Bleeding and
thrombosis are major causes of morbidity and mortality in patients with chronic
myeloproliferative disorders. We retrospectively evaluated 101 consecutive patients affected by
primary thrombocytosis (46 male, 55 female, aged 18-84 years; mean +/- SD 61 +/- 15) followed for a period ranging from 6 months up to 10 years (median 5 years) at our hematological unit. At the time of diagnosis 48 patients were asymptomatic; 26 had clinical evidence of
atherothrombosis (cerebral ischemic attacks,
ischemic heart disease, peripheral occlusive arterial disease), ten had
venous thrombosis, four experienced major
hemorrhages, 23 presented microvascular ischemic manifestations namely
erythromelalgia,
paresthesias, acrocyanosis and
dizziness. At presentation 51.2% of the patients had elevated serum lactic
dehydrogenase, 34.5%
hyperuricemia, and 23.4% serum
creatinine > 1.2 mg/dL. Color Doppler ultrasound provided evidence of vascular
stenosis or medium-intimal
hyperplasia of epiaortic vessels in 48.9% of patients studied, and similar alterations of lower limb arteries in 23.8% of cases.
Therapy modality included an
antiplatelet agent (
picotamide 300 mg/bid); a cytoreductive agent (
busulphan,
hydroxyurea,
pipobroman or
melphalan) was used when platelet count was > 800000/microL. Symptoms due to microvascular
ischemia promptly regressed after
picotamide and cytoreductive
therapy. During follow-up. nine patients suffered from atherothrombotic events (
transient ischemic attacks,
ischemic stroke,
unstable angina pectoris) and five developed
deep vein thrombosis or superficial
thrombophlebitis. Five patients experienced major
hemorrhages (two
melena, two
hematuria, one perioperative
bleeding); the two
gastrointestinal hemorrhages occurred in patients self-medicated with non steroidal anti-inflammatory drugs, and the two episodes of
hematuria occurred on oral
anticoagulant therapy and
aspirin respectively. No major
bleeding occurred in patients on continuative
therapy with
picotamide, even in the presence of upper digestive tract disorders. Seven patients died: mortality resulted from one sudden coronary death, three solid
neoplasia, one
blast crisis, one anile, and one massive
hemorrhage due to abdominal aortic
prosthesis tearing. Our study suggests that a long-term antithrombotic prophylaxis with
picotamide may be of benefit in patients affected by
primary thrombocytosis; a controlled clinical trial is warranted to assess whether
picotamide can ameliorate the natural history of the disease.