Sue Pavord

Use of recombinant activated factor VII in primary postpartum hemorrhage - The northern European registry 2000-2004

OBJECTIVE: To collect data from nine European countries for cases of obstetric hemorrhage between 2000 and 2004 in which recombinant activated factor VII (rFVIIa) was used. METHODS: The cases were identified through national surveys. Standardized case report forms included sociodemographic details, past medical and obstetric history, and details of the progress and management of labor in which the postpartum hemorrhage occurred. Clinicians were asked to describe subjectively the effect of rFVIIa administration using two mutually exclusive categories: 1) bleeding reduced or 2) bleeding unchanged or worse. RESULTS: A total of 113 forms were returned (88%) with 97 (86%) classified as treatment, and 16 (14%) as “secondary prophylaxis.” Clinicians noted improvements after a single dose for 80% of women in the treatment group, and for 75% in the secondary “prophylaxis” group. However, rFVIIa failed in 15 cases (13.8%). Few serious adverse events were noted related to rFVIIa administration; there were four cases of thromboembolism, one myocardial infarction, and one skin rash. CONCLUSION: Clinical reports and hematologic data suggest improvement for more than 80% of women after rFVIIa administration and few adverse effects. LEVEL OF EVIDENCE: II

Whole exome sequencing identifies genetic variants in inherited thrombocytopenia with secondary qualitative function defects

Inherited thrombocytopenias are a heterogeneous group of disorders characterized by abnormally low platelet counts which can be associated with abnormal bleeding. Next-generation sequencing has previously been employed in these disorders for the confirmation of suspected genetic abnormalities, and more recently in the discovery of novel disease-causing genes. However its full potential has not yet been exploited. Over the past 6 years we have sequenced the exomes from 55 patients, including 37 index cases and 18 additional family members, all of whom were recruited to the UK Genotyping and Phenotyping of Platelets study. All patients had inherited or sustained thrombocytopenia of unknown etiology with platelet counts varying from 11×109/L to 186×109/L. Of the 51 patients phenotypically tested, 37 (73%), had an additional secondary qualitative platelet defect. Using whole exome sequencing analysis we have identified “pathogenic” or “likely pathogenic” variants in 46% (17/37) of our index patients with thrombocytopenia. In addition, we report variants of uncertain significance in 12 index cases, including novel candidate genetic variants in previously unreported genes in four index cases. These results demonstrate that whole exome sequencing is an efficient method for elucidating potential pathogenic genetic variants in inherited thrombocytopenia. Whole exome sequencing also has the added benefit of discovering potentially pathogenic genetic variants for further study in novel genes not previously implicated in inherited thrombocytopenia.

How I treat postpartum hemorrhage

Worldwide, ∼800 women die every day from preventable causes related to pregnancy or childbirth. The single most common cause is severe bleeding, which can kill a healthy woman within hours if care is substandard or delayed. Improved antenatal practices have led to the early identification of at-risk women and modern technology and new techniques have enabled effective management strategies so that now, in the western world, most of the morbidity and mortality arises from those cases which occur unexpectedly and could not have been predicted. Prompt and effective management and multidisciplinary involvement is paramount to save the lives of these women. We use a case report to illustrate and discuss the main elements of management of this condition.

The effects of folic acid supplements on coagulation status in pregnancy

Thromboembolic disease remains the leading cause of maternal death in the UK. Recent literature has proposed that folate status is a strong predictor for venous thrombosis. Using thrombelastography (TEG®), we tested the hypothesis that folic acid supplementation is associated with a reduction in whole blood coagulability. Blood samples and questionnaire data were obtained at a mean gestation of 13·6 weeks (SD: 3·8, range: 6–38 weeks) from unselected consecutive women attending for their antenatal booking scan. Of 588 patients, 439 (74·7%) took folic acid. All TEG® parameters were less hypercoagulable in women that had taken folic acid compared with those that had not: mean maximum amplitude (MA) 60·3 versus 62·1; mean difference 1·8; 95% confidence interval 0·8, 2·8; P = 0·0001; mean coagulation index (CI) 0·54 versus 0·85; mean difference 0·31; 95% confidence interval 0·11, 0·5; P = 0·002. There was no difference in the incidence of the homozygous MTHFR mutation in patients taking folic acid (5·53%) compared with those that were not (4·08%). This study suggests that benefit may be derived from longer‐term treatment, although large multicentre studies are required to determine whether the relative hypocoagulability is associated with a reduction in risk of venous thrombosis.

HYdroxychloroquine to Improve Pregnancy Outcome in Women with AnTIphospholipid Antibodies (HYPATIA) Protocol: A Multinational Randomized Controlled Trial of Hydroxychloroquine versus Placebo in Addition to Standard Treatment in Pregnant Women with Antiphospholipid Syndrome or Antibodies

Women with antiphospholipid antibodies (aPL) are at risk of adverse pregnancy outcomes, including recurrent first-trimester pregnancy loss and late pregnancy complications such as preeclampsia, HELLP (hemolysis, elevated liver enzyme levels, and low platelet levels) syndrome, premature delivery, intrauterine growth restriction, placental abruption, and intrauterine death. Current standard care in obstetric antiphospholipid syndrome includes aspirin and heparin and has resulted in live-birth rates of approximately 70%. However, 30% continue to have pregnancy complications. Hydroxychloroquine (HCQ) is suggested as a new treatment approach, but no randomized controlled trials (RCTs) have assessed its efficacy. This study aims to assess pregnancy outcome in women with aPL treated with HCQ versus placebo in addition to standard treatment. The HYdroxychloroquine to improve Pregnancy outcome in women with AnTIphospholipid Antibodies (HYPATIA) study is a phase IV multicenter RCT, in which pregnant women with persistent aPL will receive either HCQ or placebo in addition to their usual medication. The primary endpoint is a composite of aPL-related adverse pregnancy outcomes: one or more pregnancy loss(es) (either   10 weeks of gestation) and premature birth before 34 weeks due to any of the following preeclampsia, eclampsia, or recognized features of placental insufficiency. The HYPATIA study is expected to provide evidence on the effect of HCQ in pregnant women with persistent aPL.

Severe primary autoimmune thrombocytopenia in pregnancy: a national cohort study

To quantify the incidence of severe autoimmune thrombocytopenia (ITP) in pregnancy in the UK, determine current treatment strategies, and establish maternal and neonatal morbidity and mortality associated with severe ITP in pregnancy.

Authors’ reply re: Severe Primary Autoimmune Thrombocytopenia (ITP) in Pregnancy: a national cohort study

and a platelet count <30 9 10/l (33.3%). We found that the decision to start treatment was not consistent with international guidelines in 33% of pregnancies (platelets >30 9 10/l; no bleeding; not to allow spinal analgesia). In conclusion and as described by Care et al., ITP can be active during pregnancy but with a low morbidity for mothers and neonates. However, we found a lower rate of postpartum haemorrhage without explanation. We also agree asymptomatic patients may be over-treated (33% in our cohort) and we need to integrate for each patient data such as history of ITP, patient activity and education to decide whom should be treated.&

The use of viscoelastic haemostatic assays in the management of major bleeding: A British Society for Haematology Guideline

Nicola S. Curry, Ross Davenport, Sue Pavord, Susan V. Mallett, Dianne Kitchen, Andrew A. Klein, Helena Maybury, Peter W. Collins and Mike Laffan Department of Haematology, Oxford University Hospitals NHS Foundation Trust, NIHR BRC, Blood Theme, Oxford University, Oxford, Centre for Trauma Sciences, Blizard Institute, Queen Mary University of London, Department of Anaesthesia, Royal Free London NHS Foundation Trust, London, UK NEQAS for Blood Coagulation, Sheffield, Department of Anaesthesia and Intensive Care, Royal Papworth Hospital, Cambridge, Department of Obstetrics, Leicester Royal Infirmary, Leicester, Department of Haematology, School of Medicine, Cardiff University, Cardiff, and Department of Haematology, Imperial College and Hammersmith Hospital, London, UK

Whole exome sequencing in patients with inherited thrombocytopenia and excessive bleeding is an efficient way to identify genetic variants in known and novel genes

Reference EPFL-CONF-212539doi:10.1111/jth.12993View record in Web of Science Record created on 2015-09-28, modified on 2017-05-12