Managing the coagulopathy of postpartum hemorrhage: an evolving role for viscoelastic hemostatic assays.

Postpartum hemorrhage (PPH) is usually caused by obstetrical complications but may be exacerbated by hemostatic impairment. Standard laboratory tests of coagulation often take too long to become available to inform treatment in a rapidly changing clinical situation. The role of point-of-care viscoelastic hemostatic assays (VHAs) in monitoring hemostatic impairment and guiding procoagulant blood product replacement during PPH is evolving, although these technologies are not available in most maternity units. We have used VHAs during PPH in our institution for the last 8 years and have developed a simple algorithm to direct blood component replacement. VHAs are useful for reassuring clinicians that hemostasis is adequate and that procoagulant blood products are not required and an obstetrical cause for bleeding needs to be sought. VHAs can be used to detect hypofibrinogenemia due to dilution or acute obstetrical coagulopathy and to guide fibrinogen replacement. The role of VHAs in guiding fresh frozen plasma infusion is less clear, but normal results suggest that fresh frozen plasma is not required. In this review, we describe 3 cases of postpartum hemorrhage to illustrate different hemostatic scenarios and discuss the controversies and evidence gaps related to each case.

Acute obstetric coagulopathy during postpartum hemorrhage is caused by hyperfibrinolysis and dysfibrinogenemia: an observational cohort study.

BACKGROUND: Postpartum hemorrhage (PPH) may be exacerbated by hemostatic impairment. Information about PPH-associated coagulopathy is limited, often resulting in treatment strategies based on data derived from trauma studies. OBJECTIVES: To investigate hemostatic changes associated with PPH. PATIENTS/METHODS: From a population of 11 279 maternities, 518 (4.6%) women were recruited with PPH ≥ 1000 mL or placental abruption, amniotic fluid embolism, or concealed bleeding. Routine coagulation and viscoelastometric results were collated. Stored plasma samples were used to investigate women with bleeds > 2000 mL or those at increased risk of coagulopathy defined as placenta abruption, amniotic fluid embolism, or need for blood components. Procoagulant factors were assayed and global hemostasis was assessed using thrombin generation. Fibrinolysis was investigated with D-dimer and plasmin/antiplasmin complexes. Dysfibrinogenemia was assessed using the Clauss/antigen ratio. RESULTS: At 1000 mL blood loss, Clauss fibrinogen was ≤2 g/L in 2.4% of women and 6/27 (22.2%) cases of abruption. Women with very large bleeds (>3000 mL) had evidence of a dilutional coagulopathy, although hemostatic impairment was uncommon. A subgroup of 12 women (1.06/1000 maternities) had a distinct coagulopathy characterized by massive fibrinolysis (plasmin/antiplasmin > 40 000 ng/mL), increased D-dimer, hypofibrinogenemia, dysfibrinogenemia, reduced factor V and factor VIII, and increased activated protein C, termed acute obstetric coagulopathy. It was associated with fetal or neonatal death in 50% of cases and increased maternal morbidity. CONCLUSIONS: Clinically significant hemostatic impairment is uncommon during PPH, but a subgroup of women have a distinct and severe coagulopathy characterized by hyperfibrinolysis, low fibrinogen, and dysfibrinogenemia associated with poor fetal outcomes.

Are we asking the right questions? Working with the LGBTQ+ community to prioritise healthcare research themes.

BACKGROUND: Conversations about research priorities with members of the public are rarely designed specifically to include people who identify as Lesbian, Gay, Bisexual, Transgender and Queer (LGBTQ+) and are not researchers. METHODS: Generally, to address this gap, and specifically, to inform future research for CLS, we carried out a rapid review of published research priority sets covering LGBTQ+ topics, and an online workshop to prioritise identified themes. RESULTS: Rapid review: results. The rapid review identified 18 LGBTQ+ research priority sets. Some focussed on specific populations such as women or men, younger or older people or people living within families. Five addressed transgender and gender non- conforming populations. All of the research priority sets originated from English-speaking, high and middle-income countries (UK, US, Canada, and Australia), and date from 2016 onwards. Prioritization approaches were wide-ranging from personal commentary to expert workshops and surveys. Participants involved in setting priorities mostly included research academics, health practitioners and advocacy organisations, two studies involved LGBTQ+ public in their process. Research priorities identified in this review were then grouped into themes which were prioritised during the workshop. Workshop: results. For the workshop, participants were recruited using local (Cambridge, UK) LGBTQ+ networks and a national advert to a public involvement in research matching website to take part in an online discussion workshop. Those that took part were offered payment for their time in preparing for the workshop and taking part. Participants personal priorities and experiences contributed to a consensus development process and a final ranked list of seven research themes and participants' experiences of healthcare, mental health advocacy, care homes, caring responsibilities, schools and family units added additional context. CONCLUSIONS: From the workshop the three research themes prioritised were: healthcare services delivery, prevention, and particular challenges / intersectionality of multiple challenges for people identifying as LGBTQ+. Research themes interconnected in many ways and this was demonstrated by the comments from workshop participants. This paper offers insights into why these priorities were important from participants' perspectives and detail about how to run an inclusive and respectful public involvement research exercise. On a practical level these themes will directly inform future research direction for CLS.

Conversations about research priorities with members of the public who identify as Lesbian, Gay, Bisexual, Transgender and Queer (LGBTQ+) and are not researchers are not common.We reviewed published research priorities covering LGBTQ+ topics and held an online workshop. The review identified 18 LGBTQ+ research published priority sets. Some focussed on specific populations such as women or men, younger or older people or people living within families. Five were on transgender and gender non- conforming populations. Priorities were achieved by different methods such as workshops and surveys. People involved in setting priorities mostly included researchers, health practitioners and advocacy organisations, two studies involved LGBTQ+ public in their process. Research priorities identified in the review were grouped into themes which were prioritised during the workshop.For the online workshop, participants were recruited using local (Cambridge, UK) LGBTQ+ networks and a national advert and offered payment for their time. Participants personal priorities and experiences contributed to agreeing a final list of seven research themes in priority order. Participants' experiences of healthcare, mental health advocacy, care homes, caring responsibilities, schools and family units were helpful.From the workshop the three top research themes were: healthcare services delivery, prevention, and particular and multiple challenges of people identifying as lesbian, gay, bisexual, transgender or queer. Research themes interconnected in many ways as shown by the comments from workshop participants. This paper describes why these priorities were important from participants' perspective and offers information about how to run an inclusive and respectful public involvement research exercise.

Evolution of an Eurasian avian-like influenza virus in naïve and vaccinated pigs.

Influenza viruses are characterized by an ability to cross species boundaries and evade host immunity, sometimes with devastating consequences. The 2009 pandemic of H1N1 influenza A virus highlights the importance of pigs in influenza emergence, particularly as intermediate hosts by which avian viruses adapt to mammals before emerging in humans. Although segment reassortment has commonly been associated with influenza emergence, an expanded host-range is also likely to be associated with the accumulation of specific beneficial point mutations. To better understand the mechanisms that shape the genetic diversity of avian-like viruses in pigs, we studied the evolutionary dynamics of an Eurasian Avian-like swine influenza virus (EA-SIV) in naïve and vaccinated pigs linked by natural transmission. We analyzed multiple clones of the hemagglutinin 1 (HA1) gene derived from consecutive daily viral populations. Strikingly, we observed both transient and fixed changes in the consensus sequence along the transmission chain. Hence, the mutational spectrum of intra-host EA-SIV populations is highly dynamic and allele fixation can occur with extreme rapidity. In addition, mutations that could potentially alter host-range and antigenicity were transmitted between animals and mixed infections were commonplace, even in vaccinated pigs. Finally, we repeatedly detected distinct stop codons in virus samples from co-housed pigs, suggesting that they persisted within hosts and were transmitted among them. This implies that mutations that reduce viral fitness in one host, but which could lead to fitness benefits in a novel host, can circulate at low frequencies.

Experimental transmission of avian-like swine H1N1 influenza virus between immunologically naïve and vaccinated pigs.

BACKGROUND: Infection of pigs with swine influenza has been studied experimentally and in the field; however, little information is available on the natural transmission of this virus in pigs. Two studies in an experimental transmission model are presented here, one in immunologically naïve and one in a combination of vaccinated and naïve pigs. OBJECTIVES: To investigate the transmission of a recent 'avian-like' swine H1N1 influenza virus in naive piglets, to assess the antibody response to a commercially available vaccine and to determine the efficiency of transmission in pigs after vaccination. METHODS: Transmission chains were initiated by intranasal challenge of two immunologically naïve pigs. Animals were monitored daily for clinical signs and virus shedding. Pairs of pigs were sequentially co-housed, and once virus was detected in recipients, prior donors were removed. In the vaccination study, piglets were vaccinated and circulating antibody levels were monitored by haemagglutination inhibition assay. To study transmission in vaccinates, a pair of infected immunologically naïve animals was co-housed with vaccinated recipient pigs and further pairs of vaccinates were added sequentially as above. The chain was completed by the addition of naive pigs. RESULTS AND CONCLUSIONS: Transmission of the H1N1 virus was achieved through a chain of six pairs of naïve piglets and through four pairs of vaccinated animals. Transmission occurred with minimal clinical signs and, in vaccinates, at antibody levels higher than previously reported to protect against infection.