Thrombin generation is increased in patients with Clostridium difficile colitis - a pilot study.

Background: There are only limited data in the literature on the thrombotic risk of patients with Clostridium difficile (CD) colitis, although this disease is widespread throughout the world. Objective: The aim of this study was to explore thrombin generation in these patients - the best way to evaluate their coagulation. Methods: A prospective observational study was conducted during 15 months on hospitalized patients with CD colitis. Thrombin generation was performed in platelet-poor plasma using a Ceveron® alpha analyzer and was compared with a group of volunteer control subjects. Results: Thirty-three patients and 51 control subjects were enrolled in the study. Two biomarkers - mean velocity index and peak thrombin - were significantly higher in patient group, compared to the control subjects (p = 0.010, respectively, p = 0.0395). This pattern of thrombin generation suggests that patients with CD colitis without septic shock have a potential thrombotic risk. The mean velocity index significantly correlated with the estimated related risk of death according to the Charlson age-comorbidity index. Conclusions: The higher values of thrombin generation suggest that CD colitis increases the thromboembolic risk. The pattern of thrombin generation could identify patients with particularly higher thromboembolic risk. They are potential candidates for thromboprophylaxis strategies and monitorization.

Clinical Evaluation of Measuring the ACT during Elective Cardiac Surgery with Two Different Devices.

Unfractionated heparin is the mainstay of anticoagulation during cardiac surgery on cardiopulmonary bypass (CPB) due to its low cost, quick onset, and ease of reversal. Since over 30 years, the activated clotting time (ACT) has been used to assess the level of heparin activity both before and after CPB. We compared two different methods of measuring the ACT: i-STAT, which uses amperometric detection of thrombin cleavage, and Hemochron Jr, which is based on detecting viscoelastic changes in blood. We included 402 patients from three institutions (Papworth Hospital, Cambridge, UK; Groote Schuur, Cape Town, South Africa; University Hospital Basel, Basel, Switzerland) undergoing elective cardiac surgery on CPB in our study. We analyzed duplicate samples on both devices at all standard measuring points during the procedure. The correlation coefficient between two Hemochron and two i-STAT devices was .9165 and .9857, respectively. The within-subject coefficient of variation (WSCV) ranged from 8.2 to 13.6% for the Hemochron and from 4.1 to 9.1% for the i-STAT. We found that the number of occasions where one of the duplicate readings was >1,000 seconds while the other was below or close to the clinically significant threshold of 400 seconds were higher for the Hemochron. We found the i-STAT to systematically return higher measurements. We conclude that the i-STAT provides a more reliable test for heparin activity and assesses safe anticoagulation during cardiac surgery on pump. The fact the that the i-STAT reads higher than the Hemochron leads to the recommendation to validate the methods against each other before changing devices.

An Adjusted Calculation Model of Reduced Heparin Doses in Cardiopulmonary Bypass Surgery in a Chinese Population.

OBJECTIVE: To investigate the safety and efficacy of an adjusted regimen of heparin infusion in cardiopulmonary bypass (CPB) surgery in a Chinese population. DESIGN: Prospective, single-center, observational study. SETTING: University teaching hospital. PARTICIPANTS: Patients having cardiac surgery with CPB were selected for this study using the following criteria: 18 to 75 years of age, undergoing first-time cardiac surgery with conventional median sternotomy, aortic clamping time between 40 and 120 minutes, and preoperative routine blood tests showing normal liver, renal, and coagulation functions. The exclusion criteria include salvage cases, a history of coagulopathy in the family, and long-term use of anticoagulation or antiplatelet drugs. INTERVENTIONS: Sixty patients were divided randomly into a control group (n = 30) receiving a traditional heparin regimen and an experimental group (n = 30) receiving an adjusted regimen. MEASUREMENTS AND MAIN RESULTS: Activated coagulation time (ACT) was monitored at different time points, ACT>480 seconds was set as the safety threshold of CPB. Heparin doses (initial dose, added dose, and total dose), protamine doses (initial dose, added dose, and total dose), CPB time, aortic clamping time, assisted circulation time, sternal closure time, blood transfusion volume, and drainage volume 24 hours after surgery were recorded. There was no significant difference in achieving target ACT after the initial dose of heparin between the 2 groups; CPB time, aortic clamping time, assisted circulation time, postoperative complication rate, and drainage volume between the 2 groups were not significantly different (p>0.05). However, initial and total dosage of heparin, initial and total dosage of protamine, sternal closure time, and intraoperative blood transfusion volume in the experimental group were significantly lower (p< 0.05). CONCLUSIONS: Adjusted regimen of heparin infusion could be used safely and effectively in Chinese CPB patients, which might reduce the initial and total dosage of heparin and protamine as well as sternal closure time and intraoperative blood transfusion volume.

[THE COMPARATIVE CHARACTERISTIC OF KAOLIN-ACTIVATED THROMBOELASTOGRAPHY IN HEALTHY NEWBORNS AND NEWBORNS WITH HEART AILMENTS].

The study was carried out to diferentiate reference values for kaolin-activated thromboelastography in newborns with congenital heart disease. The study included two groups ofpatients. The first one consisted of 62 newborns with congenital heart disease and the second one consisted of 35 healthy newborns. The results of kaolin-activated thromboelastography implemented in groups are evaluated as condition of normal coagulation. The valuable diferences of homeostasis system in healthy newborns and newborns with congenital heart disease (without severe concomitant pathology) are not established. They have similar indicators of kaolin-activated thromboelastography. The derived results can be applied as standards in full-term newborns with congenital heart disease.

Has the new USP assay for heparin affected dosage for patients undergoing cardiopulmonary bypass?

In October 2009, the U.S. Pharmacopoeia (USP) changed the monograph for heparin to bring USP units in line with international units for heparin. The result was a 10% decrease in potency as measured by in vitro laboratory tests. This decrease led to questions regarding dosing guidelines. There existed a need for an in vivo study to determine the practical changes that may need to be implemented in regard to heparin administration for cardiopulmonary bypass in the clinical setting. A retrospective study was conducted to determine the heparin dose administered and the corresponding effect on patients undergoing coronary artery bypass grafting surgery using cardiopulmonary bypass. The study compared the heparin dose requirements and activated clotting time (ACT) results using the heparin before and after the USP changes. An analysis of the data was performed to determine the increased heparin dose required to achieve the same effect as before the USP change. This new heparin dosing protocol was instituted at Concord Hospital, Concord, NH. A prospective study was then preformed to verify the effects of the dosing change. In the new heparin group, the postheparin ACT fell by 9.1% (p = .028) and the patients achieving an ACT > 479 seconds fell by 12.8% as compared with the old heparin group. After adjustment of the loading dose calculation for heparin, the prospective study demonstrated the postheparin ACT (p = .684) and the percentage of patients achieving an ACT > 479 seconds (p = 1.000) to be similar to the values obtained before the USP change. An increase of the loading dose of approximately 12% is needed to achieve the patient effects seen before the UPS change.

Monitoring fondaparinux with the Sonoclot.

Fondaparinux is a new anticoagulant that interacts with antithrombin III and activated coagulation factor X resulting in an inhibition of the coagulation system. It has been successful in doses of 2.5 mg for thromboprophylaxis as well as in higher therapeutic doses of 5-7.5 mg. No optimal method for monitoring the effects of fondaparinux has been proposed. The aim of the present study was to investigate whether a viscoelastic coagulation analyzer, the Sonoclot (Sienco, Denver, Colorado, USA), could be used for in-vitro monitoring of fondaparinux. Different concentrations of fondaparinux were added in vitro to whole blood taken from eight volunteers. The blood samples mixed with the various amounts of fondaparinux were analyzed using the Sonoclot. The whole-blood activated partial thromboplastin time with the Hemochron Jr (ITC, Edison, New Jersey, USA) was used as the reference coagulation analysis. All analyses were started expeditiously, within 30 s from sampling, and were performed at 37 degrees C. The values of the Sonoclot parameter clot rate, which measures the rate of fibrin formation, fibrin polymerization and platelet-fibrin interactions, were significantly correlated to increasing concentrations of fondaparinux (R = -0.90). The Sonoclot parameters of activated coagulation time, time to peak and clot retraction had weaker, but still significant, correlations to fondaparinux concentrations. At prophylactic doses (0.38 microg/ml blood) the clot rate decreased 15% compared with the initial unanticoagulated value, whereas at therapeutic doses (1.53 microg/ml blood) there was a 27% decrease. In conclusion, the Sonoclot parameter clot rate could be of clinical value to individualize the fondaparinux dosage, especially the higher, therapeutic, dosages.

Comparison of ACT point-of-care measurements: repeatability and agreement.

BACKGROUND: Accurate control of heparin anticoagulation is necessary during all stages of cardiopulmonary bypass (CPB). The activated clotting time, first described by Hattersley in 1966, is mostly used for determination of anticoagulation. Either celite or kaolin are used as activators. An ACT value of 480 sec is proposed to be the safe minimum level for anticoagulation during CPB. This study was designed to determine if the activated coagulation time (ACT) values of each analyser separately are repeatable, and to determine whether there exists a significant difference in ACT values measured by three different analysers: the GEM PCL (Instrumentation Laboratory), the Hemochron 801 (International Technidyne Corporation) and the ACT II Automated Coagulation Timer (Medtronic). METHODS: All patients underwent cardiovascular surgical procedures requiring heparinisation (200-300 IU/kg). Blood samples for the measurement of the ACT were taken from all patients before and after heparinisation, during CPB, and after protamine administration. All samples were measured in duplicate with the three different analysers. To compare the activated clotting time data, the method described by Bland and Altman was used. The Pearson correlation coefficient was used to determine whether the differences were related to the average ACTs. p-Values <0.05 were considered statistically significant. RESULTS: The results showed that the three tested ACT analysers met the requirements of repeatability. The mean differences and standard deviations of the ACT values measured with the GEM PCL, the Hemochron 801, and the ACT II analyser were, respectively, -8.78 +/- 37.61, -19.77 +/- 68.82, and -6.23 +/- 39.21, with p-values=0.177, 0.081 and 0.384, respectively. The Pearson correlation coefficients were too low (-0.012, -0.221 and -0.241, respectively) to show any correlation between the differences and the means. The ACT values measured with the Hemochron 801 were not significantly different from the ACT values measured with the ACT II analyser: deltaACT =-34.09 +/- 146.68, with p=0.132. However, the GEM PCL did not agree with the Hemochron 801: deltaACT= -80.2 +/- 143.06, with p=0.001, or the ACT II analyser: deltaACT= -119.13 +/- 138.51, with p<0.001. A rather strong correlation was evident between the differences and the means measured with the GEM PCL compared with the Hemochron 801 (r=0.68) and the ACT II analyser (r=0.76). CONCLUSIONS: All analysers used celite or kaolin as activator. However, it was evident that the ACT measurements depended also on the analyser that had been chosen. A precaution that ACT values could not always be interpreted in the same way seems to be necessary.

Sonoclot analysis in cardiac surgery in dialysis-dependent patients.

BACKGROUND: Dialysis-dependent patients have multiple disorders of hemostasis; however, there are no reports of viscoelastic changes during cardiac surgery in such patients. METHODS: Hemostasis in dialysis-dependent patients during cardiac operations was evaluated. Thirty patients who underwent cardiopulmonary bypass (CPB) were studied: 6 with chronic renal failure undergoing dialysis (HD group), and 24 without hemodialysis. Blood samples were obtained at four points: before sternotomy, 30 and 90 minutes after the start of CPB, and after protamine administration. RESULTS: Activated clotting time (ACT) measured with Sonoclot analyzer was significantly correlated with ACT measured traditionally (r = 0.92; p < 0.001; y = 36.1 + 0.95x). Values for ACT measured with Sonoclot analyzer as well as traditional ACT increased significantly during CPB. Values for ACT measured with Sonoclot analyzer in the HD group were significantly longer than those in the control group. Before CPB, both ACT measured with Sonoclot analyzer and traditional ACT in the HD group were significantly longer than those in the control group; however, there were no significant differences in ACT measured with Sonoclot analyzer between the groups after CPB. Clot rates and peak signal values were significantly decreased during CPB in both groups, and returned to preoperative values after protamine administration. There were no significant differences in clot rate and peak signal values between the two groups. There were no differences between the two groups in changes of time to peak. Platelet counts in the HD group were significantly higher (p < 0.05) than those in the control group. There were no differences in platelet counts after CPB between the two groups. Antithrombin III levels decreased below 50% during and after CPB. Antithrombin III in the HD group was significantly lower (p < 0.01) than those in the control group. A significant time-group interaction was observed in antithrombin III levels. CONCLUSIONS: Sonoclot signatures in HD patients showed no significant differences in viscoelastic changes compared with non-HD patients.