Stability of prothrombin time and activated partial thromboplastin time tests under different storage conditions

Prothrombin time (PT) and activated partial thromboplastin time (aPTT) are common laboratory tests that are useful in the diagnosis of coagulation disorders and monitoring anticoagulant therapy. Recent expansions in the outreach laboratory services at our institution prompted us to investigate the shipping limitations for some tests, including PT and aPTT. Although we followed NCCLS guidelines for the collection of blood specimens, we observed falsely elevated PT and aPTT values due to the different storage conditions. The objective of this study is to determine the effect of conditions and duration of storage on PT and aPTT tests using plasma and whole blood samples, respectively. For this study, 36 plasma samples with normal and prolonged PT and aPTT were exposed to different storage conditions. Blood was centrifuged immediately and plasma was stored at room temperature (RT), refrigerated at 4°C, or frozen at −20°C. The samples were analyzed at 0 h and repeated at 6, 12 and 24 h under various conditions. Although statistically significant differences were observed for plasma samples for normal PT tests after 12 h at refrigerated and frozen storage conditions, the differences would not change the clinical interpretation of the results. On the other hand, samples stored refrigerated or at RT showed significant differences for aPTT at 24 h. These differences would change clinical interpretation, especially for samples with normal or near normal aPTT times. Interestingly, aPTT was significantly higher for samples stored frozen when compared to refrigerated and RT conditions at 6 h. Similar patterns were also observed on ten whole blood samples with normal PT and aPTT values. In conclusion, either plasma or whole blood samples can be accepted for PT testing up to 24 h and for aPTT testing up to 12 h only, when transported either at RT or at 4°C.     

Continuous haemofiltration with r-hirudin (lepirudin) as anticoagulant in a patient with heparin induced thrombocytopenia (HIT II)

A 60-year-old man was admitted to the hospital with aortic dissection. An operative excision and replacement with a Y-graft was performed. Postoperatively he developed multiple organ dysfunction and required intermittent haemofiltration (anticoagulation with heparin). An ischemia of the left leg occurred at the third postoperative day. The initial platelet count was 99,000/microliter. Continuous haemofiltration (CVVH) was started three days later. Thrombotic obstructions of haemodialysis filters and catheters occurred frequently and heparin-induced thrombocytopenia (HIT II) was suspected. Antibodies against heparin were found in the HIPA test. Despite heparin free citrate dialysis and anticoagulation with danaparoid thrombotic obstructions of filters and catheters continued. Therefore the anticoagulation therapy during CVVH was changed to recombinant hirudin (lepirudin). Starting dose was a bolus of 0.01 mg/kg bw followed by the same amount as maintenance dose per hour. Anticoagulation was adjusted to an increase of aPTT (activated partial thromboplastin time) to 1.5-2 times its normal value. A dose of 0.005 mg/kg bw/h lepirudin was sufficient to maintain adequate anticoagulation. After changing to lepirudin no further catheter obstructions were observed and the platelets recovered slowly. Renal function improved and five weeks after admission endogenous creatinine clearance showed a value of 25 ml/min. We conclude that lepirudin is an effective anticoagulant during CVVH in patients with HIT II. In partly permeable polysulfon filters a dose of 0.005 mg/kg bw/h lepirudin is sufficient to maintain adequate anticoagulation. Monitoring anticoagulation by measuring the increase of aPTT (factor 1.5-2.0) seems to be safe. However, optimally the r-hirudin concentration should be measured directly using the Ecarin clotting time.     

The uncalibrated prothrombinase-induced clotting time test. Equally convenient but more precise than the aPTT for monitoring of unfractionated heparin

The activated partial thromboplastin time test (aPTT) represents one of the most commonly used diagnostic tools in order to monitor patients undergoing heparin therapy. Expression of aPTT coagulation time in seconds represents common practice in order to evaluate the integrity of the coagulation cascade. The prolongation of the aPTT thus can indicate whether or not the heparin level is likely to be within therapeutic range. Unfortunately aPTT results are highly variable depending on patient properties, manufacturer, different reagents and instruments among others but most importantly aPTT's dose response curve to heparin often lacks linearity. Furthermore, aPTT assays are insensitive to drugs such as, for example, low molecular weight heparin (LMWH) and direct factor Xa (FXa) inhibitors among others. On the other hand, the protrombinase-induced clotting time assay (PiCT?) has been show to be a reliable functional assay sensitive to all heparinoids as well as direct thrombin inhibitors (DTIs). So far, the commercially available PiCT assay (Pefakit?PiCT?, DSM Nutritional Products Ltd. Branch Pentapharm, Basel, Switzerland) is designed to express results in terms of units with the help of specific calibrators, while aPTT results are most commonly expressed as coagulation time in seconds. In this report, we describe the results of a pilot study indicating that the Pefakit PiCT UC assay is superior to the aPTT for the efficient monitoring of patients undergoing UFH therapy; it is also suitable to determine and quantitate the effect of LMWH therapy. This indicates a distinct benefit when using this new approach over the use of aPPT for heparin monitoring.     

Superior mesenteric vein thrombosis presented transient false positivity for lupus anticoagulant under heparin treatment.

A 24-year-old Japanese man was admitted because of massive haematemesis and melaena with persistent abdominal pain. Markedly bloody ascites and severely oedematous small intestine were recognized, and angiography then revealed superior mesenteric vein thrombosis. After resection of the necrotic small intestine, continuous intravenous infusion of heparin and urokinase was performed. This patient had no familial or personal history of thrombosis. On the 15th day after operation, an initial search for lupus anticoagulant revealed that the prothrombin time (PT) ratio and dilute activated partial thromboplastin time (aPTT) were positive under heparin treatment, without evidence of rheumatic or connective tissue disease. Thrombocytopenia was observed with a nearly normocellular bone marrow. A follow-up examination 1 year later still revealed an increased aPTT. However, all tests for antiphospholipid antibodies had been negative including dilute aPTT for about 2 years since the 15th day after operation. These findings suggest that, in this patient, superior mesenteric vein thrombosis has not been associated with primary antiphospholipid syndrome but is probably idiopathic. Positive tests for lupus anticoagulant in the initial period may be unreliable due to heparin treatment.     

Argatroban for heparin-induced thrombocytopenia in hepato-renal failure and CVVHD

OBJECTIVE: To report a case of significant hepatic and renal failure with the use of argatroban in a patient with heparin-induced thrombocytopenia (HIT) requiring continuous veno-veno hemodialysis (CVVHD). CASE SUMMARY: A 37-year-old Hispanic man with diabetes mellitus, ethanol abuse, and recent crank use developed a venous thrombosis and possible pulmonary embolism, followed by acute liver and renal failure requiring continuous veno-venous hemofiltration. After several days of heparin therapy, the dialyzer circuit thrombosed and the platelet count decreased to 82 x 10(3)/mm(3). Antibodies for HIT by enzyme-linked immunosorbent assay were positive. Heparin was discontinued, and an argatroban infusion was initiated. After 39 hours on argatroban, the infusion was stopped when minor bleeding was observed with a concurrent activated partial thromboplastin time (aPTT) of 100 seconds. The dialyzer circuit did not clot during the argatroban infusion and did not apparently influence dose-related aPTT measurements. Several days were required for the aPTT to decrease after stopping the argatroban infusion. Fresh frozen plasma had no apparent effect on aPTT values. DISCUSSION: Several different agents are currently available to provide effective anticoagulation in patients who have immune- mediated HIT. Argatroban is hepatically cleared and may be the preferred direct thrombin inhibitor in the presence of significant renal impairment, but conversely has prolonged effects in hepatic failure. Limited data are available regarding use of direct thrombin inhibitors in patients who have severe hepatic impairment with concurrent renal failure requiring CVVHD. Scant data are available regarding the effect of hemodialysis on the elimination of argatroban. CONCLUSIONS: The optimal anticoagulant for use in a patient with HIT and concurrent hepatic and renal failure is unclear. No direct thrombin inhibitor has a proven advantage; therefore, selection may depend on clinical factors. Dosing in these patients requires very careful management.     

N-去硫酸肝素对肾缺血-再灌注损伤防治作用的研究

目的 :研究 N去硫酸肝素对大鼠肾缺血再灌注损伤的防治作用。方法 :建立肾缺血再灌注损伤大鼠模型 ,实验动物随机分为正常对照组和 N 去硫酸肝素治疗及非治疗组。观察大鼠治疗前后肾组织中 P 选择素表达、组织病理学与肾功能的改变 ,以及凝血指标〔包括凝血酶原时间 (PT)和部分激活凝血时间 (KPTT)〕的变化。结果 :缺血再灌注后大鼠肾脏 P 选择素表达增高 ,出现明显组织病理学改变 ,血清尿素氮 (BUN)、肌酐(Cr)水平明显升高〔分别为 (14.5 4± 0 .6 7) mm ol/ L 和 (10 2 .12± 4.76 ) μmol/ L〕;N 去硫酸肝素治疗组肾脏组织中 P选择素表达受抑 (未出现棕黄色颗粒 ) ,病理学改变与肾功能损害减轻 ,且对 PT和 KPTT无明显影响。结论 :N去硫酸肝素对肾缺血再灌注损伤具有防治作用 ,且对凝血指标 PT和 KPTT无明显影响。     

Effects of telavancin on coagulation test results

Background: The lipoglycopeptide antibiotic, telavancin, may interfere with some laboratory coagulation tests including prothrombin time (PT) and activated partial thromboplastin time (aPTT). Objective: To evaluate the effects of telavancin on PT and aPTT assays in common use. Methods: Pooled normal human plasma was spiked with telavancin 10, 20, 100 or 200 μg/ml (equivalent to trough, 2 × trough, peak and 2 × peak clinical plasma concentrations, respectively) or diluent control (0.9% sodium chloride). Samples were analysed using 16 PT reagents and seven aPTT reagents. Results: Telavancin 200 μg/ml (corresponding to 2 × peak clinical plasma concentration), produced significant PT prolongation (> 9% difference vs. diluent control) with all the 16 PT reagents (range 12% to > 600%). At lower telavancin concentrations, PT prolongation was dose‐dependent and varied among reagents, but appeared greatest with preparations containing recombinant tissue factor. With telavancin 10 μg/ml (equivalent to trough), PT prolongation was 10% with HemosIL^® PT‐Fibrinogen Recombinant, while ranging from 5% to –1% with all other reagents. Significant (> 34% difference vs. baseline) and dose‐dependent aPTT prolongation was observed with all the seven reagents in samples spiked with telavancin 100 or 200 μg/ml (range 65–142% at 200 μg/ml). aPTT reagents containing a silica activator appeared to be more sensitive to telavancin interference. Telavancin 10 μg/ml was not associated with increased aPTT with any of the reagents tested. Conclusions: Telavancin has the potential to prolong both PT and aPTT in vitro. It is recommended that samples for PT or aPTT be obtained just prior to a telavancin dose (trough).     

A prospective, randomized, sequential crossover trial of large-volume versus normal-volume leukapheresis procedures: effects on serum electrolytes, platelet counts, and other coagulation measures

BACKGROUND: LVL procedures with the administration of heparin as an additional anticoagulant are increasingly performed because of the potentially higher yield of autologous peripheral blood HPCs. A prospective, randomized crossover trial was performed to evaluate the influence of leukapheresis volume-that is, large versus normal-on serum electrolytes, platelet count, and other coagulation measures in 25 patients with breast cancer and 14 patients with non-Hodgkin's lymphoma. STUDY DESIGN AND METHODS: Patients were randomly assigned to start either with an LVL on Day 1 followed by a normal-volume leukapheresis (NVL) on Day 2 or vice versa. In LVL, heparin was administered in addition to ACD-A. Bleeding complications, transfusion support, whole-blood counts, and several coagulation measures as well as plasma heparin levels were evaluated. RESULTS: Although the duration, the infused amount of ACD-A, the flow rate, the drop in platelet count, and the drop in potassium were significantly greater in LVL, and although LVL patients also received heparin, there was no significant difference in clinical tolerance or bleeding complications. After LVL, patients exhibited a significantly longer activated partial thromboplastin time (APTT), with a median of 70 seconds (range, 44-100 sec), and a median anti-factor Xa activity of 0.69 IU per mL (range, 0.10-1.29 IU/mL). The value of the APTT after LVL correlated with anti-factor Xa activity (r = 0.37, p<0.05), but not with platelet count or heparin infusion rate. Markers for coagulation activation did not increase during NVL or LVL. CONCLUSION: LVL with heparin as an additional anticoagulant seems to be a safe procedure in patients with low preleukapheresis platelet counts. No activation of coagulation occurred after NVL or LVL procedures.     

Comparing methods of establishing the aPTT therapeutic range of heparin

BACKGROUND: The American College of Chest Physicians (ACCP) recommends that the activated partial thromboplastin time (aPTT) therapeutic range for unfractionated heparin be defined as the aPTT corresponding to a heparin concentration of 0.3-0.7 micro/mL by heparin anti-factor Xa assay. This recommendation suggests that a therapeutic range defined in this manner should be superior to traditional empiric therapeutic ranges of 1.5-2.5 times the control. A pilot study was conducted to evaluate the ACCP recommendation for heparin monitoring. OBJECTIVE: To compare heparin dosage adjustments guided by a heparin concentration-derived therapeutic range (HCDTR) with those influenced by traditional empiric therapeutic ranges for the aPTT. METHODS: This study was conducted in 2 phases. In phase 1, the various aPTT therapeutic ranges were established and/or defined. The first empiric therapeutic range (E1) was established by performing an aPTT test on healthy volunteers. This E1 was defined as 1.5-2.5 times the mean normal aPTT. A second empiric therapeutic range (E2) was defined as 1.5-2.5 times the patient's baseline aPTT. The aPTT HCDTR had been defined in a previous study as 48-61 seconds. In phase 2, heparin dosage adjustment decisions guided by each empiric range and the HCDTR for the aPTT were compared with heparin dosage adjustment decisions guided by actual heparin concentrations. Decisions were in agreement when both the aPTT result and plasma heparin concentration indicated the same dosage change. Forty patients had a bedside aPTT determined prior to receiving continuous infusion heparin and again within 48 hours of heparin initiation. Plasma heparin concentration by anti-factor Xa assay was performed on the blood samples obtained after heparin initiation. Heparin dosage adjustment decisions were evaluated by determining the agreement of each aPTT test result with the corresponding plasma heparin concentration. An overall level of agreement (defined as the % of decisions that were in agreement) for each aPTT therapeutic range was determined. RESULTS: The level of agreement in dosage adjustment decisions between heparin concentration and E1, E2, and HCDTR was 28/40 (70%), 28/39 (72%), and 23/40 (58%), respectively (p = 0.34). Heparin dosage adjustment decisions based on an aPTT HCDTR did not significantly differ from heparin dosage adjustment decisions guided by traditional empiric therapeutic ranges for a bedside aPTT. CONCLUSIONS: This pilot study showed similar heparin dosage adjustment decisions using an empiric aPTT therapeutic range versus a heparin concentration-derived aPTT therapeutic range.     

Effect of lepirudin on the international normalized ratio

BACKGROUND: Many patients receiving direct thrombin inhibitor (DTI) therapy require transition to warfarin. This transition may be complicated by DTI-induced elevations in the international normalized ratio (INR). While the effect of argatroban on the INR has been characterized, data assessing the effect of lepirudin on the INR are limited. OBJECTIVE: To evaluate the effect of lepirudin on the INR. METHODS: Patients receiving lepirudin therapy between January 2000 and May 2001 were identified using the pharmacy database, and a retrospective chart review was conducted. Patients were included for analysis if they had paired activated partial thromboplastin time (aPTT) and INR data while receiving lepirudin monotherapy. RESULTS: Fifty-three paired aPTT and INR data points from 8 patients receiving lepirudin monotherapy were collected. The Organon MDA 180 instrument was used for aPTT and prothrombin time (PT) determination. Organon MDA Platelin L reagent was used for the aPTT and Organon Simplastin L reagent was used for the PT. The international sensitivity index (ISI) of the Simplastin L thromboplastin was 2.0. The mean +/- SD lepirudin dose was 0.05 +/- 0.04 mg/kg/h. Linear regression was used to identify the INRs that correspond to a therapeutic aPTT value of 45-75 seconds (1.5-2.5 times mean laboratory normal of 30 sec). The correlation between aPTT and INR was 0.77. An aPTT of 45-75 seconds with lepirudin correlated to an INR of 1.6-3.2. CONCLUSIONS: Based on laboratory results, when using a thromboplastin with an ISI of 2, lepirudin appears to elevate the INR in the absence of warfarin.     

Dabigatran deliberate overdose: two cases and suggestions for laboratory monitoring

Context: Dabigatran etexilate (dabigatran) is a direct thrombin inhibitor anticoagulant agent. There is limited information about the changes in coagulation profile and outcomes in overdose. A monoclonal antibody has been developed to neutralize the anticoagulant effect of dabigatran. Case reports describe enhanced clearance of dabigatran by haemodialysis as an intervention to prevent haemorrhagic complications – however, the threshold for initiating haemodialysis is not well defined in an asymptomatic patient with normal renal function. Case details: Two patients presented following deliberate dabigatran overdoses. A 55-year-old woman ingested 10?×?150?mg dabigatran. A 21-year-old woman with a history of systemic lupus erythematosus and pulmonary embolus ingested 100?×?110?mg dabigatran. Both were admitted to the intensive care unit and managed expectantly. Serial coagulation tests normalized over 60 h. The half-life of dabigatran was not prolonged following overdose, being calculated between 7 and 11 h in each case. There was positive correlation between international normalized ratio (INR), prothrombin time (PT) and activated partial thromboplastin time (aPTT) with plasma dabigatran levels. Conclusion: There is limited experience with dabigatran overdoses. Normal aPTT, PT and INR assays 12 h following deliberate ingestion indicate that the drug concentration is not high. Individual risk assessment of bleeding risk needs to be formulated for each patient and expectant management is reasonable in the presence of normal renal function and absent risk factors for bleeding.     

Reference intervals for coagulation tests in adults with different ABO blood types

IntroductionCoagulation tests are affected by many factors, such as age, race, and gestation. Although coagulation test results vary by ABO blood type, reference intervals of different ABO blood groups remain to be determined. This study aims to investigate the reference ranges of coagulation tests for different ABO blood groups in the Han population in South China.MethodsA retrospective study was conducted in the First Affiliated Hospital of Shantou University Medical College. In all, 9600 individuals aged between 20 and 79 years were included. Coagulation tests, including prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), thrombin time, and fibrinogen, were performed.ResultsThere was a significant difference in PT, INR, and aPTT among ABO blood groups. PT and INR varied slightly between ABO blood groups. There was a higher aPTT value in individuals in the O blood group than in those in non‐O blood groups, in both males and females across the included age range. No differences were found in thrombin time and fibrinogen between the ABO blood groups.ConclusionThe study provides reference data on coagulation tests from ABO blood groups in South China. The established reference intervals specific to ABO blood type, sex, and age may improve clinical decisions based on coagulation tests.     

Idarucizumab for dabigatran overdose

Context: An overdose of oral anticoagulants represents a challenging scenario for emergency physicians. Dabigatran, an oral direct thrombin inhibitor, is increasingly used in place of warfarin. The lack of an antidote is a concern in patients who overdose on dabigatran, even though the drug can be eliminated with hemodialysis. Idarucizumab is an antibody fragment that binds dabigatran with high affinity. It reverses the anticoagulant effect of dabigatran within minutes and is approved for the reversal of dabigatran during emergency situations.

Case details: We describe the use of idarucizumab in the management of a 68-year-old woman who was taking dabigatran 150?mg twice daily and ingested 125 capsules. Despite gastric lavage and administration of activated charcoal within two hours of drug intake, the activated partial thromboplastin time (aPTT) and prothrombin time (PT) remained prolonged. The administration of 5?g of intravenous idarucizumab promptly and completely reversed the anticoagulant activity of dabigatran as assessed by routine and specific coagulation assays (aPTT from to 75 to 26?s, PT from 26 to 11?s and diluted thrombin time from 92 to 27?s). The initially planned emergency hemodialysis was canceled.

Discussion: This case highlights the potential use of idarucizumab for the management of massive dabigatran overdoses.     

实验前相关因素对测定新生儿血浆PT、APTT的影响

目的探讨抗凝、离心、黄疸等实验前相关因素对测定新生儿血浆凝血酶原时间（PT）、活化部分凝血活酶时间（API]r）的影响,从而进一步优化试验条件。方法本试验选取100名外科术前体检无异常发现的新生儿,所有入选新生儿均无血栓性疾病及出凝血功能障碍,无心、肾、肝等重要脏器疾病。将此100名新生儿分为3组,分别为抗凝剂比例影响组（包括抗凝剂比例9：1组和抗凝剂比例校正组）、离心条件影响组[2000r／min（离心半径为10cm）离心10min;3000r／min（离心半径为10em）离心10min组;2500r／min（离心半径为10cm）离心15min组]、生理性黄疸影响组。利用STAGO全自动血凝分析仪对以上几个处理组的标本进行检测,并且使用SPSS13．0统计软件对得到的数据进行比较,从而逐步优化实验条件。结果在相同离心条件下,抗凝剂9：1组的PT、APlTr明显延长。在抗凝剂比例经过校正的情况下,2000r／min（离心半径为10em）离心10min组的PT、APTT明显延长;3000r／min（离心半径为10cm）离心10min组中大部分标本PT、APTT正常,个别出现溶血的标本PT明显延长。2500r／min（离心半径为10cm）离心15min是新生儿检测胛、APTT的最适离心条件。在抗凝剂比例经过校正,2500r／min（离心半径为10cm）离心15min的条件下,生理性黄疸组与无生理性黄疸组的胛、APTT比较差异无统计学意义。结论在处理新生儿血浆标本时,应进行抗凝剂比例校正,离心转速不宜过快,否则容易引起溶血,从而引起实验误差。可以通过适当降低离心速度,延长离心时间来避免这种情况的发生。生理性黄疸基本不影响PT、APTT的测定。     

Does continuous heparinization influence platelet function in the intensive care patient?

Objective: To study the influence of continuous administration of heparin on platelet function in intensive care patients. Design: Prospective, serial investigation. Setting: Clinical investigation on a surgical and neurosurgical intensive care unit in a university hospital. Patients: The study included 45 patients: 15 postoperative with patients sepsis (Acute Physiology and Chronic Health Evaluation II score between 15 and 25), 15 trauma patients (Injury Severity Score 15 to 25), and 15 neurosurgical patients. Interventions: Management of the patients was carried out according to the guidelines for modern intensive care therapy. Sepsis and trauma patients received standard (unfractionated) heparin continuously [aim: an activated partial thromboplastin time (aPTT) approximately 2.0 times normal value; sepsis-heparin and trauma-heparin patients], whereas neurosurgical patients received no heparin (neurosurgical patients). Measurements and results: From arterial blood samples, platelet aggregation was measured by the turbidimetric method. Platelet aggregation was induced by adenosine diphosphate (ADP; 2.0 μmol/l), collagen (10 μg/ml), and epinephrine (25 μmol/l). Measurements were carried out on the day of diagnosis of sepsis or 12 h after hemodynamic stabilization (trauma and neurosurgery patients) (baseline) and during the next 5 days at 12.00 noon. Standard coagulation parameters [platelet count and fibrinogen and antithrombin III (AT III) plasma concentrations] were also monitored. Heparin 4–10 U/kg per h (mean dose: approximately 500 U/h) was necessary to reach an aPTT of about 2.0 times normal. Platelet count was highest in the neurosurgical patients, but it did not decrease after heparin administration to the trauma and sepsis patients. AT III and fibrinogen plasma levels were similar in the three groups of patients. In the sepsis group, platelet aggregation variables decreased significantly (e. g., epinephrine-induced maximum platelet aggregation: − 45 relative % from baseline value). Platelet function recovered during the study and even exceeded baseline values (e. g., ADP-induced maximum platelet aggregation: + 42.5 relative % from baseline value). Continuous heparinization did not blunt this increase of platelet aggregation variables. In the heparinized trauma patients, platelet aggregation variables remained almost stable and were no different to platelet aggregation data in the untreated neurosurgical patients. Conclusions: Continuous administration of heparin with an average dose of approximately 500 U/h did not negatively influence platelet function in the trauma patients. Recovery from reduced platelet function in the sepsis group was not affected by continuous heparinization. Thus, continuous heparinization with this dose appears to be safe with regard to platelet function in the intensive care patient. Received: 30 July 1996 Accepted: 10 February 1997     

实验前相关因素对测定新生儿血浆PT、APTT的影响

目的探讨抗凝、离心、黄疸等实验前相关因素对测定新生儿血浆凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)的影响,从而进一步优化试验条件。方法本试验选取100名外科术前体检无异常发现的新生儿,所有入选新生儿均无血栓性疾病及出凝血功能障碍,无心、肾、肝等重要脏器疾病。将此100名新生儿分为3组,分别为抗凝剂比例影响组(包括抗凝剂比例9∶1组和抗凝剂比例校正组)、离心条件影响组[2 000 r/min(离心半径为10 cm)离心10 min;3 000 r/min(离心半径为10 cm)离心10 min组;2 500 r/min(离心半径为10 cm)离心15 min组]、生理性黄疸影响组。利用STAGO全自动血凝分析仪对以上几个处理组的标本进行检测,并且使用SPSS 13.0统计软件对得到的数据进行比较,从而逐步优化实验条件。结果在相同离心条件下,抗凝剂9∶1组的PT、APTT明显延长。在抗凝剂比例经过校正的情况下,2 000 r/min(离心半径为10 cm)离心10 min组的PT、APTT明显延长;3 000 r/min(离心半径为10 cm)离心10 min组中大部分标本PT、APTT正常,个别出现...     

N-去硫酸肝素对肝和肾缺血-再灌流损伤防治作用的研究

目的：探讨N－去硫酸肝素对肝和肾缺血－再灌注损伤的防治作用。方法：分别建立大鼠肝及肾缺血－再灌流损伤模型，观察和比较经N－去硫酸肝素处理前后大鼠肝、肾组织P－选择素表达，组织病理学改变及肝、肾功能变化，以及对凝血指标（PT和KPTT）的影响。结果：肝、肾缺血再灌流后，大鼠肝、肾组织内P－选择素广泛表达，出现明显的组织病理学改变及肝、肾功能损伤。经给予N－去硫酸肝素处理后，肝、肾组织P－选择素表达受到抑制，组织病理学改变减轻，肝、肾功能得到改善，进一步发现N－去硫酸肝素对PT和KTPP无明显影响。结论：N－去硫酸肝素可能通过间接抑制P－选择素作用，而对肝和肾缺血－再灌流损伤起到防治效果，且对凝血指标无明显影响。     

Assessment of weight-based versus standard dosing of heparin in patients with unstable angina

OBJECTIVE: To assess whether a weight-based dosing regimen (80 u/kg + 18 u/kg/h) or a standard-fixed dose regimen (5000 u + 1000 u/h) of heparin is more appropriate in patients with unstable angina (UA). METHOD: A drug use evaluation was conducted. Patient data for all patients weighing less than 100 kg who were in the coronary care unit of a Veterans Administration Hospital and who received heparin for UA (>24 h) over a 7-month period were included. For the first 4 months, patients were given standard heparin dosing and in the final 3 months patients were given heparin based on weight. The proportion of patients achieving activated partial thromboplastin times (aPTTs) that were at least therapeutic during therapy, the time to achieve the aPTT at a level that was at least therapeutic, and the number of patients with aPTTs over the therapeutic range were compared between groups. RESULTS: Patients in the group receiving weight-based heparin therapy (n = 23) were significantly more likely to achieve an aPTT that was at least therapeutic than patients receiving standard therapy (n = 42, 100% vs. 76%, respectively, P = 0.011). When all the patients in each group who achieved an aPTT that was at least therapeutic were compared, the weight-based group achieved the levels significantly faster than the standard-fixed dosing group (7.3 +/- 6.1 vs. 22.6 +/- 17.6 h, respectively, P = 0.0003). However, the use of weight-based dosing was associated with a higher incidence of achieving supertherapeutic aPTTs than standard therapy (78.3% vs. 50.0%, respectively, P = 0.049). CONCLUSION: Patients with UA may achieve therapeutic aPTTs faster than those on standard therapy but they also have a higher risk of achieving a supertherapeutic aPTT.     

Clinical assessment of Nafamstat mesilate (FUT-175): a new anticoagulant for immunoadsorption using membrane plasmapheresis (IAP)

Nafamstat mesilate (FUT-175), a new anticoagulant with a short half-life of biological activity, was used in five patients who had a history of bleeding during immunoadsorption using membrane plasmapheresis (IAP) due to excessive heparin. FUT-175 (1.2 mg/kg/h) was injected into the arterial blood line during IAP therapy. The prothrombin time (PT), activated partial thromboplastin time (APTT), bleeding time (BT), and complete blood count (CBC) were measured before and after IAP. The PT ( 17.7 ± 0.8 s) after IAP therapy was nearly 1.4 times the level of the PT (12.6 ± 0.6 s) before IAP treatment. The APTT levels after IAP (67.4 ± 2.8 s) were nearly 1.8 times the values before IAP (37.2 ± 2.3 s). There were no significant differences in red blood cell (RBC), hemoglobin (Hb) or platelet counts before and after IAP therapy. No patients developed thrombosis, hemorrhage, or other side effects during IAP. In conclusion, the optimal dosage of FUT-175 was 1.2 mg/kg body wt/h during immunoadsorption with membrane plasmapheresis (IAP). FUT-175 is recommended as a useful anticoagulant during IAP treatment of patients with an increased risk of bleeding.     

不同抗凝方式下连续组静脉-静脉血液滤过透析治疗对凝血及透析滤器使用寿命的影响研究

目的观察低分子肝素全身抗凝和枸橼酸局部抗凝在连续性静脉-静脉血液滤过透析(CVVH)时滤器使用寿命的比较研究。方法回顾性分析2016年1-4月54例患者行128例次CVVH的治疗情况,按照抗凝方式不同分为枸橼酸钠组和低分子肝素组,对两组患者的临床资料、活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)、滤器使用时间及疗效进行比较。结果两种抗凝方式下均取得显著疗效,枸橼酸钠组滤器及管路平均使用寿命显著长于低分子肝素组。结论枸橼酸局部抗凝技术在延长滤器使用时间方面有明显优势,且对患者凝血指标影响较小。