Secondary severe thrombocytosis in a patient who underwent splenectomy due to hereditary spherocytosis and its treatment using hydroxyurea
Hakan Sarbay1,&, Sinan Akbayram2
1Diyarbakir Children Hospital, Pediatric Hematology and Oncology, Turkey, 2Gaziantep University Faculty of Medicine, Pediatric Hematology and Oncology, Turkey
Hakan Sarbay, Diyarbakir Children Hospital, Pediatric Hematology and Oncology, Turkey
Thrombocytosis is a frequently seen condition during childhood. While it
usually develops secondarily due to reasons such as infection or anemia,
it may rarely develop due to clonal causes. Thrombocytosis becomes a life-threatening
condition by causing severe complications such as hemorrhage and thrombosis
development. Treatment is not recommended in patients who are asymptomatic
and with a platelet count below 1,500,000/mm3, however, treatment
is required in cases who are symptomatic and with a platelet count above
conditions such as primary thrombocytosis. This article present the outcomes
of a patient who was treated using low-dose hydroxyurea when he developed
severe thrombocytosis after splenectomy.
Thrombocytosis is one of the common hematological findings seen during
childhood. The most common causes include infections, anemia, autoimmune
diseases and splenectomy . Rarely, thrombocytosis
may also develop due to clonal causes. The most prominent examples
of this include chronic myeloid leukemia and essential thrombocytosis
The first step to approach thrombocytosis is to repeat the complete blood count
test to rule out the false high values caused by cellular destruction.
When thrombocytosis is confirmed, it is necessary to classify the
thrombocytosis based on its severity. Studies have divided thrombocytosis
based on the risk of complication development: mild thrombocytosis
moderate thrombocytosis (700,000-900,000/mm3), severe thrombocytosis
(>900,000/mm3) and very severe thrombocytosis (>1,000,000/mm3)
[3, 4]. This article present the
outcomes of a patient who was treated using low-dose hydroxyurea
when he developed severe thrombocytosis after splenectomy.
Patient and observation
Fifteen-year-old male patient who underwent splenectomy 5 years ago
due to hereditary spherocytosis, massive splenomegaly and hypersplenism
applied for outpatient clinic visit. Having no complaints other
than fatigue and intermittent abdominal pain, the patient was receiving
and acetylsalicylic acid (100mg/day) treatment. Laboratory results
included a white blood cell count of 18.760/uL, hemoglobin of 12.7gr/dL, platelet
count of 2,235,000/uL, ferritin of 68ng/mL, Vitamin B12 of 262ng/mL and folate of 6.1ng/mL and liver and kidney functions tests
were within normal
limits. The patient was hospitalized for IV hydration therapy.
Acetylsalicylic acid treatment was continued. Peripheral smear
leukocyte formula included
neutrophil of 58%, lymphocyte of 36%, monocyte of 4% and eosinophil
of 2%. No atypical cell or blast was observed. Mild hypochromia,
microspherocytes and large clusters of platelets were observed.
In the follow-up analyses
after hydration therapy, platelet counts were above 2,000,000/uL.
Analysis for Janus kinase (JAK) mutation was sent. Hydroxyurea
was initiated at a dose
of 1x500mg/day (10mg/kg/day). Platelet count regressed to 1.630.000/uL
at week 2 and to 1,568,000/uL at week 4. Experiencing no clinical
or laboratory side effect in the weekly follow-ups, the patient
had a platelet count of
1,440,000/uL at the end of week 6 (Table
1). Hydroxyurea dose was increased to 15mg/kg/day. As the patient
developed dyspeptic complaints, the dose of the medication was
decreased back to 10mg/kg/day. The patient is still being followed
Pathophysiologically, thrombocytosis is divided into two groups as
primary and secondary. Primary causes include essential thrombocytosis
and familial thrombocytosis. As with other myeloproliferative diseases,
thrombocytosis is more common in adult age groups and rarely seen
during childhood. Secondary thrombocytosis is more common during
infancy and its
incidence decreases with increasing age [5, 6].
While the patient's thrombocytosis has been considered to be due
to splenectomy, Janus kinase 2 (JAK2) mutation was studied to rule
out essential thrombocytosis.
While thrombocytosis is mostly asymptomatic, high platelet count
may cause symptoms and signs such as headache called vasomotor
phenomenon, visual disturbances,
fatigue, chest pain, abdominal pain, vertigo, aphasia and dysarthria
independent from the etiological causes . Our case
had the complaints of fatigue and intermittent abdominal pain.
Platelet count was above 2,000,000/mm3 and taking the splenectomy
into account, the risk of thrombosis was considered to be high.
The most important
point in the follow-up and treatment of thrombocytosis is to determine
the etiology. In conditions such as infection, anemia and inflammatory
diseases, thrombocytosis regresses when the underlying condition
is treated .
However, thrombocytosis may be more resistant after splenectomy.
Therefore, longer treatment may be required compared to the other
The most commonly used medication in treatment is acetylsalicylic
acid. Thromboxane causes a decrease in platelet activity by suppressing
. Our patient has been receiving acetylsalicylic
acid treatment for almost 5 years. Thrombosis was not observed
despite platelet counts were high in follow-up analyses. However,
due to high platelet count,
hydroxyurea treatment was planned to be initiated. In the literature,
cytoreductive therapy has been mostly initiated in essential thrombocytosis
and when the
platelet count is >1,500,000/mm3 [7, 8].
It is recommended to start the treatment at a dose of 15mg/kg/day
and adjust the dose based on follow-up. While there is a risk of
at long term, it was found to be well-tolerated, effective in reducing
the platelet count and reduce the risk of thrombotic events [9, 10].
In our case, hydroxyurea was initiated at a dose of 10mg/kg/day.
During the follow-up, the platelet count regressed below 1,500,000/mm3 and
no side effect was observed. The dose was increased to 15mg/kg/day.
However, as dyspeptic complaints developed after dose increase,
the dose was reduced
back to 10mg/kg/day.
There are case reports of successful use of hydroxyurea in patients
with essential thrombocytosis in the literature [7, 8].
We emphasize that in patients with secondary thrombocytosis, low-dose
hydroxyurea treatment can be used safely when the platelet count
is above 1,500,000/mm3 for
a long period of time and the risk of thrombosis is high, and platelet
count can be reduced to safe levels.
The authors declare no competing interests.
All authors participated in the design of the study. Hakan Sarbay performed the collection, statistical analysis and interpretation of the data. Sinan Akbayram participated in the interpretation of data. All authors have read and approved the final document.
Table 1: laboratory values of the patient
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