Search

Background The management of pregnant women with von Willebrand Disease (VWD) is complex as physiological pregnancy-induced increases in plasma von Willebrand Factor (VWF) may be blunted or absent. Women with VWD experience a heightened risk of postpartum haemorrhage (PPH) and special consideration must be given regarding neuraxial anaesthesia (NA) and the need for prophylaxis at time of delivery. These challenges are compounded by a lack of robust evidence to guide clinical decision making. Objectives & Methods To determine the current international clinical practises in the management of pregnancy for women with VWD, the International Society on Thrombosis and Haemostasis (ISTH) conducted an international survey of healthcare providers (HCP). Results 132 respondents from 39 countries were included in the final analysis. Variations in clinical practise were identified in antenatal (monitoring of plasma VWF and ferritin levels), peripartum (optimal plasma VWF target at delivery) and postpartum management (definitions used for PPH and postpartum monitoring). A key area of divergence was suitability for NA for women with type 2 and type 3 VWD, with many respondents advising against the use of NA even with VWF supplementation (29% type 2 VWD, 37% type 3 VWD) but others advising use once plasma VWF activity was was >50 IU/dL (57% type 2 VWD; 50% type 3 VWD). Conclusions This survey highlighted areas of uncertainty surrounding common management issues for pregnant women with VWD. These data underscore the need for international collaborative research efforts focused on peripartum management to improve care for pregnant women with VWD.

Background Coronavirus disease 2019 (COVID‐19) occurs following infection with the potentially fatal, severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) virus. Infection can be complicated by coagulopathy, at times featuring thrombocytopenia and thrombosis alongside other coagulation abnormalities, also termed COVID‐19‐associated coagulopathy (CAC). Data concerning CAC in pregnancy are limited. Better understanding of physician experiences is essential to identify current practice patterns and knowledge gaps. Objectives To determine physician experiences and practice patterns regarding CAC in pregnancy. Methods Self‐administered survey using the RedCap online platform; supported by the ISTH Subcommittee on Women's Health Issues in Thrombosis and Hemostasis. Results Seventy‐five respondents fully or partially completed the survey. Of 1546 reported cases, disease severity was specified in 1298. Sixty‐four percent of COVID‐19 infections were mild, whereas 4% were severe. Of all cases, 1% developed CAC, with 65% classified as severe. The most frequent abnormalities included thrombocytopenia, elevated C‐reactive protein, D‐dimer, and lymphopenia. Low molecular weight heparin was the anticoagulant of choice in CAC and was provided by 77% of respondents, with 60% using standard prophylactic dosing. Thrombosis occurred in seven anticoagulated patients who were receiving standard prophylactic (four) or weight‐based (three) dosing. Disease severity and additional thrombosis risk factors dictated anticoagulation duration. Conclusion In the select population reported by our survey, CAC appears to be uncommon in pregnancy. Anticoagulation practices vary and may not reflect current guidelines. Venous thromboembolism was observed in some CAC patients despite prophylactic anticoagulation (including standard and weight‐adjusted dosing). Urgent research is required to determine appropriate anticoagulant dosing and duration in pregnant women with COVID‐19 infection.

Hemophilia A and B predominantly attracts clinical attention in males due to X‐linked inheritance, introducing a bias toward female carriers to be asymptomatic. This common misconception is contradicted by an increasing body of evidence with consistent reporting on an increased bleeding tendency in hemophilia carriers (HCs), including those with normal factor VIII/IX (FVIII/IX) levels. The term HC can hamper diagnosis, clinical care, and research. Therefore, a new nomenclature has been defined based on an open iterative process involving hemophilia experts, patients, and the International Society on Thrombosis and Haemostasis (ISTH) community. The resulting nomenclature accounts for personal bleeding history and baseline plasma FVIII/IX level. It distinguishes five clinically relevant HC categories: women/girls with mild, moderate, or severe hemophilia (FVIII/IX >0.05 and

As a result of the coronavirus disease 2019 pandemic, the International Society on Thrombosis and Haemostasis (ISTH), like many societies around the world, canceled their in‐person hematology congress planned for Milan, Italy, in July 2020. As a result, the first virtual ISTH congress in the organisation’s 51‐year history was delivered, inviting free registration from across the globe. As part of the social media support, marketing, and scientific dissemination efforts for the virtual congress, the ISTH assembled a group of official Twitter Ambassadors, which represented the broad and diverse ISTH community. Ambassadors were tasked to tweet daily throughout the congress and to share their commentary on the hematology research being presented with the “#ISTH2020” hashtag. Ambassadors were also supported by Twitter activities from the two official ISTH‐affiliated journals: the Journal of Thrombosis and Haemostasis (JTH) and Research and Practice in Thrombosis and Haemostasis (RPTH). In this forum and through the Twitter ambassadors’ lens, we present the Twitter Ambassadors’ experience, reflect on the impact of social media on the ISTH 2020 congress, and share this experience with the wider scientific community. Specifically, we report on the role of Twitter communication for virtual meetings, discuss the pros and cons of the virtual congress, and offer Twitter‐related recommendations for future virtual or blended congresses. We conclude that the ISTH Twitter Ambassador program broadened social media engagement and offers a novel route to improve social connectivity in the virtual research congress setting.

SARS-CoV-2 is a new virus, to which herd immunity has not yet developed and both molecular and serological testing are not without flaws. The virus evokes a state of severe and widespread inflammation, and stimulates both innate and adaptive immune response. The angiotensin-converting enzyme 2 (ACE2), which acts as the SARS-CoV-2 receptor, is present in endothelial cells and has been noted within the human placenta. There are questions about whether pregnancy would increase the susceptibility of pregnant women to COVID-19 and disease severity within this population. In this report, we highlight physiological and immune/inflammatory considerations that may explain the susceptibility and disease pathology in response to SARS CoV-2 during pregnancy, explore testing considerations in asymptomatic individuals, discuss the potential role and of placental ACE2 receptor in the pathogenesis of COVID-19 in pregnancy and in pregnancy outcomes, and finally share our perspective with respect to an urgently needed change concerning involvement of pregnant women in research addressing COVID-19.

Background Novel coronavirus (SARS-CoV-2), which causes COVID-19, has thus far affected more than 15 million individuals, resulting in more than 600 000 deaths worldwide, and the number continues to rise. In a large systematic review and meta-analysis of the literature including 2567 pregnant women, 7% required intensive care admission, with a maternal mortality ~1% and perinatal mortality below 1%. There has been a rapid increase in publications on COVID-19-associated coagulopathy, including disseminated intravascular coagulopathy and venous thromboembolism, in the non-pregnant population, but very few reports of COVID-19 coagulopathy during pregnancy; leaving us with no guidance for care of this specific population. Methods This is a collaborative effort conducted by a group of experts that was reviewed, critiqued, and approved by the International Society on Thrombosis and Haemostasis Subcommittee for Women's Health Issues in Thrombosis and Hemostasis. A structured literature search was conducted, and the quality of current and emerging evidence was evaluated. Based on the published studies in the non-pregnant and pregnant population with a moderate to high risk of bias as assessed by Newcastle-Ottawa scale and acknowledging the absence of data from randomized clinical trials for management of pregnant women infected with SARS-CoV-2, a consensus in support of a guidance document for COVID-19 coagulopathy in pregnancy was identified. Results and conclusions Specific hemostatic issues during pregnancy were highlighted, and preliminary recommendations to assist in the care of COVID-19-affected pregnant women with coagulopathy or thrombotic complications were developed. An international registry to gather data to support the management of COVID-19 and associated coagulopathy in pregnancy was established.

Background Bleeding disorders (BD) are under-recognized in adolescents with heavy menstrual bleeding (HMB). Objectives The lack of clinical guidelines and variable symptomatic management of HMB created the imperative to standardize HMB care to identify and manage BD in adolescents. Methods We convened an international working group (WG), utilized the results of a literature review to define knowledge gaps in HMB care, and used the collective clinical experience of the WG to develop care considerations for adolescents with BD and HMB. We then solicited input on the appropriateness of HMB care considerations from expert stakeholders representing hematology, adolescent medicine, and obstetrics-gynecology. We conducted an expert panel online, using the ExpertLens platform. During a 3-round online modified-Delphi process, the expert panel rated the appropriateness of 21 care considerations using a 9-point scale to designate care as appropriate (7-9), uncertain (4-6), or inappropriate (1-3) covering screening for BD, the laboratory work-up, and management of adolescents with BD that present with HMB. We used the RAND/UCLA appropriateness method to determine the existence of consensus among the interdisciplinary panel of experts. Results Thirty-nine experts participated in the panel. The experts rated fifteen HMB care considerations as appropriate, six as uncertain, and none as inappropriate. Conclusions The HMB care statements represent the first set of HMB care considerations in adolescents with BD, developed with broad expert input on appropriateness. Although likely to be of interest to a range of clinicians who routinely manage adolescents with HMB, additional research is required in many key areas.

Platelet-type von Willebrand disease (PT-VWD) is a rare autosomal dominant platelet bleeding disorder, with 55 patients reported worldwide so far, probably frequently misdiagnosed. Currently, there are no clear guidelines for the diagnosis and management of PT-VWD and this may contribute to misdiagnosis and thus to inappropriate treatment of these patients. This report provides expert opinion-based consensus recommendations for the standardized diagnostic and management approach to PT-VWD. Tests essential in the diagnostic workup are platelet count and size, ristocetin-induced platelet agglutination with mixing studies, and sequencing of platelet GP1BA gene. Platelet transfusions and von Willebrand factor-rich concentrates (if VWF is low) are the most effective treatments. This consensus may help to avoid misdiagnosis and guide appropriate management of patients with this disease.

Thromboelastography (TEG) and rotational thromboelastometry (ROTEM) are point-of-care viscoelastic devices that use whole blood samples to assess coagulation and fibrinolysis. These devices have been studied extensively in cardiac surgery, but there is limited robust evidence supporting its use in obstetrics. The hesitancy toward its routine use in obstetrics may be due to the current lack of randomized controlled trials and large observational studies. The study aims to systematically review studies that investigated TEG/ROTEM use in pregnancy or peripartum, and to provide recommendations for future studies to fill current research gaps. We performed a systematic review of studies on viscoelastic testing in obstetrics. Included studies were original research, used TEG or ROTEM during pregnancy or peripartum, and published in English. Ninety-three studies, spanning 31 years from 1989 to 2020 and with a total of 32,817 participants, were included. Sixty-two (66.7%) of the studies used TEG and 31 (33.3%) used ROTEM. To date, there are a total of two randomized controlled trials on TEG/ROTEM use in obstetrics. ROTEM may be used to guide transfusion therapy for postpartum hemorrhage. TEG and ROTEM can detect the hypercoagulable changes associated with pregnancy. Variability between study protocols and results suggests the need for future large prospective high-quality studies with standardized protocols to investigate the utility of TEG/ROTEM in assessing risk for thrombosis and hemorrhage as well as in guiding prophylaxis and treatment in obstetric patients. This review identifies the gaps and provides concrete recommendations for future studies to fill those gaps.

Coagulopathy is an evident complication of COVID-19 with predominance of a prothrombotic state. Platelet activation plays a key role. The terms "hyper-reactivity" and "hyperactivity" used in recent literature may not be clear or sufficient to explain the pathological events involved in COVID-related thrombosis (CRT). Inflammation may play a bigger role compared to thrombosis in COVID-related mortality because a smaller percentage of patients with COVID-19 die due to direct effects of thrombosis. Not all COVID-19 patients have thrombocytopenia and a few show thrombocytosis. We believe the platelet pathology is more complex than just activation or hyper-activation, particularly due to the platelets' role in inflammation. Understanding the pathology and consequences of platelets' role may help optimize management strategies and diminish CRT-associated morbidity and mortality. In this viewpoint report, we examine the published evidence of platelet hyper-reactivity in COVID-19 with a focused analysis of the key pathologies, diverse alterations, disease outcomes, and therapeutic targets. We believe that COVID-19 is a disease of inflammation and pathologic platelets, and based on the complexity and diverse pathologies, we propose the term "thrombocytopathy" as a more reflective term of the platelets' involvement in COVID-19. In our opinion, thrombocytopathy is the unpredictable pathologic alterations of platelets in function, morphology and number, caused by different factors with a variety of presentations.

Registries provide an important tool for data collection, particularly in context of rare conditions, or questions not amenable to investigation by means of a clinical trial. The Subcommittee on Women's Health in Thrombosis and Hemostasis (WHITH); one of 20 Scientific and Standardization Subcommittees (SSCs) of the International Society on Thrombosis and Hemostasis (ISTH) has supported 12 registries related to WHITH since 2016. Despite many successes, some challenges have been observed. In this report, we attempt to review the basic tenets of value in developing a registry, discuss observed challenges, share lessons learned, and finally present our views on a potential formula for success in developing and maintaining a registry in WHITH.

Children of women with pre-eclampsia have increased risk of cardiovascular (CV) and metabolic disease in adult life. Furthermore, the risk of pregnancy complications is higher in daughters born to women affected by pre-eclampsia than in daughters born after uncomplicated pregnancies. While aberrant inflammation contributes to the pathophysiology of pregnancy complications, including pre-eclampsia, the contribution of maternal inflammation to subsequent risk of CV and metabolic disease as well as pregnancy complications in the offspring remains unclear. Here we demonstrate that 24-week-old female rats (F1) born to dams (F0) exposed to lipopolysaccharide (LPS) during pregnancy (to induce inflammation) exhibited mild systolic dysfunction, increased cardiac growth-related gene expression, abnormal glucose tolerance and coagulopathy; whereas male F1 offspring exhibited abnormal glucose tolerance and increased visceral fat accumulation compared with F1 sex-matched offspring born to saline-treated dams. Both male and female F1 offspring born to LPS-treated dams had evidence of anemia. Fetuses (F2) from F1 females born to LPS-treated dams were growth restricted, and this reduction in fetal growth was associated with increased CD68 positivity and decreased expression of glucose transporter-1 in their utero-placental units. These results indicate that abnormal maternal inflammation can contribute to increased risk of CV and metabolic disease in offspring, and that the effects of inflammation may be transgenerational. This study provides evidence in support of early screening for CV and metabolic disease, as well as pregnancy complications in offspring affected by pre-eclampsia or other pregnancy complications associated with aberrant inflammation.

The implementation of high-throughput sequencing (HTS) technologies in research and diagnostic laboratories has linked many new genes to rare bleeding, thrombotic, and platelet disorders (BTPD), and revealed multiple genetic variants linked to those disorders, many of them being of uncertain pathogenicity when considering the accepted evidence (variant consequence, frequency in control datasets, number of reported patients, prediction models, and functional assays). The sequencing effort has also resulted in resources for gathering disease-causing variants associated with specific genes, but for BTPD, such well-curated databases exist only for a few genes. On the other hand, submissions by individuals or diagnostic laboratories to the variant database ClinVar are hampered by the lack of a submission process tailored to capture the specific features of hemostatic diseases. As we move toward the implementation of HTS in the diagnosis of BTPD, the Scientific and Standardization Committee for Genetics in Thrombosis and Haemostasis has developed and tested a REDCap-based interface, aimed at the community, to submit curated genetic variants for diagnostic-grade BTPD genes. Here, we describe the use of the interface and the initial submission of 821 variants from 30 different centers covering 14 countries. This open-access variant resource will be shared with the community to improve variant classification and regular bulk data transfer to ClinVar. ispartof: JOURNAL OF THROMBOSIS AND HAEMOSTASIS vol:19 issue:10 pages:2612-2617 ispartof: location:England status: published

Vaccine-induced immune thrombotic thrombocytopenia (VITT), or thrombotic thrombocytopenic syndrome (TTS), has caused global concern. VITT is characterized by thrombosis and thrombocytopenia following COVID-19 vaccinations with the AstraZeneca ChAdOx1 nCov-19 and the Janssen Ad26.COV2.S vaccines. The clinical features of VITT include thrombosis, typically cerebral venous thrombosis, and severe thrombocytopenia developing 5 to 24 days following first dose of vaccine, with elevated D-dimer, and antibodies specific to platelet factor 4 (PF4), signifying platelet activation. As of June 1, 2021, over 1.93 billion COVID-19 vaccine doses had been administered worldwide. Currently, 467 VITT cases (0.000024%) have been reported across the UK, Europe, Canada and Australia. Clinically, VITT presents similarly to a rare autoimmune condition called “spontaneous/autoimmune heparin Induced Thrombocytopenia” (HIT) without prior heparin exposure. Guidance on diagnosis and management of VITT has been reported but the pathogenic mechanism of VITT is not fully elucidated. A definite causal relationship with the vaccine material is yet to be confirmed. To date, it is established that IgG antibodies recognizing PF4 activate platelets through FcγRIIA, however it remains unclear what triggers production of these antibodies. The fact that VITT, has only been described in association with adenoviral vector-based DNA virus vaccines, but not mRNA/lipid-based vaccines, raises the likelihood that the syndrome is somehow linked to the vector or other constituents in the vaccine preparation. Here, we propose and discuss potential mechanisms in relation to adenovirus induction of VITT. We discuss adenovirus immunogenicity and interactions with platelets and other host proteins, the role of PF4 and platelet activation. Whilst confirming a single mechanism underpinning VITT is challenging, we provide insights and clues into areas warranting investigation into the mechanistic basis of VITT, highlighting the unanswered questions. Further research is required to help solidify a pathogenic model for this condition.

Blood collection is critical for mouse research studies particularly in hemostatic testing. Cardiac puncture; a standard effective method requires anesthesia and is a terminal procedure while facial vein technique allows multiple collections. Thromboelastography (TEG) is a global hemostasis test, provides a dynamic real-time picture of coagulation. However, TEG experiments in mice require large number of animals and may not allow pre/postinterventions assessment. In this study, we aimed to investigate the feasibility of facial vein sampling for TEG analysis as an alternative to cardiac puncture and examined the impact on coagulation results. Blood samples were obtained from a total of 10 C57BL/6 and CD-1 mice via cardiac puncture and a total of another eight mice of similar strains via facial vein sampling. We compared TEG parameters in both methods using descriptive statistics and the Student t test. Results show no significant difference in any of the TEG parameters between cardiac and facial vein blood indicating the two methods are comparable. Facial vein sampling provides a less costly alternative to cardiac puncture. It is a suitable blood collection method for pre/postinterventions or follow-up studies and it better addresses reduction and refinement goals in mouse studies. A larger study to evaluate the sex or strain and genetic background differences will be valuable.

Online patient registries are used to collect data on clinical conditions with rare occurrence or unclear diagnostic and management practices. The success of these registries depends on clear definition of goals, correct identification of patient population/inclusion criteria, availability of appropriate setup and maintenance tools, and the quality of dissemination. The Scientific and Standardization Committee (SSC) for Women's Health Issues in Thrombosis and Hemostasis, one of 20 committees of the International Society on Thrombosis and Haemostasis (ISTH) has developed 6 registries for women's bleeding and thrombotic conditions over the past 2 years and are currently in various stages of progress. Here, we provide information about these registries, including rationale, objectives, and methods for data collection. The aim is to enhance worldwide participation and thus promote the success of these registries. We used ISTH REDCap, a mature and secure Web application for building and managing online surveys and databases, and the ISTH advertising platform to maximize participation. Registries (links and project details available on ISTH and Women's SSC Web sites) include: (1) WiTEAM, project on thrombophilia and placenta‐mediated obstetric complications; (2) a registry for disseminated intravascular coagulation in pregnancy; (3) severe congenital protein C deficiency—an obstetric study; (4) obstetric and gynecologic outcomes of women with platelet function disorders; (5) thrombolysis and invasive treatments for massive pregnancy‐related pulmonary embolism; (6) pregnancy and exposure to direct oral anticoagulants. The ISTH promotes online registries on women's issues to enhance understanding of current practices, identify knowledge gaps, promote research, and ultimately improve patient safety and quality of life.

Background As pregnancy is a physiological prothrombotic state, pregnant women may be at increased risk of developing coagulopathic and/or thromboembolic complications associated with COVID-19. Methods Two biomedical databases were searched between September 2019 and June 2020 for case reports and series of pregnant women with a diagnosis of COVID-19 based either on a positive swab or high clinical suspicion where no swab had been performed. Additional registry cases known to the authors were included. Steps were taken to minimise duplicate patients. Information on coagulopathy based on abnormal coagulation test results or clinical evidence of disseminated intravascular coagulation (DIC), and on arterial or venous thrombosis, were extracted using a standard form. If available, detailed laboratory results and information on maternal outcomes were analysed. Results One thousand sixty-three women met the inclusion criteria, of which three (0.28, 95% CI 0.0 to 0.6) had arterial and/or venous thrombosis, seven (0.66, 95% CI 0.17 to 1.1) had DIC, and a further three (0.28, 95% CI 0.0 to 0.6) had coagulopathy without meeting the definition of DIC. Five hundred and thirty-seven women (56%) had been reported as having given birth and 426 (40%) as having an ongoing pregnancy. There were 17 (1.6, 95% CI 0.85 to 2.3) maternal deaths in which DIC was reported as a factor in two. Conclusions Our data suggests that coagulopathy and thromboembolism are both increased in pregnancies affected by COVID-19. Detection of the former may be useful in the identification of women at risk of deterioration.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease in 2019 (COVID-19) which rapidly evolved from an outbreak in Wuhan, China into a pandemic that has resulted in over millions of infections and over hundreds of thousands of mortalities worldwide. Various coagulopathies have been reported in association with COVID-19, including disseminated intravascular coagulation (DIC), sepsis-induced coagulopathy (SIC), local microthrombi, venous thromboembolism (VTE), arterial thrombotic complications, and thrombo-inflammation. There is a plethora of publications and conflicting data on hematological and hemostatic derangements in COVID-19 with some data suggesting the link to disease progress, severity and/or mortality. There is also growing evidence of potentially useful clinical biomarkers to predict COVID-19 progression and disease outcomes. Of those, a link between thrombocytopenia and COVID-19 severity or mortality was suggested. In this opinion report, we examine the published evidence of hematological and hemostatic laboratory derangements in COVID-19 and the interrelated SARS-CoV-2 induced inflammation, with a focussed discussion on platelet count alterations. We explore whether thrombocytopenia could be a potential disease biomarker and we provide recommendations for future studies in this regard.

Major surgery is associated with an increased risk of venous thromboembolism, thus the application of mechanical or pharmacologic prophylaxis is recommended. The incidence of venous thromboembolism in patients with inherited platelet disorders undergoing surgical procedures is unknown and no information on the current use and safety of thromboprophylaxis, particularly of low-molecular-weight-heparin in these patients is available. Here we explored the approach to thromboprophylaxis and thrombotic outcomes in inherited platelet disorders patients undergoing surgery at venous thromboembolism-risk participating in the multicenter SPATA study. We evaluated 210 surgical procedures carried out in 155 patients with well-defined forms of inherited platelet disorders (venous thromboembolism-risk: 31% high, 28.6% intermediate, 25.2% low, 15.2% very low). The use of thromboprophylaxis was low (23.3% of procedures), with higher prevalence in orthopedic and gynecological surgeries, and was related to venous thromboembolism-risk. The most frequently employed thromboprophylaxis was mechanical and appeared to be effective, as no patients developed thrombosis, including patients belonging to the highest venous thromboembolism-risk classes. Low-molecular-weight-heparin use was low (10.5%) and it did not influence the incidence of post-surgical bleeding or of antihemorrhagic prohemostatic interventions. Two thromboembolic events were registered, both occurring after high venous thromboembolism-risk procedures in patients who did not receive thromboprophylaxis (4.7%). Our findings suggest that venous thromboembolism incidence is low in patients with inherited platelet disorders undergoing surgery at venous thromboembolism-risk and that it is predicted by the Caprini score. Mechanical thromboprophylaxis may be of benefit in patients with inherited platelet disorders undergoing invasive procedures at venous thromboembolism-risk and low-molecular-weight-heparin should be considered for major surgery. Fil: Paciullo, Francesco. Università di Perugia; Italia Fil: Bury, Loredana. Università di Perugia; Italia Fil: Noris, Patrizia. Universita Degli Studi Di Pavia; Italia Fil: Falcinelli, Emanuela. Università di Perugia; Italia Fil: Melazzini, Federica. Universita Degli Studi Di Pavia.; Italia Fil: Orsini, Sara. Università di Perugia; Italia Fil: Zaninetti, Carlo. Universita Degli Studi Di Pavia.; Italia Fil: Abdul Kadir, Rezan. Haemophilia Centre And Haemostasis Unit, Royal Free Fou; Reino Unido Fil: Obeng Tuudah, Deborah. Haemophilia Centre And Haemostasis Unit, Royal Free Fou; Reino Unido Fil: Heller, Paula Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Glembotsky, Ana Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Fabris, Fabrizio. Università di Padova; Italia Fil: Rivera, Jose. Universidad de Murcia; España Fil: Lozano, Maria Luisa. Universidad de Murcia; España Fil: Butta, Nora. Hospital Universitario la Paz; España Fil: Favier, Remi. French Reference Centre For Inherited Platelet Disorder; Francia Fil: Cid, Ana Rosa. Hospital Universitario y Politecnico la Fe; España Fil: Fouassier, Marc. French Reference Centre For Inherited Platelet Disorder; Francia Fil: Podda, Gian Marco. Università degli Studi di Milano; Italia Fil: Santoro, Cristina. Università degli studi di Roma "La Sapienza"; Italia Fil: Grandone, Elvira. Casa Sollievo Della Sofferenza,s.giovanni Rotondo; Italia Fil: Henskens, Yvonne. Maastricht University Medical Centre; Países Bajos Fil: Nurden, Paquita. French Reference Centre For Inherited Platelet Disorder; Francia Fil: Zieger, Barbara. Albert Ludwigs University of Freiburg; Alemania Fil: Cuker, Adam. University of Pennsylvania; Estados Unidos Fil: Devreese, Katrien. University of Ghent; Bélgica Fil: Tosetto, Alberto. Hospital San Bortolo; Italia Fil: De Candia, Erica. Istituto Nazionale di Ricovero e Cura a Carattere Scientifico "Saverio de Bellis"; Italia Fil: Dupuis, Arnaud. French Reference Centre For Inherited Platelet Disorder; Francia Fil: Miyazaki, Koji. Kitasato University School Of Medicine; Japón Fil: Othman, Maha. Queens University; Canadá Fil: Gresele, Paolo. Università di Perugia; Italia

Poor hand-hygiene adherence endangers the safety of both healthcare workers and patients. A cross-sectional Knowledge Attitudes Practicing (KAP) survey (n= 268) and an observation of hand-hygiene compliance (n= 36) were conducted among staff in a general hospital in Syria. The aim of this study was to investigate the degree of compliance with hand hygiene protocols by general health care workers including their knowledge, attitude and practice. The mean overall observed hand-hygiene compliance rate was 45.7% (95% CI 37.1 – 54.3). Nurses were observed to have better compliance than physicians. Staff were observed to be more concerned in performing hand-hygiene after than before patient contact (before mean= 32.0%, after mean= 51.2%, p< 0.05). The questionnaire showed that there was a significant correlation between knowledge, attitude, and facilities on the one hand and poor self-reported adherence on the other. Multivariate analysis showed that poor adherence was statistically significantly associated with males (63.5%), untrained staff (58.5%) and unavailability of washing basins (60.4%). Poor adherence was high in ICU, among younger and unaware participants. Keywords : compliance, hand hygiene, hospital acquired infection, healthcare workers, Knowledge-Attituded-Practice (KAP), patient safety Abstrak Kepatuhan pada kebersihan tangan yang buruk membahayakan keselamatan tenaga kesehatan dan pasien. Survei potong lintang Pengetahuan Sikap Praktek (n= 268) dan observasi kepatuhan kebersihan tangan (n= 36) dilakukan di antara staf di rumah sakit umum di Suriah. Tujuan dari penelitian ini adalah untuk mengidentifikasi tingkat kepatuhan dengan protokol kebersihan tangan oleh tenaga kesehatan termasuk pengetahuan, sikap dan praktik mereka. Rerata tingkat kepatuhan kebersihan tangan yang diamati secara keseluruhan adalah 45,7% (95% CI 37,1-54,3). Perawat diamati memiliki kepatuhan yang lebih baik daripada dokter. Staf yang diamati tampak lebih peduli melakukan kebersihan tangan setelah kontak dengan pasien dibanding sebelum kontak (rerata sebelum= 32,0%, rerata setelah= 51,2%, p< 0,05). Hasil kuesioner menunjukkan bahwa ada korelasi yang signifikan antara pengetahuan, sikap, dan fasilitas, namun disisi lain kepatuhan dilaporkan buruk. Analisis multivariat menunjukkan bahwa kepatuhan yang buruk secara statistik terkait secara signifikan dengan jenis kelamin laki-laki (63,5%), staf tidak terlatih (58,5%) dan tidak tersedianya tempat cuci tangan (60,4%). Tingkat kepatuhan yang rendah angkanya ditemukan cukup tinggi di ICU, di antara responden yang lebih muda dan tidak sadar. Kata Kunci : kebersihan tangan, kepatuhan , hospital acquired infection, tenaga kesehatan, keselamatan pasien, Pengetahuan-Sikap-Praktik

Bromelain is a crude extract from pineapple that is known for a wide array of pharmacological effects including protein digestion, fibrinolytic and anti-immune inflammatory effects and has been popularly used as a phytotherapeutic drug. However, its clinical values and applications remain understudied. The aim of this study was to investigate the effect of bromelain on the coagulability of blood using thromboelastography (TEG). We identified 0.4 U/ml as the minimum concentration of bromelain that results in modification of a normal TEG tracing. We studied the effects of this dose on whole blood samples obtained from normal and hypercoagulable individuals using TEG and evaluated their plasma using conventional tests including prothrombin time (PT) and activated partial thromboplastin time (APTT). We extended this analysis to investigate the effect of bromelain on platelet aggregation in normal blood and on the coagulability of mice blood in vivo in response to a clinically relevant dose injected intraperitoenally. The addition of bromelain ex vivo reduced coagulability of both normal and hypercoagulable blood significantly and resulted in 47 and 22% prolongation of PT and 20 and 10% prolongation of APTT in normal and hypercoagulable samples, respectively and inhibited adenosine di-phosphate (ADP)-induced platelet aggregation by 19%. In vivo, there was a considerable variation in TEG parameters in blood obtained from mice and unexpectedly a paradoxical effect toward hypercoagulability was shown in response to 1.5 mg/kg bromelain injected intraperitoneally into seven different animals. However, these results were not statistically significant when compared with the saline-injected animals. Although the in-vitro findings in this small study indicate a potential anticoagulant effect for bromelain, this needs to be interpreted with caution as neither an oral nor intravenous routes were evaluated. The paradoxical in-vivo data following intraperitoneal administration show the complexity of the effects of bromelain beyond platelets and indicate possible effects on other cells or proteins that require further investigations.

The association between hereditary thrombophilia and venous thrombosis is well established but controversial data exist with respect to arterial thrombosis. We performed a pilot study on 31 patients with acute myocardial infarction (AMI), 21 patients with unstable angina (UA), and 20 healthy volunteers to investigate the role of various hemostatic gene polymorphisms in young Egyptian patients, who survived their first ischemic heart disease (IHD). Thrombophilic gene polymorphisms were tested using multiplex polymerase chain reaction and reverse-hybridization technique. We showed an increased risk of AMI with factor V (FV) Leiden and prothrombin G20210A heterozygosity. The increased risks of UA was associated with GA and A allele of fibrinogen β-455G→A polymorphism. Conversely, factor XIII (FXIII) Val34Leu GT and T allele were protective in the UA group. Nevertheless, the prevalence of FV H1299R, plasminogen activator inhibitor 1 4G/5G, glycoprotein IIIa C1565T, 5,10-methylenetetrahydrofolate reductase C677T, and A1298C mutations did not differ between patients with IHD and controls. The data have clinical implications regarding screening and thromboprophylaxis in high-risk individuals younger than 40 years.

The main objective of this study is to investigate the utility of International Society on Thrombosis and Haemostasis-Bleeding Assessment Tool (ISTH-BAT) in comparison with the condensed form of Molecular and Clinical Markers for the Diagnosis and Management of type 1 and WHO BATs, in assessing bleeding in two well known and clinically significant platelet function defects. Thirty-eight patients previously diagnosed with Glanzmann's thrombasthenia and 10 with Bernard-Soulier syndrome (BSS) were analyzed. Bleeding scores were significantly higher than that of controls using both electronic bleeding questionnaire (eBQ) and ISTH-BAT with no significant difference between both tools. ISTH-BAT had a sensitivity, specificity, positive predictive value and negative predictive value of 100%, 76.2%, 0.9 and 1. This was closely similar to eBQ. Both ISTH-BAT and eBQ are efficient in BSS and Glanzmann's thrombasthenia. However, given the ISTH recommendation, ISTH-BAT should be adopted. Larger study including other platelet defects will enhance its utility and support the integration of bleeding scores with standardized laboratory testing to allow for a universal diagnostic approach to patients with suspected bleeding disorders.

Pregnancy is a state of heightened coagulation, exacerbated in pathological conditions such as preeclampsia. We evaluated the role of thromboelastography (TEG), compared with standard haemostasis tests, in identifying in haemostatic alterations in normotensive pregnancies and pregnancies complicated with preeclampsia. Standard haemostasis tests and TEG were performed on 28 normotensive women and 31 with preeclampsia at delivery, 6 weeks and 6 months postpartum. Results were compared between patient groups, and at different collection times. Standard haemostasis tests failed to reveal consistent differences in haemostatic function between subject groups, mirroring the inconsistency described in the literature. TEG revealed increased coagulability in preeclampsia subjects compared with normotensive subjects at delivery. Haemostatic alterations were normalized by 6 weeks postpartum and remained stable at 6 months postpartum. TEG is superior to standard laboratory haemostatic tests in evaluating antenatal and postpartum haemostatic alterations associated with pregnancy complications such as preeclampsia.

Preeclampsia remains a major cause of maternal mortality and morbidity worldwide with increased risk for cardiovascular disease later in life. Many previous studies have examined several biomarkers including E-selectin. We aimed to assess the role of sE-selectin together with platelet count and mean platelet volume (MPV) as biomarkers for the prediction of preeclampsia.This case-control study included 85 pregnant women; 40 healthy (mean age 27.1 ± 4.8 years) and 45 with preeclampsia (mean age 26.8 ± 6.7 years), recruited at the third trimester of pregnancy and subjected to full clinical and laboratory testing. This included complete blood picture, urine analysis and plasma sE-selectin using ELISA.A significant decrease in platelet count (P = 0.003), and a significant increase in MPV (P 0.001) were seen in patients versus controls. Plasma sE-selectin levels were significantly higher in patients versus control (P = 0.002). ROC curve showed the best cut-off values for sE-selectin was 64.3 ng/mL, with 58% sensitivity 80.0% specificity. Positive predictive value was 76.5; negative predictive value was 62.7 and accuracy was 68.2 with a statically significant area under curve (P = 0.002). Platelet count, MPV and sE-selectin were significantly associated with PE in univariate analysis. In multivariate analysis, only MPV and sE-selectin were independent risk factors for PE development. Higher MPV or sE-selectin were associated with PE development (P 0.001).The simultaneous use of sE-selectin and platelet count and volume may help earlier recognition of preeclampsia and thus appropriate and more efficient therapy. Larger studies are likely to help verify data and justify wider application of these markers.

Background Hemophilia is an inherited bleeding disorder. With proper treatment and self-care, persons with hemophilia can maintain an active, productive lifestyle. Hemophilia can be mild, moderate, or severe, depending on the degree of plasma clotting factor deficiency. The aim of the study was to assess the utility of ISTH-BAT in diagnosis, determining severity of the bleeding condition in newly diagnosed and known hemophilia patients, compare the bleeding score (BS) in adult and pediatric groups and investigate its association with plasma factor levels. Methods ISTH-BAT was used to assess BS in a total of 115 patients, 78 with hemophilia A, and 37 with hemophilia B and in 100 controls. Results BS was significantly higher in HA and HB patients as compared to controls, with no significant difference between HA and HB. The BS was very similar in newly diagnosed compared to known hemophilia patients, lower in pediatric compared to adult and higher in severe compared to mild HA patients. Conclusion The ISTH BAT can help identify hemophilia patients. Therefore it is a useful tool to distinguish between affected and unaffected individuals with bleeding. Moreover, an important finding of our study is that there is no major difference between the scores in known and newly diagnosed patients.

Recent years have shown increasing interest in the use of thromboelastography (TEG) (Haemonetics, Braintree, MA) and thromboelastometry (ROTEM; Munich, Germany). These are established point‐of‐care global viscoelastic hemostatic techniques with several advantages. They use whole blood samples, which are more physiological compared with conventional plasma‐based tests, require small volumes, and provide comprehensive and real‐time data on coagulation/fibrinolysis. Many successful applications have been reported, including hepatobiliary/cardiovascular surgeries, transfusion therapy, and trauma; however, the routine use of these tests remains surprisingly low in relation to pregnancy and puerperium. [...]

Protein C global is a global dotting assay that evaluates abnormalities in the protein C anticoagulant pathway. A few studies have examined this assay in relation to assisted reproductive technology (ART), but its role in infertile women with in vitro fertilization (IVF) failure remains unclear. In this study, we assessed protein C in infertile women with a history of IVF failure who were undergoing ART. We examined 45 healthy fertile women who conceived naturally, and 45 infertile women with 2 or more implantation failures undergoing ART. Both protein C and activated protein C resistance (APC-R) were evaluated. The results showed that mean protein C expressed as a normalized ratio (PCAT-NR) was significantly lower in the study group compared to the control group (0.76 ± 0.15 vs. 0.91 ± 0.14, respectively; p = 0.0001). Follow-up on ART outcomes showed that women who failed ART had significantly lower PCAT-NR compared to successful cases. PCAT-NR did not correlate with APC-R levels in the study (r = 0.125, p < 0.5) or failed ART subgroups. Using logistic regression analysis, patients with lower PCAT-NR levels showed an elevated risk of implantation failure (p = 0.04, OR 0.50, 95% CI 0.26-0.84). In conclusion, protein C global assay may play a role in the etiology of IVF failure, which might be independent of APC-R. Larger studies are encouraged to validate these findings and explore the underlying pathophysiological mechanisms.

Deficient anticoagulant activity of annexin A5 and deficient profibrinolytic activity of annexin A2 have been linked to increased risk of thrombotic events. Placental dysfunction due to fibrin deposition/microthrombi has been implicated in the pathogenesis of pre-eclampsia (PE). In this study, we aimed to assess serum levels of annexin A5 and annexin A2 in a cohort of PE patients and investigate their role as biomarkers for the development of the disease. We examined 80 women in total; 40 healthy pregnant women and 40 pregnant women with PE after 20weeks of pregnancy. Women were subjected to full clinical assessment, ultrasonography, and laboratory testing including complete blood picture, liver and kidney function tests and assessment of serum and urine proteins. Annexin A5 and annexin A2 were analyzed using enzyme-linked immunosorbent assay. The study showed serum annexin A2 but not annexin A5 was significantly reduced (P=0.029) in women with PE (total and severe cases) compared to those with normal pregnancy. The ROC analysis of annexin A2 level for the prediction of development of PE showed an area under the curve of 0.64 (P=0.029), and the best cut-off value was 0.89ng/ml with a sensitivity of 70.0% and a specificity of 70.0%. Univariate analysis showed annexin A2 of

In this report, we provide evidence of an acquired von Willebrand syndrome (AVWS) with a type 2B phenotype rather than the expected type 1 or 2A. The patient was referred prior to surgical removal of a fibrous mass within the maxillary sinus. His first bleeding 7 years earlier following a retinal tear had been complicated by monocular blindness. Several mucocutanous bleedings followed. Hematological investigations revealed von Willebrand factor (VWF):Ag 91 IU/ml, factor VIII 86 IU/ml, VWF:RCo 34 IU/ml and profound thrombocytopenia with platelet clumping. VWF multimer analysis showed a loss of high-molecular-weight multimers and his plasma aggregated normal platelets under low ristocetin concentration, consistent with type 2B von Willebrand disease (VWD). Sequencing of VWF exon 28 and of the platelet GP1BA gene to investigate the possibility of platelet-type VWD failed to reveal mutations. Serum protein electrophoresis showed a monoclonal IgG protein and led to the diagnosis of monoclonal gammopathy of unknown significance (MGUS), raising suspicion of an AVWS. Over 2 years, he experienced severe gingival bleedings and traumatic intracerebral hemorrhage. Following debridement of the sinus mass, the patient required 20 units of packed red blood cells, despite high-dose Humate-P, continuous Amicar and twice-daily platelet transfusions. Bleeding finally ceased following infusion of activated factor VIIa. A history of prior uncomplicated vasectomy and tendon laceration, no family history of bleeding, the inability to identify a causative mutation in either exon 28 VWF or platelet GP1BA and the MGUS led to diagnosis of AVWS with a type 2B phenotype. This case highlights the difficulties in assigning a diagnosis and the management of bleeding in a patient with an atypical presentation of AVWS.

Although animals housed for research purposes are strictly monitored for lighting, temperature, and humidity, the acoustic environment receives less attention. In a retrospective study, we investigated the effect of construction-induced noise on coagulation using thromboelastography in a group of healthy control rats. Animals were unintentionally exposed to noise due to construction in the vicinity of the animal care facility where these rats were housed. We compared the results to those of age-, gender-matched nonexposed rats. There was a significant shortening of the reaction (R) time ( P = .009) and a trend toward an increase in coagulation index (CI; P = .09), indicating hypercoagulability. The short R time and increase in CI were correlated with an elevated plasma cortisol and corticosterone, indicating that the hypercoagulability seen in these rats is stress induced. Noise is a stress factor for which animals need to be monitored, particularly if those animals are selected as controls for hemostasis studies.

Despite the increased worldwide awareness, over the last decade, of the platelet-type von Willebrand Disease (PT-VWD), many uncertainties remain around this rare platelet bleeding disorder. This report aims to correctly identify and study the phenotype of new patients and highlights the diagnostic and therapeutic challenges this disease remains to pose. We describe four PT-VWD cases confirmed by genetic analysis in which either the diagnosis and/or the treatment posed challenge. We provide the details of the clinical presentation, laboratory analysis, and the treatment and the responses in each case. We show that in addition to type 2B VWD, PT-VWD can be misdiagnosed as idiopathic thrombocytopenic purpura, neonatal alloimmune thrombocytopenia, and unexplained gestational thrombocytopenia. The disease can be diagnosed as early as 1 year of age and with phenotypically normal parents. Bleeding in some patients can be managed successfully using Humate P and DDAVP combined with tranexamic acid with no significant thrombocytopenia. We provide for the first time an evidence of an efficient response to rFVIIa in PT-VWD. Anaphylactic reaction to VWF preparations may be related to PT-VWD and the development of HLA antibodies is not uncommon. Progressive thrombocytopenia with normal VWF levels can be seen with PT-VWD and the platelet count was normalized at 2.5 weeks postpartum in one case. We conclude that these studies represent a record of clinical observations/interventions that help improve diagnoses/management of PT-VWD, highlight the variations in age and clinical presentations, laboratory diagnostic approaches, the importance of genetic testing for accurate diagnosis and consideration of therapeutic alternatives. Fil: Sánchez Luceros, Analía Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; Argentina Fil: Woods, Adriana Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Bermejo, Emilse. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; Argentina Fil: Shukla, Shilpa. Academia Nacional de Medicina de Buenos Aires; Argentina Fil: Acharya, Suchitra. Cohen's Children Medical Center of New York; Estados Unidos Fil: Lavin, Michelle. St. James Hospital; Irlanda Fil: Rydz, Natalia. University of Calgary; Canadá Fil: Othman, Maha. Queens University; Canadá

Inherited bleeding, thrombotic and platelet disorders (BPDs) are diseases affecting approximately 300 individuals per million births. With the exception of haemophilia and von Willebrand disease patients, a molecular analysis for patients with a BPD is often unavailable. Many specialised tests are usually required to reach a putative diagnosis and they are typically performed in a step-wise manner to control costs. This approach causes delays and a conclusive molecular diagnosis is often never reached which can compromise treatment and impede rapid identification of affected relatives. To address this unmet diagnostic need, we designed a high-throughput sequencing (HTS) platform targeting 63 genes relevant for BPDs. The platform can call single nucleotide variants (SNVs), short insertions/deletions (indels) and large copy number variants (CNVs), though not inversions, which are subjected to automated filtering for diagnostic prioritization, resulting in an average of 5.34 candidate variants per individual. We sequenced 159 and 137 samples respectively from cases with and without previously known causal variants. Among the latter group, 61 cases had clinical and laboratory phenotypes indicative of a particular molecular etiology while the remainder had ana priorihighly uncertain etiology. All previously detected variants were recapitulated and, when the etiology was suspected but unknown or uncertain, a molecular diagnosis was reached in 56 of 61 and only eight of 76 cases, respectively. The latter category highlights the need for further research into novel causes of BPDs. The ThromboGenomics platform thus provides an affordable DNA-based test to diagnose patients suspected of having a known inherited BPD.

SummaryInflammation-associated foetal loss is often linked to maternal coagulopathies. Here, we characterised the role of maternal inflammation in the development of various systemic maternal coagulopathies and foetal death during mid-to-late gestation in rats. Since nitric oxide (NO) functions as an inhibitor of platelet aggregation and antioxidant, we also tested whether the NO mimetic nitroglycerin (glyceryl trinitrate, GTN) prevents inflammation-associated coagulopathies and foetal death. To induce chronic inflammation, pregnant Wistar rats were injected with low-doses of lipopolysaccharide (LPS; 10–40 μg/kg) on gestational days (GD) 13.5–16.5. To determine whether the effects of inflammation are mediated by tumour necrosis factor-α (TNF-α), the TNF-α inhibitor etanercept was injected on GD 13.5 and 15.5. Controls consisted of rats injected with saline. GTN was administered to LPS-treated rats via daily application of a transdermal patch on GD 12.5–16.5. Using thromboelastography (TEG), various coagulation parameters were assessed on GD 17.5; foetal viability was determined morphologically. Reference coagulation parameters were established based on TEG results obtained from control animals. LPS-treated rats exhibited distinct systemic coagulopathies: hypercoagulability, hypocoagulability, hyperfibrinolysis, and disseminated intravascular coagulation (DIC) stages I and III. A specific foetal death coagulation phenotype was observed, implicating TEG as a potential tool to identify inflammation-induced haemostatic alterations associated with pregnancy loss. Treatment with etanercept reduced the incidence of coagulopathy by 47%, while continuous delivery of GTN prevented foetal death and the inflammation-induced coagulopathies. These findings provide a rationale for investigating the use of GTN in the prevention of maternal coagulopathies and inflammation-mediated foetal death.

Platelet-type von Willebrand disease (PT-VWD) is an autosomal dominant rare bleeding disorder characterized by hyperresponsive platelets. This inherent platelet function defect is due to a gain-of-function mutation within the GP1BA gene coding for the platelet surface glycoprotein Ib alpha protein, the receptor for the adhesive protein von Willebrand factor (VWF). The defect results in excessive and unnecessary platelet-VWF interaction with subsequent removal of the hemostatically efficient high molecular weight VWF as well as platelets from the circulation, leading to thrombocytopenia and bleeding diathesis. Patients with PT-VWD present with mild to moderate mucocutaneous bleeding, which becomes more pronounced during pregnancy and following aspirin ingestion or drugs that have antiplatelet activity. Laboratory testing shows low VWF:ristocetin cofactor and low or normal VWF:antigen and characteristically an enhanced ristocetin-induced platelet agglutination (RIPA). These laboratory features are also indicators of the closely similar and more common bleeding disorder type 2B VWD. Simplified RIPA mixing assays, cryoprecipitate challenge, and flow cytometry can differentiate between the two disorders. However, the gold standard is to identify mutations within the VWF gene (indicating type 2B VWD) or the platelet GP1BA gene (confirming PT-VWD). Treatment is based on making a correct diagnosis of PT-VWD where platelet concentrates instead of VWF/factor VIII preparations should be administered. A recent fairly large retrospective/prospective registry-based international study showed that PT-VWD is very rare, likely to be misdiagnosed as type 2B VWD or idiopathic thrombocytopenic purpura, and represents 15% of type 2B VWD diagnoses.

Laboratory evaluation of bleeding disorders has been performed with the standard clotting assays such as the PT and PTT for several decades. Our improved understanding of the process of blood coagulation has now revealed the important role played by the cellular elements such as platelets, monocytes and red blood cells. The need for a test that can assess clotting in a more 'global' manner, beyond the initiation of clot formation, has led to greater interest in assays such as thrombin generation and thromboelastography. Even though there are several publications using thromboelastography it remains a research tool as the methodology is not standardized. In an attempt to show reproducibility and consistency using thromboelastography, a group of investigators from different countries joined hands to form the TEG-ROTEM Working Group. Two studies were performed using PRP and FVIII deficient plasma and an intrinsic pathway activator. This article summarizes the results of the first international effort at standardization of thromboelastography. Both of the instruments using this technology (TEG(®) and ROTEM(®)) were used. Nine laboratories from countries around the globe participated in this effort. The results showed a significant inter-laboratory variance with CV's greater than 10%. Although these results were not satisfactory, this has been the first effort to standardize this methodology and significant work remains to be done to improve reliability and reproducibility. These studies were performed on PRP and the results may be more reliable when preformed on whole blood samples. We believe that it is important to continue this work so that we may investigate the usefulness and potential applications of thromboelastography in the evaluation of bleeding and thrombosis.