Aspirin Responsive Thrombotic Complications in Thrombocythemia Vera. A Novel Platelet-Mediated Arterial Thrombophilia

Erythromelalgia is the main, pathognomonic and presenting symptom in patients with Essential Thrombocythemia and thrombocythemia associated with Polycythemia Vera. Complete relief of erythromelalgic and acrocyanotic pain is obtained with the cyclooxygenase inhibitors aspirin and indomethacin, but not with sodiumsalicylate, dipyridamol, sulfinpyrozone and ticlopedine indicating that platelet-mediated cyclooxygenase metabolites are necessary for erythromelalgia to develop. Local platelet consumption in erythromelalgic areas became evident by the demonstration of arteriolar fibromuscular intimal proliferation and occlusions by platelet-rich thrombi in skin biopsies, by the findings of shortened platelet survival times, significant higher levels of platelet activation markers ß-thromboglobulin (ß-TG), thrombomoduline and increased urinary thromboxane B2 excretion in thrombocythemia patients suffering from erythromelalgia. Aspirin treatment of erythromelalgia in thrombocythemia patients resulted in disappearance of the erythromelalgic, thrombotic signs and symptoms, correction of the shortened platelet survival times, and significant reduction of the increased levels of ß-TG, PF IV, thrombomodulin and urinary T x B2 excretion to normal. Erythromelalgia is frequently preceded or followed by atypical transient neurologic, ocular or coronary ischemic symptoms, which specifically responds to low-dose aspirin or reduction of platelet counts to normal. The broad spectrum of acropareshesias, erythromelalgia and acrocyanotic ischemia together with the episodic and transient atypical TIAs and ocular or coronary ischemic symptoms all are the consequence of one underlying disorder of aspirin-responsive and platelet-mediated arterial thrombophilia precipitated by spontaneous activation and aggregation of hypersensitive platelets in the endarteial microvasculature involving the peripheral, cerebral and coronary circulation of thrombocythemia patients.