Background: Primary thrombocythemia is a rare acquired chronic disorder of the bone marrow which can occur at any age. Diagnosis is based upon elevated platelet counts, morphologically and functionally altered platelets and characteristic bone marrow alterations as well as the exclusion of related myeloproliferative disorders which can also be accompanied by increased platelet counts. Possible disease complications are thromboembolic and hemorrhagic events as well as a transformation into myelofibrosis or acute leukemia. Inhibition of platelet aggregation with aspirin for the prevention of thromboembolic complications is first-line therapy; cytoreductive therapy with drugs such as hydroxyurea or interferon-alpha or thromboreductive therapy with the platelet-reducing agent anagrelide is required when thromboembolic complications are already present at diagnosis (secondary prevention) or when platelet counts are steadily increasing or various additional risk factors are present (primary prevention). Because of the potential adverse effects of the various therapies upon long-term application a strict risk-benefit analysis is mandatory before initiation of therapy. In up to 50% of the patients the recently discovered V617F mutation in the JAK2 gene can be identified which is supposed to be involved in the pathogenesis of this disease.
Clinical studies: Because of the rarity of primary thrombocythemia thus far only two prospectively randomized studies have been carried out to compare cyto- and thromboreductive therapies. In the British PT1 study the mandatory combination of anagrelide with aspirin was compared with the combination of hydroxyurea and aspirin, in the European ANAHYDRET study monotherapy with hydroxyurea was compared with that of anagrelide. This different study design has caused an intense controversy about the results of these studies obtained thus far.
Conclusion: Due to the existence of randomized clinical studies expert opinion will, in the future, be increasingly replaced by evidence-based therapy guidelines. The improved knowledge of the molecular basis of the disease because of the discovery of the V617F mutation in the JAK2 gene has improved the molecular diagnosis and opened new avenues to molecular-targeted therapies.