[Management of pregnant women with deficiency of factor VII. Report of one case]. / Manejo de embarazada con deficiencia de factor VII. A propósito de un caso.

Tissue Factor-Factor VII complex is essential in coagulation activation. Congenital factor VII deficiency is a rare disorder that has an autosomal recessive inheritance. Clinical presentations are heterogeneous, ranging from asymptomatic carriers to severe bleeding phenotypes with factor VII replacement therapy requirements. Treatments options are plasma derived and recombinants FVII concentrates or fresh frozen plasma in case that first options are not available. In pregnancy factor VII levels increase in women with mild and moderate deficiencies but not in severe deficiency. The management of pregnant women with factor FVII deficiency must be done by a multidisciplinary team of hematologist, obstetrics and anesthetist and should be guided by the women bleeding history, the coagulations test, levels of factor FVII and rout of delivery. We present the case of a 31-year-old pregnant woman who, due to an alteration in prothrombin time, is diagnosed with Factor VII deficiency and its respective obstetric management.

Successful Conservative Treatment of Maternal Spontaneous Unilateral Adrenal Hemorrhage Causing Severe Anemia in the Third Trimester of Pregnancy-A Case Report.

We present the case of a 32-year-old pregnant woman in the 32 + 3 weeks of pregnancy who presented to the hospital with an exacerbation of pain in the right flank. The diagnostic evaluation revealed the presence of severe anemia and a spontaneous adrenal hemorrhage (SAH) in the right adrenal gland. The patient was transferred to the Perinatology, Obstetrics and Gynecology Clinic with the intention of undergoing preterm childbirth. However, the doctors made a risky decision to wait until week 37 and to terminate the pregnancy at that point. The decision was right, as a cesarean section was performed without complications, and the patient gave birth to a healthy child. Spontaneous adrenal hemorrhage (SAH) is a rare condition, defined as spontaneous hemorrhage without trauma or anticoagulant therapy. Due to bleeding and damage to the adrenal cortex, SAH can lead to adrenal insufficiency. Because of its non-specific symptoms and potentially fatal outcomes for the patient and fetus, it should be considered during diagnostics.

Obstetric antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is the most frequent acquired thrombophilia of autoimmune basis. Pregnancy complications of APS may include recurrent miscarriage, and placental dysfunction presenting as fetal death, prematurity, intrauterine growth restriction and preeclampsia. For the management of obstetric APS, a coordinated medical-obstetric management is essential, and this should start for a preconceptional visit in order to estimate the individual risk for complications, adjust therapies and establish the indications for preconceptional and first-trimester therapy. The basis of APS therapy during pregnancy is low-dose aspirin, combined in certain clinical scenarios with low-molecular weight heparin. Induction of delivery should not be routinely indicated in the absence of maternal and/or fetal complications. Postpartum management should be warranted.

Immune thrombocytopenia and pregnancy: challenges and opportunities in diagnosis and management.

INTRODUCTION: Immune thrombocytopenia (ITP) affecting pregnancy is a diagnostic and often a therapeutic challenge. AREAS COVERED: We review the current diagnostic criteria for ITP in pregnancy and the potential utility of laboratory tests. We discuss the impact of ITP on pregnancy outcomes and the effects of pregnancy on patients living with chronic ITP.  We describe the criteria for intervention, the evidence supporting first-line treatment approaches and the therapeutic decisions and challenges in cases refractory to steroids and IVIG. We review the evidence supporting the potential use of thrombopoietin receptor agonists for refractory thrombocytopenia. Finally, we describe the diagnostic, prognostic, and treatment approaches to neonatal ITP and considerations regarding breastfeeding. We searched the terms 'immune thrombocytopenia' and 'pregnancy' on PubMed to identify the relevant literature published before 31 December 2023, including within cited references. EXPERT OPINION: Decreased platelet production may play a role in pregnancy-related ITP exacerbation. Putative mechanisms include placental hormones, such as inhibin. Although IVIG and prednisone usually suffice to achieve hemostasis for delivery, second-line agents are sometimes required to allow for neuraxial anesthesia. There is growing evidence supporting the use of romiplostim during pregnancy; however, its risk of venous thromboembolism warrants further evaluation.

Prophylactic red cell transfusions for sickle cell disease pregnancy: increased use of therapy could transform outcomes.

PURPOSE OF REVIEW: Pregnancy for people with sickle cell disease (SCD) is high risk with persistently high rates of severe maternal and fetal mortality and morbidity. Transfusion therapy is the best-studied treatment for SCD in pregnancy; hydroxyurea is not usually used because of teratogenicity concerns. In high-resource settings, red cell transfusions are likely underutilized, while in low-resource settings, they may be altogether unavailable. RECENT FINDINGS: A randomized controlled trial and meta-analysis, two of the strongest forms of clinical research, show transfusion significantly reduces maternal and fetal death, painful crisis, thrombosis, and acute respiratory failure. Downstream benefits of treatment are less well measured and may include improving maternal anemia, reducing opioid exposure, and avoiding hospitalization, which presents risk for additional complications. Alloimmunization is a particular transfusion risk in SCD. However, many strategies can mitigate this risk. Accordingly, the American Society of Hematology classifies chronic transfusion in pregnancy as low risk. SUMMARY: Given the low risk classification, lack of alternative therapies, dismal, stagnant pregnancy outcomes and the potential for profound treatment benefit, wider use of chronic transfusion therapy for SCD pregnancy is likely indicated. This review discusses the benefits and potential risks of prophylactic transfusions for SCD pregnancy. Use of chronic transfusions during pregnancy is indicated to help urgently transform outcomes.

Consensus recommendations for optimising the diagnosis and treatment of paroxysmal nocturnal haemoglobinuria in Singapore.

Introduction: Paroxysmal nocturnal haemoglobinuria (PNH) is a rare haematologic disease characterised by intravascular haemolysis, thrombophilia and bone marrow failure. There is a lack of established clinical guidance on the screening, diagnosis and manage-ment of PNH in Singapore. A relatively low level of awareness among healthcare professionals regarding PNH manifestations further contributes to diagnostic delays. Additionally, limited access to complement inhibitors, like eculizumab, may delay treatment and impact patient outcomes. Method: Nine haematologists from different institu-tions in Singapore convened to formulate evidence-based consensus recommendations for optimising the diagnosis and management of patients with PNH and improving access to novel treatments. The experts reviewed the existing literature and international guidelines published from January 2010 to July 2023, focusing on 7 clinical questions spanning PNH screening, diagnostic criteria, investigations, treatment and monitoring of subclinical and classic disease, PNH with underlying bone marrow disorders, and PNH in pregnancy. A total of 181 papers were reviewed to formulate the statements. All experts voted on the statements via 2 rounds of Delphi and convened for an expert panel discussion to finetune the recommendations. Results: Sixteen statements have been formulated for optimising the screening, diagnosis and management of PNH. Upon confirmation of PNH diagnosis, individuals with active haemolysis and/or thrombosis should be considered for anti-complement therapy, with eculizumab being the only approved drug in Singapore. Conclusion: The current recommendations aim to guide the clinicians in optimising the screening, diagnosis and management of PNH in Singapore.

Prophylactic exchange transfusion in sickle cell disease pregnancy: a TAPS2 feasibility randomized controlled trial.

ABSTRACT: Serial prophylactic exchange blood transfusion (SPEBT) is increasingly used in sickle cell disease (SCD) pregnancy, despite a lack of robust evidence. The Transfusion Antenatally in Pregnant Women with Sickle Cell Disease (TAPS2) study assessed the feasibility and acceptability of conducting a definitive randomized controlled trial of SPEBT (intervention) vs standard care (control) in this population. Women aged ≥18 years with SCD, between 6+0 and 18+6 weeks of singleton gestation, were randomized 1:1 every 6 -10 weeks throughout pregnancy in 7 hospitals in England. The main outcomes were recruitment rate (primary outcome), acceptability, and retention. Secondary outcomes were safety and maternal/infant outcomes. In total, 194 women were screened over 42 months (extended because of the pandemic), 88 were eligible, and 35 (39.8%) consented to participate; 18 participants were randomized to intervention, and 17 to control. Follow-up data were collected on all participants. Twelve patients in the intervention group received at least 1 SPEBT, of these, 11 received ≥3. The remaining patient was withdrawn from SPEBT because of transfusion reaction. Sixteen control participants required at least 1 transfusion. There were no statistically significant differences in maternal, infant, and postnatal outcomes. A trend toward a lower incidence of vaso-occlusive crisis, preterm delivery, and improved birthweight was observed in the intervention. The study achieved satisfactory recruitment and retention, confirming its acceptability to participants. TAPS2 demonstrates that it is feasible to perform a definitive international trial of SPEBT in SCD pregnancy. These trials were registered at www.ClinicalTrials.gov as #NCT03975894 and International Standard Randomized Controlled Trial Number (www.isrctn.com; #ISRCTN52684446).

Neuraxial Anesthesia Following Thrombocyte Transfusion in Women with Severe Thrombocytopenia Prior to a Cesarean Delivery: A Retrospective Study and Literature Review.

BACKGROUND: Cesarean delivery (CD) is one of the most common surgeries performed worldwide, with increasing yearly rates. Although neuraxial techniques remain the preferred anesthesia method for CD, maternal thrombocytopenia remains a prominent contraindication. Formation of spinal\epidural hematomas are extremely rare, however the minimal thrombocyte count required for safe neuraxial anesthesia is still under debate. Although transfusion of thrombocytes for the purpose of neuraxial anesthesia is still not recommended, patients with severe thrombocytopenia (less than 50 × 103/uL) are given thrombocyte transfusion for surgical hemostasis. OBJECTIVES: To evaluate the anesthetic approach to caesarean deliveries in parturients with severe thrombocytopenia who received thrombocyte transfusion aimed for improved surgical hemostasis. METHODS: We conducted a single center, retrospective cohort study. Results: A total of five cases were found, four of which were given spinal anesthesia immediately following thrombocyte transfusion. One patient was denied spinal anesthesia because her thrombocyte count following transfusion failed to reach safe levels. None of our cases had anesthesia-related complications recorded. CONCLUSIONS: We examined the anesthetic management parturients with severe thrombocytopenia who needed cesarean delivery and were transfused with thrombocytes for surgical hemostasis. In such cases, spinal anesthesia may be considered due to the serious risks associated with general anesthesia.

Perinatal outcomes in pregnant women with ITP: a single tertiary center experience.

OBJECTIVES: In this study, we aimed to compare the maternal and neonatal outcomes in pregnant women diagnosed with idiopathic thrombocytopenic purpura (ITP) in our clinic between different platelet groups. METHODS: This study was designed retrospectively. A total of 62 pregnant women with ITP were included in the study. Demographic and clinical data for all cases were evaluated. Perinatal outcomes were evaluated according to platelet counts. RESULTS: The median age of the patients participating in the study was 27, and their ages ranged from 21 to 44. ITP was diagnosed before pregnancy in 32.3 % (n=20) of the patients and during pregnancy in 67.7 % (n=42). The average platelet counts of the patients during the first trimester and birth were 104.8/µL (15-168) and 84/µL (16-235), respectively. The average platelet count of newborns is 242/µL. The most common (74.2 %) ITP treatment method is the combination of steroids and IVIG. The platelet count of 80.6 % of newborns is above 151/µL. There was no statistical difference between the results of both mothers and fetuses when the groups were categorized according to maternal platelet levels. CONCLUSIONS: In this study, no difference was observed in maternal and neonatal morbidity and mortality rates, despite the different platelet counts of patients with ITP. The cooperation of the hematology, gynecology, obstetrics, and neonatology departments is responsible for this.

Hemostatic management of von Willebrand disease during childbirth with a plasma-derived von Willebrand factor/factor VIII concentrate.

BACKGROUND: Females with von Willebrand disease (VWD) do not show the same increases in von Willebrand factor and factor (F)VIII levels during pregnancy as females without VWD and are at higher risk of excessive bleeding associated with childbirth. Data on hemostatic management for childbirth in VWD patients are limited. OBJECTIVES: To evaluate the dosing, efficacy, and safety of plasma-derived von Willebrand factor/FVIII (wilate) for prevention of excessive bleeding associated with childbirth in females with any type of VWD. METHODS: Data for females with VWD who received wilate for hemostatic coverage for childbirth during 2 prospective clinical studies were analyzed. RESULTS: Ten females with VWD and a mean age at enrolment of 29.6 years were treated with wilate to prevent excessive bleeding associated with childbirth. Two patients had type 1, 4 had type 2 (2 2A, 1 2B, and 1 2M), and 4 had type 3 VWD. Of the 10 deliveries, 5 were by cesarean section. Patients received a mean of 9.5 infusions of wilate over 6.8 exposure days, with a mean total dose of 234 IU/kg per delivery and 25 IU/kg per infusion. Hemostatic management for all deliveries was rated excellent or good, with no excessive bleeding during delivery and no postpartum bleeding during the period of wilate treatment in any patient. Two patients experienced 8 possible or probable treatment-related adverse events; all were mild or moderate and resolved. No thromboembolic events were observed. CONCLUSION: The results of this case series indicate that wilate provided effective hemostatic cover for childbirth in females with VWD during delivery and postpartum.

Pregnancy-associated atypical hemolytic uremic syndrome. Case report.

Pregnancy-associated atypical hemolytic uremic syndrome (P-aHUS) is a rare disease. There are only few reports in the literature, and most are in the puerperium period. It is a thrombotic microangiopathy (TMA) characterized for microangiopathic hemolytic anemia, thrombocytopenia, and renal dysfunction. We report the case of a pregnant patient at 26.3 gestation weeks, who developed clinical features of TMA, neurological alterations, and septic shock; then after fetus and placental delivery, no clinical improvement was observed; a diagnostic protocol was performed due to suspicion of P-aHUS, showing improvement after the plasma exchange sessions and eculizumab. We present here a brief review of the case since it is an entity that needs to be suspected during pregnancy when TMA features and requires an immediate diagnosis to provide timely treatment.

Management of Primary Immune Thrombocytopenia: Turkish Modified Delphi-Based Consensus Statement for Special Considerations

Objective: Primary immune thrombocytopenia (ITP) is an acquired disorder of platelets with a complex and unclear mechanism of increased immune destruction or impaired production of platelets. While the management of ITP is evolving, there is still a need for guidance, particularly in certain circumstances such as pregnancy, emergencies, or patients requiring co-medications. We aimed to determine the tendencies of hematologists in Türkiye in the event of such special considerations. Materials and Methods: Applying a modified Delphi method, the Turkish National ITP Working Group, founded under the auspices of the Turkish Society of Hematology, developed a questionnaire consisting of statements regarding pregnancy, emergencies, and circumstances requiring co-treatment with antiaggregants or anticoagulants. A total of 107 hematologists working in university or state hospitals voted for their agreement or disagreement with the statements for two sequential rounds. Results: The participating hematologists reached an agreement on starting treatment for pregnant patients with platelets of less than 30x109/L and delivery either vaginally or by cesarean section being safe at platelet counts above 50x109/L. For emergencies and the rescue management of ITP, the panel agreed against the use of high-dose corticosteroids alone, preferring combinations with transfusions or intravenous immunoglobulin. For patients who require interventions, platelet counts of >50x109/L were regarded as safe for low-risk procedures as well as co-treatment with antiplatelets or anticoagulants. Conclusion: As the National ITP Study Group, we have observed the need to increase the practice guidance regarding patients with primary ITP requiring additional treatments including invasive interventions and co-treatments for coagulation. Decisions on the management of ITP during pregnancy should be individualized. There is a lack of consensus on the thresholds of platelet counts as well as co-morbidities and co-medications. This lack of consensus may be due to variations in practices.

Case report of thrombotic thrombocytopenic purpura during pregnancy with a review of the relevant research.

RATIONALE: Thrombotic thrombocytopenic purpura (TTP) is a syndrome characterized by widespread blood vessel clotting and bleeding. It can affect individuals of any age but is more commonly observed in females, particularly during pregnancy. Pregnancy combined with TTP is a critical and rapidly progressing condition that is often misdiagnosed as an obstetric disorder like severe preeclampsia or HELLP syndrome. To deepen the understanding of TTP during pregnancy with the help of a clinical case. PATIENT CONCERNS: A 20-year-old patient, is pregnancy 1 birth 0, 32 weeks dated by her last menstrual period, presented chest tightness, and shortness of breath after physical activity for 3 days. DIAGNOSES: TTP. INTERVENTIONS: At present, there are no preventive measures. Timely diagnosis and treatment are useful. Plasma exchange and treat to the patient hinder autoantibodies, such as gamma globulin, methylprednisolone, rituximab, and cyclosporine were effective. OUTCOMES: The patient exhibited stable vital signs, normal examination results, and experienced no complications. We continued to monitor her progress after she was discharged. LESSONS SUBSECTIONS: The acute onset of TTP is often associated with pregnancy, as it is a triggering factor. Timely identification, accurate diagnosis, and a comprehensive treatment approach involving plasma exchange, immunosuppressants, and the termination of pregnancy can lead to remission and a favorable outlook for the majority of patients.

Data integrity of 14 randomised controlled trials.

BACKGROUND: A review of the literature on iron treatments for iron-deficient anaemia in pregnancy indicated duplication of baseline and outcome tables in two separate randomised controlled trials (RCTs) that share only a single author. AIM: To assess the integrity of randomised clinical trials from Dr A.M. Darwish, Assiut University, Egypt. DESIGN: Assessment of Research Integrity. METHODS: We tabulated the characteristics of studies, compared baseline and outcome tables between articles and looked for implausible findings. We used the distribution of baseline p-values to assess whether the summary statistics of baseline characteristics were consistent with properly conducted randomisation. RESULTS: We identified 14 RCTs (1,405 participants) published between October 2004 and September 2019. Two pairs of studies showed considerable similarities in baseline characteristics, while another pair of studies was plagiarized. The analysis of baseline p-values indicated a low probability that all the studies featured randomised treatment allocation. CONCLUSION: Our analysis of the RCTs of Dr Darwish suggests possible integrity problems. We recommend a critical investigation of the studies that have not been retracted. Until that has been completed, these studies should not be used to inform clinical practice.

Guideline for the management of conception and pregnancy in thalassaemia syndromes: A British Society for Haematology Guideline.

This comprehensive guideline, developed by a representative group of UK-based medical experts specialising in haemoglobinopathies, addresses the management of conception and pregnancy in patients with thalassaemia. A systematic search of PubMed and EMBASE using specific keywords, formed the basis of the literature review. Key terms included "thalassaemia," "pregnancy," "Cooley's anaemia," "Mediterranean anaemia," and others, covering aspects such as fertility, iron burden and ultrasonography. The guideline underwent rigorous review by prominent organisations, including the Endocrine Society, the Royal College of Obstetricians and Gynaecologists (RCOG), the United Kingdom Thalassaemia Society and the British Society of Haematology (BSH) guideline writing group. Additional feedback was solicited from a sounding board of UK haematologists, ensuring a thorough and collaborative approach. The objective of the guideline is to equip healthcare professionals with precise recommendations for managing conception and pregnancy in patients with thalassaemia.

The influence of hematological profiles on the transfusion management and mortality risk of mothers presenting to the obstetric unit of a South African tertiary medical facility.

BACKGROUND: Laboratory results are frequently abnormal in pregnant mothers. Abnormalities usually relate to pregnancy or associated complications. Hematological abnormalities and age in pregnancy may increase the likelihood for transfusion and mortality. STUDY DESIGN AND METHODS: Hematological profiles and transfusion history of pregnant mothers presenting to a tertiary hospital, were evaluated over 2 years. Age, anemia, leukocytosis and thrombocytopenia were assessed for transfusion likelihood. Iron deficiency and coagulation were assessed in transfused patients. Anemia, leukocytosis, thrombocytopenia, human immunodeficiency virus (HIV) and transfusion were assessed for mortality likelihood. RESULTS: There were 12,889 pregnant mothers included. Mothers <19-years-old had the highest prevalence of anemia (31.5%) and proportion of transfusions (19%). The transfusion likelihood was increased in mothers with anemia (odds ratios [OR] = 6.41; confidence intervals at 95% [95% CI] 5.46-7.71), leukocytosis (OR = 2.35; 95% CI 2.00-2.76) or thrombocytopenia (OR = 2.71; 95% CI 2.21-3.33). Mothers with prolonged prothrombin times received twice as many blood products as their normal counterparts (p = .03) and those with iron deficiency anemia five times more blood products (p < .001). Increased likelihood for mortality was seen in patients with anemia (OR = 4.15, 95% CI 2.03-8.49), leukocytosis (OR = 2.68; 95% CI 1.19-6.04) and those receiving blood transfusion (OR = 3.6, 95% CI 1.75-7.47). DISCUSSION: Adolescence, anemia, leukocytosis and thrombocytopenia expose mothers to a high risk for transfusion and/or mortality. These risk factors should promptly trigger management and referral of patients. Presenting hematological profiles are strong predictors of maternal outcome and transfusion risk.

A Case of Pregnancy-Induced Hereditary Thrombotic Thrombocytopenic Purpura Complicated by Cerebral Vasospasm.

BACKGROUND: The aim was to explore the treatment of a case of congenital thrombotic thrombocytopenic purpura induced by pregnancy complicated with cerebral vasospasm. METHODS: We present a case study of congenital TTP where disease onset occurred during two separate pregnancies. Interestingly, the disease course exhibited distinct differences on each occasion. Additionally, following plasma transfusion therapy, there was a transient occurrence of cerebral vasospasm. RESULTS: In this case, ADAMTS13 levels reached their lowest point three days after delivery during the first pregnancy, triggering morbidity. Remarkably, a single plasma transfusion of 400 mL sufficed for the patient's recovery. Nonetheless, a recurrence of symptoms transpired during her second pregnancy at 24 weeks of gestation. Plasma transfusions were administered during and after delivery. Sudden convulsions developed. ADAMTS13 ac-tivity returned to normal, but cranial MRA revealed constrictions in the intracranial segments of both vertebral arteries, the basilar artery, and the lumen of the anterior, middle, and posterior cerebral arteries. A subsequent cranial MRA conducted a month later showed no lumen stenosis, indicating spontaneous recovery. CONCLUSIONS: These findings highlight the importance of careful consideration when administering plasma transfusions in congenital TTP during pregnancy. Moreover, the development of novel therapeutic approaches such as recombinant ADAMTS13 is crucial for minimizing complications and optimizing patient care.