Page 26 - 2020_01-Haematologica-web

Centenary Review Article
− “Are platelets derived from leukocytes?”
− “Are platelets derived from erythrocytes?”
− “Are platelets derived from megakaryocytes?” Although Ferrata openly inclined towards the hypothe-
sis that platelets are the third cellular element of blood and are produced by megakaryocytes, the topic remains a subject of discussion. Some articles published in Haematologica in 1920 were particularly relevant. The first written by Giuseppe Pianese (1864-1933) who worked at the Institute of Pathological Anatomy and Histology of Naples, concluded that platelets were not stable elements of blood and did not derive from megakaryocytes, but were formed in particular conditions, just as fibrin is formed from fibrinogen.30 Golgi’s pupil, Aldo Perroncito (1882-1929), who taught General Pathology at the University of Cagliari, Sardinia, had his doubts as to whether platelets where derived from megakaryocytes.31- 34 In fact, he suggested that the morphological evidence that supported this hypothesis was the consequence of experimental artifacts, since the medullary megakary- ocytes ingested the platelets. So, since the megakary- ocytes contained these corpuscles in their cytoplasm, it seemed that they produced them. In addition, platelets adhere to megakaryocytes and therefore the latter may seem to release them. The origin of the platelets was, therefore, according to Perroncito, still unknown. A pre- cise and determined position in favor of the theory of the origin of platelets from megakaryocytes was taken by Giovanni Di Guglielmo (1886-1961) from Naples in a work performed under the direction of Ferrata.35 Di Guglielmo observed how megakaryocytes could be pres- ent in the blood in some pathological conditions (chronic granulocytic leukemia) and were able to form platelets. He made a very accurate morphological description of this process, demonstrating that Perroncito's critical observations were wrong. In some beautiful color illustra- tions he showed the formation and release of platelets from megakaryocytes both through the fragmentation of their cytoplasm and via the emission of long cytoplasmic extroflexions.
In the years immediately following its foundation, Haematologica published numerous other works on the genesis of platelets.36-41 Their derivation from megakary- ocytes received increasing accreditation, although there was still room for alternative hypotheses. In the end, it was again Di Guglielmo who wrote the most lucid work on the origin of these corpuscles, reaffirming the correct thesis of their derivation from megakaryocytes.42 He also confirmed his previous observations that these cells can enter peripheral blood in pathological conditions. The theory that megakaryocytes are present in the circulatory system (not only in pathological conditions but also in healthy subjects) and contribute to the formation of platelets has been definitively confirmed very recently with the documentation, in the mouse, of the release of platelets by the megakaryocytes migrated through the cir- culatory stream in the lung.43
From the start, serology and serodiagnosis of infectious diseases have always found a place in Haematologica.44-50 But topics of a more hematologic nature continued to be at the center of the interests of the researchers who con- tributed to the journal. Following the cytological study of
Golgi, some works published in the journal dealt with speculative (and sometime bizarre) hypotheses about the structure and shape of red blood cells.51-54 Other investiga- tions sparked a controversy over the priority of identify- ing the granule-filamentous substance in erythrocytes.55 Haematologica has always published studies aimed at the chemical-physical characteristics of blood and hemoglo- bin.56 One of the most important was a long article writ- ten by the physiologist Mario Camis (1878-1946) dedicat- ed to the aggregating properties of hemoglobin that were rigorously studied under different conditions;57 he also published a paper on the ultramicroscopic aspect of pure colloidal hemoglobin solutions studied, once again, under different conditions by means of the Zeiss microscope model which had been developed by Richard Adolf Zsigmondy (1865-1929) and Henry Siedentopf (1872- 1940).58
However, the nature of megakaryocytes and their role in the production of platelets continued to be at the cen- ter of interest. The particular “budding” shape of the nucleus of megakaryocytes had opened up a specific question. Some cytologists/hematologists, like Ferrata and Pappenheim, believed that this aspect was the conse- quence of nuclear divisions not followed by cell separa- tion. Other authors thought that megakaryocytes derived from the fusion of several cells. This was one of the most important topics of study at the Medical Clinic of Pavia. In the mid-20s, immediately following the arrival of
Figure 6. Giovanni di Guglielmo.
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haematologica | 2020; 105(1)