Haematology Flashcards
What is deep vein thrombosis?
Formation of a blood clot (thrombus) in a deep vein of the body
What are DVTs caused by?
Poor blood flow leading to clot formation
Give 5 risk factors for a DVT
- ) Venous flow stasis (e.g. immobility)
- ) Trauma/surgery
- ) Hypercoagulability
- ) Advanced age
- ) Sickle cell disease
- ) Pregnancy
- ) Taking oestrogen (HRT, pill)
- ) Cancer
- ) Obesity
- ) Thrombophilia
- ) Increased age
Give the steps of the clotting cascade (6)
1) Platelets adhere to endothelium
2) Aggregate forms
3) Clotting factors release
4) Prothrombin to thrombin
5) Thrombin catalyses fibrinogen to fibrin
6) Fibrin reinforces clot
Give 3 symptoms/signs of a DVT
- ) May be asymptomatic
- ) Calf warmth, tenderness, swelling, redness, pain
- ) Mild fever
- ) Pitting oedema
- ) Usually in just one leg
Give 3 tests for DVT
- ) D dimer
- ) US compression
- ) Thrombophilia test before anticoagulation if abnormal presentation
What is D dimer?
A fibrin degradation product
What does a normal/positive D dimer result mean?
Normal - excludes diagnosis
Positive - doesn’t confirm diagnosis
What do we do if an US compression if negative?
Perform again after a week as the clot may have spread up and become detectable
Give 3 parts of treatment of a DVT
- ) LMWH/ warfarin
- ) DOACs
- ) Underlying cause
- ) IVC filter in active bleeding/anticoagulants fail
What does DOACs stand for?
Direct oral anticoagulants
Give 2 methods of prevention of DVTs
- ) Stop oral contraceptive pill 4 weeks pre-op
- ) Mobilise early
- ) LMWH
- ) Compression stockings
What is a thrombosis?
Inappropriate blood coagulation occurs inside a vessel
What is arterial circulation high in?
Platelets
What is venous circulation high in?
Fibrin
Name 3 places an arterial thrombosis can occur and what it can cause
- ) Coronary circulation - MI
- ) Cerebral circulation - CVA/stroke
- ) Peripheral circulation - peripheral vascular disease
What is the treatment for a stroke?
Aspirin/clopidogrel, TPA
What is an embolism?
The passage of material through the venous or arterial circulations
What is the most common process of an embolism?
Thrombo-emolus from a DVT
Give 3 symptoms for an embolism
- ) Asymptomatic possible
- ) Transient dyspnoea
- ) Chest pain
- ) Haemoptysis
- ) Secondary effusion
- ) CV collapse
- ) Sudden death
What is a paradoxical embolism?
An embolus that travels through the venous circuit and then across the heart through a patent foramen ovale
Give 2 causes of a systemic arterial embolism
- ) Atherosclerotic plaques
- ) IE
What does the Virchow triad include?
- ) Stasis of blood flow
- ) Endothelial injury
- ) Hypercoagulability
What is a pulmonary embolism?
Large embolus that blocks the pulmonary arteries
Give 3 symptoms of a pulmonary embolism
- ) Breathlessness
- ) Pleuritic chest pain
- ) May have signs/symptoms of DVT
- ) Haemoptysis
- ) Dizziness
- ) Syncope
Give 4 signs of a pulmonary embolism
- ) Tachycardia
- ) Tachypnoea
- ) Pleural rub
- ) Those of precipitating cause
- ) Cyanosis
- ) Purexia
- ) Hypotension
- ) Raised JVP
- ) Pleural effusion
What does a pulmonary embolism lead to? (if it doesn’t kill)
- ) Hypotension
- ) Cyanosis
- ) Severe dyspnoea
- ) Right heart strain/failure
What does a pulmonary embolism usually arise from?
A venous thrombosis in the pelvis or legs
What are the risk factors for a pulmonary embolism?
Same as for DVT
What investigations do we do for a pulmonary embolism?
- ) CXR
- ) ECG
- ) Blood gas
- ) D-dimer
- ) CTPA
- ) Echo
What does a blood gas show for a pulmonary embolism?
Type 1 respiratory failure of decreased PaO2 and PaCO2
What is a CTPA?
CT pulmonary angiogram
What should you consider in patients with a PE and no provoking risk factors?
Malignancy
What is the treatment for a pulmonary embolism?
As for DVT
- ) LMWH/ warfarin
- ) DOACs
- ) Treat cause
- ) IVC filter
What is the Wells score?
Pretest clinical probability scoring for DVT
What is anaemia defined as?
A low Hb concentration due to a low red cell mass or increased plasma volume
What is a low Hb for men?
<135g/L
What is a low Hb for women?
<115g/L
Give 3 symptoms of anaemia
- ) Fatigue
- ) Dyspnoea
- ) Faintness
- ) Palpitations
- ) Headache
- ) Tinnitus
- ) Anorexia
- ) Angina if pre-existing CHD
Give 2 signs of anaemia
- ) May be absent even in severe
- ) Pallor
- ) Tachycardia
- ) Flow murmurs
What is the normal MCV range?
76-96 femtolitres
What does MCV stand for?
Mean cell volume
Where are RBCs produced, and how long do they live for?
Bone marrow, 120 days
What are the 3 types of anaemia?
1) Microcytic - small
2) Normocytic - normal
3) Macrocytic - large
Give 3 causes for low MCV/ microcytic anaemia
- ) Iron deficiency anaemia
- ) Thalassaemia
- ) Anaemia of chronic disease
Give 3 causes for normal MCV/ normocytic anaemia
- ) Acute blood loss
- ) Anaemia of chronic disease
- ) Combined haematinic deficiencies (B12 and folate) (think malabsorption)
Give 3 causes for high MCV/ macrocytic anaemia
- ) B12/folate deficiency
- ) Alcohol excess/liver disease
- ) Hypothyroid
Where are RBCs removed? (4)
- ) Spleen
- ) Liver
- ) Bone marrow
- ) Blood loss
Give 3 consequences of anaemia
- ) Reduced O2 transport
- ) Tissue hypoxia
- ) Compensatory changes
How do we test for anaemia?
- ) History and exam
- ) B12, folate, ferritin
- ) FBC
Give 3 causes of iron deficient anaemia
- ) Blood loss (e.g. menstruation)
- ) Malabsorption
- ) Hookworm
Give 3 signs of iron deficient anaemia
- ) Koilonchyia (spoon shaped nails)
- ) Atrophic glossitis
- ) Lip ulceration
If there is lots of blood loss/problem with too much removal, what will there be lots of in the blood?
Reticulocytes (immature RBCs)
How do we treat iron deficiency anaemia?
Oral iron ferrous sulphate tablets
Give 3 causes of anaemia of chronic disease
- ) Chronic infection
- ) Renal failure
- ) Malignancies
Give 3 signs of anaemia of chronic disease
- ) Headache
- ) Pallor
- ) Tiredness
- ) Weakness
- ) SOB
What is the treatment for anaemia of chronic disease? (3)
- ) Treat underlying disease
- ) EPO
- ) Parenteral iron
What does EPO stand for?
Erythropoietin
What does EPO do, and what is it secreted by?
Increases rate of production of RBCs in response to decreased O2 levels in tissues, secreted by kidneys
What is pernicious anaemia?
Autoimmune condition in which atrophic gastritis leads to a lack of intrinsic factor secretion from the parietal cells of the stomach
How is B12 usually absorbed in the terminal ileum?
Binds to IF
What does B12 deficiency do?
B12 helps synthesise thymidine and hence DNA, thus deficiency causes decreased RBC production
What type of anaemia is pernicious?
Macrocytic
Give 2 causes of B12 deficiency
- ) Dietary
- ) Malabsorption
- ) Crohn’s, tapeworm
Give 2 features of B12 deficiency
-) Lemon tinge due to pallor and mild jaundice
Glossitis
-) Neuropsychiatric
-) Neurological
What is the treatment for pernicious anaemia? (2)
- ) Hydroxocobalamin (B12) if malabsorption
- ) Oral B12 if dietary
What type of anaemia is folate deficiency anaemia?
Macrocytic
What is folate deficiency anaemia caused by?
Poor diet and increased demand (pregnancy)
How do we treat folate deficiency?
Treat cause and give folic acid
What is haemolytic anaemia?
Premature breakdown of RBCs in circulation or reticuloendothelial system
Give 2 causes of haemolytic anaemia
- ) Inherited
- ) Acquired (drugs etc)
Give 2 signs for haemolytic anaemia
- ) Jaundice
- ) Hepatosplenomegaly
- ) Gallstones
- ) Leg ulcers
What type of anaemia is haemolytic?
Normocytic or macrocytic
What is aplastic anaemia?
Caused by rare stem cell disorder leading to panytopaenia and bone marrow failure
What is panytopaenia?
Deficiency of all blood cells
What are most causes of aplastic anaemia?
Autoimmune, triggered by drugs/radiation/infection
What is sickle cell anaemia?
An autosomal recessive disorder in which production of abnormal Hb results in vaso-occlusive crises
What are the 3 problems in anaemia of chronic disease?
1) Poor use of iron in erythropoiesis
2) RBC decreased survival
3) Decreased EPO production and response
What is the genetic problem behind sickle cell anaemia?
Amino acid substitution in the gene coding for the beta chain, which leads to the production of HbS rather than HbA
What is the difference between homozygotes (HbSS) and heterozygotes (HbAS) in sickle cell anaemia?
HbSS - sickle cell anaemia
HbAS - sickle cell trait
What does sickle cell trait protect the carrier from?
Falciparum malaria
What occurs to HbS when it is deoxygenated?
It polymerises, causing RBCs to deform, producing sickle cells which are fragile and haemolyse, blocking small vessels
In who is sickle cell anaemia more common?
African origin
Give 3 symptoms of sickle cell anaemia
- ) Vaso-occlusive painful crisis
- ) Aplastic crisis
- ) Sequestration crisis (children)
What is a vaso-occlusive crisis due to?
The occlusion of microvascular
Give 3 triggers for a painful vaso-occlusive crisis
- ) Cold
- ) Dehydration
- ) Infection
- ) Hypoxia
Give 3 other symptoms of sickle cell anaemia
- ) Dactylitis (<3)
- ) Stroke, seizures, cognitive defects
- ) Avascular necrosis
- ) Leg ulcers
- ) Low-flow priapism
What does the blood film look like in sickle cell anaemia?
Sickle and target cells seen
What confirms the diagnosis of sickle cell anaemia after a sickle solubility test?
Hb electrophoresis, can also distinguish between AS and SS
How do we treat sickle cell anaemia?
- ) Hydroxycarbamide - if frequent crises
- ) Prophylaxis (immunisation and antibiotics) - for splenic infarction
- ) Septicaemia risk
- ) Bone marrow transplant
- ) Genetic counselling
What is thalassaemia?
A genetic disease of unbalanced Hb synthesis with underproduction of one globin chain
What do unmatched globins do?
Precipitate and damage RBC membranes, causing their haemolysis whilst still in the marrow
What are the 3 main types of thalassaemia?
- ) Beta thalassaemia minor
- ) Beta thalassaemia intermedia
- ) Beta thalassaemia major
What are beta thalassaemias usually caused by genetically?
Point mutations in beta-globin chains on chromosome 11
What state is beta thalassaemia minor and what are its symptoms? (3)
Carrier state, usually asymptomatic, possible mild anaemia
What are the symptoms of beta thalassaemia intermedia? (3)
Moderate anaemia, not requiring transfusions, maybe splenomegaly
What is beta thalassaemia major?
Significant abnormalities in both beta-globin chains
How does beta thalassaemia major present?
In 1st year with severe anaemia and a failure to thrive
In beta thalassaemia major, what occurs in response to anaemia?
- ) Extra-medullary haematopoiesis (RBCs made outside of marrow)
- ) Skull bossing
- ) Hepatosplenomegaly
- ) Osteopenia
What do life long blood transfusions in beta thalassaemia major cause?
Iron overload/deposition seen after 10 years as endocrine failure
What does the blood film show for beta thalassaemia major?
Very hypochromic, microcytic cells, target cells, nucleated RBCs
What is the general treatment for beta thalassaemia? (6)
- ) Fitness and healthy diet
- ) Folate supplements
- ) Regular life-long transfusions
- ) Splenectomy if hypersplenism persists
- ) Hormonal replacement for endocrine complications
- ) Marrow transplant
What can we give to mitigate iron overload?
Iron-chelators (deferiprone PO and desferrioxamine)
What is it more common to be a carrier of alpha rather than beta thalassaemia?
Alpha has 4 genes coding for it rather than 2
What are the alpha thalassaemias mainly caused by?
Gene deletions
What does each number of mutations in alpha thalassaemia cause? (4)
4 - death in utero
3 - haemoglobin H disease
2 - asymptomatic carrier state
1 - clinically normal
What is relative polycythaemia?
Decreased plasma volume, normal RBC mass
What is absolute polycythaemia?
Increased RBC mass
What sort of disorder is polycythaemia?
Myeloproliferative - overactive bone marrow
What is polycythaemia?
The malignant proliferation of a clone derived from one pluripotent stem cell
Give 2 causes of absolute polycythaemia
- ) Primary (polycythaemia vera)
- ) Secondary (hypoxia or increased EPO secretion)
What is the genetic mutation in in polycythaemia vera?
JAK2
What is there an excess proliferation of in polycythaemia vera? (3)
- ) RBCs
- ) WBCs
- ) Platelets
Give 2 causes of relative polycythaemia
Acute - dehydration
Chronic - obesity, HTN, high alcohol and tobacco
Give 3 signs of polycythaemia vera due to hyperviscosity
- ) Headaches
- ) Dizziness
- ) Tinnitus
- ) Visual disturbance
Give 2 signs of polycythaemia vera due to increased urate from high RBC turnover
- ) Itching after a hot bath
- ) Erythromelalgia (burning sensation in fingers and toes)
Give 2 signs of polycythaemia vera
- ) Facial plethora
- ) Splenomegaly
- ) Features of arterial/venous thrombosis
What does the bone marrow show in polycythaemia vera?
Hypercellularity with erythroid hyperplasia
What is the treatment for polycythaemia vera in younger patients?
Venesection (blood removal) & daily aspirin
What is the treatment for polycythaemia vera in elderly patients/previous thombosis?
Hydroxycarbamide & aspirin
Transition to what occurs in polycythaemia vera patients?
30% - myelofibrosis (scarring of bone marrow)
5% - acute myeloid leukaemia
Give 3 bleeding disorders
- ) Over-anticoagulation
- ) Haemophilia
- ) Disseminated intravascular coagulation
- ) Platelet disorders (ITP and TTP)
What drug can cause over-anticoagulation?
Warfarin
Give 3 risk factors for over-anticoagulation
- ) Age
- ) Co-morbidities
- ) Polypharmacy
- ) Previous bleeding
- ) High BP
What should we give if a bleed occurs due to over-anticoagulation? (3)
- ) Withhold warfarin
- ) Vitamin K 5mg IV
- ) Prothrombin complex concentrate/fresh frozen plasma
What is haemophilia?
An inherited condition that affects the blood’s ability to clot
What is the cause of haemophilia A?
Factor VIII deficiency, inherited in an X-linked recessive patterns in males
What is the presentation of haemophilia A?
- ) Early in life or after surgery/trauma
- ) Bleeds into joints - crippling arthropathy
- ) Bleeds into muscles - haematomas
- ) High pressure - nerve palsies and compartment syndrome
What are the 2 things we diagnose haemophilia A by?
- ) Increased APTT
- ) Decreased factor VIII assay
What is the management for haemophilia A? (4)
- ) Avoid NSAIDs and IM
- ) Pressure and elevation for minor bleeding
- ) Desmopressin raises factor VIII levels
- ) Recombinant factor VIII for major bleeds (50% of normal)
- ) Life-theratening bleeds (100% of normal)
What is haemophilia B?
Factor IX deficiency, inherited in an X-linked recessive pattern
How do we treat haemophilia B?
Recombinant factor IX
What is acquired haemophilia?
A bleeding diathesis causing big mucosal bleeds in M+F
What is acquired haemophilia caused by?
Suddenly appearing autoantibodies that interfere with factor VIII
What do the tests for acquired haemophilia show? (2)
- ) Increased APPT
- ) Increased VIII autoantibody
- ) Decreased factor VIII activity
How do we treat acquired haemophilia?
Steroids
What is disseminated intravascular coagulation? (DIC)
Widespread activation of coagulation from the release of procoagulants into the circulation, with the consumption of clotting factors and platelets leading to an increased risk of bleeding
What do fibrin strands do in DIC?
Fill small vessels, haemolysing passing RBCs
Give 3 causes of DIC
- ) Malignancy
- ) Sepsis
- ) Trauma
- ) Obstetric events
Give 2 signs of DIC
- ) Bruising
- ) Bleeding anywhere
- ) Renal failure
- ) Confusion, fever
What 5 things do we find on investigation of DIC?
- ) Decreased platelets
- ) Increased PT
- ) Increased APTT
- ) Decreased fibrinogen
- ) Increased fibrin degradation products (D-dimers)
What are seen on blood films in DIC?
Broken RBCs
How do we treat DIC?
- ) Treat cause
- ) Replace platelets
- ) Cryoprecipitate to replace fibrinogen
- ) FFP to replace coagulation factors
What does APTT stand for?
Activated partial thromboplastin time
What does PT stand for?
Prothrombin time
What is immune thrombocytopaenia caused by? (ITP)
Antiplatelet autoantibodies that reduce the function of platelets
What are purpura?
Red/purple discoloured spots on the skin that do not blanch on applying pressure
What are the pathogenic steps of ITP? (3)
1) Abnormal autoantibody with specificity for platelet membrane glycoproteins binds to circulating platelets
2) Autoantibody coated platelets induce phagocytosis by macrophages primarily in the spleen
3) Platelet numbers decrease
Where is acute ITP found?
In children 2 weeks after infection
How does acute ITP present?
Sudden self-limiting purpura
Where is chronic ITP usually found?
Women
Give 3 signs of chronic ITP
- ) Bleeding
- ) Purpura
- ) Epistaxis
- ) Menorrhagia
What do we see in the marrow in ITP?
Increased megakaryocytes
What do we give as treatment in symptomatic ITP?
- ) Prednisolone - FIRST LINE
- ) IV immunoglobulin (temporary)
- ) Splenectomy
- ) B cell depletion with rituximab
What is thrombotic thrombocytopenia purpura? (TTP)
Decrease in circulating platelets due to small blood clots forming suddenly throughout the body
What is TTP caused by?
Genetic/acquired deficiency of a protease that cleaves vWf
What does less inhibition of vWf mean in TTP?
More platelet aggregation and fibrin deposition in small vessels, leading to multi system thrombotic microangiopathy
Give 4 signs of TTP
- ) Bleeding
- ) Bruising
- ) Purpura
- ) Confusion
- ) Headache
- ) Palsies, seizure, confusion, coma
- ) Fever
- ) Pallor
- ) Jaundice
- ) Proteinuria
What is the protease that usually cleaves vWf?
ADAMTS13
How do we treat TTP?
- ) Plasma infusion/exchnange
- ) Corticosteroids (prenisolone)
- ) Rituximab for non-responders/relapse
What is rituximab?
Monoclonal antibody
What is leukaemia?
Malignant proliferation of white blood cell precursors
What are the 4 types of leukaemia?
ALL - acute lymphoblastic leukaemia
CLL - chronic lymphocytic leukaemia
AML - acute myeloid leukaemia
CML - chronic myeloid leukaemia
What is the commonest acute leukaemia in adults?
AML
What is the commonest cancer in children?
ALL
Which leukaemia is most common in the elderly?
CLL
What chromosome is present in >80% of CML sufferers?
Philadephia chromosome
What syndrome is leukaemia associated with?
Down’s syndrome
Give 4 risk factors for leukaemia
- ) Irradiation (radiotherapy)
- ) Some drugs (e.g. chemo)
- ) Some chemicals
- ) Human T lymphotropic virus
- ) Family history
What cells does ALL affect?
Lymphocytes (B/T)
What cells does CLL affect?
B lymphocytes
What cells does AML affect?
Myeloblasts
What cells does CML affect?
Mature myeloblasts (basophils, neutrophils, eosinophils)
What cells do acute leukaemias affect?
Immature cells
How does acute leukaemia progress, and how curable is it?
Progresses rapidly, is curable if treated quickly
How does chronic leukaemia progress, and how curable is it?
Progresses slowly, harder to cure
What cells do chronic leukaemias affect?
Mature cells
What are the signs and symptoms of ALL?
- ) Anaemia
- ) Infection
- ) Bleeding
- ) Hepato/splenomegaly
- ) Lymphadenopathy
- ) CNS involvement
Give 2 common infections in ALL
- ) Bacterial septicaemia
- ) Zoster
- ) CMV
- ) Measles
What are the signs and symptoms of AML?
- ) Anaemia
- ) Infection
- ) Bleeding
- ) Hepato/splenomegaly
- ) Gum hypertrophy
- ) Skin involvement
What are the signs and symptoms of CLL
- ) Nodal often
- ) May present as surprise from FBC
- ) Anaemic
- ) Infection prone
- ) Weight loss and sweats if severe
What are the signs and symptoms of CML?
- ) Weight loss
- ) Tiredness
- ) Fever
- ) Sweats
- ) Gout
- ) Bleeding
- ) Splenomegaly
- ) Anaemia
- ) Bruising
Give 4 tests we do in leukaemia
- ) Bone marrow biopsy
- ) CXR and CT
- ) Lumbar puncture
- ) Immunophenotyping/genetics
- ) Blood film
What is seen on a blood film in ALL?
Characteristic blast cells
Why do we do a lumbar puncture in ALL?
CNS involvement
How do we differentiate AML from ALL?
Microscopy
What is the treatment for ALL?
- ) Blood/platelet transfusion
- ) IV fluids
- ) Allopurinol
- ) IV antibiotics for infection
- ) Chemotherapy
- ) Allogenic marrow transplant
What is the treatment for AML?
- ) Blood transfusions
- ) IV antibiotics for infection
- ) Intensive chemo
- ) Allogenic marrow transplant
- ) Allopurinol
What is the treatment for CLL?
- ) 30% never need treatment
- ) Chemo
- ) First line is fludarabine + rituximab +/- cyclophosphamide
- ) Steroids
- ) Radio
- ) Blood transfusions
- ) IV immunoglobulin if infections
What is the treatment for CML?
- ) Targeted therapies
- ) Chemo and stem cell transplant if unsuccessful
Give 2 targeted therapies for CML
- ) Imatinib
- ) Tyrosine kinase inhibitor
What does haematological remission mean?
No evidence of leukaemia in the blood
Give 2 common infections of AML
- ) Candida
- ) Aspergillus
Which leukaemia is a myeoproliferative disorder?
CML
Between what ages does CML usually occur?
40-60
What is a lymphoma?
Disorder caused by malignant proliferations of lymphocytes
Where do the lymphocytes usually accumulate in a lymphoma?
Lymph notes, lymphadenopathy
What are the characteristic cells found in Hodgkin’s lymphoma? (HL)
Reed-Sternberg cells
What are the 2 peaks of incidence of Hodgkin’s lymphoma?
Young adults and elderly
Give 3 risk factors for Hodgkin’s lymphoma
- ) Epstein Barr virus infection
- ) Family history
- ) Immunosuppression
- ) Obesity
What are the 4 HL subtypes?
- ) Nodular sclerosing
- ) Mixed cellularity
- ) Lymphocyte rich
- ) Lymphocyte depleted
Where is the mutation in HL?
DNA of a B lymphocyte
Give 3 symptoms of HL
- ) Enlarged, non-tender, rubbery superficial lymph nodes
- ) Fever, weight loss, night sweats, pruritus, lethargy (25%)
- ) Mass effect from mediastinal lymph nodes
- ) Painful lymph when drinking
Give 2 signs of HL
- ) Lymphadenopathy
- ) Cachexia
- ) Anaemia
- ) Spleno/hepatomegaly
What is a paraneoplastic complication?
Immune system attacks its own platelet cells rather than infections (ITP)
What main tests do we do for HL?
Lymph node biopsy and blood film
What are the 4 stages of lymphomas?
I - involvement of single lymph node region
II - involvement of 2 or more on same side
III - involvement of both sides
IV - involvement of extra nodal tissues, spread beyond lymph nodes
Each stage of lymphoma is either A or B - what does this mean?
A - no B symptoms
B - B symptoms present
What are B symptoms?
Systemic - weight loss, fever, night sweats
What is the treatment for HL?
- ) Radiotherapy and chemotherapy
- ) ABVD chemo 2-4 cycles or 6-8 cycles
- ) Possible autologous stem cell transplantation
What are the drugs for ABVD chemotherapy in HL?
A - adriamycin/doxorubicin
B - bleomycin
V - vinblastine
D - dacarbazine
What is Non-Hodgkin’s lymphoma? (NHL)
All lymphomas without Reed-Sternberg cells
What is the most common NHL?
Diffuse large B-cell lymphoma
Give 3 risk factors for NHL
- ) Family history
- ) Ataxia telangiectasia
- ) H. pylori infection
- ) EBV, HIV
- ) Immunosuppression
Where is the mutation for NHL?
20% - T lymphocytes
80% - B lymphocytes
What are the clinical features of NHL?
- ) 75% have superficial lymphadenopathy
- ) 50% have extra nodal disease - depends on type
- ) Small bowel lymphomas - diarrhoea, vomiting, abdominal pain, weight loss
- ) Waldeyer’s ring lymphoma - sore throat, obstructed breathing
- ) Systemic features less common than in HL
- ) Pancytopenia
What does an increase in lactate dehydrogenase mean?
Increased cell turnover, worse prognosis
What are the 2 main grades of NHL?
- ) Low grade - indolent, often incurable
- ) High grade - more aggressive, often curable (diffuse B cell)
How do we treat low grade NHLs?
- ) Radiotherapy
- ) Chlorambucil in diffuse
- ) Interferon alfa/rituximab in remission
How do we treat high grade NHLs?
R-CHOP R - rituximab C - cyclophosphamide H - hydroxydaunorubicin O - oncovin/vincristine P - prenisolone
How does rituximab work?
Kills cells by antibody directed cytotoxicity and apoptosis induction, sensitises them to CHOP
What type of cell is involved in myelomas?
Plasma cell
What is the pathophysiology of a myeloma?
The abnormal proliferation of a single clone of plasma cell leads to secretion of Ig (IgG/A) or Ig fragment, causing the dysfunction of many organs
Give 4 risk factors for myeloma
- ) Increasing age
- ) Male
- ) Afro-Caribbean
- ) Obesity
- ) Radiation exposure
- ) Family history
- ) Immunosuppression
Why is there no production of new bone in myelomas? (5)
1) Adhesion of stromal cells to myeloma cells
2) Production of RANK-L stimulated
3) RANK-L increases osteoclast formation
4) Increased bone reabsorption
5) Osteoblast activity inhibited by DKK1 produced by myeloma cells
What end organ damage can myeloma cause?
CRAB Calcium (high) Renal impairment Anaemia Bone disease
What is the preceding phase of a myeloma?
MGUS - monoclonal gammopathy of undetermined significance
Give 3 symptoms of myeloma
- ) Backache
- ) Pathological fractures
- ) Vertebral collapse
- ) Hypercalcaemia (confusion)
- ) Anaemia (tiredness)
- ) Infection
- ) Bleeding
What is a pathological fracture?
Fracture without significant trauma
What do we see on an XR in myeloma?
- ) Lytic ‘punched out’ lesions
- ) Pepper-pot skull
What are the diagnostic criteria for myeloma? (4)
High index of suspicion with bone/back pain
1) Monoclonal protein band in serum/urine electrophoresis
2) Increased plasma cells on marrow biopsy
3) Evidence of end-organ damage (CRAB)
4) Bone lesions
What is the supportive treatment for myeloma?
- ) Analgesia (avoid NSAIDs)
- ) Bisphosphonate
- ) Local radiotherapy
- ) Orthopaedic procedures
- ) Blood transfusions/EPO
- ) Rehydration
- ) Antibiotics for infection
What is the chemotherapy treatment for myeloma?
- ) Induction therapy (e.g. CTD)
- ) Autologous stem cell transplantation
What is CTD chemotherapy?
Cyclophosphamide
Thalidomide
Dexamethasone
Give 3 other chemotherapy drugs used in the treatment of myeloma (not CTD)
- ) Lenalidomide
- ) Bortezomib
- ) Dexamethasone
What are the 4 signs of systemic inflammatory response syndrome? (SIRS)
- ) Temperature >38 or <36
- ) Tachycardia >90bpm
- ) Respiratory rate >20breathspm
- ) Very high/low WBC
What is sepsis?
SIRS with an infection
What is septic shock?
Severe sepsis with hypotension
What is the treatment for SIRS?
Cultures and bloods before antibiotics, IV fluids, O2, vasopressors
What is neutrophilia?
Too many neutrophils
Give 3 causes of neutrophilia
Reactive: -) Infection -) Inflammation -) Malignancy Primary: -) CML
What is neutropaenia?
Not enough neutrophils
Give 4 causes of neutropaenia
Underproduction: -) Marrow failure -) Marrow infiltration -) Marrow toxicity Increased removal: -) Autoimmune -) Felty's syndrome -) Cyclical
What is lymphocytosis?
Too many lymphocytes
Give 3 causes of lymphocytosis
Reactive: -) Infection -) Inflammation -) Malignancy Primary: -) CLL
What is lymphocytopaenia?
Too few lymphocytes
What is thrombocytopenia?
Too few platelets
What is thrombocytosis?
Too many platelets
Give 3 causes of thrombocytosis
Reactive: -) Infection -) Inflammation -) Malignancy Primary: -) Essential thrombocythaemia
Where are platelets produced?
Bone marrow
Platelets are fragments of what?
Megakaryocytes
What is the production of platelets regulated by?
Thrombopoietin (TPO)
What is the normal lifespan of a platelet?
7-10 days
What do platelets do?
Adhere and aggregate to form platelet plug, primary haemostasis
How do platelets adhere to collagen?
Via GP1a
How do platelets adhere to vWF?
Via GP1a and IIb/IIIa
What is on the surface of platelets?
Glycoproteins
Give 3 main causes of low platelets
- ) Production failure (congenital, acquired by drugs etc)
- ) Increased removal (immune, consumption, splenomegaly)
- ) Artefactual (EDTA induced clumping)
Give 2 causes of impaired platelet function
- ) Congenital (platelet disorders vW disease)
- ) Acuquired (uraemia, drugs)
Give 3 clinical features of platelet dysfunction
- ) Mucosal bleeding
- ) Easy bruising
- ) Petechiae, purpura
- ) Traumatic haematomas
What are the 2 main causes of thrombocytopenia?
- ) Decreased production
- ) Increased destruction
Give 4 causes of decreased production in thrombocytopenia
- ) Congenital
- ) Infiltration of bone marrow (leukaemia)
- ) Reduced platelet production by bone marrow (B12/folate/TPO/chemo)
- ) Dysfunctional production of platelets in BM
Give 4 causes of increased destruction in thrombocytopenia
- ) Autoimmune (ITP)
- ) Hypersplenism
- ) Drug related immune destruction
- ) Consumption of platelets (DIC, TTP)
What are haemoglobinopathies? (2)
- ) Disorders of quality
- ) Disorders of quantity
Give an example of a disorder of quality haemoglobinopathy
Sickle cell disease
Give an example of a disorder of quantity haemoglobinopathy
Alpha/beta thalassaemia
What are membranopathies?
Deficiency of red cell membrane proteins caused by a variety of genetic lesions
What type of genetic conditions are membranopathies?
Autosomal dominant
What are the 2 most common membranopathies?
Spherocytosis and elliptocytosis
Give 2 presentations of membranopathies
- ) Neonatal jaundice
- ) Anaemia
- ) Gallstones
What is the treatment for membranopathies?
- ) Folic acid
- ) Splenectomy
What is glucose 6 phosphate dehydrogenase deficiency? (G6PD)
X-linked RBC enzyme defect
What is the non-asymptomatic presentation of G6PD?
Oxidative crises (rapid jaundice and anaemia) due to some drugs (aspirin)/illness/broad beans/henna
What do blood films show in G6PD?
Bite and blister cells and Heinz bodies
