Haematology Flashcards
What is the normal level of Hb for women?
120-160 g/L
What is the normal level of Hb for men?
135-175 g/L
What are the subunits in fetal haemoglobin?
2x alpha
2x gamma
What are the subunits in adult haemoglobin?
2x alpha
2x beta
What causes alpha thalassaemia?
A deletion of one of the genes that codes for alpha haemoglobin
How does HbF affect sickle cell disease?
Fetal haemoglobin is protective, so if there is more HbF, symptoms will be less severe.
What cell type do erythrocytes evolve from?
- Haemopoietic stem cells which then evolve into myeloid stem cells.
- Reticulocytes
What are the four types of leukaemia?
- Acute myeloid leukaemia
- Acute lymphoblastic leukaemia
- Chronic myeloid leukaemia
- Chronic lymphocytic leukaemia
What is myelodysplasia?
Very low levels of white cells, red cells and myeloid precursors.
How would you treat MGUS/ smouldering myeloma?
You dont!= Watch and wait
How does myeloma lead to bone lytic lesions?
There are too many plasma cells, which stimulate too many osteoclasts, and inhibit osteoblasts (Treated with bisphosphonates)
What things are measured in a FBC?
- Haemoglobin
- MCV
- Haemocrit percentage
- Platelet count
- WCC
- Lymphocyte count
- Monocyte count
- Basophil count
- Eosinophil count
What is haematopoiesis?
Synthesis of blood cells
Where does haematopoiesis?
- Normally in the bone marrow of the axial skeleton
- Can have extramedullary haematopoesis especially in the spleen
What stimulates production of erythrocytes?
EPO
What causes myeloproliferative neoplasms?
Gene mutations in the signalling pathway for blood cell proliferation- leading to an excess of mature cells in the blood
Give some examples of myeloproliferative neoplasms
Chronic myeloid leukaemia (CML)
Polycythaemia vera
Essential thrombocythaemia
Primary myelofibrosis
What is JAK-STAT pathway?
The signaling pathway for cell formation
What is thrombocytosis?
Elevated platelet count
How would you investigate a haematological malignancy?
- History
- Examination
- FBC
- Blood count
- Immunophenotyping
- Bone marrow biopsy
- Cytogenetics
- Molecular studies
- Imaging
What is the commonest cancer of childhood?
Acute lymphoblastic leukaemia
What causes lymphoma?
- Idiopathic
- Primary immunodeficiency= CVID
- Secondary immunodeficiency= HIV
- Infection= EBV
- Autoimmune disease
What are the “B” symptoms?
- Fever
- Weight loss
- Night sweats
How is lymphoma diagnosed?
- Clinical history and examination
- Lymph node biopsy
- Blood film/ Bone marrow biopsy
- Immunophenotyping
- Cytogenetics
- CT chest/abdomen
What sites are common to bleeds in haemophilia?
Soft tissue- iliopsoas, thigh, calf, buttock, deltoid/forearm, neck
What is the main treatment of haemophilia?
Factor replacement
- NovoSeven in children if there are inhibitors= Recombinant VIIA
- Or immune tolerance therapy if inhibitors
What are haemophilia inhibitors?
Inhibitors to the factor
What is the role of vWF?
- It causes platelet aggregation
- It is bound to factor VIII - and mediates it
What are the roles of thrombin?
It converts fibrinogen to fibrin
- It converts factor XIII to XIIIa
- It acts as a negative feedback loop to prothrombin
Which coagulation factors are vitamin K dependent?
10, 9, 7, 2
What is haemophilia A?
A deficiency of factor VIII
What is haemophilia B?
A deficiency of factor IX
What is vWD?
A deficiency of von Willebrand Factor= Causes spontaneous bleeding
Where are platelets produced and via what cell?
Produced in the bone marrow
Megakaryocyte fragments
Triggered by TPO
What are platelets?
Anucleate cells with a lifespan of 7-10 days
- They adhere and aggregate to form a platelet plug (primary haematopoesis)
- Removed by spleen
By what pathway are blood clots broken down?
- Fibrinolytic pathway
- Plasminogen forms plasmin which leads to fibrin breakdown
What causes the platelet plug to remain still?
- Prostaglandins inhibit platelet aggregation
- NO inhibits platelet aggregation
What are the causes of low platelets?
- Production failure
- Increased removal
- Artefactual
What are the components of Virchow’s triad?
- Stasis of venous circulation
- Hypercoagulability
- Endothelial injury
How may a pulmonary embolism appear on x ray?
- Westermark sign
- Palla’s sign
- Hampton’s hump
- Melting sign
What is hampton hump?
A classic wedge-shaped triangular opacity displaying a pulmonary embolus
What are the symptoms and signs of a DVT?
Symptoms: Pain, swelling
Signs: Tenderness, swelling, warmth, discolouration
What are the clinical features of a massive pulmonary embolism?
- Hypotension
- Cyanosis
- Severe dyspnoea
- Right heart strain// failure
What are the signs and symptoms of pulmonary embolism?
Symptoms: breathlessness, pleuritic chest pain, may have signs/ symptoms of DVT
Signs: tachycardia, tachypnoea, pleural rub
How is pulmonary embolism prevented?
- Early mobilsation and hydration
- Compression stockings
- Thrombophylaxis
What are the arteries of the leg
- Common iliac
- Femoral
- Popliteal
- Tibial
What are the three major branches of the abdominal aorta?
- Coeliac trunk
- Superior mesenteric
- Inferior mesenteric
At what point does the coeliac trunk come off the aorta?
T12
At what point does the superior mesenteric come off the aorta?
L1
At what point does the inferior mesenteric come off the aorta?
L3
At what point do the renal arteries come off the abdominal aorta?
L2
What are the branches of the common hepatic artery?
- Proper hepatic
- Gastroduodenal
- Right gastric
What are the three branches that come off the loop of the aorta?
- Brachiocephalic
- Left common carotid
- Left subclavian
What is intermittent claudication?
Cramping pain that is induced by exercise and relieved by rest. Pain is distal to the site of atheroma, and is due to lactic acid production as a result of reduced blood supply.
What is critical ischaemia?
Tissue is dying and suffering at rest (rest pain= typically nocturnal). Blood supply is inadequate to allow basal metabolism.
What are the 5 main types of WBC?
- Neutrophils
- Monocytes
- Eosinophils
- Basophils
- Lymphocytes
What are the causes of neutropenia?
- Infection (EBV, HIV, Hep B, Hep C
- Drugs (Phenytoin, antipsychotics)
- Endocrine
- Malignancy (myeloma)
- Autoimmune
- Excess alcohol and liver disease
What are the causes of neutrophilia?
- Infection (bacterial, VZV, HSV)
- Drugs (steroids)
- Malignancy (leukaemia, lymphoma)
- Rheumatoid arthritis
- Gout
- Hypoxia
What are the causes of lymphopenia?
- Drugs (steroids)
- Infection (post-viral = common)
- Malignancy
- Renal/hepatic impairment
- SLE, RA
- Anorexia nervosa
What are the causes of lymphocytosis?
- Infection (EBV, CMV, Pertussis)
- Stress
- Vigorous exercise
- Malignancy
- Post splenectomy
What are the causes of monocytosis?
- Malaria
- Typhoid
- TB
- Myelodysplastic Syndromes
What are the causes of eosinophilia?
- Asthma
- Parasitic infections
- Addisons
- Malignancy
- Smoking
What are the causes of thrombocytopenia?
- Viral infections
- Drugs
- Alcohol
- Malignancy
- Liver and renal disease
- Aplastic anaemias
- SLE
What are the causes of thrombocytosis?
- Reactive
- Malignancy
- Splenectomy
- Iron deficiency
What are the causes of platelet plug formation?
- von Willebrand’s Factor (vWF) adheres to the vascular injury.
- vWF then binds to GpIb receptors on surrounding platelets.
- After binding, the ADP (P2Y12) receptor on the platelet is activated leads to increased expression of GpIIb/IIIa.
- These newly expressed receptors then finally bind to fibrinogen, which leads to further platelet aggregation.
What are the 4 coagulation tests/
- PT
- APTT
- Bleeding time
- Thrombin time
What types of malaria can lay dormant for years?
- P Ovale
- P Vivax