Browsing by Subject "Thromboembolism"

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    Clinical outcomes of cardiac surgery patients undergoing therapeutic plasma exchange for heparin-induced thrombocytopenia.
    (Vox sanguinis, 2021-02) Moreno-Duarte, Ingrid; Cooter, Mary; Onwuemene, Oluwatoyosi A; Ghadimi, Kamrouz; Welsby, Ian J

    Background and objectives

    Heparin-induced thrombocytopenia (HIT) is an antibody-mediated condition that leads to thrombocytopenia and possible thrombosis. Patients with HIT who require cardiac surgery pose a challenge as high doses of heparin or heparin alternatives are required to permit cardiopulmonary bypass (CPB). Intraoperative therapeutic plasma exchange (TPE) is a valuable adjunct in the management of antibody-mediated syndromes including HIT. The clinical impact of TPE on thromboembolic events, bleeding and mortality after heparin re-exposure is not well established. We hypothesized that TPE with heparin re-exposure will not lead to HIT-related thromboembolic events, bleeding or increased mortality after cardiac surgery with CPB.

    Materials and methods

    We reviewed 330 patients who received perioperative TPE between September 2012 and September 2017.

    Results

    Twenty four patients received TPE for HIT before anticipated heparin use for CPB. Most patients were males (79%) scheduled for advanced heart failure therapies. Three patients (12·5%) died within 30 days after surgery but none of the deaths were considered HIT-related. Thromboembolic events (TE) occurred in 3 patients within 7 days of surgery; of those, two were possibly HIT-related.

    Conclusion

    Therapeutic plasma exchange with heparin re-exposure was not strongly associated with HIT-related thrombosis/death after cardiac surgery with CPB.
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    Effect of Antifibrinolytic Therapy on Complications, Thromboembolic Events, Blood Product Utilization, and Fusion in Adult Spinal Deformity Surgery.
    (Spine, 2016-07) Soroceanu, Alex; Oren, Jonathan H; Smith, Justin S; Hostin, Richard; Shaffrey, Christopher I; Mundis, Gregory M; Ames, Christopher P; Burton, Douglas C; Bess, Shay; Gupta, Munish C; Deviren, Vedat; Schwab, Frank J; Lafage, Virginie; Errico, Thomas J

    Study design

    A multicenter, prospective, consecutive database of surgical patients with adult spinal deformity (ASD).

    Objective

    This study investigated the use of antifibrinolytic (AF) therapy in ASD surgery.

    Summary of background data

    AF therapy has been shown to be effective in preventing blood loss in some settings. Its effect on major and minor perioperative complications, blood product utilization, vascular events, and postoperative fusion in patients undergoing ASD surgery remains unclear.

    Methods

    All patients with data on AF use were included. Parameters of blood utilization included transfusion rates and units of packed red blood cells and fresh frozen plasma transfused. Thromboembolic events included stroke, deep vein thrombosis, and pulmonary embolus. Multivariate regression was used, accounting for confounders.

    Results

    Four hundred three patients were included. One hundred thirty-seven patients received aminocaproic acid (EACA), 81 received tranexamic acid (TXA), and 185 received no AFs. The use of AF was associated with a decrease in transfusion (EACA: odds ratio [OR] = 0.38, P = 0.043; TXA: OR = 0.31, P = 0.047), a decrease in the number of units of packed red blood cells transfused (EACA: incidence risk ratio [IRR] = 0.45, P = 0.0005; TXA: IRR = 0.7, P = 0.0005), and a decrease in the number of fresh frozen plasma transfused (EACA: IRR = 0.65, P = 0.003; TXA: IRR = 0.67, P = 0.006). AF use was associated with an increase in minor intraoperative complications (EACA: IRR = 2.15, P = 0.008; TXA: IRR = 2.12, P = 0.011). TXA use (but not EACA) was associated with a decrease in the incidence of major perioperative complications compared with no AF (IRR = 0.37, P = 0.019). There was no difference in the incidence of thromboembolic events.

    Conclusion

    TXA or EACA use was associated with increased minor intraoperative complications. TXA was associated with decreased major perioperative complications. AF was associated with decreased utilization of blood products without an increased rate of thromboembolic events. Given the nature of this study, transfusion threshold was not standardized. Future studies with rigid criteria for transfusion should be prospectively performed to better evaluate the impact of AF during ASD surgery.

    Level of evidence

    3.
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    ItemOpen Access
    Long-term Thromboembolic Risk in Patients With Postoperative Atrial Fibrillation After Coronary Artery Bypass Graft Surgery and Patients With Nonvalvular Atrial Fibrillation.
    (JAMA cardiology, 2018-05) Butt, Jawad H; Xian, Ying; Peterson, Eric D; Olsen, Peter Skov; Rørth, Rasmus; Gundlund, Anna; Olesen, Jonas B; Gislason, Gunnar H; Torp-Pedersen, Christian; Køber, Lars; Fosbøl, Emil L
    Importance:New-onset postoperative atrial fibrillation (POAF) is a common complication of coronary artery bypass graft (CABG) surgery. However, the long-term risk of thromboembolism in patients who develop POAF after CABG surgery remains unknown. In addition, information on stroke prophylaxis in this setting is lacking. Objective:To examine stroke prophylaxis and the long-term risk of thromboembolism in patients with new-onset POAF after first-time isolated CABG surgery compared with patients with nonsurgical, nonvalvular atrial fibrillation (NVAF). Design, Setting, and Participants:This cohort study used data from a clinical cardiac surgery database and Danish nationwide registries to identify patients undergoing first-time isolated CABG surgery who developed new-onset POAF from January 1, 2000, through June 30, 2015. These patients were matched by age, sex, CHA2DS2-VASc score, and year of diagnosis to patients with nonsurgical NVAF in a 1 to 4 ratio. Data analysis was completed from February 2017 to January 2018. Main Outcomes and Measures:The proportion of patients initiating oral anticoagulation therapy within 30 days and the rates of thromboembolism. Results:A total of 2108 patients who developed POAF after CABG surgery were matched with 8432 patients with NVAF. In the full population of 10 540 patients, the median (interquartile range) age was 69.2 (63.7-74.7) years; 8675 patients (82.3%) were men. Oral anticoagulation therapy was initiated within 30 days postdischarge in 175 patients with POAF (8.4%) and 3549 patients with NVAF (42.9%). The risk of thromboembolism was lower in the POAF group than in the NVAF group (18.3 vs 29.7 events per 1000 person-years; adjusted hazard ratio [HR], 0.67; 95% CI, 0.55-0.81; P < .001). Anticoagulation therapy during follow-up was associated with a lower risk of thromboembolic events in both patients with POAF (adjusted HR, 0.55; 95% CI, 0.32-0.95; P = .03) and NVAF (adjusted HR, 0.59; 95% CI, 0.51-0.68; P < .001) compared with patients who did not receive any anticoagulation therapy. Further, the risk of thromboembolism was not significantly higher in patients with POAF compared with those who did not develop POAF after CABG surgery (adjusted HR, 1.11; 95% CI, 0.94-1.32; P < .24). Conclusions and Relevance:New-onset POAF in patients who had undergone CABG surgery was associated with a lower long-term thromboembolic risk than that of patients who had NVAF. These data do not support the notion that new-onset POAF should be regarded as equivalent to primary NVAF in terms of long-term thromboembolic risk.
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    Model predictions of deformation, embolization and permeability of partially obstructive blood clots under variable shear flow.
    (Journal of the Royal Society, Interface, 2017-11) Xu, Shixin; Xu, Zhiliang; Kim, Oleg V; Litvinov, Rustem I; Weisel, John W; Alber, Mark
    Thromboembolism, one of the leading causes of morbidity and mortality worldwide, is characterized by formation of obstructive intravascular clots (thrombi) and their mechanical breakage (embolization). A novel two-dimensional multi-phase computational model is introduced that describes active interactions between the main components of the clot, including platelets and fibrin, to study the impact of various physiologically relevant blood shear flow conditions on deformation and embolization of a partially obstructive clot with variable permeability. Simulations provide new insights into mechanisms underlying clot stability and embolization that cannot be studied experimentally at this time. In particular, model simulations, calibrated using experimental intravital imaging of an established arteriolar clot, show that flow-induced changes in size, shape and internal structure of the clot are largely determined by two shear-dependent mechanisms: reversible attachment of platelets to the exterior of the clot and removal of large clot pieces. Model simulations predict that blood clots with higher permeability are more prone to embolization with enhanced disintegration under increasing shear rate. In contrast, less permeable clots are more resistant to rupture due to shear rate-dependent clot stiffening originating from enhanced platelet adhesion and aggregation. These results can be used in future to predict risk of thromboembolism based on the data about composition, permeability and deformability of a clot under specific local haemodynamic conditions.
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    Prothrombin Complex Concentrates for Bleeding in the Perioperative Setting.
    (Anesth Analg, 2016-05) Ghadimi, Kamrouz; Levy, Jerrold H; Welsby, Ian J
    Prothrombin complex concentrates (PCCs) contain vitamin K-dependent clotting factors (II, VII, IX, and X) and are marketed as 3 or 4 factor-PCC formulations depending on the concentrations of factor VII. PCCs rapidly restore deficient coagulation factor concentrations to achieve hemostasis, but like with all procoagulants, the effect is balanced against thromboembolic risk. The latter is dependent on both the dose of PCCs and the individual patient prothrombotic predisposition. PCCs are approved by the US Food and Drug Administration for the reversal of vitamin K antagonists in the setting of coagulopathy or bleeding and, therefore, can be administered when urgent surgery is required in patients taking warfarin. However, there is growing experience with the off-label use of PCCs to treat patients with surgical coagulopathic bleeding. Despite their increasing use, there are limited prospective data related to the safety, efficacy, and dosing of PCCs for this indication. PCC administration in the perioperative setting may be tailored to the individual patient based on the laboratory and clinical variables, including point-of-care coagulation testing, to balance hemostatic benefits while minimizing the prothrombotic risk. Importantly, in patients with perioperative bleeding, other considerations should include treating additional sources of coagulopathy such as hypofibrinogenemia, thrombocytopenia, and platelet disorders or surgical sources of bleeding. Thromboembolic risk from excessive PCC dosing may be present well into the postoperative period after hemostasis is achieved owing to the relatively long half-life of prothrombin (factor II, 60-72 hours). The integration of PCCs into comprehensive perioperative coagulation treatment algorithms for refractory bleeding is increasingly reported, but further studies are needed to better evaluate the safe and effective administration of these factor concentrates.
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    Screening of Multiple Biomarkers Associated With Ischemic Stroke in Atrial Fibrillation.
    (Journal of the American Heart Association, 2020-12-09) Hijazi, Ziad; Wallentin, Lars; Lindbäck, Johan; Alexander, John H; Connolly, Stuart J; Eikelboom, John W; Ezekowitz, Michael D; Granger, Christopher B; Lopes, Renato D; Pol, Tymon; Yusuf, Salim; Oldgren, Jonas; Siegbahn, Agneta
    Background To explore the pathophysiological features of ischemic stroke in patients with atrial fibrillation (AF), we evaluated the association between 268 plasma proteins and subsequent ischemic stroke in 2 large AF cohorts receiving oral anticoagulation. Methods and Results A case-cohort sample of patients with AF from the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial, including 282 cases with ischemic stroke or systemic embolism and a random sample of 4124 without these events, during 1.9 years of follow-up was used for identification. Validation was provided by a similar case-cohort sample of patients with AF from the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial, including 149 cases with ischemic stroke/systemic embolism and a random sample of 1062 without these events. In plasma obtained before randomization, 268 unique biomarkers were measured with OLINK proximity extension assay panels (CVD II, CVD III, and Inflammation) and conventional immunoassays. The association between biomarkers and outcomes was evaluated by random survival forest and adjusted Cox regression. According to random survival forest or Cox regression analyses, the biomarkers most strongly and consistently associated with ischemic stroke/systemic embolism were matrix metalloproteinase-9, NT-proBNP (N-terminal pro-B-type natriuretic peptide), osteopontin, sortilin, soluble suppression of tumorigenesis 2, and trefoil factor-3. The corresponding hazard ratios (95% CIs) for an interquartile difference were as follows: 1.18 (1.00-1.38), 1.55 (1.28-1.88), 1.28 (1.07-1.53), 1.19 (1.02-1.39), 1.23 (1.05-1.45), and 1.19 (0.97-1.45), respectively. Conclusions In patients with AF, of 268 unique biomarkers, the 6 biomarkers most strongly associated with subsequent ischemic stroke/systemic embolism represent fibrosis/remodeling (matrix metalloproteinase-9 and soluble suppression of tumorigenesis 2), cardiac dysfunction (NT-proBNP), vascular calcification (osteopontin), metabolism (sortilin), and mucosal integrity/ischemia (trefoil factor-3). Registration URL: https://www.clinicaltrials.gov. Unique Identifiers: NCT00412984 and NCT00262600.
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    Self-monitoring of oral anticoagulation: systematic review and meta-analysis of individual patient data.
    (Lancet (London, England), 2012-01) Heneghan, Carl; Ward, Alison; Perera, Rafael; Self-Monitoring Trialist Collaboration; Bankhead, Clare; Fuller, Alice; Stevens, Richard; Bradford, Kairen; Tyndel, Sally; Alonso-Coello, Pablo; Ansell, Jack; Beyth, Rebecca; Bernardo, Artur; Christensen, Thomas Decker; Cromheecke, ME; Edson, Robert G; Fitzmaurice, David; Gadisseur, Alain PA; Garcia-Alamino, Josep M; Gardiner, Chris; Hasenkam, J Michael; Jacobson, Alan; Kaatz, Scott; Kamali, Farhad; Khan, Tayyaba Irfan; Knight, Eve; Körtke, Heinrich; Levi, Marcel; Matchar, David; Menéndez-Jándula, Bárbara; Rakovac, Ivo; Schaefer, Christian; Siebenhofer, Andrea; Souto, Juan Carlos; Sunderji, Rubina; Gin, Kenneth; Shalansky, Karen; Völler, Heinz; Wagner, Otto; Zittermann, Armin

    Background

    Uptake of self-testing and self-management of oral anticoagulation [corrected] has remained inconsistent, despite good evidence of their effectiveness. To clarify the value of self-monitoring of oral anticoagulation, we did a meta-analysis of individual patient data addressing several important gaps in the evidence, including an estimate of the effect on time to death, first major haemorrhage, and thromboembolism.

    Methods

    We searched Ovid versions of Embase (1980-2009) and Medline (1966-2009), limiting searches to randomised trials with a maximally sensitive strategy. We approached all authors of included trials and requested individual patient data: primary outcomes were time to death, first major haemorrhage, and first thromboembolic event. We did prespecified subgroup analyses according to age, type of control-group care (anticoagulation-clinic care vs primary care), self-testing alone versus self-management, and sex. We analysed patients with mechanical heart valves or atrial fibrillation separately. We used a random-effect model method to calculate pooled hazard ratios and did tests for interaction and heterogeneity, and calculated a time-specific number needed to treat.

    Findings

    Of 1357 abstracts, we included 11 trials with data for 6417 participants and 12,800 person-years of follow-up. We reported a significant reduction in thromboembolic events in the self-monitoring group (hazard ratio 0·51; 95% CI 0·31-0·85) but not for major haemorrhagic events (0·88, 0·74-1·06) or death (0·82, 0·62-1·09). Participants younger than 55 years showed a striking reduction in thrombotic events (hazard ratio 0·33, 95% CI 0·17-0·66), as did participants with mechanical heart valve (0·52, 0·35-0·77). Analysis of major outcomes in the very elderly (age ≥85 years, n=99) showed no significant adverse effects of the intervention for all outcomes.

    Interpretation

    Our analysis showed that self-monitoring and self-management of oral coagulation is a safe option for suitable patients of all ages. Patients should also be offered the option to self-manage their disease with suitable health-care support as back-up.

    Funding

    UK National Institute for Health Research (NIHR) Technology Assessment Programme, UK NIHR National School for Primary Care Research.
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    Three-factor prothrombin complex concentrates for refractory bleeding after cardiovascular surgery within an algorithmic approach to haemostasis.
    (Vox sanguinis, 2019-05) Hashmi, Nazish K; Ghadimi, Kamrouz; Srinivasan, Amudan J; Li, Yi-Ju; Raiff, Robert D; Gaca, Jeffrey G; Root, Adam G; Barac, Yaron D; Ortel, Thomas L; Levy, Jerrold H; Welsby, Ian J
    BACKGROUND/OBJECTIVES:Prothrombin complex concentrates (PCC) are increasingly administered off-label in the United States to treat bleeding in cardiovascular surgical patients and carry the potential risk for acquired thromboembolic side-effects after surgery. Therefore, we hypothesized that the use of low-dose 3-factor (3F) PCC (20-30 IU/kg), as part of a transfusion algorithm, reduces bleeding without increasing postoperative thrombotic/thromboembolic complications. MATERIALS/METHODS:After IRB approval, we retrospectively analysed 114 consecutive, complex cardiovascular surgical patients (age > 18 years), between February 2014 and June 2015, that received low-dose 3F-PCC (Profilnine® ), of which seven patients met established exclusion criteria. PCC was dosed according to an institutional perioperative algorithm. Allogeneic transfusions were recorded before and after PCC administration (n = 107). The incidence of postoperative thromboembolic events was determined within 30 days of surgery, and Factor II levels were measured in a subset of patients (n = 20) as a quality control measure to avoid excessive PCC dosing. RESULTS:Total allogeneic blood product transfusion reached a mean of 12·4 ± 9·9 units before PCC and 5·0 ± 6·3 units after PCC administration (P < 0·001). The mean PCC dose was 15·8 ± 7·1 IU/kg. Four patients (3·8%) each experienced an ischaemic stroke on postoperative day 1, 2, 4 and 27. Seven patients (6·5%) had acquired venous thromboembolic disease within 10 days of surgery. Median factor II level after transfusion algorithm adherence and PCC administration was 87%. CONCLUSIONS:3F-PCC use for refractory bleeding after cardiovascular surgery resulted in reduced transfusion of allogeneic blood and blood products. Adherence to this algorithmic approach was associated with an acceptable incidence of postoperative thrombotic/thromboembolic complications.
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    Thromboembolism and bleeding in bladder cancer.
    (Oncology (Williston Park), 2014-10) Fantony, Joseph J; Inman, Brant A
    Bladder cancer is a unique disease process in that clinically significant hemorrhage can occur simultaneously with equally significant aberrant clotting. With hematuria the key presenting symptom of bladder cancer, hemorrhage is generally thought to be a component of the natural history of the disease, and to commonly occur during its treatment. However, as those who regularly treat bladder cancer know, the need to address a predisposition to clotting is also very much part of the treatment paradigm. Physicians must be cognizant of the biochemical changes that confer a propensity for both significant bleeding and clotting occurring simultaneously in their patients. Both of these entities remain important issues, and further study is needed to find ways to mitigate and balance the associated risks. Here, we performed a review of the literature, focusing on the concomitant issues of bleeding and venous thromboembolism in both the pre- and post-operative periods in patients with bladder cancer. We formulated a general management approach with respect to these two processes, and we provide direction for further investigation.