Laparoscopic Sleeve Gastrectomy with Staple-Line Oversewing in a Patient with Factor XI Deficiency: A Case Report.

BACKGROUND Bariatric surgery (BS) has a lower percentage of complications than other abdominal surgeries. Hemorrhage in one of the most common complications and can be life-threatening. Hereditary factor XI (FXI) deficiency is a coagulation disorder that can result in excessive bleeding requiring intervention to restore hemostasis. Risks over benefits in patients with morbid obesity with BS indication, as well as those with FXI deficiency, should be carefully evaluated. This article reports the case of an obese woman with FXI deficiency -undergoing SG. CASE REPORT A 49-year-old woman with a BMI of 51 kg/m² was diagnosed as having severe FXI deficiency during preoperative exams prior to bariatric surgery. Virus-inactivated homo-group plasma 10 ml/kg infusion was administrated 1 h before surgery, during the entire procedure, and continuing until postoperative day (POD) 4. A very low-calorie ketogenic diet (VLCKD) was proposed to the patient 4 weeks before surgery. Laparoscopic sleeve gastrectomy was performed with staple-line reinforcement by oversewing the seromuscular layer using continuous suture. Subcutaneous enoxaparin 4000 U.I. was administered from POD 1 until POD 25 to prevent any thromboembolic event. The patient was discharged on POD 5 in good clinical condition. CONCLUSIONS Risks of bleeding andor thromboembolic events before or after BS are increased in patient with FXI deficiency. Bariatric surgery in these patients is safe in experienced BS centers, and the risks associated with the obesity seem to exceed those of the coagulopathy and surgery. Careful preoperative counseling, extensive hematological checks, and meticulous surgery are essential to reduce BS risks. Sleeve gastrectomy oversewing the stapler line seems a reasonable choice.

One case of surgical treatment of coagulation factor XI deficiency complicated with esophageal cancer: a case report.

BACKGROUND: Coagulation factor XI deficiency is an autosomal recessive hereditary disease with a low incidence. It usually occurs after surgery or trauma; Esophageal cancer is a common malignant tumor of the digestive tract in China. But so far, surgery-based comprehensive treatment of esophageal cancer still dominates. CASE PRESENTATION: We report a case of an Asian patient with XI factor deficiency and lower esophageal squamous cell carcinoma who was admitted to our hospital recently. After active preoperative preparation, the operation was successfully performed, and there was no obvious abnormal bleeding during and after the operation. CONCLUSIONS: Coagulation factor XI deficiency is a relatively rare disease, and patients with the disease will face a greater risk of bleeding during the perioperative period. The encouraging perioperative outcome enables us to have a deeper understanding of surgical treatment strategies for patients with Coagulation factor XI deficiency.

Factor XI deficiency: phenotypic age-related considerations and clinical approach towards bleeding risk assessment.

ABSTRACT: Factor XI (FXI) deficiency is a rare bleeding disorder that presents complex challenges in patient assessment and bleeding risk management. Despite generally causing mild to moderate bleeding symptoms, clinical manifestations can vary, and bleeding tendency does not always correlate with FXI plasma levels or genotype. Our manuscript delves into the age-related nuances of FXI deficiency across an individual's lifespan. We emphasize issues faced by specific groups, including neonates and females of reproductive age experiencing abnormal uterine bleeding and postpartum hemorrhage. Older patients present unique challenges and concerns related to the management of bleeding as well as thrombotic complications. The current assortment of diagnostic laboratory assays shows limited success in predicting bleeding risk in the perisurgical setting of patients with FXI deficiency. This review explores the intricate interplay between individual bleeding profiles, surgical sites, and FXI activity levels. We also evaluate the accuracy of existing laboratory assays in predicting bleeding and discuss the potential role of investigational global assays in perioperative assessment. Furthermore, we outline our suggested diagnostic approach to refine treatment strategies and decision making. Available treatment options are presented, including antifibrinolytics, replacement products, and recombinant activated FVII. Finally, we discuss promising nonreplacement therapies for the treatment of rare bleeding disorders that can potentially address the challenges faced when managing FXI deficiency-related bleeding complications.

"Familial Multiple Coagulation Factor Deficiencies of FXI and FXII in an Asymptomatic Saudi Woman".

Factor XI deficiency (FXI) is the third most common coagulation factor deficiency after hemophilia A and B, ie, in the hierarchy after factors VIII and IX, taking into account von Willebrand's factor deficiency, as bleeding disorders are higher than in hemophilia C. Factor XII deficiency (FXII) is a congenital condition, inherited in the vast majority of cases in an autosomal recessive manner, more often associated with thromboembolic complications. A combination of both factor deficiencies has been found very rarely, and it can be familial multiple coagulation factor deficiency (FMCFD). This study reports the case of a 39-year-old woman from Saudi Arabia who had the combination of FXI and FXII deficiencies, known to be on treatment for hypothyroidism and was referred to a hematology clinic with an incidental finding of prolonged activated partial thromboplastin time (aPTT). Although there was no history of bleeding tendency, her siblings had a family history of an unknown type of bleeding disorder. On physical examination, the patient did not show any bruising, petechiae, or ecchymosis. The aPTT was 69 seconds (27-38) with normal use of other hemostatic agents and was corrected after a 50:50 mixing study. Intrinsic coagulation factors were evaluated, and they revealed severe FXI and moderate FXII deficiencies. Due to a strong family history, the patient was diagnosed with FMCFD. In conclusion, familial combined multiple clotting factor deficiency (FCMFD) is a rare condition that requires attention and reporting. The management strategy in such cases has not been well studied, especially in the long-term symptomatic patient with severe but asymptomatic combined FXI and FXII deficiencies, which is an area for review and further study.

Resolution of cardiac surgical bleeding with the combination of 4-factor prothrombin complex concentrate and fresh frozen plasma following lack of response to fresh frozen plasma alone in a patient with severe factor XI deficiency.

Factor XI deficiency is associated with a bleeding tendency in some patients. Factor XI helps to reduce fibrinolysis. Bleeding risk is increased in factor XI-deficient patients during surgeries with high fibrinolytic activity, including nasopharyngeal/oropharyngeal and genitourinary surgeries. Treatment options for factor XI-deficient patients include fresh frozen plasma (FFP), antifibrinolytics, recombinant factor VIIa, and factor XI concentrates (available in Australia, Canada, and some European countries). 4-factor prothrombin complex concentrate (4-factor PCC) is an extract of FFP comprised of unactivated factors II, VII, IX, and X, proteins C and S, and heparin. It has been used for cardiac surgical bleeding. We report the first case of a patient with severe factor XI deficiency and cardiac surgical bleeding, which resolved with the combination of 4-factor PCC and FFP after lack of response to FFP alone.

Epidural analgesia in a patient with factor XI deficit.

FXI deficiency is a rare bleeding disorder characterised by a decreased level or activity of factor. Pregnant women are at increased risk of uterine bleeding during childbirth. Neuroaxial analgesia may increase the risk of epidural hematoma in these patients. However, there is no consensus on the anaesthetic management. We present the clinical case of a 36-year-old woman with a personal history of factor XI deficiency, pregnant with 38 weeks gestation who is scheduled to perform birth induction. Pre-induction factor levels were measured. They were less than 40%, so it was decided to transfuse 20 ml/kg of fresh frozen plasma. After the transfusion it had levels greater than 40%, so epidural analgesia was performed without incident. The patient had no complications secondary to epidural analgesia or transfusion of a high volume of plasma.

[PERIOPERATIVE MANAGEMENT OF AN ADOLESCENT GIRL WITH SEVERE FACTOR XI DEFICIENCY AND INHIBITORS].

INTRODUCTION: Factor XI (FXI) deficiency is an autosomal bleeding disorder characterized by injury-related hemorrhage, mostly associated with surgical procedures at sites noted for high fibrinolytic activity. Severe FXI deficiency is defined when the FXI level is lower than 15-20 IU/dL. Perioperative prophylactic treatment for high-bleeding-risk surgery in patients with severe FXI deficiency is based on fresh frozen plasma (FFP) transfusions or FXI concentrate (where available). Exposure to FFP and to FXI concentrate may lead to the development of inhibitory antibodies against FXI. This phenomenon occurs mostly in patients with very severe FXI deficiency (baseline FXI <1IU/dL) and is associated with an increased risk of substantial perioperative bleeding, unresponsive to FXI replacement. Thus, in individuals with severe FXI deficiency, routine testing for the presence of inhibitory antibodies against FXI is recommended. We present a 17-year-old adolescent patient with very severe FXI deficiency, who developed an inhibitor to FXI following FFP exposure associated with neurosurgery for medulloblastoma. Prophylactic treatment for subsequent invasive procedures consisted of single low dose (10 mcg/kg) recombinant activated factor VII (rFVIIa) and tranexamic acid (Hexakapron). The procedures were performed uneventfully, with no hemorrhagic or thrombotic complications. In patients with very severe FXI deficiency, the development of inhibitory antibodies following plasma replacement therapy comprises a rare and challenging occurrence. The formulation of a safe and effective evidence-based protocol for hemostatic support in these patients requires multi-center collaboration.

Obstetric and perioperative management of patients with factor XI deficiency: a retrospective observational study.

Factor XI (FXI) deficiency is an autosomal inherited, milder bleeding disorder that may predispose to a potential risk of life-threatening bleeding during childbirth or surgery. Unfortunately, data regarding obstetric and perioperative management of this condition are scarce, with limited cases reviewed in the last decade. Therefore, the present study aimed to expand this database and identify factors associated with increased bleeding risk. We performed a retrospective chart review of patients with FXI deficiency who underwent childbirth or other surgical procedures between August 2011 and April 2021 within a single academic health system and identified 198 patients who underwent 252 procedures, including 143 vaginal deliveries, 63 cesarean deliveries, and 46 other surgical procedures. Thirty-three of the 252 procedures resulted in bleeding complications. On multivariable logistic regression analysis, personal history of bleeding was the strongest predictor of perioperative or obstetric bleeding (odds ratio [OR], 5.92; P = .001). Higher FXI levels were correlated with lower odds of bleeding (OR, 0.72 with every 10 U/dL increase in FXI level; P = .05). On receiver operative characteristic analysis, FXI level of >40 U/dL predicted a lower bleeding risk with reasonable specificity (75%) but lacked sensitivity (47%). A family history of bleeding, ethnicity, genotype, preprocedural partial thromboplastin time, and platelet levels were not associated with bleeding risk. There were no cases of epidural or spinal hematoma associated with neuraxial anesthesia. FXI levels remain stable during pregnancy and repeated measurements may not be necessary.

Factor XI deficiency: About 20 cases and literature review.

INTRODUCTION: Factor XI deficiency is a rare coagulation disorder with variable bleeding manifestations. AIM: To evaluate the correlation between the degree of factorXI deficiency and the clinical expression of the disease. METHODS: Retrospective study, spanning 10 years from January 1, 2010 to December 31, 2019, concerning patients followed at the Hemophilia Center at Aziza Othmana Hospital in Tunis. The data were collected from the medical records. The determination of PT, APTT, fibrinogen level and coagulation factors are performed by coagulometric technique on STA® compact / ACL TOP®. FactorXI deficiency was confirmed on two different samples. Statistical analysis of the clinical-biological correlation was performed using the chi-square test. The significance level was 0.05. RESULTS: Twenty patients were collected. The mean age of discovery was 25 years with a sex ratio (M/F) =0.33. The circumstances of discovery were incidental in 14 patients. A family history of bleeding was reported in 30% of cases. Eight patients underwent surgery, six of whom had a simple postoperative course. The APTT was prolonged and isolated in 75% of cases. The hemostasis test was normal in 5 cases. The average FactorXI level was 24%. The tendency to bleed did not seem to be correlated with FactorXI levels. CONCLUSION: Prospective multicenter studies including molecular study would be necessary to better elucidate this rare disorder.

Report of surgeries, their outcome and the thrombin generation assay in patients with Factor XI deficiency: A retrospective single-centre study.

BACKGROUND: In patients with FXI deficiency, the risk of surgery-related bleeding is poorly correlated with plasma FXI activity (FXI:C); the latter can therefore not be used as a reliable predictor of bleeding in surgeries. OBJECTIVES: The aim of this retrospective study was to determine whether thrombin generation assay (TGA) could be used to evaluate the risk of surgery-related bleeding in FXI-deficient patients. TGA parameters were compared to FXI:C values, haemostatic treatments and surgical outcomes. PATIENTS: All patients followed at the haemophilia treatment care centre (Lyon, France) with a FXI:C < 50IU/dL, and for whom a baseline TGA was performed between January 2014 and December 2019, were included. RESULTS: Among the 175 surgeries reported herein in 49 patients, FXI concentrates were used for 11 (6%) surgeries and fresh frozen plasma was used for five (3%) surgeries; these surgeries were performed in patients with two or three impaired TGA parameters. No haemostatic treatment was prescribed for 119 (68%) surgeries. A surgery-related bleeding occurred in 12 patients during 21 (12%) surgeries. Thrombin generation was significantly reduced or delayed in patients who reported surgery related-bleeding. Among the 34 (68%) surgeries performed without haemostatic treatment in patients with three impaired TGA parameters, a surgery-related bleeding was reported in 44% of cases (15 surgeries out of 34). CONCLUSION: The present study confirmed that TGA is an interesting laboratory test in FXI deficiency, for determining the bleeding risk and guiding the haemostatic management of surgeries, while taking into account the surgical bleeding risk and the history of bleeding.

Treatment of patients with rare bleeding disorders in the Netherlands: Real-life data from the RBiN study.

BACKGROUND: Patients with rare inherited bleeding disorders (RBDs) exhibit hemorrhagic symptoms, varying in type and severity, often requiring only on-demand treatment. Prolonged bleeding after invasive procedures is common. Adequate peri-procedural therapy may reduce this bleeding risk. OBJECTIVE: To describe general treatment plans of RBD patients and evaluate the use of peri-procedural hemostatic therapy. METHODS: In the Rare Bleeding Disorders in the Netherlands (RBiN) study, RBD patients from all six Dutch Hemophilia Treatment Centers were included. General treatment plans were extracted from patient files. Patients with a dental or surgical procedure in their history were interviewed about use of peri-procedural treatment and bleeding complications. RESULTS: Two-hundred sixty-three patients with a rare coagulation factor deficiency or fibrinolytic disorder were included. Eighty-four percent had a documented general treatment plan. General treatment plans of patients with the same RBD were heterogeneous, particularly in factor XI deficiency. Overall, 308 dental and 408 surgical procedures were reported. Bleeding occurred in 50% of dental and 53% of surgical procedures performed without hemostatic treatment and in 28% of dental and 19% of surgical procedures performed with hemostatic treatment. Not only patients with severe RBDs, but also patients with mild deficiencies, experienced increased bleeding without proper hemostatic treatment. CONCLUSION: Large heterogeneity in general treatment plans of RBD patients was found. Bleeding after invasive procedures was reported frequently, both before and after RBD diagnosis, irrespective of factor activity levels and particularly when peri-procedural treatment was omitted. Improved guidelines should include uniform recommendations for most appropriate hemostatic products per RBD and emphasize the relevance of individual bleeding history.

A proposal for managing bleeding in patients on therapeutic factor XI(a) inhibitors.

Several drugs that reduce functional levels of the plasma protease zymogen factor XI (FXI), or that inhibit its activated form (FXIa), are being evaluated as treatments to prevent thrombosis. Based on the observation that individuals with inherited FXI deficiency have a relatively mild bleeding disorder, it is anticipated that therapeutic FXI(a) inhibitors will have a smaller impact on hemostasis than anticoagulants targeting thrombin or factor Xa. However, even if FXI(a) inhibitors are determined to be safer than currently used anticoagulants, some patients on these drugs will experience abnormal bleeding or require emergent surgery. Strategies for dealing with such situations are required. Treatment with antifibrinolytic agents and low doses of recombinant factor VIIa effectively prevent abnormal bleeding in FXI-deficient patients with alloantibody inhibitors to FXI who undergo surgery. We propose that a similar strategy can be used for patients on therapeutic FXI(a) inhibitors who are bleeding or require invasive procedures.

The Association between Factor XI Deficiency and the Risk of Bleeding, Cardiovascular, and Venous Thromboembolic Events.

The objective of this study was to assess the relationship between factor XI (FXI) deficiency and the risks of bleeding and cardiovascular (CV) events. We conducted a retrospective cohort study using data from Maccabi Healthcare Services (MHS). We identified adults with FXI deficiency (severe: <15%, partial: 15 to <50%, any deficiency: <50%) that had been tested for FXI between 2007 and 2018 and matched to patients from the general MHS population. We estimated 10-year risks of outcomes using the Kaplan-Meier approach. Using Cox proportional hazards regression, we compared outcomes among patients with versus without FXI deficiency. Less than 10% of patients tested for FXI activity had activity levels <50% (mean age: 39 years; 72.2% females). Compared with the general population, patients with any FXI deficiency were at higher risk of severe bleeding (adjusted hazard ratio [aHR]: 2.56, 95% confidence interval [CI]: 1.13-5.81; 10-year risk: 1.90%, 95% CI: 0.50-3.20% vs. 0.90%, 95% CI: 0.50-1.30%) and clinically relevant nonsevere bleeding (CRNSB) (aHR: 1.45, 95% CI: 1.08-1.97; 10-year risk: 11.60%, 95% CI: 8.30-14.80% vs. 9.20%, 95% CI: 8.00-10.40%). Severe FXI deficiency was associated with a greater risk of CRNSB. While few CV events (N = 2) and venous thromboembolisms (VTE) (N = 1) were observed in the FXI overall deficient group, there was a nonsignificant negative association between any FXI deficiency and CV events (aHR: 0.55; 95% CI: 0.13-2.36) and VTEs (aHR: 0.45; 95% CI: 0.06-3.47). Overall FXI deficiency was associated with an increased risk of severe bleeding and CRNSB. Further research is warranted to explore the lower risk of CV and VTE among patients with FXI deficiency compared with the general population.

Pediatric severe factor XI deficiency: A multicenter study.

BACKGROUND: Factor XI (FXI) deficiency is a rare autosomal recessive bleeding disorder. Only scarce publications address its clinical features in children. The increased prevalence of FXI deficiency in Israel enabled data collection for this large multicenter cohort study. OBJECTIVE: Some hemostatic challenges may be unique or more common in children, such as bleeding in the neonatal period or trauma-related injury. The current study was designed to explore the potential impact of these differences in children with severe FXI deficiency. METHODS: Medical files of all children with FXI level under 15% followed at five tertiary centers were evaluated. The retrieved data comprised demographic and clinical characteristics, including bleeding episodes, surgical interventions, treatment strategies, as well as laboratory features. RESULTS: Sixty children, whose median age at diagnosis was 4.2 years and their median FXI level was 4%, were included. Three children experienced triggered intracranial hemorrhage (ICH) and two children had major bleeds. No bleeding complications occurred in surgeries in which hemostatic treatment consisting mostly of tranexamic acid or fresh frozen plasma was applied (n = 45). In contrast, excessive bleeding was noted in 25% of surgical procedures performed without hemostatic preparation (p = .002). CONCLUSION: This study's findings confirm the generally favorable outcome of this rare bleeding disorder, with no spontaneous bleeds or cases of perinatal ICH. Nonetheless, proper diagnosis and adequate hemostasis in the surgical setting are imperative. Unlike previous studies in adults, our pediatric study suggests an association between the severity of FXI deficiency and bleeding tendency.

Management of factor XI deficiency in oncological liver and colorectal surgery by therapeutic plasma exchange: A case report.

INTRODUCTION: Factor XI (FXI) deficiency is a rare congenital hemostatic disorder associated with increased bleeding tendency in trauma, surgery or when other hemostatic defects are present. Perioperative hemostatic management of a patient with a severe FXI deficiency undergoing major oncological liver and colorectal surgery with therapeutic plasma exchange (TPE) with fresh frozen plasma (FFP) is reported. CASE DESCRIPTION: A 54-year-old male with severe FXI deficiency was scheduled for resection of synchronous rectal cancer and multiple liver metastases. Baseline prothrombin time (PT) was 97 %, activated partial thromboplastin time (aPTT) 89 s(s) and FXI levels <1 IU/dL. The rotational thromboelastometry (ROTEM™) presented a prolonged INTEM clotting time (CT) = 443 s (RV 100-240 s) and a clot formation time (CFT) = 110 s (RV 30-100 s). TPE with FFP was carried out achieving FXI levels up to 46 IU/dL and an aPTT of 33 s, normalizing thromboelastometry parameters to an INTEM CT = 152 s and a CFT = 86 s before the procedure. After surgery, the patient received daily FFP to maintain FXI levels above 30 IU/dL until discharge on the eighth day. A total of 30 FFP units were transfused during hospital stay. No significant bleeding events neither transfusion related complications were observed during the perioperative period. CONCLUSION: Given the lack of correlation between FXI levels and bleeding risk, a multidisciplinary approach based on daily FXI levels monitoring, close clinical assessment and factor supplementation is mandatory. In conclusion, TPE with FFP is an efficacious alternative strategy to correct severe FXI deficiency in patients undergoing major surgery.

Factor XI Deficiency in a Patient with Cervical Spondylotic Myelopathy.

STUDY DESIGN: Case report. OBJECTIVE: To summarize the clinical manifestations and treatment of Factor XI deficiency in a patient with cervical spondylotic myelopathy. SUMMARY OF BACKGROUND DATA: Factor XI deficiency is a rare genetic bleeding disorder caused by reduced levels and insufficient activity of a coagulation factor XI. It is claimed to be associated with prominent bleeding in case of trauma and surgery irrelevant to the FXI level. This is the first ever case of a patient with factor XI deficiency with cervical spondylotic myelopathy. METHODS: A case was investigated retrospectively and the relevant literature was reviewed. RESULTS: A 66-year-old man with a 2-months history of lack of finger dexterity and gait disturbance was referred to our department. He did not have a history of bleeding or coagulation disorder nor did his family. Magnetic resonance imaging (MRI) of the cervical spine revealed spinal canal stenosis at C3/4 to C5/6 and intramedullary hyperintensity at C3/4 on the :T2 weighted image (T2WI). Preoperative examination revealed no abnormal findings but a severe prolonged activated partial-thromboplastin time (APTT) of 139.8 seconds. Coagulation factor activity assay revealed severe deficiency of factor XI (<0.1%). In accordance with hematologist's recommendation, four units of fresh frozen plasma (FFP) were transfused on the day before surgery and APTT assayed early morning on the day of surgery was 70.5 seconds. An additional four units of FFP were transfused during the surgery and APTT was 60 seconds. The postoperative course was uneventful and the patient was discharged on the postoperative day 14. CONCLUSION: Factor XI deficiency patients may develop excessive bleeding after trauma or surgery. Preoperative examination with prolonged APTT should be pursued until a diagnosis of is made. Under diagnosis of Factor XI deficiency, meticulous attentions are required for perioperative bleeding management including postoperative hematoma in spinal surgery.Level of Evidence: 5.

How to Capture the Bleeding Phenotype in FXI-Deficient Patients.

Factor XI (FXI) is a serine protease involved in the propagation phase of coagulation and in providing clot stability. Several mutations in the F11 gene lead to FXI deficiency, a rare mild bleeding disorder. Current laboratory methods are unable to assess bleeding risk in FXI-deficient patients, because the degree of bleeding tendency does not correlate with plasma FXI activity as measured by routine coagulometric aPTT-based assays. Bleeding manifestations are highly variable among FXI-deficient patients and FXI replacement therapy can be associated with an increased thrombotic risk. A correct evaluation of the patient hemostatic potential is crucial to prevent under- or overtreatment. In recent years, different research groups have investigated the use of global coagulation assays as alternative for studying the role of FXI in hemostasis and identifying the clinical phenotype of FXI deficiency. This brief review article summarizes the main features of coagulation factor XI and its deficiency and resumes the principle axes of research and methods used to investigate FXI functions.