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Ultrasound in Obstetrics & Gynecology :... Jun 2024Management of placenta accreta spectrum (PAS) with the placenta kept in situ aims to preserve fertility and minimize blood loss. However, this method is associated with... (Review)
Review
OBJECTIVE
Management of placenta accreta spectrum (PAS) with the placenta kept in situ aims to preserve fertility and minimize blood loss. However, this method is associated with a risk of coagulopathy and subsequent bleeding. The aim of this study was to evaluate the occurrence and pathophysiology of coagulopathy in cases of PAS managed conservatively.
METHODS
We reviewed our database for cases of PAS in which the placenta was kept in situ. In addition, we performed a systematic review of articles on PAS in which the placenta was left in situ and was complicated by coagulopathy. PubMed was searched for publications between 1980 and 2023. Our eligibility criteria included studies in which no additional interventions were performed other than keeping the placenta entirely in situ, and in which coagulopathy was reported.
RESULTS
After screening and selection of full-text articles, 10 studies were included in the review. A review of our databases yielded a case series of PAS managed conservatively with the placenta kept in situ. When adding our case series to the results of our systematic review, a total of 87 cases were found to have been managed conservatively, with 28 cases of coagulopathy. Of these, the time at which coagulopathy developed was known in 11 cases. The median time at development of coagulopathy was 58 (interquartile range, 50-67) days postpartum.
CONCLUSIONS
Our findings highlight that conservative management of PAS with the placenta in situ poses a risk of coagulopathy. Keeping the placenta in situ after delivery prolongs the risk factors that are integral to PAS. The pathophysiology behind coagulopathy is comparable with that of concealed placental abruption, due to the disrupted uteroplacental interface and the collection of blood in the placenta. Therefore, the presence of large placental lakes could be an indicator of developing coagulopathy. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Humans; Female; Placenta Accreta; Pregnancy; Conservative Treatment; Blood Coagulation Disorders; Postpartum Hemorrhage; Adult; Placenta
PubMed: 38030960
DOI: 10.1002/uog.27547 -
Thrombosis Research Sep 2022Ranging from bleeding to thrombosis, the clinical features of congenital fibrinogen qualitative disorders, including dysfibrinogenemia and hypodysfibrinogenemia, are... (Review)
Review
Ranging from bleeding to thrombosis, the clinical features of congenital fibrinogen qualitative disorders, including dysfibrinogenemia and hypodysfibrinogenemia, are highly heterogeneous. Although the associations between some specific fibrinogen mutations and the thrombotic phenotypes have been well elucidated, the underlying mechanism between fibrinogen variants and bleeding events remains underestimated. After systematically reviewing the literature of (hypo-)dysfibrinogenemia patients with bleeding phenotypes, we identified several well-characterized bleeding-related fibrinogen variants in those patients. Several possible pathomechanisms are proposed to explain the genotype-phenotype associations: 1, mutations in the NH-terminal portion of the Aα chain hamper fibrinogen fitting into the active site cleft of thrombin and drastically slow the conversion of fibrinogen into monomeric fibrin; 2, mutations adding new N-linked glycosylation sites introduce bulky and negatively charged carbohydrate side chains and undermine the alignment of fibrin monomers during polymerization; 3, mutations generating unpaired cysteine form extra disulfide bonds between the abnormal fibrinogen chains and produce highly branched and fragile fibrin networks; 4, truncation mutations in the fibrinogen αC regions impair the lateral fibril aggregation, as well as factor XIII crosslinking, endothelial cell and platelet binding. These established relationships between specific variants and the bleeding tendency will help manage (hypo-)dysfibrinogenemia patients to avoid adverse bleeding outcomes.
Topics: Afibrinogenemia; Blood Coagulation Tests; Fibrin; Fibrinogen; Fibrinogens, Abnormal; Hemorrhage; Humans; Thrombosis
PubMed: 35853369
DOI: 10.1016/j.thromres.2022.07.005 -
Anaesthesia and Intensive Care Sep 2020Hypofibrinogenaemia during cardiac surgery may increase blood loss and bleeding complications. Viscoelastic point-of-care tests provide more rapid diagnosis than...
Hypofibrinogenaemia during cardiac surgery may increase blood loss and bleeding complications. Viscoelastic point-of-care tests provide more rapid diagnosis than laboratory measurement, allowing earlier treatment. However, their diagnostic test accuracy for hypofibrinogenaemia has never been reviewed systematically. We aimed to systematically review their diagnostic test accuracy for the identification of hypofibrinogenaemia during cardiac surgery. Two reviewers assessed relevant articles from seven electronic databases, extracted data from eligible articles and assessed quality. The primary outcomes were sensitivity, specificity and positive and negative predictive values. A total of 576 articles were screened and 81 full texts were assessed, most of which were clinical agreement or outcome studies. Only 10 diagnostic test accuracy studies were identified and only nine were eligible (ROTEM 7; TEG5000 1; TEG6S 1, = 1820 patients) (ROTEM, TEM International GmbH, Munich, Germany; TEG, Haemonetics, Braintree, MA, USA). None had a low risk of bias. Four ROTEM studies with a fibrinogen threshold less than 1.5-1.6 g/l and FIBTEM threshold A10 less than 7.5-8 mm had point estimates for sensitivity of 0.61-0.88; specificity 0.54-0.94; positive predictive value 0.42-0.70; and negative predictive value 0.74-0.98 (i.e. false positive rate 30%-58%; false negative rate 2%-26%). Two ROTEM studies with higher thresholds for both fibrinogen (<2 g/l) and FIBTEM A10 (<9.5 mm) had similar false positive rates (25%-46%), as did the two TEG studies (15%-48%). This review demonstrates that there have been few diagnostic test accuracy studies of viscoelastic point-of-care identification of hypofibrinogenaemia in cardiac surgical patients. The studies performed so far report false positive rates of up to 58%, but low false negative rates. Further diagnostic test accuracy studies of viscoelastic point-of-care identification of hypofibrinogenaemia are required to guide their better use during cardiac surgery.
Topics: Afibrinogenemia; Cardiac Surgical Procedures; Germany; Humans; Point-of-Care Systems; Thrombelastography
PubMed: 33016097
DOI: 10.1177/0310057X20948868 -
Haemophilia : the Official Journal of... Sep 2019Hereditary fibrinogen disorders (HFD) are rare quantitative or qualitative fibrinogen anomalies, including afibrinogenaemia (A), hypofibrinogenaemia (H),...
INTRODUCTION
Hereditary fibrinogen disorders (HFD) are rare quantitative or qualitative fibrinogen anomalies, including afibrinogenaemia (A), hypofibrinogenaemia (H), dysfibrinogenaemia (D) and hypodysfibrinogenaemia (HD). As fibrinogen plays an essential role in pregnancy, we addressed the issue of obstetrical and postpartum complications in women with HFD.
METHODS
A systematic literature review, restricted to English manuscripts, was conducted according to the PRISMA guidelines. We searched through the MEDLINE database for English articles, published from January 1985 until November 2018, focusing on pregnancy in A, H, D and HD. A total of 198 articles were identified, 15 articles were added from other sources. Overall, 213 articles were screened and 54 were included in the final analysis.
RESULTS
A total of 188 pregnancies from 70 women were analysed. About half of pregnancies resulted in miscarriage; more specifically in 15 (42.9%), 36 (46.8%), 27 (42.9%) and 4 (30.8%) of A, H, D and HD patients, respectively. Preterm complications were also frequent (33.5%). Metrorrhagia, mainly in the first trimester, was observed in 21.7% of the pregnancies. Placenta abruption was reported in 5 (14.3%), 4 (5.2%), 5 (7.9%) and 1 (7.7%) of A, H, D and HD, respectively. A total of 24 (12.7%) deliveries were complicated by postpartum thrombotic events (3.2%) or postpartum haemorrhage (9.6%). A fibrinogen replacement therapy was introduced in 30% of pregnancies, as prophylaxis (81.1%) or on demand (18.9%).
CONCLUSION
These results suggest that women with HFD are at high risk of obstetrical and postpartum complications. Prospective international registries may allow to identify more precisely the incidence of obstetrical and postpartum adverse outcomes and their management.
Topics: Adult; Afibrinogenemia; Female; Humans; Obstetrics; Postpartum Hemorrhage; Pregnancy
PubMed: 31368232
DOI: 10.1111/hae.13825 -
Journal of Thrombosis and Haemostasis :... May 2017Essentials Hypodysfibrinogenemia is rarely reported among the congenital fibrinogen disorders. This first systematic literature review led to identification of 51... (Review)
Review
UNLABELLED
Essentials Hypodysfibrinogenemia is rarely reported among the congenital fibrinogen disorders. This first systematic literature review led to identification of 51 hypodysfibrinogenemic cases. Diagnosis based only on functional/antigenic fibrinogen ratio may be insufficient. Family studies show an incomplete segregation of mutation with the clinical phenotypes.
SUMMARY
Background Hypodysfibrinogenemia is a rare disease characterized by decreased levels of a dysfunctional fibrinogen. It shares features with both hypo- and dysfibrinogenemia, although with specific molecular patterns and clinical phenotypes. Objectives To better define the genetics, the diagnosis and the clinical features of hypodysfibrinogenemia. Patients/Methods A systematic literature search led to 167 records. After removal of duplicates, abstract screening and full-text reviewing, 56 molecular and/or clinical studies were analyzed, including a novel FGB missense mutation in a woman with a mild bleeding phenotype. Results A total of 32 single causative mutations were reported, mainly in the COOH-terminal region of the γ or Aα chains at heterozygous or homozygous state. Seven additional hypodysfibrinogenemias were due to compound heterozygosity. The hypofibrinogenemic phenotypes were a result of an impaired assembly or secretion or an increased clearance of the fibrinogen variant, whereas the dysfibrinogenemic phenotype was mainly a result of a defective fibrin polymerization and an abnormal calcium or tPA binding. Among 51 identified index cases, a functional/antigenic fibrinogen ratio < 0.7 had a sensitivity of 86% for the diagnosis of hypodysfibrinogenemia. Eleven patients (22%) were asymptomatic at time of diagnosis, 23 (45%) had a mild bleeding phenotype with mainly obstetrical or gynecologic-related hemorrhage and 22 (43%) had experienced at least one thrombotic event, including 23 venous and eight arterial thromboses. Conclusions This first systematic review on hypodysfibrinogenemia shows the heterogeneity of causative mutations and that misdiagnosis could occur in relation to the functional and antigenic fibrinogen levels. Family studies reveal an incomplete segregation of the mutation with the clinical phenotype.
Topics: Adult; Afibrinogenemia; Blood Coagulation; Blood Coagulation Tests; DNA Mutational Analysis; Female; Fibrinogen; Genetic Markers; Genetic Predisposition to Disease; Heterozygote; Humans; Mutation, Missense; Phenotype
PubMed: 28211264
DOI: 10.1111/jth.13655 -
Thrombosis and Haemostasis Sep 2016Frequent arterial and venous thromboembolism in patients with congenital afibrinogenaemia (CA) is neither understood nor is a safe and effective treatment established.... (Review)
Review
Frequent arterial and venous thromboembolism in patients with congenital afibrinogenaemia (CA) is neither understood nor is a safe and effective treatment established. It was our objective to report on the clinical observations and laboratory data contributing to the understanding of the frequency, physiopathology, prognosis and treatment of CA. We observed the long-term clinical course and laboratory data in a cohort of four patients with CA and thromboembolic complications, and conducted a systematic review retrieving all available data. Four patients with CA developed recurrent and extensive arterial and venous thromboembolism (TE) from an age of 25-51 years. In two patients, a treatment strategy targeting at maintaining constantly measurable fibrinogen (Fbg) levels (≥0.5 g/l) either by regular Fbg replacement or by orthotopic liver transplantation resulted in long-term remissions. Radiological imaging documented resolved arterial thrombi after 6-12 months. In contrast, recurrent thromboembolic events were observed in two other patients with infrequent Fbg replacement. A systematic review of the literature revealed 48 reports of TE in patients with CA (median age at first event 31 years), and a favourable outcome in most patients with frequent application of Fbg, aimed at constantly measurable trough levels. Present data suggests that patients with CA are at high risk of arterial and venous thromboembolic events, probably caused by thrombin excess owing to lack of thrombin scavenging by Fbg/fibrin. Regular low-dose Fbg replacement might be a safe and effective treatment option in patients with CA and thromboembolic complications.
Topics: Adult; Afibrinogenemia; Female; Humans; Male; Middle Aged; Treatment Outcome; Venous Thromboembolism
PubMed: 27384135
DOI: 10.1160/TH16-02-0082 -
PloS One 2014Though rare in occurrence, patients with rare bleeding disorders (RBDs) are highly heterogeneous and may manifest with severe bleeding diathesis. Due to the high rate of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Though rare in occurrence, patients with rare bleeding disorders (RBDs) are highly heterogeneous and may manifest with severe bleeding diathesis. Due to the high rate of consanguinity in many caste groups, these autosomal recessive bleeding disorders which are of rare occurrence in populations across the world, may not be as rare in India.
OBJECTIVES
To comprehensively analyze the frequency and nature of mutations in Indian patients with RBDs.
METHODS
Pubmed search was used (www.pubmed.com) to explore the published literature from India on RBDs using the key words "rare bleeding disorders", "mutations", "India", "fibrinogen", "afibrinogenemia", "factor II deficiency", "prothrombin" "factor VII deficiency", "factor V deficiency", "factor X deficiency", "factor XI deficiency", "combined factor V and VIII deficiency", "factor XIII deficiency", "Bernard Soulier syndrome" and "Glanzmanns thrombasthenia" in different combinations. A total of 60 relevant articles could be retrieved. The distribution of mutations from India was compared with that of the world literature by referring to the Human Gene Mutation Database (HGMD) (www.hgmd.org).
RESULTS
Taken together, 181 mutations in 270 patients with different RBDs have been reported from India. Though the types of mutations reported from India and their percentage distribution with respect to the world data are largely similar, yet much higher percentage of small deletions, duplication mutations, insertions, indels were observed in this analysis. Besides the identification of novel mutations and polymorphisms, several common mutations have also been reported, which will allow to develop a strategy for mutation screening in Indian patients with RBDs.
CONCLUSION
There is a need for a consortium of Institutions working on the molecular pathology of RBDs in India. This will facilitate a quicker and cheaper diagnosis of RBDs besides its utility in first trimester prenatal diagnosis of the affected families.
Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Databases, Genetic; Fibrinogen; Humans; India; Mutation; Pathology, Molecular; Rare Diseases
PubMed: 25275492
DOI: 10.1371/journal.pone.0108683