Miscellaneous Flashcards
What is polycythaemia vera?
Myeloproliferative disorder
Caused by clonal proliferation of haematopoietic progenitor cells
What is primary polycythaemia?
Due to mutation - inherited or acquired
Main cause is polycythaemia vera
What is secondary polycythaemia?
Due to increased EPO production
Hypoxia induced rise:
smoking, CLD, COPD, obesity, OSA
Inappropriate EPO rise
Renal cell cancer, Wilm’s
Adrenal tumours
Illicit EPO use
Androgen use, testosterone replacement
What is relative polycythaemia?
Increase in haematocrit or Hb count in presence of normal red cell mass
Decrease in plasma volume
Dehydration e.g. diarrhoea, vomiting, diuretics use
What is the pathogenesis of polycythaemia vera?
98% patients have JAK2 mutation - tyrosine kinase
V617F mutation, mutations in exon 12
Mutations result in proliferation of haematopoeitic precursors
What are the clinical features of polycythaemia vera?
Some asymptomatic with raised Hb/haematocrit incidentally on blood tests
If presenting symptomatic - may have gradual creeping onset, non-specific due to increased blood viscosity
Headache, visual disturbance
Tinnitus, itching, fatigue
Vertigo, paraesthesia
Bruising, excoriation, conjunctival infection, splenomegaly, erythromelalgia
What are the investigations for polycythaemia vera?
FBC raised Hb or haematocrit
Raised serum EPO suggestive of secondary polycythaemia
Raised WCC and platelet count suggestive of PV
Serum ferritin, serum uric acid
Genetic testing for JAK2 V617F in exon 14 or mutations in exon 12
Bone marrow biopsy to distinguish PV from secondary polycythaemia
USS to identify splenomegaly, identify renal or hepatic tumours;
CT, MRI, PET-CT
When can a diagnosis of polycythaemia vera be made following investigations?
- High haematocrit (> 0.52 in men, > 0.48 in women) OR raised red cell mass (>25% above predicted)
- Mutation in JAK2
What is masked polycythaemia vera?
Haemoglobin and haemtocrit count normal despite presence of disease
Typically occurs in setting of iron deficiency where effect of JAK2 mutation blunted
What is the management of polycythaemia vera?
Reduce complications, symptoms and reduce risk of transformation to myelofibrosis or acute leukaemia
Maintain haematocrit at <0.45
Venesection - 200-500mls at a time
Low dose aspirin, 75mg once daily to reduce thrombotic events
Cytoreduction therapy in high risk patients -
hydroxycarbamide (antimetabolite)
or interferon-alpha, ruxolitinib and busulfan
Who can be considered for cytoreductive therapy?
Age >65 years and/pr
Prior PV associated arterial or venous thrombosis
Also considered in low risk with Thrombocytosis Progressive splenomegaly Progressive leucocytosis Poor tolerance of venesection
What is Budd Chiari syndrome?
Hepatic vein thrombosis
Lead to tender hepatomegaly, ascites, and sudden severe abdominal pain
What complication can arise from Polycythaemia Vera?
AML transformation
What is primary myelofibrosis?
Proliferation of haematopoietic stem cells in the marrow and at other sites leading to fibrosis
Marrow is replaced with scar tissue
At what age is primary myelofibrosis most prevalent?
60yo
What signs and symptoms are commonly seen in primary myelofibrosis?
Typically elderly present with anaemia
B Symptoms
Massive splenomegaly
\+/- Spontaneous bleeding DCIS Oesophageal varices Petechiae
What investigation findings would you expect with myelofibrosis?
Anaemia
WCC and platelets high in early disease then low
Bone marrow aspiration = dry tap
So need to do trephine biopsy
“Tear drop” poikilocytes (RBC’s) on blood film
Poikilocytosis - varying sizes of red blood cells
and immature red and white cell blasts
High urate and LDH
Homozygous JAK2 or MPL mutation
How is primary myelofibrosis managed?
Allogenic stem cell transplant is the only cure
What is the palliative/symptomatic management for primary myelofibrosis?
Red cell transfusion/EPO for anaemia
hydroxyurea or splenectomy - splenomegaly
prednisolone - cytopenic
What are the complications of primary myelofibrosis?
progress to blast phase - like AML
portal hypertension
splenic infarct
immune deficiency
What is essential thrombocythaemia?
Failure in platelet production regulation
Malignant megakaryocyte proliferation
At what age do people get essential thrombocythaemia?
60yo
What are the common signs and symptoms of essential thrombocythaemia?
Burning sensation in hands
Mixed thrombosis and bleeding in any system:
Dusky extremities
TIA and amaurosis fugax
Arterial and Venous thrombosis (leg, MI, hepatic, renal)
Bleeding - GI, gums, eyes, urinary
Sweating/Fever
Hepato/splenomegaly
Why can you see bleeding in essential thrombocythaemia?
clotting factors run out
How do you diagnose essential thrombocythaemia?
Diagnosis of exclusion
What is found in investigations of essential thrombocythaemia?
Platelet count >600
High WCC, RBC but low Hb
thrombocytes on blood spear
hypercellular bone marrow with giant megakaryocytes and increased reticulin
Impaired platelet aggregation
Philadelphia chromosome absent
Heterozygous JAK2 or MPL mutation
What factors puts a patient with essential thrombocythaemia at high risk?
> 60yo
History of thrombosis
Very high platelet count
How do you manage Essential Thrombocythaemia patients?
Aspirin
Hydroxyurea
Interferon-alpha
Why is hydroxyurea used in essential thrombocythaemia?
anti-metabolite –> reduce platelets
What are the main complications of essential thrombocythaemia?
Thrombosis
Haemorrhage
AML transformation
What is encompassed in a VTE?
Pulmonary embolism (PE): acute/chronic occlusion of pulmonary arteries. Clot breaks off and travels to the lungs (emboli).
Deep vein thrombosis (DVT): acute/chronic occlusion of deep vein(s). Commonly affects the lower limbs through the formation of a clot forms (thrombus).
Where can a DVT be located?
Distal - below popliteal trifurcation, can resolve spontaneously without symptoms
Proximal - above popliteal, may affect popliteal, femoral or iliac veins
50% develop PE within 3 months
Other - name according to vessel or location of thrombus
What can cause a DVT?
Provoked - transient or persistent risk factors, typically within three months of event
Unprovoked - no identifiable risk factor, not easily correctable
What are some of the risk factors for VTE?
Intrinsic factors Hx of DVT Cancer Obesity Acquired or inherited thrombophilia Inflammatory disorders Varicose veins Smoking Male sex Older age >60 years
Transient factors Hospitalisation Recent major surgery Recent major trauma Significant immobility Hormone therapy e.g. COCP or HRT Long distance flights Dehydration Acute infection Pregnancy + 6 weeks PP
What is Virchow’s triad?
Pathophysiology of DVT based on this
Venous stasis
Hypercoaguable state
Endothelial injury
What are the clinical features of DVT?
Classically with painful, unilateral leg swelling
Warm to touch, surrounding erythema
Calf asymmetry - diameter >3cm increases likelihood
Venous distention
Oedema
Tenderness along deep veins
What are some examples of thrombophilias?
Antiphospholipid syndrome (this is the one to remember for your exams) Antithrombin deficiency Protein C or S deficiency Factor V Leiden Hyperhomocysteinaemia Prothombin gene variant Activated protein C resistance
What VTE prophylaxis is given when admitted to hospital?
If at increased risk
LMWH e.g. enoxaparin unless contraindicated (active bleeding or existing anticoagulation with warfarin or NOAC)
Antiembolic stockings (unless significant peripheral arterial disease)
What is the Well’s score and its meaning?
10 criteria, score 0-9
Score >2 - DVT likely, proximal leg vein US within 4 hours or d-dimer, interim anticoagulant, US in 24 hrs
Score <1 - DVT 5%
D-dimer
If positive, proceed to leg vein US testing
What is the d-dimer test?
D-dimer is fibrin degradation product
Created when blood clots broken down by fibrinolytic system
