What is the aetiology of polycythaemia? (Absolute and relative polycythaemia)
ABSOLUTE:
- Due to an increase in RBC mass
- Primary – polycythaemia vera, mutations in erythropoietin receptor or high oxygen affinity haemoglobins
- Secondary – hypoxia (high altitude, chronic lung disease, heavy smoking etc), high erythropoietin secretion
RELATIVE:
- Decreased plasma volume with a normal RBC mass
- Apparent polycythaemia (chronic form associated with obesity, hypertension and high alcohol/ tobacco intake)
- Dehydration (e.g. alcohol or diuretics)
What is the pathophysiology of polycythaemia?
- Any increased in RBCs
- Defined as an increased in haemoglobin, lacked cell volume and red cell count
What is the presentation of polycythaemia?
- Non-specific lethargy and tiredness
- Arterial thrombosis (stroke, MI, DVT, PE)
- Headache
- Dizziness
- Sweating
- Peptic ulcers
- Bleeding from gums or easy bruising
- Pruritis (worse after a hot shower/bath)
How is polycythaemia investigated?
- High haemoglobin
- Bone marrow biopsy shows hypercellularity
- Low serum erythropoietin
- Splenomegaly
- JAK2 mutation
How is polycythaemia managed?
- Long-term phlebotomy to keep haematocrit <45%
- Low-dose aspirin
- Chemotherapy
- Allopurinol if high uric acid
What is the aetiology of immune thrombocytopenia?
- Broken immune tolerance and autoimmune attack against platelets
What is the pathophysiology of immune thrombocytopenia?
- Increased destruction of platelets in the spleen by anti-platelet antibodies
- Impairment/ inhibition of platelet production due to suppression of normal megakaryocyte development by autoantibodies
- T cell mediated destruction of platelets and megakaryocytes in the bone marrow
What are the risk factors of immune thrombocytopenia?
- Women of childbearing age
- Age <10
- Age >65
What is the presentation of immune thrombocytopenia?
- Bleeding
- Fatigue
- Previous viral illness
- Otherwise well (often an incidental finding)
What are the differential diagnoses of immune thrombocytopenia?
- Pseudothrombocytopenia
- Congenital thrombocytopenia
- Acquired thrombocytopenia
- Malignant hypertension
- Disseminated intramuscular coagulation
- Sepsis
How is immune thrombocytopenia investigated?
- FBC peripheral blood smear
- HIV serology
- Helicobacter pylori breath test or stool antigen test
- Heroic function tests
- Hepatitis C serology
How is immune thrombocytopenia managed?
- IV Immunoglobulins (IVIG)
- Corticosteroid
- Platelet transfusion
- Antifibronlytic
- Anti-D immunoglobulin
What is the aetiology of thrombotic thrombocytopenia purpura?
- Production of unusually large vWF multimers
What is the pathophysiology of thrombotic thrombocytopenia purpura?
- Large vWF multimers interact with platelets and triggers activation of circulating platelets at sites of high intravascular pressure, triggering thrombi in the micro vascular system
- An additional stressor (e.g. pregnancy or infection) may be needed before TTP manifests
What are the risk factors for thrombotic thrombocytopenia purpura?
- Black ethnicity
- Female gender
- Obesity
- Pregnancy (near term or post-partum)
- Cancer therapies
- HIV infection
- Bone marrow transplantation
- Anti-platelet agents
What is the presentation of thrombotic thrombocytopenia purpura?
- Non-specific prodrome
- Severe neurological syndromes (e.g. coma, focal abnormalities, seizures…)
- Mild neurological symptoms (e.g. headache, confusion…)
- Fever
- Digestive symptoms
- Weakness
What are the differential diagnoses of thrombotic thrombocytopenia purpura?
- Haemolytic uraemia syndrome
- Malignant hypertension
- Sepsis
- Pre-eclampsia
How is thrombotic thrombocytopenia purpura investigated?
- Platelet count
- Haemoglobin
- Haptoglobin
- Peripheral smear
- Reticulocyte count
- Unialysis
- Urea and creatinine
- Direct Coombs’ test (tests for autoimmune haemolytic anaemia)
How is thrombotic thrombocytopenia purpura managed?
- Plasma change
- Corticosteroids
- Caplacizumab
- Aspirin
- Folic acid and/or transfusions
- Immunosuppressive
- Splenectomy
