Aneurysm Sac Shrinkage After EVAR Can Lead to Complications: A Case Report of Complete Endograft Thrombosis Due to Kinking.

BACKGROUND: Bilateral limb occlusion after endovascular repair of abdominal aortic aneurysms (EVAR) is an uncommon entity. The relationship between graft kinking and unilateral limb occlusion is widely described in the literature. Our aim is to report a case of complete endograft thrombosis due to bilateral limb kinking secondary to aneurysm sac shrinkage, treated by endovascular means. CASE REPORT: A 67 year-old male with history of EVAR with an Incraft® endograft (Cordis, Bridgewater, NJ, USA) four years before, presented at the emergency department with disabling claudication of the right lower extremity and a better tolerated 10-month left extremity claudication. Complete endograft thrombosis with bilateral limb kinking and a remarkable reduction of the aneurysm sac was observed in the computed tomography angiography. An endovascular repair was performed, through bilateral open femoral access and with angiographic control through percutaneous left brachial access. Bilateral recanalization was achieved and the endograft was re-lined with two 10x150 mm Viabahn (WL Gore & Ass., Flagstaff, AZ, USA). Both sides were extended with a 11 × 50 mm Viabahn (WL Gore & Ass., Flagstaff, AZ, USA). The final angiographic control showed bilateral patency with no residual stenosis and the patient recovered distal pulses. Follow-up showed complete patency and no complications at 17 months. CONCLUSIONS: Bilateral limb occlusion is a rare complication with technically challenging treatment options. Aneurysm sac shrinkage can affect the endograft configuration, leading to limb distortion and occasionally to bilateral limb occlusion after EVAR. Special attention should be put on imaging follow-up to detect these complications before occlusion occurs.

Pediatric arterial thrombosis: A single-institution cohort study of patient characteristics and thrombosis outcomes.

BACKGROUND: Arterial thrombosis (AT) is an increasingly recognized complication in pediatrics. Consensus clinical practice guidelines suggest immediate removal of the indwelling arterial catheter and a short course (5-7 days) of anticoagulation. The optimal duration and modality of antithrombotic therapy in children are yet to be determined. AIMS: Describe treatment patterns and outcomes in pediatric patients with AT and explore predictors for complete thrombus resolution or long-term complications. METHODS: Single-institution retrospective study. Patients were identified by ICD-9 and ICD-10 codes for the diagnosis of AT or reports of AT on ultrasound from January 1, 2012, to October 1, 2022. Descriptive and logistic regression analyses were used. RESULTS: 101 patients were included. The median age was 2.2 months. The most common underlying diagnoses were congenital heart disease (39.6%) and infection (22.8%). A majority of patients had symptomatic thrombosis in an extremity, and 78% were catheter-associated. 81% of patients received anticoagulation with a median duration of 35 days. Out of the 70 patients who were treated with anticoagulation alone and had a follow-up imaging, 70% had complete resolution after 90 days of anticoagulation. No clear predictors of complete resolution were identified. Eighteen patients had long-term sequelae secondary to arterial insufficiency. Those with infection-associated AT were more likely to have long-term complications. The major and clinically relevant non-major bleeding rate was 11%. CONCLUSION: Duration of anticoagulation was widely variable, and 70% of patients achieved complete resolution by 90 days of anticoagulation. A significant proportion of patients developed long-term sequelae secondary to arterial insufficiency. Sepsis/infection at the time of diagnosis with AT was more likely to be associated with long-term complications.

Gaseous Nitric Oxide-Cangrelor Combination to Prevent Clots in Extracorporeal Life Support System.

INTRODUCTION: The objective of this study was to investigate the potential synergistic utility of a combination of gaseous nitric oxide (gNO)-intravenous Cangrelor as an effective pharmacological option for the prevention of thrombosis in an animal model of extracorporeal life support (ECLS) circuits. METHODS: 10 newborn lambs were placed on ECLS. 5 of them were administered a combination of gNO and intravenous Cangrelor. The remaining 5 were not administered any anticoagulant. The primary end point was duration of ECLS without clot formation. The secondary outcome measure was the absolute maximum transmembrane pressure gradient. RESULTS: The mean duration of ECLS were 168 min (standard deviation 224.98 min) in the control group and 402 min (standard deviation 287.5 min) in the experimental group (P = 0.17). The peak trans-oxygenator pressure difference was 43 mm Hg (standard deviation 23 mm Hg) in the control group and 62 mm Hg (standard deviation 71 mm Hg) in the experimental group(P = 0.64). Two animals in the experimental group were supported up to 12 h without clot formation. Clot formation in the experimental group occurred after placement of the cannulae but prior to initiation of ECLS flows after cannulation. CONCLUSIONS: A combination of gNO and Cangrelor is prevents clot formation in an experimental animal model when administered through a clean clot-free circuit. However, the combination s ineffective when there are pre-existing clots in the circuit. A bolus of anticoagulation prior to cannulation is needed prior to testing this combination in future studies with a larger sample size.

Extensive systemic thrombo-embolism including intra-cardiac thrombosis mimicking an atrial myxoma in a patient with beta thalassaemia major - a case report.

BACKGROUND: Sepsis and thrombo-embolic disease are well known complications of thalassemia major. Intracardiac thrombi are however rare and can lead to diagnostic dilemmas. CASE PRESENTATION: We report the case of a 20-year-old female splenectomised thalassaemia major patient with severe iron overload, who presented with life threatening sepsis associated with a liver abscess. Discovery of a large oscillating intra cardiac lesion on 2D echocardiogram confirmed by Contrast Enhanced Computed Tomography (CECT) chest in the right atrium extending from the left hepatic vein through the inferior vena cava complicated the clinical course. After a prolonged Intensive Care Unit (ICU) stay supported with antibiotics and anticoagulation, she recovered with evidence of resolution of the intra cardiac thrombus. CONCLUSIONS: Early recognition and prompt aggressive treatment of sepsis in patients with thalassemia is essential to prevent complications. Intracardiac thrombosis is a potentially treatable cause for an intra cardiac mass in patients with thalassemia major, which should not be missed.

Association of XIST/miRNA155/Gab2/TAK1 cascade with the pathogenesis of anti-phospholipid syndrome and its effect on cell adhesion molecules and inflammatory mediators.

Anti-phospholipid syndrome (APS) is an autoimmune disease characterized by thrombosis and miscarriage events. Still, the molecular mechanisms underlying APS, which predisposes to a wide spectrum of complications, are being explored. Seventy patients with primary and secondary APS were recruited, in addition to 35 healthy subjects. Among APS groups, the gene expression levels of XIST, Gab2, and TAK1 were higher along with declined miRNA155 level compared with controls. Moreover, the sera levels of ICAM-1, VCAM-1, IL-1ꞵ, and TNF-α were highly elevated among APS groups either primary or secondary compared with controls. The lncRNA XIST was directly correlated with Gab2, TAK1, VCAM-1, ICAM-1, IL-1ꞵ, and TNF-α. The miRNA155 was inversely correlated with XIST, Gab2, and TAK1. Moreover, ROC curve analyses subscribed the predictive power of the lncRNA XIST and miRNA155, to differentiate between primary and secondary APS from control subjects. The lncRNA XIST and miRNA155 are the upstream regulators of the Gab2/TAK1 axis among APS patients via influencing the levels of VCAM-1, ICAM-1, IL1ꞵ, and TNF-α which propagates further inflammatory and immunological streams. Interestingly, the study addressed that XIST and miRNA155 may be responsible for the thrombotic and miscarriage events associated with APS and provides new noninvasive molecular biomarkers for diagnosing the disease and tracking its progression.

Porto-spleno-mesenteric venous thrombosis after elective splenectomy: a retrospective cohort study.

Background: Elective splenectomy is the main treatment for a wide range of haematological diseases. Porto-spleno-mesenteric venous thrombosis represents one of the most severe complications of this procedure. The aim of this study was to evaluate risk factors associated with development of porto-spleno-mesenteric venous thrombosis after elective splenectomy. Methods: All cases of elective splenectomy carried out from April 1st 2017 to January 31st 2023 were included in this single centre retrospective cohort study. Patients' demographics and perioperative data were analysed and correlated with the incidence of postoperative thrombosis. All patients underwent postoperative doppler ultrasound screening for thrombosis. Analysis was performed using SPSS 28, with p-value < 0.05 considered significant. Results: Twenty-two patients (10 women, 12 men) underwent splenectomy during the study period. Indications were: immune thrombocytopenia (n: 6), myeloproliferative disorder (n: 6), hereditary spherocytosis (n: 4), thalassemia (n: 1), lymphoma (n: 1), leukaemia (n: 1), other malignancies (n: 3). Six patients developed porto-spleno-mesenteric venous thrombosis and only 2 of them were symptomatic. Patients were treated with anticoagulation therapy with complete resolution. Analysis identified three main factors associated with thrombosis: spleen diameter (p = 0.03), myeloproliferative disorder (p = 0.02), intraoperative platelet transfusion (p = 0.002) and intraoperative red blood cells transfusion (p = 0.009). Conclusion: Standardized postoperative screening allows prompt diagnosis and treatment of porto-spleno-mesenteric venous thrombosis even in asymptomatic cases. Patient with splenomegaly and affected by myeloproliferative disorder have a greater risk to develop this complication.

Association of inflammation and abnormal lipid metabolism with risk of thrombosis and thrombosis progression in patients with polycythemia vera: a retrospective study.

To date, no therapeutic strategy has been shown to be effective in reducing the risk of polycythemia vera (PV) transforming into myelofibrosis or leukemia, and the main goal of current treatment is to prevent thrombotic events. Recent studies have shown that higher levels of inflammation are associated with an increased risk of thrombosis in PV patients, while the correlation between inflammation and abnormal lipid metabolism with the risk of thrombosis in PV has not been reported. In this retrospective study, 148 patients with newly diagnosed PV who visited the Affiliated Hospitals of Nanchang University from January 2013 to June 2023 were categorized into low-risk group and high-risk group according to the risk of thrombosis, and were subsequently divided into thrombosis non-progression group and progression group. The differences of novel inflammatory markers PHR, NHR, MHR, LHR, and SIRI in each group were analyzed and compared with healthy adults who underwent physical examination in the hospitals during the same period. The results showed that PHR, NHR, MHR, and SIRI levels were significantly higher in the PV group than in the control group (P < 0.001), while HDL-C levels were considerably lower (1.09 vs. 1.31, P < 0.001). Comparisons within the groups of PV patients revealed that PHR, MHR, NHR, NLR, and SIRI levels were significantly higher in the high-risk group for thrombosis than in the low-risk group (P < 0.01); the thrombosis PHR, NHR, NLR, and SIRI levels were higher in the group with progression of thrombosis than in the group without progression of thrombosis (P < 0.05), while HDL-C levels were significantly lower (1.02 vs. 1.12, P < 0.001). The results of the ROC curve analysis showed that NHR (AUC = 0.791), HDL-C (AUC = 0.691), PHR (AUC = 0.668), NLR(AUC = 0.658), and SIRI (AUC = 0.638) had high diagnostic efficacy for identifying PV patients with thrombosis progression. Multivariate analysis showed that NHR, NLR, MHR, and LHR were independent risk factors for PV patients with thrombosis progression (P < 0.05). Kaplan-Meier survival curves showed that NHR ≥ 5.82 × 109/mmol, NLR ≥ 6.295, PHR ≥ 280.4 × 109/mmol, MHR ≥ 0.295 × 109/mmol, LHR ≥ 1.41 × 109/mmol, and SIRI ≥ 1.53 × 109/L were risk factors for PFS in PV patients. The study demonstrates for the first time that novel inflammatory markers PHR, NHR, MHR, LHR, and SIRI may be used as new predictors for PV patients with thrombosis progression. NHR has the highest value in predicting thrombosis in PV patients and is superior to NLR which was reported previously.

Dual vs. triple antithrombotic treatment after percutaneous coronary intervention in patients with non-valvular atrial fibrillation: a meta-analysis on current evidence.

OBJECTIVE: Combination and duration of antithrombotic therapy in order to prevent both stent thrombosis and thromboembolic complications after coronary artery stenting (PCI) in non-valvular atrial fibrillation (AF) is still debated. This uncertainty can be attributed mainly to the fact that the reference trials were open-label and not adequately powered in order to reach a definitive conclusion on ischemic endpoints (i.e., stent thrombosis). On these grounds, data from real-life studies could support evidence on dual antithrombotic treatment (DAT) safety (bleeding risk) and efficacy (stent thrombosis prevention). The aim of the meta-analysis is to investigate in both randomized controlled trials (RCTs) and observational studies (Obs) the risks and/or benefits related to DAT vs. triple antithrombotic treatment (TAT) regimens in patients affected by AF undergoing PCI. MATERIALS AND METHODS: RCTs and Obs were retrieved through PubMed database. The risk ratio with 95% confidence interval was used to compare the primary and the safety endpoints. RESULTS: Meta-analysis demonstrated no significant differences between DAT vs. TAT for mortality. However, a two-fold higher mortality rate was registered in Obs than in RCTs. The Obs did not confirm the expected significant reduction in bleeding risk shown by the RCTs; however, the bleeding rates in Obs were more than three-fold those of RCTs. In Obs, a significant greater risk for stent thrombosis was observed in DAT than in TAT. CONCLUSIONS: The safety and efficacy outcomes observed in RCTs are unrealistic with respect to the current clinical practice. So, more evidence is needed to have more exhaustive guidelines based on RCTs with homogeneous designs and protocols that should mimic real-life population and practice.

Thrombotic events and prophylactic anticoagulation in pediatric patients with COVID-19: a systematic review and meta-analysis.

BACKGROUND: Venous thromboembolism (VTE) can occur in children with COVID-19, and the efficacy and safety of prophylactic anticoagulant therapy are uncertain. This study aimed to assess the incidence of VTE in pediatric patients with COVID-19, the association of D-dimer with thrombus formation, and the effectiveness and safety of prophylactic anticoagulation treatment. METHODS: We systematically searched databases from January 2020 to February 2023. A systematic review and meta-analysis were conducted to determine the incidence of VTE in children and evaluate the efficacy and safety of prophylactic anticoagulant therapy. RESULTS: Thirteen cohort studies and one clinical trial were included. The pooled incidence rate of VTE in affected children was 1.5% (95% CI 0.4-2.9%). Children with D-dimer levels five times higher than normal had a higher risk of VTE (OR 4.92, 95% CI 1.60-15.11). Prophylactic anticoagulant therapy did not significantly reduce the risk of VTE (OR 1.35, 95% CI 0.74-2.49). The safety of prophylactic anticoagulant therapy was relatively high, with major bleeding and all-cause mortality rates below 0.1% (95% CI 0.0-0.2%). CONCLUSIONS: The incidence of VTE in children with COVID-19 is low, and prophylaxis based on ISTH standards is reasonable. Low-molecular-weight heparin (LMWH) for VTE prevention has a high level of safety. However, more high-quality studies are needed to understand the impact of anticoagulant therapy on VTE incidence in pediatric patients with COVID-19.

Thrombosis and APS: Lessons Learned from Another Black Swan Tale.

Antiphospholipid syndrome (APS) is a chronic systemic autoimmune disease characterized by venous, arterial, and microvascular thromboses and/or recurrent pregnancy morbidity, that occur in the persistent presence of antiphospholipid antibodies (aPL). APS can present with a wide range of clinical manifestations often reffered as "extra-criteria". These features, although apparently less common, can severely impact patients' outcome. Here, we report the case of a patient with a newly diagnosed APS. He previously experienced a recurrence of venous thrombosis after discontinuation of anticoagulant therapy in association with cutaneous ulcerations as presenting symptoms. Interestingly, skin lesions did not improve with full anticoagulant treatment. Due to concomitant presence of thrombotic and microvascular involvement, immunomodulatory therapy with steroid pulses followed by intravenous injections of belimumab was started, with progressive and significant amelioration, leading to complete recovery. Following the presentation of the current case report, we highlight the importance of suspecting APS in young patients experiencing unprovoked thrombosis. We also emphasized the critical issue of testing aPL during anticoagulant treatment and focused on the need of aPL retesting in patients with positivity at high titers. We also highlight the double nature of aPL-mediated clinical manifestations. While most patients presented with pure thrombotic complications, one should always remember that APS is an autoimmune-mediated disease, which can benefit from alternative therapeutic approaches beyond anticoagulation.

Intravascular imaging guided versus coronary angiography guided percutaneous coronary intervention: systematic review and meta-analysis.

OBJECTIVE: To assess the absolute treatment effects of intravascular imaging guided versus angiography guided percutaneous coronary intervention in patients with coronary artery disease, considering their baseline risk. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed/Medline, Embase, and Cochrane Library databases up to 31 August 2023. STUDY SELECTION: Randomized controlled trials comparing intravascular imaging (intravascular ultrasonography or optical coherence tomography) guided versus coronary angiography guided percutaneous coronary intervention in adults with coronary artery disease. MAIN OUTCOME MEASURES: Random effect meta-analysis and GRADE (grading of recommendations, assessment, development, and evaluation) were used to assess certainty of evidence. Data included rate ratios and absolute risks per 1000 people for cardiac death, myocardial infarction, stent thrombosis, target vessel revascularization, and target lesion revascularization. Absolute risk differences were estimated using SYNTAX risk categories for baseline risks at five years, assuming constant rate ratios across different cardiovascular risk thresholds. RESULTS: In 20 randomized controlled trials (n=11 698), intravascular imaging guided percutaneous coronary intervention was associated with a reduced risk of cardiac death (rate ratio 0.53, 95% confidence interval 0.39 to 0.72), myocardial infarction (0.81, 0.68 to 0.97), stent thrombosis (0.44, 0.27 to 0.72), target vessel revascularization (0.74, 0.61 to 0.89), and target lesion revascularization (0.71, 0.59 to 0.86) but not all cause death (0.81, 0.64 to 1.02). Using SYNTAX risk categories, high certainty evidence showed that from low risk to high risk, intravascular imaging was likely associated with 23 to 64 fewer cardiac deaths, 15 to 19 fewer myocardial infarctions, 9 to 13 fewer stent thrombosis events, 28 to 38 fewer target vessel revascularization events, and 35 to 48 fewer target lesion revascularization events per 1000 people. CONCLUSIONS: Compared with coronary angiography guided percutaneous coronary intervention, intravascular imaging guided percutaneous coronary intervention was associated with significantly reduced cardiac death and cardiovascular outcomes in patients with coronary artery disease. The estimated absolute effects of intravascular imaging guided percutaneous coronary intervention showed a proportional relation with baseline risk, driven by the severity and complexity of coronary artery disease. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023433568.

Low-grade endotoxemia in acute pulmonary embolism: Links with prothrombotic plasma fibrin clot phenotype.

BACKGROUND: Lipopolysaccharide (LPS) can traverse the intestinal barrier and enter bloodstream, causing endotoxemia and triggering inflammation. Increased circulating LPS was reported in arterial thromboembolism. We investigated whether increased LPS levels occur in acute pulmonary embolism (PE) and if it is associated with a prothrombotic state. METHODS: We studied 120 normotensive PE patients (aged 59 [48-68] years) on admission, after 5-7 days, and after a 3-month anticoagulation. Serum LPS levels, along with zonulin, a marker of gut permeability, endogenous thrombin potential (ETP), fibrin clot permeability (Ks), clot lysis time (CLT), fibrinolysis proteins, and platelet markers were assessed. RESULTS: Median LPS concentration on admission was 70.5 (61.5-82) pg/mL (min-max, 34-134 pg/mL), in association with C-reactive protein (r = 0.22, p = 0.018), but not with fibrinogen, D-dimer or platelet markers. Patients with more severe PE had higher LPS levels compared with the remainder. Median zonulin level was 3.26 (2.74-4.08) ng/mL and correlated with LPS (r = 0.66, p < 0.0001). Patients with baseline LPS levels in the top quartile (≥82 pg/mL; n = 29) compared to lower quartiles had 18.6 % increased ETP, 14.5 % reduced Ks, and 25.3 % prolonged CLT, related to higher plasminogen activator inhibitor type 1 (PAI-1) levels. LPS decreased by 23.4 % after 5-7 days and by 40.4 % after 3-month anticoagulation together with reduced zonulin by 18.4 % and 22.3 %, respectively, compared to baseline (all p < 0.001). LPS levels were not related with fibrin characteristics and other variables assessed at 3 months. CONCLUSIONS: Low-grade endotoxemia is detectable in patients with acute PE and may contribute to increased thrombin generation and PAI-1-mediated hypofibrinolysis.

Gut dysbiosis-related thrombosis in inflammatory bowel disease: Potential disease mechanisms and emerging therapeutic strategies.

Patients with inflammatory bowel disease (IBD) have an increased risk of developing venous thromboembolic events, which have a considerable impact on morbidity and mortality. Chronic inflammation plays a crucial role in the pathogenesis of thrombotic events in patients with IBD. However, many unresolved questions remain, particularly regarding the mechanisms that determine the persistent inflammatory state independent of disease activity. This review explored the role of gut microbiota dysbiosis and intestinal barrier dysfunction, which are considered distinctive features of IBD, in determining pro-thrombotic tendencies. Gut-derived endotoxemia due to the translocation of bacterial lipopolysaccharides (LPS) from the intestine to the bloodstream and the bacterial metabolite trimethylamine-N-oxide (TMAO) are the most important molecules involved in gut dysbiosis-related thrombosis. The pathogenic prothrombotic pathways linked to LPS and TMAO have been discussed. Finally, we present emerging therapeutic approaches that can help reduce LPS-mediated endotoxemia and TMAO, such as restoring intestinal eubiosis, normalizing intestinal barrier function, and counterbalancing the effects of LPS and TMAO.

Early 6 months usage of single anTiplAtelet OR anTicoAgulant followed by single antiplatelet after transcatheter aortic valve replacement: protocol for a multicentre, open-label, randomised controlled clinical trial.

INTRODUCTION: The strategy for initiating antithrombotic therapy to prevent bioprosthetic valve thrombosis (BPVT) after transcatheter aortic valve replacement (TAVR) remains uncertain. There is still lacking evidence on the efficacy and safety of early 6 months usage of single-antiplatelet therapy (SAPT) or oral anticoagulant (OAC) after TAVR in patients without anticoagulant indications. METHODS AND ANALYSIS: This is a multicentre, randomised controlled, open-label trial, and 650 patients undergoing TAVR from 13 top TAVR centres in China will be recruited. Each eligible participant will be randomly assigned to two groups (1:1 ratio) as (1) SAPT (aspirin 75-100 mg for 6 months) group or (2) OAC group (warfarin, therapeutic international normalised ratio at 1.8-2.5 for 6 months), both followed by sequential aspirin 75-100 mg for 6 months. Participants in both groups will be invited for three follow-up visits of 1, 6 and 12 months after discharge. We will use both the net clinical benefit endpoint (composite of all-cause mortality, myocardial infarction, stroke/transient ischaemic attacks, peripheral artery thrombosis, intracardiac thrombosis and major bleeding and disabling or life-threatening bleeding) and the BPVT endpoint evaluated by four-dimensional CT as our primary endpoints. P value of <0.05 of two-sided test will be considered statistically significant. ETHICS AND DISSEMINATION: The present study was approved by the Institutional Review Boards at Fuwai Hospital, National Center for Cardiovascular Diseases of China (Approval No. 2023-1947). All patients will be informed of the details of the study and will sign an informed consent prior to inclusion in the study. Results of this study will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT05375474.

Acute aortic thrombosis following umbilical artery catheterisation in extremely low birthweight infants: walking the tight rope of management.

Umbilical artery catheterisation (UAC) is crucial in the management of clinically sick infants. One of its dreaded complications is aortic thrombus formation which accounts for significant morbidity and mortality. We present the case of a premature infant born at 32 weeks of gestation and with a birth weight of 960 gm, who developed signs of acute lower limb ischaemia following UAC cannulation. Ultrasound Doppler scan confirmed large aortic thrombus involving iliac arteries. Heparin infusion was started with clinical improvement over the next 12 hours and eventual complete resolution of clot size. This case underscores the importance of prompt detection of acute aortic thrombosis and cautions the use of heparin infusion in preterm infants can be lifesaving. Management can be challenging as risk of bleeding from anticoagulation and thrombolytic therapy can be catastrophic in extreme low birthweight premature infants and need to weigh with risk of severe intravascular haemorrhage.

Factor XI in Carriers of Antiphospholipid Antibodies: Elevated Levels Associated with Symptomatic Thrombotic Cases, While Low Levels Linked to Asymptomatic Cases.

Antiphospholipid syndrome (APS) is a thromboinflammatory disorder caused by circulating antiphospholipid autoantibodies (aPL) and characterized by an increased risk of thrombotic events. The pathogenic mechanisms of these antibodies are complex and not fully understood, but disturbances in coagulation and fibrinolysis have been proposed to contribute to the thrombophilic state. This study aims to evaluate the role of an emerging hemostatic molecule, FXI, in the thrombotic risk of patients with aPL. Cross-sectional and observational study of 194 consecutive and unrelated cases with aPL recruited in a single center: 82 asymptomatic (AaPL) and 112 with primary antiphospholipid syndrome (APS). Clinical and epidemiological variables were collected. The profile of aPL was determined. Plasma FXI was evaluated by Western blotting and two coagulation assays (FXI:C). In cases with low FXI, molecular analysis of the F11 gene was performed. FXI:C levels were significantly higher in patients with APS than in patients with AaPL (122.8 ± 33.4 vs. 104.5 ± 27.5; p < 0.001). Multivariate analysis showed a significant association between symptomatic patients with aPL (APS) and high FXI (>150%) (OR = 11.57; 95% CI: 1.47-90.96; p = 0.020). In contrast, low FXI (<70%), mostly caused by inhibitors, was less frequent in the group of patients with APS compared to AaPL (OR = 0.17; 95%CI: 0.36-0.86; p = 0.032). This study suggests that FXI levels may play a causal role in the prothrombotic state induced by aPLs and holds the promise of complementary treatments in APS patients by targeting FXI.

Bleeding and Thrombosis in Multiple Myeloma: Platelets as Key Players during Cell Interactions and Potential Use as Drug Delivery Systems.

Multiple myeloma (MM) is a hematological malignancy originated in the bone marrow and characterized by unhindered plasma cell proliferation that results in several clinical manifestations. Although the main role of blood platelets lies in hemostasis and thrombosis, platelets also play a pivotal role in a number of other pathological conditions. Platelets are the less-explored components from the tumor microenvironment in MM. Although some studies have recently revealed that MM cells have the ability to activate platelets even in the premalignant stage, this phenomenon has not been widely investigated in MM. Moreover, thrombocytopenia, along with bleeding, is commonly observed in those patients. In this review, we discuss the hemostatic disturbances observed in MM patients and the dynamic interaction between platelets and myeloma cells, along with present and future potential avenues for the use of platelets for diagnostic and therapeutic purposes.