Aspirin responsive platelet thrombophilia in essential thrombocythemia and polycythemia vera

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.

Coronary spasm-related acute myocardial infarction in a patient with essential thrombocythemia

We report a case of essential thrombocythemia(ET) in a 30-year-old female who exhibited inferior wall ST-elevation acute myocardial infarction(AMI) without significant obstructive coronary artery disease.Right coronary vasospasm was observed after intra-coronary methylergonovine administration and she received verapamil 120 mg/d thereafter and hydroxyurea 1500 mg/d for thrombocythemia.After discontinuation of the hydroxyurea for 9 mo based on the impression of coronary spasm-related instead of coronary thrombosis-related AMI,her platelet count rose but no chest pain was observed.It is suggested that coronary spasm potentially plays a role in patients with ET,AMI and no significant coronary artery stenosis.

Risk of second primary malignancies in a population-based study of adult patients with essential thrombocythemia

AIM:To determine the risk of second primary malignancy(SPM) and survival of patients with essential thrombocythemia(ET).METHODS:We identified all patients with ET diagnosed during 2001 to 2011 from the Surveillance,Epidemiology and End Results(SEER) 18 database.Actuarial and relative survival methods were used to calculate the survival statistics.We utilized the SEER 13 database to calculate SPM.We used multiple primary standardized incidence ratio(SIR) session of the SEER*Stat software(version 8.1.5) to calculate SIR and excess risk of SPM for ET patients.RESULTS:Age standardized five-year cause-specific survival was greater for patients < 50 years vs those ≥ 50 years(99.4% vs 93.5%,P < 0.01).Five-year causespecific survival was lower for men vs women(70.2% vs 79.7%).A total of 201 patients(2.46%) developed SPM at a median age of 75 years.SPMs occurred at an observed/expected(O/E) ratio of 1.26(95%CI:1.09-1.45,P = 0.002) with an absolute excess risk(AER) of 37.44 per 10000 population.A significantly higher risk was noted for leukemia(O/E 3.78; 95%CI:2.20-6.05,P < 0.001; AER 11.28/10000).CONCLUSION:ET patients have an excellent causespecific five-year survival but are at an increased risk of SPM,particularly leukemia,which may contribute to excess deaths.

Gastroesophageal varices in a patient presenting with essential thrombocythemia:A case report

BACKGROUND Gastroesophageal varices are a rare complication of essential thrombocythemia(ET).ET is a chronic myeloproliferative neoplasm(MPN)characterized by an increased number of blood platelets.CASE SUMMARY A 46-year-old woman,who denied a history of liver disease,was admitted to our hospital on presentation of hematemesis.Laboratory examination revealed a hemoglobin level of 83 g/L,and a platelet count of 397×109/L.The appearance of gastric and esophageal varices with red colored signs as displayed by an urgent endoscopy was followed by endoscopic variceal ligation and endoscopic tissue adhesive.Abdominal computed tomography revealed cirrhosis,marked splenomegaly,portal vein thrombosis and portal hypertension.In addition,bone marrow biopsy and evidence of mutated Janus kinase 2,substantiated the onset of ET.The patient was asymptomatic with regular routine blood testing during the 6-mo follow-up period.Therefore,in this case,gastroesophageal varices were induced by ET.CONCLUSION MPN should be given considerable attention when performing differential diagnoses in patients with gastroesophageal varices.An integrated approach such as laboratory tests,radiological examination,and pathological biopsy,should be included to allow optimal decisions and management.

塞利尼索治疗PET-MF 1例报告并文献复习

目的探讨原发性血小板增多症继发骨髓纤维化(PET-MF)的临床特点及诊治方法。方法报告1例PET-MF病人,结合相关的文献复习,总结其临床特点及诊治经验。结果病人有原发性血小板增多症病史9年,期间给予羟基脲、干扰素、阿司匹林治疗,疾病进展至骨髓纤维化后,给予芦可替尼治疗一度有效,后病人血小板计数持续增高,出现剧烈骨痛,在原来方案基础上联合塞利尼索治疗,病人骨痛感消失、脾脏缩小,治疗效果明显。结论PET-MF病人疾病进展后会出现骨痛、发热,使用包括JAK2抑制剂芦可替尼在内的传统治疗方案效果不佳时,可考虑联合新药核输出蛋白1抑制剂塞利尼索控制疾病进展及缓解病人症状。

Essential thrombocythemia with non-ST-segment elevation myocardial infarction as the first manifestation:A case report

BACKGROUND We report a case of essential thrombocythemia(ET)in a 44-year-old male who exhibited non-ST-segment-elevation myocardial infarction(NSTEMI)as the first manifestation without known cardiovascular risk factors(CVRFs).For the first time,we reported a left main trifurcation lesion in NSTEMI caused by ET,including continuous stenosis lesions from the left main to the ostial left anterior descending(LAD)artery and an obvious thrombotic lesion in the ostial and proximal left circumflex(LCX)artery.There was 60%diffuse stenosis in the left main(LM)that extended to the ostial LAD,thrombosis of the ostial LAD and proximal LCX,and 90%stenosis in the proximal LCX.During the operation,thrombus aspiration was performed,but no obvious thrombus was aspirated.Performing the kissing balloon technique(KBT)in the LCX and LM unexpectedly increased the narrowness of the LAD.Then,the single-stent crossover technique,final kissing balloon technique and proximal optimization technique(POT)were performed.On the second day after percutaneous coronary intervention(PCI),the number of platelets(PLTs)still increased significantly to as high as 696×10^(9)/L.The bone marrow biopsy done later,together with JAK2(exon 14)V617F mutation,confirms the diagnosis of ET.Hydroxyurea was administered to inhibit bone marrow proliferation to control the number of PLTs.CASE SUMMARY A 44-year-old male patient went to a local hospital for treatment for intermittent chest pain occurring over 8 h.The examination at the local hospital revealed elevated cTnI and significantly elevated platelet.Then,he was diagnosed with acute myocardial infarction and transferred to our hospital for emergency interventional treatment by ambulance.During the operation,thrombus aspiration,the single-stent crossover technique,final kissing balloon technique and POT were performed.Dual antiplatelet therapy comprising aspirin and ticagrelor was used after PCI.Evidence of mutated JAK2 V617F and bone marrow biopsy shown the onset of ET.Together with JAK2(exon 14)V617F mutation,ET was diagnosed according to the World Health Organization(WHO)diagnostic criteria,and the patient was placed on hydroxyurea.During the one-year postoperative period,repeated examinations showed a slight increase in PLTs,but the patient no longer had chest tightness,chest pain or bleeding or developed new thromboembolisms.CONCLUSION Routine physical examinations and screenings are conducive to the early detection of ET,and the risk for thrombosis should be assessed.Then,active antiplatelet therapy and myelosuppression therapy should be used for high-risk ET patients.

A latent form of essential thrombocythemia presenting as portal cavernoma

Essential thrombocythemia is frequently associated with abdominal thrombotic complications including portal cavernoma as a consequence of chronic portal vein thrombosis.Essential thrombocythemia in a latent form is difficult to identify at onset due to the absence of an overt disease phenotype.In the presented case report,the diagnosis of essential thrombocythemia was initially missed because the typical disease phenotype was masked by bleeding and hypersplenism.The correct diagnosis was only reached when the patient experienced persistent thrombocytosis and pseudohyperkalemia after a shunt operation.

Leukocytosis at Diagnosis in Patients with Essential Thrombocythemia Is a Risk Factor for Transformation into Myelofibrosis

Myelofibrosis (MF) represents the major long-term complication of essential thrombocythemia (ET). There is evidence that leukocytosis at diagnosis is associated with poorer survival in patients with ET. In this study, we retrospectively evaluated 143 patients with ET, diagnosed in agreement with WHO criteria, followed in a single centre over >10 years. Nine of them transformed into MF (post-essential thrombocythemia-myelofibrosis PET-MF). We compared PET-MF data at diagnosis with that of the remaining 134 patients (ET-1) and with a selected sub-group of ET-1 (ET-2, 19 pats) sex, age and follow-up duration matched to PET-MF. The PET-MF evolution rate was 4.6 per 1000 person-years;white blood cells count (WBC) count, haemoglobin levels and hematocrit were higher in PET-MF than in ET-1 (P = 0.01) while only WBC was higher than in ET-2 (P = 0.01). With multivariate analysis, only WBC count retained its signifi-cance. Our study highlights the prognostic relevance of leukocytosis on myelofibrotic transformation of ET.

Mechanism of Inhibitory Effect of Essential Oil from Valerianae Jatamansi Rhizoma et Radix on Activation of Microglia

[Objectives]To investigate the inhibitory effect and possible mechanism of essential oil from Valerianae Jatamansi Rhizoma et Radix on microglia activation induced by lipopolysaccharide(LPS).[Methods]The LPS-induced microglia activation model was established and treated with different doses of essential oil from Valerianae Jatamansi Rhizoma et Radix.MTT assay was used to detect cell viability,ELISA to detect IL-6 secretion,RT-PCR to detect mRNA expression levels of IL-6,IL-1β,NF-κB,and IκBα,Western blotting to detect the protein expression of IL-6,IL-1β,NF-κB,IκBα,and their phosphorylated products.[Results]Compared with the normal control group,the model group showed increased IL-6 content(P<0.01),upregulated mRNA and protein levels of IL-6,IL-1β,and NF-κB(P<0.01),and elevated ratio of P-IκBα/IκBα(P<0.05).Compared with the model group,4 and 2μg/L essential oil from Valerianae Jatamansi Rhizoma et Radix reduced the content of IL-6(P<0.05),while 4,2,and 1μg/L essential oil from Valerianae Jatamansi Rhizoma et Radix down-regulated the mRNA and protein levels of IL-6,IL-1β,and NF-κB to varying degrees(P<0.05 or P<0.01),up-regulate the mRNA expression of IκBα(P<0.05 or P<0.01),and decreased the ratio of P-IκBα/IκBα(P<0.05 or P<0.01).[Conclusions]Essential oil from Valerianae Jatamansi Rhizoma et Radix can inhibit LPS-induced microglia activation,and its mechanism may be related to the inhibition of the NF-κB/IκBαsignaling pathway.

Toxicity of targeted anticancer treatments on the liver in myeloproliferative neoplasms

The liver has a central role in metabolism,therefore,it is susceptible to harmful effects of ingested medications(drugs,herbs,and nutritional supplements).Druginduced liver injury(DILI)comprises a range of unexpected reactions that occur after exposure to various classes of medication.Even though most cases consist of mild,temporary elevations in liver enzyme markers,DILI can also manifest as acute liver failure in some patients and can be associated with mortality.Herein,we briefly review available data on DILI induced by targeted anticancer agents in managing classical myeloproliferative neoplasms:Chronic myeloid leukemia,polycythemia vera,essential thrombocythemia,and myelofibrosis.

骨髓形态学对早期原发性骨髓纤维化与原发性血小板增多症的诊断价值

目的探讨骨髓巨核细胞病理特征、临床特征及基因突变在早期原发性骨髓纤维化(pre-PMF)及原发性血小板增多症(ET)鉴别诊断中的价值。方法收集2010年1月至2020年12月68例既往根据2008版世界卫生组织(WHO)骨髓增生性肿瘤(MPN)诊断标准初诊为原发性骨髓纤维化(PMF)及ET的患者,依据2016年版WHO诊断标准对患者骨髓活检组织切片进行重新评估,并收集其实验室检查、临床特征、诊断分型及基因突变检测等结果进行统计分析。结果依据更新诊断标准重新分型后,ET患者23例,PMF患者45例,其中pre-PMF 22例(占PMF的49%),明显期原发性骨髓纤维化(overt-PMF)23例(占PMF的51%)。男性35例(51%)、女性33例(49%),年龄≥65岁患者24例(35%),白细胞增多35例(51%),贫血17例(25%),血小板降低10例(15%),脾肿大25例(37%)。pre-PMF组Ⅰ型、Ⅱ型、Ⅲ型、Ⅴ型巨核细胞百分比均高于ET组(P均<0.01),ET组Ⅳ型巨核细胞百分比高于pre-PMF组(P<0.01)。ET、pre-PMF和overt-PMF组的JAK2V617F、CALR、MPL驱动基因突变差异均无统计学意义(P>0.05)。结论ET和pre-PMF患者骨髓巨核细胞病理改变不同,结合JAK2V617F、CALR、MPL驱动基因突变及纤维增生分级及临床特征对于pre-PMF和ET具有鉴别诊断价值。

原发性血小板增多症患者中JAK2、CALR及三阴性驱动突变的临床特征比较

目的:探讨原发性血小板增多症(ET)患者的突变基因与临床特征的关系。方法:对2018年10月至2022年3月69例ET患者的临床资料进行回顾性分析。将患者按突变的驱动基因类型分为JAK2组、CALR组与三阴性组,对3组患者的性别、年龄、心血管危险因素、血栓、脾肿大、血常规、凝血状态进行分析。结果:69例ET患者中,46例伴随JAK2基因突变,14例伴随CALR基因突变,8例为三阴性,1例伴随MPL基因突变。3组患者的年龄、性别无显著差异(P>0.05)。JAK2组血栓率最高,为26.09%(12/46),三阴性组为12.5%(1/8),CALR组无血栓事件。JAK2组伴随脾肿大发生率最高,为34.78%(16/46),而三阴性组无脾肿大发生。JAK2组的白细胞数为(9.00±4.86)×10^(9)/L,显著高于CALR组的(6.03±2.32)×10^(9)/L(P<0.05)。JAK2组的血红蛋白含量为(148.43±18.79)g/L,显著高于三阴性组的(131.00±15.17)g/L(P<0.05)。JAK2组的红细胞压积为(0.44±0.06)%,亦显著高于三阴性组的(0.39±0.05)%(P<0.05)。JAK2组血小板数为(584.17±175.77)×10^(9)/L,显著低于CALR组的(703.07±225.60)×10^(9)/L(P<0.05)。JAK2组和三阴性组纤维蛋白原含量分别为(2.64±0.69)g/L和(3.05±0.77)g/L,均显著高于CALR组的(2.24±0.47)g/L(P<0.05,P<0.01)。三阴性组活化部分凝血活酶时间为(28.61±1.99)s,较CALR组的(31.45±3.35)s显著降低(P<0.05)。结论:不同驱动基因突变ET患者的血细胞计数与凝血状态存在差异。与CALR组相比,JAK2组血栓率、白细胞数和纤维蛋白原含量均显著升高,而血小板数显著降低;与三阴性组相比,JAK2组脾大发生率和红细胞压积显著升高;与CALR组相比,三阴性组的纤维蛋白原含量显著升高、活化部分凝血活酶时间显著降低。

加味天麻钩藤饮对阴虚阳亢型高血压患者血浆ET、PRA、AⅡ的影响

目的 探讨加味天麻钩藤饮降压效果及对血浆内皮素 (ET)、肾素活性 (PRA)、血管紧张素 (AⅡ )的影响。方法 146例阴虚阳亢型高血压病患者随机分为两组 ,10 2例给予加味天麻钩藤饮 ,44例给予巯甲丙脯酸、硝苯地平。治疗前后测定血浆ET、PRA、AⅡ水平。结果 (1)治疗组降压总有效率 88 2 4% ,与对照组相当 ,对主要症状改善率优于对照组 ;(2 )治疗后治疗组血浆ET、AⅡ水平低于对照组 ,但均高于正常人。结论 加味天麻钩藤饮既能降低ET、AⅡ含量 ,又能明显降低血压。

老年原发性高血压患者血压控制与血浆BNP、ET-1含量的关系

目的 探讨老年原发性高血压患者经药物治疗后血脑利钠肽 (BNP)、内皮素 - 1(ET- 1)含量与血压控制情况的关系。方法 测定 5 6例经药物治疗后老年原发性高血压患者的血浆 BNP、ET- 1含量。结果 血压控制正常组血浆 BNP和 ET- 1含量均显著低于血压控制不理想组 (分别为 P<0 .0 5和 P<0 .0 1)。结论 血浆BNP、ET- l的含量能反映老年原发性高血压患者的血压控制情况 。

老年男性高血压患者血浆ADM和ET-1含量变化的意义

目的:探讨老年男性高血压患者血浆肾上腺髓质素(ADM)、内皮素-1(ET-1)含量变化的临床意义。方法:用放射免疫分析测定62例老年男性高血压患者血浆ADM、ET-1含量,并与35例年龄、性别匹配的健康老年人对照。结果:高血压组血浆ADM、ET-1含量显著高于正常对照组(P<0.01),两者均随高血压分级1、2、3级组逐渐递增(P<0.01,<0.05);血压控制不良者明显高于血压控制良好者(P<0.01),病情重组显著高于病情轻组(P<0.01);伴肾功能受损者也显著高于肾功能正常者(P<0.01);血浆ET-1含量平均增幅明显高于血浆ADM(P<0.01);高血压组血浆ADM与ET-1含量呈正相关(r=0.394,P<0.01);正常对照组两者含量不相关(r=0.172,P>0.05)。结论:老年男性高血压患者血浆舒血管活性肽ADM含量显著增高,可能是机体的一种代偿性自身调节机制,以此抑制ET-1等缩血管活性肽增高对血压调节产生不良的影响,对机体起到自身代偿性保护作用。

应用仲景下瘀血法治疗原发性血小板增多症探讨

原发性血小板增多症的病理机制主要是骨髓中巨核细胞过度增殖,导致血小板计数升高,进而积聚成瘀。对于瘀血导致的疾病,医圣张仲景应用下瘀血法进行治疗,本文对仲景所创下瘀血诸方进行辨析,总结方剂各自的组方用药特点、临床应用指征,联系到原发性血小板增多症的治疗中,从疾病分期以及不同证候灵活运用下瘀血法,为现代中医治疗原发性血小板增多症提供些许思路。

阻塞性睡眠呼吸暂停低通气综合征患者血浆ET-1、NO水平的变化及nCPAP对其影响

目的 观察阻塞性睡眠呼吸暂停低通气综合征 (OSAHS)患者经鼻持续气道内正压通气 (nCPAP)治疗前后血浆ET 1、NO水平的变化 ,并探讨其临床意义。方法 选择OSAHS无EH者 (A组 ) ,OSAHS合并EH者 (B组 ) ,正常对照 (C组 ) ,三组行PSG监测。用放免法测血浆ET 1 ,NO采用硝酸还原酶法。A、B两组施以nCPAP治疗。用袖带加压法观察血压。结果 ①与C组相比 ,A组AHI、ET 1 /NO增高 ,最低SaO2 下降 ,治疗后情况相反 ;A组治疗前后ET 1 /NO分别与AHI、最低SaO2 均明显相关 (r分别为 0 40 8、- 0 569)。②与C组相比 ,B组MBP、AHI、ET 1 /NO增高 ,最低SaO2 下降 ,治疗后情况相反 ;B组治疗前后MBP分别与ET 1 /NO、AHI、最低SaO2 均明显相关 ,r分别为 0 439、0 51 5、- 0 455。结论 ①OSAHS可引起血压升高 ,某些血管舒缩因子比例失衡可能在OSAHS合并EH中起一定的病理作用 ;

原发性高血压病伴房颤患者血浆ET和BNP的含量变化

目的 :探讨原发性高血压伴房颤患者血浆ET、BNP的含量变化。方法 :应用IRMA法测定 4 8例原发性高血压病伴房颤患者和 82例原发性高血压病无房颤患者血浆ET、BNP含量 ,并以 5 6例健康人作对照。结果 :原发性高血压病伴房颤组血浆ET、BNP含量均非常显著高于正常人组 (p <0 0 0 1)。结论 :深入研究原发性高血压病患者血浆ET、BNP的含量变化 ,对预防和治疗原发性高血压心脏病将有重要的临床意义。

JAK2V617F突变负荷量对ET患者临床表现和生存影响的研究

目的:观察JAK2V617F突变量对ET(原发性血小板增多症)患者的临床表现及生存影响。方法:病例来源于2013.10-2016.12月在云南省第一人民医院就诊和治疗的ET患者229例,采取患者的骨髓血标本2 ml,肝素抗凝,红细胞裂解液分离单个核细胞,使用DNA抽提试剂盒抽提患者基因组DNA。利用等位基因特异性PCR方法扩增目标DNA,琼脂糖凝胶电泳筛选出120例JAK2V617F突变阳性的标本。再通过实时定量PCR(RT-PCR)检测JAK2V617F突变负荷量,并通过测序方法检测PCR筛选的准确率。结果:伴有血栓形成的ET患者JAK2V617F突变负荷量高于未发生血栓组(23.2%vs 14.2%),(P <0.05);WBC计数升高组(> 10×10~9/L)及HGb浓度升高(> 150 g/L)患者JAK2V617F突变负荷量高于对照组(P <0.05),17例脾肿大患者JAK2V617F基因突变负荷量高于45例脾脏未肿大组(P <0.05),年龄、性别与JAK2V617F基因突变量之间无相关性(P> 0.05)。经单因素分析显示,JAK2V617F突变量对生存率无统计学影响;多因素分析显示,WBC计数、血红蛋白浓度、年龄、性别及脾肿大对生存率无影响(P> 0.05)。结论:JAK2V617F突变负荷量影响ET患者的临床表现,JAK2V617F突变负荷量与是否形成血栓相关,性别、年龄与基因突变负荷量无关。

原发性高血压患者治疗前后血浆ET和E选择素检测的临床意义

目的:探讨了原发性高血压患者治疗前后血浆ET和E选择素水平及临床意义。方法:应用放免法检测了39例原发性高血压患者治疗前后血浆ET水平,酶联免疫法检测E选择素水平,并与35名正常健康人作比较。结果:原发性高血压患者治疗前后血浆ET和E选择素水平非常显著地高于正常人组水平(P<0.01),经治疗3个月后则与正常人组比较无显著性差异(P>0.05)。结论:血浆ET和E选择素的异常升高是原发性高血压发病的病理因素之一,对诊断、治疗和预后均有重要的临床价值。