Haematology Flashcards
Allergy tests
Skin prick test
Most commonly used test as easy to perform and inexpensive. Drops of diluted allergen are placed on the skin after which the skin is pierced using a needle. A large number of allergens can be tested in one session. Normally includes a histamine (positive) and sterile water (negative) control. A wheal will typically develop if a patient has an allergy. Can be interpreted after 15 minutes
Useful for food allergies and also pollen
Radioallergosorbent test (RAST)
Determines the amount of IgE that reacts specifically with suspected or known allergens, for example IgE to egg protein. Results are given in grades from 0 (negative) to 6 (strongly positive)
Useful for food allergies, inhaled allergens (e.g. Pollen) and wasp/bee venom
Blood tests may be used when skin prick tests are not suitable, for example if there is extensive eczema or if the patient is taking antihistamines
Skin patch testing
Useful for contact dermatitis. Around 30-40 allergens are placed on the back. Irritants may also be tested for. The patches are removed 48 hours later with the results being read by a dermatologist after a further 48 hours
Chronic lymphocytic leukaemia
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.
Features
often none
constitutional: anorexia, weight loss
bleeding, infections
lymphadenopathy more marked than CML
Complications
anaemia
hypogammaglobulinaemia leading to recurrent infections
warm autoimmune haemolytic anaemia in 10-15% of patients
transformation to high-grade lymphoma (Richter’s transformation)
Investigations
blood film: smudge cells (also known as smear cells)
immunophenotyping
Chronic myeloid leukaemia
The causes of massive splenomegaly are as follows:
myelofibrosis, chronic myeloid leukaemia, visceral leishmaniasis (kala-azar), malaria, Gaucher’s syndrome
This narrows the diagnostic possibilities considerably leaving chronic myeloid leukaemia as the most likely diagnosis.
The Philadelphia chromosome is present in more than 95% of patients with chronic myeloid leukaemia (CML). It is due to a translocation between the long arm of chromosome 9 and 22 - t(9:22)(q34; q11). This results in part of the ABL proto-oncogene from chromosome 9 being fused with the BCR gene from chromosome 22. The resulting BCR-ABL gene codes for a fusion protein which has tyrosine kinase activity in excess of normal
Presentation (60-70 years)
anaemia: lethargy
weight loss and sweating are common
splenomegaly may be marked → abdo discomfort
an increase in granulocytes at different stages of maturation +/- thrombocytosis
decreased leukocyte alkaline phosphatase
may undergo blast transformation (AML in 80%, ALL in 20%)
Management
imatinib is now considered first-line treatment
hydroxyurea
interferon-alpha
allogenic bone marrow transplant
Imatinib
inhibitor of the tyrosine kinase associated with the BCR-ABL defect
very high response rate in chronic phase CML
DVT
Deep vein thrombosis: diagnosis and management
Diagnosis
NICE published guidelines in 2012 relating to the investigation and management of deep vein thrombosis (DVT).
If a patient is suspected of having a DVT a two-level DVT Wells score should be performed:
Clinical probability simplified score
DVT likely: 2 points or more
DVT unlikely: 1 point or less
If a DVT is ‘likely’ (2 points or more)
a proximal leg vein ultrasound scan should be carried out within 4 hours and, if the result is negative, a D-dimer test
if a proximal leg vein ultrasound scan cannot be carried out within 4 hours a D-dimer test should be performed and low-molecular weight heparin administered whilst waiting for the proximal leg vein ultrasound scan (which should be performed within 24 hours)
If a DVT is ‘unlikely’ (1 point or less) perform a D-dimer test and if it is positive arrange:
a proximal leg vein ultrasound scan within 4 hours
if a proximal leg vein ultrasound scan cannot be carried out within 4 hours low-molecular weight heparin should be administered whilst waiting for the proximal leg vein ultrasound scan (which should be performed within 24 hours)
Management
Low molecular weight heparin (LMWH) or fondaparinux should be given initially after a DVT is diagnosed.
A vitamin K antagonist (i.e. warfarin) should be given within 24 hours of the diagnosis the LMWH or fondaparinux should be continued for at least 5 days or until the international normalised ratio (INR) is 2.0 or above for at least 24 hours, whichever is longer, i.e. LMWH or fondaparinux is given at the same time as warfarin until the INR is in the therapeutic range
warfarin should be continued for at least 3 months. At 3 months, NICE advise that clinicians should ‘assess the risks and benefits of extending treatment’
NICE add ‘consider extending warfarin beyond 3 months for patients with unprovoked proximal DVT if their risk of VTE recurrence is high and there is no additional risk of major bleeding’. This essentially means that if there was no obvious cause or provoking factor (surgery, trauma, significant immobility) it may imply the patient has a tendency to thrombosis and should be given treatment longer than the norm of 3 months. In practice most clinicians give 6 months of warfarin for patients with an unprovoked DVT/PE for patients with active cancer NICE recommend using LMWH for 6 months
Haemophilia
A 17-year-old man is investigated after he bled excessively following a tooth extraction.
Plt173 * 109/l, PT 12.9 secs, APTT 84 secs
Haemophilia is a 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
Up to 10-15% of patients with haemophilia A develop antibodies to factor VIII treatment.
Hereditary spherocytosis
Basics
most common hereditary haemolytic anaemia in people of northern European descent
autosomal dominant defect of red blood cell cytoskeleton
the normal biconcave disc shape is replaced by a sphere-shaped red blood cell
red blood cell survival reduced as destroyed by the spleen
Presentation
failure to thrive
jaundice, gallstones
splenomegaly
aplastic crisis precipitated by parvovirus infection
degree of haemolysis variable
MCHC elevated
Diagnosis
the osmotic fragility test was previously the recommend investigation of choice. However, it is now deemed unreliable and is no longer recommended
the British Journal of Haematology (BJH) guidelines state that ‘patients with a family history of HS, typical clinical features and laboratory investigations (spherocytes, raised mean corpuscular haemoglobin concentration[MCHC], increase in reticulocytes) do not require any additional tests
if the diagnosis is equivocal the BJH recommend the cryohaemolysis test and EMA binding
for atypical presentations electrophoresis analysis of erythrocyte membranes is the method of choice
Management
folate replacement
splenectomy
Immune thrombocytopenia (ITP) in adults
A 34-year-old female presents due to the development of a purpuric rash on the back of her legs. Her only regular medication is Microgynon 30. She also reports frequent nose bleeds and menorrhagia. A full blood count is requested:
Hb11.7 g/dl, Platelets 62 * 109/l, WCC 5.3 * 109/l
Immune (or idiopathic) thrombocytopenic purpura (ITP) is an immune-mediated reduction in the platelet count. Antibodies are directed against the glycoprotein IIb/IIIa or Ib-V-IX complex.
ITP can be divided into acute and chronic forms:
Acute ITP
more commonly seen in children
equal sex incidence
may follow an infection or vaccination
usually runs a self-limiting course over 1-2 weeks
Chronic ITP
more common in young/middle-aged women
tends to run a relapsing-remitting course
Evan’s syndrome
ITP in association with autoimmune haemolytic anaemia (AIHA)
Vitamin B12 deficiency
Mr Brown is a 54-year-old man a new diagnosis of anaemia. He has no relevant past medical history. His haematinics values are as follows:
Reference Range Iron 10 g/l, Folate 2.1, Vitamin B12 150 ng/l
Vitamin B12 is mainly used in the body for red blood cell development and also maintenance of the nervous system. 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.
Causes of vitamin B12 deficiency
pernicious anaemia: most common cause
post gastrectomy
vegan diet or a poor diet
disorders of terminal ileum (site of absorption): Crohn’s, blind-loop etc
metformin (rare)
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
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
Von Willebrand’s disease
A 17-year-old man is investigated after he bled excessively following a tooth extraction. The following results are obtained:
Plt, 173 * 109/l, PT 12.9 secs, APTT 84 secs
Von Willebrand’s disease is the most common inherited bleeding disorder. The majority of cases are inherited in an autosomal dominant fashion* and characteristically behaves like a platelet disorder i.e. epistaxis and menorrhagia are common whilst haemoarthroses and muscle haematomas are rare
Role of von Willebrand factor
large glycoprotein which forms massive multimers up to 1,000,000 Da in size
promotes platelet adhesion to damaged endothelium
carrier molecule for factor VIII
Types
type 1: partial reduction in vWF (80% of patients)
type 2*: abnormal form of vWF
type 3**: total lack of vWF (autosomal recessive)
Investigation
prolonged bleeding time
APTT may be prolonged
factor VIII levels may be moderately reduced
defective platelet aggregation with ristocetin
Management
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
*type 2A VWD is caused by defective platelet adhesion due to decreased high molecular weight VWF multimers (i.e. the VWF protein is too small). Type 2B is characterised by a pathological increase of VWF-platelet interaction. Type 2M is caused by a decrease in VWF-platelet interaction (not related to loss of high molecular weight multimers). Type 2N is caused by abnormal binding of the VWF to Factor VIII. There is no clear correlation between symptomatic presentation and type of VWD however common themes amongst patients include excessive mucocutaneous bleeding, bruising in the absence of trauma and menorrhagia in females.
**type 3 von Willebrand’s disease (most severe form) is inherited as an autosomal recessive trait. Around 80% of patients have type 1 disease
