出凝血异常普通外科病人围手术期静脉血栓栓塞症防治策略

易栓症是外科围手术期静脉血栓栓塞症(VTE)的防治重点。对于接受手术的止凝血障碍病人,需要谨慎评估VTE的个体风险,同时兼顾手术和麻醉的性质、出血障碍类型和严重程度、年龄、体重指数(BMI)、血栓形成史、恶性肿瘤和其他高危共患病。VTE风险应与已知出血障碍病人使用抗凝相关的出血风险平衡。实验室检查有助于发现和判断血栓与出血的病因,对病人的止凝血代偿能力作出评估,并对抗凝药物的合理使用提供依据。对上述病人,建议术后不常规使用药物预防血栓,尤其是血友病病人,但围手术期因子替代和止血药物的过度应用仍存在导致血栓的风险。使用低分子肝素(LMWH)和直接口服抗凝剂前应评估肾小球滤过率。当血小板计数<50×109/L,LMWH短期减量应用可能相对安全,监测抗Хa水平可用于调整中重度血小板减少症病人LMWH的剂量。主要消化道出血停止和重新使用华法林应至少相隔7 d。对于高血栓栓塞风险和术后高出血风险病人,术后当晚和术后第1天减量应用直接口服抗凝剂是一种可取的做法。     

Cefoperazone-sulbactam and risk of coagulation disorders or bleeding: a retrospective cohort study

ABSTRACT

Objectives: Limited evidence has suggested that cefoperazone-sulbactam causes coagulation disorders and bleeding.

Methods: The authors conducted a retrospective study to compare patients receiving cefoperazone-sulbactam versus those treated with cefoperazone-tazobactam or ceftazidime. Propensity-score matching was used to explore whether treatment with cefoperazone-sulbactam increased the risk of prothrombin time (PT) prolongation, coagulation disorders, and bleeding, or decreased platelets (PLT).

Results: The cohort included 23,242 patients. Among patients receiving cefoperazone-sulbactam, the risk of PT prolongation, coagulation disorders, decreased PLT, and bleeding was 5.3%, 9.2%, 15.7%, and 4.2%, respectively. Propensity-score matching analyses suggested that cefoperazone-sulbactam increased the risk of PT prolongation (aOR 2.26, 95% CI 1.61–3.18), coagulation disorders (aOR 1.81, 95% CI 1.43–2.30), and decreased PLT (aOR 1.46, 95% CI 1.25–1.72), but not increase bleeding (aOR 1.05, 95% CI 0.79–1.40) compared with ceftazidime. Patients receiving cefoperazone-sulbactam had higher risk of PT prolongation (aOR 1.53, 95% CI 1.11–2.10), coagulation disorders (aOR 1.53, 95% CI 1.21–1.95), but not decreased PLT (aOR 0.93, 95% CI 0.81–1.07) or bleeding (aOR 1.11, 95% CI 0.87–1.42), compared with those receiving cefoperazone-tazobactam.

Conclusion: Cefoperazone-sulbactam may be associated with a higher risk of PT prolongation and coagulation disorders compared with cefoperazone-tazobactam and ceftazidime.     

Effects of acute liver injury on blood coagulation

Summary.  The mechanisms leading to the hemostatic changes of acute liver injury are poorly understood. To study these further we have assessed coagulation and immune changes in patients with acute paracetamol overdose and compared the results to patients with chronic cirrhosis and normal healthy controls. The results demonstrate that in paracetamol overdose coagulation factors (F)II, V, VII and X were reduced to a similar degree and were significantly lower than FIX and FXI (mean levels 0.28, 0.16, 0.13, 0.19, 0.51 and 0.72 IU mL⁻¹, respectively). In cirrhosis, by contrast, FII, FV, FVII, FIX and FX were equally reduced whilst FXI was lower than the other factors (mean levels 0.64, 0.69, 0.62, 0.60, 0.66 and 0.40 IU mL⁻¹, respectively). FVIII was raised in paracetamol overdose patients but normal in those with cirrhosis (mean levels 1.95 and 1.01 IU mL⁻¹, respectively). Interleukin-6 and tumor necrosis factor-α levels were raised in both patient groups, but higher levels were found in paracetamol overdose, compared to cirrhosis. Thrombin-antithrombin and soluble tissue factor levels were higher in those with acute liver injury but normal in cirrhosis. Antithrombin levels were reduced in both acute liver injury and cirrhosis. From these data we put forward a novel mechanism for the coagulation changes in acute paracetamol induced liver injury. We propose that immune activation leads to tissue factor-initiated consumption of FII, FV, FVII and FX, but that levels of FIX and FXI are better preserved because antithrombin inhibits the thrombin induced positive feedback loop that activates these latter factors.     

Effect of norethisterone acetate on serum lipid and lipoprotein parameters as well as on blood coagulation in female monkeys (M. fascicularis)

The effects of daily oral administration of a high dose of 10 mg norethisterone acetate (NET-Ac.)/kg/day over 14 weeks on serum lipid and lipoprotein parameters as well as on blood coagulation were investigated in female monkeys (M. fascicularis). Measurements of lipids and lipoprotein cholesterol were performed in weeks —5 and — 1 before treatment and in weeks 4, 8 and 12 after treatment. In addition, various blood coagulation and fibrinolytic parameters were determined in weeks 11–14 after treatment with NET-Ac. Furthermore, the serum levels of norethisterone (NET) were determined in order to monitor the real systemic compound exposure and revealed that C_max and AUC (0–3 h) values reached for norethisterone in this experiment in monkeys were about 25 times higher than those obtained after an oral contraceptive dose of NET-Ac. in women.

The results of lipid and lipoprotein cholesterol determinations showed decreases in serum total lipids, phospholipids, triglycerides and total cholesterol associated with similar decreases in HDL-, LDL- and VLDL-cholesterol fractions after NET-Ac.-treatment in monkeys. These effects were observed from week 4 onwards and maintained their magnitude up to week 12 after treatment. Since both HDL- and LDL-cholesterol fractions decreased, the HDL/LDL-ratio remained almost unchanged. Thus, the results obtained in this study after high-dose treatment with NET-Ac. in monkeys did not indicate any changes of lipid and lipoprotein parameters which in humans are supposed to be associated with an increased risk of cardiovascular lesions, namely a decrease in HDL- and increase in LDL-cholesterol fractions.

The results of blood coagulation and fibrinolytic parameters showed increased antithrombin-III and plasminogen levels besides minor changes in other parameters, thus indicating that NET-Ac. -treatment does not contribute to an increased risk of cardiovascular thrombotic events in the cynomolgus monkey.     

生脉注射液对慢性心力衰竭患者凝血功能的影响

目的研究大剂量生脉注射液对慢性心功能衰竭（简称心衰）患者凝血功能的影响。方法将60例慢性心衰患者随机分为治疗组（即生脉注射液组）和对照组，每组各30例，治疗组给予生脉注射液加西药常规治疗，对照组仅西药常规治疗，观察用药前后心功能改善程度及血浆P-选择素、血管性血友病因子（vWF）和D-二聚体水平的变化。结果治疗组临床显效率与总有效率明显高于对照组。心是患者血浆P-选择素、vWF和D-二聚体水平明显高于健康人，治疗后两组患者血浆P-选择素、vWF和D-二聚体水平均下降，治疗组优于对照组。结论慢性心衰患者，体内存在着高凝状态，大剂量生脉注射液可改善慢性心衰患者的凝血功能，可能在一定程度上减少心衰患者血栓事件的发生和发展？     

Trans-scleral application of a semiconductor diode laser

We used a diode laser with an output power of 1 W through a fiberoptic light pipe (200 microns diameter) to deliver laser energy through the sclera of pigmented rabbits. Ciliary body destruction occurred with energy levels of 300-400 mW and exposure time of 0.5 sec. Retinal photocoagulation was achieved with energy levels of 200-500 mW in 0.5 sec. Histologic examination of acute lesions demonstrated thermal destruction of ciliary body processes and retina. Chorioretinal scar formation was observed clinically and histologically within 2-3 weeks. Our data indicate that the transscleral diode laser may be used for destruction of the ciliary body processes or peripheral retinal coagulation in pigmented eyes.     

股骨干骨折扩髓腔髓内钉固定对凝血机能和肺换气功能的影响

【目的】探讨股骨干骨折扩髓与不扩髓髓内钉固定对凝血机能和肺换气功能的影响。【方法】 38例股骨干骨折分别采用扩髓 (RFN)和不扩髓 (UFN)髓内钉固定 ,在手术开始前至术后 4 8h内 7个不同时间段监测血小板、纤维蛋白原、凝血酶原时间 (PT)和部分凝血活酶激活时间 (APTT)的变化 ,并动脉血气分析 ,计算肺泡 动脉血氧分压递差 [P(A aDO2 ) ]。【结果】RFN组 ,扩髓后血小板开始减少 ,P(A aDO2 )升高 (P<0 0 5 ) ;髓钉插入后 30min纤维蛋白原减少 ,PT、APTT延长 (P <0 0 5 ) ;UFN组表现出同样的趋势 ;两组中各项指标均在 2 4～ 4 8h内恢复正常 ;动脉血气分析各时间段和组间差异无显著性 (P >0 0 5 )。【结论】扩大髓腔的髓内钉固定 ,和不扩髓相比 ,并不影响肺换气功能 ,对凝血机能的影响是一个自限过程 ,单纯股骨干骨折 ,可耐受扩髓固定手术。     

原发性肝癌凝血功能变化的临床价值

目的 :探讨原发性肝癌患者凝血功能变化情况及其临床价值。方法 :对原发性肝癌 6 0例进行凝血酶原时间 (PT)、活化部分凝血酶原时间 (APTT)、纤维蛋白原 (FIB)、凝血酶时间 (TT) 4项凝血指标进行检测和对比分析。结果 :原发性肝癌组与对照组相比 ,PT、APTT、TT均显著延长 P<0 .0 1,FIB明显降低 P<0 .0 5 ,肝癌并发症组与无并发症组相比 ,PT、APTT均显著延长 P<0 .0 1,P<0 .0 5 ,FIB显著降低 P<0 .0 1;原发性肝癌转移组与无转移组相比 ,PT、APTT明显延长 P<0 .0 5 ,FIB显著降低 P<0 .0 5。不同肝功能分级检测结果显示 PT、APTT和 FIB有显著差别。结论 :原发性肝癌患者可出现凝血功能障碍 ,而凝血功能变化情况对评估肝癌肝损害的程度、监测病情变化 ,指导临床治疗及其预后具有一定的应用价值。     

Utilization of recombinant activated factor VII in southern Ontario in 85 patients with and without haemophilia

Recombinant activated factor VII (rFVIIa) is licensed for the treatment of bleeding in individuals with haemophilia and inhibitors. The use of rFVIIa appears to be increasing, and an increase in unlicensed use is suspected. There are currently few data about the specific indications for its use. The aim of this study was to describe the patterns of utilization of rFVIIa. We performed a retrospective cohort study using rFVIIa infusion data collected prospectively and clinical data collected retrospectively. Patients were identified using a tracking system designed to account for use of all coagulation factor concentrates issued in southern Ontario. Between 1 January 2001 and 31 December 2005, 85 patients received rFVIIa. 1164 infusions were given (8246.4 mg). Haemophilia patients with inhibitors accounted for 82.9% of rFVIIa infused and represented 8.2% of patients. The total amount of rFVIIa used increased each year from 2001 to 2004 and then decreased in 2005. The total number of infusions of rFVIIa administered annually increased. Both on-label and off-label use of rFVIIa increased. The number of patients with haemophilia receiving rFVIIa remained small and constant. The number of patients receiving rFVIIa for off-label indications increased markedly. Most rFVIIa infusions were given for licensed indications; however, these infusions represented <10% of patients treated. Overall, the utilization of rFVIIa is increasing, mostly for approved indications; however, the number of patients being prescribed rFVIIa for off-label indications has increased. The tracking system used in this study is a valuable tool to describe ongoing utilization patterns of rFVIIa.