Venous thromboembolism and acute myeloid leukemia: risk factors and mortality in elderly white, black and Asian patients.

Risk factors for venous thromboembolism (VTE) in elderly patients with acute myeloid leukemia (AML) are not known by race. The aim of this study was to determine the association of VTE with known risk factors and the impact of VTE on mortality in elderly white, black and Asian patients with AML. The merged SEER-Medicare database (2000-2015) was used for patients aged at least 65 years diagnosed with AML. Multivariable logistic regression was used to examine the association of VTE with known risk factors and Cox proportional hazards regression was used to evaluate the association of VTE with mortality in white, black and Asian patients. Among 21 403 AML patients aged at least 65years, VTE was diagnosed in 10.6% of 18 731 white patients, 13.4% of 1362 black and 5.6% of 1310 Asian patients. Overall, the adjusted risk of VTE in black patients was similar to white patients, but Asian patients had a lower risk of VTE. Risk factors for VTE in white patients were age less than 75 years, female sex, chemotherapy and comorbid medical conditions, including hypertension, anemia, chronic kidney and lung disease, hyperlipidemia, heart failure and obesity. In black patients, hyperlipidemia, and heart failure and in Asian patients, age less than 75 years, female sex, chemotherapy and hypertension and myocardial infarction were associated with VTE. Central venous catheter placement was a predictor of VTE in all three races. Our study identified risk factors for VTE by race in elderly white, black and Asian AML patients.

Recombinant von Willebrand factor and tranexamic acid for heavy menstrual bleeding in patients with mild and moderate von Willebrand disease in the USA (VWDMin): a phase 3, open-label, randomised, crossover trial.

BACKGROUND: Heavy menstrual bleeding occurs in 80% of women with von Willebrand disease and is associated with iron deficiency and poor response to current therapies. International guidelines indicate low certainty regarding effectiveness of hormonal therapy and tranexamic acid. Although von Willebrand factor (VWF) concentrate is approved for bleeds, no prospective trials guide its use in heavy menstrual bleeding. We aimed to compare recombinant VWF with tranexamic acid for reducing heavy menstrual bleeding in patients with von Willebrand disease. METHODS: VWDMin, a phase 3, open-label, randomised crossover trial, was done in 13 haemophilia treatment centres in the USA. Female patients aged 13-45 years with mild or moderate von Willebrand disease, defined as VWF ristocetin cofactor less than 0·50 IU/mL, and heavy menstrual bleeding, defined as a pictorial blood assessment chart (PBAC) score more than 100 in one of the past two cycles were eligible for enrolment. Participants were randomly assigned (1:1) to two consecutive cycles each of intravenous recombinant VWF, 40 IU/kg over 5-10 min on day 1, and oral tranexamic acid 1300 mg three times daily on days 1-5, the order determined by randomisation. The primary outcome was a 40-point reduction in PBAC score by day 5 after two cycles of treatment. Efficacy and safety were analysed in all patients with any post-baseline PBAC scores. The trial was stopped early due to slow recruitment on Feb 15, 2022, by a data safety monitoring board request, and was registered at ClinicalTrials.gov, NCT02606045. FINDINGS: Between Feb 12, 2019, and Nov 16, 2021, 39 patients were enrolled, 36 of whom completed the trial (17 received recombinant VWF then tranexamic acid and 19 received tranexamic acid then recombinant VWF). At the time of this unplanned interim analysis (data cutoff Jan 27, 2022), median follow-up was 23·97 weeks (IQR 21·81-28·14). The primary endpoint was not met, neither treatment corrected PBAC score to the normal range. Median PBAC score was significantly lower after two cycles with tranexamic acid than with recombinant VWF (146 [95% CI 117-199] vs 213 [152-298]; adjusted mean treatment difference 46 [95% CI 2-90]; p=0·039). There were no serious adverse events or treatment-related deaths and no grade 3-4 adverse events. The most common grade 1-2 adverse events were mucosal bleeding (four [6%] patients during tranexamic acid treatment vs zero during recombinant VWF treatment) and other bleeding (four [6%] vs two [3%]). INTERPRETATION: These interim data suggest that recombinant VWF is not superior to tranexamic acid in reducing heavy menstrual bleeding in patients with mild or moderate von Willebrand disease. These findings support discussion of treatment options for heavy menstrual bleeding with patients based on their preferences and lived experience. FUNDING: National Heart Lung Blood Institute (National Institutes of Health).

Building the foundation for a community-generated national research blueprint for inherited bleeding disorders: research to advance the health of people with inherited bleeding disorders with the potential to menstruate.

BACKGROUND: People who have or had the potential to menstruate (PPM) with inherited bleeding disorders (BD) face particular challenges receiving appropriate diagnosis and care and participating in research. As part of an initiative to create a National Research Blueprint for future decades of research, the National Hemophilia Foundation (NHF) and American Thrombosis and Hemostasis Network conducted extensive all-stakeholder consultations to identify the priorities of PPM with inherited BDs and those who care for them. RESEARCH DESIGN AND METHODS: Working group (WG) 4 of the NHF State of the Science Research Summit distilled community-identified priorities for PPM with inherited BDs into concrete research questions and scored their feasibility, impact, and risk. RESULTS: WG4 identified important gaps in the foundational knowledge upon which to base optimal diagnosis and care for PPM with inherited BDs. They defined 44 top-priority research questions concerning lifespan sex biology, pregnancy and the post-partum context, uterine physiology and bleeding, bone and joint health, health care delivery, and patient-reported outcomes and quality-of-life. CONCLUSIONS: The needs of PPM will best be advanced with research designed across the spectrum of sex and gender biology, with methodologies and outcome measures tailored to this population, involving them throughout.

Up to 1% of cisgender women and girls have an inherited bleeding disorder (BD). Common symptoms include heavy menstrual bleeding (HMB), heavy bleeding after giving birth known as post-partum hemorrhage (PPH), nose bleeds, bleeding from the mouth, and excessive bleeding after surgery or procedures. They can also experience bleeding into their muscles, joints, and even into the brain. Uterine bleeding, such as from HMB and PPH, can impact the lives of anyone who has or had a uterus, a group we designate as people who have or had the potential to menstruate (PPM).Many PPM with an inherited BD do not receive diagnosis, treatment, and care needed due to a lack of expertise among health care professionals and the public, misunderstanding, and bias. Uncertainty about "normal" versus "abnormal" bleeding can contribute to a lack of diagnosis, treatment, and care. Language, such as the label of "carrier," can be a barrier to accessing treatment and care for PPM.People with inherited BDs, health care professionals with various expertise and focus, and researchers worked together to identify the research that would most improve the lives of PPM, in six focus areas where there are major gaps in knowledge and the lack of standards required for accurate diagnosis.

Longitudinal Analysis of Biologic Correlates of COVID-19 Resolution: Case Report.

While the biomarkers of COVID-19 severity have been thoroughly investigated, the key biological dynamics associated with COVID-19 resolution are still insufficiently understood. We report a case of full resolution of severe COVID-19 due to convalescent plasma transfusion. Following transfusion, the patient showed fever remission, improved respiratory status, and rapidly decreased viral burden in respiratory fluids and SARS-CoV-2 RNAemia. Longitudinal unbiased proteomic analysis of plasma and single-cell transcriptomics of peripheral blood cells conducted prior to and at multiple times after convalescent plasma transfusion identified the key biological processes associated with the transition from severe disease to disease-free state. These included (i) temporally ordered upward and downward changes in plasma proteins reestablishing homeostasis and (ii) post-transfusion disappearance of a subset of monocytes characterized by hyperactivated Interferon responses and decreased TNF-α signaling. Monitoring specific dysfunctional myeloid cell subsets in peripheral blood may provide prognostic keys in COVID-19.

Biologic correlates of beneficial convalescent plasma therapy in a COVID-19 patient reveal disease resolution mechanisms.

BACKGROUND: While the biomarkers of COVID-19 severity have been thoroughly investigated, the key biological dynamics associated with COVID-19 resolution are still insufficiently understood. MAIN BODY: We report a case of full resolution of severe COVID-19 due to convalescent plasma transfusion in a patient with underlying multiple autoimmune syndrome. Following transfusion, the patient showed fever remission, improved respiratory status, and rapidly decreased viral burden in respiratory fluids and SARS-CoV-2 RNAemia. Longitudinal unbiased proteomic analysis of plasma and single-cell transcriptomics of peripheral blood cells conducted prior to and at multiple times after convalescent plasma transfusion identified the key biological processes associated with the transition from severe disease to disease-free state. These included (i) temporally ordered upward and downward changes in plasma proteins reestablishing homeostasis and (ii) post-transfusion disappearance of a particular subset of dysfunctional monocytes characterized by hyperactivated Interferon responses and decreased TNF-α signaling. CONCLUSIONS: Monitoring specific subsets of innate immune cells in peripheral blood may provide prognostic keys in severe COVID-19. Moreover, understanding disease resolution at the molecular and cellular level should contribute to identify targets of therapeutic interventions against severe COVID-19.

Plasma trial: Pilot randomized clinical trial to determine safety and efficacy of plasma transfusions.

BACKGROUND: Plasma is frequently administered to patients with prolonged INR prior to invasive procedures. However, there is limited evidence evaluating efficacy and safety. STUDY DESIGN AND METHODS: We performed a pilot trial in hospitalized patients with INR between 1.5 and 2.5 undergoing procedures conducted outside the operating room. We excluded patients undergoing procedures proximal to the central nervous system, platelet counts <40,000/µl, or congenital or acquired coagulation disorders unresponsive to plasma. We randomly allocated patients stratified by hospital and history of cirrhosis to receive plasma transfusion (10-15 cc/kg) or no transfusion. The primary outcome was change in hemoglobin concentration within 2 days of procedure. RESULTS: We enrolled 57 patients, mean age 56.0, 34 (59.6%) with cirrhosis, and mean INR 1.92 (SD = 0.27). In the intention to treat analysis, there were 10 of 27 (38.5%) participants in the plasma arm with a post procedure INR <1.5 and one of 30 (3.6%) in the no treatment arm (p < .01). The mean INR after receiving plasma transfusion was -0.24 (SD 0.26) lower than baseline. The change from pre-procedure hemoglobin level to lowest level within 2 days was -0.6 (SD = 1.0) in the plasma transfusion arm and -0.4 (SD = 0.6) in the no transfusion arm (p = .29). Adverse outcomes were uncommon. DISCUSSION: We found no differences in change in hemoglobin concentration in those treated with plasma compared to no treatment. The change in INR was small and corrected to less than 1.5 in minority of patients. Large trials are required to establish if plasma is safe and efficacious.

Risk of venous thromboembolism and endocrine therapy in older women with breast cancer in the United States.

Our aim was to evaluate the risk of venous thromboembolism (VTE) with tamoxifen and aromatase inhibitor in older women with breast cancer in the United States. The SEER-Medicare-linked database (2007--2013) was used for women of at least 65 years of age diagnosed with breast cancer in the United States. Logistic regression was used to examine unadjusted and adjusted odds ratios (OR) with 95% confidence intervals (CIs) for the risk of VTE. There were 178 059 women aged at least 65 years with breast cancer in the United States. Twenty-two thousand and forty-two (12.4%) women received tamoxifen, 64 384 (36.2%) women received aromatase inhibitors and 17 419 (9.8%) women received chemotherapy. Adjusted OR = 1.18 (95% CI 1.05--1.32) for VTE with tamoxifen for 3 years or less compared with tamoxifen use more than 3 years and OR = 1.07 (95% CI 1.05--1.16) for VTE with aromatase inhibitors 4 years or less compared with aromatase inhibitors use for more than 4 years. White women had OR = 1.19 (95% CI 1.05--1.35) and black women had OR = 1.07 (95% CI 0.76--1.51) for VTE with 3 years or less tamoxifen use compared with longer use. White women had OR = 1.09 (95% CI 1.00--1.18) and black women had OR = 1.07 (95% CI 0.86--1.34) for VTE with 4 years or less aromatase inhibitors use compared with longer use. Chemotherapy was associated with an increased risk of VTE (OR = 1.77, 95% CI 1.69--1.86). Chemotherapy combined with tamoxifen had OR = 1.64 (95% CI 1.45--1.86) and chemotherapy combined with aromatase inhibitors had OR = 1.71 95% CI 1.59-1.84). The study may help to identify a treatment profile for VTE risk that may facilitate VTE prevention.

Safety and efficacy of turoctocog alfa in the prevention and treatment of bleeds in previously untreated paediatric patients with severe haemophilia A: Results from the guardian 4 multinational clinical trial.

INTRODUCTION: Turoctocog alfa is a recombinant, B domain-truncated factor VIII (FVIII) approved for patients with haemophilia A. AIM: To evaluate the safety and efficacy of turoctocog alfa in previously untreated patients (PUPs) with severe haemophilia A. METHODS: Guardian 4 was a multicentre, multinational, non-randomized, open-label phase 3 trial comprising a main and extension phase. The former concluded once ≥ 50 patients had received treatment for ≥ 50 exposure days (EDs) or developed inhibitors. Patients received turoctocog alfa intravenously for prevention and treatment of bleeds. The primary endpoint was the incidence rate of FVIII inhibitors (≥0.6 Bethesda Units) reported during the first 50 EDs. RESULTS: Of the 58 patients who completed the main phase, 25 (43.1%) patients developed inhibitors (detected within 6-24 [mean: 14.2] EDs from treatment start). High-risk mutations were identified in 60% of patients who developed inhibitors in the main phase and were a significant predictor of inhibitor development (P = .003). Of the 21 patients who started immune tolerance induction therapy, 85.7% completed treatment with a negative inhibitor test (note that data on the last 3 patients completing ITI are based on information collated from sites prior to the final database lock). Haemostatic response (including missing values as failure) was rated as 'excellent' or 'good' for 86.1% of bleeds occurring during prophylaxis. The estimated mean annualized bleeding rate for patients on prophylaxis was 4.26 bleeds/patient/year (95% CI: 3.34 - 5.44). CONCLUSIONS: Turoctocog alfa was effective at preventing and stopping bleeds and was well tolerated. Inhibitor development was within the expected range for this PUP population.

Feasibility of the Von Willebrand disease PREVENT trial.

BACKGROUND: Despite treatment, women with von Willebrand disease (VWD) have lower von Willebrand factor (VWF) levels and greater blood loss at delivery than controls. Current weight-based dosing does not account for the ~1.5-fold increase in blood volume in pregnancy. METHODS: To evaluate the feasibility of a trial to prevent postpartum hemorrhage (PPH), we reviewed pre-pregnancy and 8th month VWF levels in women with VWD with and without PPH following vaginal delivery, assessed VWF concentrate use at delivery by U.S. hemophilia treatment center physician survey, and reviewed thrombosis risk with VWF concentrate by literature review. We determined trial interest and acceptability by structured interviews of physicians and patients. Analysis was by Student's t-test for continuous data, and chi-square or Fisher's exact test for discrete data. RESULTS: PPH was associated with lower pre-pregnancy VWF:RCo, p<0.005; higher pre-pregnancy, 8th and 9th-month weight, each p<0.001; a family bleeding history, p=0.036; and VWF concentrate treatment, p=0.005. Surveyed physicians reported first-line therapy at delivery was VWF concentrate, at a mean dose 50IU/kg. A trial of a 1.5-fold volume-based dose increase was acceptable to physicians and patients, if it is safe and if costs and visits are minimized. A literature review determined thrombosis risk with VWF concentrate is low, 0.4%. CONCLUSIONS: This study suggests pre-pregnancy VWF:RCo may predict PPH, but 50-80IU/kg VWF concentrate dosing may not prevent PPH. If pharmacokinetic modeling confirms volume-based dosing achieves VWF levels comparable to pregnant controls, it may be possible to determine if volume-modified VWF concentrate dosing will reduce PPH in VWD.

Mild factor XIII deficiency and concurrent hypofibrinogenemia: effect of pregnancy.

Factor XIII (FXIII) deficiency is a rare bleeding disorder. Patients with mild congenital FXIII deficiency tend to be asymptomatic, but may demonstrate significant bleeding symptoms with surgery, trauma, and pregnancy. Postpartum hemorrhage has been described in mild FXIII deficiency. We present a case of mild FXIII deficiency and concurrent hypofibrinogenemia manifested by recurrent postpartum hemorrhage, menorrhagia, and miscarriage. Mutational analysis identified a previously unreported heterozygous mutation of the FXIIIA subunit (p.Trp315Arg). No mutation was noted in the fibrinogen gene. FXIII levels decreased approximately 50% from nonpregnant levels to their nadir during labor, whereas fibrinogen levels rose approximately 1.5-fold from decreased nonpregnant levels to their peak at the time of labor. This case illustrates the course of mild FXIII and fibrinogen deficiencies during pregnancy, labor, and postpartum, and raises possible management options for prevention of antepartum and postpartum hemorrhage in women with these deficiencies.

Characteristics and Risk Factors of Cancer Associated Venous Thromboembolism.

INTRODUCTION: The objective of this study was to examine the differences in commonly associated characteristics and risk factors of venous thromboembolism (VTE) between patients with and without cancer in a VTE population. MATERIALS AND METHODS: Uniform data were collected for patients with a diagnosis of VTE obtaining care at CDC funded Thrombosis Network Centers. Patient characteristics and risk factors were compared in VTE patients with and without cancer. Logistic regression was used to calculate the unadjusted and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) to assess patient characteristics and thrombotic risk factors more frequently identified among VTE patients with cancer compared to those without cancer. RESULTS: Between August 2003 and April 2011, 3,115 adult patients with a diagnosis of VTE including 189 (6.1%) patients with active cancer participated in the multi-site thrombosis registry. VTE patients with cancer had a higher prevalence of PE and DVT in unusual sites compared to those without cancer. Thrombophilia was more common among VTE patients without cancer than those with cancer (25.1% vs 10.6%, p<0.001). In adjusted analysis, age group≥45years (OR =5.20, 95% CI, 3.30, 8.18), surgery (OR =1.86, 95% CI, 1.19, 2.91), and hypertension (OR =1.66, 95% CI, 1.15, 2.40) were the VTE risk factors more commonly found among VTE patients with cancer. CONCLUSION: The study identified several thrombotic risk factors more likely to be found with cancer associated VTE, which may help to characterize at risk cancer patients and to develop prevention and management strategies in this population.

Whole blood gene expression profiles distinguish clinical phenotypes of venous thromboembolism.

INTRODUCTION: Recurrent venous thromboembolism (VTE) occurs infrequently following a provoked event but occurs in up to 30% of individuals following an initial unprovoked event. There is limited understanding of the biological mechanisms that predispose patients to recurrent VTE. OBJECTIVES: To identify whole blood gene expression profiles that distinguished patients with clinically distinct patterns of VTE. PATIENTS/METHODS: We studied 107 patients with VTE separated into 3 groups: (1) 'low-risk' patients had one or more provoked VTE; (2) 'moderate-risk' patients had a single unprovoked VTE; (3) 'high-risk' patients had ≥2 unprovoked VTE. Each patient group was also compared to twenty-five individuals with no personal history of VTE. Total RNA from whole blood was isolated and hybridized to Illumina HT-12V4 Beadchips to assay whole genome expression. RESULTS: Using class prediction analysis, we distinguished high-risk patients from low-risk patients and healthy controls with good receiver operating curve characteristics (AUC=0.81 and 0.84, respectively). We also distinguished moderate-risk individuals and low-risk individuals from healthy controls with AUC's of 0.69 and 0.80, respectively. Using differential expression analysis, we identified several genes previously implicated in thrombotic disorders by genetic analyses, including SELP, KLKB1, ANXA5, and CD46. Protein levels for several of the identified genes were not significantly different between the different groups. CONCLUSION: Gene expression profiles are capable of distinguishing patients with different clinical presentations of VTE, and genes relevant to VTE risk are frequently differentially expressed in these comparisons.

Characterization of antithrombin levels in pregnancy.

OBJECTIVE: To characterize antithrombin (AT) levels in normal pregnancy. METHODS: We performed secondary analyses with data from 3 studies. Using a single measurement from each subject in the first analysis (cross-sectional), we correlated AT levels with gestational age from the middle of the second trimester throughout the third trimester of pregnancy. Using serial measurements in a second analysis (cohort), we compared AT levels between the late first and second trimesters of pregnancy and baseline (the level at 6 weeks postpartum). Using serial measurements in a third analysis (cohort), we analyzed the pattern of change in AT levels in the immediate postpartum period. Assays of AT activity were performed using the Dade Behring (Siemens) Berichrom Antithrombin III Chromogenic Assay. AT levels were correlated with gestational age using the Pearson correlation coefficient and compared between the different time points using one-way ANOVA. RESULTS: Overall, AT levels were 20% lower than baseline during pregnancy (p<0.01). There was no significant difference between AT levels obtained between late first trimester and late second trimester. From midtrimester to term, however, AT levels were negatively correlated with gestational age with a 13% drop during this period of time (r=-0.26 [-0.39, -0.11]; p<0.01). Immediately after childbirth, AT levels fell precipitously to 30% below baseline (p<0.05) and reached a nadir 12 hours postpartum before rising and returning to baseline by 72 hours postpartum. CONCLUSION: It appears that antithrombin (AT) is consumed at the time of delivery. Our findings have implications for AT replacement or even anticoagulation at the time of delivery.

Differences in thrombotic risk factors in black and white women with adverse pregnancy outcome.

INTRODUCTION: Black women have an increased risk of adverse pregnancy outcomes and the characteristics of thrombotic risk factors in this population are unknown. The objective of this study was to examine the racial differences in thrombotic risk factors among women with adverse pregnancy outcomes. METHODS: Uniform data were collected in women with adverse pregnancy outcomes (pregnancy losses, intrauterine growth restriction (IUGR), prematurity, placental abruption and preeclampsia) referred to Thrombosis Network Centers funded by the Centers for Disease Control and Prevention (CDC). RESULTS: Among 343 white and 66 black women seen for adverse pregnancy outcomes, protein S and antithrombin deficiencies were more common in black women. The prevalence of diagnosed thrombophilia was higher among whites compared to blacks largely due to Factor V Leiden mutation. The prevalence of a personal history of venous thromboembolism (VTE) did not differ significantly by race. A family history of VTE, thrombophilia, and stroke or myocardial infarction (MI) was higher among whites. Black women had a higher body mass index, and a higher prevalence of hypertension, while the prevalence of sickle cell disease was approximately 27 fold higher compared to the general US black population. CONCLUSIONS: Thrombotic risk factors differ significantly in white and black women with adverse pregnancy outcomes. Such differences highlight the importance of considering race separately when assessing thrombotic risk factors for adverse pregnancy outcomes.

Characteristics of abdominal vein thrombosis in children and adults.

The demographic and clinical characteristics of adults and children with lower extremity deep-vein thrombosis and/or pulmonary embolism (LE DVT/PE) may differ from those with abdominal vein thrombosis (abdominal VT). Abdominal VT can be a presenting sign of an underlying prothrombotic state, and its presence in the setting of known disease might have prognostic implications different from LE DVT/PE. This study describes clinical presentations of abdominal VT compared to LE DVT/PE in adults and children. We analysed prospectively-collected data from consecutive consenting patients enrolled in one of seven Centers for Disease Control and Prevention (CDC) funded Thrombosis and Hemostasis Network Centers from August 2003 to April 2011 to compare the demographic and clinical characteristics of adults and children with abdominal VT. Both adults and children with abdominal VT tended to be younger and have a lower body mass index (BMI) than those with LE DVT/PE. Of patients with abdominal VT, children were more likely to have inferior vena cava (IVC) thrombosis than adults. For adults with venous thromboembolism (VTE), relatively more women had abdominal VT than LE DVT/PE, while the proportions with LE DVT/PE and abdominal VT by sex were similar in children. Children with abdominal VT were more likely to have diagnosed inherited thrombophilia, while trauma was more common in children with LE DVT/PE. In conclusion, both children and adults with abdominal VT were younger with a lower BMI than those with LE DVT/PE. Significant differences exist between children and adults in respect to abdominal VT compared to LE DVT/PE.

Association between changes in air pollution levels during the Beijing Olympics and biomarkers of inflammation and thrombosis in healthy young adults.

CONTEXT: Air pollution is a risk factor for cardiovascular diseases (CVD), but the underlying biological mechanisms are not well understood. OBJECTIVE: To determine whether markers related to CVD pathophysiological pathways (biomarkers for systemic inflammation and thrombosis, heart rate, and blood pressure) are sensitive to changes in air pollution. DESIGN, SETTING, AND PARTICIPANTS: Using a quasi-experimental opportunity offered by greatly restricted air pollution emissions during the Beijing Olympics, we measured pollutants daily and the outcomes listed below in 125 healthy young adults before, during, and after the 2008 Olympics (June 2-October 30). We used linear mixed-effects models to estimate the improvement in outcome levels during the Olympics and the anticipated reversal of outcome levels after pollution controls ended to determine whether changes in outcome levels were associated with changes in pollutant concentrations. MAIN OUTCOME MEASURES: C-reactive protein (CRP), fibrinogen, von Willebrand factor, soluble CD40 ligand (sCD40L), soluble P-selectin (sCD62P) concentrations; white blood cell count (WBC); heart rate; and blood pressure. RESULTS: Concentrations of particulate and gaseous pollutants decreased substantially (-13% to -60%) from the pre-Olympic period to the during-Olympic period. Using 2-sided tests conducted at the .003 level, we observed statistically significant improvements in sCD62P levels by -34.0% (95% CI, -38.4% to -29.2%; P < .001) from a pre-Olympic mean of 6.29 ng/mL to a during-Olympic mean of 4.16 ng/mL and von Willebrand factor by -13.1% (95% CI, -18.6% to -7.5%; P < .001) from 106.4% to 92.6%. After adjustments for multiple comparisons, changes in the other outcomes were not statistically significant. In the post-Olympic period when pollutant concentrations increased, most outcomes approximated pre-Olympic levels, but only sCD62P and systolic blood pressure were significantly worsened from the during-Olympic period. The fraction of above-detection-limit values for CRP (percentage ≥ 0.3 mg/L) was reduced from 55% in the pre-Olympic period to 46% in the during-Olympic period and reduced further to 36% in the post-Olympic period. Interquartile range increases in pollutant concentrations were consistently associated with statistically significant increases in fibrinogen, von Willebrand factor, heart rate, sCD62P, and sCD40L concentrations. CONCLUSIONS: Changes in air pollution levels during the Beijing Olympics were associated with acute changes in biomarkers of inflammation and thrombosis and measures of cardiovascular physiology in healthy young persons. These findings are of uncertain clinical significance.

Evaluation and management of acute menorrhagia in women with and without underlying bleeding disorders: consensus from an international expert panel.

Acute menorrhagia is a common gynecological disorder. Prevalence is high among women with inherited bleeding disorders and recent guidance for optimal management is lacking. Following a comprehensive review of the literature, an international expert panel in obstetrics, gynecology and hematology reached consensus on recommendations regarding the management of acute menorrhagia in women without a diagnosed bleeding disorder, as well as in patients with von Willebrand disease, platelet function disorders and other rare hemostatic disorders. The causes and predictors of acute menorrhagia are discussed and special consideration is given for the treatment of women on anticoagulation therapy. This review and accompanying recommendations will provide guidance for healthcare practitioners in the emergency management of acute menorrhagia.

Antifibrinolytics in women with menorrhagia.

Heavy menstrual bleeding is associated with increased local fibrinolysis. Antifibrinolytic agents have been used in women with menorrhagia with and without bleeding disorders, and have been demonstrated to decrease menstrual blood flow approximately 50% and improve quality of life. Most studies have been done with the antifibrinolytic agent tranexamic acid, a synthetic lysine derivative. Studies have been performed comparing tranexamic acid with placebo, non-steroidal anti-inflammatory agents, and progesterone in women with menorrhagia and have predominantly demonstrated a greater reduction in menstrual blood flow with tranexamic acid. In women with menorrhagia and an underlying bleeding disorder, tranexamic acid was compared to intranasal desmopressin and also demonstrated a greater reduction in menstrual blood flow. In aggregate the studies demonstrate that antifibrinolytic agents are effective medical management for women with menorrhagia with or without bleeding disorders, reducing menstrual blood flow and improving quality of life.

Evaluation of a screening tool for bleeding disorders in a US multisite cohort of women with menorrhagia.

OBJECTIVE: The purpose of this study was to determine the usefulness of a simple screening tool for bleeding disorders in a multisite population of women with menorrhagia. STUDY DESIGN: Women with menorrhagia between the ages of 18 and 50 years from 6 geographically diverse US centers underwent hemostatic testing for bleeding disorders, complete blood cell count, and ferritin. A questionnaire that contained all elements of the 8-question screening tool was administered. Sensitivity of the screening tool, a screening tool with a pictorial blood assessment chart (PBAC) score of >185, and a screening tool with serum ferritin were calculated for hemostatic disorders. RESULTS: Two hundred and seventeen women who were identified with a PBAC score of ≥100 participated in the study. The sensitivity of the screening tool was 89% for hemostatic defects, and sensitivity increased to 93% and 95% with a serum ferritin level of ≤20 ng/mL and a PBAC score of >185, respectively. CONCLUSION: This study confirms the usefulness of a short screening tool for the stratification of women with menorrhagia for hemostatic evaluation.

Platelet disorders in adolescents.

Acquired and inherited platelet disorders can present with bleeding symptoms during adolescence. Platelet disorders include disorders of platelet number and disorders of platelet function. In adolescent females with platelet disorders, menorrhagia is a common presenting bleeding symptom. Other associated bleeding symptoms are also primarily mucocutaneous, including epistaxis and bruising. Excessive bleeding may also occur after hemostatic challenges. Diagnosis of disorders of platelet function usually requires light transmission platelet aggregometry. Management of menorrhagia in the adolescent with platelet disorders requires both hematologic and gynecologic treatment.