Atypical thrombosis occurs in unconventional anatomical sites such as splanchnic, renal, gonadal, and cerebral venous vessels [1] . Genetic factors, as inherited thrombophilia could increase the risk of atypical thrombosis. Likewise, acquired disease, as cancer, autoimmune diseases (e.g. systemic lupus erythematosus and APS) or infections [e.g. Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections], can trigger such an inflammatory response which lead to thrombocytosis and endothelial injury, thus promoting a hypercoagulability state [2,3] . Among cancers, myeloproliferative disorders are associated to an elevated risk of atypical thrombosis due to the increase in platelets or red blood cell count and the alteration of the balance between pro-coagulant e anticoagulant endothelial factors [4-6] . Other conditions that may predispose to atypical thrombotic events are platelet disfunction or structural abnormalities, chronic vascular diseases, pregnancy and medications. This case highlights the interplay of factors contributing to the development of thrombosis in an unconventional site and underscores the importance of a comprehensive diagnostic approach.
A 35-year-old woman presented with a deep vein thrombosis (DVT) and was diagnosed with protein S deficiency. She was treated with parenteral anticoagulation before switching to a direct oral anticoagulant. She presented to our practice 5 years later, where testing was repeated, demonstrating a type III deficiency pattern and a variant of uncertain significance in PROS1: c.1424G>A; p.Cys475Tyr. This cysteine residue participates in a disulfide bond in the sex hormone-binding globulin-like domain, which interacts with C4b-binding protein and is involved in several antithrombotic roles of protein S. This case report and the biochemical context support its pathogenicity.
Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) share overlapping symptoms, and emerging evidence implicates persistent fibrinoid microclots in their pathophysiology, contributing to impaired microcirculation. This review explores the role of microclots and evaluates thromboelastography (TEG) as a potential diagnostic tool. A comprehensive literature review was conducted using major biomedical databases. Studies indicate microclots are prevalent in both conditions. Long COVID patients demonstrate a TEG profile of increased clot strength (maximum amplitude) and reduced fibrinolysis (LY30), suggesting a persistent hypercoagulable state. Despite its advantages in real-time assessment, TEG interpretation faces challenges from preanalytical variability and a lack of standardized protocols. Promising therapeutic trials, including anticoagulants (e.g., apixaban) and fibrinolytics (e.g., lumbrokinase), require further validation. Technological advancements like AI-driven TEG analysis and portable devices could improve diagnostic precision. In conclusion, persistent microclots are a key pathophysiological feature. TEG provides a promising, novel approach for detecting coagulation abnormalities and could guide treatment, but requires standardization in future clinical trials. Future research should integrate multiomics biomarkers for precision therapeutics to improve patient outcomes.
BACKGROUND:Uterine fibroids are a prevalent gynecologic condition traditionally associated with heavy menstrual bleeding and pelvic pressure. However, emerging evidence suggests that large uterine fibroids may also contribute to venous thromboembolism (VTE) by causing mechanical compression of pelvic veins and the inferior vena cava, leading to venous stasis and subsequent thrombosis. This narrative review aims to consolidate current knowledge, discuss diagnostic strategies and management approaches for fibroid-associated VTE, and raise clinical awareness about this often-overlooked complication. METHODS:A comprehensive literature search was conducted across PubMed, PubMed Central, Embase, Scopus, and Google Scholar from January 2000 to April 2024. Studies examining the relationship between uterine fibroids and VTE, including case reports, observational studies, reviews, and management guidelines, were included. A descriptive synthesis of findings was performed. RESULTS:Twenty-four studies were included, demonstrating a consistent association between large uterine fibroids and increased VTE risk. Key mechanisms included venous compression, hormonal influences, and a fibroid-associated hypercoagulable state. Clinical presentations ranged from isolated deep vein thrombosis (DVT) to life-threatening pulmonary embolism (PE). Early diagnosis often relied on pelvic imaging such as ultrasound and MRI. Management strategies involved prompt anticoagulation, individualized surgical planning (primarily hysterectomy), and multidisciplinary coordination. In select cases, prophylactic anticoagulation was suggested for high-risk patients pending surgery. CONCLUSION:Uterine fibroids should be recognized as a potential etiology for unexplained VTE, particularly in women without classic risk factors. Early imaging, anticoagulation, and surgical intervention, when appropriate, can optimize outcomes. Further research is needed to establish standardized screening and management guidelines for this underrecognized cause of thromboembolic disease.
Glanzmann thrombasthenia is an inherited platelet disorder resulting from defects in the integrin αIIbβ3 complex due to mutations in the ITGA2B or ITGB3 genes. This study aimed to elucidate the molecular and clinical characteristics of Glanzmann thrombasthenia in a Tunisian cohort. Twelve patients from 11 unrelated families were evaluated using clinical examination, platelet function assays, and comprehensive genetic analysis. Genomic DNA was extracted from peripheral blood, and the entire coding regions along with intron-exon boundaries of ITGA2B were amplified and sequenced via Sanger sequencing. Molecular analysis identified seven likely pathogenic variants in 9 out of 12 patients, including five missense mutations, of which two were novel (p.Tyr221Asp and p.Gly929Trp), one frameshift mutation, and one large deletion spanning exons 19-29. Additionally, three benign variants were detected in five patients, while one patient exhibited no ITGA2B mutation, suggesting a potential defect in ITGB3 . Three previously reported missense variants (p.Gln165His, p.Arg584Gln, and p.Ser957Leu) and an intronic splicing variant (c.2095-22_2095-19del) were also identified. Clinically, patients presented with heterogeneous bleeding phenotypes, predominantly epistaxis and gingival bleeding. Genotype-phenotype correlations underscore that mutation type and location critically influence disease severity. These findings expand the mutational spectrum of ITGA2B and emphasize the need for further functional studies to inform targeted therapies.
