Thomas Bombeli

Citrate storage affects Thrombelastograph® analysis

Background Thrombelastograph® analysis (TEG®) is used to evaluate blood coagulation. Ideally, whole blood is immediately processed. If impossible, blood may be citrated and assessed after recalcification. No data describe the effect of such treatment and storage on TEG® parameters. Methods Three studies were performed in 90 surgical patients. In 30 patients, blood was citrated (1:10, 0.129 M) and recalcified (20 &mgr;l 2 M CaCl2 to 340 &mgr;l citrated blood), and TEG® was performed with native blood and after recalcification after 0, 15, and 30 min of citrate storage. In another 30 patients, TEG® was performed with citrated blood recalcified immediately and after 1–72 h storage. In a third study, thrombin–antithrombin complex, prothrombin fragment 1+2, and &bgr;-thromboglobulin were measured (using enzyme-linked immunoabsorbant assay tests) at corresponding time points. Data were compared using repeated-measures analysis of variance and post hoc paired t tests. Results TEG® parameters were different in recalcified citrated blood compared with native blood (P < 0.05) and changed significantly during 30-min (P < 0.025) and 72-h (P < 0.001) citrate storage. TEG® parameters measured between 1 and 8 h of citrate storage were stable. Thrombin–antithrombin complex and prothrombin fragment 1+2 values were not elevated in native blood. After 30 min of citrate storage a gradual thrombin activation was observed, as evidenced by increasing thrombin–antithrombin complex and prothrombin fragment 1+2 values (P < 0.05). &bgr;-Thromboglobulin level was increased after 2 and 8 h of citrate storage (P < 0.01). Conclusions Analysis of native blood yields the most reliable TEG® results. Should immediate TEG® processing not be possible, citrated blood may be used if recalcified after 1–8 h.

Low- and medium-molecular-weight hydroxyethyl starches: comparison of their effect on blood coagulation.

BackgroundHigh-molecular-weight hydroxyethyl starch (HES) compromises blood coagulation more than medium-molecular-weight HES. The authors compared medium molecular weight HES (200 kd [HES200]) and low-molecular-weight HES (70 kd [HES70]). MethodsIn a prospective, double-blind, randomized-sequence crossover study, 22 male volunteers received 15 ml/kg HES200 and HES70. Blood samples were taken before and 5 min, 30 min, 1 h, 2 h, 4 h, 8 h, and 24 h after infusion. The following parameters were analyzed at all time points: prothrombin time, activated partial thromboplastin time, fibrinogen, factor VIII, antigenetic and functional von Willebrand factor, platelets, Thrombelastograph® analysis parameters (reaction time, coagulation time, maximum amplitude, angle &agr;, and clot lysis 30 and 60 min after maximum amplitude), ionized calcium, hematocrit, HES plasma concentration, molecular weight (weight average and number average), molar substitution, and polydispersity (weight average/number average). Repeated-measures analysis of variance (P < 0.05) was used to compare the response of the aforementioned parameters to the infusion of HES70 and HES200. ResultsBoth HES solutions had a significant impact on all parameters. A slightly greater compromise with HES200 was found in activated partial thromboplastin time (P = 0.010), factor VIII (P = 0.009), antigenetic von Willebrand factor (P = 0.041), functional von Willebrand factor (P = 0.026), maximum amplitude (P = 0.008), and angle &agr; (P = 0.003). No difference was established with the other parameters. HES concentration (P < 0.001), weight average (P < 0.001), number average (P < 0.001), and polydispersity (P < 0.001) were higher with HES200. There was no difference with molar substitution (P = 0.091). ConclusionsLow-molecular-weight hydroxyethyl starch (70 kd) compromises blood coagulation slightly less than HES200, but it is unclear whether this is clinically relevant.

Pregnant patient with primary pulmonary hypertension : Inhaled pulmonary vasodilators and epidural anesthesia for cesarean delivery

Address reprint requests to Dr. Weiss: Department of Anesthesiology, University Hospital, Raemistr 100, CH-8091 Zurich, Switzerland. Address electronic mail to: branko.weiss@ifa.usz.ch plicated delivery of a neonate. She refused treatment at that time. During her second pregnancy, at 15 weeks’ gestation, Doppler echocardiography showed a right atrial diameter of 6.2 cm (normal diameter, 2.2-4.1 cm), a short-axis end-diastolic diameter of the right ventricle of 5.1 cm (normal, 1.9 4.0 cm), a right ventricle with eccentric hypertrophy and fractional area shortening of 3396, and a small, normally contracting left ventricle. The patient was lost to further follow-up examinations and reappeared at 31 weeks’ gestation, severely dyspneic at rest and with dilated neck veins and lower limb edema. Ultrasonograph showed a growth-retarded fetus. The patient’s systemic arterial pressure (AP) was 108/69 mmHg, with a regular heart rate of 94 beatshin. Electrocardiography showed a sinus rhythm, prominent P waves in V,-V,, and a partial right bundle branch block. Oxygen saturation by pulse oximetry (Sp,,) of 88% increased to more than 94% with supplemented nasal oxygen. Hemoglobin was 11.4 g/dl, and platelet count was 177 1030 /~ l . Radial artery and thermodilution pulmonary artery catheters were inserted to test the response to nitric oxide (NO) and to oxygen breathing at inspiratory fraction ( F I ~ ] ~ ) of 1.0. Nitric oxide (40 ppm) failed to improve pulmonary hemodynamics, but oxygen breathing slightly decreased pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) and the catheters were removed. Dalteparin (Fragmin; Pharm Upjohn, Stockholm, Sweden), a lowmolecular-weight heparin, was administered subcutaneously at 5,000 and 7,500 IU/day. .The patient received digoxin, magnesium for its tocolitic properties, and betamethasone at 31 weeks and 32 weeks of gestation to promote fetal lung maturation. Continued right-sided heart dilatation (atrial diameter = 6.3 cm, end-diastolic ventricular diameter = 5.4 cm) and a decrease of right ventricular fractional arrd shortening to 25?4 were found at 32 weeks’ gestation. Ultrasound biometry showed insufficient fetal growth, and the decision was made to proceed with cesarean delivery at 34 weeks’ gestation. In the operating room, the patient was placed in a supine position with left uterine displacement. Radial artery, thermodilution pulmonary artery, and lumbar epidural (L2-3) catheters were placed during local anesthesia. After baseline measurements, 6 I/min 0, by mask increased Sp,,, from 90 to 96%. The hemodynamic parameters, hemo

In patients with deep-vein thrombosis elevated levels of factor VIII correlate only with von Willebrand factor but not other endothelial cell-derived coagulation and fibrinolysis proteins.

Several studies have shown that patients with venous thrombosis have elevated levels of factor VIII (FVIII) at an increased frequency. Most such patients also have high von Willebrand factor (vWF) levels. Since vWF is synthesized by the vascular endothelium, we hypothesized that elevated FVIII levels would also be associated with an increase of other endothelial cell-derived coagulation proteins suggesting perturbation of the endothelium. In 100 healthy individuals and 129 patients with venous thromboembolism, we have determined antigenic FVIII levels along with several endothelial proteins including vWF, soluble thrombomodulin (sTM), tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitor 1 (PAI-1). Levels of FVIII, vWF, PAI-1 and t-PA were significantly increased in patients compared with the controls (FVIII, vWF, and PAI-1, P < 0.001; t-PA, P < 0.05). Levels of sTM, however, were higher in the controls than in the patients (P < 0.001). Whereas the FVIII levels correlated well with the vWF levels in the patients (correlation, 0.61;P < 0.001) and the controls (correlation, 0.70;P < 0.001), there was neither a relevant correlation between FVIII and sTM, PAI-1, and t-PA, nor between vWF and sTM, PAI-1, and t-PA in the patients and the controls. In conclusion, although levels of PAI-1 and t-PA can be found, on average, at increased levels in patients with thrombosis, FVIII levels correlate only with vWF but not other endothelial cell-derived coagulation and fibrinolysis proteins including sTM, PAI-1, and t-PA.

Novel starches : Single-dose pharmacokinetics and effects on blood coagulation

Background:Carboxymethyl starch (CMS) and carboxymethylated hydroxyethyl starch (CM-HES) might offer advantages over hydroxyethyl starch (HES) with regard to their volume expansion effect and their pharmacokinetic characteristics. The goal of the current study was to determine the pharmacokinetics of CMS and CM-HES and to investigate their influence on blood coagulation in comparison with the standard low-molecular, low-substituted HES (130/0.42) used in Europe. Methods:The study was conducted as a randomized, blinded, parallel three-group study in 30 pigs. Twenty ml/kg of 6% HES (control), 6% CMS, or 6% CM-HES was infused as a single dose, and serial blood sampling was performed over 20 h to measure plasma concentration and molecular weight and to assess blood coagulation. Concentration–effect relations were assessed by pharmacokinetic–pharmacodynamic analysis. Results:CMS and CM-HES showed significantly higher plasma concentrations and molecular weights over 20 h (P for both < 0.001) with smaller volumes of distribution and longer elimination rates during the terminal phase (P for both < 0.01) when compared with HES. CMS and CM-HES impaired whole blood coagulation more than HES as assessed by Thrombelastograph® analysis (Haemoscope Corporation, Niles, IL). However, similar effects of all three starch preparations on blood coagulation were found when related to the plasma concentrations in mass units. Conclusions:Carboxymethylation of starch results in an increased intravascular persistence and a slower fragmentation compared with HES. The greater impairment of blood coagulation by CMS and CM-HES seems to be caused by the higher plasma concentrations.

Novel polyanionic starches: pharmacokinetics and effect on blood coagulation: A-287

Department of Anaesthesiology, University Hospital Lausanne (CHUV), Lausanne, Switzerland Background and Goal of Study: Linkage of carboxy-methyl (CM) residues to the glucose units of starch results in CM starch (CMS) and – when combined with hydroxyethylation – in CM-hydroxyethyl (HE) starch (CM-HES). These polyanionic starches are more hydrophilic than conventional HES and might be promising alternatives as plasma substitutes. The goal of this study was to investigate the pharmacokinetics of these novel starches and to study their impact on blood coagulation. Materials and Methods: This trial was conducted as a randomized controlled in vivo study in 30 pigs (40 5 kg). After infusion of 20 ml/kg of HES (130/0.4) (control), CMS or CM-HES (6% each) over 30 minutes, serial blood samples were obtained over 20 hours. Plasma concentration was determined and blood coagulation was assessed by Thromboelastograph® (TEG®) analysis and plasma coagulation assays. Pharmacokinetic (PK)-pharmacodynamic (PD) analysis was performed based on a twocompartment model, using a linear model relating predicted concentration values to the observed effects. PK-PD parameters were compared by oneway ANOVA followed by Scheffé’s multiple comparisons test. Results: Data are given as mean (SD).