Blood disorders Flashcards
What is thrombocytosis
Abnormally high platelet count usually >400*10^9/L
Causes of thrombocytosis
Reactive: platelets are an acute phase reactant- platelet count can increase in response to stress such as an severe infection, surgery
Iron deficiency anaemia can also cause a reactive thrombocytosis
Malignancy
Essential thrombocytosis or as part of another myeloproliferative disorder sch as CML or PCV
What is essential thrombocytosis
One of the myeloproliferative disorders which overlaps with chronic myeloid leukaemia, polycythaemia rubra vera and myelofirbosis.
Features of essential thrombocytosis
Features
platelet count > 600 * 109/l
both thrombosis (venous or arterial) and haemorrhage can be seen
a characteristic symptom is a burning sensation in the hands
a JAK2 mutation is found in around 50% of patients
Management of thrombocytosis
Hydroxyurea (hydoxycarbamide widely used to reduce the platelet count
Interferon- alpha is also used in younger patients
Low-dose aspirin may be used to reduce the thrombotic risk
Causes of massive splenomegaly
Myelofibrosis Chronic myeloid leukaemia Visceral leishmaniasis Malaria Gaucher's syndrome
Other causes of splenomegaly
Portal hypertension- secondary to cirrhosis
Lymphoproliferative disease- CLL, Hodgkin’s
Haemolytic anaemia
Infection - hepatitis, glandular fever
Infective endocarditis
Sickle-cell thalassemia
Rheumatoid arthritis
Hereditary spherocytosis features
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 of hereditary spherocytosis
Failure to thrive
- Jaundice, gallstones
- Splenomegaly
- Aplastic crisis precipitated by parvovirus infection
- Degree of haemolysis variable
- MCHC elevated
Diagnosis of hereditary spherocytosis
The osmotic fragility test - FIRST line
Diagnosis- equivocal - BJH recommend te EMA binding test and the cryohaemolysis test
Management
Acute haemolytic crisis- treatment is generally supportive
Transfusion if necessary
Longer term treatment
Folate replacement
Splenectomy
Beta-thalassemia trait
Group of genetic disorders charcterised by reduced production rate of either alpha or beta chains
Beta-thalassemia trait is an autosomal recessive condition characterised by a mild hypochromic, microcytic anaemia- USUALLY Asymptomatic
Features of Beta-thalassemia trait
Mild hypochromic, microcytic anaemia- microcystosis characteristically disproportionate to the anaemia
BhA2 raised- >3.5%
How does secondary polycythaemia in COPD work
Impaired oxygen exchange in the lungs - resulting in a low PaO2 which results in stimulation of EPO release from the kidneys.
EPO stimulates erythropoeises and increases red cell mass- resulting in polycythaemia.
Relative causes of polycythaemia
Dehydration
Stress: Gaisbock syndrome
Primary causes of Polycythaemia
Polycythaemia rubra vera
Secondary causes
COPD
Altitude
Obstructive sleep apnoea
Excessive erythropoeitin, cerebellar haemangioma, hypernephroma, hepatoma, uterine fibroids
Sickle-cell crises example
- Thrombotic painful crises
- Sequestration
- Acute chest syndrome
- Aplastic
- Haemolytic
Thrombotic crises features
Painful crises or vaso-occlusive crises
Precipitated by infection, dehydration, deoxygenation
Painful vaso-occlusive crises- diagnoses CLINICALLY
Sequestration crises
Sickling within organs - such as spleen or lungs causes pooling of blood with worsening of the anaemia
Acute chest syndrome features
Dyspnoea, chest pain, pulmonary infiltrates, low pO2
The most common cause of death after childhood
Aplastic crisis features
Caused by infection with pravovirus
Sudden fall in haemoglobin
Haemolytic crises features
Rare
Fall in haemoglobin due to increased rate of haemolysis
Investigation of Von Willebrand disease results
prolonged bleeding time
APTT may be prolonged
factor VIII levels may be moderately reduced
defective platelet aggregation with ristocetin
Management of Von Willebrand’s disease
Tranexamic acid for bleeding
Despmopressin (DDAVP) raises levels of vWF by inducing release of vWF from Weibel- Palade bodies in endothelial cells
Factor VIII concentrate
Why are irradiated blood products used
To avoid transfusion-associated graft versus host disease
Classical description of Reed-Sternberg cells
A blood film shows large cells with a bilobed nucleus and prominent eosinophilic inclusion-like nucleoli.
When is CMV negative packed red cells recommended
They are recommended for pregnant and neonatal transfusion
FFP use ?
Clotting studies
Features of lead poisoning
Abdominal pain Peripheral neuropathy Fatigue Constipation Blue lines on gum margin (only 20% of adults- very rare in children)
Investigations
The blood lead level is usually used for diagnosis, levels greater than 10mcg/dl are considered significant
Full blood count: microcytic anaemia. Blood films- basophilic stippling and clover-leaf morphology
Raised serum and urine levels
Management - various chelating agents are currently used
dimercaptosuccinic acid (DMSA)
D-penicillamine
EDTA
dimercaprol
Autoimmune haemolytic anaemia classification
warm and cold
AIHA Cooms test result
Positive result
Causes of warm AIHA
autoimmune disease: e.g. systemic lupus erythematosus*
neoplasia: e.g. lymphoma, CLL
drugs: e.g. methyldopa
Causes of cold AIHA
Causes of cold AIHA
neoplasia: e.g. lymphoma
infections: e.g. mycoplasma, EBV
Indications
- 1) Background a lymphoma (risk factor for cold AIHA)
- 2) Raynaud’s phenomenon
- 3) Symptoms worse in the cold
- 4) New macrocytic anaemia, the macrocytosis here is occurring due to reticulocytosis (new immature RBCs which are larger) to compensate for the haemolysis.
Which temperature does cold AIHA work at
<4 hours- IgM mediated haemolysis occurs
G6PD deficiency
Male, African and Mediterranean descent
Neonatal jaundice
Infection/drugs precipitate haemolysis
Gallstones
Heinz bodies on the blood film
Dx- measure enzyme activity of G6PD
Hereditary spherocytosis features
Male and female- autosomal dominant Northern European descent Neonatal jaundice Chronic symptoms although haemolytic crises may be precipitated by infection Gallstones Splenomegaly is common
Spherocytes- round, lack of central pallor
EMA binding
What is Richter’s transformation?
Leukaemia cells enter the lymph node and change into a high-grade, fast-growing non-Hodgkin’s lymphoma
Lymphnode swelling Fever without infection Weight loss Night sweats Nausea Abdominal pain
Route of administration of transexamic acid
Given as IV bolus slowly
MOA of transexamic acid
Synthetic derivative of lysine. Primary mode of action is an antifibrinolytic that reversibly binds to lysine receptor sites on plasminogen or plasmin.
Transexamic acid - most commonly prescribed to help treat menorrhagia
Treatment of antiphospholipid syndrome in pregnancy
Aspirin and LMWH - enoxaparin
AVOID WARFARIN in pregnancy
Which factors are affected with the administration of Heparin
Prevents activation of factors 2,9,10,11
Warfarin- which factors does it affect
Affects synthesis of factors 2,7,9,10
Which factors does DIC affect
Factors 1,2,5,8,11
Liver disease clotting factors affected
Factors 1,2,5,7,9,10,11
What is the beta- thalassemia trait?
It is an autosomal recessive condition characterised by a mild hypochromic, microcytic anaemia- usually asymptomatic
Features:- mild hypochromic, microcytic anaemia- microcytosis is characteristically disproportionate to the anaemia
HbA2 raised
Infective causes of lympadenopathy
infectious mononucleosis HIV, including seroconversion illness eczema with secondary infection rubella toxoplasmosis CMV tuberculosis roseola infantum
Neoplastic causes of lymphadenopathy
infectious mononucleosis HIV, including seroconversion illness eczema with secondary infection rubella toxoplasmosis CMV tuberculosis roseola infantum
Other causes of generalised lymphadenopathy aside from neoplastic and infective
autoimmune conditions: SLE, rheumatoid arthritis
graft versus host disease
sarcoidosis
drugs: phenytoin and to a lesser extent allopurinol, isoniazid
Contraindications to platelet transfusion
Chronic bone marrow failure
Autoimmune thrombocytopenia
Heparin-induced thrombocytopenia, or
Thrombotic thrombocytopenic purpura.
Isolated thrombocytopenia on blood test leads to diagnosis of what in a middle aged woman with frequent menorrhagia and frequent nose-bleed
Idiopathic (immune) mediated thrombocytopenia
Antibodies are directed against the glycoprotein IIb/IIIa or Ib-V-IX complex.
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
Management of IP
first-line treatment for ITP is oral prednisolone
pooled normal human immunoglobulin (IVIG) may also be used
splenectomy is now less commonly used
Components of cryoprecipitate
Factor VII, Fibrinogen, von Willebrand factor, Factor XIII
Which combination of platelets and Fibrin degradation products make DIC most likely
Low platelets and raised FDP
Drugs thought to cause haemolysis
anti-malarials: primaquine
ciprofloxacin
sulph- group drugs: sulphonamides, sulphasalazine, sulfonylureas
