Incidence Of Venous Thrombotic Events Research Articles

Communication from the ISTH SSC Subcommittee on Hemostasis and Malignancy: a meta-analysis to assess the risk of bleeding and thrombosis following chimeric antigen receptor T-cell therapy

BackgroundChimeric antigen receptor T-cell (CAR T-cell) therapy is increasingly utilized for treatment of hematologic malignancies. Hematologic toxicities including thrombosis and bleeding complications have been reported. Accurate estimates for thrombotic and bleeding outcomes are lacking. ObjectivesWe performed a systematic review and meta-analysis in patients who received CAR T-cell therapy for an underlying hematologic malignancy with the objective to: a) assess the thrombosis and bleeding risk associated with CAR T-cell therapy, b) assess the impact of CRS and ICANS on the risks of thrombosis and bleeding, and c) assess the safety of anticoagulant or antiplatelet use in the period following treatment with CAR T-cell therapy. MethodsWe searched MEDLINE, EMBASE, and Cochrane CENTRAL up to February 2022 for studies reporting thrombotic or bleeding outcomes in patients receiving CAR T-cell therapy. Pooled event rates were calculated using a random-effects model. We performed subgroup analyses stratified by follow-up duration, CAR T-cell target antigen, and underlying hematologic malignancy. ResultsWe included 47 studies with a total of 7040 patients. High heterogeneity between studies precluded reporting of overall pooled rates of thrombotic and bleeding events. In studies with follow-up duration of ≤6 months, the pooled incidence of venous thrombotic events was 2.4% (95% CI, 1.4%-3.4%; I2 = 0%) per patient-month, whereas the rate was 0.1% (95% CI, 0%-0.1%; I2 = 0%) per patient-month for studies with longer follow-up periods (>6 months). The pooled incidences of any bleeding events per patient-month in studies with follow-up duration of ≤6 months and >6 months were 1.9% (95% CI, 0.6%-3.1%; I2 = 78%) and 0.3% (95% CI: 0%-0.8%, I2 = 40%), respectively. Secondary analyses by CAR T-cell target antigen, underlying malignancy, and primary outcome of the studies did not reveal significant differences in the rates of thromboembolism, any bleeding events, or major bleeding events. ConclusionThe risk of both thrombosis and bleeding following CAR T-cell therapy appears to be highest in the initial months following infusion.

Validation of the CoVID-TE model as a tool to predict thrombosis, bleeding, and mortality in the oncology patient with Sars-Cov-2 infection: a study by the SEOM cancer and thrombosis group

PurposeThe CoVID-TE model was developed with the aim of predicting venous thrombotic events (VTE) in cancer patients with Sars-Cov-2 infection. Moreover, it was capable of predicting hemorrhage and mortality 30 days following infection diagnosis. The model is pending validation.Methods/patientsMulticenter retrospective study (10 centers). Adult patients with active oncologic disease/ antineoplastic therapy with Sars-Cov-2 infection hospitalized between March 1, 2020 and March 1. 2022 were recruited. The primary endpoint was to study the association between the risk categories of the CoVID-TE model and the occurrence of thrombosis using the Chi-Square test. Secondary endpoints were to demonstrate the association between these categories and the occurrence of post-diagnostic Sars-Cov-2 bleeding/ death events. The Kaplan–Meier method was also used to compare mortality by stratification.Results263 patients were enrolled. 59.3% were men with a median age of 67 years. 73.8% had stage IV disease and lung cancer was the most prevalent tumor (24%). A total of 86.7% had an ECOG 0–2 and 77.9% were receiving active antineoplastic therapy. After a median follow-up of 6.83 months, the incidence of VTE, bleeding, and death 90 days after Sars-Cov-2 diagnosis in the low-risk group was 3.9% (95% CI 1.9–7.9), 4.5% (95% CI 2.3–8.6), and 52.5% (95% CI 45.2–59.7), respectively. For the high-risk group it was 6% (95% CI 2.6–13.2), 9.6% (95% CI 5.0–17.9), and 58.0% (95% CI 45.3–66.1). The Chi-square test for trends detected no statistically significant association between these variables (p > 0.05). Median survival in the low-risk group was 10.15 months (95% CI 3.84–16.46), while in the high-risk group it was 3.68 months (95% CI 0.0–7.79). The differences detected were not statistically significant (p = 0.375).ConclusionsThe data from our series does not validate of the CoVID-TE as a model to predict thrombosis, hemorrhage, or mortality in cancer patients with Sars-Cov-2 infection.

NEOnatal Central-venous Line Observational study on Thrombosis (NEOCLOT): evaluation of a national guideline on management of neonatal catheter-related venous thrombosis

BackgroundIn critically ill (preterm) neonates, catheter-related venous thromboembolism (CVTE) can be a life-threatening complication. Evidence on optimal management in the literature is lacking. In the Netherlands, a consensus-based national management guideline was developed to create uniform CVTE management. ObjectivesTo evaluate the efficacy and safety of the national guideline. MethodsThis prospective, multicenter, observational study included all infants aged ≤6 months with CVTE in the Netherlands between 2014 and 2019. CVTE was divided into thrombosis in veins and that in the right atrium, with their own treatment algorithms. The primary outcomes were recurrent venous thrombotic events (VTEs) and/or death due to CVTE as well as major bleeding. ResultsOverall, 115 neonates were included (62% male; 79% preterm). The estimated incidence of CVTE was 4.0 per 1000 neonatal intensive care unit admissions. Recurrent thrombosis occurred in 2 (1.7%) infants and death due to CVTE in 1 (0.9%) infant. Major bleeding developed in 9 (7.8%) infants: 2 of 7 (29%) on recombinant tissue plasminogen activator, which was given for high-risk right-atrium thrombosis, and 7 of 63 (11%) on low-molecular-weight heparin (LMWH). Five of the 7 bleedings because of LMWH were complications of subcutaneous catheter use for LMWH administration. ConclusionThe management of neonatal CVTE according to the Dutch CVTE management guideline led to a low incidence of recurrent VTEs and death due to VTEs. Major bleeding occurred in 7.8% of the infants. Specific guideline adjustments may improve efficacy and, especially, safety of CVTE management in neonates.

Predictors of Early Thrombotic Events in Adult Patients with Acute Myeloid Leukemia: A Real-World Experience.

Information regarding the incidence and the prognostic impact of thrombotic events (TE) in non-promyelocytic acute myeloid leukemia (AML) is sparse. Although several risk factors associated with an increased risk of TE development have been recognized, we still lack universally approved guidelines for identification and management of these complications. We retrospectively analyzed 300 consecutive patients with newly diagnosed AML. Reporting the incidence of venous TE (VTE) and arterial TE (ATE) was the primary endpoint. Secondarily, we evaluated baseline patient- and disease-related characteristics with a possible influence of VTE-occurrence probability. Finally, we evaluated the impact of TE on survival. Overall, the VTE incidence was 12.3% and ATE incidence was 2.3%. We identified three independent predictors associated with early-VTE: comorbidities (p = 0.006), platelets count >50 × 109/L (p = 0.006), and a previous history of VTE (p = 0.003). Assigning 1 point to each variable, we observed an overall cumulative incidence of VTE of 18.4% in the high-risk group (≥2 points) versus 6.4% in the low-risk group (0-1 point), log-rank = 0.002. Overall, ATE, but not VTE, was associated with poor prognosis (p < 0.001). In conclusion, TE incidence in AML patients is not negligible. We proposed an early-VTE risk score that could be useful for a proper management of VTE prophylaxis.

Neutrophil to Lymphocyte Ratio (NLR) at Diagnosis Is a Predictor of Venous Thrombosis and Poor Outcome in Patients with Prefibrotic Primary Myelofibrosis

Background Thrombosis is a common complication in patients (pts) with myeloproliferative disease: it represents the product of a dysfunctional interaction between erythrocytes, platelets, leukocytes and endothelium. A pro-inflammatory microenvironment appears to be associated with an increased thrombotic risk. Neutrophil-to-lymphocyte ratio (NLR) reflects the balance between systemic inflammation and immunity and is emerging as a prognostic biomarker in several diseases, including hematological ones. Recently Carobbio et al. [BCJ, 2022] described NLR as a predictor of venous thrombosis in Polycythemia Vera. No score was specifically developed to assess thrombotic risk in myelofibrosis (MF), and even less is known in the setting of prefibrotic primary myelofibrosis (pre-MF). Aims In a multicenter cohort of pre-MF pts, we retrospectively investigated the relationship between NLR values at diagnosis and the risk of: 1) thrombosis 2) disease progression into overt-MF, accelerated (AP) or blast phase (BP); 3) overall survival (OS). Methods We collected clinical, histopathological and hematological data of 176 pts with a diagnosis of pre-MF, revised according to 2016 World Health Organization criteria, followed at 4 Hematological Centers between 2002 and 2022. NLR values were calculated using data obtained from the complete blood count at diagnosis, as the ratio between absolute neutrophilic count (ANC) and absolute lymphocyte (ALP) count. Pts were dichotomized using the best threshold identified by ROC analysis. Thrombotic complications included arterial (ischemic stroke, myocardial infarction, peripheral arterial disease) and venous (deep vein thrombosis, pulmonary embolism, cerebral and splanchnic vein thrombosis) events. Thrombosis-free survival (TFS) and OS were determined from pre-PMF diagnosis to the first thrombotic event and to death or last contact, respectively. TFS/OS were estimated by Kaplan-Meier analysis; the log-rank test was used to compare TFS/OS differences between risk stratified groups. Results Overall, 176 pts were included in this study. Median age was 63.6 (range 25-80) years; 88 (50%) were male. Majority of pts were JAK2V617F mutated (76,1%). Median NLR value at diagnosis was 3 (range 0,64-41,5). By ROC analysis, 6 was identified as the best cut-off value to dichotomize pts based on NLR; 23 pts (13%) presented NLR >6 at diagnosis. A major thrombotic event occurred before or at diagnosis in 53 pts (30,1%): 29 arterial and 25 venous (one patient had both a venous and arterial event). During the follow-up (FU), 30 pts (17%) developed a thrombosis, for a total of 38 thrombotic events (20 venous and 18 arterial events, accounting for an incidence rate of 1,67 and 1,50 per 100 pts-year, respectively). In statistical analysis, factors significantly associated to thrombosis during the FU were previous thrombosis (p=0.05) and JAK2 V617F mutation (p=0.03). Total leucocyte and platelets count, as well as age, sex and IPSET thrombosis score did not correlate with thrombotic events. Pts with ANC > 9 x10^9/L or ALP count < 1,5x10^9/L at diagnosis showed a trend towards a greater incidence of thrombosis in FU (p=0.06 and p=0.07, respectively). Pts with NLR value > 6 at diagnosis had a significantly higher incidence of venous thrombotic events (p=0.03) and a shorter venous TFS (p=0.004, Figure 1) compared to patients with NLR <6. The NLR value was not predictive of arterial thrombotic risk. After a median FU of 6.14 years (range 0,5-27,96) years, 32 pts (18,2%) died; 22 pts (12,5%) had disease progression: of them, 13 (7,4%) experienced overt MF and 9 (5,1%) evolved into an AP or BP. Pts with NLR value > 6 at diagnosis had a significant shorter OS compared to the group with NLR <6 (median OS 4,93 vs 6,22 months respectively, p=0.02). Conclusions This multicenter study investigated for the first time whether the NLR value at diagnosis could be a predictive marker of thrombotic risk and poor outcome in pre-PMF setting. Previous thrombosis and JAK2V617F mutation are confirmed to be risk factors for thrombotic events also in pre-MF setting. Notably, NLR > 6 at diagnosis emerged as a simple marker to identify pts at higher risk of thrombosis and poor outcome in the pre-PMF setting: pts with a NLR value > 6 have a significantly higher venous thrombotic risk and a shorter venous TFS. Furthermore, NLR group > 6 appears to have a shorter OS. These data are promising but require to be confirmed on a larger scale. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

P46. TXA vs no TXA: tranexamic acid in lumbar fusion, a retrospective study comparison

<h3>BACKGROUND CONTEXT</h3> Tranexamic Acid (TXA) has been proven safe and efficacious in procedures with large volume blood loss (joint replacement and cardiac surgery). Its role as a pharmaceutical agent for blood loss preservation for long-segment spinal fusion (complex spinal fusion, deformity cases) has also shown promising results. However, it remains unclear if the risk of potential thrombogenesis that could lead to venous thrombotic events (VTE) outweighs its benefits in shorter cases less likely to need blood transfusion. TXA is widely available in various forms, (ie, oral, topical, intravenous [IV]); consensus is lacking with regards to the optimal dosing regimen for spinal fusion. <h3>PURPOSE</h3> Our study objective is to evaluate IV TXA use in lumbar fusion. <h3>STUDY DESIGN/SETTING</h3> Retrospective/single center. <h3>PATIENT SAMPLE</h3> Patients undergoing 2-5 level lumbar fusion with instrumentation. <h3>OUTCOME MEASURES</h3> EBL, POD 1 hemoglobin, blood transfusion requirements, LOS, post-dose incidence of VTE. <h3>METHODS</h3> A total of 251 patients were included in this retrospective case series (2018-2019). Demographics, patient characteristics, estimated blood loss (EBL), postoperative day (POD) 1 hemoglobin, transfusion requirements, VTE, and length of stay (LOS) were compared between a group who received TXA (TXA) and a control group who did not (No TXA). The No TXA group are historical patients 6 months preTXA use, and those with contraindications during the treatment period (ie, history of hypersensitivity, bleeding, clotting, recent trauma or significant kidney disease). Treatment modality was 2 grams infused over 30 minutes perioperatively (1 gram prior to incision and repeated at closure). Data was analyzed with t-test (or Wilcoxon test) and Chi-squared test (or Fisher's exact test). P< 0.05 are to be considered statistically significant. <h3>RESULTS</h3> The two groups were similar in characteristics. There were no differences in age, gender, BMI and ASA score, all p>0.05. Both groups had similar smoking status (p=0711) and preoperative hemoglobin values (No TXA 13.9mg/dL ± 1.3mg/dL vs TXA 14.1± 1.5mg/dL, p=0.305). All patients had degenerative disease, approximately 10% had concurrent scoliotis. Number of levels intrumented: 2 (37%), 3 (23%), 4 (22%) and 5 (18%). No difference in the distribution in terms of primary vs revision surgery (p=0.209). Thirty-six percent (n-91) received 1-2 doses. Of the 91 treated patients, 90% (n-82) received the two doses, at preincision and closure; 99% (n-90) received a dose at preincision and 91% (n-83) at closure. With two doses, the average dose administered was 22mg/kg ±6.1mg/kg. EBL was skewed with outliers, No TXA median (IQR): 300 (150-450) vs TXA median (IQR): 250 (150-300), p=0.078. Cell saver utility by both groups were similar (No TXA 27%, TXA 24%); no difference in amount returned (p=0.739). Although the TXA group had significantly higher hemoglobin level on POD1 (No TXA 10.8±1.5 g/dL vs TXA 11.5±1.5 g/dL, p<0.001), both groups had similar low incidence of severe postoperative anemia requiring blood transfusion (No TXA 7.5% vs TXA 3.3%, p=0.268). A difference in LOS was observed (No TXA 3.5+1.3 days vs TXA 3.2+1.1 days, p=0.02). While hospitalized, one patient in the control group developed deep vein thrombosis on POD4; no VTE was reported in the TXA group. <h3>CONCLUSIONS</h3> With or without TXA, EBL was comparable in 2-5 level lumbar fusion. Patients in the TXA group, however, had a higher POD 1 hemoglobin and had shorter length of hospitalization. No VTE was reported among the TXA treated population. <h3>FDA DEVICE/DRUG STATUS</h3> This abstract does not discuss or include any applicable devices or drugs.

Thromboembolic Disease in Patients With Cancer and COVID-19: Risk Factors, Prevention and Practical Thromboprophylaxis Recommendations-State-of-the-Art.

Cancer and COVID-19 are both well-established risk factors predisposing to thrombosis. Both disease entities are correlated with increased incidence of venous thrombotic events through multifaceted pathogenic mechanisms involving the interaction of cancer cells or SARS-CoV2 on the one hand and the coagulation system and endothelial cells on the other hand. Thromboprophylaxis is recommended for hospitalized patients with active cancer and high-risk outpatients with cancer receiving anticancer treatment. Universal thromboprophylaxis with a high prophylactic dose of low molecular weight heparins (LMWH) or therapeutic dose in select patients, is currentlyindicated for hospitalized patients with COVID-19. Also, prophylactic anticoagulation is recommended for outpatients with COVID-19 at high risk for thrombosis or disease worsening. However, whether there is an additive risk of thrombosis when a patient with cancer is infected with SARS-CoV2 remains unclear In the current review, we summarize and critically discuss the literature regarding the epidemiology of thrombotic events in patients with cancer and concomitant COVID-19, the thrombotic risk assessment, and the recommendations on thromboprophylaxis for this subgroup of patients. Current data do not support an additive thrombotic risk for patients with cancer and COVID-19. Of note, patients with cancer have less access to intensive care unit care, a setting associated with high thrombotic risk. Based on current evidence, patients with cancer and COVID-19 should be assessed with well-established risk assessment models for medically ill patients and receive thromboprophylaxis, preferentially with LMWH, according to existing recommendations. Prospective trials on well-characterized populations do not exist.

Risk of venous thromboembolism in children and adolescents with inflammatory bowel disease: A systematic review and meta-analysis.

BACKGROUNDA two- to three-fold increased risk of venous thrombotic events (VTE) has been demonstrated in patients with inflammatory bowel disease (IBD) compared to the general population, but less is known about the risk of VTE in child- and pediatric-onset IBD. In recent years, several studies have reported the rising incidence rate of VTE in juvenile patients with IBD, and the related risk factors have been explored.AIMTo evaluate the risk of VTE in children and adolescents with IBD.METHODSArticles published up to April 2021 were retrieved from PubMed, Embase, Cochrane Library, Web of Science, SinoMed, CNKI, and WANFANG. Data from observational studies and clinical work were extracted. The outcome was the occurrence of VTE according to the type of IBD. The available odds ratio (OR) and the corresponding 95% confidence interval (CI) were extracted to compare the outcomes. Effect size (P), odds ratio (OR), and 95%CI were used to assess the association between VTE risk and IBD disease. Subgroup analyses stratified by subtypes of VTE and IBD were performed. RESULTSTwelve studies (7450272 IBD patients) were included in the meta-analysis. Child and adolescent IBD patients showed increased VTE risk (P = 0.02, 95%CI: 0.01-0.03). Subgroup analyses stratified by IBD (ulcerative colitis (UC): P = 0.05, 95%CI: 0.03-0.06; Crohn’s disease (CD): P = 0.02, 95%CI: 0.00-0.04) and VTE subtypes (portal vein thrombosis: P = 0.04, 95%CI: 0.02-0.06; deep vein thrombosis: P = 0.03, 95%CI: 0.01-0.05; central venous catheter-related thrombosis: P = 0.23, 95%CI: 0.00-0.46; thromboembolic events: P = 0.02, 95%CI: 0.01-0.03) revealed a significant correlation between VTE risk and IBD. Patients with IBD were more susceptible to VTE risk than those without IBD (OR = 2.99, 95%CI: 1.45-6.18). The funnel plot was asymmetric, suggesting the presence of significant publication bias. Pediatric and adolescent IBD patients have an increased VTE risk. UC and CD patients exhibited a high risk of VTE. The risk of VTE subtypes was increased in IBD patients.CONCLUSIONThe current meta-analysis showed that the incidence and risk of VTE are significantly increased in pediatric and adolescent IBD patients. Thus, IBD might be a risk factor for VTE in children and young adults. High-quality prospective cohort studies are necessary to confirm these findings.

Incidence of venous thrombotic events and events of special interest in a retrospective cohort of commercially insured US patients

ObjectiveTo estimate the US incidence of thrombotic events and related rare diagnoses.DesignClaims-based retrospective cohort study of incidence.SettingUS commercial health insurance administrative claims database.ParticipantsAdults 25–64 years of age between 2015 and...

Evaluation of Bivalirudin as the Primary Anticoagulant in Patients Receiving Extracorporeal Membrane Oxygenation for SARS-CoV-2-Associated Acute Respiratory Failure.

Extracorporeal membrane oxygenation (ECMO) is a potential option for the management of severe acute respiratory failure secondary to COVID-19. Conflicting the use of this therapy is the known coagulopathy within COVID-19, leading to an incidence of venous thrombotic events of 25% to 49%. To date, limited guidance is available on optimal anticoagulation strategies in this population. The purpose of this study was to evaluate the utilization of a pharmacist-driven bivalirudin dosing protocol for anticoagulation in the setting of ECMO for COVID-19-associated respiratory failure. This was a single-center retrospective chart review over a 9-month period of patients receiving bivalirudin while on ECMO. All patients with acute respiratory failure requiring ECMO with a positive SARS-CoV-2 polymerase chain reaction were included. Bivalirudin was dosed via aPTT monitoring after a starting dose of 0.2 or 0.3 mg/kg/h. There were 33 patients included in this study, all receiving mechanical ventilation. The most common starting dose of bivalirudin was 0.2 mg/kg/h, with an average time to therapeutic range of 20 hours. Compared to previous reports, rates of bleeding were low at 15.1%, and 6.1% of patients developed a new venous thromboembolic event while on ECMO. ECMO survival was 51.5%, with an ICU mortality rate of 48.5%. In the first published report of its use within this population, bivalirudin was found to be a viable choice for anticoagulation in those patients on ECMO for severe respiratory failure secondary to COVID-19.

Thrombotic events in patients treated with immune checkpoint inhibitors for non-small cell lung cancer: A retrospective multicentric cohort study.

e21198 Background: Venous thromboembolism is a frequent complication of non-small cell lung cancer (NSCLC) and is associated with a worse prognosis, a reduced quality of life, and increased healthcare costs. Immune checkpoint inhibitors (ICI) are revolutionizing the management of NSCLC, but little is known about their impact on thrombosis. This study aims to define the incidence and clinical relevance of thrombosis in NSCLC patients receiving these treatments. Methods: A retrospective multicentric cohort study including 593 patients from three centers in Canada and France was performed. The cumulative incidence of venous thrombotic events after ICIs was calculated, and the impact of these events on survival and response to treatment was determined. Finally, univariate log-rank tests were performed to identify thrombosis risk factors. Results: The incidence of venous thrombosis in the cohort was 9.9% for an incidence rate of 76.5 thrombosis per 1000 person-years, with most thromboses occurring rapidly after treatment initiation. Thrombosis was not correlated with overall survival, progression-free survival, or objective response to ICIs (summarized in the table below). Age ˂ 65 years old (HR = 1.66; 95 % CI = 1.00 – 2.82) and a delay of less than 12 months from diagnosis to the first ICI treatment (HR = 1.74; 95 % CI = 1.03 – 2.87) were associated with an increased risk of thrombosis. Tumors with PD-L1 &gt; 1% were associated with more thrombosis in the first year since the beginning of therapy (HR = 3.06; 95 % CI = 1.19 – 4.76, p=0.015). Conclusions: This study suggests that the time distribution and incidence of thrombotic events in NSCLC patients treated with ICI are comparable to what is reported in other cohorts of patients treated with chemotherapy. In our cohort, thrombosis was not a prognostic factor for survival or response to therapy. Patient age &lt; 65 and tumors with PD-L1 &gt; 1% were associated to a higher risk of thrombotic events.[Table: see text]

Heparins and 2019-nCoV infection: a narrative review.

Patients with 2019-nCoV infection have a high risk to develop venous thrombotic events. Several guidelines recommend the use of either unfractionated heparin or low molecular weight heparins in preventing thrombotic events in these patients. However, results from clinical studies, so far published, reached controversial conclusions on heparin efficacy in this kind of patients since the incidence of venous thromboembolism remains high despite prophylaxis. This narrative review aims to provide an overview of the antiviral and anti-inflammatory properties of heparins and their efficacy and safety in SARS-CoV-2 medical ward-patients. Moreover, anatomical findings and ongoing trials are also reported. Finally, this narrative review tries to explain why heparins fail to prevent venous thrombosis. We searched for the most relevant published studies on heparins and 2019-nCoV infected patients using the MEDLINE electronic database in the period between January and December 2020. Articles were preliminarily defined as eligible if they: a) were in English language, b) enrolled 250 or more medical ward-patients and 100 or more ICU-patients, c) reported results on patients treated with heparins in a percentage of at least 70% and d) performed an objectively confirmed diagnosis of VTE. Data from medium to large scientific studies show that the incidence of venous thrombotic events in medical ward-patients with SARS-CoV-2 vary between 0% and 8.3%, while this rate is higher, from 6.2% to 49%, in Intensive Care Unit-patients. However, heparins reduce the mortality rate in these patients of about 50%. Histological findings show that thrombosis could affect capillaries, main and small-mid-sized vessels, and it is associated with diffuse alveolar damage. Heparins have anti-inflammatory and anti-viral properties, which may be of help in reducing mortality in SARS-CoV-2 patients. Failure of heparins at prophylactic dosages in preventing VTE, especially in ICU-patients, could be due to the severity of the disease. Data on the use of heparins in an early phase of the 2019-nCoV infection are still lacking.

What is the ideal route of administration of tranexamic acid in total knee arthroplasty? A meta-analysis based on randomized controlled trials

Tranexamic acid (TXA) was conducive in total knee arthroplasty (TKA) to reduce blood loss and transfusion demand. The purpose of this meta-analysis was to assess the efficacy and safety of different administration of TXA in primary TKA. Database PubMed, Medline, Web of Science and Embase were searched. The relative risks (RRs) with 95% confidence intervals (CIs) were calculated to analysis dichotomous outcomes. The mean differences (MD) with 95% CIs were calculated to analysis dichotomous outcomes. Data was analyzed using RevMan 5.3. Twenty-eight randomized controlled trials (RCTs) studies were included in this meta-analysis involving a total of 4,200 participants. There were no obvious differences between oral, intravenous or topical TXA group in total blood loss (intravenous vs. topical: MD =11.55, 95% CI, -10.23 to 33.34, oral vs. intravenous or topical: MD =-52.25, 95% CI, -121.28 to 16.78), transfusion rate (intravenous vs. topical: RR =1.04, 95%CI, 0.64 to 1.69, oral vs. intravenous or topical: RR =0.75, 95% CI, 0.36 to 1.54), incidence of venous thrombotic events (VTE) (intravenous vs. topical: RR =1.43, 95% CI, 0.81 to 2.54). The topical TXA administration had significantly increased postoperative hemoglobin (HB) level compared with the intravenous TXA administration (MD =-0.37, 95% CIs, -0.47 to -0.26). In the combined group, the total blood loss (MD =-119.58, 95% CI, -181.68 to -57.49) and postoperative HB level (MD =0.54, 95% CI, 0.45 to 0.64) were more acceptable than the single-route group. Combined administration of TXA can reduce total blood loss, postoperative HB drop compared with intravenous, topical or oral TXA alone. Oral administration of TXA is similar to intravenous or topical TXA use alone.

Thrombosis as a treatment complication in Hodgkin lymphoma patients: a comprehensive analysis of three prospective randomized German Hodgkin Study Group (GHSG) trials.

The prognosis of Hodgkin lymphoma (HL) is excellent rendering research into treatment complications highly important. An important complication of cancer and its treatment is thrombosis. Thrombotic events are regularly observed in HL patients but precise information on incidence and risk factors is lacking and the value of prophylactic anticoagulation unclear. Thus, we comprehensively studied thrombotic events in 5773 patients from the German Hodgkin Study Group (GHSG) HD13-15 trials in early-favorable, intermediate and advanced HL. We estimated the incidence of and identified risk factors for thrombotic events. Additionally, we provide detailed data on the time course and characteristics of thrombotic events. A total of 193 thrombotic events occurred for an incidence of 3.3%. Out of these, 175 (90.7%) were venous thromboses, 3 (1.5%) newly emerging post-thrombotic syndromes and 15 (7.8%) arterial thromboses. There were 11 (0.7%) events in early-favorable, 27 (1.3%) in early-unfavorable and 155 (7.3%) in advanced patients, the latter incidence being significantly higher (P < 0.001). The most common locations were deep vein thrombosis of the arm (46.3%) and leg (24.6%). Most venous thrombotic events occurred during chemotherapy (78.9%). We observed 59 (30.6%) catheter-associated events and a descriptively increased risk of venous thrombotic events in patients with oral contraception use during treatment (6.8% versus 3.9%). In advanced HL, the incidence of venous thrombotic events was increased upon treatment with BEACOPP-14 (9.4%, P = 0.0079) compared with 5.1% with 6×BEACOPPesc and 5.7% with 8×BEACOPPesc. Among commonly applied risk factors, including the Khorana score, only age and smoking were prognostic. The incidence of thrombotic events in advanced stage HL is comparable to other high-risk cancer patients, especially if treated with dose-dense regimens. Additional risk factors are higher age and smoking. Selected HL patients could benefit from prophylactic anticoagulation, however, further interventional studies are needed before general recommendations can be made.

Incidence and Risk Factors of Symptomatic Venous Thromboembolism Following Foot and Ankle Surgery.

The incidence rate of venous thrombotic events (VTEs) following foot and ankle surgery is low. Currently, there is no consensus regarding postoperative prophylaxis or evidence to support risk stratification. A 2-part study assessing the incidence and factors for the development of VTE was conducted: (1) a retrospective observational cohort study of 22 486 adults to calculate the overall incidence following foot and/or ankle surgery from January 2008 to May 2011 and (2) a retrospective matched case-control study to identify risk factors for development of VTE postsurgery. One control per VTE case matched on age and sex was randomly selected from the remaining patients. The overall incidence of VTE was 0.9%. Predictive risk factors in bivariate analyses included obesity, history of VTE, history of trauma, use of hormonal replacement or oral contraception therapy, anatomic location of surgery, procedure duration 60 minutes or more, general anesthesia, postoperative nonweightbearing immobilization greater than 2 weeks, and use of anticoagulation. When significant variables from bivariate analyses were placed into the multivariable regression model, 4 remained statistically significant: adjusted odds ratio (aOR) for obesity, 6.1; history of VTE, 15.7; use of hormone replacement therapy, 8.9; and postoperative nonweightbearing immobilization greater than 2 weeks, 9.0. The risk of VTE increased significantly with 3 or more risk factors ( P = .001). The overall low incidence of VTE following foot and ankle surgery does not support routine prophylaxis for all patients. Among patients with 3 or more risk factors, the use of chemoprophylaxis may be warranted. Level III, retrospective case series.

Incidence and characteristics of venous thrombotic events in pediatric cancer patients: A 20-year experience in the Maritimes, Canada

ABSTRACTObjective: Venous thrombotic events (VTE) are a well-recognized complication in pediatric cancer patients. Population-based data on the incidence and characteristics of VTE in all pediatric cancer patients are limited. This information is crucial to identify patients at high risk and design targeted interventions accordingly. The present study was designed to determine the incidence and characteristics of VTE in the pediatric oncology population. Participants: We conducted a retrospective, population-based, cohort study of patients treated in the Maritimes, Canada between 1995 and 2015. Results: There were 1210 pediatric hematology/oncology patients from the Maritimes, Canada, treated at the IWK Health Centre between 1995 and 2015. Fifty-eight (4.8%) experienced at least 1 VTE and the majority of patients experienced it within 6 months of cancer diagnosis. The median age of patients who experienced VTE was 10.7 years (SD = 6.0). The most common presenting symptom of thrombosis was central venous line dysfunction, and the most common location for thrombosis was within the upper venous system. We observed that 65.6% of the patients with VTE required >1 central venous catheters (CVC). The presence of a VTE increased the odds of requiring >1 CVC to 3.6 (95% confidence interval: 1.76–7.3). Conclusion: Thus, in this large, population-based study, we present the incidence and characteristics of VTE in the pediatric oncology population and demonstrate the clinical impact of VTE in terms of loss of CVC. Larger, prospective studies are required to confirm these findings and to develop a risk model for managing and preventing VTE in this patient population.

On both sides of the ocean.

On both sides of the ocean.

Incidence of Venous Thrombotic Events Following Gynecologic Surgery.

Incidence of Venous Thrombotic Events Following Gynecologic Surgery.

Incidence of Venous Thrombotic Events following Gynecologic Surgery

Incidence of Venous Thrombotic Events following Gynecologic Surgery

Incidence of Thrombotic Events in Patients Admitted to a Dedicated Tuberculosis Center in the Netherlands

IntroductionTuberculosis (TB) claims over 1 million deaths per year. Some patients die despite institution of effective chemotherapy. As epidemiological and fundamental research show that acute or chronic inflammatory diseases are a risk factor for thrombotic events, TB-patients may especially be at high risk for venous thrombotic events (VTE) as TB is an infectious disease that can be seen as an acute-on-chronic inflammatory process and is often associated with a double/triple infectious burden caused by HIV or hepatitis. Consequently, VTE may explain a part of TB related mortality, which may in turn be preventable through institution of thromboprophylaxis. We therefore set out to explore the burden of thrombotic disease in a cohort of TB patients.SettingBeatrixoord TB Center, Groningen, the Netherlands, is a multidisciplinary referral Center for complicated TB. The case mix of TB patients mostly comprises patients that have a relatively stable somatic condition but need inpatient care because of socio-psychological factors, but also patients who have severe debilitating infectious disease with comorbidities requiring long term inpatient care are admitted.MethodsIn this retrospective cohort study, we reviewed all charts of cases discharged (alive or deceased) with a first admission to the center in the years 2000 through 2010. Cases were defined as suspected and treated or confirmed infection with Mycobacterium tuberculosis complex. We excluded cases younger than 18 years and those already on therapeutic anticoagulant therapy. Primary outcome was VTE, with no restriction on localization. A VTE was defined as confirmed if relevant imaging was done or if VTE-related anticoagulant therapy was administered for at least 3 months. We assumed VTEs were related to TB if they occurred in the six months before institution of anti-tuberculosis therapy until discharge. We recorded date of diagnosis and relevant exposure (up to six weeks before VTE) to classic risk factors (surgery, pregnancy, malignancy and immobilization) and hospitalization. For patients without an event, we noted any exposure to classic risk factors and hospitalization. Patients were defined as hospitalized if they had been admitted to a hospital elsewhere. Patients were defined as immobilized if they had a plaster cast on/fracture/paralysis of any extremity or if they had been clearly bedridden for >7 days.Results750 patients were included for the analysis of incidence of VTE (figure 1).Eighteen patients had a VTE according to our definition, 17 of these were diagnosed before admission to the clinic. Three VTEs were unprovoked. One patient died in circumstances highly suspicious of pulmonary embolism but autopsy was not performed. Consequently, we excluded this case from our analysis. Patients with an HIV co-infection or disseminated TB had the highest risk of VTE (odds ratio 11.2 95%CI [4.3-29.2] and 3.3 [1.3-8.8] respectively, compared to patients without these risk factors). Other characteristics are presented in table 1.Discussion:In this cohort of TB patients, 2.4% of patients had a VTE. The majority of VTEs had a provoking factor. However, there was still an event rate of 1% in patients not exposed to classic risk factors/hospitalization. This seems higher than an expected incidence of 0.1%. Patients with a HIV co-infection or disseminated TB had the highest risk of developing a VTE. This may warrant the use of primary prophylaxis in these patients. Our findings may be an overestimation of the true incidence as our clinic is a tertiary center. However, social (and not medical) complexity was the most common reason for referral. Nonetheless, these results need confirmation.Table 1VTE rates stratified by clinical characteristics & univariate analysisVTE: N=18Odds of VTE in risk factor positive cases (%)Odds of VTE in risk factor negative cases (%)Odds ratio (95%CI)Male sex16/522 (3%)2/210 (1%)3.3 (0.7 – 14.2)HIV status10/77(11%)8/690 (1%)11.2 (4.3 – 29.2)No provoking risk factor (classic/ hospitalization)3/293 (1%)15/449 (3%)0.3 (0.1 – 1.0)Hospitalized14/427 (3%)4/305 (1%)2.5 (0.8 – 7.6)Immobilized3/51 (6%)15/681 (2%)2.6 (0.7 – 9.5)Characteristics of TB infectionsMultidrug resistance1/67 (1%)17/665 (2%)0.6 (0.1 – 4.5)Pulmonary TB11/465 (2%)7/267 (2%)0.9 (0.3 – 2.4)Extrapulmonary TB2/164 (1%)16/568 (3%)0.4 (0.1 – 1.9)Disseminated (more than one organ)7/117 (6%)11/615 (2%)3.3 (1.3 – 8.8) [Display omitted] DisclosuresNo relevant conflicts of interest to declare.