Blood, 1953, Vol. 8, No. 1, pp. 26-64.
© 1953 American Society of Hematology, Inc.
Studies on Platelets
IX. Observations on the Properties and Mechanism of Action of a
Potent Platelet Agglutinin Detected in the Serum of a Patient
with Idiopathic Thrombocytopenic Purpura (with a Note
on the Pathogenesis of the Disease)
MARIO STEFANINI M.D.1,
WILLIAM DAMESHEK M.D.1,
JYOTI B. CHATTERJEA M.D.1,
EDWARD ADELSON M.D.1, and
IRMA B. MEDNICOFF 1
1 Ziskind Laboratories (Hematology Section) of the Joseph H. Pratt and New
England Center Hospital and the Department of Medicine, Tufts College Medical School,
Boston, Mass.
1. A case of chronic idiopathic thrombocytopenic purpura (I.T.P.) exhibited
a circulating platelet agglutination of high titer. This could be demonstrated not
only through its ability to clump various platelet preparations at extremely high
titers, but also to interfere with the functional activity of normal platelets.
The agglutinin could be absorbed upon packed platelets and, when eluted from
them, its agglutinating activity remained intact. Platelets obtained from the
patient were found to be "coated" by an agent capable of reacting with antihuman globulin rabbit serum. Complement played no role in the reaction of
agglutinin and platelets. Various properties of the agglutinin were established
and this was also characterized and purified by electrophoretic technics. The
agglutinin was found to be in the 
2 globulin area and to represent 9.33 per cent
of the entire serum protein. All indications pointed to the characterization of
the agglutinin as a platelet iso- (and auto-) antibody, although this could not be
definitely proven.
2. Platelets injected into the circulation of the patient disappeared very
promptly. When the patient's plasma was injected into normal recipients, a
series of effects followed: (a) striking degenerative changes of the bone marrow
megakaryocytes with lack of formation of platelets; (b) an extreme degree of
platelet reduction with the development of hemorrhagic phenomena; (c) detectable platelet agglutinin in the recipient's serum persisting for twelve to fourteen days. The recipient platelets were also found to be coated with a substance
capable of reacting with antihuman globulin rabbit serum (positive Coombs
test).
3. Various procedures including the administration of cortisone and splenectomy failed to modify the thrombocytopenic response of normal recipients to the
patient's plasma, although appreciable individual variations in thrombocytopenic response were observed. Repeated venesections, however, resulted in a
definite reduction in the concentration of platelet agglutinin. The titer of agglutinin in the patient remained unmodified after splenectomy.
4. Splenectomy was followed by a complete arrest of the bleeding manifestations and a temporary rise in the platelet count, which soon fell to a relatively
low level, although somewhat higher than that prior to splenectomy. Prothrombin
utilization during clotting and capillary fragility slowly returned to normal.
On the other hand, the appearance of the platelets in the peripheral blood and
of the bone marrow megakaryocytes remained unmodified, and the bleeding
time remained prolonged.
5. The response of splenectomized recipients to the patient's plasma was of
the same immediate intensity, but of much shorter duration than that of normal
recipients. Since, furthermore, splenectomy induced a moderate rise in the patient's platelet count, but failed to reduce the concentration of the serum platelet
agglutinin, it is postulated that, in this particular case, the thrombocytopenia
was probably due to the direct injury of circulating platelets and of the bone marrow megakaryocytes by the circulating agglutinin, thus resulting not only in
increased destruction but in reduced formation and release of platelets. Some of
our experimental results in animals also indicate the possibility of removal of
"sensitized" injured platelets by the intact spleen.
Submitted on August 2, 1952
Accepted on September 3, 1952
