Prevalence and aetiologies of anaemia among first trimester pregnant women in Sri Lanka; the need for revisiting the current control strategies.

BACKGROUND: The Sustainable development goals, which focus strongly on equity, aim to end all forms of malnutrition by 2030. However, a significant cause of intergenerational transfer of malnutrition, anaemia in pregnancy, is still a challenge. It is especially so in the low- and middle-income settings where possible context-specific aetiologies leading to anaemia have been poorly explored. This study explores the prevalence of etiological factors significantly contributing to anaemia in pregnancy in Sri Lanka, a lower-middle-income country with a high prevalence of malnutrition albeit robust public health infrastructure. METHODS: All first-trimester pregnant women registered in the public maternal care programme in the Anuradhapura district from July to September 2019 were invited to participate in Rajarata Pregnancy Cohort (RaPCo). After a full blood count analysis, high-performance liquid chromatography, peripheral blood film examination, serum B12 and folate levels were performed in anaemic participants, guided by an algorithm based on the red cell indices in the full blood count. In addition, serum ferritin was tested in a random subsample of 213 participants. Anaemic women in this subsample underwent B12 and folate testing. RESULTS: Among 3127 participants, 14.4% (95%CI 13.2-15.7, n = 451) were anaemic. Haemoglobin ranged between 7.4 to 19.6 g/dl. 331(10.6%) had mild anaemia. Haemoglobin ≥13 g/dl was observed in 39(12.7%). Microcytic, normochromic-normocytic, hypochromic-normocytic and macrocytic anaemia was observed in 243(54%), 114(25.3%), 80(17.8%) and two (0.4%) of full blood counts in anaemic women, respectively. Microcytic anaemia with a red cell count ≥5 * 106 /µl demonstrated a 100% positive predictive value for minor haemoglobinopathies. Minor hemoglobinopathies were present in at least 23.3%(n = 105) of anaemic pregnant women. Prevalence of iron deficiency, B12 deficiency and Southeast Asian ovalocytosis among the anaemic was 41.9% (95%CI 26.4-59.2), 23.8% (95%CI 10.6-45.1) and 0.9% (95%CI 0.3-2.3%), respectively. Folate deficiency was not observed. CONCLUSION: Even though iron deficiency remains the primary cause, minor hemoglobinopathies, B 12 deficiency and other aetiologies substantially contribute to anaemia in pregnancy in this study population. Public health interventions, including screening for minor hemoglobinopathies and multiple micronutrient supplementation in pregnancy, should be considered in the national programme for areas where these problems have been identified.

Effectiveness of Caplacizumab Nanobody in Acquired Thrombotic Thrombocytopenic Purpura Refractory to Conventional Treatment.

Acquired thrombocytopenic thrombotic purpura (aTTP) is an autoantibody-mediated disease against the enzyme A Disintegrin and Metalloprotease domain with ThromboSpondin-1 type motif 13, which until now has been treated with plasma exchange (PEX) and corticosteroids. A 29-year-old female patient, who presented with aTTP in the context of pregnancy, has developed multiple relapses after treatment with PEX, corticosteroids, and rituximab. Recently, caplacizumab, a nanobody against von Willebrand factor, has been approved for the treatment of aTTP. In our patient, caplacizumab achieved better disease control, with a lower platelet count restoration time, days of PEX and hospitalization duration, as compared to standard therapy, reproducing the results of clinical trials. Caplacizumab represents a significant advance in the treatment of aTTP, especially in cases of recurrent relapses.

Pregnancy in special populations: challenges and solutions practical aspects of managing von Willebrand disease in pregnancy.

Pregnancy and childbirth pose an important hemostatic challenge for women with von Willebrand disease (VWD) and can be associated with an increased risk of maternal and neonatal bleeding complications. VWD is a genetically and clinically heterogeneous bleeding disorder caused by a deficiency or an abnormality in the function of von Willebrand factor. Understanding inheritance pattern, hemostatic response to pregnancy, and response to treatment is essential for provision of individualized obstetric care and optimal outcome. A multidisciplinary approach to management with a close liaison between the obstetric team and the hemophilia treatment center is required for continuity of care from preconception counseling through to antenatal, peripartum, and postpartum care. Delivery plan must be coordinated by the multidisciplinary team and include decisions on place and mode of delivery, implementation of safe analgesia/anesthesia, and peripartum hemostasis. In this clinical case-based review, we aim to deliver evidence-based practical guidance for challenges encountered during pregnancy and management of childbirth and puerperium.

Mild Anemia May Affect Thyroid Function in Pregnant Chinese Women During the First Trimester.

Background: Pregnant women are often susceptible to anemia, which can damage the thyroid gland. However, compared with moderate and severe anemia, less attention has been paid to mild anemia. The purpose of this study was to evaluate the effect of mild anemia on the thyroid function in pregnant women during the first trimester. Methods: A total of 1,761 women in the first trimester of their pregnancy were enrolled from Shenyang, China, and divided into mild anemia and normal control groups based on their hemoglobin levels. Thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) levels were compared between the two groups. Results: The TSH levels of pregnant women with mild anemia were higher than those of pregnant women without mild anemia (p < 0.05). Normal control women were selected to set new reference intervals for TSH, FT3, and FT4 levels during the first trimester, which were 0.11-4.13 mIU/l, 3.45-5.47 pmol/l, and 7.96-16.54 pmol/l, respectively. The upper limit of TSH 4.13 mU/l is close to the upper limit 4.0 mU/l recommended in the 2017 American Thyroid Association (ATA) guidelines, indicating that exclusion of mild anemia may reduce the difference in reference values from different regions. Mild anemia was related to 4.40 times odds of abnormally TSH levels (95% CI: 2.84, 6.76) and 5.87 increased odds of abnormal FT3 (95% CI: 3.89, 8.85). The proportion of hypothyroidism and subclinical hypothyroidism in patients with mild anemia was higher than that in those without anemia (0.6% vs. 0, p = 0.009; 12.1% vs. 1.9%, p < 0.001). Mild anemia was related to 7.61 times increased odds of subclinical hypothyroidism (95% CI: 4.53, 12.90). Conclusions: Mild anemia may affect thyroid function during the first trimester, which highlights the importance of excluding mild anemia confounding when establishing a locally derived specific reference interval for early pregnancy.

High maternal blood lipid levels during early pregnancy are associated with increased risk of congenital heart disease in offspring.

INTRODUCTION: This study aimed to investigate whether maternal blood lipid levels during early pregnancy are associated with the occurrence of congenital heart disease (CHD) in their offspring. MATERIAL AND METHODS: In this single-center case-control study, mothers of offspring with CHD (n = 230) and without CHD (n = 381) were included. Maternal lipid levels were determined on fasting blood samples taken in the first trimester. Relevant demographic and clinical data were extracted from the medical records. Maternal lipid profile was compared between the two groups, and regression analysis was performed to evaluate the association between lipid profile and CHD risk in offspring. RESULTS: Compared with the control group, levels of triglyceride, apolipoprotein-A1, and apolipoprotein-B in early pregnancy were significantly higher in the CHD group. Multivariate analyses showed that triglyceride (odds ratio [OR] 2.46, 95% CI 1.62-3.73, p < 0.01), total/high-density lipoprotein cholesterol (OR 2.10, 95% CI 1.07-4.13, p = 0.03), and apolipoprotein-A1 (OR 2.73, 95% CI 1.16-6.40, p = 0.02) were positively associated with CHD risk in offspring. CONCLUSIONS: Elevated maternal lipid profile was associated with increased risk of CHD in offspring.

Coronavirus disease 2019 (COVID-19) in a pregnant women with treatment resistance thrombocytopenic purpura with and suspicion to HELLP syndrome: a case report.

BACKGROUND: Coronavirus disease 2019 (COVID-19) still is a global emergency. According to the studies, pregnant women are of the at risk populations and any underlying disease(s) might even worsen their condition. The aim of this study is reporting a complex case of immune thrombocytopenic purpura (ITP) during pregnancy who has been diagnosed with COVID-19 as well as suspicion of HELLP syndrome. CASE PRESENTATION: A 24-year-old woman with a platelet count of 6000/mL and resistance to conventional therapies was referred. A day after starting 0.5 g/day of methylprednisolone for her, fever and a decrease in SpO2 presented. According to the paraclinical investigations, COVID-19 was diagnosed and the conventional COVID-19 treatments started for her (the methylprednisolone pulse stopped). Due to the increased liver enzymes and low platelet count, with suspicion of HELLP syndrome, cesarean section surgery was performed which resulted in a healthy neonate. Then, the methylprednisolone pulse was restarted for and she developed an increase in the platelet count. CONCLUSION: It is not clear how COVID-19 and pregnancy affected the patient's condition and the underlying disease; however, it seems the delivery and/or restarting the methylprednisolone pulses caused improvement in her condition.

Development of a High Resolution Melting Curve Analysis for the Detection of Hemoglobin δ-Chain Variants in Thailand and Identification of Hb A2-Walsgrave [codon 52 (GAT>CAT), Asp→His; HBD:c.157G>C] in a Pregnant Woman from Southern Thailand.

Background: Delta-chain (δ-chain) variants are a group of rare hemoglobin (Hb) variants resulting from mutations within the δ-globin gene. Although quantification of Hb A2 levels is a useful screening tool for the beta-thalassemia trait, the coinheritance of a δ-globin gene mutation can lead to misinterpretation of diagnostic results. Objective: To identify an unreported Hb A2 variant in Thailand and to develop a high resolution melting (HRM) curve assay for the four δ-globin chain variants found in the Thai population. Materials and Methods: Allele-specific polymerase chain reaction (ASPCR) was used to analyze a total of 18 DNA samples for Hb variants comprising 10 wild-type controls, 4 Hb A2-Melbourne, 1 Hb A2-Lampang, 2 Hb A2-Kiriwong, and an unknown variant via HRM assays. Results: The unreported Hb A2 variant in Thailand was found to be Hb A2-Walsgrave resulting from δ-globin gene mutation at codon 52 (GAT>CAT). This was also confirmed using ASPCR. In addition, we demonstrated that the HRM curve profile for Hb A2-Melbourne, Hb A2-Lampang, Hb A2-Walsgrave, and Hb A2-Kiriwong could be identified so as to distinguish the mutant alleles from one another and from wild-type alleles. Conclusion: This HRM assay detected both known and unknown mutations with simultaneous differentiation between heterozygous and homozygous alleles on a polymerase chain reaction fragment spanning four of the δ-globin variants found in Thailand. This assay may help to support the prevention and control of thalassemias and hemoglobinopathies in Thailand.

Gestational thrombocytopenia: a case-control study of over 3,500 pregnancies.

Gestational thrombocytopenia (GT) affects an estimated nine million women annually. Women with GT have recurrent episodes on subsequent pregnancies suggesting that GT is related to a maternal factor rather than a factor unique to the individual pregnancy. We performed a case-control study of over 3 500 pregnancies at a single hospital during 2017. We defined GT as any pregnancy with a platelet count <150 000/µl during the 100 days prior to delivery. We excluded women with platelet counts <50 000/µl or with conditions known to cause thrombocytopenia. GT was present in 12% of pregnancies. The median platelet count at delivery was 134 500/µl in cases versus 208 000/µl in controls, P < 0·0001. During the pregnancy, the platelet count declined 31·8% in cases compared with 18·3% in controls (P < 0·0001) in association with a significant increase in mean platelet volume during each trimester. Among women with GT, platelet counts rapidly increased during the first week postpartum, consistent with a mechanism directly related to high blood flow rates in the gravid uterus. GT, a recurrent condition of at-risk women, is a common haematological disorder of pregnancy. Future research may focus on genetic gain-of-function polymorphisms resulting in increased turnover of platelets uncovered only during periods of high-shear blood flow.

Meta-analysis on aspirin combined with low-molecular-weight heparin for improving the live birth rate in patients with antiphospholipid syndrome and its correlation with d-dimer levels.

BACKGROUND: Antiphospholipid antibody syndrome (APS) is a systemic, autoimmune, prothrombotic disease characterized by persistent antiphospholipid antibodies, thrombosis, recurrent abortion, complications during pregnancy, and occasionally thrombocytopenia. At present, there is no consensus on the treatment of this disease. Long-term anticoagulation is recommended in most cases in patients with thrombotic APS. This study aimed to evaluate whether aspirin combined with low-molecular-weight heparin (LMWH) can improve the live birth rate in antiphospholipid syndrome and its correlation with D-dimer. METHODS: The data were retrieved from the WanFang Data, CBM, VIP, CNKI, the Cochrane Library, PubMed, EMBASE, OVID, and Web of Science databases. We collected data on randomized controlled trials of aspirin combined with LMWH in the treatment of pregnant women with APS. The "Risk of Bias Assessment" tool and the "Jadad Scale" provided by the Cochrane Collaboration were used to evaluate the risk of bias and quality of the collected literature. The risk ratio (RR) and its 95% confidence interval (CI) were determined using Statase-64 software. RESULTS: In this study, a total of 11 studies were included, comprising a total of 2101 patients. The live birth rate in pregnant women with APS was higher on administration of aspirin combined with LMWH than with aspirin alone (RR = 1.29, 95% CI = 1.22-1.35, P < .001). d-dimer concentration in plasma predicted the live birth rate, which was higher below the baseline than above it (RR = 1.16, 95% CI = 1.09-1.23, P < .001). The subgroup analysis of the live birth rate was carried out based on the course of treatment, and the results were consistent with the overall results. Begg funnel plot test revealed no publication bias. Sensitivity analysis showed that deleting any study did not affect the results. CONCLUSION: Aspirin combined with LMWH for APS may improve live birth rate, and detection of d-dimer levels in APS pregnant women may predict pregnancy complications and guide the use of anticoagulants.

Comparative efficacy and safety of intravenous ferric carboxymaltose and iron sucrose for iron deficiency anemia in obstetric and gynecologic patients: A systematic review and meta-analysis.

INTRODUCTION: Iron deficiency anemia (IDA) is common among obstetric and gynecologic patients. This systematic review aimed to assess the comparative efficacy and safety of commonly used intravenous (IV) iron formulations, ferric carboxymaltose (FCM), and iron sucrose (IS) in the treatment of IDA in obstetric and gynecologic patients. METHODS: We systematically searched PubMed, EMBASE, Cochrane CENTRAL, and Google Scholar for eligible randomized controlled trials (RCTs) comparing IV iron replacement using FCM and IS up to October 2019. The primary outcome was to compare the efficacy of FCM and IS, assessed by measuring serum hemoglobin (Hb) and ferritin levels before and after iron replacement. The secondary outcome was to compare the safety of FCM and IS, assessed by the incidence of adverse events during iron replacement. The meta-analysis was performed using RevMan 5.3. RESULTS: We identified 9 RCTs with 910 patients (FCM group, n = 456; IS group, n = 454). Before iron replacement, FCM and IS group patients had similar baseline Hb (mean difference [MD], 0.04 g/dL; 95% confidence interval [CI], -0.07 to 015; I2 = 0%; P = 0.48) and ferritin levels (MD, -0.42 ng/mL; 95% CI, -1.61 to 0.78; I2 = 45%; P = 0.49). Following iron replacement, patients who received FCM had higher Hb (MD, 0.67; 95% CI, 0.25-1.08; I2 = 92%; P = 0.002) and ferritin levels (MD, 24.41; 95% CI, 12.06-36.76; I2 = 75%; P = 0.0001) than patients who received IS. FCM group showed a lower incidence of adverse events following iron replacement than IS group (risk ratio, 0.53; 95% CI, 0.35-0.80; I2 = 0%; P = 0.003). Serious adverse events were not reported in any group. CONCLUSION: FCM group showed better efficacy in increasing Hb and ferritin levels and a favorable safety profile with fewer adverse events compared with IS group for IDA treatment among obstetric and gynecologic patients. However, this meta-analysis was limited by the small number of RCTs and high heterogeneity. TRIAL REGISTRATION: The review was prospectively registered with the International Prospective Registry of Systematic Reviews (https://www.crd.york.ac.uk/prospero/, registration number CRD42019148905).

Anesthetic Management of Von Willebrand Disease in Pregnancy: A Retrospective Analysis of a Large Case Series.

BACKGROUND: Although Von Willebrand disease (vWD) is the most common heritable bleeding disorder, there are limited reports regarding the safety of neuraxial anesthesia in the obstetric population and no definitive guidelines specifying recommended pretreatment or therapies for patients with vWD. The aim of this study is to describe the anesthetic management of pregnant patients with vWD at a large tertiary-care center. METHODS: In this retrospective analysis, the study population was identified from vWD patients evaluated by our high-risk obstetric anesthesia consultation service and by diagnosis codes from our institutional research database registry. We manually reviewed records of patients with vWD in pregnancy who delivered at our institution between January 1, 2000 and January 1, 2019 for demographic characteristics, circumstances of vWD diagnosis, history of bleeding, laboratory studies, and overall management of vWD. Anesthetic management of vWD was at the discretion of individual providers, based on multidisciplinary consensus and the specific circumstances of each patient's disease and obstetric presentation. RESULTS: We identified 106 deliveries among 71 individual vWD patients. Of the unique patients, 54 had vWD type 1, 6 had vWD type 2, and 11 had vWD type unknown. Forty-three cases (40.6%) were cesarean deliveries. Neuraxial techniques were used in 94 of 106 deliveries (88.7%). Treatment with desmopressin or Von Willebrand factor/factor VIII concentrate before neuraxial anesthesia occurred in 27 of 94 neuraxial anesthetics (28.7%). Eleven deliveries (10.4%) were complicated by postpartum hemorrhage (PPH), defined as estimated blood loss of ≥1000 mL. There were no noted adverse anesthetic outcomes (0 of 106; 0% [95% confidence interval, 0-3.4]), including neuraxial hematoma or thromboembolic events. CONCLUSIONS: In this large case series, the majority of vWD patients received neuraxial anesthesia for labor and delivery, with no noted adverse events. This suggests that neuraxial anesthesia can be safely performed with the peripartum management that we describe. Pretreatment was dictated by the type and severity of vWD. Multidisciplinary planning is important to optimize the coagulation status of patients with vWD and facilitate options for analgesia and anesthesia.

The effect of Lactiplantibacillus plantarum 299v together with a low dose of iron on iron status in healthy pregnant women: A randomized clinical trial.

INTRODUCTION: Iron deficiency during pregnancy is a global health problem and is associated with adverse pregnancy outcomes. The aim of this randomized, double-blind, placebo-controlled study was to evaluate the effect of Lactiplantibacillus plantarum 299v (Lp299v, 1010 colony forming units), 4.2 mg iron, 12 mg ascorbic acid and 30 µg folic acid (Lp) on iron status in healthy, non-anemic, pregnant Swedish women. MATERIAL AND METHODS: A total of 326 women were randomized to receive Lp (n = 161) or placebo (n = 165) twice daily from gestational week 10-12 until end of pregnancy or until the potential start of iron therapy. The primary endpoint was serum ferritin at week 28. RESULTS: Intake of Lp attenuated the decrease in serum ferritin from baseline to week 28 (p = 0.003) and week 35 (p Ë‚ 0.001) and resulted in reduced prevalence of iron deficiency (59% vs 78%, p = 0.017) and iron deficiency anemia (7.4% vs 21%, p = 0.023) at week 35. Intake of Lp also resulted in beneficial effects on the soluble transferrin receptor (p = 0.011) and total body iron (p Ë‚ 0.001) at week 35. Gestational length and birthweight were comparable between groups. The proportion of women reporting adverse events during the study was comparable between groups. CONCLUSIONS: Intake of Lp from early pregnancy was safe, attenuated the loss of iron stores and improved iron status in healthy pregnant women.

Disseminated intravascular coagulation: epidemiology, biomarkers, and management.

Disseminated intravascular coagulation (DIC) is a systemic activation of the coagulation system, which results in microvascular thrombosis and, simultaneously, potentially life-threatening haemorrhage attributed to consumption of platelets and coagulation factors. Underlying conditions, e.g. infection, cancer, or obstetrical complications are responsible for the initiation and propagation of the DIC process. This review provides insights into the epidemiology of DIC and the current understanding of its pathophysiology. It details the use of diagnostic biomarkers, current diagnostic recommendations from international medical societies, and it provides an overview of emerging diagnostic and prognostic biomarkers. Last, it provides guidance on management. It is concluded that timely and accurate diagnosis of DIC and its underlying condition is essential for the prognosis. Treatment should primarily focus on the underlying cause of DIC and supportive treatment should be individualised according to the underlying aetiology, patient's symptoms and laboratory records.

Slower response to treatment of iron-deficiency anaemia in pregnant women infected with HIV: a prospective cohort study.

OBJECTIVE: Antenatal anaemia is associated with increased peripartum transfusion requirement in South Africa. We studied whether HIV was associated with the response to treatment of iron-deficiency anaemia. DESIGN: Prospective cohort study. SETTING: Hospital-based antenatal anaemia clinic in South Africa. SAMPLE: Equal-sized cohorts of pregnant women testing positive for HIV (HIV+) and testing negative for HIV (HIV-) with iron-deficiency anaemia. METHODS: Haemoglobin trajectories of women with confirmed iron-deficiency anaemia (ferritin < 50 ng/ml) were estimated from the initiation of iron supplementation using mixed-effects modelling, adjusted for baseline HIV status, ferritin level, maternal and gestational ages and time-varying iron supplementation. MAIN OUTCOME MEASURES: Haemoglobin trajectories. RESULTS: Of 469 women enrolled, 51% were HIV+, 90% of whom were on antiretroviral therapy (with a mean CD4+ lymphocyte count of 403 cells/mm3 ). Anaemia diagnoses did not differ by HIV status. A total of 400 women with iron-deficiency anaemia were followed during treatment with oral or intravenous (6%) iron therapy. In multivariable analysis, haemoglobin recovery was 0.10 g/dl per week slower on average in women who were HIV+ versus women who were HIV- (P = 0.001), 0.01 g/dl per week slower in women with higher baseline ferritin (P < 0.001) and 0.06 g/dl per week faster in women who were compliant with oral iron therapy (P = 0.002). CONCLUSIONS: Compared with women who were HIV-, women who were HIV+ with iron-deficiency anaemia had slower but successful haemoglobin recovery with iron therapy. Earlier effective management of iron deficiency could reduce the incidence of peripartum blood transfusion. TWEETABLE ABSTRACT: Among pregnant women with iron-deficiency anaemia in South Africa, HIV slows haemoglobin recovery in response to oral iron therapy.

Accidentally discovered high INR in pregnancy unmasks an inherited factor VII (FVII) deficiency that is paradoxically associated with thrombotic tendency.

A 32-year-old multiparous obese woman was referred to our center at 37 weeks of twin gestation. She was referred for birth planning following an accidentally discovered high international normalised ratio (INR) in routine preoperative labs. Her history was significant for recurrent pregnancy-associated deep venous thrombosis as well as two early pregnancy losses. Further work-up revealed transaminitis, mild splenomegaly and high lupus anticoagulant titre. A multidisciplinary team of physicians from the high-risk pregnancy, anaesthesiology, haematology, gastroenterology and hepatology departments put a management plan; it culminated into uncomplicated delivery of the patient by repeated caesarian section. The team was also able to figure out the cause of the patient's high INR that is associated with thrombophilia rather than haemophilia.

Implementation of early management of iron deficiency in pregnancy during the SARS-CoV-2 pandemic.

Iron deficiency is the commonest cause for anaemia worldwide making it a formidable issue particularly during pregnancy because of increased iron demands. This study looked at establishing a lower limit of normal for haemoglobin concentration (Hb) in our population and to proactively address potentially symptomatic iron deficiency during the current SARS-CoV-2 pandemic. The lower limit of normal for Hb in our 1715 first trimester pregnancy cohort was 116 g/L. This is in contrast with guidance suggesting Hb levels down to 110 g/L are normal. In addition there was evidence of limited testing performed to look for iron deficiency with only 18 % having a serum ferritin checked. Most anaemia was normocytic suggesting that microcytosis is only a late marker of iron deficiency lacking sensitivity. A strategy to avoid hospital contact during the COVID-19 pandemic is proposed.

"Part of the Ritual": Exploring Patient and Physician Decision Making Regarding Anticoagulation Use in Obstetric Antiphospholipid Syndrome.

BACKGROUND: Antiphospholipid syndrome is associated with recurrent pregnancy loss. Low-molecular-weight heparin (LMWH) and/or aspirin (ASA) prophylaxis during pregnancy to prevent future loss is based on limited trial data with mixed results. OBJECTIVES: Given the clinical equipoise, we sought to understand how patients and physicians navigate the decision-making process for use of LMWH and/or ASA in pregnancy. METHODS: We interviewed 10 patients and 10 thrombosis physicians in Ottawa, Canada from January 2017 to March 2018. Patients who had ≥1 late pregnancy loss or ≥2 early losses and persistently positive antiphospholipid antibodies based on the revised Sapporo/Sydney criteria were identified in the a Thrombosis Clinic. Patients were also identified by the TIPPS Study screening logs of excluded patients. Data collection and analysis occurred iteratively, in keeping with constructivist grounded theory methodology. RESULTS: Our analysis generated three themes, present across both patient and physician interviews, which captured a patient-led decision-making experience: (1) managing high stakes, (2) accepting uncertainty, and (3) focusing on safety. Patients and physicians acknowledged the high emotional burden and what was at stake: avoiding further pregnancy loss. Patients responded to their situation by taking action (i.e., using LMWH injections became a "ritual"), whereas physicians reacted by removing themselves from the final decision by "[leaving] it up to the patient." CONCLUSION: Our findings should be considered when designing future research on studying the role for LMWH/ASA in this population, as it suggests that the perceived benefits of treatment go beyond improving pregnancy rates. Rather, patients described potential benefit from the process of taking action, even in the absence of a guaranteed good outcome.