Haematology 3 Flashcards
Features of spinal cord compression?
back pain
the earliest and most common symptom
may be worse on lying down and coughing
lower limb weakness
sensory changes: sensory loss and numbness
neurological signs depend on the level of the lesion. Lesions above L1 usually result in upper motor neuron signs in the legs and a sensory level. Lesions below L1 usually cause lower motor neuron signs in the legs and perianal numbness. Tendon reflexes tend to be increased below the level of the lesion and absent at the level of the lesion
Investigations for spinal cord compression?
Urgent MRI
Management of spinal cord compression?
high-dose oral dexamethasone
urgent oncological assessment for consideration of radiotherapy or surgery
Where is vitamin B12 absorbed?
It is absorbed after binding to intrinsic factor (secreted from parietal cells in the stomach) and is actively absorbed in the terminal ileum. A small amount of vitamin B12 is passively absorbed without being bound to intrinsic factor.
What is haemophilia?
Haemophilia is an X-linked recessive disorder of coagulation. Up to 30% of patients have no family history of the condition. Haemophilia A is due to a deficiency of factor VIII whilst in haemophilia B (Christmas disease) there is a lack of factor IX
Features
haemoarthroses
haematomas
prolonged bleeding after surgery or trauma
Blood tests
prolonged APTT
bleeding time, thrombin time, prothrombin time normal
What electroylte disturbance is cisplatin most associated with?
Hypomagnesaemia
What are the different forms of allergy testing?
What are the histological classification of Hodgkin’s lymphoma?
Hodgkin’s lymphoma is a malignant proliferation of lymphocytes characterised by the presence of the Reed-Sternberg cell.
What symptoms are associarted with poor prognosis in Hodgkin’s lymphoma?
‘B’ symptoms also imply a poor prognosis
weight loss > 10% in last 6 months
fever > 38ºC
night sweats
Other factors associated with a poor prognosis identified in a 1998 NEJM paper included:
age > 45 years
stage IV disease
haemoglobin < 10.5 g/dl
lymphocyte count < 600/µl or < 8%
male
albumin < 40 g/l
white blood count > 15,000/µl
What is multiple 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 multiple myeloma?
**CRABBI **
Calcium - hypercalcaemia
Renal dysfunction
Anaemia
Bleeding
Bone pain
Infection
Other features include
amyloidosis e.g. macroglossia
carpal tunnel syndrome
neuropathy
hyperviscosity
causes of hypercalcaemia in multiple myeloma?
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
What causes renal dysfunction in multiple myeloma?
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
Causes of anaemia and bleeding in multiple myeloma?
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
Causes of bone pain in multiple myeloma?
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
Causes of increased risk of infection in multiple myeloma?
a reduction in the production of normal immunoglobulins results in increased susceptibility to infection
Investigations for multiple myeloma?
full blood count: anaemia
peripheral blood film: rouleaux formation
urea and electrolytes: renal failure
bone profile: hypercalcaemia
Protein electrophoresis
raised concentrations of monoclonal IgA/IgG proteins will be present in the serum
in the urine, they are known as Bence Jones proteins
Bone marrow aspiration
confirms the diagnosis if the number of plasma cells is significantly raised
Imaging
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’
Diagnostic criteria in multiple 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.
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
Minor criteria
10% to 30% plasma cells in a bone marrow sample.
Minor elevations in the level of M protein in the blood or urine.
Osteolytic lesions (as demonstrated on imaging studies).
Low levels of antibodies (not produced by the cancer cells) in the blood.
MGUS vs smouldering multiple myeloma vs multiple myeloma?
Monoclonal Gammopathy of Uncertain Significance (MGUS):
▪︎M protein <30 g/l
▪︎BM plasma cells <10%
▪︎No CRAB features
Smoldering Multiple Myeloma:
▪︎M protein > 30 g/l
▪︎BM plasma cells 10-60%
▪︎No CRAB features
▪︎Rx: Observe + monitor
Multiple myeloma:
▪︎M protein >30g/l
▪︎BM plasma cells >10%
▪︎CRAB features
What is anastrozole ?
aromatase inhibitor
Anastrozole and letrozole are aromatase inhibitors that reduces peripheral oestrogen synthesis. This is important as aromatisation accounts for the majority of oestrogen production in postmenopausal women and therefore anastrozole is used for ER +ve breast cancer in this group.
What cytotoxic agents can cause peripheral neuropathy?
Vincristine/vinblastine
Cisplatin
What is Leucocyte alkaline phosphatase raised in?
myelofibrosis
leukaemoid reactions
polycythaemia rubra vera
infections
steroids, Cushing’s syndrome
pregnancy, oral contraceptive pill
What is Leucocyte alkaline phosphatase low in?
chronic myeloid leukaemia
pernicious anaemia
paroxysmal nocturnal haemoglobinuria
infectious mononucleosis
Pulmonary causes of eosinophillia?
Other causes
Drugs/derm
asthma
allergic bronchopulmonary aspergillosis
Churg-Strauss syndrome
Loffler’s syndrome
tropical pulmonary eosinophilia
eosinophilic pneumonia
hypereosinophilic syndrome
Other causes
drugs: sulfasalazine, nitrofurantoin
psoriasis/eczema
eosinophilic leukaemia (very rare)
Infective causes of Eosinophilia?
schistosomiasis
nematodes: Toxocara, Ascaris, Strongyloides
cestodes: Echinococcus
Pathophysiology of Hereditary angioedema?
The primary pathophysiological defect is in the complement cascade and deficiencies in factors C4 and C1-esterase inhibitor are seen in type I. In type II HAE C1-esterase inhibitor levels are normal but the enzyme is dysfunctional and activity is low. An acquired form of HAE is described in which all complement levels are low. In type III HAE the clinical features of angioedema are present but immunological testing reveals normal levels and activity of complement factors. Ultimately, failure of C1-esterase inhibitor leads to upregulation of the rest of the complement system and membrane attack complex, but also it leads to activation of the signalling protein kallikrein which acts directly on the vascular wall to increase permeability, and it cleaves high molecular weight kininogen to release bradykinin, again a potent peripheral vasodilator giving rise to the symptoms of HAE.
HAE should be recognised as a separate entity from anaphylaxis since the clinical signs are different, as is the pathophysiology of the condition and its treatment. Anaphylaxis is an IgE mediated immune phenomenon related to a specific allergen causing massive mast cell degranulation and histamine release. HAE is driven by complement dysregulation and consequent release of the inflammatory cytokines bradykinin and kallikrein.
Since the driving mechanism is not histamine in HAE, steroids and antihistamines are of no value.
Causes of Warm vs Cold autoimmune haemolytic anaemia?
Causes of warm AIHA
idiopathic
autoimmune disease: e.g. systemic lupus erythematosus*
neoplasia
lymphoma
chronic lymphocytic leukaemia
drugs: e.g. methyldopa
Causes of cold AIHA
neoplasia: e.g. lymphoma
infections: e.g. mycoplasma, EBV
What are the three types of cryoglobulinaemia?
Three types
type I (25%):
monoclonal - IgG or IgM
associations: multiple myeloma, Waldenstrom macroglobulinaemia
type II (25%)
mixed monoclonal and polyclonal: usually with rheumatoid factor
associations: hepatitis C, rheumatoid arthritis, Sjogren’s, lymphoma
type III (50%)
polyclonal: usually with rheumatoid factor
associations: rheumatoid arthritis, Sjogren’s
Immunoglobulins which undergo reversible precipitation at 4 deg C, dissolve when warmed to 37 deg C. One-third of cases are idiopathic
What are the possible features of Cryoglovulinaemia?
Raynaud’s only seen in type I
cutaneous
vascular purpura
distal ulceration
ulceration
arthralgia
renal involvement
diffuse glomerulonephritis
Investigations and management of cryoglobulinaemia?
Investigations
low complement (esp. C4)
high ESR
Management
treatment of underlying condition e.g. hepatitis C
immunosuppression
plasmapheresis
What is the best screening tool for hereditary angioedema?
Serum C4
What is likely to be seen on blood gas in Acquired methaemoglobinaemia ?
Normal pO2 but decreased oxygen saturation is characteristic of methaemoglobinaemia
In methaemoglobinaemia, the haemoglobin has been oxidised from Fe2+ to Fe3+. There is tissue hypoxia as Fe3+ cannot bind oxygen. Hence saturations are low. The ability for oxygen to dissolve in the plasma is unaffected so remains normal.
Features of SVC obsruction?
dyspnoea is the most common symptom
swelling of the face, neck and arms - conjunctival and periorbital oedema may be seen
headache: often worse in the mornings
visual disturbance
pulseless jugular venous distension
Causes of SVC obsrtuction?
common malignancies: small cell lung cancer, lymphoma
other malignancies: metastatic seminoma, Kaposi’s sarcoma, breast cancer
aortic aneurysm
mediastinal fibrosis
goitre
SVC thrombosis
Management of SVC obstruction?
Management is dependant on the individual patient and malignancy and advice should be taken from the oncology team. Options include:
endovascular stenting is often the treatment of choice to provide symptom relief
certain malignancies such as lymphoma, small cell lung cancer may benefit from radical chemotherapy or chemo-radiotherapy rather than stenting
the evidence base supporting the use of glucocorticoids is weak but they are often given
Isolated thrombocytopenia in an otherwise well patient?
immune thrombocytopaenic purpura (ITP) - often presenting as isolated thrombocytopaenia in an otherwise well patient.
1st line management for ITP?
oral pred
Why is Haptoglobin low in haemolysis?
Haptoglobin levels are reduced in intravascular haemolysis because they bind to free haemoglobin released from lysed erythrocytes. The complexes are then removed from the plasma by the hepatic reticulo-endothelial cells. Haptoglobin levels decrease if the rate of haemolysis is greater than the rate of haptoglobin production.
Management of Antiphospholipid syndrome in pregnancy?
low-dose aspirin should be commenced once the pregnancy is confirmed on urine testing
low molecular weight heparin once a fetal heart is seen on ultrasound. This is usually discontinued at 34 weeks gestation
these interventions increase the live birth rate seven-fold
complications of antiphospholipid syndrome in pregnancy?
recurrent miscarriage
IUGR
pre-eclampsia
placental abruption
pre-term delivery
venous thromboembolism
