Bone marrow disorders Flashcards
What is polycythaemia?
An increase in Hb concentration above the upper limit for a person’s age and sex.
How is polycythaemia classified?
Relative (normal red cell mass but LOW PLASMA VOLUME) and absolute (true) polycythaemia (raised red cell mass)
What is the aetiology of absolute polycythaemia? (x2 (x3 and x5))
- PRIMARY: polycythaemia vera or polycythaemia rubra vera is when excess RBCs are produced by the bone marrow.
- SECONDARY: APPROPRIATE INCREASED ERYTHROPOIETIN caused by chronic hypoxia (for example, chronic lung disease, sleep apnoea or altitude) leasing to upregulation of erythropoiesis. INAPPROPRIATE INCREASED ERYTHROPOIETIN caused by renal carcinoma, renal cysts, hepatocellular carcinoma, fibroids, cerebellar hemangioblastoma.
What is polycythaemia vera?
Neoplastic clonal haematopoietic disorder characterised clinically by erythrocytosis and often thrombocytosis, leukocytosis, and splenomegaly. Aka polycythaemia rubra vera.
What is the pathophysiology of polycythaemia vera?
In 95% of cases, a JAK2 tyrosine kinase mutation gives haematopoietic stem cells in the bone marrow a proliferative advantage causing a trilineage expansion of morphologically normal RBCs, WBCs and platelets.
What is the aetiology of relative polycythaemia? (x2)
Dehydration, Gaisbock’s syndrome (seen in young male smokers with raised vasomotor tone and hypertension resulting in reduced plasma volume and relative increase in RBC count).
What is the epidemiology of polycythaemia: Incidence? Age?
Polycythaemia rubra vera has annual UK incidence of 1.5 in 100 000. Peak age is 45-60 years.
What are the signs and symptoms of polycythaemia? How is this related to pathophysiology? (x10 +6) How ‘Bout DaT, TPPSSH (sassy ‘tutting’)
- Related to hyper viscosity: headaches, dyspnoea, tinnitus, blurred vision
- Thrombosis (from hyperviscosity and pro-inflammatory environment produced by raised WCC)
- Plethoric complexion (red)
- Pruritus after hot bath, night sweats
- Splenomegaly in 75% of patients
- Hypertension
- Pain from peptic ulcer disease, conjunctival suffusion (redness like in conjunctivitis without inflammatory exudate), retinal venous engorgement, angina, gout, choreiform movements (jerky)
What does FBC show in polycythaemia? (x3)
Raised Hb, raised Hct, low MCV (because most also present with iron deficiency anaemia)
What additional investigations are there in polycythaemia vera? (x4)
- FBC also shows raised WCC, platelets, decreased serum erythropoietin
- JAK2 mutation screen – present in almost all but not specific to polycythaemia vera
- Bone marrow trephine biopsy – shows erythroid hyperplasia and raised megakaryocytes
- USS showing splenomegaly
What additional investigations are there for secondary polycythaemia? (x3)
- Raised erythropoietin
- Pulse oximetry, ABG and CXR to exclude chronic lung disease
- Abdominal CT or brain MRI to look for erythropoietin-secreting tumours
How are isotope dilution techniques used to investigate polycythaemia?
Infusion of radiolabelled albumin and RBCs allow confirmation of plasma volume and red cell mass and distinguish between relative (low PV, normal RCM) and absolute (normal PV, raised RCM) polycythaemia.
What is myelofibrosis?
Disorder of haematopoietic stem cells characterised by abnormal production of RBCs, WBCs and platelets, in association with progressive marrow fibrosis, extramedullary haematopoiesis (outside medulla of bone) and splenomegaly. It is REACTIVE and REVERSIBLE.
What is the aetiology of myelofibrosis? (x1 and x4)
- Primary myelofibrosis – unknown aetiology characterised by leukoerythroblasts (myeloid cell precursor – gives rise to erythrocytes, multinucleated WCCs and platelets) and splenomegaly
- Secondary myelofibrosis – reactive to malignant bone marrow disorders such as leukaemia, benign bone marrow disorders such as polycythaemia vera, hypothyroidism or drugs.
What is the pathophysiology of primary myelofibrosis? (x4 points)
- Thrombocytosis and megakaryocytic dysplasia and clustering leads to cytokine release, fibroblast proliferation and collagen deposition in bone marrow
- This also causes extramedullary haematopoiesis mostly in liver and spleen
- Circulating levels of TGF-beta are increased which impairs osteoclast formation and promotes osteosclerosis (abnormal bone hardening).
- There is also increased marrow angiogenesis