Essential thrombocythaemia is a chronic myeloproliferative haematological disease characterized by accelerated platelet production and gradually increasing thrombocythaemia.
Epidemiology
Estimated number of new cases 1-2 / 100 000 people / year
Average age at diagnosis 40-50 years in women and 60-70 years in men (Finnish population)
Women/men ratio = 3/1
Large number of undiagnosed cases
Aetiology
Unknown
Diagnostic criteria
Sustained thrombocytosis exceeding 450 × 109 /l
Bone marrow sample showing an increased number of megakaryocytes and abnormal morphology. Morphological changes are sometimes quite slight.
JAK2, calreticulin (CALR) or MPL mutation detected.
Either all 4 of the above primary criteria or the first 3 criteria plus demonstration of clonal change or exclusion of reactive causes as secondary criterion have to be fulfilled for the diagnosis to be established.
Essential thrombocythaemia cannot be diagnosed without bone marrow biopsy.
Differential diagnosis
More than 80% of all thrombocytoses are secondary. Common causes include acute or chronic haemorrhage, a rebound effect during recovery from thrombocytopenia, connective tissue disorders, acute or chronic infection, intensive exercise, delivery, adrenaline, iron deficiency, haemolytic anaemia, a sequel of splenectomy, neoplasms and malignant tumours, tissue damage and postoperative states.
Other myeloproliferative disorders (polycythaemia vera, myelofibrosis and chronic myelogenous leukaemia)
At the time of diagnosis, a specialist in internal medicine or a haematologist should be consulted about the lines of treatment and follow-up.
Treatment is aimed at preventing thrombosis and bleeding complications and at treating any symptoms.
Careful assessment and treatment of cardiovascular risk factors
Smoking must be stopped.
IPSET (International Prognostic Score for Thrombosis in Essential Thrombocythemia) or its modification, the revised IPSET, should be used to assess the risk of thrombosis. In the latter, risk factors include age over 60 years, a history of vascular occlusion and detection of the JAK2 mutation.
Classification into four groups
Very low risk: no risk factors
Low risk: below 60 years of age, no occlusive events, JAK2 mutation detected
Intermediate risk: over 60 years of age, no JAK2 mutation or vascular occlusion
High risk: history of vascular occlusion or over 60 years of age with the JAK2 mutation detected
Basic principles
Very low risk patients (young people with no occlusive events and no JAK2 mutation) without cardiovascular risk factors can be followed up without medication.
For low risk patients, aspirin should be started, particularly if they have cardiovascular risk factors.
For intermediate risk patients, aspirin should be started, as well as cytoreductive treatment, as considered necessary.
High risk patients always need cytoreductive medication in addition to aspirin.
Aspirin is needed whenever there is a history of haemorrhage or occlusion associated with the disease.
If the platelet level exceeds 1 500 × 109 /l, acquired von Willebrand disease may develop and aspirin is contraindicated.
In an asymptomatic patient below 60 years of age with no or appropriately treated risk factors for atherosclerosis the platelet level requires no treatment.
Patients over 60 should basically always be treated, aiming to achieve the most normal platelet level possible.
Instead of platelet-reducing medication, patients who are very old or debilitated due to their other diseases may be treated with radiophosphorus. Its most significant adverse effect is an increased risk of leukaemia.
Pregnancy
Pregnancy in a patient with ET is a high-risk pregnancy and should be managed with cooperation between obstetricians and haematologists.
If the patient is otherwise asymptomatic, aspirin should be given throughout pregnancy at a dosage of 100 mg/day and low molecular weight heparin for 6-8 weeks after delivery.
If there is a history of occlusion, treatment should be individually tailored.
Associated problems are primarily fetal and less maternal.
Barbui T, Finazzi G, Carobbio A et al. Development and validation of an International Prognostic Score of thrombosis in World Health Organization-essential thrombocythemia (IPSET-thrombosis). Blood 2012;120(26):5128-33; quiz 5252. [PubMed]
Barbui T, Vannucchi AM, Buxhofer-Ausch V et al. Practice-relevant revision of IPSET-thrombosis based on 1019 patients with WHO-defined essential thrombocythemia. Blood Cancer J 2015;5():e369. [PubMed]
Barbui T, Finazzi G, Carobbio A et al. Development and validation of an International Prognostic Score of thrombosis in World Health Organization-essential thrombocythemia (IPSET-thrombosis). Blood 2012;120(26):5128-33; quiz 5252. [PubMed]