Point of care management of heparin administration after heart surgery

Objectives Determination of activated partial thromboplastin time (aPTT) is used in coagulation management after heart surgery. Results from the central laboratory take long to be obtained. We sought to shorten the time to obtain coagulation results and the desired coagulation state and to reduce blood loss and transfusions using point of care (POC) aPTT determination.Design Randomized, controlled trial.Setting University-affiliated 20-bed surgical ICU.Patients and participants Forty-two patients planned for valve surgery (Valves) and 84 for coronary artery bypass grafting (CABG) with cardiopulmonary bypass.Interventions Valves and CABG were randomized to postoperative coagulation management monitored either by central laboratory aPTT (Lab group) or by POC aPTT (POC group). Heparin was administered according to guidelines.Measurements and results POC aPTT results were available earlier than Lab aPTT after venipuncture in Valves (3 ± 2 vs. 125 ± 68 min) and in CABG (3 ± 4 vs. 114 ± 62 min). Heparin was introduced earlier in the POC group in Valves (7 ± 23 vs. 13 ± 78 h, p = 0.01). Valves of the POC group bled significantly less than Valves in the Lab group (647 ± 362 ml vs. 992 ± 647ml, p < 0.04), especially during the first 8 h after ICU admission. There was no difference in bleeding in CABG (1074 ± 869 ml vs. 1102 ± 620, p = NS). In Valves, fewer patients in the POC group than in the Lab group needed blood transfusions (1/21 vs. 8/21; p = 0.03). No difference was detected in CABG.Conclusions In Valves in the POC group the time to the desired coagulation state was reduced, as was the thoracic blood loss, reducing the number of patients transfused. This improvement was not observed in CABG. Side effects were similar in the two groups.Electronic supplementary material The electronic reference of this article is . The online full-text version of this article includes electronic supplementary material. This material is available to authorised users and can be accessed by means of the ESM button beneath the abstract or in the structured full-text article. To cite or link to this article you can use the above reference.Presented in part at the annual congress of the European Society of Intensive Care Medicine (ESICM) in Amsterdam, 6–8 October 2003.     

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.     

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).     

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.     

Complete clinical course of envenomation by Protobothrops mangshanensis: delayed coagulopathy and response to Trimeresurus albolabris antivenom

Introduction: Protobothrops mangshanensis, the Mangshan pit viper, is a rare pit viper native to the area surrounding Mount Mang in China’s Hunan province. Toxicity from envenomation is not well characterized. Case details: A 33-year-old male presented to an emergency department (ED) after being bitten on the forearm by his P. mangshanensis. He complained of mild swelling and pain at the bite site. He was admitted for observation and toxicology consultation. Following initially normal coagulation studies including platelets, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and D-dimer, fibrinogen decreased to 121?mg/dL and D-dimer concurrently rose to 377?ng/mL over 24?h. On hospital day 2 fibrinogen stabilized at 109?mg/dL and he was discharged with outpatient laboratory monitoring. Three days later, he returned with bruising to the contralateral arm. Fibrinogen was undetectable (<40?mg/dL) and PT was 14.6?s. He declined admission but returned 2 d later with bruising to the nose. Bloodwork revealed immeasurably prolonged PT, aPTT, and thrombin time, but he eloped. Late that evening he returned and was treated with three vials of Green pit viper (Trimeresurus albolabris) antivenom. Within 24 h coagulopathy improved markedly; at five days, coagulation abnormalities resolved. Discussion: Mangshan pit viper envenomations may cause isolated hemotoxicity, despite molecular studies suggesting additional neurotoxicity and myotoxicity. T. albolabris antivenom appears effective in treating the resultant coagulopathy. Conclusion: We report the natural history of envenomation by the Mangshan pit viper. A delayed coagulopathy, apparently fibrinolytic in nature, is unaccompanied by local tissue destruction and responsive to Green pit viper antivenom.     

Coagulopathy parameters in patients with Crimean‐Congo hemorrhagic fever and its relation with mortality

Background: Crimean‐Congo hemorrhagic fever (CCHF) is an acute illness affecting multiple organ systems and characterized by ecchymosis, visceral bleeding, and hepatic dysfunction. In this study, we aimed to investigate the profile of coagulopathy markers (platelet count, activated partial tromboplastin time (aPTT), prothrombin time (PT), international normalized ratio (INR), fibrinogen, protein C, protein S, antithrombin III, activated protein C resistance (APCR), and D‐dimer) and their clinical significance in 83 CCHF‐infected patients. Subjects and methods: We studied 83 CCHF patients who were admitted to Ankara Numune Education and Research Hospital during the spring and summer of2007. We compared the coagulopathy markers of fatal CCHF patients (n=9) with nonfatal cases (n=74). Results: Platelet count, PT, aPTT, INR, and fibrinogen were prognostic factors associated with mortality for CCHF. Especially, platelet count<20×10⁹ cells/l and aPTT>60 sec were important. Protein C, protein S, APCR, and antithrombin III levels were not associated with mortality. Conclusion: Laboratory tests including classical parameters (platelet count, PT, aPTT, INR, and fibrinogen) of coagulopathy seem to be enough for the followup of CCHF. Protein S, protein C, APCR, and D‐dimer levels were not associated with mortality. J. Clin. Lab. Anal. 24:163–166, 2010. © 2010 Wiley‐Liss, Inc.     

Effects of the oral,direct factor Xa inhibitor rivaroxaban on commonly used coagulation assays

Summary. Introduction: Rivaroxaban is an oral direct factor Xa inhibitor developed for prophylaxis and treatment of thromboembolic disorders. Laboratory monitoring is not necessary but the dose‐dependent effects on common reagents and assay procedures are largely unknown. Objectives: To investigate the effect of rivaroxaban on commonly used coagulation assays. Materials and Methods: Rivaroxaban was added to plasma from healthy subjects in the concentration range 0–1000 μg L^?1 and analyzed using different reagents for activated partial thromboplastin time (APTT), prothrombin time (PT), antithrombin, fibrinogen and activated protein C (APC) resistance assays. Results: At an expected peak concentration of rivaroxaban in clinical use, the APTTs were almost invariably prolonged but at lower concentrations the effect was weak. The concentration needed to double the APTT varied between 389 ± 106 and 617 ± 149 μg L^?1 for different reagents. The PT assays showed a marked degree of difference. In general, the Quick PT type assays were more sensitive compared with the Owren type PT assays. The results from antithrombin assays were dependent on the type of reagent, with the Xa‐based assay being sensitive for rivaroxaban with an estimated increase of 0.09 IU mL^?1 per 100 μg L^?1 rivaroxaban. There were only minor effects on fibrinogen assays based on thrombin reagents. The APTT‐based assay for APC resistance is affected in a dose‐dependent manner whereas an assay based on the activation of coagulation at the prothrombinase level was unaffected. Conclusions: Different assays, and even different reagents within an assay group, display variable effects by therapeutic concentrations of rivaroxaban.     

The aPTT assay as a monitor of heparin anticoagulation efficacy in clinical settings

Activated partial thromboplastin time (aPTT) and prothrombin time (PT) are 2 major methods of screening patients for bleeding tendency. Heparin is an anticoagulant commonly used for various clinical conditions and will thus affect the coagulation profile. The influence of heparin on PT vs aPTT, seldom addressed in the past, should be carefully investigated. Prospective data on 35 patients who were heparinized for clinically indicated conditions were collected and analyzed for the change in PT (dPT) and aPTT (daPTT) at 3 time points after treatment, all of which were compared with baseline data checked before therapy. Age, sex, and the results of a complete blood count and liver and renal function tests were also evaluated for each patient to determine their effects on dPT and daPTT. The therapeutic goal of keeping the aPTT within a desirable range was achieved in ∼75% of patients by the last day of heparin therapy. Within this range, dPTs were not statistically significant, nor was the effect of age, sex, hemoglobin level, serum albumin level, white cell count, platelet count, or renal or hepatic function. In patients with thrombosis, dPT was not significantly influenced by heparin dose. During an overlap in the periods of coumadin and heparin administration, PT was used as a guide for adjusting the coumadin dose. The anticoagulant effect, indicated by a PT in the target range, would occur primarily secondary to coumadin administration and would make it relatively easy to decide when to discontinue heparin.     

新型血管内液体栓塞剂中有效组分的体外促凝血作用研究

目的研究用于颅内动脉瘤治疗的新型血管内液体栓塞剂中有效栓塞成分(白芨多糖与二醋酸纤维素聚合物)的体外促凝血作用。方法将有效栓塞成分按质量比不同分为4组,观察各组样品对凝血酶原时间(PT)与活化部分凝血活酶时间(aPTT)的影响。结果新型血管内液体栓塞剂能显著缩短PT,且缩短程度与主要栓塞成分白芨多糖所占比例成正相关;同时此栓塞剂也可缩短aPTT。结论新型血管内液体栓塞剂在体外实验中明显促进凝血,并偏重于影响外源性凝血途径;此外,主要栓塞成分白芨多糖在促进凝血过程中起关键作用。     

High survival rate in 122 ARDS patients managed according to a clinical algorithm including extracorporeal membrane oxygenation

Objective: We investigated whether a treatment according to a clinical algorithm could improve the low survival rates in acute respiratory distress syndrome (ARDS). Design: Uncontrolled prospective trial. Setting: One university hospital intensive care department. Patients and participants: 122 patients with ARDS, consecutively admitted to the ICU. Interventions: ARDS was treated according to a criteria-defined clinical algorithm. The algorithm distinguished two main treatment groups: The AT-sine-ECMO (advanced treatment without extracorporeal membrane oxygenation) group (n = 73) received a treatment consisting of a set of advanced non-invasive treatment options, the ECMO treatment group (n = 49) received additional extracorporeal membrane oxygenation (ECMO) using heparin-coated systems. Measurements and results: The groups differed in both APACHE II (16 ± 5 vs 18 ± 5 points, p = 0.01) and Murray scores (3.2 ± 0.3 vs 3.4 ± 0.3 points, p = 0.0001), the duration of mechanical ventilation prior to admission (10 ± 9 vs 13 ± 9 days, p = 0.0151), and length of ICU stay in Berlin (31 ± 17 vs 50 ± 36 days, p = 0.0016). Initial PaO₂/FIO₂ was 86 ± 27 mm Hg in AT-sine-ECMO patients that improved to 165 ± 107 mm Hg on ICU day 1, while ECMO patients showed an initial PaO₂/FIO₂ of 67 ± 28 mm Hg and improvement to 160 ± 102 mm Hg was not reached until ICU day 13. Q˙_S/Q˙_T was significantly higher in the ECMO-treated group and exceeded 50 % during the first 14 ICU days. The overall survival rate in our 122 ARDS patients was 75 %. Survival rates were 89 % in the AT-sine ECMO group and 55 % in the ECMO treatment group (p = 0.0000). Conclusions: We conclude that patients with ARDS can be successfully treated with the clinical algorithm and high survival rates can be achieved. Received: 9 April 1997 Accepted: 13 May 1997     

The effects of sampling from a peripheral venous catheter compared to repeated venepunctures on markers of coagulation,inflammation, and endothelial function

Abstract

Peripheral venous (PV) catheters are often used for serial blood sampling, but studies suggest that PV catheters increase markers of coagulation activation and inflammation. Whether the increase is caused by irritation of the vessel wall or diurnal variation is unknown. We therefore compared the effects of a PV catheter and repeated venepunctures on markers of coagulation, inflammation, and endothelial function.

A PV catheter was inserted at 07:45 in a hand vein in 10 healthy subjects, and blood samples were collected at 8:00, 10:00, 12:00, and 14:00. In the contralateral arm, blood was simultaneously obtained by venepunctures. Measures of coagulation, i.e., activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen, prothrombin fragment 1?+?2 (F1?+?2) and thrombin-antithrombin (TAT), inflammation, i.e., interleukin 6 (IL-6) and C-reactive protein (CRP), and endothelial function, i.e., plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator (tPA), von Willebrand factor (vWF), and tissue factor (TF) were measured in plasma.

The concentrations of TAT and F1?+?2 were significantly increased (10:00; p?<?.01, 12:00; p?<?.05, and 14:00; p?<?.01) in PV catheter samples compared with venepuncture samples. There was a minor increase in PT and INR and no increase in APTT, fibrinogen, CRP, PAI-1, tPA, vWF, and TF, with no differences between sampling methods. IL-6 concentrations increased in many PV catheter samples and venepuncture samples, but the response varied between the subjects.

Blood collection through a PV catheter induces coagulation activation, whereas endothelial function is not affected. More studies are needed to disclose the effect of blood sampling on IL-6.     

Non-frozen transports of whole blood samples do not cause relevant bias for global coagulation tests in clinical trials evaluating the drug safety

Sample shipments with dry ice have a large economic impact on clinical research. Therefore, the bias caused for global coagulation tests by non-frozen transports of whole blood instead of frozen plasma was investigated experimentally and by a meta-analysis of 6-year central laboratory data. In the experiment, aliquots from 14 healthy volunteers were kept as whole blood at 20+/-2 degrees C and as frozen plasma until an analysis of prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), and antithrombin III (ATIII) at day 0, 1, 2, and 3 from collection. Within these 3 days only PT and aPTT demonstrated any changes: in blood samples kept at 20+/-2 degrees C these amounted about 10% for both. In frozen plasma, aPTT did not change whereas PT increased by 14%. In a meta-analysis of central laboratory data, PT and aPTT results were grouped across various phase II-IV trials by the type of sample transfer, either as frozen plasma on dry ice or non-frozen as whole blood. For the latter the mean difference to a reference group of phase I trials with same-day analysis was in line with the amount of bias found in the experiment (aPTT, 34.6+/-6.0 vs. 31.6+/-3.5 s; PT, 87.7+/-13.3 vs. 97.3+/-7.9%). The consistent bias resulted in shifted, but still normal distribution curves with a total rate of clinically relevant outliers of about 1.9% for aPTT and 2.4% for PT. Biases thus appear irrelevant for a common safety evaluation within clinical trials. Non-frozen whole blood transports for the measurement of global coagulation tests appear justified for this purpose, if protocols do not require frozen shipments for other reasons. However, transit time must not exceed 2 days and pre-analytical conditions should be consistent within the same trial.     

Influence of prothrombin complex concentrates on plasma coagulation in critically ill patients

Objective: To evaluate thrombogenicity of prothrombin complex concentrates (PCCs) in critically ill patients.¶Design: Prospective clinical study.¶Setting: Medical intensive care unit at a university hospital.¶Patients: 16 consecutive patients suffering from acquired deficiencies of coagulation factors and with either overt bleeding from any site or a planned invasive procedure.¶Interventions: 2000 factor IX units of PCCs intravenously.¶Measurements and results: Prothrombin time (PT), activated partial prothrombin time, fibrinogen, platelet count, plasma levels of coagulation factors II, V, VII, VIII, IX, X, antithrombin, protein C, thrombin-antithrombin complex (TAT), prothrombin fragment F₁₊₂, and the fibrin degradation product D-dimer were measured prior to and 1, 3, and 24 h after administration of PCCs. PT as well as coagulation factors II, VII, IX, and X, TAT, and F₁₊₂ showed a significant increase after administration of PCCs. All other parameters remained unchanged.¶Conclusions: Administration of PCCs induces thrombin generation. No evidence for induction of disseminated intravascular coagulation in biochemical terms could be found. When rapid correction of acquired coagulation factor disturbances is warranted, the use of PCCs seems reasonable, but the elevated risk of intravascular thrombus formation should be kept in mind.     

Persistent hypocoagulability in patients with septic shock predicts greater hospital mortality: impact of impaired thrombin generation

Purpose

Sepsis induces hypercoagulability, hypofibrinolysis, microthrombosis, and endothelial dysfunction leading to multiple organ failure. However, not all studies reported benefit from anticoagulation for patients with severe sepsis, and time courses of coagulation abnormalities in septic shock are poorly documented. Therefore, the aim of this prospective observational cohort study was to describe the coagulation profile of patients with septic shock and to determine whether alterations of the profile are associated with hospital mortality.

Methods

Thirty-nine patients with septic shock on ICU admission were prospectively included in the study. From admission to day 7, analytical coagulation tests, thrombin generation (TG) assays, and thromboelastometric analyses were performed and tested for association with survival.

Results

Patients with septic shock presented on admission prolongation of prothrombin time, activated partial thromboplastin time (aPTT), increased consumption of most procoagulant factors as well as both delay and deficit in TG, all compatible with a hypocoagulable state compared with reference values (P?P?=?0.007) and persistence of TG deficit (P?=?0.024) on day 3 were strong predictors of mortality, independently from disease severity scores, disseminated intravascular coagulation score, and standard coagulation tests on admission.

Conclusions

Patients with septic shock present with hypocoagulability at the time of ICU admission. Persistence of hypocoagulability assessed by prolonged aPTT and unresolving deficit in TG on day 3 after onset of septic shock is associated with greater hospital mortality.     

Correlations between rotational thromboelastometry (ROTEM) and standard coagulation tests following viper snakebites

BackgroundA high prevalence of venom-induced consumption coagulopathy has been reported in individuals with viper snakebites. Rotational thromboelastometry (ROTEM) is a rapid technique that could be advantageous in assessing and monitoring coagulation disorders.PurposeTo explore correlations between ROTEM and standard coagulation tests.Patients and methodsThis prospective observational study was performed among 41 patients with viper envenomation admitted to the Vietnam Poison Control Center from April 2016 to October 2017. Standard coagulation measurements [platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen level] and ROTEM indicators [clotting time (CT), amplitude (at set time: 5 and 10 minutes), clot information time (CFT) and maximum clot firmness (MCF) for extrinsic (EXTEM), intrinsic (INTEM), and fibrin based (FIBTEM) ROTEM] were obtained.ResultsFor INTEM, EXTEM, the FIBTEM, proportions of patients with prolonged CT were 34.1%, 63.4%, and 61.0% respectively and the proportions of patients with decreased MCF were 62.2%, 62.2%, and 35.5%, respectively. Moderate correlations were observed between PT and EXTEM CT (r = 0.627), aPTT and INTEM CT (r = 0.626), fibrinogen and FIBTEM MCF (r = 0.723), and platelet count and EXTEM MCF (0.60).ConclusionROTEM indicated a hypocoagulation state in patients with viper snakebite and was moderately correlated with standard coagulation parameters.     

Anticoagulation monitoring part 2: Unfractionated heparin and low-molecular-weight heparin

OBJECTIVE: To review the availability, mechanisms, limitations, and clinical application of point-of-care (POC) devices used in monitoring anticoagulation with unfractionated heparin (UFH) and low-molecular-weight heparins (LMWHs). DATA SOURCES: Articles were identified through a MEDLINE search (1966-August 2004), device manufacturer Web sites, additional references listed in articles and Web sites, and abstracts from scientific meetings. STUDY SELECTION AND DATA EXTRACTION: English-language literature from clinical trials was reviewed to evaluate the accuracy, reliability, and clinical application of POC monitoring devices. DATA SYNTHESIS: The activated partial thromboplastin time (aPTT) and activated clotting time (ACT) are common tests for monitoring anticoagulation with UFH. Multiple devices are available for POC aPTT, ACT, and heparin concentration testing. The aPTT therapeutic range for UFH will vary depending upon the reagent and instrument employed. Although recommended by the American College of Chest Physicians Seventh Conference on Antithrombotic and Thrombolytic Therapy, establishing a heparin concentration-derived therapeutic range for UFH is rarely performed. Additional research evaluating anti-factor Xa monitoring of LMWHs using POC testing is necessary. CONCLUSIONS: Multiple POC devices are available to monitor anticoagulation with UFH. For each test, there is some variability in results between devices and between reagents used in the same device. Despite these limitations, POC anticoagulation monitoring of UFH using aPTT and, more often, ACT is common in clinical practice, particularly when evaluating anticoagulation associated with interventional cardiology procedures and cardiopulmonary bypass surgery.     

Preferential consumption of coagulation factors I, V, and VIII in rat endotoxemia

To ascertain the time course of prolonged coagulation time and the coagulation factors that were consumed preferentially after injection of Escherichia coli endotoxin (ETX, 3 mg/kg, intravenously) in rats, the activated partial thromboplastin time (aPTT) and prothrombin time (PT) were measured. Using aPTT and PT, the residual levels of the major coagulation factors were quantified by partial replacement of ETX-injected rat plasma with individual factor-deficient human plasma. The residual levels of prekallikrein and high molecular weight (HMW) kininogen were also measured. After ETX injection, aPTT and PT showed gradual increasing prolongation, which was marked at 3-5 h after the injection. The residual level of fibrinogen was markedly reduced between 1 and 3 h after ETX injection and dropped to the determination limit 7 h after the injection. Ratios of the consumed coagulation factors, prekallikrein, and HMW kininogen in rat plasma collected 7 h after intravenous injection of ETX were obtained as follows: prekallikrein (18.0 +/- 4.8%), HMW kininogen (36.2 +/- 1.9 %), factor XII (54.0 +/- 0.7%), factor VIII (86.1 +/- 1.8%), factor VII (35.6 +/- 7.7%), factor V (90.6 +/- 0.8%), and factor I (fibrinogen) (>89.6 +/- 0.0%). Thus, coagulation factor I (fibrinogen) and factors V and VIII (cofactors) were consumed preferentially. The extrinsic coagulation pathway was dominantly activated, whereas the intrinsic coagulation pathway, including plasma kallikrein-kinin system, played less important role in the ETX-induced consumption coagulopathy in rat.     

Correlation between activated clotting time and activated partial thromboplastin times

OBJECTIVE: To evaluate the correlation between clotting time tests and heparin concentration, the correlation between activated clotting time (ACT) and activated partial thromboplastin time (aPTT) results, and to compare the clinical decisions based on ACT results with those based on aPTT results. METHODS: Retrospective evaluation of a large database containing heparin concentrations, ACT results (1 device), and aPTT results (3 different instruments: 2 bedside, 1 laboratory-based). Correlations between heparin concentrations and clotting time tests and between ACT results and aPTT results were determined. Clinical decisions regarding heparin dosage adjustments based on ACT results were compared with those based on aPTT results. RESULTS: Correlations between clotting time tests and heparin concentrations were r = 0.72 for ACT and r = 0.74-0.86 for the aPTT instruments. The laboratory-based aPTT had the highest correlation to heparin concentrations. The correlation between ACT and aPTT results ranged from r = 0.64-0.67. Heparin dosage adjustment decisions based on ACT results agreed with decisions based on aPTT results 59-63% of the time. CONCLUSIONS: The laboratory-based aPTT has a stronger correlation to heparin concentration than the bedside-based aPTT and ACT. The correlation between ACT and aPTT was similar among 3 different aPTT instruments. Decisions to adjust heparin therapy based on ACT results differed from decisions based on aPTT results more than one-third of the time.     

Analysis of costs in a pediatric ICU

Objective: To analyze the actual cost of pediatric intensive care and its different components, particularly the differences between various patient groups, with special reference to the variable cost and the elements included in it. Design: Prospective, observational study. Setting: Multidisciplinary 12-bed pediatric intensive care unit (PICU) in a tertiary university hospital. Patients: 495 admissions to the unit over 17 consecutive months; 64.2 % were medical patients and 35.8 % were surgical patients; the mean (SE) stay in the PICU was 6.6 ± 0.4 days. Measurements and results: The fixed cost per day per patient was calculated, including the costs of physicians, nurses, auxiliary and other personnel who worked during the study period, and the costs of structural depreciation, maintenance, consumption, and disposable material. The variable cost was individually calculated from the costs of routine procedures and also included expenditure on pharmaceuticals, blood products, biochemical, hematological, and bacteriologic tests, radiology, image diagnosis procedures, and other procedures. The Physiologic Stability Index (PSI) was obtained in the first 24 h after admission. The mean fixed cost per patient per day was u. s. $ 608, which represents 72 % of the total patient cost during this study; 86 % of this amount was for personnel (58 % for nurses and auxiliary staff). Variable costs came to 28 % of the total amount, and were $ 218 ± 100 (M± SEM) per patient per day. In addition to the costs of their longer stay in the PICU, the daily variable costs of nonsurvivors were higher than those of survivors ($ 542 ± 52 vs $ 179 ± 7; p < 0.001). We classified the patients into four groups according to their PSI score in the first 24 h; variable daily costs increased (p < 0.05) in all comparisons with the PSI level: group I: < 4 points ($ 155 ± 0.5), group II: 5–9 points ($ 210 ± 13), group III: 10–14 points ($ 324 ± 54), group IV: > 15 points ($ 480 ± 42). However, this pattern was not found for all resources: the cost of treatment techniques and biochemical and hematological tests increased, but the consumption of antibiotics, parenteral nutrition, blood products, and bacteriologic tests reached their maximum level in groups I–III and radiology was not significantly influenced by PSI level. Conclusions: The cost of personnel was the biggest factor in intensive care costs: 62.4 % of the total costs. Nonsurvivors generated 3 times the mean variable daily expenditure on survivors and had longer stays in the PICU. The increase in PSI score on the first day was associated with a global increase in variable costs. The cost of treatment techniques significantly increased as the illness became more severe but consumption of antibiotics and parenteral nutrition and use of bacteriologic tests and radiology did not. Received: 28 February 1995 Accepted: 8 October 1996     

Relationship between spontaneous echo contrast in the thoracic aorta and plasma von Willebrand factor

Purpose To clarify the relationships between spontaneous echo contrast (SEC) detected by transesophageal echocardiography (TEE) and coagulopathy, ultrasonographic findings that may correlate to biochemical coagulation markers were examined. Methods TEE was performed on 49 consecutive patients (mean age 64 ± 14 years; 28 men, 21 women). Blood samples were taken at the same time as TEE was carried out. Aortic SEC (Ao-SEC) and left atrial SEC (LA-SEC) were classified into three grades: absent, mild and marked. Levels of von Willebrand factor (vWF), thrombin antithrombin III complex (TAT), prothrombin fragments 1+2 (F1+2) and fibrinopeptide A (FPA) were measured. Results Mean plasma vWF levels by Ao-SEC grade were 144 ± 39% for absent, 177 ± 55% for mild and 210 ± 73% for marked, with significantly higher levels in the Ao-SEC marked group than in the Ao-SEC absent group (P < 0.05). Mean plasma vWF levels by LA-SEC were 185 ± 73% for absent, 180 ± 49% for mild and 201 ± 62% for marked, with no significant differences apparent between groups. Moreover, no relationships were identified between Ao-SEC grade and plasma levels of coagulation indicators TAT, F1+2 and FPA. Conclusion Plasma vWF levels correlated to grade of aortic SEC. Characteristics of the coagulation system differ between Ao-SEC and LA-SEC. Ao-SEC offers a clinical indicator of platelet thrombus formation.