Thrombotic and hemorrhagic complications in chronic myeloproliferative disorders

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 ischeemic 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 > 800 000/μL. 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 hi