Agnostic identification of plasma biomarkers for postpartum hemorrhage risk.

BACKGROUND: Postpartum hemorrhage is difficult to predict, is associated with significant maternal morbidity, and is the leading cause of maternal mortality worldwide. The identification of maternal biomarkers that can predict increased postpartum hemorrhage risk would enhance clinical care and may uncover mechanisms that lead to postpartum hemorrhage. OBJECTIVE: This retrospective case-control study employed agnostic proteomic profiling of maternal plasma samples to identify differentially abundant proteins in controls and postpartum hemorrhage cases. STUDY DESIGN: Maternal plasma samples were procured from a cohort of >60,000 participants in a single institution's perinatal repository. Postpartum hemorrhage was defined as a decrease in hematocrit of ≥10% or receipt of transfusion within 24 hours after delivery. Postpartum hemorrhage cases (n=30) were matched by maternal age and delivery mode (vaginal or cesarean) with controls (n=56). Mass spectrometry was used to identify differentially abundant proteins using integrated peptide peak areas. Statistically significant differences between groups were defined as P<.05 after controlling for multiple comparisons. RESULTS: By study design, cases and controls did not differ in race, ethnicity, gestational age at delivery, blood type, or predelivery platelet count. Cases had slightly but significantly lower predelivery and postdelivery hematocrit and hemoglobin. Mass spectrometry detected 1140 proteins, including 77 proteins for which relative abundance differed significantly between cases and controls (fold change >1.15, P<.05). Of these differentially abundant plasma proteins, most had likely liver or placental origins. Gene ontology term analysis mapped to protein clusters involved in responses to wound healing, stress response, and host immune defense. Significantly differentially abundant proteins with the highest fold change (prostaglandin D2 synthase, periostin, and several serine protease inhibitors) did not correlate with predelivery hematocrit or hemoglobin but identified postpartum hemorrhage cases with logistic regression modeling revealing good-to-excellent area under the operator receiver characteristic curves (0.802-0.874). Incorporating predelivery hemoglobin with these candidate proteins further improved the identification of postpartum hemorrhage cases. CONCLUSION: Agnostic analysis of maternal plasma samples identified differentially abundant proteins in controls and postpartum hemorrhage cases. Several of these proteins are known to participate in biologically plausible pathways for postpartum hemorrhage risk and have potential value for predicting postpartum hemorrhage. These findings identify candidate protein biomarkers for future validation and mechanistic studies.

What do we know about why women bleed and what do we not know?

Women or people with a uterus are vulnerable to both normal and abnormal bleeding. During the reproductive years, the uterus is prepared physiologically to accept an embryo and support its growth and development during pregnancy, or in the absence of implantation of an embryo, recycle through the process of menstruation and accept an embryo a month or so later. If fertilization takes place and an embryo or embryos implant in the uterus, the fetal trophoblast, or outer cell layer of the embryo, invades and dilates the maternal spiral arteries and forms the placenta. No matter when in gestation a pregnancy ends, at the conclusion of pregnancy, the placenta should separate from the wall of the uterus and be expelled. Abnormal bleeding occurs during pregnancy or after delivery when the normal uteroplacental interface has not been established or is interrupted; during miscarriage; during ectopic pregnancy; during premature separation of the placenta; or during postpartum hemorrhage. Heavy menstrual bleeding, a subset of abnormal menstrual bleeding, can be quantitatively defined as >80 mL of blood loss per cycle. Unlike postpartum hemorrhage, heavy menstrual bleeding is significantly associated with an underlying bleeding disorder. While there is other reproductive tract bleeding in women, notably bleeding at the time of ovulation or with a life-threatening ruptured ectopic pregnancy, the unique bleeding that women experience is predominantly uterine in origin. Many of the unique aspects of uterine hemostasis, however, remain unknown.

CT-001, a novel fast-clearing factor VIIa, enhanced the hemostatic activity in postpartum samples.

ABSTRACT: The hemostatic system is upregulated to protect pregnant mothers from hemorrhage during childbirth. Studies of the details just before and after delivery, however, are lacking. Recombinant factor VIIa (rFVIIa) has recently been granted approval by the European Medicines Agency for the treatment of postpartum hemorrhage (PPH). A next-generation molecule, CT-001, is being developed as a potentially safer and more efficacious rFVIIa-based therapy. We sought to evaluate the peripartum hemostatic status of pregnant women and assess the ex vivo hemostatic activity of rFVIIa and CT-001 in peripartum blood samples. Pregnant women from 2 study sites were enrolled in this prospective observational study. Baseline blood samples were collected up to 3 days before delivery. Postdelivery samples were collected 45 (±15) minutes after delivery. Between the 2 time points, soluble fibrin monomer and D-dimer increased whereas tissue factor, FVIII, FV, and fibrinogen decreased. Interestingly, the postdelivery lag time and time to peak in the thrombin generation assay were shortened, and the peak thrombin generation capacity was maintained despite the reduced levels of coagulation proteins after delivery. Furthermore, both rFVIIa and CT-001 were effective in enhancing clotting activity of postdelivery samples in activated partial thromboplastin time, prothrombin time, thrombin generation, and viscoelastic hemostatic assays, with CT-001 demonstrating greater activity. In conclusion, despite apparent ongoing consumption of coagulation factors at the time of delivery, thrombin output was maintained. Both rFVIIa and CT-001 enhanced the upregulated hemostatic activity in postdelivery samples, and consistent with previous studies comparing CT-001 and rFVIIa in vitro and in in vivo, CT-001 demonstrated greater activity than rFVIIa.

How I treat sickle cell disease in pregnancy.

ABSTRACT: Fifty years ago, people with sickle cell disease (SCD) were discouraged from becoming pregnant, but now, most should be supported if they choose to pursue a pregnancy. They and their providers, however, should be aware of the physiological changes of pregnancy that aggravate SCD and pregnancy's unique maternal and fetal challenges. Maternal problems can arise from chronic underlying organ dysfunction such as renal disease or pulmonary hypertension; from acute complications of SCD such as acute anemia, vaso-occlusive crises, and acute chest syndrome; and/or from pregnancy-related complications such as preeclampsia, sepsis, severe anemia, thromboembolism, and the need for cesarean delivery. Fetal problems include alloimmunization, opioid exposure, fetal growth restriction, preterm delivery, and stillbirth. Before and during pregnancy, in addition to the assessment and care that every pregnant patient should receive, patients with SCD should be evaluated and treated by a multidisciplinary team with respect to their unique maternal and fetal issues.

Management of pregnant women who have bleeding disorders.

Bleeding disorders, including von Willebrand disease (VWD), hemophilia, other coagulation factor deficiencies, platelet disorders, defects of fibrinolysis, and connective tissue disorders, have both maternal and fetal implications. Successful management of bleeding disorders in pregnant women requires not only an understanding of bleeding disorders but also an understanding of when and how bleeding occurs in pregnancy. Bleeding does not occur during a normal pregnancy with a healthy placenta. Bleeding occurs during pregnancy when there is an interruption of the normal utero-placental interface, during miscarriage, during an ectopic pregnancy, or at the time of placental separation at the conclusion of pregnancy. Although mild platelet defects may be more prevalent, the most commonly diagnosed bleeding disorder among women is VWD. Other bleeding disorders are less common, but hemophilia carriers are unique in that they are at risk of bleeding themselves and of giving birth to an affected male infant. General guidance for maternal management of a woman who is moderately or severely affected includes obtaining coagulation factor levels at a minimum in the third trimester; planning for delivery at a center with hemostasis expertise; and anticipating the need for hemostatic agents. General guidance for fetal management includes pre-pregnancy counseling; the option of preimplantation genetic testing for hemophilia; delivery at a tertiary care center with pediatric hematology and newborn intensive care; consideration of cesarean delivery of a potentially severely affected infant; and avoidance of invasive procedures such as scalp electrodes and operative vaginal delivery in any potentially affected infant.

Projected impact of guidelines on incidence of venous thromboembolism after cesarean delivery in the United States.

BACKGROUND: There is large variation in recommended for postcesarean delivery venous thromboembolism (VTE) prophylaxis among commonly used guidelines. OBJECTIVES: The aim of the study is to estimate implications of adoption of VTE prevention guidelines for rates of receipt of VTE prophylactic therapy and VTE following cesarean delivery (CD). METHODS: We used administrative data from the 2015-2019 Nationalwide Readmissions Database to identify cesarean deliveries and rates of VTE stratified by risk factors, leading to different prophylactic strategies based on several national guidelines. We used input parameters from the literature to construct a hybrid decision tree/Markov model to project the implications of guideline adoption on VTE rates for the first 6 weeks following delivery. RESULTS: Adoption of either the 2011 American College of Obstetricians and Gynecologists or the 2018 American Society for Hematology guidelines would avert a relatively small proportion (5%) of VTE cases, albeit with little low-molecular-weight heparin (LMWH) use (87-115 doses per 1000 CD patients). The 2012 American College of Chest Physicians guidelines were predicted to be more effective at averting VTE (21.2% reduction) with more LMWH usage (570 doses per 1000 deliveries). The 2015 Royal College of Obstetricians and Gynaecologists guidelines and universal use of 6 weeks of LMWH would avert an even larger proportion of cases (37.4% and 57.6%, respectively), at the cost of much higher rates of LMWH utilization (7233 doses per 1000 patients and 38 648 doses per 1000 patients). CONCLUSIONS: Adoption of different guidelines would have notably varying implications for clinical practice and potential for alteration of the national rate of VTE following CD.

High rates of venous thromboembolism among deliveries complicated by cancer.

BACKGROUND: Venous thromboembolism (VTE) risk is increased independently by both cancer and pregnancy. OBJECTIVES: To estimate VTE risk in the postpartum period among patients delivering with a cancer diagnosis, stratified by cancer type and delivery route. METHODS: We performed a retrospective cohort study utilizing the large, all-payer Nationwide Readmissions Database from October 2015 through December 2020. We identified delivery hospitalizations, cancer diagnoses, and VTE using patient demographics and diagnosis codes. The primary outcome was VTE incidence at 42 and 330 days from delivery admission date, comparing patients with and without cancer diagnoses. A secondary analysis included VTE risk stratified by cancer diagnosis and delivery route. Outcomes were compared using inverse probability-weighted survival curves. RESULTS: The study population included 9 793 503 delivery hospitalizations (weighted estimate, 18 207 346), with a weighted estimate of 10 428 (0.06%) pregnant patients with cancer. Individuals with cancer were older, with higher rates of comorbid conditions, than those without cancer. VTE incidence in individuals with cancer at 42 and 330 days was 1.11% and 2.19%, respectively, vs 0.11% and 0.14%, respectively, in those without cancer. At 330 days, this finding was significant in both unadjusted (relative risk, 15.52; 95% CI, 11.54-19.51) and adjusted (relative risk, 9.68; 95% CI, 7.18-12.18) models. Stratification by cancer type and delivery route demonstrated elevated VTE risk across cancer types, with cesarean delivery conferring a greater risk. CONCLUSION: Cancer in pregnancy confers excess thromboembolic risk extending beyond the immediate postpartum period. Further study is needed to identify optimal VTE prophylactic strategies for this population.

American Society of Hematology 2023 guidelines for management of venous thromboembolism: thrombophilia testing.

Hereditary and acquired thrombophilia are risk factors for venous thromboembolism (VTE). Whether testing helps guide management decisions is controversial. These evidence-based guidelines from the American Society of Hematology (ASH) intend to support decision making about thrombophilia testing. ASH formed a multidisciplinary guideline panel covering clinical and methodological expertise and minimizing bias from conflicts of interest. The McMaster University GRADE Centre provided logistical support, performed systematic reviews, and created evidence profiles and evidence-to-decision tables. The Grading of Recommendations Assessment, Development, and Evaluation approach (GRADE) was used. Recommendations were subject to public comment. The panel agreed on 23 recommendations regarding thrombophilia testing and associated management. Nearly all recommendations are based on very low certainty in the evidence due to modeling assumptions. The panel issued a strong recommendation against testing the general population before starting combined oral contraceptives (COCs) and conditional recommendations for thrombophilia testing in the following scenarios: (a) patients with VTE associated with nonsurgical major transient or hormonal risk factors; (b) patients with cerebral or splanchnic venous thrombosis, in settings where anticoagulation would otherwise be discontinued; (c) individuals with a family history of antithrombin, protein C, or protein S deficiency when considering thromboprophylaxis for minor provoking risk factors and for guidance to avoid COCs/hormone replacement therapy; (d) pregnant women with a family history of high-risk thrombophilia types; and (e) patients with cancer at low or intermediate risk of thrombosis and with a family history of VTE. For all other questions, the panel provided conditional recommendations against testing for thrombophilia.

Von Willebrand Disease, Hemophilia, and Other Inherited Bleeding Disorders in Pregnancy.

Inherited bleeding disorders, which comprise von Willebrand disease (VWD), hemophilia, other congenital clotting factor deficiencies, inherited platelet disorders, defects of fibrinolysis, and connective tissue disorders, have both maternal and fetal implications. Although mild platelet defects may actually be more prevalent, the most common diagnosed bleeding disorder among women is VWD. Other bleeding disorders, including hemophilia carriership, are much less common, but hemophilia carriers are unique in that they are at risk of giving birth to a severely affected male neonate. General guidance for maternal management of inherited bleeding disorders includes obtaining clotting factor levels in the third trimester, planning for delivery at a center with hemostasis expertise if factor levels do not meet the minimum threshold (eg, less than 0.50 international units/1 mL [50%] for von Willebrand factor, factor VIII, or factor IX), and using hemostatic agents such as factor concentrates, desmopressin, or tranexamic acid. General guidance for fetal management includes prepregnancy counseling, the option of preimplantation genetic testing for hemophilia, and consideration of delivery of potentially affected male neonates with hemophilia by cesarean delivery to reduce the risk of neonatal intracranial hemorrhage. In addition, delivery of possibly affected neonates should occur in a facility where there is newborn intensive care and pediatric hemostasis expertise. For patients with other inherited bleeding disorders, unless a severely affected neonate is anticipated, mode of delivery should be dictated by obstetric indications. Nonetheless, invasive procedures such as fetal scalp clip or operative vaginal delivery should be avoided, if possible, in any fetus potentially affected with a bleeding disorder.

Pregnancy Outcomes in Patients With Interstitial Lung Disease.

OBJECTIVE: Women with interstitial lung disease (ILD) are recommended to avoid pregnancy based on limited data. This study seeks to determine maternal and pregnancy outcomes in the largest-to-date cohort of patients with ILD. METHODS: Medical records in the Duke University Health System were reviewed for pregnancies in patients with a diagnosis of ILD with underlying autoimmune disease. Pregnancies were classified as having very severe, severe, mild-moderate, or normal lung function based on pulmonary function tests (PFTs). Adverse pregnancy outcomes (APOs) were defined using the Predictors of Pregnancy Outcome in Systemic Lupus Erythematosus and Antiphospholipid Syndrome APO (PROMISSE-APO) and Severe PROMISSE-APO criteria. RESULTS: Among 86 pregnancies in 60 women, 85% women were Black, 71% had sarcoidosis, and 29% had connective tissue disease (CTD)-associated ILD (CTD-ILD). Of the pregnancies with available PFTs (n = 59), 12% had very severe ILD, 25% had severe ILD, 51% had mild-moderate ILD, and 12% had normal lung function. PROMISSE-APOs occurred in 32% of pregnancies, including all pregnancies with very severe ILD (P = 0.02 across severity groups), 56% of pregnancies with CTD-ILD, and 23% with sarcoidosis (P = 0.02). Severe PROMISSE-APOs occurred in 15% of pregnancies, including 60% with very severe ILD and 28% with CTD-ILD. There were no maternal deaths. One woman required an intensive care hospital stay during pregnancy. Three women had volume overload after delivery that resolved with medical management. Seven women received oxygen during delivery, although none were intubated. CONCLUSION: Although APOs were common in women with very severe ILD and underlying CTD, overall maternal morbidity and mortality were low. These data suggest women with ILD may be able to safely attempt pregnancy.

Novel Antithrombotic Agents in Pregnancy Anticoagulants and Antiplatelet Agents.

Increasing rates of thromboembolic complications have required increasing use of anticoagulant and antiplatelet agents during and after pregnancy. Furthermore, thromboembolism is both a cause and a complication of severe maternal morbidity requiring intensive care. As a consequence, almost all patients admitted to intensive care units receive an anticoagulant or an antiplatelet agent (or both) for either treatment or prevention of thromboembolism. In this review, we summarize commonly used anticoagulants and antiplatelet agents and outline the potential role of newly developed (novel) antithrombotic agents for pregnant and postpartum patients.

Prospective Observational Study of N-terminal Pro-Brain Natriuretic Peptide Levels in Obese and Nonobese Women during Pregnancy.

OBJECTIVE: N-terminal pro-brain natriuretic peptide (NT-proBNP), a marker of ventricular dysfunction, varies by body mass index (BMI) outside of pregnancy. This study aimed to determine whether obesity affects NT-proBNP levels in pregnancy. STUDY DESIGN: This was a prospective observational study of healthy pregnant people in the third trimester (3TM) and postpartum (PP). Patients were excluded if they had significant medical comorbidities or if their fetuses had anomalies, growth restriction or aneuploidy. NT-proBNP was measured at 28 weeks (3TM), predelivery (PD), 1 to 2 days PP (immediate postpartum [IPP]), and 4 to 6 weeks PP (delayed postpartum [DPP]). LogNT-proBNP levels were analyzed using linear mixed effects models, including BMI < or ≥30, time, and time-by-BMI interactions. RESULTS: Fifty-five people (28 [51%] with BMI ≥ 30 and 27 [49%] with BMI < 30) were enrolled. A greater proportion of obese than nonobese subjects developed hypertensive disorders of pregnancy (50 vs. 15%, p = 0.010) and obese patients had higher systolic blood pressures at all time points (p < 0.05). NT-proBNP levels (median [interquartile range] in pg/mL) were 18 (6-28) versus 26 (17-48) at 3TM, 16 (3-38) versus 43 (21-60) at PD, 58 (20-102) versus 63 (38-155) at IPP, and 33 (27-56) versus 23 (8-42) at DPP for obese compared with nonobese patients. In linear mixed effects models, logNT-proBNP was lower in obese patients at 3TM (ß = -0.89 [95% confidence interval, CI: -1.51, -0.26]) and PD (ß = -1.05 [95% CI: -1.72, -0.38]). The logNT-proBNP trends over time differed by BMI category, with higher values in obese patients at both PP time points compared with the 3TM (IPP ß = 1.24 [95% CI: 0.75, 1.73]; DPP ß = 1.08 [95% CI: 0.52, 1.63]), but only IPP for nonobese patients (ß = 0.87 [95% CI: 0.36, 1.38]). CONCLUSION: Obese patients had lower NT-proBNP levels than nonobese patients during pregnancy but not PP. The prolonged PP elevation in NT-proBNP in obese patients suggests that their PP cardiac recovery may be more prolonged. KEY POINTS: · NT-proBNP levels are lower in obese than nonobese patients during pregnancy.. · Levels remain elevated in obese, but not nonobese, patients up to 4 to 6 weeks' postpartum.. · A lower threshold for concern regarding NT-proBNP levels may be needed in obese pregnant people..

Sickle cell disease and the incidence and etiology of preterm birth.

BACKGROUND: Medically indicated delivery can be defined as delivery owing to intervention for maternal or fetal well-being-most commonly because of preeclampsia or nonreassuring fetal status. Among the general population of the United States, approximately two-thirds of preterm deliveries are because of spontaneous labor and/or premature rupture of membranes, whereas the remaining one-third are medically indicated. Despite the increased risk of preterm birth among women with sickle cell disease, the specific etiologies have not been described in the medical literature. Without an understanding of the etiologies of preterm birth in women with sickle cell disease, it is difficult to develop preventative strategies. OBJECTIVE: This study aimed to estimate the incidence and etiologies of preterm births (spontaneous vs medically indicated) in women with sickle cell disease. STUDY DESIGN: This was a retrospective, institutional review board-exempt cohort study of deliveries at >20 weeks' gestation in women with sickle cell disease at Duke University Hospital (2013-2020). We screened pregnancy-linked hospitalizations with International Classification of Diseases-9/10 codes for sickle cell disease (n=373). We excluded cases of pregnancy with <20 weeks' gestation, multiple gestation, or unproven sickle cell disease. We limited inclusion to deliveries within Duke (n=66). We compared the proportion of preterm birth cases between the sickle cell disease cohort and the overall Duke population (n=18,365), and the proportion of spontaneous vs medically indicated preterm births between the sickle cell disease cohort and a racially matched US population. RESULTS: Of the 66 pregnancies, 65 occurred in patients who self-described as Black (98.5%). There were 60.6% (n=40) term and 39.4% (n=26) preterm births vs 85.9% term (n=15,771) and 14.1% preterm (n=2594) births in the Duke population as a whole. The sickle cell disease cohort was nearly 3 times more likely to deliver preterm than the Duke cohort (risk ratio, 2.79; 95% confidence interval, 2.06-3.77; P<.001). Among the 26 preterm births in the sickle cell disease cohort, 30.8% (n=8) were spontaneous and 69.2% (n=18) were medically indicated. In the US Black population comparison cohort, 65.4% (n=392,984) of preterm births were spontaneous and 34.6% (n=207,614) were medically indicated. The sickle cell disease cohort had 2 times the risk of medically indicated preterm birth compared with the US population cohort (risk ratio, 2.00; 95% confidence interval, 1.55-2.59; P<.001). CONCLUSION: Maternal sickle cell disease confers nearly triple the risk of preterm birth, which is twice as likely to be medically indicated.

Transfusion Requirements with Hybrid Management of Placenta Accreta Spectrum Incorporating Targeted Embolization and a Selective Use of Delayed Hysterectomy.

OBJECTIVE: This study compares the number of units of red blood cells (RBCs) transfused in patients with placenta accreta spectrum (PAS) treated with or without a multidisciplinary algorithm that includes placental uterine arterial embolization (P-UAE) and selective use of either immediate or delayed hysterectomy. STUDY DESIGN: This is a retrospective study of deliveries conducted at a tertiary care hospital from 2001 to 2018 with pathology-confirmed PAS. Those with previable pregnancies or microinvasive histology were excluded. To improve the equity of comparison, analyses were made separately among scheduled and unscheduled cases, therefore patients were assigned to one of four cohorts as follows: (1) scheduled/per-algorithm, (2) scheduled/off-algorithm, (3) unscheduled/per-algorithm, or (4) unscheduled/off-algorithm. Primary outcomes included RBCs transfused and estimated blood loss (EBL). Secondary outcomes included perioperative complications and disposition. RESULTS: Overall, 95 patients were identified, with 87 patients meeting inclusion criteria: 36 treated per-algorithm (30 scheduled and 6 unscheduled) and 51 off-algorithm patients (24 scheduled and 27 unscheduled). Among scheduled deliveries, 9 (30.0%) patients treated per-algorithm received RBCs compared with 20 (83.3%) patients treated off-algorithm (p < 0.01), with a median (interquartile range [IQR]) of 3.0 (2.0, 4.0) and 6.0 (2.5, 7.5) units transfused (p = 0.13), respectively. Among unscheduled deliveries, 5 (83.3%) per-algorithm patients were transfused RBCs compared with 25 (92.6%) off-algorithm patients (p = 0.47) with a median (IQR) of 4.0 (2.0, 6.0) and 8.0 (3.0, 10.0) units transfused (p = 0.47), respectively. Perioperative complications were similar between cohorts. CONCLUSION: A multidisciplinary algorithm including P-UAE and selective use of delayed hysterectomy is associated with a lower rate of blood transfusion in scheduled but not unscheduled cases. KEY POINTS: · An algorithm with delayed hysterectomy had less transfusion in scheduled, but not unscheduled, cases.. · Over time, more cases were managed per algorithm; among scheduled cases, the transfusion rate and volume transfused decreased.. · There were similar transfusion outcomes among off-algorithm cases, regardless if delivery was scheduled..

Disparities in obstetric hemorrhage outcomes.

Both the maternal and fetal outcomes of pregnancy vary greatly according to a pregnant woman's community and her condition. The most devastating outcome is the death of a mother. In 2017, there were ≈295,000 maternal deaths globally with dramatic differences in maternal mortality based on geographic region, country, and women's underlying conditions. Worldwide, the leading cause of maternal death is hemorrhage, comprising 94% of maternal deaths, with most cases occurring in low- or middle-income countries. Whether a hemorrhage originates from inside the uterus (80%-90%), from lacerations or incisions (10%-20%), or from an underlying coagulopathy (<1%), an acute acquired coagulopathy will evolve unless the hemorrhage is controlled. In low- or middle-income countries, the full range of resources to control hemorrhage is not available, but besides the usual obstetric measures, blood availability, hemostatic medication, and hematologic expertise are necessary to save mothers' lives. Hemostasis and thrombosis experts can address the disparities in obstetric hemorrhage outcomes not only as providers but as consultants, researchers, and advocates.

Iron Deficiency Anemia in Pregnancy.

Anemia is defined as a low red blood cell count, a low hematocrit, or a low hemoglobin concentration. In pregnancy, a hemoglobin concentration of less than 11.0 g/dL in the first trimester and less than 10.5 or 11.0 g/dL in the second or third trimester (depending on the guideline used) is considered anemia. Anemia is the most common hematologic abnormality in pregnancy. Maternal anemia is associated with adverse fetal, neonatal and childhood outcomes, but causality is not established. Maternal anemia increases the likelihood of transfusion at delivery. Besides hemodilution, iron deficiency is the most common cause of anemia in pregnancy. The American College of Obstetricians and Gynecologists recommends screening for anemia with a complete blood count in the first trimester and again at 24 0/7 to 28 6/7 weeks of gestation. Mild anemia, with a hemoglobin of 10.0 g/dL or higher and a mildly low or normal mean corpuscular volume (MCV) is likely iron deficiency anemia. A trial of oral iron can be both diagnostic and therapeutic. Mild anemia with a very low MCV, macrocytic anemia, moderate anemia (hemoglobin 7.0-9.9 g/dL) or severe anemia (hemoglobin 4.0-6.9 g/dL) requires further investigation. Once a diagnosis of iron deficiency anemia is confirmed, first-line treatment is oral iron. New evidence suggests that intermittent dosing is as effective as daily or twice-daily dosing with fewer side effects. For patients with iron deficiency anemia who cannot tolerate, cannot absorb, or do not respond to oral iron, intravenous iron is preferred. With contemporary formulations, allergic reactions are rare.

Knowledge gaps in reproductive and sexual health in girls and women with sickle cell disease.

There is an immediate need to address long-standing questions about the reproductive health of girls and women with sickle cell disease (SCD). There are many SCD-related reproductive risks and uncertainties across girls' and women's reproductive life span, with particularly outstanding concerns about menstruation, contraception, fertility and pregnancy. Extant literature addressing women's reproductive health topics is mostly descriptive; there are few high-quality interventional studies. In 2020, the Centers for Disease Control and Prevention and the Foundation for Women and Girls with Blood Disorders convened an expert panel to assess the knowledge gaps in women's reproductive health in SCD. The panel identified significant limitations to clinical care due to the need for research. The panel also identified prominent barriers to research and care. In this report, we frame these issues, providing a roadmap for investigators, funding agencies, and policy makers to advance care for girls and women with SCD.

Illustrated State-of-the-Art Capsules of the ISTH 2020 Congress.

This year's Congress of the International Society of Thrombosis and Haemostasis (ISTH) was hosted virtually from Philadelphia July 17-21, 2021. The conference, now held annually, highlighted cutting-edge advances in basic, population and clinical sciences of relevance to the Society. Despite being held virtually, the 2021 congress was of the same scope and quality as an annual meeting held in person. An added feature of the program is that talks streamed at the designated times will then be available on-line for asynchronous viewing. The program included 77 State of the Art (SOA) talks, thematically grouped in 28 sessions, given by internationally recognized leaders in the field. The SOA speakers were invited to prepare brief illustrated reviews of their talks that were peer reviewed and are included in this article. The topics, across the main scientific themes of the congress, include Arterial Thromboembolism, Coagulation and Natural Anticoagulants, COVID-19 and Coagulation, Diagnostics and Omics, Fibrinogen, Fibrinolysis and Proteolysis, Hemophilia and Rare Bleeding Disorders, Hemostasis in Cancer, Inflammation and Immunity, Pediatrics, Platelet Disorders, von Willebrand Disease and Thrombotic Angiopathies, Platelets and Megakaryocytes, Vascular Biology, Venous Thromboembolism and Women's Health. These illustrated capsules highlight the major scientific advances with potential to impact clinical practice. Readers are invited to take advantage of the excellent educational resource provided by these illustrated capsules. They are also encouraged to use the image in social media to draw attention to the high quality and impact of the science presented at the congress.

The Society for Obstetric Anesthesia and Perinatology Interdisciplinary Consensus Statement on Neuraxial Procedures in Obstetric Patients With Thrombocytopenia.

Because up to 12% of obstetric patients meet criteria for the diagnosis of thrombocytopenia in pregnancy, it is not infrequent that the anesthesiologist must decide whether to proceed with a neuraxial procedure in an affected patient. Given the potential morbidity associated with general anesthesia for cesarean delivery, thoughtful consideration of which patients with thrombocytopenia are likely to have an increased risk of spinal epidural hematoma with neuraxial procedures, and when these risks outweigh the relative benefits is important to consider and to inform shared decision making with patients. Because there are substantial risks associated with withholding a neuraxial analgesic/anesthetic procedure in obstetric patients, every effort should be made to perform a bleeding history assessment and determine the thrombocytopenia etiology before admission for delivery. Whereas multiple other professional societies (obstetric, interventional pain, and hematologic) have published guidelines addressing platelet thresholds for safe neuraxial procedures, the US anesthesia professional societies have been silent on this topic. Despite a paucity of high-quality data, there are now meta-analyses that provide better estimations of risks. An interdisciplinary taskforce was convened to unite the relevant professional societies, synthesize the data, and provide a practical decision algorithm to help inform risk-benefit discussions and shared decision making with patients. Through a systematic review and modified Delphi process, the taskforce concluded that the best available evidence indicates the risk of spinal epidural hematoma associated with a platelet count ≥70,000 × 106/L is likely to be very low in obstetric patients with thrombocytopenia secondary to gestational thrombocytopenia, immune thrombocytopenia (ITP), and hypertensive disorders of pregnancy in the absence of other risk factors. Ultimately, the decision of whether to proceed with a neuraxial procedure in an obstetric patient with thrombocytopenia occurs within a clinical context. Potentially relevant factors include, but are not limited to, patient comorbidities, obstetric risk factors, airway examination, available airway equipment, risk of general anesthesia, and patient preference.