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
Features of Cold AIHA
Raynaulds
Acrocyanosis
What should a Heinz body make you think of?
G6PD deficiency
What is aplastic anaemia?
Pancytopenia due to bone marrow failure
Features of aplastic anaemia
Anaemia = fatigue, pallor
Thrombocytopenia = mucosal bleeding, petechiae
Leukopenia = recurrent infection
Investigation results for aplastic anaemia
Low RBC, low PLT, low WCC
Raised Epo
Bone marrow biopsy = dry tap
Causes of aplastic anaemia
Idiopathic Congenital - most often Fanconi syndrome Infections Toxins Drugs
What is the most common congenital cause of aplastic anaemia?
Fanconi syndrome
What infections cause aplastic anaemia?
EBV
Hepatitis
Parvovirus
HIV
What toxins cause aplastic anaemia?
Radiation
Benzene
What drugs cause aplastic anaemia?
Cytotoxics Sulfonamides Chloramphenicol Phenytoin Gold
Management of aplastic anaemia
Haemopoietic stem cell transplant
Immunosuppression
Blood and PLT transfusions
Where is vitamin B12 absorbed?
terminal ileum once bound to intrinsic factor
Where is intrinsic factor released?
Parietal cells in the stomach
Causes of B12 deficiency
Pernicious anaemia
Post gastrectomy
Vegan diet, poor diet
Disorders of terminal ileum e.g. crohns
Features of B12 deficiency
Anaemia features Paraesthesia, numbness Cognitive changes Mood disturbance Glossitis Oral ulceration
B12 deficiency investigations
Macrocytic anaemia
Intrinsic factor antibody
Management of B12 deficiency
1mg IM hydroxocobalamin 3x a week for 2 weeks, then once every 3 months
Why is it important to replace B12 before replacing folate?
To avoid subacute combined degeneration of the cord
What is pernicious anaemia?
Autoimmune disorder affecting the gastric mucosa causing B12 deficiency
Pathophysiology of pernicious anaemia
Intrinsic factor antibodies - block vit B12 binding site
Gastric parietal cell antibodies - cause atrophic gastritis to reduce intrinsic factor production
Features of pernicious anaemia
Anaemia = lethargy, pallor, dyspnoea Peripheral neuropathy Subacute combined degeneration of the cord Memory loss Confusion Irritable
What are the symptoms of subacute combined degeneration of the cord?
progressive weakness, ataxia and paresthesias that may progress to spasticity and paraplegia
Investigation results for pernicious anaemia
Macrocytic anaemia Hypersegmented polymorphs on blood film Vit B12 and folate deficiency Anti intrinsic factor antibodies Anti gastric parietal cell antibodies
Risk factors for pernicious anaemia
Female
Middle/old age
Blood group A
Other autoimmune disorders
Management of pernicious anaemia
Vit B12 replacement
May also need folate replacement
Inheritance of haemophilia
X-linked recessive
Clotting factor affected in haemophilia A
Factor VIII
Clotting factor affected in haemophilia B
Factor IX
Factor VIII deficiency?
haemophilia A
Factor IX deficiency?
Haemophilia B
Which is the most common haemophilia?
A
Presentation of haemophilia
Excessive bleeding Haemarthrosis Haematoma Haematuria GI bleeding
Haemophilia Investigations
APTT prolonged
Normal PT, bleeding time and fibrinogen
Management of haemophilia
Prophylactic VIII in haemophilia A
Prophylactic IX in haemophilia B
What is the most common inherited thrombophilia?
Factor V leiden
What is factor V leiden?
Inherited thromophilia
Which clotting factor is damaged in factor V leiden?
Factor V
Inheritence of factor V leiden
Autosomal dominant
Factor V Leiden presentation
Thrombophilia screen after VTE or recurrent pregnancy loss
Management of factor V leiden
Anticoagulation if get a clot
If pregnant + previous VTE then LMWH
What is prothrombin gene mutation?
Second most common inherited thrombophilia
What is protein S deficiency?
Inherited or acquired thrombophilia
What is protein S?
A natural anticoagulant
Inheritance of protein S deficiency
Autosomal dominant
What is protein C deficiency?
Inherited or acquired thrombophilia
What is protein C?
A natural anticoagulant
What is antithrombin III deficiency?
Inherited or acquired thrombophilia
What is antithrombin III?
A natural anticoagulant
What is hereditary spherocytosis?
Haemolytic anaemia caused by abnormal sphere shaped red blood cells
Inheritance of hereditary spherocytosis
Autosomal dominant
Presentation of hereditary spherocytosis
FTT Jaundice Gallstones Splenomegaly Aplastic crisis due to parvovirus
Investigations for hereditary spherocytosis
Raised MCHC
Raised reticulocytes
Spherocytes on blood film
Definitive investigation for hereditary spherocytosis
EMA binding test
Hereditary spherocytosis - chronic management
Folate replacement
Splenectomy
Hereditary spherocytosis - acute haemolytic crisis management
Supportive
Transfusion if necessary
What is paroxysmal nocturnal haemoglobinuria?
Acquired disorder causing haemolysis of haematological cells
Can affect RBC, WCC, PLT or stem cells
Features of paroxysmal nocturnal haemoglobinuria
Haemolytic anaemia Thrombosis Pancytopenia Haemoglobinuria - classically in the morning Aplastic anaemia
Investigations for paroxysmal nocturnal haemoglobinuria
Flow cytometry
Ham’s test - acid induced haemolysis
Treatment for paroxysmal nocturnal haemoglobinuria
Blood product replacement
Anticoagulation
Stem cell transplant
Relative causes of polycythaemia
Dehydration
Stress - Gaisbock syndrome
Causes of secondary polycythaemia
COPD
Altitude
OSA
Excessive EPO
Typical features of polycythaemia vera
Hyperviscosity
Pruritis
Splenomegaly
What is polycythaemia vera?
Myeloproliferative disorder caused by proliferation of marrow stem cells, causing increased red cell volume
Features of polycythaemia vera
Hyperviscosity Pruritis Splenomegaly Haemorrhage - due to abnormal PLT Plethoric appearance HTN
Mutation implicated in polycythaemia vera
JAK2
Investigations for polycythaemia vera
Raised haematocrit Raised neutrophils, raised basophils Raised platelets Low ESR JAK2 mutations Bone marrow biopsy if JAK2 negative
Management for polycythaemia vera
Aspirin
Venesection
Chemotherapy
Prognosis of polycythaemia vera
Thrombosis
5-15% progress to myelofibrosis
5-15% progress to acute leukaemia
What is myelofibrosis?
Bone marrow cancer
Myeloproliferative disorder where the bone marrow is replaced with scar tissue/fibrosis
What blood disorder is associated with Ashkenazi Jews?
Myelofibrosis
Which is the most common acute leukaemia in adults?
Acute myeloid leukaemia
Drugs causing pancytopenia
Cytotoxics Trimethoprim, chloramphenicol Anti-rheumatoid: gold, penicillamine Aarbimazole Carbamazepine Tolbutamide
Inheritance of Fanconi anaemia
Autosomal recessive
Features of Fanconi anaemia
Aplastic anaemia AML Short stature Thumb abnormalities Cafe au lait spots
What is Wiskott-Aldrich syndrome?
Primary immunodeficiency with B and T cell dysfunction
Genetics of Wiskott-Aldrich syndrome
X linked recessive
Mutation in the WASP gene
Features of Wiskott-Aldrich syndrome
Recurrent bacterial infections
Eczema
Thrombocytopenia
Low IgM
What is immune thrombocytopenia?
Immune mediated reduction in platelets
Immune thrombocytopenia - presentation
Incidental finding
Petechia, purpura
Bleeding
Immune thrombocytopenia - management
Oral prednisolone
IVIg
Splenectomy (rare)
What is Evan’s syndrome?
immune thrombocytopenia in association with autoimmune haemolytic anaemia
Heredtiary spherocytosis - common abdominal complication
gallstones
Which factor is deficient in haemophilia A?
VIII
Which factor is deficient in haemophilia B?
IX
Ca125 is a tumour marker for which cancers?
ovarian cancer
Ca19-9 is a tumour marker for which cancers?
pancreatic cancer
Ca15-3 is a tumour marker for which cancers?
breast cancer
AFP is a tumour marker for which cancers?
HCC
Teratoma (which is a non-seminomatous testicular cancer)
CEA is a tumour marker for which cancers?
colorectal
What drug can cause a false negative PSA?
Finasteride
What is Meig’s syndrome?
ovarian fibroma + pleural effusion + ascites
Myelofibrosis - presentation
Weight loss, night sweats, low fever
Massive splenomegaly
Myelofibrosis - investigations
Anaemia
Raised urate
Raised LDH
Tear drop shaped RBC
BM aspirate: dry tap
What is essential thrombocythaemia?
Megakaryocyte proliferation increases circulating platelets
which increases risk of thrombosis and bleeding
Essential thrombocythaemia - presentation
Burning pain and dusk discolouration of extremities
Splenomegaly
Livedo reticularis
What is haemolytic uraemic syndrome?
Triad:
1) Acute renal failure
2) Microangiopathic haemolytic anaemia
3) Thrombocytopenia
Haemolytic uraemic syndrome - causes
Dysentry Tumours Pregnancy Ciclosporin SLE HIV oral contraceptive pill
Haemolytic uraemic syndrome - typical presentation
Diffuse diarrhoea that turns bloody
may have fever, abdo pain, vomiting
Haemolytic uraemic syndrome - investigations
Low Hb Low platelets Raised LDH Fragmented blood film Acute renal failure
Haemolytic uraemic syndrome - management
IV fluids
Dialysis
Acute lymphoblastic leukaemia - presentation
Fever Fatigue Lymphadenopathy Hepatosplenomegaly Painless unilateral testicular enlargement Bone pain
Acute lymphoblastic leukaemia - investigations
Low Hb Low platelets Low or high WCC Blood film: lymphoblasts BM biopsy: >30% lymphoblasts
Acute myeloid leukaemia - presentation
SOB, pallor, fatigue Recurrent infection Muscosal bleeding, petechiae Hepatosplenomegaly Lymphadenopathy Gum hypertrophy
Acute myeloid leukaemia - investigations
Low Hb
Low or high WCC
Blood film: blasts, Auer rods
BM biopsy: >20% blasts
Chronic myeloid leukaemia - pathophysiology
Philadelphia Chromosome:
t (9:22)
BCR-ABL gene mutation
Chronic myeloid leukaemia - presentation
Middle age
Anaemia, weight loss
Splenomegaly
Increased WCC may cause visual changes, priapism, deafness, confusion
Chronic myeloid leukaemia - management
Imatinib (tyrosine kinase inhibitor)
3 most common tumours causing bone metastases
Prostate
Breast
Lung
Top 5 most common site of bone metastases
Spine Pelvis Ribs Skull Long bones
Features of bone metastases
Pathological fractures
Hypercalcaemia
Raised ALP
3 most common cancers in women
Breast
Lung
Colorectal
5 most common causes of cancer deaths in the UK
Lung Colorectal Breast Prostate Pancreas
Risk factors for nausea and vomiting from chemotherapy
Anxiety
Age <50
Concurrent opioid use
Type of chemotherapy used
First line treatment for nausea for low risk patients getting chemotherapy
Metoclopramide
First line treatment for nausea for high risk patients getting chemotherapy
Ondanestron
can be combined with dexamethasone
Side effects of cyclophosphamide
Haemorrhagic cystitis - reduced by hydration and mesna
Myelosuppression
Transitional cell carcinoma
Main cause of neoplastic spinal cord compression
Extradural compression due to vertebral body metastases
Features of neoplastic spinal cord compression
Back pain
Lower limb weakness
Sensory loss and numbness
Neurological signs
Investigations for neoplastic spinal cord compression
Urgent MRI
Management of neoplastic spinal cod compression
High dose oral dexamethasone
Oncology assessment to consider radiotherapy or surgery
What is superior vena cava obstruction?
Compression of the SVC
Usually by lung cancer
SVC obstruction - features
Dyspnoea Swelling of the face, neck, arms Headache Visual disturbance Pulseless jugular venous distension
SVC - causes
Malignancy Aortic aneurysm Mediastinal fibrosis Goitre SVC thrombosis
SVC - management options
SVC stent
Radical radio or chemo-radiotherapy
S-100 is a tumour marker for which cancers?
Melanoma
Schwannoma
Bombesin is a tumour marker for which cancers?
Small cell lung cancer
Neuroblastoma
Gastric cancer
What type of drug is ondanestron?
5HT3 receptor antagonist
Give an example of a 5HT3 antagonist
Ondanestron
Side effects of bleomycin
Lung fibrosis
Side effects of doxorubicin
Cardiomyopathy
Side effects of fluorouracil
Myelosuppression
Mucositis
Dermatitis
Side effects of 6-mercaptopurine
Myelosuppression
Side effects of cytarabine
Myelosuppression
Ataxia
Side effects of vincristine
Peripheral neuropathy
Paralytic ileus
Side effects of vinblastine
Myelosuppression
Side effects of docetaxel
Neutropenia
Side effects of cisplatin
Ototoxicity
Peripheral neuropathy
Hypomagnesaemia
3 most common cancers in men
Prostate
Lung
Bowel