Thrombosis and haemostasis最新文献

{"title":"Potential of Sulodexide in the Treatment of Diabetic Retinopathy and Retinal Vein Occlusion","authors":"Elsa Wilma Böhm, Francesco Buonfiglio, Christina A. Korb, Alice Dauth, Norbert Pfeiffer, Andrzej Bręborowicz, Adrian Gericke","doi":"10.1055/s-0044-1791232","DOIUrl":"https://doi.org/10.1055/s-0044-1791232","url":null,"abstract":"<p>Retinal vascular diseases, such as diabetic retinopathy or retinal vein occlusion, are common causes of severe vision loss. Central to the pathophysiology of these conditions are endothelial dysfunction, inflammation, capillary leakage, ischemia, and pathological neoangiogenesis. Capillary damage leads to leakage and the development of macular edema, which is associated with vision loss and requires complex treatment. Sulodexide, a glycosaminoglycan composed of heparan sulfate and dermatan sulfate with high oral bioavailability, exhibits several favorable pharmacologic properties, including antithrombotic, anti-inflammatory, and endothelium-protective effects. Additionally, treatment with sulodexide has been associated with the reduction of oxidative stress and decreased expression of angiogenic growth factors, such as vascular endothelial growth factor. This review aims to provide an overview of the pharmacological properties, mechanisms of action, and therapeutic effects of sulodexide. Furthermore, its potential for clinical application in venous and diabetic diseases, such as venous thromboembolism, chronic venous insufficiency, peripheral artery disease, or diabetic nephropathy, is summarized. We also present experimental and clinical studies evaluating the potential of sulodexide in ocular conditions and discuss its therapeutic implications for the treatment of retinal vascular diseases.</p> ","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":"19 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142260036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unravelling the Causal Relationship between Endometriosis and the Risk for Developing Venous Thromboembolism: A Pooled Analysis.","authors":"Pauline De Corte, Igor Milhoranca, Sylvia Mechsner, Anna Sara Oberg, Tobias Kurth, Klaas Heinemann","doi":"10.1055/a-2407-9498","DOIUrl":"10.1055/a-2407-9498","url":null,"abstract":"<p><strong>Objective: </strong> To investigate the effect of endometriosis on venous thromboembolism (VTE) in oral contraceptive (OC) users. Pooled analysis on a harmonized dataset compromising international patient-centric cohort studies: INAS-VIPOS, INAS-SCORE, and INAS-FOCUS. Eleven European countries, the United States, and Canada. Individuals being newly prescribed an OC with or without an endometriosis and no VTE history.</p><p><strong>Methods: </strong> Detailed information was captured using self-administered questionnaires at baseline and every 6 to 12 months thereafter. Self-reported VTEs were medically validated and reviewed by an independent adjudication committee. Incidence rates (IRs) were calculated per 10,000 woman-years. The association of endometriosis on VTE was determined in a time-to-event analysis, calculating crude and adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) using stabilized inverse probability of treatment weighting (IPTW).</p><p><strong>Results: </strong> A total of 22,072 women had an endometriosis diagnosis, and 91,056 women did not. Women with endometriosis contributed 78,751 woman-years during which 41 VTE events occurred (IR: 5.2/10,000, 95% CI: 3.7-7.1) compared to 127 VTEs during 310,501 woman-years in women without endometriosis (IR: 4.1/10,000, 95% CI: 3.4-4.9). The hazard ratio of VTE in women with endometriosis was 1.79 (95% CI: 1.24-2.57) using stabilized IPTW controlling for age, body mass index, smoking, education, age at menarche, and family history of VTE. Subgroup and sensitivity analyses showed similar results.</p><p><strong>Conclusion: </strong> These results highlight the importance of considering endometriosis as a potential factor contributing to VTE in women using OC; however, further research on the relationship between endometriosis and VTE is warranted.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamics of Thrombogenicity and Platelet Function and Correlation with Bleeding Risk in Patients Undergoing M-TEER Using the PASCAL System","authors":"Miriam Euper, Jürgen Schreieck, Mareike Bladt, Monika Zdanyte, Andreas Goldschmied, Manuel Sigle, Dominick J. Angiolillo, Diana A. Gorog, Mia Ravn Jacobsen, Rikke Sørensen, Dominik Rath, Meinrad Gawaz, Tobias Geisler","doi":"10.1055/s-0044-1790604","DOIUrl":"https://doi.org/10.1055/s-0044-1790604","url":null,"abstract":"<p>\u0000<b>Background</b> Transcatheter mitral valve repair is performed in a patient population at risk for thrombotic and bleeding events. The effects on platelet function and reactivity and their association with bleeding events after mitral transcatheter edge-to-edge therapy (M-TEER) have not been systematically examined.</p> <p>\u0000<b>Objectives</b> We sought to investigate the association of different parameters of platelet function and thrombogenicity with bleeding events post M-TEER.</p> <p>\u0000<b>Methods</b> In this single-center study, 100 consecutive patients with mitral regurgitation receiving TEER were analyzed. Blood was taken directly from the guide-catheter in the left atrium before and after placing the device. Blood samples were analyzed using impedance aggregometry (Multiplate) and TEG6s. The results were compared pre- and postprocedural. The primary outcome was any bleeding complication according to the Bleeding Academic Research Consortium classification within 6 months.</p> <p>\u0000<b>Results</b> A total of 41 patients experienced bleeding events. TEG analysis showed a significant decrease in ADP aggregation and increase in ADP inhibition. In ROC-analysis, TEG ADP aggregation and inhibition and Multiplate ADP aggregation showed moderate predictive values for bleeding events. The delta-ADP-Test (Multiplate) showed the strongest prediction of bleeding (area under the curve: 0.69). Adding platelet function and TEG markers to a model of clinical bleeding risk factors improved the prediction for bleeding events.</p> <p>\u0000<b>Conclusion</b> This study indicates that thrombogenicity might be affected immediately after M-TEER probably due to changes in flow conditions. In particular, platelet aggregation involving the ADP receptor pathway significantly correlated with postprocedural bleeding events. Whether these results could guide peri-interventional antithrombotic therapy and improve peri- and postprocedural outcome requires further investigation.</p> ","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":"29 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142260344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shear Stress Promotes Remodeling of Platelet Glycosylation via Upregulation of Platelet Glycosidase Activity: One More Thing.","authors":"Yana Roka-Moiia, Sabrina Lewis, Estevan Cleveland, Joseph E Italiano, Marvin J Slepian","doi":"10.1055/a-2398-9532","DOIUrl":"10.1055/a-2398-9532","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt; Mechanical circulatory support (MCS) is a mainstay of therapy for advanced and end-stage heart failure. Accompanied by systemic anticoagulation, contemporary MCS has become less thrombogenic, with bleeding complications emerging as a major cause of readmission and 1-year mortality. Shear-mediated platelet dysfunction and thrombocytopenia of undefined etiology are primary drivers of MCS-related bleeding. Recently, it has been demonstrated that deprivation of platelet surface glycosylation is associated with the decline of hemostatic function, microvesiculation, and premature apoptosis. We test the hypothesis that shear stress induces remodeling of platelet surface glycosylation via upregulation of glycosidase activity, thus facilitating platelet count decline and intense microvesiculation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt; Human gel-filtered platelets were exposed to continuous shear stress in vitro. Platelets and platelet-derived microparticles (PDMPs) were quantified via flow cytometry using size standard fluorescent nanobeads. Platelet surface glycosylation and NEU1 expression were evaluated using lectin- or immune-staining and multicolor flow cytometry; lectin blotting was utilized to verify glycosylation of individual glycoproteins. Platelet neuraminidase, galactosidase, hexosaminidase, and mannosidase activities were quantified using 4-methylumbelliferone-based fluorogenic substrates.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt; We demonstrate that shear stress promotes selective remodeling of platelet glycosylation via downregulation of 2,6-sialylation, terminal galactose, and mannose, while 2,3-sialylation remains largely unchanged. Shear-mediated deglycosylation is partially attenuated by neuraminidase inhibitors, strongly suggesting the involvement of platelet neuraminidase in observed phenomena. Shear stress increases platelet NEU1 surface expression and potentiates generation of numerous NEU1+ PDMPs. Platelets exhibit high basal hexosaminidase and mannosidase activities; basal activities of platelet neuraminidase and galactosidase are rather low and are significantly upregulated by shear stress. Shear stress of increased magnitude and duration promotes an incremental decline of platelet count and immense microvesiculation, both being further exacerbated by neuraminidase and partially attenuated by neuraminidase inhibition.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt; Our data indicate that shear stress accumulation, consistent with supraphysiologic conditions of device-supported circulation, promotes remodeling of platelet glycosylation via selective upregulation of platelet glycosidase activity. Shear-mediated platelet deglycosylation is associated with platelet count drop and increased microvesiculation, thus offering a direct link between deglycosylation and thrombocytopenia observed in device-supported patients. Based on our findings, we propose a panel of molecular markers to be used for reliable detection of shear-medi","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phase 1b PK/PD Study to Demonstrate Antigen Elimination with RLYB212, a Monoclonal Anti-HPA-1a Antibody for FNAIT Prevention.","authors":"Christof Geisen, Erika Fleck, Stephan Martin Gastón Schäfer, Carmen Walter, Susanne Braeuninger, Jens Søndergaard Jensen, Douglas Sheridan, Kiran Patki, Róisín Armstrong, Bjørn Skogen, Frank Behrens, Erhard Seifried, Jens Kjeldsen-Kragh, Mette Kjær, Michaela Köhm","doi":"10.1055/a-2398-9344","DOIUrl":"10.1055/a-2398-9344","url":null,"abstract":"<p><strong>Background: </strong> Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare bleeding disorder of the fetus/newborn caused by development of maternal alloantibodies against fetal human platelet antigens (HPAs), predominantly HPA-1a. Currently there are no treatments available to prevent maternal alloimmunization to HPAs or FNAIT.</p><p><strong>Methods: </strong> This proof-of-concept study (EudraCT Number: 2021-005380-49) was designed to assess the ability of subcutaneous (SC) RLYB212, a monoclonal anti-HPA-1a antibody, to eliminate HPA-1a-positive platelets in an antigen challenge model of a 30 mL fetal-maternal hemorrhage. Subjects were randomized to receive a single SC dose of RLYB212 or placebo on day 1 in a single-blinded manner, followed by transfusion of 10 × 10⁹ HPA-1a-positive platelets on day 8.</p><p><strong>Results: </strong> Four subjects received 0.09 mg SC RLYB212, five received 0.29 mg SC RLYB212, and two received placebo. RLYB212 achieved rapid elimination of HPA-1a-positive platelets in a concentration-dependent manner, with concentrations as low as 3.57 ng/mL meeting the prespecified proof-of-concept criterion of ≥90% reduction in platelet elimination half-life versus placebo. Following HPA-1a-positive platelet transfusion, a rapid decline was observed in the concentration of RLYB212 over a period of 2 to 24 hours, corresponding to the time needed for RLYB212 to bind to ∼10% of HPA-1a on cell surfaces. RLYB212 was well tolerated with no reports of drug-related adverse events.</p><p><strong>Conclusion: </strong> The data from this study are consistent with preclinical efficacy data and support the potential use of RLYB212 as a prophylactic treatment for FNAIT that prevents maternal HPA-1a alloimmunization during at-risk pregnancies.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Final Analysis Results from the AGEHA Study: Emicizumab Prophylaxis for Acquired Hemophilia A with or without Immunosuppressive Therapy.","authors":"Midori Shima, Nobuaki Suzuki, Hidekazu Nishikii, Kagehiro Amano, Yoshiyuki Ogawa, Ryota Kobayashi, Ryoto Ozaki, Koichiro Yoneyama, Narumi Mizuno, Emiko Sakaida, Makoto Saito, Takashi Okamura, Toshihiro Ito, Norimichi Hattori, Satoshi Higasa, Yoshinobu Seki, Keiji Nogami","doi":"10.1055/a-2384-3585","DOIUrl":"10.1055/a-2384-3585","url":null,"abstract":"<p><strong>Background: </strong> Primary analysis of the phase III AGEHA study suggested a favorable benefit-risk profile for emicizumab prophylaxis in patients with acquired hemophilia A (PwAHA); however, only patients undergoing immunosuppressive therapy (IST; Cohort 1) were included.</p><p><strong>Objectives: </strong> To present final analysis results of AGEHA, including data on IST-ineligible patients (Cohort 2) and on long-term prophylaxis with emicizumab.</p><p><strong>Methods: </strong> For patients in both Cohorts 1 and 2, emicizumab was administered subcutaneously at 6 mg/kg on Day 1, 3 mg/kg on Day 2, and 1.5 mg/kg once weekly from Day 8 onward.</p><p><strong>Results: </strong> Twelve patients (Cohort 1) and two patients (Cohort 2) were enrolled. Duration of emicizumab treatment was 8 to 639 days (median: 44.5 days) in Cohort 1 and 64 and 450 days in Cohort 2. In both cohorts, no major bleeds were observed after initial emicizumab administration. Six patients started their first rehabilitation sessions during emicizumab treatment and no rehabilitation-related bleeds occurred. Twenty-three surgeries were performed under emicizumab prophylaxis and there were no bleeds related to surgeries. Although asymptomatic deep vein thrombosis was reported in one patient in the primary analysis, no other thrombotic events occurred thereafter. Two patients developed anti-emicizumab antibodies, one of whom showed accelerated emicizumab clearance. Tailored IST approaches (delayed initiation, no use, or reduced dose) were successfully executed in three patients undergoing emicizumab prophylaxis.</p><p><strong>Conclusion: </strong> These results suggest that emicizumab prophylaxis has a favorable benefit-risk profile in PwAHA regardless of eligibility for IST.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time Trends and Excess Mortality Compared to Population Controls after a First-Time Pulmonary Embolism or Deep Vein Thrombosis.","authors":"Katarina Glise Sandblad, Carl Johan Svensson, Kristina Svennerholm, Jacob Philipson, Aldina Pivodic, Sam Schulman, Mazdak Tavoly","doi":"10.1055/a-2402-6192","DOIUrl":"10.1055/a-2402-6192","url":null,"abstract":"<p><strong>Background: </strong> Recent data on temporal trends in excess mortality for patients with pulmonary embolism (PE) and deep vein thrombosis (DVT) compared with the general population are scarce.</p><p><strong>Methods: </strong> A nationwide Swedish register study conducted from 2006 to 2018 including 68,960 PE and 70,949 DVT cases matched with population controls. Poisson regression determined relative risk (RR) for 30-day and 1-year mortality trends while Cox regression determined adjusted hazard ratios (aHRs). A significance level of 0.001 was applied.</p><p><strong>Results: </strong> In PE cases, both 30-day mortality (12.5% in 2006 to 7.8% in 2018, RR: 0.95 [95% CI: 0.95-0.96], <i>p</i> < 0.0001) and 1-year mortality (26.5 to 22.1%, RR: 0.98 [0.97-0.98], <i>p</i> < 0.0001) decreased during the study period. Compared with controls, no significant change was seen in 30-day (aHR: 33.08 [95% CI: 25.12-43.55] to 24.64 [95% CI: 18.81-32.27], <i>p</i> = 0.0015 for interaction with calendar year) or 1-year (aHR: 5.85 [95% CI: 5.31-6.45] to 7.07 [95% CI: 6.43-7.78], <i>p</i> = 0.038) excess mortality. The 30-day excess mortality decreased significantly (aHR: 39.93 [95% CI: 28.47-56.00) to 24.63 [95% CI: 17.94-33.83], <i>p</i> = 0.0009) in patients with PE without known cancer before baseline, while the excess 1-year mortality increased (aHR: 3.55 [95% CI: 3.16-3.99] to 5.38 [95% CI: 4.85-5.98], <i>p</i> < 0.0001) in PE cases surviving to fill a prescription of anticoagulation. In DVT cases, 30-day and 1-year mortality declined, while excess mortality compared with controls remained stable.</p><p><strong>Conclusion: </strong> In general, the improved mortality following PE and DVT paralleled population trends. However, PE cases without cancer had decreasing excess 30-day mortality, whereas those surviving to fill a prescription for anticoagulant medication showed increasing excess 1-year mortality.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unfavorably altered fibrin clot phenotype in women following postpartum hemorrhage of unknown cause: effect of lower coagulation factors.","authors":"Magdalena Piróg,Michał Ząbczyk,Joanna Natorska,Elżbieta Broniatowska,Robert Jach,Anetta Undas","doi":"10.1055/a-2413-2966","DOIUrl":"https://doi.org/10.1055/a-2413-2966","url":null,"abstract":"Background Increased clot permeability and susceptibility to lysis have been reported in women with heavy menstrual bleeding. We hypothesized that similarly altered fibrin clot properties in women with postpartum hemorrhage (PPH) of unknown cause. Objective To determine fibrin clot properties and their determinants in women after PPH of unknown cause. Methods We studied 52 consecutive women, aged 35 years (27-40), after at least 3 months since PPH of unknown cause and 52 matched controls for age, weight, and fibrinogen. Coagulation factors (F), antithrombin, thrombin generation, along with a comprehensive plasma fibrin clot analysis including fibrin polymerization, clot permeability (Ks), and fibrinolysis efficiency were determined. Results Women with PPH showed reduced activity of FII (-10.3%), FV (-6.6%), FIX (-6.5%), FX (-7.2%), and FXI (-5.7%) compared to the controls, though all values were within ranges (all p<0.05). There were no intergroup differences in fibrinogen, FVIII, FXIII, and thrombin generation. The PPH group formed with a delay looser plasma fibrin network (Ks; +16.3%, p=0.008) with lower maximum absorbance and shorter clot lysis time (CLT; -13.5%, p=0.001) compared to the controls. On multivariable logistic regression, PPH was independently associated with higher C-reactive protein (per 1 mg/L, OR=1.70, 95% CI 1.09-2.68), lower FII (per 1%, OR=0.93, 95% CI 0.89-0.98), lower FV (per 1%, OR=0.93, 95% CI 0.89-0.97), and shorter CLT (per 1 min, OR=0.94, 95% CI 0.90-0.98). Conclusion Prohemorrhagic fibrin clot properties, with lower, though normal coagulation factors characterize women with PPH of unknown cause, which suggests novel mechanisms contributing to this type of bleeding.","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":"7 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated thrombin generation and VTE incidence in patients undergoing cytoreductive surgery with HIPEC compared with minimally invasive rectal surgery.","authors":"Mikkel Lundbech,Andreas Engel Krag,Lene Hjerrild Iversen,Birgitte Brandsborg,Nina Madsen,Anne-Mette Hvas","doi":"10.1055/a-2413-4989","DOIUrl":"https://doi.org/10.1055/a-2413-4989","url":null,"abstract":"INTRODUCTION Surgical treatment of colorectal cancer carries a risk for venous thromboembolism (VTE). We investigated changes in coagulation and fibrinolysis and the VTE incidence within 30 days in patients undergoing open cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) for peritoneal metastases from colorectal cancer and minimally invasive surgery (MIS) for localized rectal cancer. METHODS This cohort study included 45 CRS+HIPEC and 45 MIS patients. Blood samples were obtained preoperatively, at the end of surgery, and postoperative day (POD) 1, 3-4, and 5-7. Systematic ultrasonographic screening for VTE was performed between POD 3-7. Computed tomography scan was performed if complications were suspected. The primary endpoint was the difference in mean change ( with [95% confidence intervals] from preoperative to end of surgery in prothrombin fragment 1+2 (F1+2) levels. Secondary endpoints were the difference in mean change in biomarkers of coagulation and fibrinolysis from preoperative to POD 5-7, and the VTE incidence. RESULTS F1+2 levels increased from preoperative to the end of surgery in both groups. The mean increase from preoperative to end of surgery in F1+2 levels was significantly greater in CRS+HIPEC patients than MIS patients: 1322 [1040:1604] pmol/l, P = 0.001. The VTE incidence was significantly higher after CRS+HIPEC than MIS (24% vs. 5%, P = 0.012). CONCLUSION F1+2 levels were increased after both procedures, but to a far greater extent following CRS+HIPEC. The VTE incidence within 30 days was significantly higher in patients treated with CRS+HIPEC than in MIS patients.","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":"99 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mepacrine flow cytometry assay for the diagnosis of platelet δ-granule defects : literature review on methods - towards a shared detailed protocol.","authors":"Mehdi Khourssaji,Marion Bareille,Lorenzo Alberio,Delphine Borgel,Marc Fouassier,Marie Christine Bene,Thomas Lecompte,François Mullier","doi":"10.1055/a-2413-2870","DOIUrl":"https://doi.org/10.1055/a-2413-2870","url":null,"abstract":"Accurate assessment of platelet secretion is essential for the diagnosis of inherited or acquired platelet function disorders (PFDs) and more specifically in identifying δ-storage pool disease. Mepacrine, a fluorescent dye, specifically accumulates in platelet δ-granules. The mepacrine flow cytometry (FCM) assay has been used for more than half a century in the clinical laboratory as a diagnostic tool for platelet δ-granule disorders. The assay requires a small volume of blood, can be performed in thrombocytopenic patients, provides rapid assessment of δ-granule content and secretion and, thus, enables differentiation between storage and release defects. FCM has been shown to have added value compared to light transmission aggregometry. There is however a broad heterogeneity in methods, reagents, and equipment used. Lack of standardization and limited data on analytical and clinical performances have led the 2022 ISTH SSC Subcommittee on Platelet Physiology expert consensus to rate this assay as simple but of uncertain value. Yet, the data used by experts to formulate the recommendations were not discussed and even not mentioned. Guidance for laboratory studies of platelet secretion assay would be very helpful for clinical laboratories and health authorities especially considering the implications of the new In Vitro Diagnostic Regulation (IVDR) in Europe. The purpose of the present work was to systematically review the reported methodologies for the mepacrine FCM assay and to offer an example of detailed protocol. This would help standardization and pave the way for more rigorous comparative studies.","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":"21 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}