Haem Misc. Flashcards
What is Anaemia
Reduced red blood cells
Define anaemia for men and women in terms of Hb and Hct
Men –> Hb < 130 g/l ; Hct 0.38 - 0.52
Women –> Hb < 120 g/l ; Hct 0.37 - 0.47
What is haematocrit
The ratio of whole blood made up of red cells if a sample were left to settle
Decreased production/ Increased destruction of RBC’s will give which different blood results
Increased destruction = increased reticulocytes
Reduced production = decreased reticulocytes
What is the normal range of MCV
80 - 100 femtolitres
<80 MCV means what
Microcytosis
> 100 MCV means what
Macrocytosis
Name the 2 main categories of hypochromic microcytic anaemias
Haem deficiency
Globin deficiency
Name 2 causes for a lack of iron for erythropoiesis
Iron deficiency
Anaemia of chronic disease
Name 3 possible causes of porphyrin synthesis problem
Lead poisoning
Sideroblastic anaemia
Pyridoxine responsive anaemias
Name the main cause of Globin deficiency which leads to hypochromic, microcytic anaemia
Thalassaemia
What is spurious macrocytosis
The size of the mature red cell is NORMAL, but the MCV is measured as being high
What are the 2 broad categories of causes of macrocytosis
Megaloblastic
Non-megaloblastic
What is a megaloblast
An abnormally large nucleated red cell precursor with an immature nucleus.
What are the two most common causes of megaloblastic macrocytic anaemia
B12/Folate deficiency
Which of B12 or folate should you replace first
B12
What can B12/ folate deficiency cause
Symptoms/signs of anaemia
weight loss, diarrhoea, infertility
Sore tongue, jaundice
Developmental problems
What can B12 deficiency cause specifically
Dorsal column abnormalities
Neuropathy
Subacute Combined Degeneration of Spinal cord
Dementia
Blood film will show what 2 things in b12/folate deficiency
Hypersegmented (>5) neutrophils
Macro-ovalocytes
Which red flag haem sign can b12/folate deficiency cause
Pancytopenia
Where are B12 and folate absorbed
B12 –> ileum
Folate –> Duodenum, Jejunum
Which autoimmune disease could be at play with B12 deficiency and which antibodies could you look for
Pernicious Anaemia
Anti- Gastric Parietal Cell (more sensitive)
Anti- Intrinsic Factor (more specific)
FFP must be frozen within how many hours of collection
8 hours
Which 3 criteria must be met by someone who is wanting to be a blood donor
Minimum 50kg
Must be able to spare 465mls of blood
Males ( >13.5 Hb) Females (>12.5 Hb)
How often can you give blood
Must wait 12 weeks between donations
max 5 a year
What are the shelf lives of red cells, platelets and FFP
Red cells –> 35 days
Platelets –> 7 days
FFP –> 3 years
What temperatures are red cells, platelets and FFP kept at
RBC’S –> 4 degrees (give or take 2)
Platelets –> 22 degrees
FFP –> -30 degrees
The genes for alpha chains in Hb is on which chromosome
Chromosome 16
The gene for beta chains in Hb is on which chromosome
Chromosome 11
Alpha thalassaemias result from what kind of mutation
Deletion
Beta thalassaemias result from what kind of mutation
Point
What is HbH
Clumping together of Beta chains into a tetramer
The point mutation in sickle cell results in Glutamine being replaced by what
Valine
Name 4 long term treatments of sickle cell anaemia
Prophylactic penicillin
Vaccination
Folic acid
Hydroxycarbamide
What should you vaccinate against in someone with sickle cell anaemia/ hyposplenism
Meningooccus
Pneumococcus
H. Influenza
Which type of haemolysis is more common
Extravascular
Compare blood products in Intravascular and Extravascular haemolysis
Intravascular –> abnormal blood products
Extravascular –> normal blood products in excess
Name 3 causes of intravascular haemolysis
Transfusion reaction G6PD deficiency Severe Malaria (Blackwater fever)
Pink urine which turns black on standing is a result of which biochemical abnormality in intravascular haemolysis
Haemoglobinuria
Which two abnormal blood products end up in the circulation in intravascular haemolysis
Haemoglobin
Methaemalbumin
Which two abnormal blood products end up in the urine in intravascular haemolysis
Haemoglobin
Haemosiderin
What is the mucosal iron transporter called
DMT-1
What is the serosal iron transporter called
Ferroportin
Which factor downregulates ferroportin and when is it produced
Hepcidin
Produced in the liver in response to iron load and inflammation
Which genetic disease results in unchecked iron absorption and which gene is affected
Haemochromatosis
HFE gene
How does Haemochromatosis present and how is it treated
Weakness, joint pain, impotence, cirrhosis, diabetes
Tx –> Venesection
How does secondary iron overload occur and how can it be prevented
Repeated transfusions
Iron-chelating drugs –> desferrioxamine
What is the antidote for Heparin reversal
Protamine Sulphate
What are the 5 stages of normal haemopoiesis
Self- renewal Proliferation Differentiation Maturation Apoptosis
What is the most common childhood cancer
Acute Lymphoblastic Leukaemia
What is Acute Lymphoblastic Leukaemia
Malignant disease of primitive lymphoid cells
Name 3 ways in which ALL could present
Marrow failure
Bone Pain
CNS/Testes involvement
What is a malignant disease of primitive myeloid precursors
Acute Myeloid Leukaemia
AML is more common in which age group
Older
>60
Name a characteristic blood film appearance of AML and 2 characteristic symptoms
Auer rods on blood film
DIC and Gum infiltration
What is a characteristic and specific symptom of Hodgkin’s Lymphoma
Drinking alcohol causes chest pain
Hodgkin’s lymphoma is associated with which infection
EBV infection
E.g glandular fever
Which cells are seen in Hodgkin’s lymphoma and what is their CD number
Reed Sternberg cells
CD 30
What is the CD number of the cells seen in Non-Hodgkins lymphoma and which drug targets this
CD 20
Rituximab
Which autoimmune disease will cause Hypo-cellular marrow
Aplastic anaemia
Hyper/Hyposplenism causes Pancytopenia
Hyper
Name 3 causes of Hypersplenism
Splenic congestion (CCF, Portal hypertension)
Felty’s (Rheumatoid Arthritis, neutropenia, splenomegaly)
Splenic lymphoma
What are the 2 types of cytotoxic therapy
Cell- Cycle specific
Non- Cell specific
Dose/Duration is more important for cell cycle-specific therapy
Duration is more important
Vinca alkaloids are which type of drugs and can cause which side effect
Mitotic spindle inhibitors
Neuropathy
Alkylating agents are which type of cytotoxic therapy and can cause what
Non-cell cycle specific
Can cause infertility
Which cytotoxic therapy can cause cardiomyopathy
Anthracyclines
Platinum derivatives such as Cisplatinum can cause what
Nephropathy
What drug regime should be initiated in neutropenic sepsis
Piperacillin/ Tazobactam
+ gentamicin if severe
Myeloproliferative disorders can be divided into which two groups
BCR-ABL 1 negative or positive
Which MPD comes under BCR-ABL 1 negative
Polycythaemia Rubra Vera
Essential Thrombocythaemia
Idiopathic Myelofibrosis
Which MPD comes under BCR-ABL 1 positive
Chronic Myeloid Leukaemia
What are the three stages of Chronic Myeloid Leukaemia
Chronic
Accelerated
blast crisis
What will be seen in the blood of someone with CML
Leucocytosis, Neutrophilia, Myeloid precursors
Which chromosome is a hallmark of CML and how does it come about
Philadelphia
9,22 translocation
What does the Philadelphia chromosome result in
Tyrosine kinase expression
Which drug inhibits Tyrosine Kinase and can be used to treat CML
Imatinib
How does Essential Thrombocythaemia result in acquired vWF deficiency
Excess abnormal platelets mop up all the available vWF
How is Essential Thrombocythaemia treated
Aspirin
Hydroxycarbamide
JAK2 mutation is associated with which MPD
Polycythaemia Rubra Vera
Which MPD will show leukoerythroblastic blood film with teardrop shaped RBC’s
Idiopathic Myelofibrosis
What is a unique symptom of Polycythaemia Rubra Vera
Aquagenic Itch
How can Polycythaemia Rubra Vera be treated
JAK2 inhibitors
How can Idiopathic Myelofibrosis be treated
Allogeneic stem cell transplantation
JAK 2 inhibitors
Splenectomy
Which 3 systems are activated in DIC
Complement
Coagulation
Kinin
What are the 4 most common causes of DIC
Hypovolaemic Shock
Sepsis
Malignancy
Obstetric emergency
Asides from treating the underlying cause, what else can be done for DIC
Fresh Frozen Plasma
Contains clotting factors
How is haemophilia inherited
X-linked recessive
Which factors are deficient in Haemophilia A and B and which one is more common
A –> VIII (more common)
B –> IX
Which clotting test will be abnormal in Haemophilia
isolated prolonged APTT
How will Haemophilia present
Recurrent Haemarthroses
Soft tissue bleeds
Prolonged bleed after surgery
Name 3 examples of naturally occurring anti-coagulants
Serine protease inhibitors –> AT III
Protein C and S
Protein C and S inhibit which factors
V, VII, IX, Xa
What is factor V Leiden
An autosomal dominant disease where a variant of factor V which can’t be inhibited very well by protein C is made
Which receptors do platelets bind to each other via and which drug can block these
Glycoprotein IIb/IIIa
Abciximab
How is INR calculated and how can the results be interpreted
INR = [PTpatient ÷ MNPT]ISI >1.5 = bleeding risk
Howell- Jolly bodies are seen in which condition
Hyposplenism
What are Heinz bodies and when can they be seen
Clumps of denatured Hb
Seen in intravascular haemolysis (decreased haptoglobin)
In which state can iron bind O2 in haem
Fe2+
How is iron kept in the Fe2+ state
NADH from glycolysis
What are the 3 methods of Co2 transport
Dissolved
Bound to Hb
As bicarbonate
What is the problem in Sideroblastic Anaemia
Porphyrin Ring disturbance
Uridine is changed to what in the Folate cycle
Thymidine
Which cycle is b12 involved in
Methionine cycle
How is pernicious anaemia treated
b12 injections + folate tablets for life
Transfusions if severe
Name 4 non-megaloblastic causes of macrocytosis and which one of these is associated with anaemia
Liver failure
Alcohol
Hypothyroidism
Marrow failure –> associated with anaemia
Where and how are the cells break down in a delayed transfusion reaction
In spleen by macrophages
How are thalassaemias diagnosed
HPLC
Which disease are those with thalassaemia slightly less at risk of
Malaria
Why does splenomegaly occur in thalassaemia
Extramedullary haematopoiesis
Define warm and cold autoimmune haemolysis
Warm –> IgG
Cold –> IgM
Which lymphoma is basically incurable and why
Low-grade B cell NHL
Slow growing so chemo doesn’t work
How can you diagnose Fanconi Anaemia
Chromosome fragility testing
What is paraprotein
Monoclonal Immunoglobulin
How is paraprotein detected and classified
Serum electrophoresis and then serum immunofixation
What are Bence Jones Proteins and how are they detected
Precipitates of Ig light chains
Urine electrophoresis
How can you calculate marrow cellularity
100 - age
Cast Nephropathy is seen in which disease
Multiple myeloma
Which Immunoglobulins are usually involved in myeloma
IgG or IgA
Why is lytic bone disease seen in myeloma
Plasma cells produce iL-6 which stimulates Osteoclasts and inhibits Osteoblasts
What disease can be described as a clonal disorder of cells intermediate between lymphocytes and plasma cells (lymphoplasmacytoid neoplasm)
Waldenstrom’s Macroglobulinemia
Which Ig is involved in Waldenstrom’s Macroglobulinemia
IgM
How will failure of primary haemostasis present and give an example
Mucosal bleeding e.g epistaxis, GI bleeds, Menorrhagia
A prolonged PT suggests a problem with which factors
Tissue Factor / VII
extrinsic pathway
A prolonged APTT suggests a problem with which factors
VIII, IX (also XI, XII)
intrinsic pathway
An ECG showing S1 Q3 T3 suggests what
P.E
What are the 2 types of heparin and how are they monitored
Unfractionated –> APTT
LMWH –> Anti-Xa assay
What is the difference in the mechanism of action of heparin and LMWH
Heparin inhibits both Xa and IIa
LMWHs inhibit factor Xa, but not thrombin (IIa)
How will the effects of protamine sulphate differ on heparin and LMWH
A complete reversal of Heparin
A partial reversal of LMWH
Define Haemostasis
The arrest of bleeding AND maintenance of vascular patency
What kind of drug is dabigatran
direct thrombin inhibitor
NOAC
WHich of the New Oral Anti-Coagulants is safest in a renally impaired patient
Apixaban
What is the antidote to Dabigatran
Idarucizumab
An elderly person presenting with anaemia and massive splenomegaly should make you think of what
Myelofibrosis
Which types of Hodgkin’s lymphoma have the best and worst prognoses
Lymphocyte predominant –> best
Lymphocyte depleted –> worst
What are the B type symptoms of lymphoma
Night Sweats
Weight loss
Fever
Above what age is the prognosis worse for lymphoma
45
Which gender tends to have a worse prognosis for lymphoma
Males
Normochromic, normocytic anaemia + Leukopenia + Thrombocytopenia should make you think of what
Aplastic anaemia
Name 3 specific drugs that can cause aplastic anaemia
Chloramphenicol
Gold
Phenytoin
What biochemical changes can a blood transfusion cause
Hyperkalaemia
Hypocalcaemia
What steps should you take in a suspected acute haemolytic transfusion reaction
Stop the transfusion
Plenty of fluids
Inform lab
What is the most common cause of isolated thrombocytopenia
Immune/Idiopathic Thrombocytopenia
Antibodies against which structures are produced in ITP
Glycoprotein IIb/IIIa
Acute ITP is more common in which age group
Children post infection
What is the mode of inheritance of G6PD deficiency and which population is it more common in
X-linked recessive
Afro-Caribbean
How can G6PD deficiency be diagnosed
G6PD enzyme assay
Name 3 drugs can cause haemolysis in someone with G6PD deficiency
Quinine drugs
Ciprofloxacin
Nitrofurantoin
What factors does cryoprecipitate contain and what two other things does it contain
VIII
XIII
Fibrinogen
vWF
What are the major criteria for considering cryoprecipitate administration
Low Fibrinogen
Name 3 biochemical abnormalities seen in tumour lysis syndrome and how is it treated
Hyperkalaemia
Hyperphosphotaemia
Hypocalcaemia
IV allopurinol
One of which 3 things must be present to diagnose tumour lysis syndrome
Arrhythmia
Increased creatinine
Seizure
Which score is used to work out the likelihood of someone having a DVT
Wells score
How should you manage a DVT
Start LMWH (stop once INR is 2-3) Start Warfarin for 3 months if provoked DVT (6 months if unprovoked or active cancer)
Which 2 symptoms should make you think of myeloma until proven otherwise and how would you investigate
Raised ESR
Osteoporosis
serum electrophoresis
A monoclonal proliferation of well-differentiated lymphocytes describes what
Chronic Lymphocytic Leukaemia
Which cells will be seen on blood film of CLL
Smudge/smear cells
Name two complications of CLL
Warm (IgG) haemolysis
Recurrent infection due to decreased Ig
Richter’s transformation is the change from CLL to what
High-grade lymphoma
How does desmopressin work in treatment for bleeding in vWF disease
Stimulates vWF release from endothelial cells
What is the mode of inheritance of Hereditary Spherocytosis and how is it diagnosed
Autosomal dominant
EMA binding test
Which virus can cause haemolysis in Hereditary Spherocytosis
Parvovirus
If a blood transfusion patient seems well and has an increase in temperature of < 1.5, how do you treat this
Febrile, non-haemolytic reaction
IV/Po paracetamol
A starry sky blood film and myc gene translocation suggests what disease
Burkitt’s Lymphoma
Painful heavy calves, pruritis should make you think of what
Post-thrombotic syndrome
Graduated compression stockings
How will RBC’s and platelets be affected by alcoholic liver disease
Macrocytic anaemia
Thrombocytopenia
What are the Hb’s cutoffs for transfusion
With acute coronary syndrome –> < 80
Without acute coronary syndrome –> < 70
What is the platelet cutoff for platelet transfusion
< 30
< 100 in severe bleeding or bleeds in critical areas e.g CNS
Name a bleeding disorder which will have prolonged bleeding time and one which will not
Prolonged bleeding time suggests a primary haemostasis problem
vWF = prolonged
Haemophilia = normal
