Information ⬇
Editors
Essential Thrombocythaemia (Et)
Definition
- 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
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.
- Non-fulfilment of criteria for other myeloproliferative conditions (such as polycythaemia vera Polycythaemia Vera (Pv), chronic myelogenous leukaemia Chronic Myelogenous Leukaemia (CML) or myelofibrosis Myelofibrosis (Mf))
- 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)
- Myelodysplastic syndrome Myelodysplastic Syndromes (MDS), particularly the 5q and RARS-T subtypes
Clinical picture and complications
- Asymptomatic, detected incidentally
- Arterial or venous thrombosis
- Cerebrovascular disorder, headache
- Peripheral ischaemic symptoms (erythromelalgia)
- Major haemorrhage
- Complication of pregnancy
- Transformation into myelofibrosis, leukaemic transformation is rare.
Findings
- Platelet count repeatedly > 450 × 109 /l
- Typical bone marrow
- Splenomegaly in 25% of patients at the time of diagnosis
- JAK2, CALR or MPL mutation in about 70-80%
Prognosis
- Chronic course
- Life expectancy quite similar to reference population.
- 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.
- Drugs used for the treatment of thrombocytosis
- Interferon
- First-line treatment for young patients
- In Finland, only long-acting interferon is used, with no approved indication or reimbursibility
- Hydroxyurea
- Most commonly used
- Rapid acting and effective
- A risk of leukaemia in association with long-term use is under discussion - the risk is probably negligible
- Anagrelide
- A first-line option for young patients. Use in older patients is restricted by cardiac adverse effects.
- Does not increase the risk of leukaemia.
- May accelerate the development of myelofibrosis but the results are inconsistent.
- Must not be used during pregnancy.
- Busulphan
- For the treatment of older patients
- May increase the risk of leukaemia
- 4- to 6-week courses
- 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.
References
- Nordic care program for patients with essential thrombocythemia, polycythemia vera and primary myelofibrosis. 4th version March 2017. Nordic MPN Study Group http://www.nmpn.org/index.php/guidelines/17-nmpn-care-program-2017/file
- 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]
Evidence Summaries ⬆