Blood Coagulation & Fibrinolysis最新文献

Heparin-induced thrombocytopenia (HIT) is an immune-mediated condition characterized by a decrease in platelet count and an increased thrombotic risk. HIT event is caused by antiplatelet factor/heparin (PF4/H) antibodies that can activate the platelets. The diagnosis of HIT is based on a clinical evaluation and laboratory results. Aim of our study was to evaluate whether the combined use of two rapid assays for diagnosis of HIT provides a diagnostic advantage over the use of a single automate assay. We extracted from the laboratory informatic system all the determinations requested for the detection of antibodies against heparin/PF4 complexes from July 2020 to June 2024 (n. 229). In our laboratory, total antibodies against heparin/PF4 complex [HemosIL HIT-Ab-(PF4-H), Instrumentation Laboratory] and IgG Ab (HemosIL AcuStar HIT-IgG, Instrumentation Laboratory) are measured simultaneously with two different instruments. Two hundred six samples tested negative for both methods, 23 samples tested positive for at least one method and nine samples tested positive for both methods. The grade of concordance between the two assays shows a weighted Kappa of 0.536 (moderate agreement). No sample tested positive only for IgG-Ab. The sensitivity of HIT-Ab-(PF4-H) was 1, whereas the specificity was 0.95. For the HIT-IgG (PF4-H) method, sensibility and specificity were 0.77 and 1, respectively. Our results suggest that performing these two tests simultaneously does not provide additional useful information in patients with suspicion of HIT. The total Ab assay seems to be sufficient, as it shows higher sensitivity although at the expense of lower specificity.

Objective: The purpose of this study was to determine the molecular basis of a Chinese family with factor XI (FXI) deficiency.

Methods: The qRT-PCR was used to detect the transcription of F11 mRNA in transfected cells. ELISAs and western blot were used to detect the expression of FXI protein in culture media and lysates.

Results: Genetic analysis revealed that the proband carried a heterozygous nonsense mutation c.1107C>A (p.Tyr351stop) in exon 10 and a heterozygous missense mutation c.1562A>G (p.Tyr503Cys) in exon 13. The expression study revealed that p.Tyr351stop mutation resulted in the degradation of F11 mRNA. The p.Tyr503Cys mutation, however, had no effects on biosynthesis and secretion of FXI protein, but it had affected the catalytic activity of FXI.

Conclusion: The inherited FXI deficiency of this family is related to nonsense mutation p.Tyr351stop and missense mutation p.Tyr503Cys.

Venous thromboembolism (VTE) risk in pregnant women is four to five-fold higher than in nonpregnant women, and the risk of VTE is an additional four-fold higher after Cesarean section compared to normal vaginal delivery. Recommendations regarding anticoagulant prophylaxis are inconsistent across international guidelines, and VTE remains one of the leading causes of maternal morbidity and mortality. This study aimed to compare the need for postcesarean anticoagulation for VTE prophylaxis based on three major guidelines and our own institutional protocol. It was a retrospective cohort study that reviewed the medical records of patients who underwent a cesarean section at a tertiary-level care hospital in the United Arab Emirates (UAE). The need for anticoagulation was assessed using clinical tools from the American College of Obstetricians and Gynecologists (ACOG), Royal College Obstetricians and Gynecologists (RCOG), American College of Chest Physicians (ACCP), and the study site hospital protocol. A total of 1134 postcesarean women, aged 18-55 years, were included in the study. Most patients (87%) were at moderate risk for VTE. According to the study site hospital tool, 90.7% qualified for anticoagulant prophylaxis, while the ACOG, RCOG, and ACCP tools indicated that 0.5, 90.9, and 36.7% qualified, respectively. Enoxaparin was the primary anticoagulant used in 95% of cases. Only one patient developed VTE during the follow-up period. Anticoagulation needs assessment tools vary extensively in their estimations, highlighting the need for a uniform tool across multiple societies to establish a consistent standard of care and guide the development of evidence-based, site-specific protocols.

Background: Congenital dysfibrinogenemia is characterized by reduced fibrinogen activity, but normal immunoreactive fibrinogen levels. Here, we present a novel case with an elevated risk of thrombosis.

Methods: Coagulation assays, gene analysis, in silico tools, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), fibrin polymerization, thrombin generation assay, and electron microscopy scanning were utilized to elucidate the pathogenic mechanism.

Results: The proband manifested with a normal immunologic fibrinogen (2.13 g/l) but reduced functional fibrinogen (0.39 g/l). Subsequent genetic analysis unveiled a novel heterozygous mutation, c.1030G>C (p.Asp318His), in the γ-chain D domain of fibrinogen, which was highly conserved in homologous species and led to enhanced thrombin generation capability. The ability of the proband's fibrinogen to polymerize was significantly impaired, with decreased final turbidity. Scanning electron microscopy indicated that the fibers of the proband were thinner than normal, with smaller pores. Thromboelastography (TEG) results demonstrated prolonged K time, decreased angle value, and a normal confidence interval value in the proband.

Conclusion: We present a novel case displaying the γAsp318His mutation, which resulted in dysfibrinogenemia.

Hereditary antithrombin (AT) deficiency due to mutations in SERPINC1 is known to be the most severe form of thrombophilia. We report three members in a family with hereditary AT deficiency with a novel mutation in exon 2 of SERPINC1, that is c.119 G>A (p.Cys40Tyr). Two brothers presented with acute pulmonary thromboembolism (PTE) at 18 and 21 years of age, whereas their 58-year-old father did not have any thrombotic episode till date. The in-silico prediction of the variant was found to be highly damaging by PolyPhen-2, SIFT and MutationTaster. Clinical exome sequencing did not show any strong coinherited thrombophilia genes, except SERPINE1 -844 G>A variant in homozygous state in the two affected brothers as compared to the father who was heterozygous for this variant. The additive effect of SERPINE1 variant in the clinical expression in two siblings cannot be ruled out, in the absence of any other known environmental triggering factors.

Protein C deficiency is a rare autosomal recessive disorder associated with a high risk of thromboembolic complications. This case report describes the challenges in managing a 23-year-old woman with severe homozygous protein C type 1 deficiency diagnosed since early infancy. Her medical history included misdiagnosed cellulitis, recurrent thrombosis, and permanent vision loss in one eye. The laboratory workup confirmed a diagnosis of severe protein C deficiency. Management involved a combination of fresh frozen plasma (FFP), protein C concentrate, warfarin, and heparin, with ongoing challenges due to recurrent thrombosis and anaphylaxis to FFP. This case highlights the challenges in the diagnosis and management of severe protein C deficiency. Although current treatment options provide partial control, further research is crucial to develop safer and more effective therapies to improve long-term outcomes for affected patients.

Hereditary antithrombin (AT) deficiency due to mutations in SERPINC1 is known to be the most severe form of thrombophilia. We report three members in a family with hereditary AT deficiency with a novel mutation in exon 2 of SERPINC1, that is c.119 G>A (p.Cys40Tyr). Two brothers presented with acute pulmonary thromboembolism (PTE) at 18 and 21 years of age, whereas their 58-year-old father did not have any thrombotic episode till date. The in-silico prediction of the variant was found to be highly damaging by PolyPhen-2, SIFT and MutationTaster. Clinical exome sequencing did not show any strong coinherited thrombophilia genes, except SERPINE1 -844 G>A variant in homozygous state in the two affected brothers as compared to the father who was heterozygous for this variant. The additive effect of SERPINE1 variant in the clinical expression in two siblings cannot be ruled out, in the absence of any other known environmental triggering factors.

Background: Congenital dysfibrinogenemia is characterized by reduced fibrinogen activity, but normal immunoreactive fibrinogen levels. Here, we present a novel case with an elevated risk of thrombosis.

Methods: Coagulation assays, gene analysis, in silico tools, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), fibrin polymerization, thrombin generation assay, and electron microscopy scanning were utilized to elucidate the pathogenic mechanism.

Results: The proband manifested with a normal immunologic fibrinogen (2.13 g/l) but reduced functional fibrinogen (0.39 g/l). Subsequent genetic analysis unveiled a novel heterozygous mutation, c.1030G>C (p.Asp318His), in the γ-chain D domain of fibrinogen, which was highly conserved in homologous species and led to enhanced thrombin generation capability. The ability of the proband's fibrinogen to polymerize was significantly impaired, with decreased final turbidity. Scanning electron microscopy indicated that the fibers of the proband were thinner than normal, with smaller pores. Thromboelastography (TEG) results demonstrated prolonged K time, decreased angle value, and a normal confidence interval value in the proband.

Conclusion: We present a novel case displaying the γAsp318His mutation, which resulted in dysfibrinogenemia.

Factor XIII (FXIII), a plasma transglutaminase, is a coagulation factor that plays a crucial role in blood clotting and patient blood management. The studies have demonstrated that FXIII targets a wide range of additional substrates that have an important role in hemostasis, especially in posttraumatic patients, patients undergoing surgery or obstetrics, being involved in wound healing and tissue repair. Morover, FXIII deficiency has also been described and an extensive research has shown that FXIII deficiency is a rare coagulopathy that leads to longer bleeding time, perioperative and postoperative complications and slower wound healing. Present article aims to overview the diverse functions of FXIII and to highlight its role in patient blood management.

Factor VII deficiency is a rare hemostatic disorder that can lead to severe clinical outcomes. Due to the scarcity of reported cases, treatment guidelines for this condition remain unclear. In this report, we present a case of acquired factor VII deficiency (aFVII) in an elderly female with medullary aplasia. The initial clinical manifestation was hemarthrosis, accompanied by a rapid increase in prothrombin time. Prompt intervention involved supplementation to address the deficiency. Subsequent laboratory testing failed to detect any specific factor VII inhibitor. Considering the patient's frailty, immunosuppressive therapy comprising only corticosteroids was administered. The potential triggering mechanisms may include recurrent episodes of sepsis or an underlying autoimmune condition. Further research is necessary to better understand the etiology and optimal management of aFVII deficiency.