Abstract

  Acetylsalicyl acid (Aspirin^R Bayer) cures erythromelalgia and migraine-like microvascular cerebral microvascular ischemic disturbances by irreversible inhibition of platelet cyclooxygenase (COX-1) mediated arteriolar inflammation and platelet thrombi in JAK2^V617F mutated thrombocythemia patients with Essential Thrombocythemia (ET) and Polycythemia Vera (PV). Aspirin responsive active platelet prostaglandin metabolism of hypersensitive platelet in thrombocythemia is the mechanism for erythromelalgia and erythromelalgic circulation disturbances to develop caused by acquired or germline gain of function mutations in the TPO, JAK2 and MPL gene and to be labeled as Sticky Platelet Syndrome or Platelet Arterial Thrombophilia. Salicylic acid does not inhibit platelet COX-1 and does not cure aspirin responsive erythromelalgia. Acetylsalicylic acid (Aspirin, synthesized by Hoffmann, Bayer 1897) has been discovered by Michiels between 1975 and 1985 as a wunder drug that cures platelet mediated erythromelalgia and microvascular disturbances. The platelet ADP-receptor inhibitors ticlopedin and clopidrogrel, other platelet affecting agents like dipyridamol, analgetics like sodium salicylate and anticoagulation with coumadin or direct oral anticoagulant (DOAC IIa/Xa-inhibitors) do not inhibit COX-1 activity and are ineffective in the treatment of erythromelalgia and its associated cerebral and coronary ischemic events. Aspirin responsive erythromelalgia and erythromelalgic acrocyanotic and ocular, cerebral and coronary microvascular circulation disturbances in JAK2, MPL or TPO mutated thrombocythemia are alleviated by reduction of platelet count to normal (less than 350x109/L) with the non-leukemogenic agent pegylated interferon alpha (IFN) to postpone or eliminate the use of the leukemogenic myelosuppressive agents busulphan and hydroxyurea. The ‘Early IFN Intervention Strategy’ is an effective non-leukemogenic first line curative treatment option in JAK2, CALR and MPL thrombocythemia in ET and PV to improve health care status, quality of life and life expectance by control and reduction of myeloproliferative disease burden.

Keywords:Myeloproliferative Neoplasms; Essential Thrombocythemia; Polycythemia vera; Myelofibrosis; JAK2^V617FMutation; MPL⁵¹⁵ Mutation; Calreticulin Mutation; Pegylated Interpheron-alpha: Hydroxyurea; Bone Marrow Histology

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Citation

Citation: Jan Jacques Michiels and Huub Van Vliet. “Aspirin Responsive Erythromelalgia, Cerebral and Coronary Microvascular Thrombotic Manifestations and the ‘Early Interferon First Line Intervention strategy’ as Curative Treatment Option in Essential Thrombocythemia and Polycythemia Vera". Acta Scientific Pharmaceutical Sciences 4.2 (2020): 32-41.