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•18 •国际眼科纵览202丨年 2 月第45 卷第丨期Int Rev Ophthalmol，Feb. 2021，Vol. 45, No. 1•综述•糖尿病患者白内障手术的相关风险赵鑫慧周南齐艳华哈尔滨医科大学附属第二医院眼科150086通信作者：齐艳华，Email :qyh86605643@ 126. com【摘要】白内障是糖尿病患者常见眼部并发症之一。
与非糖尿病患者相比，搪尿病患者白内障发病年龄更早，进展更迅速。
虽然超声乳化白内障手术和传统白内障幾外摘除手术相比手术时间短，视力恢复快，但对于糖尿病患者，白内障手术风险仍远远高于非糖尿病患者术中小瞳孔的出现概率较大，手术可导致糖尿病视网膜病变加重，术后更易发生黄斑水肿、眼内炎、角膜损伤、干眼症等。
(国际眼科纵览，2021，45:18-22)【关键词】白内障;糖尿病;并发症DOI ：10. 3760/ cma. j. issn. 1673-5803. 2021. 01. 004Risk of cataract surgery in diabetic patientsZhao Xinhui, Zhou Nan, Qi YanhuaDepartment of Ophthalmology, the Secorul AJfiliated Hospital, Harbin Medical University, Harbin 150086,ChinaCorresponding author：Ql Yanhua, Em ail：(/yh86605643@ 126. com【Abstract】Cataract is one of the most common eye disorders in diabetic patients. Compared withnon-diabetic patients, the diabetic patients always have cataract disease and perlorm the operation in earlierage. Although phacoemulsification makes cataract surger\ in short time and vision recovery faster, hut therisk of cataract surgery complications for diabetic patients are still much higher than that of normal patients,such as small pupil during the surgery, and progress of diabetic retinopathy, macular edema, endophthalmitis, corneal damages, dry eye after the surgery. (Int Rev Ophthalmoly2021 ^45：18-22)【Key words】cataract; diabetes mt*llitus; complicationDOI：10. 3760/ cma. j. issn. 1673-5803. 2021. 01. 004糖尿病是最常见的慢性系统性疾病之一，全球 约4.25亿患者，发病率仍在逐年上升,预计在2040 年糖尿病患病人数可能超过6.4亿I。
2021欧洲临床营养与代谢协会ESPEN外科营养治疗实践指南（全文）导读2021年4月19日，欧洲临床营养与代谢协会（European Society for Clinical Nutrition and Metabolism, ESPEN）在其官方杂志Clinical Nutrition上在线发布了最新版的外科患者营养治疗实践指南（ESPEN Practical Guideline: Clinical Nutrition in Surgery）。
该指南从临床实用性出发，对2017年ESPEN外科患者营养治疗指南进行缩减，从外科患者营养治疗的总体原则到特殊类型外科患者的个体化营养治疗，总计给出37条推荐（内容没有变化），并添加了流程图，更加便于临床医师、营养师及护士等在临床实践中使用。
一、总则1.1 术前是否需要禁食？推荐1Preoperative fasting from midnight is unnecessary in most patients. Patients undergoing surgery, who are considered to have no specific risk of aspiration, shall drink clear fluids until two hours before anesthesia. Solids shall be allowed until six hoursbefore anesthesia. (Grade of recommendation A –strong consensus)大部分患者不需要从术前当晚开始禁食。
无误吸风险的患者可在麻醉前2小时饮用清流质，麻醉前6小时进食固体食物。
（推荐等级A-强烈同意）1.2 择期手术患者使用碳水化合物进行术前代谢准备能否获益？推荐2In order to reduce perioperative discomfort including anxiety oral preoperative carbohydrate treatment (instead of overnight fasting, the night before and two hours before surgery) should be administered (B). To impact postoperative insulin resistance and LOS, preoperative carbohydrates can be considered in patients undergoing major surgery (0). (Grade of recommendation B/0 –strong consensus)手术前夜以及术前2小时口服碳水化合物（不需要术前禁食禁饮）有助于减少焦虑等不适（B）。
•综述•隆突性皮肤纤维肉瘤的诊疗进展刘珍如 周 园 刘梦茜 王晓晴 综述，王大光 审校（南京医科大学第一附属医院皮肤科 江苏 南京 210029）[摘要]隆突性皮肤纤维肉瘤（Dermatofibrosarcoma protuberans,DFSP）是一种低度恶性肿瘤，早期DFSP临床症状不典型、特异性低，导致临床医师容易漏诊、误诊，此外,DFSP经手术治疗后仍有高复发率，部分病变更会出现纤维肉瘤化改变，增加其转移风险、并提示预后不佳。
近年来，许多研究开始关注DFSP的诊断及治疗，透过皮肤镜、病理活检帮助医师早期诊断，提高疾病检出率，并通过手术、放疗及化疗等治疗，有效降低病变复发率、避免远处转移，本文就DFSP的最新治疗进展作一综述。
[关键词]隆突性皮肤纤维肉瘤；纤维肉瘤样隆突性皮肤纤维肉瘤；莫氏手术；皮肤镜；伊马替尼[中图分类号]R739.5 [文献标志码]A [文章编号]1008-6455(2021)03-0171-04Research Progress in Diagnosis and Treatment of Dermatofibrosarcoma ProtuberansLIU Zhen-ru,ZHOU Yuan,LIU Meng-xi,WANG Xiao-qing,WANG Da-guang(Department of Dermatology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029,Jiangsu,China)Abstract: Due to the atypical and low specificity clinical symptoms in early stage,Dermatofibrosarcoma protuberans (DFSP) is a low grade malignant tumor which might likely be misdiagnosis. In addition, even after surgical treatment DFSP still has a high recurrence rate. Lesions with fibrosarcomatous changes were associated with increased the risk of metastasis and poor prognosis. In recent years, many studies have begun to focus on the diagnosis and treatment of DFSP. Recent study showed with dermoscopy and pathological biopsy can help with early diagnosis and signicfanctly improve the detection rate. Also, with optimal treatment through surgery, radiotherapy and chemotherapy, recurrence and distant metastasis rate could be effectively reduced. This article reviews the recent progress of DFSP.Key words:dermatofibrosarcoma protuberan;fibrosarcomatous dermatofibrosarcoma protuberans; Mohs microgrsphic surgery;dermoscopy; imatinib基金项目：国家自然科学基金（编号：81000703、81472896）；江苏省自然科学基金（编号：BK2009437）；江苏省六大人才高峰资助项目 （编号：2015-WSW-026）通信作者：王大光，南京医科大学第一附属医院皮肤科，主任医师；E-mail:*****************第一作者：刘珍如，南京医科大学第一附属医院皮肤科，硕士研究生；E-mail:*****************隆突性皮肤纤维肉瘤是一种生长速度缓慢、起源于皮肤,并可累及皮下组织的低度恶性肿瘤，于1924年由Darier 及Ferrandh首次报道[1-2]，DFSP病理改变主要呈“蟹足样”浸润生长，男性发病率略高于女性。
A Neuro-Fuzzy Approach to MedicalDiagnostics∗†Patrik EklundDepartment of Computer Science,˚A bo Akademi University, Lemmink¨a inengatan14,SF-20520˚A bo,FinlandRobert Full´e rDepartment of Computer Science,E¨o tv¨o s Lor´a nd University, P.O.Box157,H-1502Budapest112,HungaryAbstractThere has been growing interest and activity in the area of medical decision making,especially in the last20years.As it has been pointed out by manyauthors[Adl86,Hay90,San92,Wan91],fuzzy set theory and neural nets havea number of properties that make them suitable for formalizing the uncertaininformation upon which medical diagnosis and treatment is usually based.Generalizing the earlier results of thefirst author[Ekl92],we provide a formal model of this process using the neuro-fuzzy theory,and illustrate ourapproach on a two-symptom artificial disease.1IntroductionIn[Ekl92a]we proposed an architecture(Diagai D)for a generic tool which supports data analysis and developement of diagnostic modules in clinical medicine.This architecture contains three main modules,each of which constitute different software packages.Thefirst one extracts related data(symptoms and signs)from hospital databases.The prepocessing module transforms(by the help of sigmoid functions)the ex-tracted raw data into a corresponding logical form.Finally,the third one is a single ∗Supported by GeDeMeDeS-project at˚A bo Akademi University funded by the Technology Development Centre,Helsinki.†in:P.Eklund and J.Mattila eds.,Proceedings of Fuzziness in Finland’93Workshop,˚A bo Akademis Tryckeri,˚A bo,199319-22;also in:Proceedings of EUFIT’93Conference,September 7-10,1993,Aachen,Germany,Verlag der Augustinus Buchhandlung,Aachen,1993810-813;also in:Fuzzy Systems&A.I.,3(1994),53-56.1layer backpropagation network,where the weights and the parameters of prepocess-ings functions are tuned in order to optimize the diagnostic performance.In[Ekl92]we demonstrated how preprocessed(fuzzified)data from single layer net-works can provide faster convergence and better diagnostic performance than raw data from multi-layered networks in backpropagation networks.In this paper we show that by adding a fourth module(in which we tune the exponents of a polynomial combination of the modified inputs)to Eklund’s method even better diagnostic performance can be reached without enlarging the network structure.We illustrate our ideas on a two-class discriminant problem.2Improving the diagnostic performanceA full description of the three modules is outside of the scope of this short paper and we refer to[Ekl92,Ekl92a]for futher reading.Suppose that after the backpropaga-tion learning algorithm we obtained the weights,w1,...w n,where n is the number of symptoms.Then in the additional fourth module(which is a single layer backpropagation network),instead of the weighted sum of the inputs we use their polynomial combi-nation as followsnsign(w i)(|w i|x pi)λii=1where x pi is the(preprocessed)value of the i-th symptom of the p-th patient,and we tune onlyλi,i=1,...,n,from the initial valuesλ1=1,...,λn=1.It is clear(because it is easier to separate by a continuous curve than by a line)that in many cases the new module provides a better diagnostic performance.However,as it was pointed out by many authors,it is impossible to provide the correct diagnosis in every case,because two persons can have approximately the same symptoms,and one suffers the disease and the other is healthy.We would need more information(additional significant symptoms)to separate them.3IllustrationFor simplicity,we illustrate our approach on a two-symptom artificial disesase.Sup-pose that a linear transformation of the raw data into the unit interval resulted in the following picture2: healthy : illIt is clear that there does not exist a line separating the ill persons from the healthy ones(due to the presense of many XOR structures).The meaning of the prepocession is to move as much as possible the ill persons to the direction of the top-right corner and the healthy ones to the direction of the bottom-left corner.Then we shall have more freedom to separate them.Sup-pose that after the backpropagation learning algorithm(third module)we got the following pictureIt is easy to see that by the help of fuzzification we could separate more persons than by a simple linear transformation.However,in certain cases we are still not able to separate them via a line.The fourth module provides a moreflexible curve for separation,but as we can see from the following picture,we could not provide the correct answer in every case.34SummaryWe have proposed to add a new module to Diagai D architecture,which can improve the diagnostic performance in many cases.The network structure is still kept small and explainable,which allows to spare time at computerized implementation and provides an easy way to communicate with the users of the software package. References[Adl86]K.P.Adlassing,Fuzzy set theory in medical diagnostics,IEEE Trans.on Systems,Man,and Cybernetics,Vol.SMC-16(1986)260-264.[Ekl92]P.Eklund,Network size versus propocessing,in:R.R.Yager and L.A.Zadeh eds.,Fuzzy Sets,Neural Networks and Soft Computing,(to appear). [Ekl92a]P.Eklund,Mrten Fogstrm and Jari Forsstrm,A generic neuro-fuzzy tool for developing medical decision support,in:P.Eklund ed.,Proceedings ofthe MEPP’92,˚A bo Akademi Press,˚A bo,199211-27.[Hay90]Y.Hayashi and A.Imura,Fuzzy neural expert system and its application to medical diagnosis,in:C.N.Manikopoulos,ed.,Proceedings of the8thInternational Congress of Cybernetics and Systems,New Jersey Instituteof Technology Press,Newark,NJ,199054-61.[San92] E.Sanchez,Fuzzy logic knowledge systems and artificial neural networks in medicine and biology,in:R.R.Yager and L.A.Zadeh,eds.,An In-troduction to Fuzzy Logic Applications in Intelligent Systems,Kluwer,Dordrecht-Boston,1992235-252.[Wan91]Y.Wang,The fuzzy neural network system for diagnosing silicosis,in: T.Terano,M.Sugeno,M.Mukaidono and K.Shigemasu eds.,Proceedingsof the International Fuzzy Engineering Symposium’91,I.O.S.Press,1992546-549.4。
医学常用治疗方法英语翻译In this article, we will explore commonly used medical treatment methods and provide their English translations. Please note that the following translations are provided for reference purposes and may vary depending on the context and usage.1. Hand washing: 手部洗净Hand washing is a fundamental practice in preventing the spread of infections. It involves using soap and water to clean the hands thoroughly.2. Vaccination: 接种疫苗Vaccination is the administration of vaccines to stimulate the immune system and provide protection against specific diseases. It helps prevent illness and reduce the spread of infectious agents.3. Antibiotics: 抗生素Antibiotics are medications used to treat bacterial infections. They work by inhibiting the growth or destroying bacteria, effectively treating the infection.4. Chemotherapy: 化疗Chemotherapy is a cancer treatment that uses drugs to destroy cancer cells. It can be administered orally or intravenously, and sometimes in combination with other treatments.5. Radiation therapy: 放射治疗Radiation therapy uses high-energy radiation to destroy cancer cells and shrink tumors. It can be delivered externally or internally, depending on the cancer type and location.6. Surgery: 手术Surgery is a medical procedure that involves an incision or manipulation of tissues to treat a condition or disease. It can be performed for various purposes, including removing tumors, repairing injuries, or correcting abnormalities.7. Physical therapy: 物理治疗Physical therapy is a rehabilitation treatment that focuses on improving mobility, function, and quality of life. It includes exercises, manual therapy, and other techniques to address musculoskeletal issues.8. Psychotherapy: 心理治疗Psychotherapy, also known as talk therapy, is a treatment that aims to improve mental health and well-being. It involves speaking with a trained therapist to explore thoughts, emotions, and behaviors.9. Acupuncture: 针灸疗法Acupuncture is an alternative medical practice originating from traditional Chinese medicine. It involves inserting thin needles into specific points on the body to relieve pain or treat various conditions.10. Herbal medicine: 中草药Herbal medicine utilizes plants and plant extracts to treat illnesses and promote overall health. Different herbs are used to target specific symptoms or imbalances in the body.11. Homeopathy: 顺势疗法Homeopathy is a system of alternative medicine that uses highly diluted substances to stimulate the body's self-healing abilities. It operates on the principle that "like cures like."12. Massage therapy: 按摩疗法Massage therapy involves manipulating muscles, soft tissues, and joints to promote relaxation and relieve tension. It can be used for pain management, stress reduction, and improving circulation.13. Herbal tea: 草药茶Herbal tea is an infusion of herbs, flowers, or other plant materials in hot water. Different herbs offer various benefits, such as reducing inflammation, aiding digestion, or promoting relaxation.14. Meditation: 冥想Meditation is a practice that involves focusing the mind to achieve mental clarity and calmness. It can help reduce stress, enhance self-awareness, and promote overall well-being.15. Yoga: 瑜伽Yoga is a mind-body practice that combines physical postures, breathing exercises, and meditation. It promotes flexibility, strength, and relaxation while improving mental and emotional well-being.Conclusion:These are some commonly used medical treatment methods and their English translations. It's important to consult with medical professionals to determine the most appropriate treatment for specific conditions. Remember, this article provides translations for reference purposes and may not always capture the full meaning or nuances of the original terms.。
妇产科英语试题及答案一、选择题（每题1分，共10分）1. Which of the following is a common gynecological examination?A. Blood pressure testB. Pap smearC. Chest X-rayD. Electrocardiogram2. What is the medical term for the first stage of labor?A. Latent phaseB. Active phaseC. Transition phaseD. Expulsion phase3. The hormone responsible for the development of female reproductive organs is:A. EstrogenB. ProgesteroneC. TestosteroneD. Insulin4. Which of the following is not a symptom of polycystic ovary syndrome (PCOS)?A. Irregular menstrual cyclesB. AcneC. InfertilityD. Excessive thirst5. What is the term used to describe the process of a fertilized egg implanting into the uterine lining?A. ImplantationB. ConceptionC. EmbryogenesisD. Parturition6. The most common type of birth is:A. Vaginal birthB. Cesarean sectionC. Breech birthD. Forceps-assisted birth7. Which of the following is a prenatal diagnostic test?A. UltrasoundB. AmniocentesisC. Blood pressure monitoringD. Fetal heart rate monitoring8. The hormone that stimulates the production of breast milk is:A. OxytocinB. ProlactinC. EstrogenD. Cortisol9. What is the medical term for the surgical removal of the uterus?A. HysterectomyB. OophorectomyC. SalpingectomyD. Cystoscopy10. Which of the following is a risk factor for gestational diabetes?A. Family history of diabetesB. SmokingC. Alcohol consumptionD. All of the above二、填空题（每空1分，共10分）1. The process of childbirth is divided into three stages: the _______ phase, the _______ phase, and the _______ phase.2. The medical condition characterized by the presence of cysts in the ovaries is known as _______.3. A _______ is a type of imaging technique used to visualize the fetus during pregnancy.4. The hormone _______ is responsible for the thickening of the uterine lining during the menstrual cycle.5. A _______ is a surgical procedure used to remove fibroids from the uterus.6. The _______ is the process by which a baby is born through the vagina.7. The _______ is a condition that affects the female reproductive system and can cause infertility.8. The _______ is the process of a woman's body preparing for childbirth.9. The _______ is a condition where the cervix opens too early during pregnancy, leading to a risk of preterm birth.10. The _______ is the period of time after childbirth when the mother's body returns to its pre-pregnancy state.三、简答题（每题5分，共20分）1. Explain the difference between a Pap smear and a colposcopy.2. Describe the stages of labor and the signs that indicate the onset of labor.3. What are the common symptoms of menopause, and how are they managed?4. Discuss the importance of prenatal care and the types of tests that are typically performed.四、论述题（每题15分，共30分）1. Discuss the various methods of contraception and their effectiveness, side effects, and suitability for different individuals.2. Elaborate on the role of a midwife in the process of childbirth and the importance of continuous support during labor.五、病例分析题（共30分）A patient presents to the gynecologist with complaints of heavy menstrual bleeding and severe cramps. She also mentions that she has been experiencing these symptoms for the pastsix months. Based on the information provided, discuss the possible causes of these symptoms, the diagnostic tests that may be performed, and the potential treatment options.答案：一、选择题1. B2. A3. A4. D5. A6. A7. B8. B9. A 10. A二、填空题1. First, second, third2. Polycystic ovary syndrome (PCOS)3. Ultrasound4. Progesterone5. Myomectomy6. Vaginal delivery7. Endometriosis8. Childbirth9. Cervical insufficiency10. Postpartum period三、简答题1. A Pap smear is a screening test for cervical cancer, whilea colposcopy is a more detailed examination of the cervix using a magnifying instrument.。
广1血病•淋巴瘤2021 年丨月第 30 卷第丨期Journal of Leukemia & Lymphoma，January 2021，Vol. 30，No. 1专题综论-多发性骨髓瘤免疫治疗进展林全德刘德龙宋永平郑州大学附属肿瘤医院河南省肿瘤医院血液科河南省血液病研究所，郑州 450003通信作者：宋永平，Emaihsongyongping()01@126_com扫码阅读电子版【摘要】嵌合抗原受体T细胞(CAR_T)和新型靶向治疗等生物免疫疗法的临床应用开辟了多发性骨髓瘤(MM)治疗的新领域靶向B细胞成熟抗原(BCM A)、同种异体CAR-T、抗体偶联药物(ADC)及靶向BCMA的双特异性抗体在多项临床研究中获得了令人瞩目的疗效及较好的安全性。
文章结合第62届美国血液学会(A SH)年会的相关报道对MM免疫治疗进展进行介绍。
【关键词】多发性骨髓瘤；嵌合抗原受体T细胞；B细胞成熟抗原；抗体偶联药物；双特异性抗体基金项目：河南省医学科技攻关计划联合共建项目（LHGJ20190649);河南省科技攻关计划(202102310372)DOI：10.3760/rma.j.ml 15356-20210111-00011Progress of immunotherapy for multiple myelomaLin Quande, Liu Delong, Song YongpingDepartment of Hematology, Affiliated Cancer Hospital of Zhengzhou University. Henan Cancer Hospital, HenanInstitute of Hematology, Zhengzhou 450003, ChinaCorresponding author: Song Yongping, Email:***********************【Abstract】The clinical application of biological immunotherapy such as chimeric antigen receptor Tcells (CAR-T) and novel targeted therapy has explored a new therapy for multiple myeloma (MM) treatment.Targeting B-cell maturation antigen (BCMA), allogeneic CAR-T, antihody-drug conjugate (ADC) and bispecificantibody targeting BCMA have achieved remarkable efficacy and safety in many clinictal studies. This articleintroduces the latest immunotherapy for M M at the 62nd American Society of Hematology (ASH) AnnualMeeting.【Key words】Multiple myeloma; Chimeric antigen receptor T cells; B - cell mature antigen;Antibody-drug conjugate; Bispecific antibodyFund program: Co-construction Project of iMedical Science and Technology Development Program ofHenan Province (LHGJ20190649); Science and Technology Development Program of Henan Province(202102310372)DOI： 10.3760/rma.j.rnl 15356-20210111-00011在过去的半个世纪里，多发性骨髓瘤（M M)的治 疗取得了显著进展，蛋白酶体抑制剂、免疫调节剂、单克隆抗体和嵌合抗原受体T细胞（CAR-T)等疗法的 临床应用，使的治疗进入靶向免疫治疗时代1'4。
Nplate® (romiplostim)(Subcutaneous)Document Number: IC‐0089 Last Review Date: 02/02/2023Date of Origin: 01/01/2012Dates Reviewed: 12/2011, 02/2013, 02/2014, 12/2014, 10/2015, 09/2016, 12/2016, 03/2017, 06/2017, 12/2017, 03/2018, 06/2018, 10/2018, 01/2019, 12/2019, 02/2020, 02/2021, 02/2022, 02/2023I.Length of Authorization 1Coverage will be provided for 3 months and may be renewed, unless otherwise specified.∙Coverage for use to treat Hematopoietic Syndrome of Acute Radiation Syndrome (HS-ARS) cannot be renewed.II.Dosing LimitsA.Quantity Limit (max daily dose) [NDC Unit]:-Nplate 125 mcg single-dose vial for injection: 40 vials per 28 days-Nplate 250 mcg single-dose vial for injection: 20 vials per 28 days-Nplate 500 mcg single-dose vial for injection: 12 vials per 28 daysB.Max Units (per dose and over time) [HCPCS Unit]:-ITP and CIT: 125 billable units weekly-MDS: 100 billable units weekly-HS-ARS: 125 billable units x 1 doseIII.Initial Approval Criteria 1Coverage is provided in the following conditions:Universal Criteria 1∙Patient is not on any other thrombopoietin receptor agonist or mimetic (e.g.,lusutrombopag, eltrombopag, avatrombopag, etc.) or fostamatinib; AND∙Romiplostim is not being used to attempt to normalize platelet count (i.e., use is limited to decreasing the risk of bleeding from thrombocytopenia by increasing platelet levels and notnormalizing them); AND∙Laboratory values for platelet count are current (i.e., drawn within the previous 28 days);ANDImmune (idiopathic) Thrombocytopenia (ITP) † Ф 1,5∙The patient is at increased risk for bleeding as indicated by platelet count less than 30 × 109/L (30,000/mm³); ANDo Patient has acute ITP; AND▪Patient is at least 18 years of age; AND▪Patient has previously failed any of the following treatments for ITP:-Patient has failed previous therapy with corticosteroids; OR-Patient has failed previous therapy with immunoglobulins; OR-Patient has had a splenectomy; ORo Patient has had chronic ITP for at least 6 months (or meets the corticosteroid requirement below); AND▪Patient is at least 1 year of age; AND▪Patient has previously failed any of the following treatments for ITP:-Patient has failed previous therapy with corticosteroids (i.e., patienthad no response to at least a 3-month trial or is corticosteroid-dependent); OR-Patient has failed previous therapy with immunoglobulins; OR-Patient has had a splenectomyHematopoietic Syndrome of Acute Radiation Syndrome (HS-ARS) † Ф1∙Patient has suspected or confirmed exposure to radiation levels greater than 2 gray (Gy) Chemotherapy-Induced Thrombocytopenia (CIT) ‡ 2,15-19∙Patient is at least 18 years of age; AND∙Patient has a platelet count less than 100 × 109/L (100,000/mm³) for at least 3 to 4 weeks after the last chemotherapy administration and/or after delays in chemotherapy initiation related to thrombocytopeniaMyelodysplastic Syndromes (MDS) ‡ 2,3,13,14∙Patient is at least 18 years of age; AND∙Patient has lower risk disease [i.e., IPSS-R (Very Low, Low, Intermediate)]; AND∙Patient has severe or refractory thrombocytopenia (i.e., platelet count <20 x 109/L or higher with a history of bleeding); AND∙Patient progressed or had no response to hypomethylating agents (e.g., azacitidine, decitabine, etc.) or immunosuppressive therapy† FDA-labeled indication(s); ‡ Compendia recommended indication(s); Ф Orphan DrugIV.Renewal Criteria 1Coverage can be renewed based upon the following criteria:∙Patient continues to meet the universal and other indication-specific relevant criteria such as concomitant therapy requirements (not including prerequisite therapy), performancestatus, etc. identified in section III; AND∙Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: thrombotic/thromboembolic complications, risk of progression of myelodysplastic syndromes to acute myelogenous leukemia, loss of response to romiplostim/presence of neutralizingantibodies to romiplostim, etc.; ANDImmune (idiopathic) Thrombocytopenia (ITP) †1∙Disease response as indicated by the achievement and maintenance of a platelet count of at least 50 × 109/L (not to exceed 400 x 109/L) as necessary to reduce the risk for bleeding Hematopoietic Syndrome of Acute Radiation Syndrome (HS-ARS) †1∙Coverage cannot be renewedChemotherapy-Induced Thrombocytopenia (CIT) ‡ 2,15-19∙Patient continues to receive chemotherapy; AND∙Disease response as indicated by the achievement and maintenance of a platelet count of at least 100 × 109/L (not to exceed 400 x 109/L)Myelodysplastic Syndromes (MDS)‡ 2,3∙Patient has not developed acute myeloid leukemia (AML) (Note: romiplostim induces an increase in immature white blood cells and peripheral blasts which is not indicative ofdevelopment of AML); ANDDisease response as indicated by an increase in platelet count compared to pretreatment baseline (not to exceed 450 x 109/L), reduction in bleeding events, or reduction in platelettransfusion requirementsV.Dosage/Administration 1,3,19ITP Adult and Pediatric patients:Initial: 1 mcg/kg subcutaneously weekly∙Adjust dose weekly by increments of 1 mcg/kg to achieve and maintainplatelet count of ≥ 50 × 109/L (50,000/mm³) as necessary to reduce the riskfor bleeding∙Do not exceed the maximum weekly dose of 10 mcg/kg∙Adjust the dose as follows for all patients:-If the platelet count is < 50 × 109/L, increase the dose by 1 mcg/kg.-If platelet count is > 200 × 109/L and ≤ 400 × 109/L for 2 consecutiveweeks, reduce the dose by 1 mcg/kg.-If platelet count is > 400 × 109/L, do not dose. Continue to assess theplatelet count weekly. After the platelet count has fallen to < 200 × 109/L,resume Nplate at a dose reduced by 1 mcg/kg.HS-ARS Adult and Pediatric patients:∙10 mcg/kg subcutaneously x 1 dose administered as soon as possible aftersuspected or confirmed exposure to radiation.CIT Initial: 2 to 4 mcg/kg subcutaneously weekly∙Increase by no more than 1 to 2 mcg/kg per week to target platelet count of100 × 109/L to 150 × 109/L.∙Do not exceed the maximum weekly dose of 10 mcg/kg.MDS Initial: 750 mcg subcutaneously weekly∙Adjust dose in 250 mcg increments (from 250 mcg every other week up to1000 mcg weekly) based on platelet countso If platelet count is <50 x 109/L for 3 consecutive weeks, thenincrease to the next highest dose level∙Withhold the dose if platelet count >450 x 109/Lo Reinitiate at a reduced dose when platelet count is <200 x 109/LVI.Billing Code/Availability InformationHCPCS Code:∙J2796 – Injection, romiplostim, 10 micrograms; 10 mcg = 1 billable unitNDC(s):∙Nplate 125 mcg single-dose vial: 55513-0223-xx∙Nplate 250 mcg single-dose vial: 55513-0221-xx∙Nplate 500 mcg single-dose vial: 55513-0222-xxVII.References1.Nplate [package insert]. Thousand Oaks, CA; Amgen Inc; February 2022. AccessedDecember 2022.2.Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCNCompendium®) for romiplostim. National Comprehensive Cancer Network, 2022. TheNCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONALCOMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® aretrademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to /. AccessedDecember 2022.3.Giagounidis A, Mufti GJ, Fenaux P, et al. Results of a randomized, double-blind study ofromiplostim versus placebo in patients with low/intermediate-1-risk myelodysplasticsyndrome and thrombocytopenia. Cancer. 2014 Jun 15;120(12):1838-46.mbert MP, Gernsheimer TB. Clinical updates in adult immune thrombocytopenia. Blood.2017. 129:2829-2835. Doi:10.1182/blood-2017-03-754119.5.Neunert C, Terrell DR, Arnold DM, et al. American Society of Hematology 2019 guidelinesfor immune thrombocytopenia. Blood Adv. 2019 Dec 10;3(23):3829-3866.6.Newland A, Godeau B, Priego V, et al. Remission and platelet responses with romiplostim inprimary immune thrombocytopenia: final results from a phase 2 study. Br J Haematol. 2016 Jan;172(2):262-73. Doi: 10.1111/bjh.13827.7.Bussel JB, Buchanan GR, Nugent DJ, et al, “A Randomized, Double-Blind Study ofRomiplostim to Determine Its Safety and Efficacy in Children With ImmuneThrombocytopenia,” Blood, 2011, 118(1):28-36.8.Bussel JB, Kuter DJ, Pullarkat V, et al, “Safety and Efficacy of Long-Term Treatment WithRomiplostim in Thrombocytopenic Patients With Chronic ITP,” Blood, 2009, 113(10):2161-71.9.Kuter DJ, Bussel JB, Lyons RM, et al, “Efficacy of Romiplostim in Patients With ChronicImmune Thrombocytopenic Purpura: A Double-Blind Randomised Controlled Trial,” Lancet, 2008, 371(9610):395-403.10.Kuter DJ, Rummel M, Boccia R, et al, “Romiplostim or Standard of Care in Patients WithImmune Thrombocytopenia,” N Engl J Med, 2010, 363(20):1889-99.11.Kuter DJ, Bussel JB, Newland A, et al. Long-term treatment with romiplostim in patientswith chronic immune thrombocytopenia: safety and efficacy. Br J Haematol. 2013May;161(3):411-23. Doi: 10.1111/bjh.12260.12.Tarantino MD, Bussel JB, Blanchette VS, et al. Romiplostim in children with immunethrombocytopenia: a phase 3, randomised, double-blind, placebo-controlled study. Lancet.2016 Jul 2;388(10039):45-54. Doi: 10.1016/S0140-6736(16)00279-8.13.Kantarjian H, Fenaux P, Sekeres MA, et al. Safety and efficacy of romiplostim in patientswith lower-risk myelodysplastic syndrome and thrombocytopenia. J Clin Oncol. 2010 Jan 20;28(3):437-44.14.Kantarjian HM, Giles FJ, Greenberg PL, et al. Phase 2 study of romiplostim in patients withlow- or intermediate-risk myelodysplastic syndrome receiving azacitidine therapy. Blood.2010 Oct 28;116(17):3163-70.15.Soff GA, Miao Y, Bendheim G, et al. Romiplostim Treatment of Chemotherapy-InducedThrombocytopenia. J Clin Oncol. 2019 Nov 1;37(31):2892-2898. Doi: 10.1200/JCO.18.01931.16.Al-Samkari H, Parnes AD, Goodarzi K, et al. A multicenter study of romiplostim forchemotherapy-induced thrombocytopenia in solid tumors and hematologic malignancies.Haematologica. 2021 Apr 1;106(4):1148-1157. Doi: 10.3324/haematol.2020.251900.17.Miao J, Leblebjian H, Scullion B, et al. A single center experience with romiplostim for themanagement of chemotherapy-induced thrombocytopenia. Am J Hematol. 2018Aug;93(4):E86-E88. Doi: 10.1002/ajh.25022.18.Parameswaran R, Lunning M, Mantha S, et al. Romiplostim for management ofchemotherapy-induced thrombocytopenia. Support Care Cancer. 2014 May;22(5):1217-22.Doi: 10.1007/s00520-013-2074-2.19.Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology(NCCN Guidelines®) for Hematopoietic Growth Factors 1.2023. National Comprehensive Cancer Network, 2023. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc.” To view the most recent and complete version of the Guidelines, go online to . Accessed December 2022.20.CGS Administrators, LLC. Local Coverage Article: Billing and Coding: ImmuneThrombocytopenia (ITP) Therapy (A57160). Centers for Medicare & Medicaid Services, Inc.Updated on 02/23/2022 with effective date 03/03/2022. Accessed December 2022. Appendix 1 – Covered Diagnosis Codes1010C93.10 Chronic myelomonocytic leukemia not having achieved remissionD46.0 Refractory anemia without ring sideroblasts, so statedD46.1 Refractory anemia with ring sideroblastsD46.20 Refractory anemia with excess of blasts, unspecifiedD46.21 Refractory anemia with excess of blasts 1D46.4 Refractory anemia, unspecifiedD46.9 Myelodysplastic syndrome, unspecifiedD46.A Refractory cytopenia with multilineage dysplasiawith multilineage dysplasia and ring sideroblastscytopeniaD46.B RefractorysyndromesD46.Z OthermyelodysplasticD69.3 Immune thrombocytopenic purpuraD69.59 Other secondary thrombocytopeniaunspecifiedD69.6 Thrombocytopenia,T45.1X5A Adverse effect of antineoplastic and immunosuppressive drugs, initial encounterT45.1X5D Adverse effect of antineoplastic and immunosuppressive drugs, subsequent encounterT45.1X5S Adverse effect of antineoplastic and immunosuppressive drugs, sequelaT66 Radiation sickness, unspecifiedAppendix 2 – Centers for Medicare and Medicaid Services (CMS)Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determination (NCD), Local Coverage Determinations (LCDs), and Local Coverage Articles may exist and compliance with these policies is required where applicable. They can be found at:https:///medicare-coverage-database/search.aspx. Additional indications may be covered at the discretion of the health plan.Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCD/LCA):A57160(s):DocumentJurisdiction(s): 15 NCD/LCD/Articlehttps:///medicare-coverage-database/new-search/search-results.aspx?keyword=a57160&areaId=all&docType=NCA%2CCAL%2CNCD%2CMEDCAC%2CTA%2CM CD%2C6%2C3%2C5%2C1%2CF%2CPJurisdiction Applicable State/US Territory ContractorE (1) CA, HI, NV, AS, GU, CNMI Noridian Healthcare Solutions, LLCF (2 & 3) AK, WA, OR, ID, ND, SD, MT, WY, UT, AZ Noridian Healthcare Solutions, LLC5 KS, NE, IA, MO Wisconsin Physicians Service Insurance Corp (WPS)6 MN, WI, IL National Government Services, Inc. (NGS)H (4 & 7) LA, AR, MS, TX, OK, CO, NM Novitas Solutions, Inc.8 MI, IN Wisconsin Physicians Service Insurance Corp (WPS) N (9) FL, PR, VI First Coast Service Options, Inc.J (10) TN, GA, AL Palmetto GBA, LLCM (11) NC, SC, WV, VA (excluding below) Palmetto GBA, LLCL (12) DE, MD, PA, NJ, DC (includes Arlington &Novitas Solutions, Inc.Fairfax counties and the city of Alexandria in VA)K (13 & 14) NY, CT, MA, RI, VT, ME, NH National Government Services, Inc. (NGS)15 KY, OH CGS Administrators, LLC。
ORIGINAL ARTICLERomiplostim as early treatment for refractory primary immune thrombocytopeniaAnne Contis •Estibaliz Lazaro •Carine Greib •Jean-Luc Pellegrin •Jean-Franc ¸ois ViallardReceived:19March 2013/Revised:7September 2013/Accepted:9September 2013/Published online:26September 2013ÓThe Japanese Society of Hematology 2013Abstract Romiplostim is a thrombopoietin-receptor agonist approved to treat chronic immune thrombocyto-penia (ITP).We treated eight patients with acute or per-sistent primary ITP,severe clinical bleeding,and resistance to corticosteroids and/or intravenous immunoglobulins (IVIg).Romiplostim,initially administered at 2or 3l g/kg/week,was subsequently increased to achieve and maintain platelet-count responses and control bleeding.Seven patients’platelet counts rose above 30G/L,representing C twofold increases,within a median of 14days after 1–5infusions.The weekly dose reached 9l g/kg at week 5for three patients;the other patients’ITPs were controlled with B 6l g/kg/week.No thromboembolic events occurred.Five patients received rituximab concomitantly with romiplo-stim,four of whom could stop romiplostim within 2months,thereby demonstrating rituximab efficacy.All three patients treated with romiplostim alone required maintenance therapy.Thus,romiplostim represents an alternative for patients with severe acute or persistent ITP refractory to conventional therapy.Keywords Platelets ÁPrimary immunethrombocytopenia ÁRomiplostim ÁThrombopoietin-receptor agonistsIntroductionPrimary immune thrombocytopenia (ITP)is an autoimmune disorder characterized by a platelet count \100G/L in the absence of another etiology [1].It is caused by a combination of different factors,with the three most important being increased autoantibody-induced platelet destruction,sub-optimal platelet production and low endogenous thrombo-poietin (TPO)levels [2–4].Treatments differ according to ITP evolution.For chronic ITP,three therapeutic alternatives are recommended as second-line treatments:splenectomy,rituximab and TPO-receptor agonists (TPO-RAs)[5].For acute ITP with severe thrombopenia,treatment is aimed at rapidly raising the platelet count to stop or reduce life-threatening bleeding.To reach this objective,intrave-nous immunoglobulins (IVIg)or intravenous anti-D (1–3days)have the shortest time to initial response,fol-lowed by corticosteroids (2–14days),which remain the standard first-line therapy [1].However,some patients with ‘‘severe ITP’’have clinically relevant bleeding symptoms resistant to conventional therapies,leading many clinicians to turn towards other treatments (including vincristine,plasmapheresis,cyclophosphamide,platelet transfusions and/or rituximab),which are not always effective and can be responsible for some complications.In this context,given the high efficacy of TPO-RAs,despite their longer time to response (10–15days to mount an effect on platelet count),clinicians should consider their potential benefits in situa-tions of acute severe bleeding.TPO-RA administration for a short period could control hemorrhaging,until the efficacy of other molecules with delayed action,like rituximab,kicks in,and it does not carry the risk of immunosuppression.Herein,we report our experience with romiplostim given to patients with severe,newly diagnosed or persistent ITP unresponsive to at least IVIg and prednisone.A.Contis Ázaro ÁC.Greib ÁJ.-L.Pellegrin ÁJ.-F.Viallard (&)Service de Me´decine Interne et Maladies Infectieuses,Ho ˆpital Haut-Le´ve ˆque,Avenue de Magellan,33604Pessac Cedex,Francee-mail:jean-francois.viallard@chu-bordeaux.fr zaro ÁJ.-L.Pellegrin ÁJ.-F.ViallardUniversite´Victor-Segalen,Bordeaux,France Int J Hematol (2013)98:520–524DOI 10.1007/s12185-013-1439-0T a b l e 1I n d i v i d u a l I T P p a t i e n t s ’c h a r a c t e r i s t i c s a n d t h e r a p e u t i c r e s p o n s e sC h a r a c t e r i s t i c P a t i e n t 1P a t i e n t 2P a t i e n t 3P a t i e n t 4P a t i e n t 5P a t i e n t 6P a t i e n t 7P a t i e n t 8A g e (y e a r s )/s e x 65/m a l e29/m a l e26/m a l e 64/f e m a l e 73/m a l e 29/f e m a l e 58/m a l e 80/f e m a l eI T PC o u r s e aA c u t eP e r s i s t e n t (4r e l a p s e s )P e r s i s t e n t (4r e l a p s e s )A c u t e P e r s i s t e n t (6r e l a p s e s )A c u t e A c u t eP e r s i s t e n t (3r e l a p s e s )H e m o r r h a g i c s y m p t o m sG E P ,M BG E P ,M BG P P ,M B G P P ,M B G E P ,M B G P P ,M B ,M G E P ,M B ,H G E P ,M BE p i s o d e d u r a t i o n (d a y s )2666331390302120U n s u c c e s s f u l t r e a t m e n t s b I V I g (2c y c l e s ),p r e d n i s o n eI V I g (2c y c l e s ),d a p s o n eI V I g (2c y c l e s ),p r e d n i s o n e I V I g ,p r e d n i s o n e I V I g (3c y c l e s )p r e d n i s o n e ,d a p s o n e I V I g ,p r e d n i s o n e I V I g ,p r e d n i s o n e ,v i n c r i s t i n eI V I g ,p r e d n i s o n eR o m i p l o s t i mI T P d u r a t i o n b e f o r e u s e (d a y s )2797121131913729326I n f u s i o n s b e f o r e r e s p o n s e c ,n2113125(n o r e s p o n s e )5T i m e t o r e s p o n s e c(d a y s )10882182140(n o r e s p o n s e )28E f f e c t i v e d o s e d(l g /k g )9336399(n o r e s p o n s e )9C o n c o m i t a n t r i t u x i m a bY e sN oY e s Y e s N o Y e sY e sN oM a i n t e n a n c e N oY e sY e s N o Y e sN oN oY e sP l a t e l e t c o u n t s (G /L )B e f o r e r o m i p l o s t i m 572486214A f t e r r o m i p l o s t i m 194273601681266032115B l e e d i n g s c o r eeB e f o r e r o m i p l o s t i m 1198811121914A f t e r 3w e e k s o f r o m i p l o s t i m20002138G E P g e n e r a l i z e d e c c h y m o t i c p u r p u r a ,G P P g e n e r a l i z e d p e t e c h i a l p u r p u r a ,M B m u c o s a l b l e e d i n g ,H h e m a t u r i a ,M m e n o /m e t r o r r h a g i aaE v e r y r e l a p s e w a s t r e a t e d w i t h I V I g (1g /k g /d a y )o r p r e d n i s o n e (1m g /k g /d a y )g r a d u a l l y t a p e r e d ,e x c e p t p a t i e n t 80s t h i r d r e l a p s e ,w h i c h h a d b e e n t r e a t e d w i t h r i t u x i m a b 9m o n t h s b e f o r e t h e b l e e d i n g e p i s o d e t r e a t e d w i t h r o m i p l o s t i mbI V I g (1g /k g /d a y )w e r e i n f u s e d o v e r 2d a y s ;p r e d n i s o n e d o s e :1m g /k g /d a ycR e s p o n s e w a s d e fin e d a s a c h i e v i n g a p l a t e l e t c o u n t C 30G /L a n d C t w o f o l d i n c r e a s e a b o v e t h e b a s e l i n e c o u n t ,a n d t h e a b s e n c e o f b l e e d i n g dE f f e c t i v e r o m i p l o s t i m d o s e w a s t h a t u s e d t o m a i n t a i n p l a t e l e t s [50G /L a n d a b s e n c e o f b l e e d i n geB l e e d i n g s c o r e w a s c a l c u l a t e d a c c o r d i n g t o K h e l l a f e t a l .[7]Romiplostim for early ITP521Patients and methodsPatientsEight patients(five men,three women;median age: 53years)with platelet counts\20G/L and hemorrhagic symptoms are described(Table1).According to the new definitions of ITP[1],four had acute(within3months of diagnosis)and four persistent disease(3–12months since diagnosis).All patients had persistent,severe,bleeding ing the bleeding score devised by Khellaf et al.[6],seven patients had scores[8,defining severe ITP, requiring combined corticosteroids and IVIg.None of these patients had antiphospholipid antibodies associated with their thrombopenia.Response criteriaParameters of response were retrospectively evaluated according to standardized criteria[1].Overall response was defined as achieving platelet counts C30G/L and C two-fold higher than the baseline value,and the absence of bleeding;complete response meant the platelet count was C100G/L in the absence of any bleeding;nonresponse was a persistent platelet count\30g/L or B twofold higher than the baseline value or no effect on bleeding;time-to-response(TTR)was the interval between romiplostim onset and overall or complete response;loss-of-response was declared when the platelet count fell\30G/L or \twofold higher than the baseline value;response duration was measured from thefirst established response to its disappearance.TreatmentsAll patients receivedfirst-line IVIg(1g/kg/day infused over2days)and prednisone(1mg/kg/day),except patient 2whose psychotic syndrome was a contraindication for high-dose corticosteroids.This regimen failed to increase platelet counts and control the bleeding symptoms,leading to the administration of a new IVIg cycle for four patients, and adjunction of dapsone for patients2and5,and vin-cristine for patient7.Due to the inefficacy of those drugs and the persistence of bleeding deemed life-threatening, weekly romiplostim administration was initiated,in addi-tion to ongoing steroids,at a starting dose of2l g/kg(for elderly patients4and8)or3l g/kg(other patients).To achieve the target platelet count of50–200G/L,doses could be increased by3l g/kg(2l g/kg for patients4and 8)every week,to9l g/kg,the maximum dose we used. This strategy bypassed the standard protocol to obtain a more rapid effect on the platelet count and/or the bleeding. Moreover,five patients received rituximab(375mg/m2/week for4weeks),a monoclonal antibody directed against B cell antigen CD-20,in combination with romiplostim. Patients1,4and6received their weekly infusions of rit-uximab and romiplostim simultaneously.Patient6stopped both agents after two infusions because her platelet count exceeded500G/L.Because of a stationary platelet count around30G/L and a brief relapse of hemorrhagic symp-toms(otorrhagia),patient3started rituximab4weeks after starting romiplostim.Patient7began rituximab after romiplostim failed.We monitored patients’platelet counts and bleeding scores to determine the need for maintenance therapy with romiplostim.ResultsAmong the eight romiplostim-treated ITP patients,only patient7was a nonresponder,despite prolonged high-dose romiplostim(9l g/kg/week for4weeks)(Table1).This patient required rituximab and vincristine to raise his platelet counts[30G/L.Other patients’plateletcounts Fig.1Evolution of mean±SEM platelet counts in responders to romiplostim(1–6weeks after thefirstinfusion)Fig.2Mean(±SEM)bleeding-score evolutions during weeks1–6 after thefirst romiplostim infusion for responders to romiplostim alone(open square)or combined with rituximab(open circle)522 A.Contis et al.increased with romiplostim (Fig.1).The majority of patients given romiplostim responded quickly,within a median of 14days,after the first (patients 2,3and 5)or second infusion (patients 1and 6)of 3l g/kg,or after the third or fifth infusion for patients 4and 8,respectively.The median romiplostim dose subsequently infused was 6l g/kg.Bleeding scores declined from a median of 11.5–3.1after only 3weeks of romiplostim and had reached \8after a median of 1week.Thus,patients’bleeding scores improved faster than their platelet counts rose.Five of our eight patients received rituximab concomi-tantly with romiplostim.The aim of combining the two agents was to rapidly increase platelet counts until ritux-imab efficacy kicked in.Only patient 3,who had received both agents,pursued romiplostim maintenance therapy.Therefore,four of the five patients who received rituximab were able to stop romiplostim within 2months,demon-strating rituximab’s contribution.No patient had an excessive increase of platelets.Patients treated with romi-plostim and rituximab vs.those given romiplostim alone were comparable concerning their TTR,i.e.,to achieve a safe platelet count (14.6±6.7vs.15±3.5days)or bleeding score \8(1.6±0.7vs.1±0.02weeks)(Figs.2,3).Pertinently,TTR for a safe platelet count with romi-plostim (alone or combined with rituximab)was shorter than the 4weeks required for rituximab alone [7].All the three patients treated with romiplostim alone required maintenance therapy,which is an important observation to keep in mind,because romiplostim is a recent agent with limited long-term safety data.Perhaps it would be better to use other curative treatments available before resorting to high-dose romiplostim,which should be reserved for short-term rescue therapy.DiscussionThree cases were previously reported,describing the positive impact of romiplostim on acute and refractory ITP:one each to stop hemorrhage [8],maintain anticoagulation treatment [9]and undergo splenectomy [10].The firstpatient’s platelet count increased from 6to 76G/L 4days after the first romiplostim infusion (1l g/kg/week),but a deep-vein thrombosis occurred when the patient’s platelet count was 300G/L.The second patient was given romi-plostim at a starting dose of 1l g/kg/week,subsequently increased to 3l g/kg/week over the next 2weeks;a platelet response was observed 10days after the first infusion.For case 3,after eltrombopag failure,romiplostim was administered with an initial dose of 1l g/kg/week,subse-quently increased to 4l g/kg/week and then decreased to 2l g/kg/week because of arthralgias.A response was obtained only when IVIg were administered concomitantly with romiplostim,even though IVIg alone had previously proven to be ineffective,thereby allowing the splenectomy.The usual starting dose of romiplostim is 1l g/kg,and,according the platelet count,it is increased by 1l g/kg every week or two,with the maximum allowed dose being 10l g/kg [11].With this protocol,a target platelet count of C 50G/L (platelet response)was achieved after 1week by 25%of the patients and within 2–3weeks by half of them [11].For our patients,we decided to exceed the recom-mended doses by starting with 3l g/kg,based on the results of a Japanese,phase-III clinical trial on chronic ITP [12],or 2l g/kg for elderly patients,who are at higher risk of thrombosis,and to adjust the dose by 3l g/kg (or 2l g/kg,respectively)to obtain a rapid impact on the clinical bleeding.With this administration scheme,seven of the eight patients achieved good responses and no thrombo-embolic events were observed.Based on these preliminary data,romiplostim seems to improve the bleeding score before the platelet count.This observation suggests that TPO-Ras not only dramatically increase platelet count but also induce platelet activation.The hemostatic efficacy could rely on the newly produced platelets,more functional,or on the stimulation of the preexistent platelets [13].Indeed,despite TPO mimetics do not directly activate platelets,they reduce the threshold for platelet activation by 50%[14].Moreover,a previous report demonstrated romiplostim involvement in restoring platelet function in a patient with ITP and antibody to platelet glycoprotein VI (GPVI)[15].In this case,aFig.3Comparisons of the times to response to achieve a safe platelet count (a )andbleeding score \8(b )in patients treated with romiplostim alone or combined with rituximabRomiplostim for early ITP 5236months treatment with romiplostim improved the func-tion of GPVI receptors and corrected aggregation tests in response to GPVI agonists.In conclusion,romiplostim appears to be a valid treat-ment for severe,acute or persistent ITP.In these critical clinical situations and in the absence of thrombotic factors, our experience showed that,to rapidly achieve an accept-ably safe platelet count,romiplostim had to be used at higher than usual doses.Moreover,concomitant adminis-tration of rituximab and romiplostim,the latterfilling in until rituximab’s delayed efficacy becomes apparent,seems effective but the validation of this strategy requires further investigations on a larger number of patients.Conflict of interest JFV has participated in advisory boards and Amgen and Glaxo SmithKline symposia(honoraria of less than 10,000USD).References1.Rodeghiero F,Stasi R,Gernsheimer T,Michel M,Provan D,Arnold DM,et al.Standardization of terminology,definitions and outcome criteria in immune thrombocytopenic purpura of adults and children:report from an international working group.Blood.2009;113:2386–93.2.Cooper N,Bussel J.The pathogenesis of immune thrombocyto-penic purpura.Br J Haematol.2006;133:364–74.3.Aledort LM,Hayward CP,Chen MG,Nichol JL,Bussel J,ITPStudy Group.Prospective screening of205patients with ITP, including diagnosis,serological markers,and the relationship between platelet counts,endogenous 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