Studies of interaction of a low-molecular-weight heparinoid (Org 10172) with cloxacillin and ticarcillin in healthy male volunteers.

Pharmacokinetic and pharmacodynamic interactions between Org 10172 (intravenous bolus injection of 3,250 anti-Xa units), which is a low-molecular-weight heparinoid, cloxacillin (500 mg orally four times daily for 3 days), and ticarcillin (4,000 mg intravenously four times daily for 2 days) were evaluated in two separate studies with healthy male volunteers (n = 18). Both cloxacillin and ticarcillin caused a significant increase in elimination half-life of anti-Xa activity, i.e., from 31 +/- 10 to 54 +/- 23 h and from 27 +/- 6 to 42 +/- 13 h, respectively (P less than 0.05). Ticarcillin decreased clearance (11%) and increased apparent volume of distribution (35%) (P less than 0.05), while for cloxacillin, these differences did not reach statistical significance. These changes in disposition of Org 10172 by the penicillins were not accompanied by important pharmacodynamic changes as evaluated by coagulation tests, platelet aggregation, and bleeding time. Cloxacillin appeared to influence blood coagulation (prolongation of the activated partial thromboplastin time and shortening of thrombin time; P less than 0.05) and facilitated thrombin-induced platelet aggregation, which coincided with a shorter bleeding time during the combined treatment in comparison with the time during treatment with Org 10172 alone (P less than 0.05). In conclusion, the disposition of Org 10172 was slightly changed by cloxacillin and ticarcillin, and, unexpectedly, cloxacillin appeared to have mild procoagulant effects.     

Automated amidolytic method for determining heparin, a heparinoid, and a low-Mr heparin fragment, based on their anti-Xa activity

Using the chromogenic substrate S-2222, we have optimized and automated an amidolytic assay for heparin. The assay is based on the detection of anti-Xa activity generated by heparin in plasma. The method is reproducible (intra- and interassay CVs of 2.4 and 3.3%, respectively) and reliable in antithrombin III-deficient plasma. Results of this assay, obtained for plasma samples from patients and volunteers treated with heparin, correlate well (r = 0.899) with those of the test for activated partial thromboplastin time. Upon administration of a low-Mr heparinoid (Org 10172) and heparin fragment ( Kabi 2165), however, the activated partial thromboplastin time failed to detect anticoagulant activity, whereas the chromogenic heparin assay revealed anti-Xa activity. This automated amidolytic assay for heparin is therefore suitable not only for monitoring standard therapy with heparin but also for measuring the activity of recently developed heparin fractions.     

低分子量肝素在血液透析应用中的评价

目的：比较低分子量肝素与普通肝素在常规血液透析抗凝中的有效性和安全性。方法：40例血液透析患分别用低分子量肝素和普通肝素抗凝进行自身对照，并作低分子肝素组与普通肝素组的组间对照。观察透析器及透析管道的凝血状态，内瘘穿刺点的压迫止血时间，抗因子Xa活性(AFXa)、凝血酶时间(TT)和活化部分凝血活酶时间(APTT)。结果：两组患均能顺利完成5小时透析，透析器及透析管道凝血程度及穿刺点压迫止血时间两组均无显差异(P＞0．05)。两组患使用低分子肝素抗凝透析结束时AFXa较血液透析前有显性差异(P＜0．001)，且透析开始后30分钟及透析结束时均明显高于普通肝素组，而APTT、TT在LMWH抗凝过程中无显延长，而普通肝素组则明显延长。结论：低分子量肝素在血液透析抗凝过程中较之普通肝素更有效，安全，方便，可替代普通肝素。     

Standard heparin, low molecular weight heparin, low molecular weight heparinoid, and recombinant hirudin differ in their ability to inhibit transduction by recombinant adeno-associated virus type 2 vectors.

Recombinant adeno-associated virus type 2 (rAAV) is a promising vector for in vivo gene therapy. Transduction by rAAV requires binding to heparan sulfate proteoglycan on the cell surface, and heparin can block this binding. Because heparin is administered to most patients undergoing cardiovascular gene transfer in order to prevent thrombotic events, it is important to identify anticoagulants which do not interfere with rAAV transduction. Therefore, we examined the influence of different anticoagulants on rAAV transduction in vitro. rAAV transduction was inhibited by 40.5 +/- 7.9% at heparin concentrations of 0.1 U/ml, and by 81.7 +/- 3.6% at 1.0 U/ml. The low molecular weight (LMW) heparin tinzaparin inhibited rAAV transduction by 20.2 +/- 3.8% at 0.1 U/ml and 37.1 +/- 1.8% at 1.0 U/ml. The inhibitory effect was significantly weaker compared with heparin at 1.0 U/ml, (P < 0.01). The LMW heparinoid danaparoid inhibited rAAV transduction by 8.8 +/- 3.5% at 0.1 U/ml (P < 0.01 compared with heparin). In contrast, recombinant hirudin did not interfere at all with rAAV transduction. In summary, the results demonstrate that inhibition of rAAV transduction by heparin occurs rapidly and at therapeutically used concentrations. LMW heparinoids and above all recombinant hirudin might be alternatives for heparin when vascular gene transfer with rAAV requires transient anticoagulation.     

Heparin monitoring during cardiac surgery. Part 2: Calculating the overestimation of heparin by the activated clotting time

Activated clotting time (ACT) values were converted to heparin concentration, enabling an assessment of the accuracy of the ACT and a quantification of the prolongation imposed by bypass. Blood samples were obtained from 42 adult cardiopulmonary bypass (CPB) patients before and during bypass surgery. Samples were analysed for ACT (HemoTec ACT) and anti-factor Xa (anti-Xa) plasma heparin concentration. The mean heparin concentration calculated before bypass was an accurate reflection of plasma heparin; however, calculated values rose to around 170% of anti-Xa values upon connection to bypass. By adjusting for this rise, for 95% of cases the calculated heparin concentration would vary between 0.60 and 1.65 times anti-Xa values. Without accounting for artificial prolongation or individual sensitivities, the ACT may give values between 0.8 and 3.0 times that indicated by the anti-Xa assay. When both individual heparin sensitivities and the effects of bypass are considered, the ACT may provide a more suitable indication of heparin levels; however, typical use may overestimate heparin up to threefold.     

Heparin-induced platelet aggregation in anorexia nervosa and in severe peripheral vascular disease

Abstract. We have previously demonstrated that platelets obtained from patients with anorexia nervosa or severe peripheral vascular disease are hyperaggregable. Since conventional heparins are known to activate platelets in vitro and occasionally induce thrombosis and consumptive thrombocytopenia in vivo , we have investigated the direct effect of a conventional heparin on platelets obtained from patients with anorexia nervosa or severe peripheral vascular disease. Heparin at therapeutic concentrations was found to induce platelet aggregation of such platelets in vitro. In contrast, a recently developed low molecular weight heparinoid (Org 10172), at therapeutic concentrations, had no effect on these hyperaggregable platelets. We conclude that: (i) heparin may be potentially harmful to patients with hyperaggregable platelets; (ii) thrombocytopenia and thrombosis associated with heparin therapy may be mediated through a direct effect of heparin on platelets; (iii) it is unlikely that heparin induced thrombocytopenia is always mediated by classical immunological mechanisms, especially in patients with hyperaggregable platelets; and (iv) low molecular weight heparinoids may be safer anticoagulants in patients with platelet hyperaggregability.     

Evaluation of a new point of care heparin test for cardiopulmonary bypass: the TAS heparin management test

Patients undergoing cardiopulmonary bypass (CPB) require anticoagulation with heparin to avoid thrombosis within the bypass circuit. The common method used to monitor the degree of anticoagulation is the activated clotting time (ACT). We evaluated a novel point of care device, the TAS (Pharmanetics, Raleigh, NC, USA) heparin management test (HMT), for its suitability in monitoring anticoagulation during CPB. In vitro analysis showed a dose-response (r2=0.988) of the HMT from 0.078-10.0 U/ml heparin, covering the range of heparin used during cardiac surgery (2-5 U/ml). Fifty randomly selected patients undergoing CPB were studied. Preheparin clotting times for these patients were 143+/-32 s for the HMT and 146+/-18 s for the ACT; 435+/-60 s HMT and 438+/-39 s ACT during CPB; 145+/-50 s HMT and 128+/-14 s ACT post-protamine (r2=0.797). epsilon-Aminocaproic acid treatment for inhibition of fibrinolysis did not affect the HMT. We conclude that the HMT correlates well with the ACT and may be useful for monitoring heparin during CPB. Advantages of the HMT are small sample volume and good sensitivity to heparin.     

人胎盘抗凝蛋白变体的抗凝与抗栓作用

探索新型抗凝蛋白质--人胎盘抗凝蛋白变体(annexin V derivative,AND)抗凝和抑制动脉血栓形成的作用.方法比较实验组动物和对照组动物在用药前,用药后15,30,60 min及停药2 h活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)、凝血酶时间(TT)、血浆纤维蛋白原(Fg)含量.用药15 min后用球囊剥脱股动脉内皮并监测股动脉远端的血压,记录脉压为0的时间即血栓完全闭塞血管的时间.最后剪取球囊损伤的股动脉,测量所形成血栓的长度、血栓的湿重和干重.结果抗凝指标用药组在用药后15 min时,其APTT值最长,且APTT值明显长于生理盐水组(P＜0.05),短于肝素组(P＜0.01),肝素组的APTT、TT值明显长于其他3组,PT值各组间差异无统计学意义;对Fg的影响大剂量用药组似乎可以降低Fg的血浆含量;血栓质量无论是湿重还是干重AND组都明显轻于对照组(P＜0.001),大剂量AND组血栓干重显著轻于小剂量组(P＜0.05);小剂量AND组血栓的长度明显短于生理盐水组(P＜0.05),但和肝素组相比,差异无统计学意义(P=0.485),大剂量AND组明显短于生理盐水组(P＜0.01)和肝素组(P＜0.05);脉压为0的时间AND组显著长于对照组(P＜0.05)和肝素组相比,差异无统计学意义.结论AND是一种安全有效的抗凝和抗栓剂,其抗凝作用在用药后15 min时最强.AND抗凝作用弱于普通肝素,但抗栓能力强于普通肝素,在临床治疗血栓性疾病有应用前景.     

低剂量鱼精蛋白拮抗肝素围体外循环期血浆肝素浓度变化与凝血功能损害

目的：探讨低剂量鱼精蛋白拮抗肝素围体外循环(CPB)期血浆肝素浓度变化的规律及其与术后凝血功能损害的关系。方法：采用发光底物法测定25例风湿性心脏瓣膜病瓣膜置换手术病人低剂量鱼精蛋白拮抗肝素下围CPB期血浆肝素浓度，并同时检测凝血功能指标：激活凝血时间(ACT)、血浆凝血酶原时间(PT)和活化部分凝血活酶时间(APTT)。结果：CPB结束时血浆肝素平均水平(11．06U／mL)显著地降低到肝素化初期浓度(13．16U／mL)的0．84左右(P<0．05)，低剂量鱼精蛋白拮抗肝素后5h内血浆肝素水平基本上稳定在CPB前水平(P>0．05)；当鱼精蛋白中和肝素后，ACT值迅速接近至术前水平(P>0．05)，并稳定于术前水平，而PT、APTT则仍显著异常高于正常水平(P<0．05)，但有明显恢复至正常的趋势。结论：CPB结束时采用低剂量鱼精蛋白拮抗肝素(0．8mg鱼精蛋白：100U肝素)能充分有效地中和血中肝素：CPB后凝血功能并不立即恢复正常，主要原因不是肝素中和不足，而是CPB本身使凝血功能受到损害。     

Anticoagulation during extracorporeal circulation under conditions of an ongoing systemic inflammatory response syndrome: effects of heparin

OBJECTIVE: Open-heart surgery with cardiopulmonary bypass (CPB) causes changes in haemostasis. Artificial surfaces are bioincompatible and, thus, may initiate a reaction similar to an acute inflammation. In some patients, this 'postperfusion syndrome' (PPS), which includes changes in haemostasis, is the beginning of a systemic inflammatory response syndrome (SIRS). However, it is not clear whether the changes in coagulation represent a consequence or a main cause of the inflammatory reaction. Thus, the aim of our study was to investigate the cascade of coagulation and the effects of heparin under special circumstances of an ongoing SIRS. METHODS: In a prospective evaluation using standardized operative procedures with CPB, we compared Group A (control group with normal postoperative course, n =20) with Group B (patients with postoperative SIRS, n =12). At six time points beginning before and ending two days after surgery, we measured platelet counts, leucocyte counts and plasma levels of fibrinogen, factor XII and antithrombin III (ATIII), in addition to standard coagulation tests (PTT, TT and ACT). Furthermore, we determined parameters of inflammation, such as C-reactive protein, PCT, IL-6, IL-8, IL-10 and TNF-alpha. RESULTS: In Group B (SIRS), we found a reduced anticoagulation during CPB with significantly lower values for PTT (60+/-7 versus 160+/-11 s), ACT (270+/-33 versus 532+/-44 s) TT (40+/-3 versus 150+/-15 s) compared to the control Group A. Simultaneously, we found a significant increase of factor XII in the SIRS group (191+/-16 versus 10+/-2%). There were no significant differences concerning the preoperative ATIII levels and the intraoperative dosage of heparin; the intraoperative decrease of fibrinogen, ATIII and platelets was comparable in both groups. Furthermore, we could see that significant changes of inflammatory parameters in the SIRS group (increasing levels of TNF-alpha, Il-6, IL-8 and IL-10) occurred at least 30 min after the observed reduction of anticoagulatory effect. CONCLUSIONS: With our results, it could be demonstrated that the development of inflammatory complications after CPB is correlated to a significantly reduced intraoperative effect of heparin. As this reduction of anticoagulation significantly preceded the changes of inflammatory parameters in SIRS patients, we think that a hypercoagulatory state, especially in cases of ongoing inflammation, is an additional trigger of SIRS.     

DVT and pulmonary embolism: Part II. Treatment and prevention

Treatment goals for deep venous thrombosis include stopping clot propagation and preventing the recurrence of thrombus, the occurrence of pulmonary embolism, and the development of pulmonary hypertension, which can be a complication of multiple recurrent pulmonary emboli. About 30 percent of patients with deep venous thrombosis or pulmonary embolism have a thrombophilia. An extensive evaluation is suggested in patients younger than 50 years with an idiopathic episode of deep venous thrombosis, patients with recurrent thrombosis, and patients with a family history of thromboembolism. Infusion of unfractionated heparin followed by oral administration of warfarin remains the mainstay of treatment for deep venous thrombosis. Subcutaneously administered low-molecular-weight (LMW) heparin is at least as effective as unfractionated heparin given in a continuous infusion. LMW heparin is the agent of choice for treating deep venous thrombosis in pregnant women and patients with cancer. Based on validated protocols, warfarin can be started at a dosage of 5 or 10 mg per day. The intensity and duration of warfarin therapy depends on the individual patient, but treatment of at least three months usually is required. Some patients with thrombophilias require lifetime anticoagulation. Treatment for pulmonary embolism is similar to that for deep venous thrombosis. Because of the risk of hypoxemia and hemodynamic instability, in-hospital management is advised. Unfractionated heparin commonly is used, although LMW heparin is safe and effective. Thrombolysis is used in patients with massive pulmonary embolism. Subcutaneous heparin, LMW heparin, and warfarin have been approved for use in surgical prophylaxis. Elastic compression stockings are useful in patients at lowest risk for thromboembolism. Intermittent pneumatic leg compression is a useful adjunct to anticoagulation and an alternative when anticoagulation is contraindicated.     

Heparin monitoring during cardiac surgery. Part 1: Validation of whole-blood heparin concentration and activated clotting time

There is limited published data on the agreement between techniques for monitoring heparin levels. The aim of this study was to validate the Hepcon/HMS, with particular focus on the agreement with laboratory anti-Xa assay. The performances of two ACT instruments--Hemochron and HemoTec--were also evaluated, including an assessment for interchangeability. Blood samples from 42 adult cardiopulmonary bypass (CPB) patients were analysed for activated clotting time (ACT), whole-blood heparin concentration (Hepcon/HMS) and anti-factor Xa (anti-Xa) plasma heparin concentration. Agreement between measures was determined using the method of Bland and Altman. Simple analysis of agreement between the Hepcon and anti-Xa heparin revealed the Hepcon has a mean bias of -0.46 U/mL, with the limits of agreement +/- 1.12 U/mL. The comparison between ACT instruments indicated a mean difference of -96 seconds for the HemoTec, with limits of +/- 265 seconds. The Hepcon/ HMS instrument displayed satisfactory agreement with anti-Xa plasma heparin concentration, as the expected variation would not be expected to cause problems in the clinical setting. Agreement between the two measurements of ACT may be satisfactory, provided each is assigned a different target value.     

AFFECT: a prospective,open-label,multicenter trial to evaluate the feasibility and safety of a short-term treatment with subcutaneous certoparin in patients with persistent non-valvular atrial fibrillation

BACKGROUND: Patients with persistent atrial fibrillation (AF) scheduled for electrical cardioversion need immediate anticoagulation. Unfractionated heparin (UFH) is often used for early anticoagulation in these patients before oral anticoagulation becomes effective. However, dose adjustment is required to achieve a two- to three-fold prolongation of the activated partial thromboplastin. Low molecular weight heparins, given in body weight-adjusted or independent fixed dosage, require less laboratory monitoring and are also effective within hours of first dosing. They seem to be an attractive alternative to UFH. Previous evidence has shown that these drugs are safe and effective in this indication. PATIENTS AND METHODS: In this prospective, open-label, multicenter pilot study, 203 patients were enrolled with persistent non-valvular AF scheduled for electrical cardioversion. Patients received a fixed dose of 8000 U anti-Xa certoparin twice daily starting immediately after enrolment and before cardioversion was performed. Patients with AF > 48 h underwent transoesophageal echocardiography (TEE) before cardioversion to exclude intra-atrial thrombi. After cardioversion, overlapping oral anticoagulation was started. Treatment with certoparin was stopped only after two consecutive days with INR values >2. OBJECTIVES: The objective was to document the feasibility and safety of a short-term treatment with a fixed, body weight-independent certoparin regimen (2 x 8000 U anti-Xa). RESULTS: Out of 203 patients enrolled, 200 received at least one dose of certoparin and were included in the analysis (safety population). Median treatment duration with certoparin was 7 days. Bleedings were observed in 8 patients (4.0%) and were classified as major (1.5%) or minor (2.5%). Cerebral ischemia was reported for 1 patient (0.5%). One patient showed mild thrombocytopenia (0.5%). There were no reports of venous thromboembolism or death during the treatment period. CONCLUSION: Certoparin administered at 8000 U anti-Xa twice daily independent of body weight was safe and appeared to be effective in patients with non-valvular AF undergoing electrical cardioversion. Its ease of use and the possibility of treatment on an outpatient basis make it an attractive option for early anticoagulation in AF.     

血液透析应用低分子量肝素和普通肝素相关实验参数比较

目的 研究血液透析应用低分子量肝素和普通肝素抗凝时相关实验参数的变化。方法 22例血液透析的尿毒症患者分别用低分子量肝素和普通肝素抗凝,监测指标包括抗因子Xa活性(AFXa)、凝血酶时间(TT)和活化部分凝血活酶时间(APTT)。结果 应用低分子量肝素抗凝时APTT、TT在透析过程中延长不明显(P>0.05),普通肝素组APTT、TT于透析30分钟及透析结束时明显延长,甚至部分血液不凝。低分子量肝素组透析结束时血浆抗FXa活性较透析前有显著性差异,且透析后30分钟及透析结束时均明显高于普通肝素组(P<0.001)。结论 低分子量肝素抗凝作用同APFF、TT无一定相关,低分子量肝素抗凝作用可由抗-FXa水平作为可靠根据,低分子量肝素在血液透析抗凝过程中比普通肝素更为安全、有效。     

两种冲洗液对持续行中心静脉压监测患者的临床效果观察

目的探讨两种冲洗液对持续行中心静脉压监测患者凝血功能及导管堵塞情况的影响。方法选取持续行中心静脉压监测的患者80例,按照随机数字表分为实验组和对照组,各40例。实验组的冲洗液选择0.9%的氯化钠溶液250 ml,对照组选用浓度为2.5 U/ml的肝素盐水作为冲洗液。两组分别于持续行中心静脉压(CVP)监测后,比较1 d、3 d、5 d、7 d的活化部分凝血酶原时间(APTT)、凝血酶原时间(PT)、血浆凝血酶时间(TT),同时观察两组中心静脉导管堵塞情况。结果对照组持续行中心静脉压监测后3 d、5 d、7 d的APTT、PT、TT均高于实验组,对照组持续行中心静脉压监测后1 d、3 d、5 d、7 d的APTT、PT、TT与治疗前相比均升高,差异均有统计学意义(P0.05)。使用两种冲洗液后导管阻塞情况比较差异无统计学意义(P0.05)。结论对于持续行中心静脉监测的患者,宜采用未加肝素的生理盐水作为冲洗液。     

Plasma exchange for heparin-induced thrombocytopenia in patients on extracorporeal circuits: A challenging case and a survey of the field

Current management of heparin-induced thrombocytopenia (HIT) involves prompt discontinuation of all heparin products and concomitant initiation of a direct thrombin or anti-Xa inhibitor for anticoagulation. In the setting of HIT complicated by an urgent need for cardiopulmonary bypass (CPB), the safety and the efficacy of short-term heparin-based anticoagulation after therapeutic plasma exchange (TPE) have been previously demonstrated. Patients with HIT requiring TPE are frequently on extracorporeal circuits (either CPB, extracorporeal membrane oxygenation [ECMO] or external ventricular assist devices [VADs]). Performing TPE in parallel with these circuits involves additional consideration for circuit size, anticoagulant/citrate management, as well as flow rates, and risk of air embolus. We report a case of a patient with HIT on external biventricular assist device (BiVAD) requiring urgent CPB who experienced thrombotic and hemolytic complications related to anticoagulation management around apheresis line placement for TPE. We also present results from a national survey of academic apheresis services regarding specific practices in managing patients with HIT on extracorporeal circuits who require TPE. In addition, we demonstrate the utility of TPE in patients with HIT on extracorporeal circuits and the risks of this procedure and the need to develop practice guidelines.     

Whole blood heparin concentrations do not correlate with plasma antifactor Xa heparin concentrations in pediatric patients undergoing cardiopulmonary bypass

This study was designed to test the validity of whole blood heparin concentration (WHBC) measurements using an on-site protamine titration assay with the Hepcon instrument (Medtronic Blood Management, Parker, CO, USA) in pediatric patients less than 1 year old undergoing cardiopulmonary bypass (CPB). The validity of the Hepcon measurements was examined via a test of correlation with the gold standard plasma antifactor Xa activity (anti-Xa) assay. Fifty-one patients (23 females and 28 males) under 1 year old (mean age 5.3 months) were studied prospectively. Blood samples were taken at 5 min into CPB and at the end of CPB for the WBHC, plasma anti-Xa activity, and hematocrit (Hct). The WBHC was converted to plasma heparin level using a formula taking into account the collection of blood into citrate solution and the effect of the citrate on the hematocrit. While a nonparametric statistical analysis revealed that the mean corrected values from the Hepcon instrument were not significantly different from the mean anti-Xa values (p = 0.070 at 5 min on CPB, p = 0.518 at the end of CPB), there was no significant correlation between these values at either 5 min into CPB (r = 0.113, p = 0.429) or at the end of CPB (r = -0.247, p = 0.080). The lack of correlation between the two assays may be related to the extreme hemodilution observed during CPB in small children, which leads to very low concentrations of coagulation proteins. Due to this discrepancy, whole blood heparin monitors should be further evaluated in children undergoing CPB.     

利伐沙班在恶性肿瘤预防性抗凝中的疗效评价

目的评价新型口服抗凝药物利伐沙班在恶性肿瘤患者预防性抗凝中的疗效。方法选择Khorana评分≥3分的血栓高危患者30例(高危组),Khorana评分1~2分的血栓中低危患者20例(中低危组),比较两组患者间凝血指标差异。高危组给予利伐沙班预防性抗凝(口服10mg/d),并比较该组用药前,用药4、24h后的凝血酶原时间(PT)、国际标准化比值(INR)、活化部分凝血活酶时间(APTT)、纤维蛋白原(FIB)、凝血酶时间(TT)、抗凝血酶(AT)、D-二聚体(D-dimer)、纤维蛋白与纤维蛋白原降解产物(FDP)、抗Ⅹa活性(Anti-Ⅹa)的差异,分析这些指标变化的临床意义。结果高危组患者用药前较中低危组PT、INR、D-dimer、FDP明显升高(P<0.05),APTT、FIB、TT、AT、Anti-Ⅹa差异无统计学意义(P>0.05)。高危组预防性抗凝4h后PT、INR、APTT、Anti-Ⅹa均明显升高(P<0.05),用药后24h与用药4h比较,差异有统计学意义(P<0.05)。结论对于恶性肿瘤血栓高危患者应进行预防性抗凝,利伐沙班预防性抗凝可抑制外源性、内源性两大凝血途径,从而降低血栓风险;不同个体间采用相同剂量利伐沙班预防性抗凝效果差异较大,建议采取个体化预防抗凝方案。     

与血液透析中低分子量肝素抗凝相关的护理工作探讨

观察低分子量肝素在血液透析中的抗凝效果 ,比较与普通肝素在护理方面的不同处理。对 2 6例维持血液透析患者分别用速避凝 (n =10 )和普通肝素 (n =16)进行抗凝 ,分别测定透析前、透析 2h和透析 4h的APTT ,并观察透析器凝血情况和透析后穿刺部位压迫时间及两者的出血并发症的发生率。结果表明 ,普通肝素组透析 2h、4hAPTT明显延长 ,出血发生率高 ,穿刺点压迫时间明显长于低分子量肝素组 ,低分子量肝素组APTT无明显变化 ,未发现出血和透析器凝血等并发症。在血液透析中应用低分子量肝素较普通肝素安全、稳定 ,抗凝效果好 ,出血的并发症少 ,较普通肝素有很大优越性。对患者透析中及透析后的护理有指导意义     

Normothermic Cardiopulmonary Bypass Increases Heparin Requirements Necessary to Maintain Anticoagulation

Objective. With the practice of warm cardiopulmonary bypass (CPB) at our institution we have observed an apparent increase in heparin requirements. CPB temperature predictability affects pharmacokinetics and differences in drug metabolism can be expected. We hypothesized that heparin requirements would increase with increasing CPB temperature. Methods. Following Institutional Review Board approval, we reviewed the charts of 354 patients undergoing primary coronary artery bypass graft surgery. We recorded patient demographic data, CPB duration, heparin requirements, and temperature during CPB. CPB was conducted between 24 °C and 37 °C. The Spearman's correlation coefficient, Pearson chi-square, and rank-sum tests were used for data analysis. Results. Core temperature during CPB correlated with heparin requirements (r = 0.13, p < 0.02). However, CPB duration was shorter in warm patients than in cold patients (r = –0.455, p < 0.0001). Additional heparin requirements adjusted for duration of CPB (units/minute) were also significantly greater in the warm group (p = 0.018). Conclusions. Maintenance of adequate heparin anticoagulation during CPB is clinically important. Warm CPB patients required more heparin per minute than those undergoing cold CPB. More frequent assessment of anticoagulation and administration of additional heparin should be considered in patients undergoing warm CPB.