Haematology Flashcards
What is the most common inherited bleeding disorder?
Von Willebrand’s disease
Inheritance of Von Willebrand disease?
Type 1 (80%) is autosomal dominant
Type 3 is autosomal recessive
What does von Willebrand do?
Promotes platelet adhesion to damaged epithelium
Binds to factor VIII to prevent its clearance
Presentation of von Willebrand’s disease?
Mucosal bleeding - epistaxis, menorrhagia
Investigations for von Willebrand’s disease
Prolonged bleeding time
APTT may be prolonged
Factor VIII moderately reduced
Defective platelet aggregation with ristocetin
Management of von Willebrand’s disease
Tranexamic acid
Desmopressin
Factor VIII concentrate
How does desmopressin help in von Willebrand’s disease?
Increases levels of vWF by inducing vWF release from Weibel-Palade bodies in endothelial cells
Types of von Willebrand’s disease
Type 1: partial reduction in vWF
Type 2: abnormal form of vWF
Type 3: total lack of vWF
What should you consider if enlarged lymph nodes + itch?
Lymphoma
What is Hodgekin’s Lymphoma?
Malignant proliferation of lymphocytes characterised by presence of Reed Sternberg cells
In which condition do you see Reed Sternberg cells?
Hodgekin’s lymphoma
Risk factors for Hodgekin’s lymphoma
EBV
HIV
Immunosuppression
Smoking
Features of Hodgekin’s lymphoma
Lymphadenopathy - painless, tender, asymmetrical Fever, weight loss, night sweats Pruritis Alcohol induced lymph node pain Mediastinal mass
What should alcohol induced lymph node pain make you think of?
Hodgekin’s lymphoma
Hodgekin’s lymphoma - blood results findings and investigations
Normocytic anaemia, eosinophilia Raised LDH Raised ESR HIV testing LN biopsy CXR
Management of Hodgekin’s lymphoma
Chemo + radio
If relapse then high dose chemo + autologous stem cell transplant
Prognosis for Hodgekin’s lymphoma
80-90% achieve remission
What is the staging system for Hodgekin’s lymphoma called?
Ann Arbour
Name three direct oral anticoagulants
Dabigatran
Rivaroxaban
Apixaban
How does dabigatran work?
Direct thrombin inhibitor
How does rivaroxaban work?
Direct factor Xa inhibitor
How does apixaban work?
Direct factor Xa inhibitor
Reversal agent for dabigatran
Indarucizumab
Reversal agent for rivaroxaban and apixaban
Andexanet alfa
Indications for direct oral anticoagulants
Prevention of VTE in hip/knee surgery
Treatment of DVT/PE
Preventing stroke in non-valvular AF
What is the most common form of leukaemia in adults?
Chronic lymphocytic leukaemia
What is chronic lymphocytic leukaemia?
Monoclonal proliferation of well differentiated lymphocytes
almost always B cells
Features of CLL
Often asymptomatic Reduced appetite, weight loss Bleeding Infections Lymphadenopathy Splenomegaly, hepatomegaly
Investigations for CLL
Anaemia Lymphocytosis Peripheral blood film - smear cells Increased LDH BM biopsy
Which chromosomal abnormality is associated with CLL?
Philadelphia chromosome
Due to BCR ABL mutation
Management of CLL
Tyrosine kinase inhibitor - imatinib
Bone marrow transplant
Stages of CLL
1) Chronic
2) Accelerated stage
3) Blastic crisis - quickly fatal
Complications of CLL
Anaemia
Hypogammaglobulinaemia
Warm autoimmune haemolytic anaemia
Transformation to high grade lymphoma (Richter’s transformation)
What is Richter’s transformation?
When CLL transforms due to high grade lymphoma
Excretion of riveroxaban
Liver
Excretion of apixaban
Faeces
Excretion of dabigatran
Renal
Drug causes of pancytopenia
Cytotoxics Trimethoprim, chloramphenicol Anti-rheumatoid: gold, penicillamine Carbimazole Carbamazepine Tolbutamide
Treatment when a patient is both B12 deficient and folate deficient
B12 replacement
Start oral folic acid when B12 levels normal
Macrocytic anaemia - megaloblastic causes
Vit B12 deficiency
Folate deficiency
Macrocytic anaemia - normoblastic causes
Alcohol Liver disease Hypothyroidism Pregnancy Reticulocytosis Myelodysplasia Cytotoxics
What is antiphospholipid syndrome?
Autoimmune disorder characterised by
1) Arterial and venous thromboembolism
2) Recurrent pregnancy loss
3) Thrombocytopenia
Investigations in antiphospholipid disorder
Raised aPL antibodies
Thrombocytopenia
Who should be screened for antiphospholipid disorder?
Stroke <50 years
3 or more miscarriages before 10 weeks
Conditions associated with antiphospholipid disorder
SLE
Management of antiphospholipid disorder
Low dose aspirin once positive urinary test
LMWH once fetal heart beat on ultrasound (till 34 weeks)
Pregnancy complications in antiphospholipid disorder
Recurrent miscarriage IUGR Pre-eclampsia Placental abruption Preterm delivery Venous VTE
Who should get prophylaxis for neutropenic sepsis?
Patients anticipated to have neutrophil count <0.5
What is the prophylaxis for neutropenic sepsis?
fluoroquinolone
Empirical antibiotics for neutropenic sepsis
Tazocin (piperacillin with tazobactam)
At what time does neutropenic sepsis typically occur?
7-14 days after chemotherapy
Inheritance of sick cell haemoglobin
Autosomal recessive
When does sickle cell disease present?
Age 3 to 6 months after drop in HbF
Presentation of sickle cell disease
Anaemia Pallor Jaundice FTT Increased infections Splenomegaly
Types of sickle cell crises
Thrombotic Sequestration Acute chest syndrome Aplastic crises Haemolytic crises
Sickle cell disease - thrombotic crises
Painful/vasoocclusive
Clinical diagnosis
Can infarct organs and bones
What triggers a thrombotic crisis in sickle cell disease?
Infection
Dehydration
Deoxygenation
Sickle cell disease - sequestration
Sickling in organs causes pooling of blood and worsening anaemia
Raised reticulocyte count
Sickle cell disease - what happens to the reticulocyte in sequestration crises?
Increases
Sickle cell disease - acute chest syndrome
Dyspnoea
Chest pain
Pulmonary infiltrates
Reduced pO2
Sickle cell disease - aplastic crisis
Sudden drop in Hb
Due to parvovirus
Reduced reticulocyte due to bone marrow suppression
What triggers aplastic crisis in sickle cell disease?
Parvovirus
Sickle cell disease - what happens to the reticulocyte count in aplastic crisis?
Reduces due to bone marrow suppression
Sickle cell disease - haemolytic crisis
Fall in Hb due to increased haemolysis
Sickle cell disease - management of crises
Analgesia Fluids Oxygen Antibiotics if infection Blood transfusion Exchange infusion if neurological symptoms
Long term management of sickle cell disease
Hydroxyurea
Pneumococcal vaccine 5 yearly
What are Heinz bodies?
Clumps of damaged haemoglobin attached to red cells
Inheritance of G6PD deficiency
X linked recessive
Features of G6PD deficiency
Asymptomatic in most Neonatal jaundice Intravascular haemolysis Gallstones Splenomegaly Back/abdo pain
Investigations for G6PD deficiency
Blood film - heinz bodies
G6PD enzyme assay
Raised reticulocyte count
When should you do the G6PD enzyme assay?
3 months after acute haemolysis to avoid false negative
G6PD deficiency - what is the reticulocyte count?
Raised
G6PD deficiency - what are the precipitants of crises?
Infections Broad (fava) beans Antimalarials - primaquine Ciprofloxacin Sulph-group drugs: sulphonamides, sulphasalazine, sulpfonylurea
What is myeloma?
Neoplasm of the bone marrow plasma cells
Features of myeloma
Bone pain, osteoporosis, pathological #, osteolytic lesions
lethargy
Infection
Hypercalcaemia
Amyloidosis = cardiac failure, nephrotic syndrome
Investigations to diagnosis myeloma
Anaemia, leukopenia, thrombocytopenia Raised calcium Impaired renal function Serum protein electrophoresis Urine electrophoresis for Bence Jones protein IgG, IgA, IgM levels
Investigations to be done once myeloma is diagnosed
Bone marrow aspirate
Skeletal survey with whole body MRI
Treatment of myeloma in young patients
Autologous stem cell transplant
What is ITP?
Immune mediated reduction in platelets
What course does ITP take in adults?
Chronic
Presentation of ITP in adults
Incidental finding on routine bloods
Petechia, purpura
Bleeding e.g. epistaxis
Management of ITP in adults
Oral prednisolone
IVIg
Splenectomy
What is Evan’s syndrome?
ITP in association with autoimmune haemolytic anaemia
Investigations for autoimmune haemolytic anaemia
Direct antiglobulin test (Coombs) - positive
Antibody responsible in Warm AIHA
IgG
Causes of Warm AIHA
Autoimmune e.g. SLE
Lymphoma
CLL
Drugs e.g. methyldopa
Where does haemolysis take place in Warm AIHA?
Body temperature, haemolysis occurs in extravascular sites such as the spleen
Management of Warm AIHA
Steroids
Immunosuppression
Splenectomy
Antibody responsible in Cold AIHA
IgM
Causes of Cold AIHA
Lymphoma
Infection - mycoplasma, EBV
Where does haemolysis take place in Cold AIHA?
At 4 degrees
Occurs in extremities so is generally intravascular