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Blood, 1946, Vol. 1, No. 1, pp. 27-51.
© 1946 American Society of Hematology, Inc.
THE MEGAKARYOCYTES IN IDIOPATHIC THROMBOCYTOPENIC
PURPURA, A FORM OF HYPERSPLENISM
WILLIAM DAMESHEK M.D.1 and
EDWARD B. MILLER A.U.S.1
1 Blood Laboratory of the Boston Dispensary, and the J. H. Pratt Diagnostic Hospital;
aided by grants from the Charlton Fund, Tufts College Medical School, and the Upjohn Company.
1. The megakaryocytes of the sternal bone marrow at biopsy were studied in 11
cases of idiopathic thrombocytopenic purpura and compared with those of 10 normal cases, 5 of thrombocytopenic purpura associated with various types of splenomegaly, and of a large group of miscellaneous hematologic conditions, including
leukemia, associated with a reduction in platelets.
2. Megakaryocyte counts expressed in terms of a million nucleated red cells and
differential counts of megakaryocytes were performed. The megakaryocytes were
classified as megakaryoblasts, promegakaryocytes, and mature forms, and were
further subdivided into those showing granularity, platelet production, degenerated forms, and mitoses.
3. In the normal cases, not more than 300 megakaryocytes per million nucleated
red cells were present, and an average of 68.6 per cent showed platelet production.
4. In acute idiopathic thrombocytopenic purpura, although the platelets in the
circulating blood were rare, megakaryocytes were increased, being present in a
proportion of 366 to 743 per million nucleated red cells. Platelet production was,
however, greatly diminished and found in only 8 to 19 per cent of all megakaryocytes. Following splenectomy, there was a striking increase in platelet production, which was now present in 69 to 85 per cent of all cells; the large masses of new
platelets in the marrow were often very striking.
5. In chronic idiopathic thrombocytopenic purpura, the megakaryocytes were
considerably increased over normal values, but showed great diminution in platelet
production; following splenectomy, extreme degrees of platelet production from
megakaryocytes took place.
6. In splenomegaly of nonleukemic origin (cirrhosis, splenic vein thrombosis,
Gaucher's disease, Felty's syndrome), the megakaryocytes were somewhat increased, but platelet production was normal.
7. In aplastic anemia, lymphosarcoma, acute leukemia, and other diseases invading or destroying the bone marrow, the megakaryocytes were conspicuously
reduced, the few remaining cells present being of normal morphology.
8. The origin of the blood platelets from megakaryocytes, certain regulatory
mechanisms for platelet production and delivery, and the possible relationship of
the spleen to these mechanisms are discussed.
9. The findings of increased megakaryocytes and greatly diminished platelet production in the marrow before splenectomy and the striking increase in platelet
production after splenectomy indicate a definite pathogenetic relationship of the
spleen to the disease. Idiopathic thrombocytopenic purpura is probably a form of
hypersplenism (splenic thrombopenia) in which, through a possible hormonal
mechanism, the megakaryocytes of the bone marrow are inhibited from normal
platelet production and delivery.
10. The marrow findings in idiopathic thrombocytopenic purpura are sufficiently
characteristic to be of diagnostic value in differentiating the disease from leukemia
and other conditions associated with a low blood platelet count.
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