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Background: Several studies reported the role platelet activation, platelet volume (MPV) and other Indices in breast cancer but the data is inconsistent and/or diverse. The aim of this study was to systematically evaluate the role of platelet activation and platelet volume indices in women with BC as predictors for cancer progression and poor prognosis. Methods: Patients were recruited from our local oncology center between 2019 to 2020 following ethics approval. 80 patients with locally invasive BC, 20 metastatic and 100 controls were recruited. ADP-induced platelet activation was assessed by light-transmission aggregometry. Platelet P-selectin (CD62P) expression with and without ADP stimulation was assessed by flow cytometry. A comprehensive analysis of platelet count and platelet volume indices (PVIs) (MPV, PDW, MPV/P and PDW/P) was conducted. Data were analyzed in relation to tumor pathology, hormone receptors (ER, PR, HER-2) and proliferation index Ki-67. Regression analyses were conducted for the prediction of poor prognosis, tumor aggression and metastatic potential. Results: We found a significant increase in platelet aggregation (MA), CD62P expression, CD62P+ADP, MPV, PDW, MPV/P and PDW/P in the metastatic group compared to the locally invasive group. Univariate regression analysis showed significance for ADP, MA, CD62P+ADP, MPV and PDW/P. Conclusion: MPV/P and PDW/P can be used as simple low-cost predictors for cancer progression and poor prognosis. We conclude platelet activation and specific platelet indices can help predict prognosis in females with BC.

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.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) has been reported in association with the coronavirus disease 2019 preventative adenovirus vector-based vaccines ChAdOx1 nCoV-19 (Oxford/AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson) in hundreds of recipients across the globe. VITT is characterized by thrombosis, typically at unusual sites, low fibrinogen, and elevated plasma D-dimer, generally manifesting between 4 and 28 days following vaccination. Detection of anti-platelet factor antibodies using an enzyme-linked immunosorbent assay (ELISA) is often confirmatory. Although several similar principles subside in most diagnostic criteria for VITT, the presentation of a positive ELISA assay, use of expert hematology and neurology opinion, and exclusion of possible VITT cases outside the “standard” 4 to 28-day timeframe have contributed a lack of global standardization for defining VITT. Accordingly, the global and regional incidence of VITT differs according to the diagnostic pathway and case definition used. This has influenced the public perception of VITT's severity and the decision to use adenovirus vector-based vaccines for limiting severe acute respiratory syndrome coronavirus 2 infection. We hereby delineate the recognized pathogenic mechanisms, global incidence, discrepancies in diagnostic criteria, recommended treatments, and global implications to vaccine hesitancy from this coagulopathy.

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.

Thrombosis is one of the leading causes of death in cancer. Cancer-induced hypercoagulable state contributes to thrombosis and is often overlooked. Prostate cancer may not be of high thrombogenic potential compared with other cancers, but its high prevalence brings it into focus. Pathological evidence for venous thromboembolisms (VTEs) in prostate cancer exists. Factors such as age, comorbidities, and therapies increase the VTE risk further. There is a need to systematically identify the risk of VTE in regard to patient-, cancer-, and treatment-related factors to risk stratify patients for better-targeted and individualized strategies to prevent VTE. Sensitive tests to enable such risk assessment are urgently required. There is sufficient evidence for the utility of thromboelastography (TEG) in cancer, but it is not yet part of the clinic and there is only limited data on the use of TEG in prostate cancer. One study revealed that compared with age-matched controls, 68.8% of prostate cancer patients demonstrated hypercoagulable TEG parameters. The absence of clinical guidelines is a limiting factor in TEG use in the cancer population. Cancer heterogeneity and the unique cancer-specific microenvironment in each patient, as well as determining the hypercoagulable state in each patient, are added limitations. The way forward is to combine efforts to design large multicenter studies to investigate the utility and clinical effectiveness of TEG in cancer and establish longitudinal studies to understand the link between hypercoagulable state and development of thrombosis. There is also a need to study low thrombogenic cancers as well as high thrombogenic ones. Awareness among clinicians and understanding of test applicability and interpretation are needed. Finally, expert discussion is critical to identify the investigation priorities.

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.

Coxsackie Virus and Adenovirus Receptor (CXADR or CAR) is involved in the pathogenesis of inflammatory dilated cardiomyopathy (DCM). We aimed to examine the relationship of CAR expression on platelets and cardiomyocytes with virus persistence, local and systemic inflammation and platelet activity in patients with DCM.Endomyocardial biopsy (EMB) samples of 38 patients (mean age 39.5±11.3 years, 20 male) with DCM were analyzed for CAR expression, local inflammation grade by immunohistochemistry and virus persistence by real-time PCR. Platelet morphology was analyzed in all patients and 30 healthy subjects (HS) using scanning electron microscopy, platelet activity by light transmission aggregation, and CAR persistence by immunofluorescence. Platelets of 20 patients were analyzed for cytomegalovirus and herpes simplex virus 1-2 by immunofluorescence. Serum levels of tumor necrosis factor alpha (TNF α) and Interleukin-6 were assessed using ELISA in all studied subjects.CAR expression in EMB samples was related to the heart failure functional class and the level of IL-6. Platelets from DCM patients showed enhanced spontaneous and ADP induced aggregation. Platelets' CAR expression was4 fold higher in DCM than HS and was observed predominantly at sites of intercellular communications in microaggregates and leukocyte-platelet aggregates. CAR-positive patients showed significantly higher TNF-α and IL-6 serum levels in CAR-negative patients. Platelets of 6 (30%) DCM patients revealed the mature cytomegalovirus and herpes simplex viruses particles.Tight junction protein CAR may serve as a docking pin creating a new type of contact structure that could be responsible for signaling between neighboring cells in pathological conditions.

BackgroundCoxsackie-adenovirus receptor (CAR) is involved in the pathogenesis of inflammatory dilated cardiomyopathy (DCM). We aimed to examine the relationship of CAR expression on platelets and cardiomyocytes with virus persistence, local and systemic inflammation and platelet activity in patients with DCM. MethodsEndomyocardial biopsy (EMB) samples of 38 patients (mean age 39.5±11.3 years, 20 male) with DCM were analyzed for CAR expression, local inflammation grade by immunohistochemistry and virus persistence by real-time PCR. Platelet morphology was analyzed in all patients and 30 healthy subjects (HS) using scanning electron microscopy, platelet activity by light transmission aggregation, and CAR persistence by immunofluorescence. Platelets of 20 patients were analyzed for cytomegalovirus and herpes simplex virus 1-2 by immunofluorescence. Serum levels of tumor necrosis factor alpha (TNF α) and Interleukin-6 were assessed using ELISA in all studied subjects.Results:CAR expression in EMB samples was related to the heart failure functional class and the level of IL-6. Platelets from DCM patients showed enhanced spontaneous and ADP induced aggregation. Platelets’ CAR expression was >4 fold higher in DCM than HS and was observed predominantly at sites of intercellular communications in microaggregates and leukocyte-platelet aggregates. CAR-positive patients showed significantly higher TNF-α and IL-6 serum levels in CAR-negative patients. Platelets of 6 (30%) DCM patients revealed the mature cytomegalovirus and herpes simplex viruses particles. ConclusionTight junction protein CAR may serve as a docking pin creating a new type of contact structure that could be responsible for signaling between neighboring cells in pathological conditions.

Severe congenital protein C deficiency (SCPCD) is rare and there is currently substantial variation in the management of this condition. A joint project by three Scientific and Standardization Committees of the ISTH: Plasma Coagulation Inhibitors, Pediatric/Neonatal Thrombosis and Hemostasis, and Women's Health Issues in Thrombosis and Hemostasis, was developed to review the current evidence and help guide on diagnosis and management of SCPCD. We provide a summary of the clinical presentations, differential diagnoses, appropriate investigations to confirm the diagnosis, approaches for management of the acute situation, and options for long-term management including subsequent pregnancies. We finally provide a set of recommendations to help in this regard.

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.

Thromboembolic disease is one of the major causes of mortality and morbidity in pregnancy and the puerperium, with 1 death per 100 000 births attributed to venous thromboembolism (VTE). Factors associated with development of thrombosis are all present in pregnancy, with some of these changes seen from conception.Given how common early pregnancy loss is, the aim of this review is to evaluate the uncertainty surrounding the risk of VTE following early pregnancy loss and termination of pregnancy.A structured literature search was conducted to identify existing evidence as well as international pregnancy-specific guidelines regarding assessment and prevention of VTE risk in pregnant women. This review was reviewed, critiqued, and approved by all members of the International Society on Thrombosis and Haemostasis subcommittee for Women's Health Issues in Thrombosis and Haemostasis.Four published original research studies, one clinical comment paper, and six guidelines were reviewed. Despite clear evidence of the increased risk of VTE in pregnancy, there is a lack of guidance regarding evaluation and management after early pregnancy loss.International collaborative research to determine the risk of VTE and its prevention in women undergoing surgical termination of pregnancy or following surgical management of early pregnancy loss is urgently needed. Pregnancy-specific risk assessment taking into account preexisting risk factors is advocated. Education of health care professionals involved in early pregnancy care and guidance on management, albeit based on limited existing evidence, are necessary to highlight the need for individualized care.

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.