Haematology Flashcards
What infection is assocaited with hodgkin lymphoma?
Epstein barr virus
(also more common in people with HIV)
What is the treatment for neutropenic sepsis?
Administer high flow oxygen
Take blood cultures, other cultures, consider source control
Give appropriate IV antibiotics within ONE hour
Measure serum lactate concentration
Start IV fluid resuscitation
Assess/measure urine output
Resuscitation – ABC
Broad spectrum I.V. antibiotics
- Tazocin and Gentamicin
If a gram positive organism is identified add vancomycin or teicoplanin
If no response at 72 hours add I.V. antifungal treatment e.g. Caspofungin - empiric therapy
CT chest/abdo/pelvis to look for source
Modify treatment based on culture results
What is the most common blood group?
Type O
What mutation is assocaited with primary Myelofibrosis?
JAK2 (50%)
MPL (5-10%)
What is the treatment for 22q11 deletion syndrome?
Thymus transplantation
What is the role of platelets in haemostasis?
Adhere
Activate
Aggregate
Provide a phospholipid surface for coagulation
What is the cause of polycythaemia rubra vera?
Clonal proliferation of a marrow stem cell leading to an increased red cell volume, often accompanied by an increase in neutrophils and platelets as well
What are different types of venous thromboembolisms?
Limb deep vein thrombosis
Pulmonary embolism
Visceral venous thrombosis
Intracranial venous thrombosis
Superficial thrombophlebitis
What type of monoclonal proteins are usually found in the serum in multiple myeloma?
IgG or IgA
What are the symptoms of hereditary spherocytosis?
Anaemia
Jaundice (neonatal)
Splenomegaly
Pigmented gallstones
What is the treatment for chronic lymphocytic leukaemia?
Often nothing – “watch and wait”
Cytotoxic chemotherapy e.g. fludarabine, bendamustine
Monoclonal antibodies e.g. Rituximab, obinutuzamab
Novel agents (these are targeted therapies)
Bruton tyrosine kinase inhibitor eg ibrutinib
(think of Brutus on a tyrosine kinase inhibitor)
PI3K inhibitor eg idelalisib
(Think of Pie eaten by KKK)
BCL-2 inhibitor eg venetoclax
(Think of a female venus on Jeremy Clarkson)
What is the managment of TRALI?
Stop transfusion immediately and follow other steps for managing suspected transfusion reactions.
Provide cardiovascular and airway support. Administer supplemental oxygen and employ ventilation as necessary. Diuretics are not beneficial.
How is the diagnosis of multiple myeloma made?
X-ray - lytic bone lesions of the skull, long bones and the spine
CT scan - radiodense bone lesions and lesions found in the spleen, lymph nodes and lungs as a result of chronic disease
MRI
FISH (fluorescent in situ hybridisation)
LAB results: leukopenia, thrombocytopenia, creased monoclonal proteins, bence jones proteins, raised calcium
Bone marrow biopsy - over 30% plasma cells
What are the platelets like in myelofibrosis?
Platelets are increased, abnormally shaped and they have decreased survival
What are poor prognostic indicators for chronic lymphocytic leukaemia?
Advanced disease (Binet stage B or C)
Atypical lymphocyte morphology
Rapid lymphocyte doubling time (<6 mth), or over 50% increase in less than 2 months
CD 38+ expression
Loss/mutation p53; del 11q23 (ATM gene) - p53 is a tumour suppressor gene - loss in this is a bad prognostic indicator for ANY cancer pretty much - good tip for exams to include this as an answer.
Unmutated IgVH gene status
Raised LDH (lactate dehydrogenase - this is a measure of haemolysis)
Male Sex
Age over 70
Lymphocyte count over 50
I think another poor prognostic indicator would be mutation on short arm of chromosome 17 as opposed to the long arm of 13
Who gets acute lymphoblastic leukaemia?
Ususally children less than 6 years of age
How do innate immune diosrders present?
Defects in phagocyte funtion
(staph aureus, sepsis, skin lesions, abscesses internal organs)
(Aspergillus infections (lung, bones, brain)
(Complement deficiencies)
N, Meningitidis
Why does the liver and spleen get bigger in primary myelofibrosis?
As a result of myeloid metaplasia
Liver and spleen start making haematopeitic stem cells
What are the vitamin K dependant factors?
4,7,9,10
Warfarin reduces the amount of these factors
What is the treatment of hereditary angiodema?
Acute managment of pharyngeal / laryngeal obstruction
Acute abdominal pain
Requires C-1 inhibitor infusion OR fresh frozen plasma
Red cell donor table
What are poor prognostic factors for acute lymphoblastic leukaemia?
Poor prognosis factors:
Increasing age
Increased white cell count
Immunophenotype (more primitive forms)
Cytogenetics/molecular genetics
t(9;22); t(4;11)
t(9;22) is the philidelphia chromosome I think
Slow/poor response to treatment
What is the error in haemoglobin for sickle cell and thalassaemia?
Sickle cell = abnormal haemoglobin
Thalasaemia =
What mediates immediate tissue rejection?
Immediate rejection is mediated by ABO/HLA antibodies and compliment activation which damages blood vessels (rapid intravascular thrombosis and necrosis)
What is the presentation of acute leukaemia?
Thrombocytopenic bleeding (Purpura and mucosal membrane bleeding). Petechial bleeding that is non blanching.
- Infection because of neutropenia (predominantly bacterial and fungal) e.g cellulitis
- Bone marrow failure - there is a complete replacement of bone marrow with blast cells. These cells are undifferentiated.
What are investigations for chronic lymphocytic leukaemia?
Blood count : lymphocytosis (over 5000 per mm3), thrombocytopenia
Bone marrow is over 30% lymphocytes
Loss of immunoglobulin production
Haemolytic anaemia
Smudge cells on blood film
Immunophenotyping
What is the diagnostic test for G6PD deficiency?
G6PD enzyme assay
What is the cause of death in myelofibrosis?
Death is usually due to bone marrow failure (haemorrhage, anaemia, or infection), transformation to acute leukaemia, portal or pulmonary hypertension, heart failure, cachexia, or myeloid metaplasia with organ failure.
What is the presentation of acute myeloid leukaemia?
- Anaemia (SOB, fatigue, pallor)
- Thrombocytopenia (bruising, petechiae, epistaxis)
- Neutropenia (bacterial infections, pneumonia, sepsis)
Neoplastc infiltration:
- Bone marrow (bone pain)
- Thymus (palpable mass/airway compression)
- Liver and spleen (hepatosplenomegaly)
- Lymphadenopathy
- Headaches, vomitting, nerve palsies, nuchal rigidity
Can also cause gum swelling which is classic for acute myeloblastic leukaemia
What is the character of the lymphadenopathy found in lymphoma?
Painless and typically has a rubbery feeling. If it were metastatic cancer from the lung it would typically feel very hard.
How do we prevent graft rejection?
Treatment of rejection:
Corticosteroids
Anti-thymocyte globulin
Plasma exchange
Prevention of graft rejection:
ABO matching
Tissue typing (class 1 and 2 HLA)
Prophylactic immunosuppression
Immunosuppression:
Corticosteroids (prednisolone)
Calcineurin inhibitors (tacrolimus) - blocks interleukin 2 gene transcription
Antiproliferatives (MMF) (mycophenolate mofetil) - these prevent lymphocyte proliferation
What are causes of iron deficiency anaemia?
Menorrhagia
Dyspepsia
PR bleeding
Symptoms of malabsorption (diarrhoea, weight loss)
Jaundice
Splenomegaly
What are the indications of platelet transfusion?
Massive haemorrhage
Bone marrow failure
Prophylaxis for surgery
Cardiopulmonary bypass
What is the cause of factor V leiden?
Increases chances of VTE
mis-sense mutation is that activated factor V (a clotting factor) is inactivated 10 times more slowly by activated protein C than normal
What mediates acute tissue rejection?
Acute rejection is mediated by cell and antibody defences. Cellular infiltration of graft by Tc cells, B - cells, NK cells and Macrophages. Causes endothelial inflammation and parenchymal damage.
What is the presentation of essential thrombocytosis?
Characteristic symptom is a burning sensation in the hands
Thrombosis (venous or arterial) and haemorrhage can be seen.
Symptoms of arterial and venous thromboses, digital ischaemia, gout, headache
Mild splenomegaly
What is the time period recquired for immedaite tissue rejection, acute tissue rejection and chronic tissue rejection?
Immediate rejection = within minutes
Acute rejection = less than 6 months
Chronic rejection = more than 6 months
What are the two types of haemolysis seen in normocytic anaemia?
Immune is mosty extravascular
Non-immune is mostly intravascular
What is the cause of essential thrombocytopenia?
Megakaryocyte proliferation results in an overproduction of platelets.
What are exmamples of warm antibody?
Autoimmune
Drugs
CLL
What is the mechanism of G^PD deficiency?
↓ G6PD → ↓ glutathione → increased red cell susceptibility to oxidative stress
What are hallmarks for primary myelofibrosis?
Leukoerythroblastosis and splenomegaly
Splenomegaly happens as a result of extra medullary haematopoeisis
Trephine biopsy shows an excess of megakaryocytes, increased reticulin and fibrous tissue replacement
Presence of a JAK2 mutation supports the diagnosis
What are the symptoms of TRALI?
Acute onset of fever, chills, dyspnoea, tachypnoea, tachycardia, hypotension, hypoxaemia and noncardiogenic bilateral pulmonary oedema leading to respiratory failure during or within 6 hours of transfusion. (shock picture)
What are the B cell markers found on immnophenotyping?
CD19, 20 and 23 and CD5 positive
CD19 and 20 are common markers to which we target therapy
Prognosis for acute lymphoblastic leukaemia?
Prognosis:
Adults with ALL
complete remission rate 78–91%
leukaemia-free survival at 5y 30–35%
Children with ALL
5y overall survival ~90%
Poor risk patients (slow response to induction or Philadelphia positive) 5y OS 45%
(most children survive, half of adults survive)
What are the symptoms of TACO?
(transfusion associated circulatory overload)
Acute respiratory distress
Tachycardia
Raised blood pressure
Acute worsening pulmonary oedema on CXR
Evidence of positive fluid balance
Orthopnea
(shortness of breath, peripheral and pulmonary oedema, high blood pressure)
What causes chronic lymphocytic leukaemia?
Monoclonal proliferation of mature functionally abnormal B cells, these mature B lymphocytes accumulate in the bone marrow - physical suppression, prevents maturation
How does sickle cell disease present?
Painful criris
Stroke
Gallstones
Chest crisis:
- Chest pain
- Fever
- Worsening hypoxia
Why might factor 8 be reduced in von willebrands disease?
Von willebrand factor is a carrier molecule of factor 8
How do innate immune disorders arise?
Defects in phagocyte function
Complement deficiencies
Absence or polymorphisms in pathogen recognition receptors
What causes hereditary angiodema?
Caused by a C1 inhibitor deficiency
Autosomal dominant
What are the treatments available for primary myelofibrosis?
Low risk for thrombosis
Antiplatelet drugs (aspirin, anagrelide)
High risk for thrombosis
Hydroxyurea, interferon-alpha
Folate to prevent deficiency
Ruxolitinib is a JAK2 inhibitor that has recently been licensed for use
Haematopoietic stem cell transplant is the only treatment option with a potential for cure.
What is the treatment for haemolytic anaemia?
Treatment for haemolytic anaemia
Support marrow function
–Folic acid
Correct cause
–Immunosuppression if autoimmune
- Steroids
- Treat trigger eg.CLL, Lymphoma
–Remove site of red cell destruction
•Splenectomy
–Treat sepsis, leaky prosthetic valve, malignancy etc. if intravascular
Consider transfusion
Causes for haemolysis:
autoimmune - give steroids / immunosuppressants
DRUGS
CLL - treat
CHAD
Infections - treat sepsis
(so basically, give steroids if autoimmune, treat any infections and cancers)
What are the types of macrocytic anaemia?
Megaloblastic = vitamin B12 and folate
Normoblastic =
- Alcohol
- Liver disease
- Hypohyroidism
- Pregnancy
- Reticulocytosis
- Myelodysplasia
- Cytotoxic drugs
What is the treatment of chronic myeloid leukaemias?
Tyrosine kinase inhibitors
Says to not give blood - will exacerbate hyperviscosity (I think this is in respect to tumour lysis syndrome)
What is the investigation for sickle cell disease?
Lab results:
- Target cells
- Reticulocytosis
- Increased WBC
Evidence of haemolysis (increased unconjugated bilirubin, increased lactate dehydrogenase, decreased haptoglobin)
Haemoglobin electrophoresis = definitive diagosis
What is the diagnosis of acute lymphoblasic leukaemia?
Blood count - increased WBC, increased lymphoblasts
Bone marrow smear (hypercellular bone marrow, lymphoblast domination)
Immunophenotyping - Terminal deoxynucleotidyl transferase (TdT) is a marker found in premature T and pre-mature B lymphoblasts that is used to diagnose acute lymphoblastic leukemia.
What is the effect of cellular immunodeficiency?
Unusual or opportunistic infections often combined with failure to thrive
pneumocystis jirovecii
CMV
What is the cause of sickle cell disease?
Point mutation in the beta globin gene
Produces haemaglobin S (HbS) - these cells containing HbS tend to crescent chapes when they are deoxygenated
They have one normal and one abnormal beta globin chain
What antibodies are present in A group blood?
Antibodies against type B blood
Note on 22q11
Most common microdeletion syndrome
Incidence is higher in those with down’s syndrome
2nd most common cause of developmental delay and major congenital heart disease
What is the treatment of hodgkin lymphoma?
Combination chemotherapy (ABVD)
+/- radiotherapy
Monoclonal antibodies (anti-CD30)
Immunotherapy (checkpoint inhibitors)
Use of PET scan to assess response to treatment and to limit use of radiotherapy
Rituximab an be used as well
What are the different types of acute lymphoblstic leukaemia?
Composed of T cell precursors or B cell precursors
These cells are stuck in the blast phase (undifferentiated)
Divide uncontrollably - take up a lot of space and nutrients in the bone marrow - cytopenias (anaemia, thombocytopenias, leukopenias)
What is responsible for fibrinolysis?
Plasmin
What are the blood findings in tumour lysis syndrome?
High potassium
High phosphate
Low calcium
High uric acid
High urea and nitrogen containing compounds
What are the different types of von wilebrand disease?
Type 1 = quantitive deficiency (80% of patients)
Type 2 = qualititive deficiency
Type 3 = severe (complete) deficiency
How does myeloma affec tthe kidneys?
Small molecular weight molecules can pass through the glomerulus - bence jones protein in the urine - causes proximal tubular necrosis
Cast nephropathy
Nephrocalcinosis as a result of hypercalciuria
Free light chains deposit in the kidneys, heart and other organs - causing AL amyloidosis
What is the most common cause of death in patients with sickle cell disease?
URTI
What type of blood should you give in emergencies? (minutes)
O RhD neg red cells (AB plasma)
Who gets G6PD deficiency?
It is X linked recessive so Males
Common in people from mediterranean and africa
What is the treatment for essential thrombocytosis?
hydroxyurea (hydroxycarbamide) is widely used to reduce the platelet count
Anagrelide
interferon-α is also used in younger patients
low-dose aspirin may be used to reduce the thrombotic risk
What are the complications of chronic lymphocytic leukaemia?
Abnormal Ig secretion (hypogammaglobulinaemia, autoimmunity)
Richter syndrome- can progress to aggressive lymphoma (large B cell lymphoma)
What is the presentation of anaemia?
General features due to reduced oxygen delivery to tissues:
Tiredness/pallor
Breathlessness
Swelling of ankles
Dizziness
Chest pain
Potential History:
–Dyspepsia GI bleeding
–Other bleeding, eg menorrhagia
–Diet (NB children and elderly)
Increased requirement - pregnancy
Malabsorption from gastrectomy and coeliacs
Atrophic tongue
Angular Chelitis
Hypochromic, microcytic cells
Koilonychia
B12/folate deficiency = anaemia, neurological symptoms (subacute combined degeneration of the cord in B12 deficiency.)
Megaloblastic anaemia:
“Lemon yellow” tinge
–Bilirubin, LDH
–Red cells friable
What is the investigation for acute lymphoblastic leukaemia?
Low haemoglobin
Raised WCC (this is incontrast to myeloma which has leukopenia)
Low platelets
Bone marrow (90% B - Lymphoblasts)
What is the presentation for polycythaemis rubra vera?
Incidence peaks in the 6th decade
hyperviscosity (stroke, vascular occlusion, thrombosis, TIA)
pruritus, typically after a hot bath
splenomegaly
haemorrhage (secondary to abnormal platelet function)
plethoric appearance
hypertension in a third of patients
Symptoms of hyperviscosity include loss of concentration, headaches, dizziness, blackouts, pruritis and epistaxis
What are some of the complications of sickle cell disease?
Aplastic crisis (temporary arrest of erythropoeisis, can be caused by parovirus B19)
Vaso-occlusion, tissue ischaemia and infarction
Daytylitis
Hyposplenism means increase risk of infection
MI
VTE
Dysrhythmias
Acute chest syndrome (fever, chest pain, hypoxemia, wheezing, cough, respiratory distress)
Pulmonary hypertension
Osteoporosis
Proliferative retinopathy
Multi-organ failure
Priapism
What is the point in the coombs test?
Tests for auto immune haemolytic anaemia
Used to detect antibodies or compliment proteins attached to red cells
f the red cells then agglutinate, the direct Coombs test is positive, a visual indication that antibodies or complement proteins are bound to the surface of red blood cells and may be causing destruction of those cells.
What does megaloblastic mean?
Impairment of DNA synthesis, cell cycle cannot progress from G2 growth stage to the mitosis stage - continued cell growth without division
What is the presentation of primary myelofibrosis?
Massive splenomegaly
Fatigue
Erythromelalgia
constitutional symptoms (weight loss, night sweats, low-grade fever, cachexia, fatigue, and pruritus)
What is staging of chronic lymphcytic leukaemia?
Binet staging
What are causes of ITP?
EBV
HIV
Collagenosis
Lymphoma
Drug induced (quinine)
What clotting factor is reduced in Haemophilia type A and type B?
A = factor 8
B = factor 9
What are the causes of microcytic anaemia?
Iron deficiency anaemia
Thalassaemia
Congenital sideroblastic anaemia
Lead poisoning
Anaemia of chronic disease (although this is more commonly a normocytic picture)
What antibodies are present in O type blood?
Antibodies against A and B
What casues primary myelofibrosis?
Proliferation of myeloid haematopoetic stem cells
Overproduction of megakaryocytes in the bone marrow leading to bone marrow fibrosis
What are the types of non-hodgkine lymphoma?
Burkitt (very aggressive)
Diffuse large B cell (aggressive) - most common subtype of lymphoma
Extranodal marginal zone MALT - slow growth
Follicular (slow growth) - 2nd most common subtype
Low grade lymphoma - indolent, often asymptomatic, responds to chemotherapy but is itself incurable
HIgh grade - aggressive and fast growing, can be cured
What is the mechanism of disease in acute myeloid leukaemia?
Neoplastic monoclonal proliferation of myelogenous stem cells (myeloblasts) in bone marrow
Immature myeloblasts accumulate in
bone marrow
→
physical suppression
→
prevents maturation
Where does the structural abnormality lie in hereditary spherocytosis?
Defect in the cytoskeleton in red blood cells
Red blood cell survival is reduced due to destruction by the spleen
What is diagnosis of venous thrombosis?
Pretest probability scoring
Wells score
Geneva score
Laboratory testing if pretest probability low
D-dimer
Imaging
Doppler US - compression ultrasonography, contrast venography, CT venography, MRA
DVT thrombosed vein enlarged, non-compressible, echogenic material might be seen
Ventilation perfusion scan
CT pulmonary angiogram
What type of blood do we give in non-urgent scenarios?
Full cross match
ABO / RhD specific
Choose antigen negative blood if there are alloantibodies
What might precipitate a haemolytic crisis in G6PD deficiency?
Infection
Fava beans
Drugs (NSAIDs, aspirin, nitrofurantoin, quinine)
What is the essential investigation if there is a macrocytic picture?
Folate/B12 + bone marrow
What are risk factors for stasis/hypercoagulability?
Increasing age
Pregnancy
Surgery
Obesity
Systemic disease
Family history
Tissue trauma
Immobility
Hormonal therapy (COCP/HRT)
COCP = combined oral contraceptive pill
Antipsychotics
What is the treatment of megaloblastic anaemia?
Treatment for megaloblastic anaemia:
Replace vitamin
B12 deficiency
–B12 intramuscular injection
–Loading dose then 3 monthly maintenance
Folate deficiency
–Oral folate replacement
–Ensure B12 normal if neuropathic symptoms
Why is screening for factor v leiden not indicated?
Screening for factor V Leiden is not recommended, even after a venous thromboembolism. The logic behind this is that a previous thromboembolism itself is a risk factor for further events and this should dictate specific management in the future, rather than the particular thrombophilia identified.
What is the treatment for iron deficiency anaemia?
Correct the deficiency -
Oral iron usually sufficient
IV iron if intolerant of oral
Blood transfusion rarely indicated
Correct the cause -
Diet
Ulcer therapy
Gynae interventions
Surgery
What are examples of cold antibody haemolysis?
CHAD
Infections
Lymphoma
What is treatment for haemophilia?
- Coagulation factor replacement FVIII/IX
- Now almost entirely recombinant products
- DDAVP (desmopressin) (this can be used in patients with haemophilia A, von willebrand disease and thrombocytopenia, cannot be used for haemophilia type B. The drug works by increasing the amount of von willebrand factor and factor 8.
- Tranexamic Acid
- Emphasis on prophylaxis in severe haemophilia
- Gene therapy?
- Splint
- Physiotherapy
- Analgesia
- Synovectomy
- Joint replacement
Treatment is designed to get the person to the point where they are no longer severely haemophilic (we want to make sure they no longer bleed spontaneously which is the definition of severe)
What is the role of von willebrand factor?
Promotes platelet adhesion to damaged endothelium
Why is prothrombin time different to activated partial thromboplastin time?
PTT = intrinsic pathway (intrinsic pathway contains factor 8 and 9)
PT = extrinsic pathway
What is managment of b=von willebrands disease?
tranexamic acid for mild bleeding
desmopressin (DDAVP): raises levels of vWF by inducing release of vWF from Weibel-Palade bodies in endothelial cells
factor VIII concentrate
VW factor concentrate
What is prognosis for chronic lymphocytic leukaemia?
Median survival:
Stage A - same as matched controls
Stage B - around 8 years
Stage C = around 6 years
What are the features of multiple myeloma?
Clinical features
bone disease: bone pain, osteoporosis + pathological fractures (typically vertebral), osteolytic lesions
lethargy
infection
hypercalcaemia
renal failure
other features: amyloidosis e.g. Macroglossia, carpal tunnel syndrome; neuropathy; hyperviscosity (hyperviscosity syndrome caused by malignant cells producing lots of paraproteins)
Bleeding tendancy (retinal, oral, nasal or cutaneous)
What are the causes of DIC?
Septicaemia
Malignancy (acute myeloid leukaemia can cause DIC)
Eclampsia
What is the presentation of hodgkin lymphoma?
lymphadenopathy (75%) - painless, non-tender, asymmetrical
systemic (25%): weight loss, pruritus, night sweats, fever (Pel-Ebstein)
alcohol pain in HL
normocytic anaemia, eosinophilia
LDH raised
Note on multiple myeloma
Its a neoplastic disorder of plasma proteins that usually results in the excessive production of a single type of immunoglobulin (paraprotein)
Peaks in 7th decade
More common in black people than white.
How does hereditary angiodema present?
Recurrent episodes of painless, non-pitting, non-pruritis, non-erythematous swellings
Swellings can be:
- Subcutaneous
- Intestinal
- Oropharynx
What type of blood should we give in urgent scenarios?
ABO / RhD specific
What is the managment for arterial clots?
Thromolysis
Antiplatelet/anticoagulant drugs
What structural defects cause hereditary spherocytosis?
Ankyrin
Alpha spectrin
Beta spectrin
Band 3
Protein 4.2
Who gets hodgkin lymphoma?
It has a bimodal age distributions being most common in the third and seventh decades
What causes severe combined immunodeficiency?
Cytokine receptor defects are the most common cause - most commonly adenosine deaminase deficiency - low levels of this enyme result in a decline of T cells and B cells
What are causes of normocytic anaemia?
Chronic kidney disease
Haemolytic anaemia
Aplastic anaemia
Anaemia of chronic disease
What is the treatment for multiple myeloma?
Chemotherapy
Immunomodulators such as thalidomide
Proteasome inhibitors, IMiDs, monoclonal antibodies
Bisphosphonate therapy (Zoledronic acid) - these prevent bone loss
Radiotherapy
Steroids
Surgery
Pinning of long bones; decompression of spinal cord
Autologous stem cell transplant
Antibiotics to treat infections
What is th ehallmark feature of PV?
Iron deficiency
You don’t give iron because that will cause a stroke
What causes beta thalassaemia major?
Absence of beta chains
Chromosome 11
What are the symptomsof hypercalcaemia associated with Multiple Myeloma?
Thirst
Constipation
Solomnence
Confusion
Nausea
What are investigations for chronic myeloid leukaemia?
Blood count shows increased granulocytes (basophils, eosinophils and neutrohpils)
Bone marrow biopsy shows hypercellularity (cells of myeloid cell line / precursors)
FISH/PCR for karyotypic analysis: BCR-ABL 1 gene mapping
Small chromosome 22 = philidelphia chromosome. Small chromosome is the result of balanced translocation with chromosome 9. You are left with a small 22 and a BCR - ABL on 22 - this then results in an increased amount of ABL.
What is the treatment of acute lymphblastic leukaemia?
Chemotherapy
Consolidation therapy
Maintenance treatment
Stem cel transplant if high risk
Large portion of care is to ensure children continue to grow and develop - keep up with school etc
CNS directed therapy (chemotherapy doesn’t penetrate well and it often spreads to the CNS) - give medicines intrathecally by lumbar tap or lumbar puncture
Maintenance treatment for 18 months
Bone marrow transplant in those that are likely to relapse
Newer therapies:
1) Bispecifc T-cell engagers (BiTe molecules) – e.g. Blinatumumab - draws t cells to cancerous cells to destroy the cancer
2) CAR (chimeric antigen receptor T-cells)
Patient/ healthy 3rd party T-cells harvested
Transfected to express a specific T-cell receptor expressed on leukaemia cells (CD19)
Expanded in vitro
Re-infused into patient
CAR - T cells have risk of cytokine release syndrome - signs include fever, hypotension and dyspnoea
What is the treatment for hereditary spherocytosis?
Folci acid
Transfusion
Splenectomy
What are potential side effects from transfusion?
Febrile non-haemolytic transfusion reaction
TACO
TRALI
Allergic
Transfusion assocaited graft vs host disease
Prion disease such as CJD
What is the treatment of PV?
Venessection to keep the haematocrit below 0.45 and 0.43 in women
Aspirin
Hydroxycarbamide
Ruxolitinib - JAK 2 inhibitor
Interferon alpha
What is the essential test if there is hypochromic and microcytic anaemia?
Need to do serum ferritin, reduced serum ferritin means iron deficiency anaemia
If male you might want to do a GI endoscopy to check for bleeding
How is the diagnosis of acute myeloid leukaemia made?
Blood count will show leukocytosis and anaemia
Bone marrow aspirate (over 20% of the cells withh be myeloblasts)
Myeloblasts containing Auer rods
Others:
- Immunophenotyping of leukaemic blasts (remember that acute lymphoblastic will contain terminal deoxynucleotidyl transferase)
- CSF examination if there are symptoms
What can PV beceom
AML
What are the relevant investigations for multiple myeloma?
- IgG, IgA paraproteins - these are produced by mature plasma cells after isotype switching
What are the characteristics of the hodgkin lymphoma cell?
Presence of reed-sternberg cells
Giant B cells with bilobed nuclei that have prominent eosinophilic inclusions
What is the presentation of beta thalassaemia major?
Failure to thrive
Hepatosplenomegaly
Bony deformities
Growth retardation
What does myelodysplastic syndromes become?
bone marrow failure or AML
HSTC is the only curative option
What activates platelets?
Abnormal surface or physiological activator
What is the treatment for sickle cell disease?
Life long prophylaxis
–Vaccination
–Penicillin (and malarial) prophylaxis
–Folic acid
Acute Events
–Hydration
–Oxygenation
–Prompt treatment of infection
–Analgaesia
- Opiates
- NSAIDs
Blood transfusion
–Episodic and chronic
–Alloimmunisation
–Iron overload
Disease modifying drugs
–Hydroxycarbamide - this increases the amount of fetal haemoglobin in the blood and so therefore decreases the number of crisis’
- L glutamine - duces sickling
Bone marrow transplantation
Gene therapy
Treatment for painful crisis:
•Severe pain- often requires opiates
- Analgesia should be given within 30 mins of presentation
- Effective analgesia by 1hour
- Avoid pethidine
- Hydration
- Oxygen
- Consider antibiotics
No routine role for transfusion
Treatment for a chest crisis:
Respiratory Support
Antibiotics
IV Fluids
Analgaesia
Transfusion – top up or exchange target HbS <30%
What is the managment of beta thalassaemia major?
Repeated blood transfusions
To prevent iron overloading you have to use a chelation therapy
s/c desferroxamine is gold standard - oral alternative is deferasirox
Bone marrow transplant = curative
What are the main risks assocaited with PV?
Cerebrovascular or coronary events occur in up to 60% of patients. The disease may convert to another myeloproliferative disorder with about 25% developing acute leukaemia or myelofibrosis
What parts of the platelets are responsible for the following functions?
Adhering
Activating
Aggregating
Coagulation
Involved in adherence = GP 1b and GP 1a
Involved in activation = ADP and COX
Involved in aggregation = thromboxane A2
Involved in coagulation = scramblase
What are indications for red cell transfusion?
Correct anaemia which may cause organ damage if left uncorrected
To improve quality of life in a patient with otherwise uncorrectable anaemia
To prepare a patient for surgery or to speed up recovery
To reverse damage caused by patients own red cells
How do antibody deficiencies normally present?
Recurrent bacterial infections of the upper and or lower respiratory tract
S.pneumoniae
H.influenzae
What is the investigation for hereditary spherocytosis?
DAT - not an immune reaction therefore there is a negative result
No tests necessary if there is a family history, typica clinical features and typical lab findings (spherocytes, raised MCHC, raised reticulocytes)
Cryohaemolysis test and EMA binding
What is the investigations for polycythaemia vera?
Raised haemoglobin concentration and haematocrit
Tendancy to also have a raised white cell count and platelet count
Raised uric acid since there is an increased cell turnover
Increase in red cell mass when the blood volume is measured
Presence of JAK2 mutation - in JAK 2 negative cases you have to rule out secondary causes of erythrocytosis
What is the presentation of haemophilia?
- Haemarthrosis
- Muscle haematoma
- CNS bleeding
- Retroperitoneal bleeding
- Post surgical bleeding
Complications can include:
Synovitis
Chronic Haemophilic Arthropathy
Neurovascular compression (compartment syndromes)
Other sequelae of bleeding (Stroke)
What are the natural anticoagulants?
Protein C
Protein S
TFPI (tissue factor pathway inhibitor)
Antithrombin
These confine the clot to the area of tissue damage
What is therapy for non-hodgkin lymphoma?
Both are treated with combination chemotherapy
Both are treated with combination chemotherapy – typically anti-CD20 monoclonal antibody + chemo
CD20 monoclonal antibody is rituximab
What is the bleeding pattern of von Willebrands disease?
Behaves like a platelet disorder i.e. epistaxis and menorrhagia are common whilst haemoarthroses and muscle haematomas are rare
How do antibody deficiencies arise?
Defective B cell function
Absence of mature B cells
What causes B12 deficiency?
Pernicious anaemia, caused by gastric / ileal disease
Antibodies against intrinsic factor (diagnostic)
Gastric parietal cells (less specific)
Malabsorption of dietary B 12
Symptoms / signs take 1-2 years to develop
produced by the parietal cells of the stomach. It is necessary for the absorption of vitamin B12 later on in the ileum of the small intestine.
What are systemic symptoms of lymphoma?
Fever
Drenching sweats, loss of weight, prutitis, fatigue
B symptoms: fever, drenching sweats, 10% non-deliberate weight loss, fatigue, pruritis
High grade makes you feel ill very quickly - not usually found by accident
Low grade grows slowly and are often found by accident
What are relecant investigations for neutropenic sepsis?
History and examination
Blood cultures -Hickman line & peripheral
CXR
Throat swab & other clinical sites of infection (if UTI do MSSU)
Sputum if productive
FBC, renal and liver function, coagulation screen
What is the presentation of G6PD deficiency?
Neonatal jaundice (like HS)
Drug, borad bean or infection precipitated jaundice and anaemia (haemolysis)
Intravascular haemolysis (HS is extravascular)
Splenomegaly
Pigment gallstones
What are chromosonal changes assocaited with chronic lymphocytic leukaemia?
Chromosomal Changes:
Deletion of the long arm of chromosome 13 (del 13q) is the most common abnormality, being seen in around 50% of patients. It is associated with a good prognosis
Deletions of part of the short arm of chromosome 17 (del 17p) are seen in around 5-10% of patients and are associated with a poor prognosis
What is the presentation of chronic myeloid leukaemia?
Anaemia
Splenomegaly, often massive
Weight loss
Hyperleukostasis - fundal haemorrhage and venous congestion, altered consciousness, respiratory failure. Also known as tumour lysis syndrome
Gout from a high cell turnover
What mediates chronic tissue rejection?
Other innate components
Cytokines and antibodies cause myointimal proliferation in the arteries - blocks blood vessels and leads to ischaemia and fibrosis
What is platelet count in ET?
Greater than 600 x 10^9
What is the presentation of neutropenic sepsis?
Fever with no localising signs
Single reading of >38.50C or 380C on two readings one hour apart
Rigors
Chest infection/ pneumonia
Skin sepsis - cellulitis
Urinary tract infection
Septic shock
What mutation is assocaited with polycythaemia vera
JAK2V617F in 95%
Fresh frozen plasma table
What is the disease mechanism of chronic myeloid leukaemia?
Neoplastic monoclonal proliferation of ature granulocytes/precursors
Mature granulocytes accumulate in the bone marrow causing physical suppression which prevents maturation
Chronic myeloid leukaemia is assocaited with the philidelphia chromosome - t(9,22) BCR-ABL1 fusion - chimeric protein with strong tyrosine kinase activity (in over 90% of individuals)
What is the presentation of 22q11 deletion syndrome?
CATCH 22
Cardiac abnormalities
Abnormal facies
Thymic hypoplasia
Cleft palate
Hypocalcaemia
Also includes:
- Learning difficulties
What type of anaemia does beta thalassaemia cause?
Microcytic
What causes non-hodgkin lymphoma?
B/T cell tumours
No Reed-sternberg cells
What is the most common presentation for haemophilia?
Most presentation is between 6 months and 2 years. The baby starts walking and then all of a sudden stops walking, because they have had a bleed in their joint and don’t want to walk on it. Don’t jump to non accidental injury until you rule out bleeding disorder.
What antibodies does the person have if they have AB type blood?
No antibodies
What is myeloma a cancer of?
Bone marrow plasma cells
What is the essential test to do if there is a normocytic anaemia?
Want to perform a reticulocyte count and establish if the bone marrow is working correctly
What is the immunological presentation of 22q11 syndrome?
Recurrent RTI’s during infancy
Low T cell numbers
Low IgA and IgM
Reduced antibody response
Autoimmune phenomena:
-Anaemia/thrombocytopenia
Juvenile chronic arthritis (JIA)
Raynauds
Thyroid disease
What is the presentation of chronic lymphocytic leukaemia?
Most common leukaemia in adults
Agent Orange exposure
- Anaemia (SOB, fatigue, pallor)
- Thrombocytopenia (bruising, petechiae, epistaxis)
- Neutropenia (bacterial infections, pneumonia, sepsis)
Neoplastc infiltration:
- Bone marrow (bone pain)
- Thymus (palpable mass/airway compression)
- Liver and spleen (hepatosplenomegaly)
- Lymphadenopathy
- Headaches, vomitting, nerve palsies, nuchal rigidity
How is the diagnosis of haemophilia made?
Prolonged APTT (activated partial thromboplastin time) Normal PT (prothrombin time)
What is the supply of blood in someone who has received a massive haemorrhage?
6 units of red cells
4 units of fresh frozen plasma
1 units of platelets
What are indicators for treatment for chronic lymphocytic leukaemia?
Progressive bone marrow failure
Massive lymphadenopathy
Progressive splenomegaly
Lymphocyte doubling time <6 months or >50% increase over 2 months
Systemic symptoms
Autoimmune cytopenias
Drugs for DVT
Drugs for DVT:
Anticoagulants:
LMWH
Warfarin
DOACs
Thrombolysis only in selected cases:
Massive PE
E.g streptokinase, tissue plasminogen activator
What causes alloantibodies?
Transfusion reactions
How do cellular immnodeficiencies arise?
Impaired T cell function or the absence of normal T cells
What is the treatment of acute myeloblastic leukaemia?
Anti-leukaemic chemotherapy (to achieve consolidation and remission)
Danorubicin
Cytosine arabinoside
Gemtuzumab
Ozgamicin
CPX351
All trans retinoic acid and arsenic trioxide in low risk acute promyelocytic leukaemia (chemo free) high cure rate - 90%
Targeted Treatment:
Midostaurin in FLT3 mutated AML
Targeted antibodies:
Gemtuzumab Ozogamicin anti-CD33 with Calicheomycin (Mylotarg) - (think of Milo playing tig)
Targeted small molecules
Midostaurin, Tyrosine Kinase Inhibitor including inhibiting FLT3
New delivery systems
CPX -351 - old fashioned chemotherapy but in a lipid molecule
What is the difference between a venous and an arterial clot?
Arterial thrombus = white clot - platelets and fibrin, results in ischaemia and infarction, principally secondary to atherosclerosis.
‘Red thrombus’~fibrin and red cells
Results in back pressure
Principally due to stasis and hypercoagulability
What are investigations for lymphoma?
IgM paraproteins
Biopsy (lymph node, bone marrow)
CT scan
Bone marrow aspirate and trephine
What are the symptoms of acute lymphoblastic leukaemia?
2-3 week history of bone marrow failure or bone/joint pain.
Anaemia
Tiredness
Fatigue
Infection
Bone marrow can necrose because it is full of rapidly dividing cells
Bone pain
Limp or hip pain (red flag symptom in children)
Osmosis:
- Anaemia (SOB, fatigue, pallor)
- Thrombocytopenia (bruising, petechiae, epistaxis)
- Neutropenia (bacterial infections, pneumonia, sepsis)
Neoplastc infiltration:
- Bone marrow (bone pain)
- Thymus (palpable mass/airway compression)
- Liver and spleen (hepatosplenomegaly)
- Lymphadenopathy
- Headaches, vomitting, nerve palsies, nuchal rigidity
What is virchows triad?
Stasis
Hypercoagubility
Vessel damage
Stasis = bed rest, travel
Hypercoagulability = pregnancy, trauma
Vessel damage = atherosclerosis
What is a potential treatment for SCID?
HSCT - haematopoeitic stem cell transplantation
How is non-hodgkin lymphma classified?
B cell or T cell lineage
Grade of disease (high grade or low grade)
Histological features of the disease
What is the treatment for FNHTR and urticaria following blood transfusion?
FNHTR = anti-pyretics
Urticaria = Antihistamines
How do you distinguish TACO from TRALI?
TACO is frequently confused with TRALI as a key feature of both is pulmonary oedema and it is possible for these complications to occur concurrently. Hypertension is a constant feature in TACO whereas it is infrequent and transient in TRALI.
What are the signs and symptoms of thrombocytopenia?
- Petechia (Venous pressure is higher in the leg than anywhere else – more likely to have petechiae)
- Ecchymosis (discolouration of the skin resulting from bleeding underneath, typically caused by bruising)
- Mucosal Bleeding
- Rare CNS bleeding
What is necessary for the diagnosis of acute myeloid leukaemia?
Blast cell count has to be greater than 20% for the diagnosis
Less than 20% may indicate myelodysplastic syndrome
What is seen on blood film of G6PD deficiency?
Hein Bodies
How does SCID present?
Recurrent infections
Diarrhoea, malabsorption and failure to thrive
Oral candidiasis with prominent thrush
Complications in clude susceptibility to severe infections such as:
andida albicans, pseudomonas, pneumocystiss jiroveci, cytomegalovirus, varicella
What mutation is assocaited with essential thrombocytopenia?
JAK2 mutation in around 50% of patients
Can also be associated with the CALR mutation in around 25% of individuals
What are the causes of thrombocytopenia?
Decreased production:
Marrow failure
Aplasia
Infiltration
Increased consumption
Immune ITP
Non immune DIC (caused by septicaemia, malignancy and eclampsia)
Hypersplenism
What is the managment of TACO?
Stop transfusion immediately and follow other steps for managing suspected transfusion reactions.
Place the patient in an upright position and treat symptoms with oxygen, diuretics and other cardiac failure therapy.
How do we figure out if haemolysis is immune or non-immune?
DAT test will tell you wether or not it is immune or non-immune. DAT positive = immune, DAT negative = not immune. Of the immune reactions the positive types can be further subdivided into warm-autoantibody, cold antibody and allo antibody.
What are complications in therapy for haemophilia?
Viral infection: HIV, HBV, HCV
Development of inhibatory antibodies for factor 8 (up to 10-15% of patients with haemophilia A)
DDAVP SE include MI and hyponatraemia
