Haem/Onc Flashcards
causes of neutropenia
viral HIV Epstein-Barr virus hepatitis drugs cytotoxics carbimazole clozapine benign ethnic neutropaenia common in people of black African and Afro-Caribbean ethnicity requires no treatment haematological malignancy myelodysplastic malignancies aplastic anemia rheumatological conditions systemic lupus erythematosus: mechanisms include circulating antineutrophil antibodies rheumatoid arthritis: e.g. hypersplenism as in Felty's syndrome severe sepsis haemodialysis
indication for treatment in CLL
progressive marrow failure: the development or worsening of anaemia and/or thrombocytopenia
massive (>10 cm) or progressive lymphadenopathy
massive (>6 cm) or progressive splenomegaly
progressive lymphocytosis: > 50% increase over 2 months or lymphocyte doubling time < 6 months
systemic symptoms: weight loss > 10% in previous 6 months, fever >38ºC for > 2 weeks, extreme fatigue, night sweats
autoimmune cytopaenias e.g. ITP
CLL management
patients who have no indications for treatment are monitored with regular blood counts
fludarabine, cyclophosphamide and rituximab (FCR) has now emerged as the initial treatment of choice for the majority of patients
ibrutinib may be used in patients who have failed a previous therapy
methaemoglobinaemia causes
Congenital causes
haemoglobin chain variants: HbM, HbH
NADH methaemoglobin reductase deficiency
Acquired causes
drugs: sulphonamides, nitrates (including recreational nitrates e.g. amyl nitrite ‘poppers’), dapsone, sodium nitroprusside, primaquine
chemicals: aniline dyes
methaemoglobinuria management
NADH - methaemoglobinaemia reductase deficiency: ascorbic acid
IV methylthioninium chloride (methylene blue) if acquired
most common cause of thrombophilia
factor V Leiden (activated protein C resistance)
prothrombin gene mutation (second most cause)
deficiencies of naturally occuring anticoagulants
antithrombin III deficiency
protein C deficiency
protein S deficiency
examples of sickle cell crisis
thrombotic, 'painful crises' sequestration acute chest syndrome aplastic haemolytic
what is thrombotic crisis?
also known as painful crises or vaso-occlusive crises
precipitated by infection, dehydration, deoxygenation
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 sequestration crisis?
sickling within organs such as the spleen or lungs causes pooling of blood with worsening of the anaemia
what is acute chest syndrome?
dyspnoea, chest pain, pulmonary infiltrates, low pO2
the most common cause of death after childhood
what is aplastic crisis?
caused by infection with parvovirus
sudden fall in haemoglobin
what is haemolytic crisis?
rare
fall in haemoglobin due an increased rate of haemolysis
CLL 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
CLL pathophysiology
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.
CLL investigations
full blood count:
lymphocytosis
anaemia
blood film: smudge cells (also known as smear cells)
immunophenotyping is the key investigation
ITP management
Emergency treatment: life-threatening or organ threatening bleeding Platelet transfusion, IV methylprednisolone and intravenous immunoglobulin
Platelet count >30*109/L Observation
Platelet count <30*109/L Oral prednisolone
ITP pathophysiology
Antibodies are directed against the glycoprotein IIb/IIIa or Ib-V-IX complex.
Children with ITP usually have an acute thrombocytopenia that may follow infection or vaccination. In contract, adults tend to have a more chronic condition.
ITP presentation
may be detected incidentally following routine bloods
symptomatic patients may present with
petichae, purpura
bleeding (e.g. epistaxis)
catastrophic bleeding (e.g. intracranial) is not a common presentation
what is Evan’s syndrome>
ITP in association with autoimmune haemolytic anaemia (AIHA)
paroxysmal nocturnal haemoglobinuria pathophysiology
an acquired disorder leading to haemolysis (mainly intravascular) of haematological cells. It is thought to be caused by increased sensitivity of cell membranes to complement (see below) due to a lack of glycoprotein glycosyl-phosphatidylinositol (GPI). Patients are more prone to venous thrombosis
Pathophysiology
GPI can be thought of as an anchor which attaches surface proteins to the cell membrane
complement-regulating surface proteins, e.g. decay-accelerating factor (DAF), are not properly bound to the cell membrane due a lack of GPI
thrombosis is thought to be caused by a lack of CD59 on platelet membranes predisposing to platelet aggregation
paroxysmal nocturnal haemoglobinuria features
haemolytic anaemia
red blood cells, white blood cells, platelets or stem cells may be affected therefore pancytopaenia may be present
haemoglobinuria: classically dark-coloured urine in the morning (although has been shown to occur throughout the day)
thrombosis e.g. Budd-Chiari syndrome
aplastic anaemia may develop in some patients
paroxysmal nocturnal haemoglobinuria diagnosis
flow cytometry of blood to detect low levels of CD59 and CD55 has now replaced Ham’s test as the gold standard investigation in PNH
Ham’s test: acid-induced haemolysis (normal red cells would not)
paroxysmal nocturnal haemoglobinuria management
blood product replacement
anticoagulation
eculizumab, a monoclonal antibody directed against terminal protein C5, is currently being trialled and is showing promise in reducing intravascular haemolysis
stem cell transplantation