ALPF Medical Research

Essential 1 thrombocythaemia ET

ET (syn. primary or idiopathic thrombocythaemia) is characterised by persistent thrombocytosis that is neither reactive (i.e. secondary to another condition; pXXX) nor due to another myeloproliferative or myelodys-plastic disorder. It is a diagnosis of exclusion and may be biologically heterogeneous.

Incidence

True incidence unknown; slight excess in 3; median age at diagnosis 60 years; frequently occurs <40 years; very rare <20 years.

Pathogenesis

Aetiology unknown. No association with radiation, drugs, chemicals or viral infection. Not all cases are clonal. Clonal and non-clonal cases may have different natural histories: thrombosis is less common in polyclonal 250 ET as is the risk of leukaemic transformation. Platelets in ET are often functionally abnormal showing impaired aggregation in vitro. High platelet counts (>1000 x 109/L) are associated with an acquired von Willebrand syndrome; reduction in the platelet count corrects the abnormality and reduces haemorrhagic episodes.

Clinical features

• Diagnosis often follows routine FBC; up to 30% patients asymptomatic.

• Presentation may be due to 'vasomotor', thrombotic and/or haemor-rhagic symptoms.

• Vasomotor symptoms occur in 40%: headache, light-headedness, syncope, atypical chest pain, visual upset, paraesthesiae, livedo reticularis and erythromelalgia (erythema and burning discomfort in hands or feet due to digital microvascular occlusion).

• Haemorrhagic symptoms occur in 25% (major <5%): easy bruising, mucosal or GI bleeding or unexplained or prolonged bleeding after trauma or surgery.

• Thrombosis occurs in ~20% (major <10%): arterial > venous, e.g. MI, CVA

• Splenomegaly is found in <40% (less common and less marked than in other myeloproliferative disorders).

• Splenic atrophy may occur from repeated microvascular infarction.

• Recurrent abortions and fetal growth retardation due to multiple placental infarctions may occur in young women with ET.

Investigation and diagnosis

- Platelets persistently >600 x 109/L (may be as high as 5000 x 109/L).

- Hb usually normal; may to chronic blood loss.

- WBC usually normal; raised platelet distribution width (PDW).

- Mean platelet volume (MPV) usually normal.

- Automated FBC may give erroneous data in severe cases as giant platelets may be counted as RBCs.

- Thrombocytosis, variable shapes and sizes (platelet anisocytosis), giant platelets and platelet clumps; megakaryocyte fragments; basophilia may be present; variable degree of RBC abnormality:

may be hypochromic and microcytic; may be changes of hypos-plenism (p44).

• Bone marrow aspirate: not reliable for diagnosis; may show 4 platelet clumps, atypical megakaryocytes including micromegakaryocytes and other maturation abnormalities.

• Bone marrow trephine biopsy: cellularity usually 4; megakaryocytes 4, with clustering, nuclear pleomorphism and atypical nuclear ploidy. Other elements may show abnormal distribution and maturation abnormalities. Reticulin normal or 4 (25%); no fibrosis.

• Cytogenetics: abnormal in 5%; no recognised diagnostic abnormalities; occasionally 20q- or 21q-.

• Pseudohyperkalaemia: in 25%.

• Acute phase proteins: CRP and fibrinogen, and ESR usually normal.

• Bleeding time: usually normal (4 in ~20%)—rarely necessary; platelet aggregation studies not clinically helpful nor diagnostic.