Sonoclot Coagulation Analyzer Research Articles

Comparative study of hemostatic profile between conventional methods and “Sonoclot Coagulation and Platelet Function Analyzer” in patients with septicemia

Abstract: BACKGROUND: Sonoclot Coagulation and Platelet Functional Analyzer (Sonoclot) operating on the principle of micro-viscometry is known to provide comprehensive information on the entire hemostatic process. We hypothesized that performing global hemostasis assessment in patients with sepsis would identify many more patients with altered hemostasis than the conventional tests. OBJECTIVES: We compared the hemostatic status determined by Sonoclot and that by conventional hemostatic tests. METHODS: It was a prospective analytical study conducted for 18 months in a tertiary care hospital. Sixty-one cases of septicemia admitted in the intensive care units were included in the study. RESULTS: Conventional hemostatic tests (platelet count, prothrombin time [PT], international normalized ratio, and activated partial thromboplastin time [APTT]) were compared with the Sonoclot parameters. Conventional hemostatic parameter PT was prolonged in 60.7% and APTT in 31.1%. Overall, 65.6% of the patients had prolonged coagulation on assessment by conventional hemostatic parameters. Sonoclot-derived parameter-activated clotting time was prolonged in 31.1%, indicating 31.1% of cases to have a hypocoagulable state. The clot rate was increased in 93.4% of subjects, indicating 93.4% to have a hypercoagulable state. Thrombocytopenia was seen in 34.4% and thrombocytosis in 10%. Defective platelet function was observed in 92% of the cases in Sonoclot, and all of them had normal platelet counts. This finding was statistically significant. CONCLUSION: Information about hemostatic status identified by Sonoclot is significantly higher and more complete than that identified by conventional coagulation tests in septicemic patients.

Model construction and application for predicting pre-eclampsia by Sonoclot coagulation analyzer

Maternal age has significantly increased among Chinese women, thereby posing risk of pregnancy-related complications. Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality, and coagulation analysis in conjunction with clinical signs and symptoms are generally used for its diagnosis with limited efficacy. Sonoclot coagulation analyzer is effective in assessing coagulation function used during cerebral surgery and cardiovascular surgery. However, its use has not been explored in preeclampsia. Here, we investigated the potential use of Sonoclot in diagnosing preeclampsia in obstetrics cases. Subjects meeting the screening criteria were divided either into a test group or a control group, according to whether they were preeclamptic or not. We recorded the Sonoclot-derived coagulation and the routine coagulation parameters including platelet function (PF), activated clotting time (ACT) and clot rate (CR), prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (FIB), and platelet count. Regression analysis was done on the relevant parameters to assess the feasibility of Sonoclot analyzer in preeclampsia diagnosis. In parallel, changes in preeclampsia lncRNAs was also evaluated. Significant differences were recorded in PT and ACT between the two groups. In the monovariant logistic regression, PT and ACT appeared to be reliable predictor variables. In the multinomial logistic regression, a total of five regression steps were performed with decreasing AIC values. The K-fold cross validation resulted in an accuracy rate (ACC) of 77.5%, a false positive rate of 16.4%, and a false negative rate of 33.2%. lncRNAs ANRIL and HOXD-AS1 were found deregulated. Our findings indicate that Sonoclot may be useful for diagnosis of preeclampsia in obstetrics.

Bleeding risk assessment in immune thrombocytopenia.

The bleeding risk in immune thrombocytopenia (ITP) is related not only to low platelet count but also to the presence of platelet dysfunction. However, diagnosing a concomitant platelet dysfunction is challenging as most of the available platelet function assays (PFAs) require a platelet count of greater than 100,000/μL. Sonoclot coagulation and platelet function analyzer works on the principle of viscoelastometry, and results remain unaffected by the platelet counts. To assess the platelet function in adult acute ITP patients with the help of sonoclot coagulation and platelet function analyzer and correlate it with the risk of bleeding. Newly diagnosed acute ITP patients with a platelet count less than 20,000/μL were divided into two groups based on WHO bleeding grade: ITP non-bleeder (ITP-NB) group (WHO bleeding grade ≤1) and ITP bleeder (ITP-B) group (WHO bleeding grade ≥2). Platelet function was assessed by sonoclot in both groups. The patients without significant bleeding (ITP-NB) were followed up monthly for six months with the assessment of platelet function during each contact. Eighty patients (30 ITP-B and 50 ITP-NB) were prospectively included in this study. The median age of patients in the two groups was 37 years and 30 years, respectively. The female-to-male ratio was 4:1 and 1:1 in ITP-B and ITP-NB groups. The median platelet count in ITP-B and ITP-NB was 12000/μL (range 1000-19000/μL) and 8000/μL (range 1000-19000/μL), respectively. Mean platelet functions by sonoclot in both groups were lower than the normal cut-off (>1.6). However, the mean platelet function in the ITP-B group (0.2 + 0.17) was significantly lower than the ITP-NB group (1.2 ± 0.52) (p = 0.01). During the follow-up period of 6 months, patients in ITP-NB with a normal platelet function (>1.6) on sonoclot had lesser episodes (one episode) of clinically significant bleeding than patients with a low platelet function (4 episodes). Patients with acute severe thrombocytopenia and bleeding phenotype have a greater abnormality on platelet function by sonoclot than patients with non-bleeding phenotype. This information may help in taking therapeutic decisions in patients with acute ITP.

Evaluation of mean platelet volume and platelet count in ischemic stroke and its subtypes: focus on degree of disability and thrombus formation

Background: Platelets are crucial players in thrombus formation during ischemic stroke. Platelet (PLT) count and Mean platelet volume (MPV) are important parameters that affect platelet functions. The current study has been carried out with an aim to evaluate the association of MPV and PLT count with ischemic stroke in a population from the Malwa region of Punjab. Material and Methods: The study included one hundred and fifty ischemic stroke patients. The extent of disability occurs by stroke was measured by mRS. MPV and PLT was evaluated using cell counter. Further, PLT count was confirmed in 50% of patients using flow cytometer. Clot formation rate was evaluated using Sonoclot Coagulation and Platelet Function Analyzer. All the statistical analysis was carried out using SPSS. Results: A significant association of increased MPV (p < 0.02) was found with the ischemic stroke. However, PLT count did not show a significant association with the disease (p < 0.07). Further, a stepwise multiple logistic regression (MLR) analysis controlling the other confounding risk factors evaluated the association of hypertension and MPV with the disease. Patients with higher mRS were found to have high MPV values confirming that higher MPV is correlated with disability occurs by ischemic stroke. MPV was also found to be significantly associated with large artery atherosclerosis (p < 0.001). Clot formation analysis revealed that ischemic stroke patients bear higher clot rate (CR) and Platelet function (PF) values. Conclusions: Elevated MPV is an independent risk factor for Ischemic stroke along with hypertension. In addition, higher MPV associated significantly with stroke disability as well.

Quantification and optimization of clot retraction in washed human platelets by Sonoclot coagulation analysis

Clot retraction is a pivotal process for haemostasis, where platelets develop a contractile force in fibrin meshwork and lead to the increased rigidity of clot. The pathophysiological alteration in contractile forces generated by the platelet-fibrin meshwork can lead to haemostatic disorders. Regardless of its utter significance, clot retraction remains a limited understood process owing to lack of quantification methodology. Sonoclot analysis is a point-of-care technique used in clinical laboratories for whole blood analysis that providesin vitroqualitative as well as quantitative assessment of coagulation process from initial fibrin formation to clot retraction. Human washed platelets were isolated by differential centrifugation method and analysed via optical imaging, microscopy and Sonoclot analysis using 1-2×108 /mL of washed platelets, 1U/mL of thrombin, 1mg/mL of fibrinogen and 1mM of calcium chloride. In this study, we demonstrate the novelty of this instrument in the quantitative evaluation of clot retraction in washed platelets and attempted to optimize the reference range of Sonoclot parameters including ACT - 87.3±20.997, CR - 16.23±3.538 and PF - 3.57±0.629, (n=10). Sonoclot analysis provides a simple and quantitative method to better understand in vitro clot retraction and its modulation by retraction components including platelet count, fibrinogen and platelet-fibrin interaction compared with existing conventional methods. Sonoclot may prove to be a valuable tool in thrombus biology research to understand fundamental basis of blood clot retraction.

Utility of the Sonoclot analyzer to assess hyperfibrinolysis in dogs.

Coagulation abnormalities, including hyperfibrinolysis, have been documented in sick veterinary patients. Viscoelastic tests, including the Sonoclot Coagulation and Platelet Function Analyzer, are useful in detecting hyperfibrinolysis. Tissue plasminogen activator (tPA) assays have been used to quantify fibrinolysis using thromboelastography. We aimed to document and evaluate changes in the whole blood of healthy dogs exposed to in vitro tPA at varying concentrations using the Sonoclot analyzer. Ten milliliters of blood was collected from healthy adult dogs. Sonoclot tests were run in duplicate and included a control sample and five tPA concentrations: 50, 75, 100, 150, and 200IU/mL of blood. Eleven dogs were enrolled in the study. Based on standard Sonoclot Signature changes, a numeric value fibrinolysis time (FTi) was derived to aid in the quantification of hyperfibrinolysis. Activated clotting time and clot rate Sonoclot values were not significantly affected by any tPA concentration. There was a significant decrease in platelet function (PF) at tPA concentrations equal to and above 75IU/mL on channel 1 and tPA concentrations of 150IU/mL and higher on channel 2. There was a progressive decrease in FTi at increasing tPA concentrations. The Sonoclot analyzer can be used to evaluate hyperfibrinolysis. Predictable changes were seen in the Sonoclot Signature and a decrease in PF and FTi was found with increasing tPA concentrations. The Sonoclot assay with a tPA concentration of 100IU/mL is suggested a baseline measure of hyperfibrinolysis and has a resultant median FTi of 42minutes, which is a practical time for clinical applications.

Poor Platelet Function on Sonoclot Signature Is Associated with High Incidence of Bleeding in Severe Immune Thrombocytopenia

Introduction: Patients of immune thrombocytopenia (ITP) are at an high risk of bleeding, and the risk of bleeding is maximum when platelet counts fall below 30,000/μL (severe ITP). Though it is not known not all patients have a similar risk of bleeding at a given platelet count. In 59th ASH annual meeting, 2017 (poster 2320) Mishra K et al showed that the platelet function measured by ‘Sonoclot coagulation and platelet function analyzer’ is significantly different in bleeders as compared to non-bleeders severe ITP patients. We aimed to investigate and follow up the non-bleeder severe ITP patients, whose platelet count remains <30,000 with or without treatment, and find out the incidence of bleed.Method: The study was conducted at the department of internal medicine, postgraduate institute of medical education and research, Chandigarh, India. In this prospective observational study, severe ITP (newly diagnosed) and without active bleeding (WHO bleeding grade <2) were included. All these patient were clinically evaluated, and blood samples were collected as per unit protocol for ITP including Sonoclot analysis. For Sonoclot analysis, fresh blood samples were drawn in citrated vacutainer and analyzed by Sonoclot coagulation and platelet function analyzer made by Sienco, Inc, model SCP1 (USA). The sonoclot signature assessment gives activated clotting time (ACT), clot rate (R1) and platelet function (PF). The samples for sonoclot analysis were monthly drawn for six months in patients who continued to have severe ITP.Results: A total of 50 patients with severe ITP were included. Twenty patients were not included in the final analysis as their platelet remained above 30,000/μL during follow up. The remaining 30 patients were divided into two groups based on normal platelet function (PF) (>1.5) and low PF (<1.5) as measured by the Sonoclot analyzer. The normal PF group (n= 17) had only one patient who had clinically significant bleeding (WHO grade > 2), while low PF group had four patients with clinically significant bleeding (Figure 1). Though the statistical significance level could not be achieved, likely due to a small cohort of patients, the results look promising and shows the potential of sonoclot to give valuable input regarding the risk of bleeding in severe ITP.Conclusion: The patients with poor platelet function as measured by ‘Sonoclot coagulation and platelet function analyzer’ had more bleeding episodes as compared to patients with normal platelet function. Therefore, Sonoclot may work as a point of care investigation to predict the risk of bleeding in severe ITP patients. This will help the clinician in being more conservative in the management of severe ITP patients with low risk of bleeding and avoid unnecessary therapy. We conclude that the use of Sonoclot during follow-up in severe ITP patients has prognostic significance. DisclosuresNo relevant conflicts of interest to declare.

Sonoclot coagulation analysis

Disseminated intravascular coagulation (DIC) contributes to high mortality. The study was performed to investigate Sonoclot as a potential predictor of 30-day survival in overt DIC. This cohort included 237 consecutive critically ill patients with overt DIC, admitted to a 15-bed multidisciplinary ICU between July 2010 and July 2013. Hemostasis was analyzed with Sonoclot, including activated clotting time (ACT), clot rate, and platelet function, as well as routine clotting test at admission to the critical care center. Sonoclot variables differed in survivors and nonsurvivors. Mean ACT was prolonged (289.9 ± 200.5 vs. 194.8 ± 126.6 s; P < 0.001) and platelet function (1.2 ± 0.9 vs. 1.6 ± 1.2; P = 0.010) was reduced in nonsurvivors. The clot rate was not different. Cox proportional-hazard model showed that ACT and platelet function correlated independently with survival (P < 0.05). Kaplan-Meier survival curve analysis suggested that patients with one pathological Sonoclot findings have better outcome (P < 0.05). After ACT and platelet function were introduced, the receiver-operating characteristic area under the curve of model achieved 0.876 (P < 0.05), with a specificity of 82.6% and a sensitivity of 80.5% in prediction of 30-day survival by multivariate analyses. Our data suggest that the Sonoclot can predict mortality in critically ill patients with overt DIC.

Diagnosis of overt disseminated intravascular coagulation in critically Ill adults by Sonoclot coagulation analysis.

Disseminated intravascular coagulation (DIC) diagnosis is hampered by the limited availability of reliable clinical or laboratory tests. Currently available tests are time consuming and expensive. We investigated whether coagulation and platelet function analyses using the Sonoclot system were suitable for overt DIC diagnosis in critically ill adults. This was an observational diagnostic study performed in 498 patients presenting with an underlying disorder associated with DIC. Overt DIC patients were identified according to an International Society on Thrombosis and Hemostasis (ISTH) score of >5. Coagulation and platelet parameters were analyzed using the Sonoclot system, and compared with ISTH as the gold standard. Receiver operating characteristic curves and area under the curves were used to evaluate the value of the Sonoclot parameters. There were no differences for age or gender between the groups. Significant correlations were observed between activated clotting time (ACT) and ISTH score (r = 0.7; P < 0.001), clot rate (CR) and ISTH score (r = 0.5; P < 0.001), platelet function (PF) and ISTH score (r = -0.6; P < 0.001), and PF and platelet count (r = 0.5; P < 0.001). An ACT cut-off value of 213.5 s alone or combined with CR presented good sensitivity (76.7 and 86.8 %, respectively) and specificity (96.2 and 93.3 %, respectively). Sonoclot analysis can be performed using a point-of-care device that effectively discriminates low and high ISTH scores, and that effectively predicts coagulation dysfunction in patients with overt DIC.

PM166 Evaluation of Platelet Reactivity in Coronary Heart Disease Patients on Clopidogrel Treatment by Sonoclot Coagulation and Platelet Function Analyzer

PM166 Evaluation of Platelet Reactivity in Coronary Heart Disease Patients on Clopidogrel Treatment by Sonoclot Coagulation and Platelet Function Analyzer

Protamine dosage effects on complement activation and sonoclot coagulation analysis after cardiac surgery

Background: An optimal dosage and infusion regime for protamine reversal of heparin after cardiopulmonary bypass is important. Methods: Protamine dosages of either 2mg/kg or 4mg/kg bodyweight were compared in 40 patients after first time coronary arterial bypass grafting. Protamine was infused with a syringe driver over 20 minutes. Arterial blood sampling was performed prior to and during surgery, before and at 0.3, 0.6, 1, 3, 6 and 25h after the protamine infusion. C3a-desArg and C4a-desArg were analysed by radioimmunoassay. Coagulation was assayed with Sonoclot and activated clotting time. Results: Significantly higher inter-group plasma levels of C3a-desArg were seen with the greater protamine dose from 0.3- 0.6h, but none for C4a-desArg. Sonoclot parameters and leucocyte count differed significantly between the groups up to 6h, indicating hypercoagulabilty with the higher protamine dose. Significantly longer ACT in the low protamine dosage group indicited unblocked heparin with nonsignificant increased drainage bleeding and transfusions. There were no signs of allergic or anaphylactic reactions in any of the groups. Conclusion: Keeping the protamine dose low, minimizes complement activation with less viscoelastic signs of hypercoagulability. However there is an increased risk for drainage bleeding and unnecessary transfusion if heparin is not fully reversed with protamine post cardiopulmonary bypass. The present study was underpowered to detect significant differences in bleeding. (Less)

Evaluation of the Coagulation Profile Among Oral and Vaginal Combined Hormonal Contraceptive Users Using Sonoclot Coagulation Analyzer

Combined hormonal contraceptives possess an inherent risk of thrombus-related events. The purpose of this study is to elucidate alterations in the coagulation profile among young women using combined oral contraceptive (COC) or combined vaginal contraceptive (CVC) compared to a normal, healthy, female control group using the Sonoclot coagulation analyzer. We enrolled 159 participants (64 control individuals, 51 COC users, and 44 CVC users). Each participant completed a survey of medical history, family medical history, and lifestyle choices. Citrated venous whole blood was collected and analyzed using the Sonoclot coagulation analyzer. After adjusting for age, race, alcohol consumption, sleeping habits, and family history of cardiovascular disease, and stroke, we observed COC and CVC users had mostly similar coagulation profiles except when compared to the control, and COC and CVC users had an elevated glass bead peak signal while COC users had a shorter peak time.

Assessment of heparin anticoagulation by Sonoclot Analyzer in arterial reconstruction surgery

Since heparin has been in use as an anticoagulant during vascular surgery and medical problems such as DVT or pulmonary embolism, there has been no consensus as to the best method of monitoring its effect on anticoagulation. In this study we used Sonoclot Analyzer to detect hemostasis changes resulting from heparin administration. The study involved 16 randomly selected male patients undergoing peripheral reconstructive surgery. Blood samples were drawn and analyzed in the operating room on the Sonoclot Coagulation and Platelet Function Analyzer. Results showed that patients respond to heparin differently. The Sonoclot monitors the hemodynamics of blood using four variables: SonACT (activated clotting time) time, rate, peak, and contraction rate. Heparin has three effective on the Sonoclot Signature; prolonged ACT result, lower clot rate, and reduction in clot retraction. The SonACT time is the time for first fibrin to form. Prolong this time indicates the presence of anticoagulation. The Sonoclot Analyzer results confirm that it is a reliable and sensitive device for monitoring heparinization levels.

Coagulation Monitoring

In Response: Casutt and Schüpfer1 commented on the concept of the platelet function (PF) measured by the Sonoclot Analyzer (Sonoclot Coagulation & Platelet Function Analyzer, Sienco, Arvada, CO). Figure 3B in our article2 presented an initial characterization of the Sonoclot Signature and attempted to illustrate that there is both a time component related to platelet activation as well as a clot retraction quality component. Although the graph only introduced the concept of PF, the text clearly states that PF as reported on the Sonoclot Analyzer is “derived from the timing and quality of the clot retraction.” The actual algorithm for the numerical PF result was beyond the scope of the article. It is a numerical integration of the Sonoclot Signature that sums both the speed of platelet activation and quality of clot retraction. A description of the algorithm is available by contacting the manufacturer, Sienco. Historically, many publications have used the earlier Time-to-Peak result as a useful PF indicator. As Dr. Casutt correctly points out, Time-to-Peak is limited as a PF indicator because it fails to include the quality of clot retraction in its result. Furthermore, regarding Dr. Casutt’s comment about the obvious influence of heparin, no PF interpretation should be attempted on samples anticoagulated with heparin that rely on thrombin formation to activate platelets. Activated tests that include heparinase to neutralize the effects of heparin are available for the Sonoclot Analyzer.3 Christoph K. Hofer, MD, DEAA Institute of Anesthesiology and Intensive Care Medicine Triemli City Hospital Zurich Zurich, Switzerland [email protected] Michael T. Ganter, MD, DEAA Institute of Anesthesiology University Hospital Zurich Zurich, Switzerland

The application of Sonoclot,a coagulation and platelet function analysis system in cardiopulmonary bypass surgery

Objective To explore Sonoclot clinic value observing coagulation and platelet function in 135 cardiopulmonary bypass surgery.Methods 135 cases of cardiopulmonary bypass surgery were taken venous blood before anesthesia,before CPB and protamine administration,respectively.The Sonoclot coagulation and platelet function analysis appliance detected ACT,CR and PF.Meanwhile,the ACT,PT,APTT,FIB and PLT were detected using routine methods.Results The ACT,CR and PF were markedly increased after CPB (P<0.05)using Sonoclot.And also the ACT,PT,APTT,FIB and PLT were markedly increased after CPB (P<0.05)using routine methods.And the ACT value between two methods exited positive correlation.Condusion Sonoclot detecting coagulation and platelet function can replace routine methods. Key words: Sonoclot; Coagulation; Cardiopulmonary bypass

Perioperative Sonoclot analysis in patients given flurbiprofen

Perioperative Sonoclot analysis in patients given flurbiprofen

Sonoclot coagulation analysis: new bedside monitoring for determination of the appropriate heparin dose during haemodialysis.

Thrombotic and haemorrhagic complications affect cardiovascular morbidity and mortality in haemodialysis patients. We investigated whether a new bedside Sonoclot analysis is useful for determining an appropriate heparin dose during haemodialysis. Twenty-two haemodialysis patients (15 males and seven females) treated with unfractionated heparin were recruited. Sonoclot parameters, including activated clotting time (ACT), clot rate (CR), time to peak (TP) and peak amplitude (PA), were examined before and after haemodialysis, coupled with conventional coagulable variables, platelet count and fibrinogen level. Some indices were determined and verified to control heparin dose. Thrombotic and haemorrhagic complications were observed for 3 months. Sonoclot analysis was subsequently performed before initiation, 1 h later, 2.5 or 3 h later (before cessation of heparin infusion), and at the end of haemodialysis. Both CR and PA were positively correlated with platelet count and fibrinogen level. Sonoclot parameters except for PA were significantly correlated with heparin dose. Heparin dose was reduced without causing complications in 12 patients with DeltaACT >/=40 s and/or CR after haemodialysis (CRpost) <20 U/min. Thrombotic complications occurred in five patients who had CRpost >30 U/min. ACT and TP increased during heparin treatment. ACT was reversed but TP did not change after cessation of heparin. CR significantly decreased after initiation of heparin and was reversed, although not completely, after cessation of heparin. PA showed no significant changes during haemodialysis. Sonoclot analysis can monitor accurate coagulable states and determine an appropriate heparin dose during haemodialysis.

Analysis of the information content in Sonoclot data and reconstruction of coagulation test variables.

The Sonoclot Coagulation Analyzer is a viscoelastometer used for in vitro analysis of the coagulation process from the start of fibrin formation, through polymerization of the fibrin monomer, platelet interaction, and eventually to clot retraction and lysis. In this paper, we have analyzed series of Sonoclot curves and simultaneously obtained coagulation tests (APT, PT, Fibrinogen, Platelet Count, and D-dimer) from patients who underwent total hip replacements (THA). By using the Principal Component Analysis method (PCA), we found that the most important coagulation test variables as reflected in the Sonoclot signature, are Platelet Count, PT, and Fibrinogen. Also, by using a Back-Propagation Neural Network (BP), we were able to reconstruct the coagulation variables Platelet Count, PT, and Fibrinogen from the Sonoclot curve with a reasonable accuracy. This would also indicate that these three coagulation test variables are most important in determining the appearance of the Sonoclot signature.

Sonoclot coagulation analysis of in-vitro haemodilution with resuscitation solutions.

The colloid and crystalloid solutions used for resuscitation should preferably be free from effects on coagulation. In 10 volunteers, the effects of haemodilution with various concentrations of 0.9% sodium chloride and 4% succinylated gelatin were assessed by Sonoclot analysis, which describes the whole coagulation process. Small and moderate haemodilution (up to 40%) with 0.9% sodium chloride promoted coagulation. Similar haemodilution with 4% succinylated gelatin impaired coagulation, and at 60% haemodilution coagulation was very poor. These findings need to be confirmed in vivo and their clinical relevance determined.

Sonoclot coagulation analysis: A study of test variability

Objective: To test the reproducibility of Sonoclot coagulation analysis (SCA; Sienco Inc, Morrison, CO). The authors wished to determine if the mix/release of the preloaded celite activator in standard Sono-cuvettes could be responsible for the high variation coefficients for SCA parameters with citrated whole blood and if citrated whole blood is optimal for SCA. Design: A prospective trial. Setting: A large academic teaching medical center. Participants: Eight healthy volunteers. Interventions: Repeated blood sampling was performed through indwelling radial artery catheters. Seven different Sonoclot analyzers were used to test seven different types of analysis procedures in the volunteers, involving activators of different types and amounts and in different forms, and the use of citrated or native whole blood. Measurements and Main Results: Two-way and one-way ANOVA, variance, variance analysis, and Tukey's test were used to evaluate differences in SCA methods and volunteer influence. A high variance, with SDs up to 200% of the median values of the SCA parameters with recalcified citrated blood and the standard Sono-cuvette, was confirmed. SCA with native blood and/or the use of other types of preloaded activators, ie, kaolin, significantly ( p < 0.05) reduced this variance. Repeated SCAs further reduced the variance to 10% to 35% of the variance for a single analysis (standard cuvette and native blood). Conclusion: Improvement of the activator in the Sonocuvette, use of native whole blood, and repeated Sonoclot analyses reduced the previously reported high variability of this instrument.