Successful treatment of linezolid-induced severe lactic acidosis with continuous venovenous hemodiafiltration: A case report

Linezolid is an oxazolidinone antibiotic. Linezolid-associated lactic acidosis has been reported in 6.8% of linezolid-treated patients. Lactic acidosis is associated with poor clinical outcomes, with high blood lactate levels resulting in organ dysfunction and mortality. This case report describes the development of lactic acidosis in a 64-year-old Chinese woman who had received 33 days of treatment with antituberculosis drugs and 28 days of treatment with oral linezolid for tuberculous meningitis. Severe lactic acidosis was reversed by withdrawing antituberculosis drugs and using continuous venovenous hemodiafiltration (CVVH). When the patient's condition was stable, she was transferred to the infectious disease department, and antituberculosis drugs, with the exception of linezolid, were reintroduced. This did not result in recurrence of lactic acidosis. The causal relationship between lactic acidosis and linezolid was categorized as ‘probable’ on the Adverse Drug Reaction Probability Scale. This case demonstrates that CVVH has potential as an alternative to discontinuation of linezolid alone for rapid reversal of linezolid-associated severe lactic acidosis.     

地黄不同炮制品薄层色谱鉴别方法的建立

目的:建立地黄不同炮制品的薄层色谱鉴别方法。方法:以D-果糖、梓醇、蔗糖、棉子糖、水苏糖、蜜二糖及甘露三糖为对照品,考察提取溶剂(水,20%甲醇,50%甲醇,80%甲醇),展开剂(正丁醇-甲醇-三氯甲烷-冰乙酸-水,乙酸乙酯-吡啶-冰乙酸-水,正丁醇-冰乙酸-水),显色剂(苯胺-二苯胺-磷酸溶液,茚三酮溶液),点样量(2,4,6μL),检视条件(日光,日光底部灯,365 nm和254 nm)对薄层色谱分析的影响,确定生地黄及熟地黄饮片的供试品溶液制备方法和最佳薄层色谱条件。结果:采用薄层色谱高效硅胶G板,以正丁醇-甲醇-三氯甲烷-冰乙酸-水(13∶5∶5∶1∶2)为展开剂展开,喷以苯胺-二苯胺-磷酸溶液,110℃下加热显色,于日光底部灯下进行检视,所得地黄不同炮制品薄层色谱分离效果和显色效果较佳,斑点清晰且特征性好。结论:该薄层色谱鉴别方法操作简便易行,定性特征明显、结果直观,可有效鉴别地黄不同炮制品,并可为熟地黄的炮制终点确定提供实验依据。     

建立和完善“精准医疗”相关政策，促进体外诊断试剂产业创新与升级

目的：聚焦"精准医疗"，探讨"精准医疗"工作中体外诊断试剂产业发展需求，以期促进我国"精准医疗"涉及的高端诊断医疗产品发展。方法：从我国"精准医疗"涉及的体外诊断试剂产业现状、创新体系以及相关技术等方面，分析体外诊断试剂产业发展面临的问题并提出相关建议，为发展"精准医疗"涉及的高端诊断试剂产业提供参考。结果与结论：随着我国"精准医疗"工作的开展，为高端诊断产品发展带来了机遇，同时也面临诸多挑战，如研发投入严重不足，创新体系配套政策欠缺，国家及行业标准制修订滞后等问题。应从加速配套政策建立、加强体外诊断试剂标准、质量管理体系建设等方面着手，提升我国"精准医疗"核心竞争力，推动诊断产品创新体系建设，促进体外诊断试剂产业发展。     

Influence of sample centrifugation on plasma platelet count and activated partial thromboplastin time using patient samples

BackgroundDiagnostic coagulation testing is vulnerable to factors of the pre-analytical phase such as sample centrifugation. Despite this, centrifugation conditions differ widely among European laboratories. Here we use samples from patients referred for Activated partial thromboplastin time (APTT) testing to investigate if different centrifugation conditions result in platelet-poor plasma (PPP) (plasma platelet count < 10 × 10⁹/L) and how the variation in centrifugation conditions affect APTT measurements.MethodsCentrifugation of 2000g (10 min) were compared with 3000g (10 min) using samples from patients referred for APTT testing (n = 70). Plasma platelet count and APTT were measured to investigate the influence of the centrifugation conditions. Differences were evaluated using Bland Altman Plots and Student’s t-test.ResultsCentrifugation at 3000g for 10 min produced PPP for more of the samples (64%) than centrifugation at 2000g (6%) (p < 0.001). No statistically significant difference for APTT (p = 0.265) was found for samples with APTT < 37 s while samples with prolonged APTT (>37 s) showed a statistically significant difference (p = 0.025). The Bland Altman plot did not reveal a clinically significant difference (mean difference 0.30 s/0.68%) when compared to a maximum acceptable bias of 10%.ConclusionNone of the centrifugation conditions used in this study adequately secured PPP for all samples. Despite a statistically significant difference between samples with prolonged APTT, no clinically significant difference was observed when comparing all APTT measurements.     

乳腺癌患者血浆凝血四项水平的变化及临床意义

目的 探讨乳腺癌患者凝血四项指标即血浆凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)、纤维蛋白原(FIB)的水平变化与乳腺良性肿瘤、病理类型及远处淋巴结转移的关系,以利于对乳腺癌患者病情和预后的评估。方法 选取乳腺癌患者100例为试验组,同期收治的乳腺良性肿瘤患者100例为对照组,检测比较两组患者治疗前血浆凝血四项的水平,以及乳腺癌患者不同病理类型及是否远处转移各指标水平的变化情况。结果 试验组血浆TT水平明显高于对照组,P<0.05;而PT、APTT和FIB的差异均无统计学意义。此外,不同病理类型及有无远处淋巴结转移的乳腺癌患者其凝血四项水平差异不具有统计学意义。结论 乳腺癌患者的TT水平明显高于乳腺良性肿瘤患者,监测乳腺癌患者血浆TT水平有助于对患者病情及预后进行更好地评估。     

APTT法监测体外循环中血浆肝素含量及临床应用

目的 探讨活化的部分凝血活酶时间（APTT）与血浆肝素含量之间的关系，及其在体外循环中的应用。方法 用APTT法检测血浆中不同浓度的肝素含量，建立工作曲线，并用基质血浆与患者血浆进行倍比稀释测定。结果 发现血浆肝素含量在一定范围内与凝固时间的对数值呈良好的线性关系（直线回归，r=0.99)，批内变异系数为2.3%-3.2%，批间变异系数为2.7%-4.9%。结论 APTT较为准确地反映血浆中肝素含量，通过倍比稀释，扩大了检测范围，可适用于大剂量肝素抗凝体外循环的监测，为实行剂量个体化给药提供了基础。     

不同妊娠期孕妇及妊高征患者凝血四项指标变化的意义

目的探讨正常妊娠妇女和妊高征患者凝血酶原时间(PT)、部分凝血活酶时间(APTT)、凝血酶凝固时间(TT)及血浆纤维蛋白原(Fbg)等反映凝血功能4项指标的检测及临床意义。方法厌PT、APTT、TT测定为凝固法,Fbg测定为发色底物法,均在CulterACL-200全自动血凝仪上进行,试剂及定标血浆均为IL公司产品。结果妊娠中、晚期妇女与正常对照组或早期妊娠者比较,PT、APTT、TT时间明显缩短、Fbg含量明显增高,差异有显著性(P<0.05或P<0.01);妊高征组与晚期妊娠组比较,PT、APTT、TT时间进一步缩短,差异有显著性(P<0.05或P<0.01);Fbg水平明显增高,其中65例中、晚孕妇女中39例大于4g/L,占60%;58例中、重度妊高征组中有46例Fbg>4g/L,占80%,某妊高征患者最高Fbg达7.5g/L。结论妊娠各期及妊高征患者由于凝血功能增强、抗凝及纤溶功能减弱,出现所谓妊娠期高凝状态。这一妊娠期生理变化为产后快速有效止血提供了物质基础,但也是导致妊娠期血栓病形成的重要原因,并可能与多种产科疾患有关。妊娠期间检测凝血4项指标的变化对预防血栓形成并及时进行抗凝治疗有着关键的作用。     

Measurement of thrombin generation intra-operatively and its association with bleeding tendency after cardiac surgery

Introduction

Patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) are susceptible to haemostatic disturbances. Monitoring the haemostatic capacity by conventional clotting tests is challenging.

Materials and Methods

Thrombin generation (TG) by Calibrated Automated Thrombography, clotting tests and tissue factor pathway inhibitor (TFPI) measurements were performed to describe the relationship between haemostatic changes and alterations in these tests. Blood samples were collected before, during and after CPB. Furthermore, it was investigated whether TG measured intraoperatively, is associated with increased risk of bleeding postoperatively.

Results

TG diminished significantly (p < 0.01) after heparinization in the presence and absence of platelets (37% and 50%) compared to baseline. After the start of CPB, TG elevated and persisted till the end of surgery but remained lower than preoperatively. Activated clotting time increased after heparinization and after the start of bypass compared to baseline (400% and 500%). Anti-FXa activity reduced on the start of CPB compared to the level after heparinization, to almost the baseline value following protamine reversal of heparin. The plasma levels of total and free TFPI elevated 9 and 14 fold during bypass and remained after protamine administration higher than preoperatively. Plasma D-dimer levels reduced (p < 0.01) when bypass started. However, a marked elevation was observed in the following time points. TG in platelet-rich plasma measured after heparinization and after the start of CPB associated (p < 0.05) with postoperative blood loss.

Conclusions

TG can be determined during CPB despite the high heparinization level, it reflects the haemostatic capacity better than clotting-based assays and might better predict bleeding when performed intraoperatively.     

Tamoxifen induces resistance to activated protein C

Introduction

The estrogen antagonist tamoxifen (TAM) increases the thrombotic risk similar to estrogen containing oral contraceptives (OC). In OC users this risk is attributed to alterations of hemostasis resulting in acquired resistance to activated protein C (APC). TAM-induced APC resistance has not been reported yet.

Materials and Methods

Blood samples were collected prospectively from women with breast cancer before (n = 25) and monthly after start of adjuvant TAM treatment (n = 75). APC resistance was evaluated on basis of the effect of APC on the endogenous thrombin generation potential. To detect increased in vivo APC generation APC plasma levels were measured using a highly sensitive oligonucleotide-based enzyme capture assay. Routine hemostasis parameters were measured additionally.

Results

APC sensitivity decreased by 41% (p = 0.001) compared to baseline after one month of TAM application and remained significantly decreased during the study period. Free protein S increased (p = 0.008) while other analyzed procoagulant factors, inhibitors, and activation markers of coagulation decreased or did not change significantly. In five patients the APC concentration increased to non-physiological levels but an overall significant increase of APC was not observed.

Conclusions

This is the first study showing acquired APC resistance under TAM therapy. Acquired APC resistance might explain the increased thrombotic risk during TAM treatment. Observed changes of hemostasis parameters suggest different determinants of TAM-induced APC resistance than in OC-induced APC resistance. The presence of acquired APC resistance in TAM patients warrants further evaluation if these patients may benefit from antithrombotic prophylaxis in the presence of additional thrombotic risk factors.