Idiopathic Thrombocythaemia: A Review of Seven Cases in Western Australia**

Abstract

Summary: A persistently elevated platelet count is seen occasionally as a presumed neoplastic phenomenon in polycythaemia vera, myelofibrosis and chronic granulocytic leukaemia, all variants of the myeloproliferative syndrome. More rarely a group of cases is seen where the elevated platelet count appears the dominant finding and the condition is variously called idiopathic or essential thrombocythaemia, haemorrhagic thrombocythaemia, megakaryocytic myelosis or a variety of other synonyms. The clinical, haematological and cytogenetic features of seven cases in Western Australia over a ten year period have been reviewed. The clinical picture was dominated by haemorrhage in three patients and thromboembolic phenomena occurred in four, on occasion concurrently with bleeding. Splenomegaly was present in all cases. No patient manifested erythrocytosis either at presentation or on follow‐up. All had peripheral blood platelet counts persistently over 800,000/μl and megakaryocytic hyperplasia was the principle finding on bone marrow examination. Where performed tests of platelet function were normal. Chromosome analysis was carried out in all patients; direct bone marrow preparations were studied in five patients and peripheral blood cultures in two patients. There was a high degree of aneuploidy and a high polyploidy index. One case was found to have a marker chromosome. None had any G group chromosome abnormality. With adequate control of the platelet count using 32P or busulphan, the prognosis appears to be good. These patients have survived for a mean of 7.5 years from the onset of symptoms (but only a mean of 3.0 years from establishment of a definite diagnosis). One patient has died from termination as acute leukaemia, a rare event in this condition. It is concluded that the features found in these patients are distinctive enough to warrant consideration of idiopathicthrombocythaemia as a distinct nosological entity in the spectrum of the myeloproliferative disorders.

Essential Thrombocythaemia

“…Bone marrow examina tion showed panmyelosis with a striking increase in megakaryocytes which were large and tended to have many lobes, as has been described by others (32,43,55). The NAP scores, serum lysozyme and vitamin Bi2 levels were variably abnormal in our patients, in keeping with the findings of others (13,19,26,29,32,34,43,57).…”

“…The 3 patients described displayed the characteristic clinical and haematological features of ET (25,29,32,43,51,62), and at no time displayed features suggestive of polycythaemia vera, myeloid leukaemia or myelofibrosis. All pa tients had splenomegaly and suffered from both haemorrhage and thrombosis.…”

“…Ultrastructural studies of the platelets showed proliferation of the dense tubular system with deficiency of the surface-connected canalicular system. Megakaryocyte electron microscopy showed abnormal distribution of demarcation membrane complex and granules.The precise functional abnormality of the platelets in ET has not yet been defined, but a release defect of variable severity with corresponding morphological abnormalities of the dense tubular and surface-connected canalicular systems, seems the most likely explanation.Essential thrombocythaemia (ET) is now a well-recognised entity within the spectrum of the myeloproliferative disorders, and the clinical picture and general laboratory features are reasonably well defined (19,25,29,32,43,51,62). However, investigations of the bleeding tendency using qualitative platelet func tion tests and studies of platelet and megakaryocyte morphology and ultrastruc ture have not shown consistent abnormalities.…”

Megakaryoblastic Transformation of Primary Thrombocythemia

“…Philadelphia chromosome-negative PT) the progres sion to acute leukemia is very rare, since only 14 ob servations have been reported [2][3][4][5][6][7][8][9][10][11]. The role of chemotherapy in the genesis of leukemia could be dis cussed in 11 patients, who were previously treated by alkylating agents (4 patients) [2,7,10], radioactive phosphorus (6 cases) [4][5][6][7]11] or total body irradia tion (1 case) [3]. Three patients were treated by busulfan [8,11].…”

“…In some rare patients, the leukemic cells had monoblastic or myelomonocytic differentiation (3 cases) [2,10,11] while a myeloblastic transformation was identified in 9 other patients [3,4,[6][7][8][9]11]. How ever, in 2 of these latter patients a megakaryoblastic differentiation was demonstrated in a minority of peripheral blood cells which reacted with a mono clonal antibody specific for megakaryocyte-platelet glycoproteins Ilb-IIIa [11], In our patient, the mega karyoblastic origin of blood and bone marrow blast cells was demonstrated by the PPO reaction.…”