Haematology Flashcards
Acute myeloid leukaemia
-Is this found in adults or children?
-How does this occur
Acute myeloid leukaemia is the more common form of acute leukaemia in adults. It may occur as a primary disease or following a secondary transformation of a myeloproliferative disorder.
Give 5 features of AML>=
Features are largely related to bone marrow failure:
anaemia: pallor, lethargy, weakness neutropenia: whilst white cell counts may be very high, functioning neutrophil levels may be low leading to frequent infections etc thrombocytopenia: bleeding splenomegaly bone pain
Acute promyelocytic leukaemia M3
-What is this assoc with?
-What gene fusion is this assoc with?
-When does this present?
-What is seen on myeloperoxidase stain?
-What is the prognosis?
Acute promyelocytic leukaemia M3
associated with t(15;17) fusion of PML and RAR-alpha genes presents younger than other types of AML (average = 25 years old) Auer rods (seen with myeloperoxidase stain) DIC or thrombocytopenia often at presentation good prognosis
What is the classification of acute myeloid leukaemia?
Classification - French-American-British (FAB)
MO - undifferentiated M1 - without maturation M2 - with granulocytic maturation M3 - acute promyelocytic M4 - granulocytic and monocytic maturation M5 - monocytic M6 - erythroleukaemia M7 - megakaryoblastic
what is ALL?
-Who does this affect?
-when is the peak incidence?
Acute lymphoblastic leukaemia (ALL) is the most common malignancy affecting children and accounts for 80% of childhood leukaemias. The peak incidence is at around 2-5 years of age and boys are affected slightly more commonly than girls
what are three features of ALL predictable by bone marrow failure?? And features that are not predictable by bone marrow failure
Features may be divided into those predictable by bone marrow failure:
anaemia: lethargy and pallor neutropaenia: frequent or severe infections thrombocytopenia: easy bruising, petechiae
And other features
bone pain (secondary to bone marrow infiltration) splenomegaly hepatomegaly fever is present in up to 50% of new cases (representing infection or constitutional symptom) testicular swelling
What are three types of ALL?
Types
common ALL (75%), CD10 present, pre-B phenotype T-cell ALL (20%) B-cell ALL (5%)
What are poor prognostic factors for ALL?
Poor prognostic factors
age < 2 years or > 10 years WBC > 20 * 109/l at diagnosis T or B cell surface markers non-Caucasian male sex
What is CLL? who is this seen in?
Chronic lymphocytic leukaemia (CLL) is caused by a monoclonal proliferation of well-differentiated lymphocytes which are almost always B-cells (99%). It is the most common form of leukaemia seen in adults.
What are the features of CLL (4)
Features
often none: may be picked up by an incidental finding of lymphocytosis constitutional: anorexia, weight loss bleeding, infections lymphadenopathy more marked than chronic myeloid leukaemia
What are the investigations of CLL? 3
Investigations
full blood count:
lymphocytosis
anaemia: may occur either due to bone marrow replacement or autoimmune hemolytic anaemia (AIHA)
thrombocytopenia: may occur either due to bone marrow replacement or immune thrombocytopenia (ITP)
blood film: smudge cells (also known as smear cells)
immunophenotyping is the key investigation
most cases can be identified using a panel of antibodies specific for CD5, CD19, CD20 and CD23
What are the complications of CLL? 4
Complications
anaemia hypogammaglobulinaemia leading to recurrent infections warm autoimmune haemolytic anaemia in 10-15% of patients transformation to high-grade lymphoma (Richter's transformation)
What is richters transformation?
Ritcher’s transformation occurs when leukaemia cells enter the lymph node and change into a high-grade, fast-growing non-Hodgkin’s lymphoma. Patients often become unwell very suddenly.
Ritcher’s transformation is indicated by one of the following symptoms:
lymph node swelling fever without infection weight loss night sweats nausea abdominal pain
What warrants a very urgent FBC to investigate leukaemia in aged 0-24?
Any of the following features in a person aged 0-24 years should prompt a very urgent full blood count (within 48 hours) to investigate for leukaemia:
Pallor Persistent fatigue Unexplained fever Unexplained persistent infections Generalised lymphadenopathy Persistent or unexplained bone pain Unexplained bruising Unexplained bleeding
What is hodgkins lymphoma?
Hodgkin’s lymphoma (HL) is a malignant proliferation of lymphocytes characterised by the presence of the Reed-Sternberg cell. It has a bimodal age distributions being most common in the third and seventh decades
What are 2 risk factors for hodgkins lymphoma?
Risk factors
HIV Epstein-Barr virus
Describe the lymphadenopathy found in hodgkins lymphoma?
Features
lymphadenopathy (75%)
most commonly in the neck (cervical/supraclavicular) > axillary > inguinal
usually painless, non-tender, asymmetrical
alcohol-induced lymph node pain is characteristic of Hodgkin's lymphoma but is seen in less than 10% of patients
What are B symptoms in lymphoma?
systemic - ‘B symptoms’ (25%)
weight loss
pruritus
night sweats
fever (Pel-Ebstein)
In hodgkins lymphoma what may be seen on CXR?
other possible presentations include a mediastinal mass
may be symptomatic (e.g. cough) or found incidentally on a chest x-ray
What four investigations are indicated in hodgkins lymphoma?
Investigations
-normocytic anaemia
may be multifactorial e.g. hypersplenism, bone marrow replacement by HL, Coombs-positive haemolytic anaemia etc
-eosinophilia
caused by the production of cytokines e.g. IL-5
-LDH raised
-lymph node biopsy
Reed-Sternberg cells are diagnostic: these are large cells that are either multinucleated or have a bilobed nucleus with prominent eosinophilic inclusion-like nucleoli (thus giving an ‘owl’s eye’ appearance)
What is burkitts lymphoma?
Burkitt’s lymphoma is a high-grade B-cell neoplasm. There are two major forms:
endemic (African) form: typically involves maxilla or mandible
sporadic form: abdominal (e.g. ileo-caecal) tumours are the most common form. More common in patients with HIV
What gene translocation is assoc. with burkitt’s lymphoma?
Burkitt’s lymphoma is associated with the c-myc gene translocation, usually t(8:14). The Epstein-Barr virus (EBV) is strongly implicated in the development of the African form of Burkitt’s lymphoma and to a lesser extent the sporadic form.
What gene translocation is assoc. with burketts lymphoma
Burkitt’s lymphoma is associated with the c-myc gene translocation, usually t(8:14). The Epstein-Barr virus (EBV) is strongly implicated in the development of the African form of Burkitt’s lymphoma and to a lesser extent the sporadic form.
Burketts lymphoma
-what is seen on miscroscopy?
Microscopy findings
'starry sky' appearance: lymphocyte sheets interspersed with macrophages containing dead apoptotic tumour cells
What is the management of of burkitt’s lymphoma
-what is given before chemo in burkitts
-
Management is with chemotherapy. This tends to produce a rapid response which may cause ‘tumour lysis syndrome’. Rasburicase (a recombinant version of urate oxidase, an enzyme which catalyses the conversion of uric acid to allantoin*) is often given before the chemotherapy to reduce the risk of this occurring.
What are 5 compliactions of tumour lysis syndrome?
Complications of tumour lysis syndrome include:
hyperkalaemia hyperphosphataemia hypocalcaemia hyperuricaemia acute renal failure
What is myeloma?
Multiple myeloma (MM) is a haematological malignancy characterised by plasma cell proliferation. It arises due to genetic mutations which occur as B-lymphocytes differentiate into mature plasma cells.
Features of myeloma
-What is the age at presentation?
-CRABBI pneumonic
-What are other features?
The median age at presentation is 70 years old.
Use the mnemonic CRABBI:
Calcium
hypercalcaemia
primary factor: due primarily to increased osteoclastic bone resorption caused by local cytokines (e.g. IL-1, tumour necrosis factor) released by the myeloma cells
much less common contributing factors: impaired renal function, increased renal tubular calcium reabsorption and elevated PTH-rP levels
this leads to constipation, nausea, anorexia and confusion
Renal
monoclonal production of immunoglobulins results in light chain deposition within the renal tubules
this causes renal damage which presents as dehydration and increasing thirst
other causes of renal impairment in myeloma include amyloidosis, nephrocalcinosis, nephrolithiasis
Anaemia
bone marrow crowding suppresses erythropoiesis leading to anaemia
this causes fatigue and pallor
Bleeding
bone marrow crowding also results in thrombocytopenia which puts patients at increased risk of bleeding and bruising
Bones
bone marrow infiltration by plasma cells and cytokine-mediated osteoclast overactivity creates lytic bone lesions
this may present as pain (especially in the back) and increases the risk of pathological fractures
Infection
a reduction in the production of normal immunoglobulins results in increased susceptibility to infection
Other features include
amyloidosis e.g. macroglossia carpal tunnel syndrome neuropathy hyperviscosity
What is including in investigations for myeloma
Bloods
Protein electrophoresis
Bone marrow biopsy/aspiration
Imaging
What is seen on bloods in myeloma?
-FBC
-Blood film
-U+Es
-Bone profile
Bloods
full blood count: anaemia peripheral blood film: rouleaux formation urea and electrolytes: renal failure bone profile: hypercalcaemia
What is seen on bone marrow aspiration in myeloma?
Bone marrow aspiration
confirms the diagnosis if the number of plasma cells is significantly raised
Describe the imaging in myeloma
maging
historically a skeletal survey has been done to look for bone lesions however, whole-body MRI is increasingly used and is now recommended in the 2016 NICE guidelines X-rays: 'rain-drop skull' (likened to the pattern rain forms after hitting a surface and splashing, where it leaves a random pattern of dark spots). Note that a very similar, but subtly different finding is found in primary hyperparathyroidism - 'pepperpot skull'
What is the diagnostic criteria in myeloma?
The diagnostic criteria for multiple myeloma requires one major and one minor criteria or three minor criteria in an individual who has signs or symptoms of multiple myeloma.
What are the major criteria in myeloma?
Major criteria
Plasmacytoma (as demonstrated on evaluation of biopsy specimen) 30% plasma cells in a bone marrow sample Elevated levels of M protein in the blood or urine
What is MGUS and does this lead to myeloma?
Monoclonal gammopathy of undetermined significance (MGUS, also known as benign paraproteinaemia and monoclonal gammopathy) is a common condition that causes a paraproteinaemia and is often mistaken for myeloma. Differentiating features are listed below. Around 10% of patients eventually develop myeloma at 10 years, with 50% at 15 years
Is MGUS symptomatic? IS there bone pain? is there a risk of infection? what can this cause in some patients?
Features
usually asymptomatic no bone pain or increased risk of infections around 10-30% of patients have a demyelinating neuropathy
Differentiating features MGUS from myeloma
-immune function
-beta 2 microglobulin levels
-paraproteinaemia levels
-clinical features
Differentiating features from myeloma
normal immune function normal beta-2 microglobulin levels lower level of paraproteinaemia than myeloma (e.g. < 30g/l IgG, or < 20g/l IgA) stable level of paraproteinaemia no clinical features of myeloma (e.g. lytic lesions on x-rays or renal disease)
What is waldenstom’s macrogloulinaemia?
-who is this seen in?
Waldenstrom’s macroglobulinaemia is an uncommon condition seen in older men. It is a lymphoplasmacytoid malignancy characterised by the secretion of a monoclonal IgM paraprotein
What are the 5 clinical features of macroglobulinaemia?
Features
systemic upset: weight loss, lethargy
hyperviscosity syndrome e.g. visual disturbance
the pentameric configuration of IgM increases serum viscosity
hepatosplenomegaly
lymphadenopathy
cryoglobulinaemia e.g. Raynaud’s
what are the investigations for macroglobulinaemia?
Investigations
monoclonal IgM paraproteinaemia
bone marrow biopsy is diagnostic
infiltration of the bone marrow with lymphoplasmacytoid lymphoma cells
What is the management of macroglobulinaemia?
Management
typically rituximab-based combination chemotherapy
What is seen on:
-FBC
-Ferritin
-TIBC
-Transferrin
In iron deficiency anaemia
Full blood count (FBC) demonstrates hypochromic microcytic anaemia
Serum ferritin this will likely be low, as serum ferritin correlates with iron stores. However, it is important to recognise that ferritin can be raised during states of inflammation; so a raised ferritin does not necessarily rule out iron deficiency anaemia if the is co-occurring inflammation. For patients with co-occurring inflammatory disease, other iron studies can be performed.
Total iron-binding capacity (TIBC)/transferrin this will be high. A high TIBC reflects low iron stores. . Note that the transferrin saturation will however be low
What is seen on blood film in iron deficiency anaemi?
Blood film anisopoikilocytosis (red blood cells of different sizes and shapes) , target cells, ‘pencil’ poikilocytes
Who warrants endoscopy for iron deficiency anaemia
Endoscopy to rule out malignancy, males and post-menopausal females who present with unexplained iron-deficiency anaemia should be considered for further gastrointestinal investigations. Post-menopausal women with a haemoglobin level ≤10 and men with a haemoglobin level ≤11 should be referred to a gastroenterologist within 2 weeks.
How can you divide up macrocytic anaemia?
Macrocytic anaemia can be divided into causes associated with a megaloblastic bone marrow and those with a normoblastic bone marrow
What are megaloblastic causes of macrocytic anaemia? 2
Megaloblastic causes of macrocytic anaemia
vitamin B12 deficiency folate deficiency e.g. secondary to methotrexate
What are normoblastic causes of macrocytic anaemia? 7
Normoblastic causes of macrocytic anaemia
alcohol liver disease hypothyroidism pregnancy reticulocytosis myelodysplasia drugs: cytotoxics
What are 5 causes of vit b12 deficiency?
Causes of vitamin B12 deficiency
pernicious anaemia: most common cause
post gastrectomy
vegan diet or a poor diet
disorders/surgery of terminal ileum (site of absorption)
Crohn's: either diease activity or following ileocaecal resection
metformin (rare)
What are four features of B12 deficiency?
Features of vitamin B12 deficiency
macrocytic anaemia
sore tongue and mouth
neurological symptoms
the dorsal column is usually affected first (joint position, vibration) prior to distal paraesthesia
neuropsychiatric symptoms: e.g. mood disturbances
What is the management of B12 deficiency?
Management
if no neurological involvement 1 mg of IM hydroxocobalamin 3 times each week for 2 weeks, then once every 3 months if a patient is also deficient in folic acid then it is important to treat the B12 deficiency first to avoid precipitating subacute combined degeneration of the cord
What is the long term management of sickle cell anaemia? do they receive vaccines?
hydroxyurea
increases the HbF levels and is used in the prophylactic management of sickle cell anaemia to prevent painful episodes
NICE CKS suggest that sickle cell patients should receive the pneumococcal polysaccharide vaccine every 5 years
What are the 4 types of sickle cell crisis?
A number of types of crises are recognised:
thrombotic, ‘vaso-occlusive’, ‘painful crises’
acute chest syndrome
anaemic
aplastic
sequestration
infection
What is sickle cell thrombotic crisis? what are they precipitated by? how is this diagnosed?
Thrombotic crises
also known as painful crises or vaso-occlusive crises precipitated by infection, dehydration, deoxygenation (e.g. high altitude) painful vaso-occlusive crises should be diagnosed clinically - there isn't one test that can confirm them although tests may be done to exclude other complications infarcts occur in various organs including the bones (e.g. avascular necrosis of hip, hand-foot syndrome in children, lungs, spleen and brain
what is sickle cell acute chest syndrome?
-what is this cause by?
-What clinical features exist?
Acute chest syndrome
vaso-occlusion within the pulmonary microvasculature → infarction in the lung parenchyma
dyspnoea, chest pain, pulmonary infiltrates on chest x-ray, low pO2
What is the management of sickle cell crisis acute chest syndrome? is this common?
management
pain relief
respiratory support e.g. oxygen therapy
antibiotics: infection may precipitate acute chest syndrome and the clinical findings (respiratory symptoms with pulmonary infiltrates) can be difficult to distinguish from pneumonia
transfusion: improves oxygenation
the most common cause of death after childhood
What is sickle cell aplastic crisis caused by? what is seen on blood tests?
Aplastic crises
caused by infection with parvovirus sudden fall in haemoglobin bone marrow suppression causes a reduced reticulocyte count
