxygen
Methylene blue (reduces ferric iron to ferrous iron)
Skin manifestation of a fat embolism
Mutliple petechiae in both axillae and skin folds of the upper body
What Hb level has to be raised for a diagnosis of B thalassaemia
A2 level
Triad of felty syndrome
RA
Splenomegaly
Neutropenia
What does Kostmanns syndrome cause
Severe congenital neutropenia
S/Es of vincristine (chemotherapy agent)
Neuropathic pain
Sensory loss
Parasethesia
Difficuly in walking
Slapped gait
Loss of deep tendon reflexes
Ataxia
Paresis
Foot drop
CN palsies
Ocular and laryngeal nerve palsies
Best test for protein C deficiency
Copperhead snake venom assay
What is the most useful test in distinguishing B thalassaemia from IDA
Haemoglobin A2 levels
(high in B thalassaemia)
(low in IDA)
What are protein C and S dependent on
Vitamin K
Microangiopathic haemolytic anaemia and thrombocytopenia is what until proven otherwise?
TTP
What confirms diagnosis of TTP
ADAMTS13 assay (severely reduced) combined with
IgG antibodies
Causes of microangiopathic haemolytic anaemia
TTP
HUS
SLE
Infection
Pre eclampsia
HELLP
Prosthetic heart valves
Carcinomatosis
Vasculitis
Glomerulonephritis
Malignant HTN
Classic TTP presentation
Fever
COnfusion
Altered neurology
Jaundice
Renal impairment
May be palpable splenomegaly
Treatment of TTP
Plasma exchange (within 4-8 hrs)
Caplacizumab binds to VWF reducing clot formation
In patients with B12 deficiency, what can happen to the rest of the blood tests
Low red cell folate (B12 necessary for normal folate metabolism)
Erythrocytes cannot mature - consequently haemolysis and therefore hyperbiliruaemia
The combination of anaemia and gallstones should indicate what
Hereditary spherocytosis
Hypothyroidism anaemia changes blood and bone marrow
Anaemia
Elevated MCV
No megaloblastic changes in the bone marrow
1st line Tx for CML
Imatinib
What is anaemia known to cause in the eyes
Retinopathy (including cotton wool spots and retinal haemorrhages)
Radiological findings of multiple myeloma
Lytic lesions
Raindrop skull appearance (random pattern of dark spots like rain hitting a surface and splashing)
Which of NHL or HL is more assosiated with cold agglutins
NHL
Age NHL vs HL
NHL tends to be seen in older age
WHat can cause iron overload syndrome
Repeated blood transfusions
Treatment of iron overload syndrome
Desferrioxamine (iron chelator)
What can iron overload syndrome present as
Pericarditis
What does haemolysis do to reticulocyte counts
Increased reticulocyte counts
What is ITP
An isolated thrombocytopenia with no evidence of anaemia or haemolysis
What is a particular clinical pointer to DIC
Leaking from venflon sites
Triad of anti-phospholipid syndrome
Thrombocytopenia
Recurrent thrombosis
Recurrent miscarriages
Skin manifestation of anti-phospholipid syndrome
Livedo reticularis
What is the most important prognostic marker in AML
Bone marrow karyotype
Haemophilia B is a deficiency of what
Factor IX
Treatment of haemoarthropathy in a patient with a Hx of haemophilia B
Factor IX concentrate
What is hairy cell leukaemia
Rare form of NHL
Features of hairy cell leukaemia
Pancytopenia
Splenomegaly
Low monocyte count
High lymphocyte count - these are larger than lymphocytes, without a visible nucleus and abudant cytoplasm with broad based projections
If a patient is unstable with a high iNR, what should they be given
Vitamin K
Prothrombin complex concentrate
What do low haptoglobin levels i nthe context of anaemia indicate
Haemolysis
Treatment of essential thrombocytosis
Aspirin and hyroxycarbamide
What genetic abnormality is assosiated with the worst prognosis in AML
Chromosome 7 abnormalities
What type of haemolytic anaemia is therapetuci plasmapheresis the most effective treatment for
HA assosiated with mycoplasma pneumonia
What is the standard translocation found in CML
t(9;22)
Where is vitamin B12 absorbed
Terminal ileum
What chromosomal translocation is assosiated with acute promyelocytic leukaemia
t(15,17)
Pathology of protein C deficiency
Reduced degradation of factors Va and VIIIa
What is the target for immunotherapy for B cell lymphomas
CD20
WHat does acute promyelocytic leukaemia have a strong link with
DIC
What is the significance of the bcr/abl translocation
It codes a production for tyrosine kinase
(to do with the philadelphia chromosome/CML)
What is evans syndrome
ITP co-existing with autoimmune haemolytic anaemia
WHat endocrine condition can sickle cell disease be assosiated with?
Diabetes insipidus
What antibodies are responsible for the development of HIT type II
Anti-PF4 heparin Abs
1st line management of ITP
Iv immunoglobulin or corticosteriods
What is blackwater fever
Rare complication of acute malaria treatment
Intravascular haemolysis
Most commonly assosiated with plasmodium falciparum
WHat mutation is seen in hairy cell leukaemia
Activating BRAF mutation
What causes TRALI
Donor Antibodies
AML on blood film
Auer rods
What is seen in the blood film with megaloblastic anaemia
Hypersegmented neutrophils
Most common complication of HIT
DVT
Treatment of TTP
Plasma exchange
What vaccinations should patients undergo when having an elective splenectomy and when
At least 14 days prior
Strep pneumonia, haemorphillus influenzae and neisseria meningitis vaccinations
What does rituximab act against
CD20-positive lymphocytes
Presentation of transfusion assosiated graft vs hsot disease
Pancytopenia
Liver dysfunction
Diarrhoea
Rash
WHat white blood cell differential is characteristic of CML
Predominance of myelocytes and neutrophils
What type of disease is the translocation t(11;14) assosiated with
Mantle cell lymphoma
What is mantle cell lymphoma a type of
NHL
EPO level in PV
Low
What skin/nail manifestiation is chracteristic of IDA
Kolinychia
What is the most common inherited prothrombotic disorder of patients of northern european origin
Heterozygois factor V Leiden
WHat can very significant proteinuria predispose you to
Low anti-thrombin III levels, which can contribute to venous thrombosis
How does LMWH work
Binds to anti-thrombin III
What is the commonest pathogen transmitted via platelet transfusion
Staphylococcus
Life span of erythrocyte once in bloodstream
120 days
Life span of platelets
8-9 days
Life span of neutrophil
5.4 days
How to reverse alteplase
FFP and tranexamic acid
Which subtype of hodgkins lymphoma has a better prognosis
Lymphocyte predominant
Presentation of an acute haemolytic reaction during PRBCs transfusion
Abdominal pain
Flank pain
Fever
Systemic upset
Two main symptoms of PV
Itching
Headache
Major complications of PV
Bleeding
Thrombosis
WHat is the difference between AML and APML?
DIC in APML
What does urine dipstick positive for blood, but negative on microscopy indicate?
Paroxysmal nocturnal haemoglobinura (intravascular haemolysis)
Treatment of PNH
Eculizumab (monoclonal antibody which inhibits complement)
How are reticulocytes different to erythrocytes
They have reticular staining of ribosomal ribonucleic acid
Key differentiating feature between MGUS and myeloma
Absence of complications
- immune paresis
- hypercalcaemia
- bone pain
Adverse effects of TNF blockers
Reactivation of latent TB
Demyelination
What causes a risk of thrombosis in a patient with Factor V Leiden mutation
Protein C resistance
Haemaglobin form of beta thalassaemia trait
Haemoglobin A2
Haemaglobin form of sickle cell disease
Haemoglobin S
What form of haemoglobin is seen in alpha thalassaemia
Haemoglobin H
Who is acquired haemophilia A seen in
Patients with autoimmune disease e.g. SLE / RA and haematological malignancies
What clotting test is the best initial investigation for Factor V Leiden carriage
Dilute Russell’s viper venom time
Investigation for skeletal involvement in myeloma
Whole body MRI
Mechanism of action of hydroxycarbamide
Ribonucleotide reductase inhibitor
What clotting factor is inhibited by warfarin
Factor VII, II, IX and X
translocation found in APML
t(15;17)
Philadelphia chromosome and what is this seen in
t(9;22) - BCR/ABL fusion producing an abnormal tyrosine kinase
CML and ALL
In someone who has evidence of a new diagnosis of AML, what needs done
Urgent clotting screen - to ensure no evidence of DIC that may suggest acute promyelocytic leukaemia
Underlying cause of haemolysis in G6PD deficiency
Reduced levels of NADPH
