Whole blood clotting time: Current practices among Thailand National External Quality Assessment Scheme for blood coagulation member laboratories.

INTRODUCTION: The Thai National Guidelines for Hemostatic Laboratory Testing were established in 2018. The guidelines recommend that the 20-min whole blood clotting time (20WBCT) method be used to diagnose/monitor snake bites. The aim of this study was to survey members of the Thailand National External Quality Assessment Scheme (NEQAS) for Blood Coagulation to investigate the use of 20WBCT testing compared between the 2021 post-guideline and 2007 pre-guideline periods. METHODS: In July 2021, questionnaires were sent from the Faculty of Medicine Siriraj Hospital, Mahidol University to 521 Thailand NEQAS for Blood Coagulation member laboratories to survey their WBCT practices. Current WBCT practices were compared with pre-guideline WBCT practices, and chi-square test (x2) was used to test for differences between groups. RESULTS: Ninety-seven (18.6%) of 521 surveys were returned. Seventy-one laboratories (73.2%) reported knowing about 20WBCT from the Thai national guidelines. The reported average frequency of overall WBCT testing in 2021 was 12.4 times/month. The proportion of laboratories that reported using the 20WBCT test increased from 2.0% in 2007 to 46.4% in 2021 (p < 0.001), and the indications for performing WBCT were virtually unchanged from 2007 to 2021. The proportion of laboratories that reported having problems with WBCT testing decreased from 32.7% in 2007 to 16.5% in 2021. CONCLUSION: Despite our findings that almost three-quarters of respondent laboratories reported knowing about 20WBCT testing from the WBCT guidelines, and that WBCT-specific problems decreased significantly from 2007 to 2021, more work and training is needed to improve WBCT guideline dissemination, understanding, and adherence in Thailand.

Ex Vivo and In Vivo Biocompatibility Assessment (Blood and Tissue) of Three-Dimensional Bacterial Nanocellulose Biomaterials for Soft Tissue Implants.

Bacterial nanocellulose (BNC) is a promising biomedical material. However, the haemocompatibility (haemolysis and thrombogenicity) and acute and sub-chronic immune responses to three-dimensional (3D) BNC biomaterials have not been evaluated. Accordingly, this manuscript focused on the effect of 3D microporosity on BNC haemocompatibility and a comparison with 2D BNC architecture, followed by the evaluation of the immune response to 3D BNC. Blood ex vivo studies indicated that compared with other 2D and 3D BNC architectures, never-dried 2D BNC presented antihemolytic and antithrombogenic effects. Nevertheless, in vivo studies indicated that 3D BNC did not interfere with wound haemostasis and elicited a mild acute inflammatory response, not a foreign body or chronic inflammatory response. Moreover, compared with the polyethylene controls, the implant design with micropores ca. 60 µm in diameter showed a high level of collagen, neovascularization and low fibrosis. Cell/tissue infiltration increased to 91% after 12 weeks and was characterized by fibroblastic, capillary and extracellular matrix infiltration. Accordingly, 3D BNC biomaterials can be considered a potential implantable biomaterial for soft tissue augmentation or replacement.

Assessment of whole blood coagulation with a microfluidic dielectric sensor.

Essentials ClotChip is a novel microsensor for comprehensive assessment of ex vivo hemostasis. Clinical samples show high sensitivity to detecting the entire hemostatic process. ClotChip readout exhibits distinct information on coagulation factor and platelet abnormalities. ClotChip has potential as a point-of-care platform for comprehensive hemostatic analysis. SUMMARY: Background Rapid point-of-care (POC) assessment of hemostasis is clinically important in patients with a variety of coagulation factor and platelet defects who have bleeding disorders. Objective To evaluate a novel dielectric microsensor, termed ClotChip, which is based on the electrical technique of dielectric spectroscopy for rapid, comprehensive assessment of whole blood coagulation. Methods The ClotChip is a three-dimensional, parallel-plate, capacitive sensor integrated into a single-use microfluidic channel with miniscule sample volume (< 10 µL). The ClotChip readout is defined as the temporal variation in the real part of dielectric permittivity of whole blood at 1 MHz. Results The ClotChip readout exhibits two distinct parameters, namely, the time to reach a permittivity peak (Tpeak ) and the maximum change in permittivity after the peak (Δεr,max ), which are, respectively, sensitive towards detecting non-cellular (i.e. coagulation factor) and cellular (i.e. platelet) abnormalities in the hemostatic process. We evaluated the performance of ClotChip using clinical blood samples from 15 healthy volunteers and 12 patients suffering from coagulation defects. The ClotChip Tpeak parameter exhibited superior sensitivity at distinguishing coagulation disorders as compared with conventional screening coagulation tests. Moreover, the ClotChip Δεr,max parameter detected platelet function inhibition induced by aspirin and exhibited strong positive correlation with light transmission aggregometry. Conclusions This study demonstrates that ClotChip assesses multiple aspects of the hemostatic process in whole blood on a single disposable cartridge, highlighting its potential as a POC platform for rapid, comprehensive hemostatic analysis.

Assessment of Heparin Anticoagulation Measured Using i-STAT and Hemochron Activated Clotting Time.

OBJECTIVE: Adequate anticoagulation, measured using activated clotting time (ACT), is important during vascular and cardiac surgeries. Unfractionated heparin is the most common anticoagulant used. The purpose of this analysis was to compare the i-STAT ACT (iACT) to the Hemochron ACT (hACT), both of which were then compared to anti-factor Xa (anti-Xa) assay, a representation of heparin level and activity. DESIGN: Prospective study. SETTING: Tertiary care cardiovascular center. PARTICIPANTS: Eleven consecutive elective adult cardiac surgical patients. INTERVENTIONS: Prior to cardiopulmonary bypass, ACTs were measured using i-STAT and Hemochron technologies and compared to each other and to anti-Xa assay prior to and during a cumulative administration of heparin. Data were compared using bias analyses. MEASUREMENTS AND MAIN RESULTS: Heparin (300 U/kg) was administered in quarterly doses. Coagulation labs were collected prior to and 3 minutes after each quarterly dose of heparin. The baseline ACTs for i-STAT and Hemochron were 147 and 142 seconds, respectively. A significant association was found between iACT and hACT (p = 0.002). The iACT measurements underestimated hACT at ACT levels >180 seconds or anti-Xa levels >0.75 U/mL. No significant difference was found between ACT data at anti-Xa levels <0.5 U/mL. CONCLUSION: There was a good association between the iACT and hACT; however, the 2 tests are not equivalent. Overall, the iACT underestimated the hACT. Agreement between the ACT technologies was good at lower ACTs and anti-Xa levels, but declined with an anti-Xa >0.75 U/mL.

Evaluación del kit de pruebas para control de hemostasia por tromboelastometría / Avaliação do kit de teste para controle da hemostase por tromboelastometria

ANTECEDENTES: La evaluación del estado de coagulación de los pacientes durante el trasplante hepático y el postoperatorio inmediato es de vital importancia para evitar problemas de hemorragia. • Las pruebas de laboratorio estándares ofrecen información útil aunque limitada del estado hemostático del paciente. • El TEM y TEG describen en tiempo real la interacción entre los factores de la coagulación, fibrinógeno, plaquetas y sistema fibrinolítico; ofreciendo una visión amplia del estado hemostático del paciente. METODOLOGIA: La presente revisión tiene como objetivo evaluar los beneficios del TEM, en comparación con el TEG, en la evaluación del estado de coagulación de los pacientes con cirrosis hepática durante el trasplante hepático y el postoperatorio inmediato. RESULTADOS: Se encontró que el TEG y el TEM son parte fundamental de la evaluación del estado hemostático de los pacientes durante el trasplante hepático que deben ser usados conjuntamente con las pruebas de laboratorio estándares. La utilización de cualquiera de estos dispositivos se asocia a un menor uso de derivados sanguíneos, menor morbilidad y mortalidad postoperatoria y ahorros en costos económicos. CONCLUSION: Existen escasos estudios que comparen específicamente los beneficios del uso de TEM con los del TEG que permitan discernir sobre la superioridad de un equipo sobre el otro. Sin embargo, el hecho que los metanálisis consideran ambos dispositivos en un mismo grupo (equipos viscoelásticos) sugiere que estos equipos tienen similares beneficios en la evaluación de estado de hemostasia de los pacientes.

Preoperative hemostatic assessment: a new and simple bleeding questionnaire.

PURPOSE: Current recommendations for the assessment of the risk of perioperative bleeding limit coagulation testing to patients with a personal and/or family history of bleeding. As no simple preoperative screening questionnaire is currently available, we assessed the performance of a novel screening questionnaire for its ability to detect bleeding disorders. METHODS: A dichotomized, seven-point questionnaire named HEMSTOP (Hematoma, hEmorrhage, Menorrhagia, Surgery, Tooth extraction, Obstetrics, Parents) was applied to three groups of subjects: patients referred to hemostasis specialists for bleeding symptoms for whom any kind of perioperative hemostatic precautions were subsequently recommended (n = 38); patients referred to hemostasis specialists for whom precautions were not required (n = 75); healthy volunteers (n = 70). We calculated the sensitivity and specificity of HEMSTOP scores and compared them with the discriminative performances of standard blood coagulation assays (prothrombin time, activated partial thromboplastin time). RESULTS: Patients requiring perioperative hemostatic precautions had greater median [interquartile range] HEMSTOP scores (2 [2-3]) than patients not requiring precautions (1 [1-2]) and healthy controls (0 [0-0]); P < 0.001. A HEMSTOP score ≥ 2 had a specificity of 98.6% [95% confidence interval (CI), 92.3 to 100] and a sensitivity of 89.5% (95% CI, 75.2 to 97.1). The 26.3% (95% CI, 13.4 to 43.1) sensitivity of the standard coagulation times was much lower. CONCLUSION: The HEMSTOP score discriminates patients at an elevated risk for bleeding with recommended perioperative precautions from those without such recommendations as well as from healthy participants. Further evaluation of the HEMSTOP score is required for a better evaluation of its definitive usefulness to predict the risk of perioperative bleeding.

Assessment of rotation thromboelastometry parameters in patients with essential thrombocythemia at diagnosis and after hydroxyurea therapy.

Patients with essential thrombocythemia suffer from thrombotic complications that are the main source of mortality. Due to its complex pathogenesis, no existing single laboratory method is able to identify the patients at highest risk for developing thrombosis. Twenty patients with essential thrombocythemia at diagnosis, 15 healthy volunteers and 20 patients treated with hydroxyurea were compared with regard to certain rotation thromboelastometry parameters. Clotting time (CT), clot formation time (CFT), α-angle, and maximum clot firmness (MCF) were assessed by using the INTEM, EXTEM, FIBTEM, and NATEM tests. Patients with essential thrombocythemia at diagnosis demonstrated significantly higher mean platelet count and markedly lower mean red blood count than controls. CT and CFT readings were found to be markedly lower in essential thrombocythemia patients at diagnosis than in the control group according to the EXTEM test. Patients at diagnosis had markedly lower CT values (EXTEM, FIBTEM) than patients on hydroxyurea therapy. Alpha angle values were markedly higher in essential thrombocythemia patients at diagnosis than in controls, according to the EXTEM, FIBTEM and NATEM tests. MCF readings were significantly higher in essential thrombocythemia patients at diagnosis than in controls according to EXTEM, INTEM, FIBTEM, and NATEM tests. Patients on hydroxyurea therapy had markedly lower MCF values according to EXTEM test than patients at diagnosis. Patients with essential thrombocythemia demonstrate a prothrombotic state at the time of diagnosis, which is reflected in changes by certain rotation thromboelastometry parameters. The hydroxyurea therapy induces downregulation of the prothrombotic features seen in essential thrombocythemia patients at diagnosis.

A simple clot based assay for detection of procoagulant cell-derived microparticles.

BACKGROUND: Cell-derived microparticles (MPs) are important biomarkers in many facets of medicine. However, the MP detection methods used till date are costly and time consuming. The main aim of this study was to standardize an in-house clot based screening method for MP detection which would not only be specific and sensitive, but also inexpensive. METHODS: Four different methods of MP assessment were performed and the results correlated. Using the flow cytometry technique as the gold standard, 25 samples with normal phosphatidylserine (PS) expressing MP levels and 25 samples with elevated levels were selected, which was cross checked by the commercial STA Procoag PPL clotting time (CT) assay. A simple recalcification time and an in-house clot assay were the remaining two tests. The in-house test measures the CT after the addition of calcium chloride to MP rich plasma, following incubation with Russell viper venom and phospholipid free plasma. RESULTS: The CT obtained by the in-house assay significantly correlated with the results obtained by flow cytometry (R2=0.87, p<0.01). CONCLUSIONS: Though preliminary, the in-house assay seems to be efficient, inexpensive and promising. It could definitely be utilized routinely for procoagulant MP assessment in various clinical settings.

Activated coagulation time vs. intrinsically activated modified rotational thromboelastometry in assessment of hemostatic disturbances and blood loss after protamine administration in elective cardiac surgery: analysis from the clinical trial (NCT01281397).

BACKGROUND: Excessive bleeding after cardiopulmonary bypass (CPB) is risk factor for adverse outcomes after elective cardiac surgery (ECS). Although many different point-of-care devices to diagnose hemostatic disturbances after CPB are available, the best test is still unclear. The study aim was to compare the accuracy of hemostatic disorder detection between two point-of-care devices. METHODS: We enrolled 148 patients (105 male and 43 female) undergoing ECS in a prospective observational study. Rotational thromboelastometry (TEM, with InTEM test), and Activated coagulation time (ACT) measurement were performed 15 min after protamine administration. The cohort group was divided into two subgroups according to occurrence of excessive postoperative bleeding. Endpoints were defined in two ways: as total amount of chest tube output (CTO) and blood product transfusion requirements. RESULTS: Total amount of CTO value of 1507,50 mL presented 75th percentile of distribution, thus cut-off value for bleeder category. InTEM parameters, but not ACT, correlated significantly with CTO. InTEM parameters with the strongest correlation to CTO were tested for accuracy in predicting excessive postoperative bleeding using ROC analysis. InTEM A 10 value of 38 mm, InTEM A 20 value of 49 mm and InTEM A 30 value of 51 mm delineated bleeding tendency. Patients with total amount of CTO exceeding 75th percentile were more frequently transfused with fresh frozen plasma (51.4% vs. 9.9%, p < 0.001), fibrinogen concentrate (21.6% vs. 2.7%, p = 0.001) and platelet concentrate (13.5% vs. 0.9%, p = 0.004). CONCLUSION: Our study showed that InTEM test, but not ACT is useful in prediction of bleeding tendency after protamine administration following weaning from CPB. InTEM test could be used as a first line test in screening of possible hemostatic disorder following protamine administration.

Utility of interim ROTEM(®) values of clot strength, A5 and A10, in predicting final assessment of coagulation status in severely injured battle patients.

BACKGROUND: Proactive management of trauma-related coagulopathy requires early identification and rapid assessment in order to allow targeted resuscitation. This study determined whether early (interim) ROTEM(®) (TEM International GmbH, Munich, Germany) values could predict hypocoagulopathy in seriously injured military patients. METHODS: Normal ranges for ROTEM(®) values were obtained from 50 volunteers. 108 samples were collected during the early phase of clinical management from 48 severe trauma patients. The blood was subject to EXTEM analysis and compared to the 95% tolerance limits from the volunteers. Coagulopathy (was deemed to be present if EXTEM MCF was below 40 mm, which is in the range indicating clinical concern defined by the ROTEM(®) Expert Working Group. RESULTS: The normal range data was broadly similar to ROTEM(®) published data. Admission samples were available from 31 battlefield casualties, and 39% of these were coagulopathic 51% of the samples from all 48 patients were coagulopathic (EXTEM MCF<40 mm) and interim EXTEM values of these at 5 and 10 min (A5 and A10) predicted coagulopathy with sensitivities/specificities of 0.96/0.58 (A5) and 1.00/0.70 (A10). In addition, statistical comparison of clotting domains between normal volunteers and trauma patients suggests a difference in clot strengths due to a difference in platelet function rather than platelet number (mean 142 × 10(9)l(-1)). CONCLUSIONS: The A10 value of ROTEM(®) provides an early sensitive and specific assessment of coagulopathy after military trauma and may be of utility in guiding bespoke resuscitation. We found some speculative evidence that in major trauma platelet function is particularly affected.

Assessment of toxicity and potential risk of the anticoagulant rodenticide diphacinone using Eastern screech-owls (Megascops asio).

In the United States, new regulatory restrictions have been placed on the use of some second-generation anticoagulant rodenticides. This action may be offset by expanded use of first-generation compounds (e.g., diphacinone; DPN). Single-day acute oral exposure of adult Eastern screech-owls (Megascops asio) to DPN evoked overt signs of intoxication, coagulopathy, histopathological lesions (e.g., hemorrhage, hepatocellular vacuolation), and/or lethality at doses as low as 130 mg/kg body weight, although there was no dose-response relation. However, this single-day exposure protocol does not mimic the multiple-day field exposures required to cause mortality in rodent pest species and non-target birds and mammals. In 7-day feeding trials, similar toxic effects were observed in owls fed diets containing 2.15, 9.55 or 22.6 ppm DPN, but at a small fraction (<5%) of the acute oral dose. In the dietary trial, the average lowest-observed-adverse-effect-level for prolonged clotting time was 1.68 mg DPN/kg owl/week (0.24 mg/kg owl/day; 0.049 mg/owl/day) and the lowest lethal dose was 5.75 mg DPN/kg owl/week (0.82 mg/kg owl/day). In this feeding trial, DPN concentration in liver ranged from 0.473 to 2.21 µg/g wet weight, and was directly related to the daily and cumulative dose consumed by each owl. A probabilistic risk assessment indicated that daily exposure to as little as 3-5 g of liver from DPN-poisoned rodents for 7 days could result in prolonged clotting time in the endangered Hawaiian short-eared owl (Asio flammeus sandwichensis) and Hawaiian hawk (Buteo solitarius), and daily exposure to greater quantities (9-13 g of liver) could result in low-level mortality. These findings can assist natural resource managers in weighing the costs and benefits of anticoagulant rodenticide use in pest control and eradication programs.

Multiple electrode whole blood aggregometry, PFA-100, and in vivo bleeding time for the point-of-care assessment of aspirin-induced platelet dysfunction in the preoperative setting.

BACKGROUND: Acquired platelet dysfunction due to aspirin ingestion may increase bleeding tendency during surgery. Thus, we examined the diagnostic accuracy of in vivo bleeding time (BT) and 2 platelet function assays for the preoperative assessment of a residual antiplatelet effect in patients treated with aspirin. METHODS: Consecutive patients scheduled for surgery were prospectively enrolled in this study. The patients' last aspirin ingestion had occurred within the previous 48 hours before blood sampling in the "full aspirin effect" group, between 48 and 96 hours before in the "variable aspirin effect" group, and >96 hours before in the "recovered aspirin effect" group. The control group had not taken any aspirin. Multiple electrode aggregometry, platelet function analyzer (PFA)-100, and in vivo BT were performed to assess the effects of aspirin. One-way analysis of variance on ranks with a post hoc multiple-comparison procedure (Dunn) was used to detect differences among the groups. Categorical data were compared using the z test. Receiver operating characteristic (ROC) curves were created to determine the diagnostic accuracy of the platelet function assays investigated. The area under the ROC curve (AUC), sensitivity, and specificity of the assays were calculated. The level of statistical significance was set at P < 0.05. RESULTS: Three hundred ninety-four patients were included in the analysis (133 control and 261 aspirin-treated patients). All 3 methods were able to detect the antiplatelet effect of aspirin in the full aspirin effect group. Furthermore, no difference in the measurement values between the recovered aspirin effect and control group was found, irrespective of the assay performed. Measurement values in the variable aspirin effect group were different from those of the control group in the ASPItest using multiple electrode aggregometry and COL-EPI using PFA-100 but not in BT. ROC analysis showed the highest diagnostic accuracy in excluding the residual aspirin effect in the ASPItest (AUC 0.81, P < 0.001), followed by COL-EPI (AUC 0.78, P < 0.001) and BT (AUC 0.56, P = 0.05). The cutoff value of 53 U in the ASPItest excluded the effect of aspirin with a sensitivity of 88% and specificity of 71%. CONCLUSIONS: The full therapeutic antiplatelet effects of aspirin can be expected within 48 hours of the patient's last aspirin ingestion. Platelet function recovered in our study if aspirin cessation occurred >96 hours (4 days) before; thus, in these patients, preoperative platelet function testing is not useful. To quantify any residual aspirin effect in patients who ceased their intake of aspirin between 48 and 96 hours before surgery, the ASPItest might have the highest diagnostic accuracy.

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.

Heparin dose response is independent of preoperative antithrombin activity in patients undergoing coronary artery bypass graft surgery using low heparin concentrations.

BACKGROUND: Unfractionated heparin's primary mechanism of action is to enhance the enzymatic activity of antithrombin (AT). We hypothesized that there would be a direct association between preoperative AT activity and both heparin dose response (HDR) and heparin sensitivity index (HSI) in patients undergoing coronary artery bypass graft surgery. METHODS: Demographic and perioperative data were collected from 304 patients undergoing primary coronary artery bypass graft surgery. AT activity was measured after induction of general anesthesia using a colorimetric method (Siemens Healthcare Diagnostics, Tarrytown, NY). Activated coagulation time (ACT), HDR, and HSI were measured using the Hepcon HMS Plus system (Medtronic, Minneapolis, MN). Heparin dose was calculated for a target ACT using measured HDR by the same system. Multivariate linear regression was performed to identify independent predictors of HDR. Subgroup analysis of patients with low AT activity (<80% normal; <0.813 U/mL) who may be at risk for heparin resistance was also performed. RESULTS: Mean baseline ACT was 135 ± 18 seconds. Mean calculated HDR was 98 ± 21 s/U/mL. Mean baseline AT activity was 0.93 ± 0.13 U/mL. Baseline AT activity was not significantly associated with baseline or postheparin ACT, HDR, or HSI. Addition of AT activity to multivariable linear regression models of both HDR and HSI did not significantly improve model performance. Subgroup analysis of 49 patients with baseline AT <80% of normal levels did not reveal a relationship between low AT activity and HDR or HSI. Preoperative AT activity, HDR, and HSI were not associated with cardiac troponin I levels on the first postoperative day, intensive care unit duration, or hospital length of stay. CONCLUSION: Although enhancing AT activity is the primary mechanism by which heparin facilitates cardiopulmonary bypass anticoagulation, low preoperative AT activity is not associated with impaired response to heparin or to clinical outcomes when using target ACTs of 300 to 350 seconds.

Adaptive force sonorheometry for assessment of whole blood coagulation.

BACKGROUND: Viscoelastic diagnostics that monitor the hemostatic function of whole blood (WB), such as thromboelastography, have been developed with demonstrated clinical utility. By measuring the cumulative effects of all components of hemostasis, viscoelastic diagnostics have circumvented many of the challenges associated with more common tests of blood coagulation. METHODS: We describe a new technology, called sonorheometry, that adaptively applies acoustic radiation force to assess coagulation function in WB. The repeatability (precision) of coagulation parameters was assessed using citrated WB samples. A reference range of coagulation parameters, along with corresponding measurements from prothrombin time (PT) and partial thromboplastin time (PTT), were obtained from WB samples of 20 healthy volunteers. In another study, sonorheometry monitored anticoagulation with heparin (0-5 IU/ml) and reversal from varied dosages of protamine (0-10 IU/ml) in heparinized WB (2 IU/ml). RESULTS: Sonorheometry exhibited low CVs for parameters: clot initiation time (TC1), <7%; clot stabilization time (TC2), <6.5%; and clotting angle (theta), <3.5%. Good correlation was observed between clotting times, TC1 and TC2, and PTT (r=0.65 and 0.74 respectively; n=18). Linearity to heparin dosage was observed with average linearity r>0.98 for all coagulation parameters. We observed maximum reversal of heparin anticoagulation at protamine to heparin ratios of 1.4:1 from TC1 (P=0.6) and 1.2:1 from theta (P=0.55). CONCLUSIONS: Sonorheometry is a non-contact method for precise assessment of WB coagulation.

Monitoring therapeutic anticoagulation with low molecular weight heparins: is it useful or misleading?

Weight adapted low molecular weight heparin (LMWH) treatment is recommended as initial anticoagulant therapy of deep vein thrombosis, pulmonary embolism, in patients with myocardial ischemia or when oral anticoagulation (OAC) must be interrupted peri- operatively. Traditionally unfractioned heparin (UFH) was used as standard short acting anticoagulant, with the therapy monitored by frequent laboratory testing. Currently LMWH have broadly replaced UFH as first- choice anticoagulant due to more preferable pharmacokinetics and a better safety profile. Therapeutic anticoagulation with LMWH can be achieved by subcutaneous weight adapted application and measurement of anti-factor Xa- activity (anti-Xa) has been established as gold standard for LMWH- monitoring. However, since almost all LMWH dosing regimens have been developed empirically without laboratory monitoring, there is still a debate ongoing about the usefulness and impact of anti-Xa-testing. Data are lacking that prove a clear correlation between obtained levels of anti-Xa and the patients' clinical outcome. Newer methods have been developed aiming to determine a broader spectrum of LMWH depending anticoagulant activity. Even though there are some promising preliminary results, these alternative methods are not ready for routine clinical use yet. Nevertheless, current guidelines advise determination of anti-Xa in special patient populations with markedly altered LMWH metabolism or to exclude residual LMWH- activity before surgery at very high risk of bleeding. The aim of this article is to review critically the usefulness of anti- Xa guidance of LMWH- therapy and to give new perspectives on upcoming methods of LMWH- monitoring.

Establishment of a replacement batch for heparin sodium biological reference preparation.

An international collaborative study was organised to replace the current European Pharmacopoeia biological reference preparation for heparin sodium. The project was organised by the European Directorate for the Quality of Medicines & HealthCare in the frame of its Biological Standardisation Programme. A suitable candidate batch representative of the quality of heparin products currently marketed in Europe was donated to the EDQM and included in a collaborative study involving 19 laboratories from 10 European countries, the Americas, Australia and the Council of Europe. Laboratories were requested to perform their routine assays following the prescriptions of the Ph. Eur. for the assay and the identification of unfractionated heparin and for the assay of protamine. The results made it possible to demonstrate that the candidate batch was suitable for its intended use and it was therefore established by the European Pharmacopoeia Commission as the Ph. Eur. heparin sodium BRP batch 3 in June 2007.

Frequency and timing of activated clotting time levels for sheath removal.

Guidelines currently exist that describe the medical management of patients undergoing percutaneous coronary interventions (PCI), but these guidelines do not include nursing management of the patient post procedure. The nursing staff on an intermediate care unit believed there were numerous and unnecessary activated clotting time (ACT) levels obtained on post PCI patients. The purpose of this study was to identify the most appropriate time to begin analyzing ACT levels. Results from a retrospective chart audit of 44 patients indicated that 3 hours after the last dose of heparin, only 7% of the patients met the criteria of ACT < 150 seconds in order to have their femoral sheaths removed, and 21% of patients had an ACT of < 160 seconds. It is recommended that current standard orders be changed to begin drawing ACT levels at 3 hours post last heparin dose and removing sheaths when ACT is < 160 seconds. This change would save the hospital nearly dollars 5000 in nursing time alone.

More selective antenatal coagulation screening tests could reduce costs and save time without compromising maternal safety.

Antenatal coagulation testing is commonly performed and yet there is no evidence on which to base practice. This retrospective review of testing and the results obtained in a one-year period at the Southern General Hospital, Glasgow, UK, showed that the majority of the tests were normal regardless of the clinical indication for testing. However, there was a significant association between thrombocytopaenia and an abnormal coagulation result (p < 0.001). This analysis showed that the platelet count might be used to select patients who require subsequent coagulation studies without compromising maternal or fetal safety and with attendant savings in time and money.