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2018, 20(4)
HighLights More»   
· Overcoming clinical inertia, improving the management of anticoagulation therapy
· Efficacy and risk of bleeding of new oral anticoagulants in treatment of acute venous thromboembolism: a network meta-analysis
· Analysis on incidence and risk factors of hemorrhagic events during anticoagulation therapy with warfarin in patients with liver cirrhosis and portal vein thrombosis after trans-jugular intrahepatic portosystemic shunt
· Analysis of situation of bleeding due to warfarin in anticoagulant clinic patients
· Literature analysis of dabigatran-induced esophageal injury
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  --2018, 20 (4)   Published: 28 August 2018
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Overcoming clinical inertia, improving the management of anticoagulation therapy Hot!
Hua Lu, Jing Zhicheng
. 2018, 20 (4): 241-244. ;  doi: 10.3760/cma.j.issn.1008-5734.2018.04.001
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Focus on the cardiovascular safety of febuxostat
Yang Xue, Xue Yu, Zhu Xiaoxia, Zou Hejian
. 2018, 20 (4): 245-248. ;  doi: 10.3760/cma.j.issn.1008-5734.2018.04.002
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Efficacy and risk of bleeding of new oral anticoagulants in treatment of acute venous thromboembolism: a network meta-analysis Hot!
Li Ting, Feng Yufei, Ni Qian, Zhou Deping
. 2018, 20 (4): 249-258. ;  doi: 10.3760/cma.j.issn.1008-5734.2018.04.003
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ObjectiveTo systematically evaluate the efficacy and bleeding risk of new oral anticoagulants (NOAC) in treatment for acute venous thromboembolism (VTE).MethodsRandomized controlled trials (RCT) about NOAC treatment for VTE in related databases collected up to December 2017 were searched. The literature in accordance with the inclusion criteria were selected and evaluated. The outcome measures included recurrence rate of VTE, all-cause mortality, incidence of hemorrhea or incidence of clinically relevant non-major (CRNM) bleeding. The results of RCT in accordance with inclusion criteria were combined using network meta-analysis. The effect measures were expressed in odds ratio (OR) with its corresponding 95% confidence interval (CI). ResultsA total of 9 RCT comprising 27 827 patients and 5 anticoagulant drugs (rivaroxaban, apixaban, edoxaban, dabigatran, and warfarin) were enrolled in the study. The quality evaluation showed that 4 of 9 RCT′s bias risks were low, 2 were uncertain, and 3 were high. Network meta-analysis results showed that neither the differences of recurrence rate of symptomatic VTE nor that of all-cause mortality among the patients with acute VTE using 5 different anticoagulant drugs were statistically significant. The results of surface under the cumulative ranking probability (SUCRA) showed that apixaban had the highest probability of having the optimal curative effect in decreasing symptomatic recurrence rate and all-cause mortality (SUCRA: 69.0%, 77.1%), followed by rivaroxaban (SUCRA: 60.7%, 51.4%). About the safety of the drugs, the risk of hemorrhoea induced by apixaban was lower than that induced by dabigatran and edoxaban (dabigatran vs. apixaban, OR=2.36, 95%CI: 1.16-4.83; edoxaban vs. apixaban, OR=2.64, 95%CI: 1.36-5.13). The risk of CRNM bleeding associated with apixaban was lower than that associated with rivaroxaban and edoxaban (edoxaban vs. apixaban, OR=1.67, 95%CI: 1.26-2.20; rivaroxaban vs. apixaban, OR=2.09, 95%CI: 1.59-2.74). The risk of CRNM bleeding associated with dabigatran was lower than that due to edoxaban and rivaroxaban (edoxaban vs. dabigatran, OR=1.36, 95%CI: 1.01-1.84; rivaroxaban vs. dabigatran, OR=1.71, 95%CI: 1.27-2.30). The results of SUCRA showed that the probability of hemorrhoea induced by apixaban was the lowest (SUCRA: 98.2%), followed by rivaroxaban, dabigatran, edoxaban, and warfarin; the probability of CRNM bleeding induced by apixaban was the lowest (97.0%), then followed by dabigatran, edoxaban, rivaroxaban, and warfarin.ConclusionsFor adult patients with new-onset or relapsed acute VTE, the efficacy of NOAC and warfarin were similar. The risk of bleeding with NOAC treatment was significantly lower than that with warfarin, of which, apixaban had the highest probability of having the best efficacy and the lowest risk of bleeding.
Analysis on incidence and risk factors of hemorrhagic events during anticoagulation therapy with warfarin in patients with liver cirrhosis and portal vein thrombosis after trans-jugular intrahepatic portosystemic shunt Hot!
Wang Zhengyu, Luo Bohan, Lyu Yong, Niu Jing, Yuan Jie, Han Na, Li Xiaomei, Zhu Ying,Chen Hui, He Chuangye, Yin Zhanxin, Song Hange, Han Guohong
. 2018, 20 (4): 259-265. ;  doi: 10.3760/cma.j.issn.1008-5734.2018.04.004
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ObjectiveTo understand the incidence and risk factors of warfarin related hemorrhagic events during anticoagulation therapy with warfarin in patients with cirrhosis and portal vein thrombosis(PVT) after transjugular intrahepatic portosystemic shunt (TIPS).MethodsThe patients with liver cirrhosis who were treated with warfarin after TIPS due to portal hypertension were followed up from January 2012 in Xijing Hospital of Digestive Diseases, Air Force Military Medical University. The data of medical records and follow-up records up to the end of December 2015 in patients undergoing TIPS were collected and retrospectively analyzed. Cumulative incidence of hemorrhagic events related to warfarin treatment was calculated by Kaplan-Meier method. The patients were divided into warfarin-related bleeding group (bleeding group) and non warfarin-related bleeding group (non-bleeding group). The risk factors of hemorrhagic events related to warfarin treatment were analyzed using Cox regression model and the hazard ratio (HR) and the 95% confidence interval (CI) were calculated.ResultsA total of 179 patients were enrolled, including 117 males and 62 females with ages of 25-79 years and average age of (52±12) years; the bleeding group comprised 47 patients (26.3%) and the non-bleeding group comprised 132 patients (73.7%). The follow-up time after discharge ranged 1-74 months and the average time was (28±21) months. The average portal pressure gradient dropped from (25.4±5.2) to (8.7±3.7) mmHg before and after TIPS (P<0.001). The median dose of oral warfarin in patients in the bleeding group was 2.5 (ranged from 2.5 to 3.75) mg and the median INR was 3.12 (ranged from 2.04 to 9.41); the median dose of oral warfarin in patients in the non-bleeding group was 1.8 (ranged from 0.63 to 2.5) mg and the median INR was 1.85 (ranged from 1.5 to 3.38). Fifty eight cases of hemorrhagic events occurred in 47 patients in the bleeding group, including 24 cases of gingival bleeding, 16 cases of epistaxis, 8 cases of cutaneous purpura, 4 cases of conjunctival hemorrhage, 2 cases of hemorrhage of digestive tract, 2 cases of intracranial hemorrhage, 1 cases of hematuria, and 1 cases of menorrhagia. Nine of the 47 patients in the bleeding group had bleeding from multiple sites. The results of Kaplan-Meier analysis showed that the 1-, 2-, 3-, 4-, 5- and 6-year cumulative incidences of hemorrhagic events related to warfarin treatment after operation were 19%, 23%, 24%, 30%, 41%, and 45%, respectively. Warfarin was stopped in 11 patients and given at reduced doses in 36 patients among the 47 patients in the bleeding group. After that, 43 patients′ hemorrhagic symptoms disappeared and 3 patients′ symptoms relieved, and then warfarin treatments were continued, except that 1 patient with a long history of hypertension died of intracranial hemorrhage. Multiple Cox regression analysis showed that the baseline serum creatinine level >115 μmol/L was an independent risk factor for hemorrhagic events related to warfarin treatment (HR=1.82, 95%CI: 1.01-3.28, P=0.045).ConclusionsIt is relatively safe for patients with liver cirrhosis and PVT receiving warfarin anticoagulation therapy after TIPS. Elevated serum creatinine is an independent risk factor for hemorrhagic events related to warfarin treatment.
Analysis of situation of bleeding due to warfarin in anticoagulant clinic patients Hot!
Li Nan, Gao Xin, Mao Yi, Hua Lu
. 2018, 20 (4): 266-271. ;  doi: 10.3760/cma.j.issn.1008-5734.2018.04.005
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ObjectiveTo analyze the situation of bleeding in patients during oral warfarin treatment in an anticoagulant clinic.MethodsThe medical record data of patients who received warfarin treatment in Anticoagulant Clinic of Fuwai Hospital, Chinese Academy of Medical Sciences from May 1st, 2016 to April 30th, 2017 were collected from the hospital outpatient information system and analyzed retrospectively. According to age, the patients were divided into the youth group (<45-year-old), middle age group (45-65-year-old), and older age group (>65-year-old). According to indications of anticoagulation therapy, the patients were divided into the postoperative group of valve replacement (postoperative group), the atrial fibrillation/atrial flutter group, and the thromboembolic disease group. The situation of bleeding events during warfarin treatments in patients in the different age groups and the different indication groups were compared.ResultsA total of 915 patients were enrolled into the study, including 468 males and 447 females with ages from 14 to 89 years and an average age of (58±14) years. The youth group, the middle age group, and the older age group comprised 127, 482, and 306 patients, respectively. The postoperative group, the atrial fibrillation/atrial flutter group, and the thromboembolic disease group comprised 574, 271, and 70 patients, respectively. The number of patients whose warfarin dosage were ≤5 mg/d or 5-9 mg/d was 847 or 69, respectively. There were more patients with valve replacement in the youth and the middle age groups[87.40% (111/127), 73.86% (356/482)] and more patients with atrial fibrillation/ atrial flutter in the older age group[55.88% (171/306)]. Of the 915 patients, 87 developed bleeding events during warfarin treatment, which were evaluated to be induced by warfarin and the incidence of bleeding was 9.51%. Seven of the 87 patients were with severe bleeding and the incidence was 0.77%. The incidence of bleeding in the older age group was significantly higher than that in the middle age group[15.03% (46/306) vs. 7.05% (34/482), P<0.001] and the youth group[15.03% (46/306) vs. 5.51% (7/127), P=0.006]. The incidence of bleeding in the atrial fibrillation/atrial flutter group was significantly higher than that in the postoperative group[14.76% (40/271) vs. 6.62% (38/574), P<0.001]. The incidence of bleeding in the thromboembolic disease group was 12.86% (9/70). The differences of incidences of bleeding between the thromboembolic disease group and above-mentioned 2 groups were not statistically significant (all P>0.05). Of the 87 patients with bleeding, 75 (86.21%) were with single time bleeding, 71 (81.61%) were with single site bleeding, 80 (91.85%) were with slight bleeding; warfarin dosages in 82 (94.25%) patients were ≤5 mg/d, international normalized ratios (INR) in 77 (88.51%) patients were ≤3.00. Twelve (13.79%) patients received combined use of other drugs during warfarin treatment. A total of 113 times of bleeding events occurred in 87 patients, including 31 times of skin mucosal hemorrhage, 19 times of gingival bleeding, 13 times of hemorrhinia hemorrhage and ocular hemorrhage, 10 times of hemoptysis, 7 times of fecal occult blood and/or hemorrhoidal bleeding, 6 times of hemorrhage of digestive tract and urine occult blood, 5 times of gross hematuria, 1 time of menstrual extension, colporrhagia, and intracranial hemorrhage.ConclusionsThe incidence of bleeding in outpatients during warfarin treatment in Anticoagulant Clinic in Fuwai Hospital is 9.51%. The bleeding mainly occurred in elders and patients with auricular fibrillation or atrial flutter. The bleeding in most patients is mild.
Literature analysis of dabigatran-induced esophageal injury Hot!
Tian Huichun, Zeng Han
. 2018, 20 (4): 272-275. ;  doi: 10.3760/cma.j.issn.1008-5734.2018.04.006
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ObjectiveTo explore the clinical characteristics, prevention, and treatment of esophageal injury caused by dabigatran.MethodsThe databases of PubMed, Wan Fang, CNKI, and VIP were searched, and the literature of esophageal injury induced by dabigatran was collected by the end of 2017, and the relevant data were obtained for descriptive analysis.ResultsThe study comprised 12 literature on esophageal injury caused by dabigatran in total, including 1 clinical retrospective study and 11 case reports. The 12 articles included 32 patients with esophageal injury caused by dabigatran, including 22 males (68.8%) and 10 females (31.2%), aged 58-90 years, and of whom 28 patients (87.6%) were from Japan, 1 from the United States, 1 from Germany, 1 from New Zealand and 1 from the United Kingdom. Eleven patients (34.4%) had previous history of digestive system diseases. Of the 32 patients, 25 patients (78.1%) had clinical symptoms, including chest pain (7 cases), odynophagia (6 cases), dysphagia (6 cases), heartburn in the chest or stomach (6 cases), epigastralgia (4 cases) and hemorrhage (4 cases). Endoscopic findings were mainly esophageal mucosal exfoliation (28 cases) and ulceration (8 cases). The esophageal injuries mostly occurred in the middle lower part of the esophagus. Esophagus injury was not related to the duration and dosage of dabigatran therapy, but it might be related to an incorrect drug use. Five patients with mild esophageal injury did not stop using dabigatran and their symptoms improved with a corrected way of taking medicine. However, in severe cases, dabigatran should be stoped. The patients might take other anticoagulants, use proton pump inhibitors, and should have a restrictive diet, and then the injury of the esophagus was gradually improved. ConclusionsDabigatran might cause esophagus injury and it mainly manifested as esophageal mucosal exfoliation and ulceration, whose prognosis was better in general. Therefore, the guidance on the correct use of dabigatran for the patients should be strengthened to prevent esophageal injury occurring.
Analysis of potentially inappropriate medications in elderly inpatients in internal medicine ward based on the new edition of Beers and the STOPP criteria
Hou Kaixuan, Xing Xiaoxuan, Yan Suying
. 2018, 20 (4): 276-283. ;  doi: 10.3760/cma.j.issn.1008-5734.2018.04.007
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ObjectiveTo evaluate and compare the condition of potentially inappropriate medications (PIM) in elderly inpatients in our hospital by the new edition of Beers and the STOPP criteria.MethodsThe patients who were ≥65 years old and discharged from the internal medicine ward of Xuanwu Hospital, Capital Medical University in March 2017 were enrolled into the study. The patients′  basic information (gender, age), coexistence diseases, Chalson Comorbidity Index (CCI) scores, types of drug used during hospitalization, expenses for medicine, and total hospitalization expenses were collected. The Beers criteria (2015) and the STOPP criteria (2014) were used respectively to evaluate the PIM in inpatients and logistic regression analysis was used to analyze related factors of PIM occurrence.ResultsA total of 453 patients were enrolled into the study, including 247 males and 206 females, aged 65-97 years with the mean age of (74±7) years. The hospitalization time was 2 to 57 days, the median hospitalization time was 10 (7, 13) days; the number of coexistence diseases was 1 to 42, the median number of coexistence diseases was 8 (5, 12); the number of drug types during hospitalization was 1 to 57, the median number of drug types was 12 (8, 17); CCI scores were 0 to 7 points, the median CCI score was 1 (1, 2). Two hundred and ninety patients (290/453, 64.0%) were prescribed at least 1 PIM by the Beers criteria, mainly including vasodilators (131/709, 18.48%), diuretics (123/709, 17.35%), and benzodiazepines (107/709, 15.09%). One hundred and eighty-nine patients (189/453, 41.7%) were prescribed at least 1 PIM by the STOPP criteria, mainly including benzodiazepines (101/283, 35.69%), first generation antihistamines (49/283, 17.31%), and repeated use of the same kind of drugs (30/283, 10.60%). The difference in PIM incidence assessed by the Beers and STOPP criteria among the patients with different gender was not statistically significant (P=0.161, P=0.438). The differences in PIM incidences assessed by the Beers and STOPP criteria at different ages, different hospitalization time, kinds of coexistence diseases, types of drug use, and CCI scores were all statistically significant (Beers criteria: P values were <0.001, <0.001, <0.001, <0.001, and 0.003, respectively; STOPP criteria: P values were <0.001, <0.001, <0.001, <0.001, and 0.010, respectively). The mortality and total hospitalization expenses in patients with PIM use identified by the Beers and STOPP criteria were higher than those in patients without PIM use (Beers criteria: P values were 0.001 and <0.001, respectively; STOPP criteria: P values were 0.001 and 0.006, respectively). The result of Kappa consistency test reviewed that the 2 criteria had general consistency. Aged 75-84 years, hospitalization time≥15 days, 6-10 and≥16 kinds of coexistence diseases, and ≥10 drugs types were risk factors of PIM occurrence in patients.ConclusionsMore PIM users could be determined by the Beers criteria. The PIM evaluated by STOPP criteria in elderly patients was more beneficial to clinical diagnosis and treatment. More PIM in elderly patients could be found by combining the results of the 2 criteria.
Clinical analysis of antibacterial-associated diarrhea in adult inpatients
Song Zhihui, Zhao Huanyu, Wang Jiawei
. 2018, 20 (4): 284-288. ;  doi: 10.3760/cma.j.issn.1008-5734.2018.04.008
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ObjectiveTo understand the occurrence of antibacterial-associated diarrhea (AAD) in adult inpatients, the main antibacterials leading to AAD, and the main clinical characteristics of AAD, so as to strengthen the prevention of this adverse reaction.MethodsThe medical records in adult patients who were treated with antibacterials during their hospitalization in Beijing Tongren Hospital, Capital Medical University from January 1, 2016 to May 31, 2017 were collected and retrospectively analyzed. The electric medical records data of patients with AAD were collected from hospital information system, related data were extracted, and antibacterials associated with diarrhea and clinical features and prognosis of AAD were descriptively analyzed. The main medical units where AAD occurred and major antibacterials leading to AAD were analyzed using Pareto analysis, and the rationality of antibacterials use in patients with AAD was evaluated.ResultsA total of 2 406 adult inpatients with antibacterial treatments were collected, of which 85 suffered from AAD (incidence 3.5%). Of the 85 patients, 48 were males and 37 females, the median age was 68 (31, 93) years, and 70 patients (82.3%) were ≥60 years old; 28 patients were from intensive care unit (ICU, 32.9%), 22 from health care unit for cadres (25.9%), 18 from general medical ward (21.6%), 13 from emergency comprehensive ward (15.3%), and 4 from surgical ward (4.7%). Pareto chart showed that the main medical units where AAD occurred were ICU ward, the health care unit for cadres, and the general medical ward. The application condition of antibacterials was as follows. Of the 85 patients, 62 (72.9%) were treated with a single antibacterial, including 23 cases receiving the third or fourth generation cephalosporins, 13 cephamycins, 11 broad-spectrum penicillins, 10 carbapenems, 3 quinolones, and 2 second generation cephalosporins; 23 (27.1%) were treated with 2 antibacterials, one of whose drugs was the third or fourth generation cephalosporins, broad-spectrum penicillins or cephamicins. Pareto chart showed that the main drugs causing AAD were the third or fourth generation cephalosporins, cephamicins, and broad-spectrum penicillins. Diarrhea occurred at 1-30 days after antibacterial treatments with an average period of (7.5±6.4) days. In the 85 patients, 26 patients (30.6%) were Clostridium difficile toxin positive in stools, of which 8 were diagnosed as pseudomembranous conjunctivitis, accounting for 9.4% of AAD and 30.8% of Clostridium difficile diarrhea. After 2-40 days′ treatment with intestinal micro-ecological drugs (80 cases), montmorillonite powder (60 cases), metronidazole (18 cases), vancomycin (10 cases), and etc., 48 patients (56.5%) were cured, 35 (41.2%) improved, and 2(2.3%) ineffective. The evaluation results of rationality of antimicrobials in clinical application showed that 4(4.7%) of the 85 patients with AAD received irrational use of antimicrobials, including 2 cases of unreasonable dosage and 2 cases of unreasonable combined use of drugs.ConclusionsThe incidence of AAD in adult inpatients in Beijing Tongren Hospital was 3.5%, and in patients with AAD, 30.6% suffered from Clostridium difficile diarrhea and 9.4% suffered from pseudomembranous conjunctivitis. The main drugs causing AAD were the third or fourth generation cephalosporin, cephamicins, and broad-spectrum penicillins.
Progress of liver injury caused by new oral anticoagulants
Hui Xiang, Fan Qingqing, Duan Yan, Yang Dihong, Ge Weihong
. 2018, 20 (4): 289-295. ;  doi: 10.3760/cma.j.issn.1008-5734.2018.04.009
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Novel oral anticoagulants (NOAC) include direct thrombin inhibitors (ximelagatran and dabigatran etexilate) and coagulation factor Xa inhibitors (rivaroxaban, apixaban and edoxaban). Ximelagatran was withdrawn from the market in 2006 because of its high incidence of liver injury after listing in 2004, which has aroused concern about the hepatotoxicity of NOAC. No significant evidence of hepatotoxicity was found in pre-clinical studies on dabigatran etexilate, rivaroxaban, apixaban, or edoxaban and their risks of liver injury were low. However, pre-marketing clinical studies, post-marketing literature reports, and pharmacovigilance data showed that the incidence of NOAC-related liver injury was 0.1% to 1.0%. Reports of liver adverse events related to rivaroxaban were more than those related to apixaban and dabigatran etexilate. The patients who use NOAC have underlying diseases. Once liver injury occurs, it is more serious and the mortality is higher. Clinicians should be highly vigilant. The mechanism of NOAC-related hepatotoxicity is still unclear and further study is needed in the future.

. 2018, 20 (4): 295-295. ;  doi: 10.3760/cma.j.issn.1008-5734.2018.04.010
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Vaccine safety management: foreign experience
Cai Haodong, Wang Yuqin, Li Yuzhen
. 2018, 20 (4): 296-301. ;  doi: 10.3760/cma.j.issn.1008-5734.2018.04.011
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Vaccination is one of the most successful public health achievements of human history. However, like any drug, no vaccine is absolutely safe. As the incidence of vaccine-preventable diseases has been effectively controlled by vaccines, the safety of vaccines inoculated in healthy people has attracted more and more attention. The United States is the earliest country to start vaccine safety management. After some major vaccine safety incidents, vaccine safety management has gradually developed and improved. Vaccine safety regulator in the United States mainly consists of 4 federal agencies: the Food and Drug Administration (FDA), the Centers for Disease Control and Prevention (CDC), the National Institutes of Health (NIH), and the Health Resources & Services Administration (HRSA). FDA is mainly responsible for pre-market registration and approval of vaccines, and supervision and inspection of vaccine manufacturers. CDC is mainly responsible for making immunization planning, monitoring of vaccine adverse reactions, and management of free vaccine projects of government. NIH is mainly responsible for vaccine research and development. HRSA is mainly responsible for vaccine accident compensation. In addition, the experience of European Medicines Agency in limitation of validity period of vaccine license and vaccine quality management and the experiences in safety management of vaccines in Canada, Britain, Australia and New Zealand, including "cold chain" management, surveillance of vaccine adverse events, etc. are worthy of learning.
Eczema-like drug eruption induced by clopidogrel
Zhang Fangming, Xie Cheng
. 2018, 20 (4): 302-304. ;  doi: 10.3760/cma.j.issn.1008-5734.2018.04.012
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A 69-year-old male patient received oral aspirin (100 mg once daily), ticagrelor (45 mg twice daily), amlodipine besylate (5 mg once daily), losartan potassium (50 mg once daily), metoprolol sustained release tablets (47.5 mg once daily), and atorvastatin (10 mg once daily) after coronary angiography. After 28 days of treatments, ticagrelor was discontinued for economic reason and changed to clopidogrel (75 mg once daily). The next day, symmetrical erythema and needle-shaped papules appeared on skin of the abdomen and limbs, and gradually throughout the whole body. Then, mung bean-sized blisters and papulo-vesicle appeared and part of them fused into lamella with a small amount of exudation and severe itching. Two weeks later, the skin of the distal extremities thickened and the skin surface was rough and desquamated. The patient had developed 2 episodes of similar symptoms in the past. Six years ago, the similar symptoms occurred for the first time. The patient developed rashes 4 to 5 days after taking aspirin and clopidogrel after PCI. Clopidogrel was discontinued after 10 months and, half a month later, the skin symptoms completely subsided. Fourteen months ago, the similar skin symptoms occurred for the second time. Clopidogrel was given after PCI and rashes appeared 2 days later. The skin rash was relieved after anti-allergic treatments. The patient stopped taking clopidogrel herself 9 months later, the skin symptoms completely subsided half a month later. Clopidogrel-induced eczema-like drug eruption was considered. Clopidogrel was withdrawn and antihistamine, glucocorticoid, and antipruritic were given. Two weeks after drug withdrawal, the papules on the trunk were flattened and became dry, the part of the ruptured vesicles on the abdomen healed, scales of the limbs reduced, itching subsided, and no new skin lesions appeared.
Itraconazole induced erectile dysfunction
Yang Yue, Zhan Cheng, Zhang Yingchun
. 2018, 20 (4): 304-305. ;  doi: 10.3760/cma.j.issn.1008-5734.2018.04.013
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A 30-year-old male patient was treated with 3 courses of itraconazole capsules for toenail onychomycosis (each treatment course was 4 weeks, itraconazole capsules 200 mg twice daily was given for 7 successive days at the first week of each course). The patient took the medicine regularly and did not take other medicines simultaneously according to the doctor′s advice. At the end of the first course, erectile dysfunction occurred; the patient did not care about it and continued taking the medicine. The patient′s toenail onychomycosis was cured after 3 courses of treatment; however, the score of International Index of Erectile Function (IIEF-5) was 10 (a moderate erectile dysfunction). Itraconazole capsules were stopped and his life style was adjusted, 3 months later, his symptom was not improved markedly. Sildenafil citrate tablets and treatment with therapeutic device for sexual dysfunction were given and, 3 months later, his IIEF score was 22 and erectile function was greatly improved.
Severe lower gastrointestinal bleeding due to concomitant use of aspirin and ticagrelor
Du Qingqing, Wang Na, Liu Rui, Zhao Chunjing, Qian Yan, Zhao Li
. 2018, 20 (4): 306-308. ;  doi: 10.3760/cma.j.issn.1008-5734.2018.04.014
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A 66-year-old male patient received aspirin enteric-coated tablets (100 mg once daily) and ticagrelor tablets (90 mg twice daily) after percutaneous coronary intervention (PCI). After 2 weeks of treatments, a small amount of melena appeared and gradually worsened with dizziness and weakness. The symptoms were not markedly improved after treatments with acid suppression, gastric protection, hemostasis, and repeated blood transfusions. Aspirin enteric-coated tablets and ticagrelor were stopped, fasting, infusion of suspended red blood cells, intravenous esomeprazole (80 mg once every 8 hours) via an infusion pump, oral almagate suspension (1.5 g thrice daily), and nutritional support treatments were given. On day 4, the symptoms were not improved and intravenous pumping of octreotide 0.6 g once every 12 hours was added; on day 8, the patient developed tar-like stools approximately 1000 g, blood pressure 92/62 mmHg, and hemoglobin (Hb) 43 g/L. Gastroscopy showed superficial gastritis. Colonoscopy failed because rectal mucosa was covered. Lower gastrointestinal bleeding was considered continuously and Yunnanbaiyao (云南白药) and thrombin were applied. On day 13 after aspirin enteric-coated tablets and ticagrelor withdrawal, the patient′s Hb dropped to 37 g/L, BP 85/59 mmHg, and developed severe anemia. On day 25, laparotomy was performed. During the operation, it was found that the small intestine was significantly dilated, the cavity was black and there were a large number of diffuse petechiae on the mucosa which were at 100 to 200 cm from the Treitz ligament. The bleeding intestinal segment was removed and acid suppression, hemostasis, and nutritional fluid support treatments were given. After that, melena did not recur and anemia was gradually improved. On the 16th day after the partial small intestine resection, the abdominal incision healed well and laboratory tests showed Hb 88g/L.
Apatinib induced hypothyroidism
Zhao Shenhui, Zhang Li, Yang Hong
. 2018, 20 (4): 309-310. ;  doi: 10.3760/cma.j.issn.1008-5734.2018.04.015
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A 68-year-old male patient received apatinib 850 mg orally once daily for advanced gastric cancer with liver and lymph node metastasis despite previous treatments with multiple lines of chemotherapy, which induced myelosuppression. About 1 month after the medication, the patient developed fatigue and poor appetite. Thyroid function tests showed serum free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) levels of 3.1 pmol/L, 9.9 pmol/L and, 8.9 mU/L. It was considered that hypothyroidism was induced by apatinib. Then apatinib was discontinued and levothyroxine sodium tablets 50 μg by mouth once daily was given. Ten days later, the patient′s symptoms relieved and the serum FT3, FT4, and TSH levels were 5.4 pmol/L, 15.8 pmol/L, and 5.7 mU/L. Then oral apatinib was given at a reduced dose of 500 mg once daily. Five days later, the patient developed fatigue again and then apatinib was stopped again. The patient′s symptoms relieved 10 days after the drug withdrawal and the serum FT3, FT4, and TSH levels returned to 4.9 pmol/L, 10.8 pmol/L, and 5.4 mU/L.
Iatrogenic botulinum toxin poisoning misdiagnosed as myasthenia gravis
Wang Liuqing, Xiao Yuelan, Zhang Shoucheng, Wang Hong
. 2018, 20 (4): 311-312. ;  doi: 10.3760/cma.j.issn.1008-5734.2018.04.016
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A 26-year-old female patient received injections of botulinum toxin in a private clinic for cosmetology. One hundred units of botulinum toxin were injected firstly into the mandible, and then 200 units were injected into each gastrocnemius 14 days later. On day 2 after the second injection, the patient suffered from fatigue and oppression in chest, which did not affect her daily life. Above-mentioned symptoms aggravated 3 weeks later and even difficulty in walking and limbs lifting, bucking in drinking, and bilateral blepharoptosis appeared. She was admitted to hospital 4 weeks after the onset of the disease. Physical examination showed that the patient had bilateral blepharoptosis, difficulty in head-raising, grade 4, 5, and 3 muscle strength respectively in the proximal limbs, distal limbs, and lower extremities, and unable to stand up after squatting. Myasthenia gravis was considered. However, results of the prostigmin test and repetitive electrical nerve stimulation test did not support above diagnosis. Swelling in the patient′s lower jaw was found during the doctor′s regular ward rounds on day 4 after the admission and the diagnosis of botulinum toxin poisoning was confirmed by inquiring the history of disease. After 12 days of symptomatic treatments, the patient′s weakness of limbs and oppression in chest relieved, bilateral blepharoptosis markedly improved, and her muscle strength returned to normal basically.
Thrombocytopenia caused by regorafenib
Zhang Juan, Wu Dongyuan, Wang Yongjie, Dong Mei
. 2018, 20 (4): 313-314.
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A 39-year-old female patient with sigmoid colon and rectal adenocarcinoma received an oral regorafenib 160 mg once daily because of the disease progression. The treatment course was 21 days. The results of routine blood test showed her PLT 159×109/L before regorafenib treatment. Seven days after medication, the patient developed asthenia and gingival bleeding. Laboratory test showed PLT 38×109/L and thrombocytopenia was diagnosed. Regorafenib was stopped and infusion of platelets was given twice, 2.5 U totally. On day 7 after the drug withdrawal, the patient′s PLT restored to 159×109/L and on day 15, PLT 217×109/L. Oral regorafenib 80 mg once daily was given again. On day 10 after regorafenib treatment again, laboratory test showed PLT 69×109/L, the patient developed fistula bleeding on renal pelvis and small intestine. Regorafenib was stopped again and replaced with capecitabine. On the next day after the drug withdrawal, the bleeding disappeared. At 2 weeks of follow-up, bleeding did not recur in the patient.
Organizing pneumonia resulting from rituximab
Wang Chunhui, Xu Qing, Wu Wei, Li Xiaoyu, Lyu Qianzhou
. 2018, 20 (4): 315-317. ;  doi: 10.3760/cma.j.issn.1008-5734.2018.04.018
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A 15-year-old boy with diffuse large B cell lymphoma received treatment with a R-CHOP chemotherapy regimen consisting of rituximab, cyclophosphamide, epirubicin, vincristine and prednisone. During the second cycle of chemotherapy, on day 24 after intravenous infusion of rituximab 600 mg, he developed cough and expectoration and his symptoms did not relieve after 2 weeks of treatment with ceftazidime. High resolution CT (HRCT) of the chest showed air bronchogram and mottling in his left upper lung and right lower lung, and inflammatory consolidation was considered. After receiving treatment with biapenem and azithromycin, his symptoms, inflammatory indices, and imaging findings did not significantly improve. According to the temporal correlation as well as pathological and etiological examination results, interstitial pneumonia and cancerous obstructive pneumonia associated with pulmonary infection or connective tissue disease were excluded, and organizing pneumonia induced by rituximab was considered. Rituximab was stopped and replaced by a CHOP chemotherapy regimen. In addition, antibacterial drugs were withdrawn and oral prednisolone 15 mg thrice daily was given. Thirty days later, the patient′s cough slightly relieved. However, when the dose of glucocorticoid was reduced to 15 mg/d, his cough and expectoration was slightly aggravated. Subsequently, the dose of prednisolone was increased to 40 mg/d, and 42 days later, was decreased to 20 mg/d. Eighty eight days later, the patient′s cough significantly  improved, HRCT of the chest revealed no abnormal findings in the left lung and no pleural effusion in the thoracic cavity, having mottling in the lower lobe of his right lung, and unobstructed bronchial.
Accepts
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