CASE PRESENTATION
A 16-year-old male with hemoglobin
SS sickle cell disease (SCD) presented with vaso-occlusive pain and
extreme thrombocytosis (platelet count 2,428,000 – 2,795,000/µL).
History was significant for frequent episodes of pain and priapism and
intermittent thrombocytosis over the 12 months prior to this
presentation (range 228,000 – 1,885,000/µL; mean 927,000/µL). Corporal
irrigation with phenylephrine injection for priapism was required 4
times in the past year. There were no neurological disturbances or
gastrointestinal symptoms. Physical exam and abdominal ultrasound showed
no lymphoproliferation, hepatosplenomegaly, or thrombosis. Hydroxyurea
therapy at 20 mg/kg had been started 18 months prior, and low dose
aspirin therapy had been administered intermittently for 10 months. He
had a lifetime transfusion history of 3 packed red blood cell (RBC)
units with no transfusion in the past year.
White blood cell count was 10.15 x103/µL, hemoglobin
9.3 g/dL, mean corpuscular volume (MCV) 80.9 fL, fetal hemoglobin
12.1%. Serum ferritin was 100 ng/mL, total iron binding capacity 290
µg/dL, serum iron 78 µg/dL, iron saturation 27%. Peripheral blood smear
(Figure 1, panel A) demonstrated sickle cells, target cells, a subset of
hypochromic red blood cells (RBC), markedly increased platelets. Bone
marrow aspirate smear (Figure 1, panel B) showed a decreased
myeloid:erythroid ratio (<1:1) with normal myeloid maturation.
Erythroid maturation showed mild megaloblastic changes. Megakaryocytes
were present in increased number with occasional hyperlobated forms.
Iron stain of the aspirate smear showed absent iron stores, and no
ringed sideroblasts. Bone marrow core biopsy (Figure 1, panel
C) showed increased cellularity
of 90%, minimal reticulin fibrosis, and no evidence of dysplasia.
Peripheral blood BCR-ABL fluorescent in situ hybridization was
negative
Genetic sequencing with deletion and duplication analysis of the
following genes associated with myeloproliferative disorders and
thrombocytosis identified no variants:JAK2 , CALR ,MPL , ABL1 , BCR , AR , CBL ,CEBPA , IDH1 , IDH2 , SF3B1 , SRSF2 ,TET2 , THPO . BCR/ABL1 mRNA qualitative analysis was
negative. Thrombopoietin (TPO) level was 8 pg/mL (reference range 7 –
99 pg/mL).
Platelet function analysis performed using the PFA-100 while on aspirin
therapy demonstrated a collagen-ADP closure time of 82 seconds,
collagen-EPI closure time of >300 seconds with platelet
count 2,533,000/µL. Von Willebrand factor (VWF) testing showed low VWF
ristocetin cofactor activity (VWF:RCoF) and decreased high molecular
weight (MW) multimers (Table 1). For treatment of severe thrombocytosis,
the hydroxyurea dose was increased to 30 mg/kg daily. Aspirin therapy
was continued, and oral iron therapy was initiated. Repeat VWF testing
occurred 9 days later, including VWF:Glycoprotein Ib (GPIb) measured by
gain-of-function mutant GPIb binding assay (VWF:GPIbM). Platelet count
decreased to normal, however intermittent thrombocytosis
>1,000,000/µL continued. Approximately 6 months later, VWF
testing showed normal antigen and VWF:RCoF levels, normal VWF GPIbM
activity, and normal multimer pattern. Priapism frequency and severity
have decreased. He has had no evidence of bleeding on aspirin therapy.