Hypersensitive(sticky) platelets in JAK2-mutated essential thrombocythemia(ET) and polycythemia vera(PV) with thrombocythemia spontaneously activate at high shear in arterioles, secrete their inflammatory prostaglandi...Hypersensitive(sticky) platelets in JAK2-mutated essential thrombocythemia(ET) and polycythemia vera(PV) with thrombocythemia spontaneously activate at high shear in arterioles, secrete their inflammatory prostaglandin endoperoxides and induce plateletmediated arteriolar fibromuscular intimal proliferation. Constitutively activated JAK2 mutated hypersensitive(sticky) platelets spontaneously aggregate at high shear in the endarteriolar circulation as the cause of aspirin responsive erythromelalgia and platelet arterial thrombophilia in JAK2-mutated thrombocythemia patients. Increased production of prostglandin endoperoxides E2 and thromboxane A2 released by activated sticky platelets in arterioles account for redness warmth and swelling of erythromelalgia and platelet derived growth factor can readily explain the arteriolar fibromuscular intimal proliferation. Von Willebrand factor(VWF) platelet rich occlusive thrombi in arterioles are the underlying pathobiology of erythromelalgic acrocyanosis, migraine-like transient cerebral attacks(MIAs), acute coronary syndromes and abdominal microvscular ischemic events. Irreversible platelet cyco-oxygenase inhibition by aspirin cures the erythromelalgia, MIAs and microvascular events, corrects shortened platelet survival to normal, and returns increased plasma levels of betaTG, platelet factor 4, thrombomoduline and urinary thromboxane B2 excretion to normal in symptomatic JAK2-thrombocythemia patients. In vivo activation of sticky platelets and VWF-platelet aggregates account for endothelial cell activation to secrete thrombomoduline and sVCAM followed by occlusion of arterioles by VWF-rich platelet thrombi in patients with erythromelalgic thrombotic thrombocythemia(ETT) in ET and PV patients. ETT is complicated by spontaneous hemorrhagic thrombocythemia(HT) or paradoxical ETT/HT due to acquired von Willebrand disease type 2A at platelet counts above 1000 × 10~9/L and disappears by cytoreduction of platelets to normal(< 400 × 10~9/L).展开更多
Essential thrombocythemia(ET) and polycythemia vera(PV) frequently present with erythromelalgia and acrocyanotic complications, migraine-like microvascular cerebral and ocular transient ischemic attacks(MIAs) and/or a...Essential thrombocythemia(ET) and polycythemia vera(PV) frequently present with erythromelalgia and acrocyanotic complications, migraine-like microvascular cerebral and ocular transient ischemic attacks(MIAs) and/or acute coronary disease. The spectrum of MIAs in ET range from poorly localized symptoms of transient unsteadiness, dysarthria and scintillating scotoma to focal symptoms of transient monocular blindness, transient mono- or hemiparesis or both. The attacks all have a sudden onset, occur sequentially rather than simultaneously, last for a few seconds to several minutes and are usually associated with a dull, pulsatile or migraine-like headache. Increased hematocrit and blood viscosity in PV patients aggravate the microvascular ischemic syndrome of thrombocythemia to major arterial and venous thrombotic complications. Phlebotomy to correct hematocrit to normal in PV significantly reduces major arterial and venous thrombotic complications, but fails to prevent the platelet-mediated erythromelalgia and MIAs. Complete long-term relief of the erythromelalgic microvascular disturbances, MIAs and major thrombosis in ET and PV patients can be obtained with low dose aspirin and platelet reduction to normal, but not with anticoagulation. Skin punch biopsies from the erythromelalgic area show fibromuscular intimal proliferation of arterioles complicated by occlusive plateletrich thrombi leading to acrocyanotic ischemia. Symptomatic ET patients with erythromelalgic microvascular disturbances have shortened platelet survival, increased platelet activation markers β-thromboglobulin(β-TG), platelet factor 4(PF4) and thrombomoduline(TM), increased urinary thromboxane B2(TXB2) excretion, and no activation of the coagulation markers thrombin fragments F1+2 and fibrin degradation products. Inhibition of platelet cyclooxygenase(COX1) by aspirin is followed by the disappearance and no recurrence of microvascular disturbances, increase in platelet number, correction of the shortened platelet survival times to normal, and reduction of increased plasma levels of β-TG, PF4, TM and urinary TXB2 excretion to normal. These results indicate that platelet-mediated fibromuscular intimal proliferation and platelet-rich thrombi in the peripheral, cerebral and coronary end-arterial microvasculature are responsible for the erythromelalgic ischemic complica-tions, MIAs and splanchnic vein thrombosis. Baseline platelet P-selectin levels and arachidonic acid induced COX1 mediated platelet activation showed a highly significant increase of platelet P-selectin expression(not seen in ADP and collagen stimulated platelets), which was significantly higher in JAK2V617 F mutated compared to JAK2 wild type ET.展开更多
目的评价改善循环、营养神经方法治疗红斑肢痛症的疗效和安全性。方法 7例临床诊断的红斑肢痛症患者给予营养神经:水溶性维生素1支(0.486 g/支),iv drip,qd,奥德金1.2 g,iv drip,qd;改善循环:参麦60 ml iv drip,qd,的方法治疗,约3周后,...目的评价改善循环、营养神经方法治疗红斑肢痛症的疗效和安全性。方法 7例临床诊断的红斑肢痛症患者给予营养神经:水溶性维生素1支(0.486 g/支),iv drip,qd,奥德金1.2 g,iv drip,qd;改善循环:参麦60 ml iv drip,qd,的方法治疗,约3周后,观察其疗效和安全性。结果 7例红斑肢痛症的患者,经过约3周的治疗,其临床症状消失;治疗前后检查血尿常规,肝肾功能,心电图,未见异常。跟踪观察3月,1例患者症状复发,但症状较治疗前减轻。重复治疗2周,患者症状完全缓解,跟踪观察3月,患者症状未再复发。结论改善循环、营养神经方法治疗红斑肢痛症安全有效。展开更多
文摘Hypersensitive(sticky) platelets in JAK2-mutated essential thrombocythemia(ET) and polycythemia vera(PV) with thrombocythemia spontaneously activate at high shear in arterioles, secrete their inflammatory prostaglandin endoperoxides and induce plateletmediated arteriolar fibromuscular intimal proliferation. Constitutively activated JAK2 mutated hypersensitive(sticky) platelets spontaneously aggregate at high shear in the endarteriolar circulation as the cause of aspirin responsive erythromelalgia and platelet arterial thrombophilia in JAK2-mutated thrombocythemia patients. Increased production of prostglandin endoperoxides E2 and thromboxane A2 released by activated sticky platelets in arterioles account for redness warmth and swelling of erythromelalgia and platelet derived growth factor can readily explain the arteriolar fibromuscular intimal proliferation. Von Willebrand factor(VWF) platelet rich occlusive thrombi in arterioles are the underlying pathobiology of erythromelalgic acrocyanosis, migraine-like transient cerebral attacks(MIAs), acute coronary syndromes and abdominal microvscular ischemic events. Irreversible platelet cyco-oxygenase inhibition by aspirin cures the erythromelalgia, MIAs and microvascular events, corrects shortened platelet survival to normal, and returns increased plasma levels of betaTG, platelet factor 4, thrombomoduline and urinary thromboxane B2 excretion to normal in symptomatic JAK2-thrombocythemia patients. In vivo activation of sticky platelets and VWF-platelet aggregates account for endothelial cell activation to secrete thrombomoduline and sVCAM followed by occlusion of arterioles by VWF-rich platelet thrombi in patients with erythromelalgic thrombotic thrombocythemia(ETT) in ET and PV patients. ETT is complicated by spontaneous hemorrhagic thrombocythemia(HT) or paradoxical ETT/HT due to acquired von Willebrand disease type 2A at platelet counts above 1000 × 10~9/L and disappears by cytoreduction of platelets to normal(< 400 × 10~9/L).
文摘Essential thrombocythemia(ET) and polycythemia vera(PV) frequently present with erythromelalgia and acrocyanotic complications, migraine-like microvascular cerebral and ocular transient ischemic attacks(MIAs) and/or acute coronary disease. The spectrum of MIAs in ET range from poorly localized symptoms of transient unsteadiness, dysarthria and scintillating scotoma to focal symptoms of transient monocular blindness, transient mono- or hemiparesis or both. The attacks all have a sudden onset, occur sequentially rather than simultaneously, last for a few seconds to several minutes and are usually associated with a dull, pulsatile or migraine-like headache. Increased hematocrit and blood viscosity in PV patients aggravate the microvascular ischemic syndrome of thrombocythemia to major arterial and venous thrombotic complications. Phlebotomy to correct hematocrit to normal in PV significantly reduces major arterial and venous thrombotic complications, but fails to prevent the platelet-mediated erythromelalgia and MIAs. Complete long-term relief of the erythromelalgic microvascular disturbances, MIAs and major thrombosis in ET and PV patients can be obtained with low dose aspirin and platelet reduction to normal, but not with anticoagulation. Skin punch biopsies from the erythromelalgic area show fibromuscular intimal proliferation of arterioles complicated by occlusive plateletrich thrombi leading to acrocyanotic ischemia. Symptomatic ET patients with erythromelalgic microvascular disturbances have shortened platelet survival, increased platelet activation markers β-thromboglobulin(β-TG), platelet factor 4(PF4) and thrombomoduline(TM), increased urinary thromboxane B2(TXB2) excretion, and no activation of the coagulation markers thrombin fragments F1+2 and fibrin degradation products. Inhibition of platelet cyclooxygenase(COX1) by aspirin is followed by the disappearance and no recurrence of microvascular disturbances, increase in platelet number, correction of the shortened platelet survival times to normal, and reduction of increased plasma levels of β-TG, PF4, TM and urinary TXB2 excretion to normal. These results indicate that platelet-mediated fibromuscular intimal proliferation and platelet-rich thrombi in the peripheral, cerebral and coronary end-arterial microvasculature are responsible for the erythromelalgic ischemic complica-tions, MIAs and splanchnic vein thrombosis. Baseline platelet P-selectin levels and arachidonic acid induced COX1 mediated platelet activation showed a highly significant increase of platelet P-selectin expression(not seen in ADP and collagen stimulated platelets), which was significantly higher in JAK2V617 F mutated compared to JAK2 wild type ET.
文摘目的评价改善循环、营养神经方法治疗红斑肢痛症的疗效和安全性。方法 7例临床诊断的红斑肢痛症患者给予营养神经:水溶性维生素1支(0.486 g/支),iv drip,qd,奥德金1.2 g,iv drip,qd;改善循环:参麦60 ml iv drip,qd,的方法治疗,约3周后,观察其疗效和安全性。结果 7例红斑肢痛症的患者,经过约3周的治疗,其临床症状消失;治疗前后检查血尿常规,肝肾功能,心电图,未见异常。跟踪观察3月,1例患者症状复发,但症状较治疗前减轻。重复治疗2周,患者症状完全缓解,跟踪观察3月,患者症状未再复发。结论改善循环、营养神经方法治疗红斑肢痛症安全有效。
