Research at the heart of hematology: thrombocytopenias and platelet function

disorders
Natural selection drove the evolution of all living beings for millions of years until
mankind acquired the ability to interfere with this mechanism by counteracting the
natural hazards that tend to eliminate the weakest humans and select the strongest
ones for the continuation of the species. Medicine, which has acquired the ability to cure
many common diseases that were previously lethal, is an important result of the attempt
to oppose natural selection. Medical progress was initially very slow, but with the advent
of the scientific revolution in the 18th century, this has continued to get faster and has
played a role in doubling the life expectancy in Western countries since the beginning of
the 19th century.1
Strenuous research, brilliant insights and, much more rarely, serendipity, were at the
basis of medical progress. Importantly, some major advances in medicine derived from
a widening of knowledge in other disciplines. For example, the development of the
microscope (the “occhiolino” or “little eye” of Galileo Galilei) in the early 17 th century was
the prerequisite for recognizing blood cells and starting to identify blood disorders. Thus,
a major advance in optical science made the birth of hematology possible.
Platelets, because of their small size and the limited resolution of early microscopes,
escaped identification for a long time, and when, in 1735, the German physician and
poet Paul Gottlieb Werlhof provided the first detailed description of ‘morbus maculosus
haemorrhagicus’,2 now known as immune thrombocytopenia (ITP), these blood cells
were unknown (Figure 1). The discovery of platelets had to wait until 1882, when the
Italian pathologist Giulio Bizzozzero, also thanks to a major technical improvement in
microscope technology (correction of chromatic aberration), described in detail these
small elements and the relationship between platelet adhesion and aggregation, and the
subsequent fibrin formation and deposition.3 A year after the brilliant insight of
Bizzozero, the link between thrombocytopenia and ITP was identified by Brohm. 4 So,
150 years after its description, we finally had an explanation for the ‘morbus maculosus
haemorrhagicus’. Also subsequent advances in knowledge of ITP were made thanks to
ingenious intuition and laborious research. The intuition of Kaznelson, in 1916, that the
spleen was responsible for platelet destruction led to the identification of splenectomy
as an effective treatment for this disease.5 A few decades later, in 1951, Harrington
observed a child with transient purpura born to a mother with ITP and suspected that
the passage of a humoral factor from mother to child was responsible for platelet
destruction.6 In the same year, Evans hypothesized that the ITP had an immune
genesis,7paving the way to immunosuppressants as an effective treatment for this
disorders.8Finally, the search for the humoral substance responsible for causing the
platelet count to rise in response to thrombocytopenia, which had involved many groups
of researchers for many decades, led in 1994 to the purification and cloning of
thrombopoietin (TPO).9This achievement opened the way to the development of TPO
mimetics, which have proven effective not only in ITP, but also in other forms of
thrombocytopenia and in bone marrow aplasia.
Acquired Platelet Dysfunction with
Eosinophilia (APDE) Syndrome: A Case
Report

Abstract
Acquired platelet dysfunction with eosinophilia
(APDE) is a syndrome which has transient state of
platelet dysfunction in the presence of marked
eosinophilia. This bleeding disorder, otherwise
known as “non-thrombocytopenic purpura with
eosinophilia”, occurs commonly in children from
South-East Asia. We report an 11 years old male
child, who presented with ecchymotic patches over
lower limbs, of recent onset. His hemogram
revealed increased eosinophils with a normal
platelet count. Coagulation screen revealed normal
parameters except increase in bleeding time.
Platelet aggregation studies showed normal platelet
aggregation with ristocetin, reduced aggregation
with ADP and no aggregation was seen with
collagen.
The presentation and management of
platelet disorders in pregnancy

Abstract
Thrombocytopenia, defined as a platelet count less than 150 000
per microlitre, occurs in 7%‐12% of all pregnancies. Apart from
anaemia, it is the most common haematological disorder in
pregnancy. Despite its frequent occurrence, thrombocytopenia
often leads to difficulties of diagnosis and management in
pregnancy. Typically, a pregnant woman will have platelet counts
of 150 000 to 450 000 per microlitre and platelet counts may be
slightly lower than those of healthy, non‐pregnant controls.
Approximately, 8% of pregnant women will develop mild
thrombocytopenia (100 000‐150 000 per microlitre) and while
65% of these women will have no underlying pathology, all
pregnant women with platelet counts of less than 100 000 per
microlitre should undergo further clinical and laboratory
assessment. Thrombocytopenia in pregnancy occurs as a result
of multiple distinct conditions, we present four cases of
thrombocytopenia in pregnancy encountered in our unit over a 12‐
month period. These include gestational thrombocytopenia,
immune thrombocytopenic purpura (ITP), thrombotic
thrombocytopenic purpura (TTP) and thrombocytopenia absent
radius (TAR) syndrome. The literature review of these cases
highlights the significance of identification, understanding
pathophysiology and a multidisciplinary approach to these
conditions. We refresh knowledge on these conditions and
emphasise the importance of thrombocytopenia in pregnancy.
A case of gray platelet syndrome masked by
immune thrombocytopenia at presentation.

Abstract
We report a case of gray platelet syndrome (GPS)
associated with immune thrombocytopenia (ITP) at
presentation. A 22-year-old male patient presenting with
petechiae on his limbs was diagnosed with ITP due to a
gradual decrease of his platelet count to a minimum of 26
× 10(9) /liter and an elevated platelet-associated IgG (PA-
IgG) level in the absence of any other specific cause of
thrombocytopenia. Administration of prednisolone
increased his platelet count, but this dropped again to
approximately 50 × 10(9) /liter as the dose was tapered,
and remained at the same level after the treatment was
terminated. Thirteen years later, we reassessed the cause
of the thrombocytopenia because the PA-IgG level was
found to be within the normal range. There were large
hypogranular platelets on the blood film and a deficit of α-
granules in the platelets on electron microscopy. On this
basis, we diagnosed his thrombocytopenia as GPS. To
our knowledge, this is the first report of a GPS case
associated with ITP at presentation. This case illustrates
the importance of carefully reviewing blood film results in
the differential diagnosis of thrombocytopenia.