Haematology Flashcards
What is multiple myeloma?
Cancer of plasma cells
Accumulation of malignant plasma cells that leads to destructive bone disease + hypercalceamia
BM + renal failure
Which of the following is associated with the accumulation of monoclonal immunoglobin or light chains (Bence Jones protein) in plasma?
a) ALL
b) Hodgkin’s lymphoma
c) Multiple myeloma
d) Non-Hodgkin’s lymphoma
Multiple myeloma is associated with the accumulation of monoclonal immunoglobin or light chains (Bence Jones protein) in plasma
What causes the destruction of bone in multiple myeloma?
Destruction of bone in MM is due to the malignant plasma cells stimulating the osteoclasts to erode the bone
What does MGUS stand for in relation to multiple myelome?
MGUS = Monoclonal gammopathy of undetermined significance. The first stage.
<30g/dl, <10% plasma cells in BM, no ROTI, no evidence of amyloid or other LPD
What are the 3 aims of treatment for multiple myeloma?
Antimyeloma treatment - chemo
Prevent and treat bone damage - bisphosphates, surgery, dialysis
Improve QOL + survival - infection prophalaxis & anaemia treatment
Combination chemotherapies are used with multiple myeloma. Give an example of 3 types of combinations drugs.
Thalidomide-based
Velcade-based
Supportive (pain killers, bisphosphates, blood transfusions)
What are the treatment options after a first relapse in multiple myeloma?
Same treatment if lenghty remmission
Second transplant if first transplant remission >2yrs
What is lymphoma?
Malignant growth of WBC
Most cases of lymphoma are due to unknow causes. However give 3 possible causes (broad).
Immunodeficiency
Infections (EBV, Helicobacter pylori)
Autoimmune
Which haematological disease has the following presenting features?
Tiredness/malasie.
Bone/back pain
Infections
Multiple myeloma
Tiredness/malasie.
Bone/back pain
Infections
Which haematological disease has the followig presenting features?
Nodal disease
Compression syndromes
Systemic symptoms
Lymphoma
Of the WBC - commonly found in nodes, accumulation –> lumps
How would you diagnose lymphoma?
Blood film
BM biopsy
Immunophenotyping (CD20 on B cells for monoclonal Ab treatment with rituximab)
Cytogenetics
molecular techniques
What are the investigations that we use to stage a lymphoma case?
Blood tests
CT Scan chest/abdo/pelvis
Bone marrow biopsy
PET Positron emiting - metabolically active cells take up the positrons
Staging = how bad is it?
What are the two main subtypes of lymphoma?
Hodgkin’s
NHL
Give the 3 grades and an example of NHL
Low grade e.g. Follicular Lymphoma
High grade e.g. Diffuse Large B Cell Lymphoma (most common)
Very high grade e.g. Burkitt’s Lymphoma (most aggressive)
Which haematological disease is being described?
Painless lymphadenopathy
B symptoms
Presence of Reed-Steinberg cells
Painless lymphadenopathy
B symptoms
Presence of Reed-Steinberg cells <– hallmark cell
Hodkin’s lymphoma
In which age group in Hodgin’s lymphoma most common?
Children
Teenage and young adult
Middle age
Elderly
Teenage and young adult
In Hodgkin’s lymphoma… what is the difference between stage 2 and stage 3?
Stage 2 - 2/< areas with cancer on the same side of the diaphram
Stage 3 - 2/< areas of cancer on both sides of the diaphram
Which treatment would the following stages of Hodgkin’s lymphoma receive?
a) Stage 1-2A
b) Stage 2B-4
a) Stage 1-2A = short course of combined chemo + radiotherapy
b) Stage 2B-4 = combined chemo
Give an example of a monoclonal Ab
Rituximab
Anti CD20 found on B cells
Chimeric mouse/human protein - chance of allergic reactions
Which haematological disease is being described?
‘a clonal expansion of myeloid blasts in the bone marrow, blood or other tissues’
Acute myeloid leukemia = a clonal expansion of myeloid blasts in the bone marrow, blood or other tissues
Which type of leukeamia is associated with the t(9,22) translocation?
a) AML
b) CML
c) ALL
d) CLL
Chronic myeloid leakeamia
t(9,22)
Philaelphia gene
- fusion of activated tyrosine kinade - ‘on’ for many cellular functions
What is leaukaemia?
Malignant proliferation of haemopoietic cells
A patient with acute myeloid leukaemia needs supportive care.
What does supportive care include here?
Blood product support
Early diagnosis and treatment of infections
Recognition of atypical/unusual infections
For AML - is the following true of false?
Outcomes increase with increased age
False
Outcomes decrease with increased age. Less able to tollerate the treatments
Describe acute promyelocytic leukaemia
Subtype of AML
Accumulation of promyelocytes
t(15;17) Blocks differentation of promyelocytes –> granulocytes. Cannot swtich on the coagulation cascade = bleeding
Haematological emergency
Acute promyelocytic leakaemia is the most treatable with 90% remission rate.
Exaplain why.
Acute promyelocytic leakaemia is the most treatable with 90% remission rate.
Due to targetted ATRA therapy
CML is most common in which age group?
a) children
b) teenage and young adults
c) Middle age 40-60
d) elderly 60<
CML is most common from 40-60
Explain the treatment for CML
Targeted molecular therapy
Tyrosine kinase inhibitors (uImatinib (Glivec)
uNilotinib, Dasatinib, Ponatinib)
Now a chronic condition
Which of the following disease is being described?
Leucocytosis, basophilia, change in platelets
Normocytic anaemia
Abnormal leukocytes
Increase in B12
Slenomegaly
Philadelphia choromosome
Chronic myloid leukaemia
Leucocytosis, basophilia, change in platelets
Normocytic anaemia
Abnormal leukocytes
Increase in B12
Slenomegaly
Philadelphia choromosome
Which is the most common leukaemia in children?
Acute lymphoblastic leukaemia is the most common in childran 3-7 years
A 5 year old girl presents with fever, chest infection, anaemia, tachycardia. She is pale, fatigued with a headache.
What tests do you send for and what diagnosis would you heamatological disease do you suspect?
A 5 year old girl presents with fever, chest infection, anaemia, tachycardia. She is pale, fatigued with a headache.
Tests: Blood film, BM biopsy, lymph node biopsy, immunophenotyping
Diagnosis: Acute lymphoblastic leukaemia
Explain the treatment for ALL
Chemotherapy phases Remission induction, consolidaion, intensification, maintenance
CNS therapy
Stem cell transplant
Aim is to induce a long lasting remission.
Adults with the philadelphia chromosome have a poorer prognosis
Which is the most common leukaemia?
Chronic lymphocytic leukaemia is the most common leukaemia
Describe the clinical course of CLL
Variable
Progressive lymphadenopathy / hepatosplenomegaly
Auto-immune - haemolysis, ITP
Bone marrow failure - due to marrow replacement
Hypogammaglobulinaemia & infection
Give the Hb values for anaemia
a) female
b) male
The Hb values for anaemia
a) female = <115g/l
b) male = <130g/l
What are the pathological consequences of anaemia?
Fatty change in myocardim and liver
Aggravate angina
Skin and nail atrophic changes
CNS cell death
Give examples of problems of the failure of production which can lead to anaemia.
Haematological deficiencies = B12, folate & iron
Chronic disease - inflammation, infection, neoplasm
Hypoplasia
Dyserythroiesis
Marrow infiltration
Give examples of increased destruction that can lead to anaemia.
Hypersplenism
Acute blood loss
Red cell abnormality (membrane/enzyme defects)
Abnormality outside of red cell (immune haemolytic anaemias, drugs, toxins)
Give the 3 main causes of microcytic anaemia and the MCV range
Microcytic anaemia - MCV <80
Iron deficiency
Thalassaemia
Chronic disease
Give the 3 main causes of normocytic anaemia and the MCV range
Normocytic anaemia
Acute blood loss
Chronic disease
Combined haematinic deficiency
MCV 80-100
Give the 3 main causes of macrocytic anaemia and the MCV range
Macrocytic anaemia
B12/folate deficiency
Alcohol/liver disease
Hypothyroid
Heamatological
MCV >80
How do you test for a B12 deficiency?
IF Ab
Schilling test
Coeliac Ab
Explain the life course of platelets
Produced: megakaryokes in BM
Circulation: 7-10 days
Destroyed: Spleen by splenic macrophages
What is the production of platelets controlled by?
Platelet production is controlled by thrombopoietin (TPO)
Produced by the liver
Binds to plts & MK - feedback
Give the clotting cascade
Intrinsic - XII, XI, IX, VII
Extrinsic - VII (TF)
Joined - V, X, prothrombin –> thrombin –> fibrinogen –> fibrin
The followin are targets for antiplatelet drugs. What are their normal actions and the drugs which target them?
a) P2Y12
b) COX
c) GPIIBIIIA
The followin are targets for antiplatelet drugs. Their normal are actions…
a) P2Y12 - amplifies activation of platelets - Clopidogrel
b) COX - produces thromboxane A2 which induces platelet aggregation and vasoconstriction - Aspirin
c) GPIIBIIIA - Aids platelet aggregation and adherence -Tirofiban
What is the normal range for platelet numbers?
150-400 X109
Give the clinical features of platelet dysfunction
Easy bruising
Mucosal bleeding
Petechiae, purpura
Traumatic haematomas
For thrombocytopenia… Give the values.
a) Normal platelet range
b) No clinical defects with thrombocytopenia
c) Increased bleeding post trauma
d) Spontaneous skin and mucosal bleeding
For thrombocytopenia… the values are:
a) Normal platelet range 150-400x109
b) No clinical defects >80x109
c) Increased bleeding post trauma 40-50x109
d) Spontaneous skin and mucosal bleeding <20x109
A 32 year old male presents with the following blood results
Platelets: 60x109/l
WBC: 6x109 g/l
Hb: 150x109/l
Is this likely to be due to decreased production or increase destruction?
A 32 year old male presents with the following blood results
Platelets: 60x109/l range = 150-400x109 = low
WBC: 6x109 g/l range = 4-11x109 = normal
Hb: 150x109/l range = 135-180x109 = normal
Defect due to increased destruction
What are the two most common causes of thrombocytopenia due to increased destruction?
Autoimmune thrombocytopenic purpura & disseminated intravascular coagulation are the two most common causes of thrombocytopenia due to increased destruction
Describe immune thrombocytopenia
Give examples of when a primary and secondary infection will occur
Immune thrombocytopenia purpura (ITP)
IgG antibodies against platelets + MK glycoproteins
Opsonization = removal by reticuloendothelial system in speen
Primary infection: following a vaccination/infection
Secondary infection: association with malignancies (CLL), infections (HIV/Hep C), drugs (heparin, quinine, sulphonamides)
What are the treatments for immune thrombocytopenia
Immunosuppression - steroids/IVIG
Treat the underlying cause
Platelets - if bleeding
Tranexamic acid - if mucosal bleeding
Describe thrombic thrombocytopenic purpura (TTP)
Thrombic thrombocytopenic purpura (TTP)
Microscopic clots in small blood vessels around the body
Schistocytes
Vascular lesions
Sporodic episodes
Associated with high moleular weight von Willebrand factor
Leads to organ dysfunction, renal failure & neurological abnormalities
What is the treatment for thrombic thrombocytopenic purpura (TTP)
The treatment for thrombic thrombocytopenic purpura (TTP) is:
High volume plasma exchange
Rituximab - monoclonal Ab
Describe disseminated intravascular coagulation (DIC)
Disseminated intravascular coagulation (DIC)
A complicating factor of an underlying condition
Causes both clotting and bleeding
Vascular occlusion –> organ dysfunction
Consumption of platelets and clotting factors –> Haemorrhage
Which disorder of coagulation is being described?
Patient who has already been on the ward for 6 months now presents with :
Haemorrhage, multi-organ failure, haemolytic anaemia, bleeding from mucosal membranes
Diseminated Intravascular Coagulation (DIC)
Haemorrhage, multi-organ failure, haemolytic anaemia, bleeding from mucosal membranes
Give the nomal values and units for the following:
a) MCV (mean corpsular volume)
b) MCH (mean corpsular Hb)
c) MCHV (mean corpsular Hb volume)
a) MCV 78-98 fl
b) MCH 26-33 pg
c) MCHV 30-35 g/dl
Describe thalassaemia
Globin chain disorder with leads to a reduction in Hb
How do you monitor haemoglobinopathies?
Ferratin
Cardia and liver MRI
Endocrine testing
DEXA scanning
Explain the problems with iron over load
No physiological mechanism to excrete iron.
Excess iron deposits in the liver and the spleen causing fibrosis and cirrhosis. It can also deposit in the endocrine glands and in the heart.
Explain how enzymopathies cause damage to RBC and two main causes
Shortened cell life due to oxidative damage
Mainly caused by glucose-6-phosphate deficiency and pyruvate kinase deficiency
Which of the following is being described?
Due to a variety of mutations, most are asymptomatic, X-linked. In a crisis haemoloysis, jaundice & anaemia occurs
a) G6PD
b) Pyruvate kinase deficiency
c) Iron deficincy
d) Thalassaemia
Glucose-6-phosphate deficiency
Due to a variety of mutations, most are asymptomatic, X-linked. In a crisis haemoloysis, jaundice & anaemia occurs
Decribe febrile neuropenia and who is at risk?
Febrile = fever >38
Neutrophils = <1.0 x109
People at risk: Chemo, haematological malignancies, BM failure syndromes, cyclical neutropenia
How do you treat febrile neuropenia?
Start broad spectrum antibiotics without waiting for the results
Identify those at risk
Which of the following could be a possible diagnosis if a patient presents with:
Lethary, headaches, confusion, visual disturbances, cranial nerve defects, ataxia, retinal haemorrhage
a) Febrile neuropenia
b) Hyperviscosity
c) Alpha thalassaemia
d) Beta thalassaemia
Hyperviscosity
Lethary, headaches, confusion, visual disturbances, cranial nerve defects, ataxia, retinal haemorrhage
Describe the treatment and prevention measures used with tumour lysis syndrome
Tumour lysis syndrome
Hydrate - aggrresive IV before and after chemo
Watch kidneys
Prevent hyperuricaemia - Lower uric acid
