Browsing by Subject "THROMBOSIS"

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  • Pettilä, Ville; Kyhälä, Lea; Kylänpää, Marja-Leena; Leppäniemi, Ari; Tallgren, Minna; Markkola, Antti Thor Olavi; Puolakkainen, Pauli; Repo, Heikki; Kemppainen, Esko (2010)
  • Jarvis, Kirsten Brunsvig; LeBlanc, Marissa; Tulstrup, Morten; Nielsen, Rikke Linnemann; Albertsen, Birgitte Klug; Gupta, Ramneek; Huttunen, Pasi; Jonsson, Olafur Gisli; Rank, Cecilie Utke; Ranta, Susanna; Ruud, Ellen; Saks, Kadri; Trakymiene, Sonata Saulyte; Tuckuviene, Ruta; Schmiegelow, Kjeld (2019)
    Introduction: Thromboembolism is a serious toxicity of acute lymphoblastic leukemia treatment, and contributes to substantial morbidity and mortality. Several single nucleotide polymorphisms have been associated with thromboembolism in the general population; however, their impact in patients with acute lymphoblastic leukemia, particularly in children, remains uncertain. Materials and methods: We collected constitutional DNA and prospectively registered thromboembolic events in 1252 patients, 1-45 years, with acute lymphoblastic leukemia included in the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol in the Nordic and Baltic countries (7/2008-7/2016). Based on previously published data and a priori power calculations, we selected four single nucleotide polymorphisms: F5 rs6025, F11 rs2036914, FGG rs2066865, and ABO rs8176719. Results: The 2.5 year cumulative incidence of thromboembolism was 7.1% (95% confidence interval (CI) 5.6-8.5). F11 rs2036914 was associated with thromboembolism (hazard ratio (HR) 1.52, 95%CI 1.11-2.07) and there was a borderline significant association for FGG rs2066865 (HR 1.37, 95%CI 0.99-1.91), but no association for ABO rs8176719 or F5 rs6025 in multiple cox regression. A genetic risk score based on F11 rs2036914 and FGG rs2066865 was associated with thromboembolism (HR 1.45 per risk allele, 95%CI 1.15-1.81), the association was strongest in adolescents 10.0-17.9 years (HR 1.64). Conclusion: If validated, a F11 rs2036914/FGG rs2066865 risk prediction model should be tested as a stratification tool for prevention of thromboembolism in patients with acute lymphoblastic leukemia.
  • Tikkinen, Kari A. O.; Craigie, Samantha; Schünemann, Holger J.; Guyatt, Gordon H. (2018)
    Objectives: The Grading of Recommendations Assessment, Development and Evaluation approach to rating certainty of evidence includes five domains of reasons for rating down certainty. Only one of these, precision, is easily amenable through the confidence interval to quantitation. The other four (risk of bias, inconsistency, indirectness, and publication bias) are not. Nevertheless, conceptually, one could consider a quantified "certainty range" within which the true effect lies. The certainty range would be at least as wide as the confidence interval and would expand with each additional reason for uncertainty. Study Design and Setting: We have applied this concept to rating the certainty of evidence in the baseline risk of venous thromboembolism (VTE) and bleeding in patients undergoing urological surgery. We considered rating up moderate or low quality evidence when the net benefit of VTE prophylaxis was unequivocally positive, that is, when the smallest plausible value of VTE reduction was greater than the largest plausible value of increased bleeding. To establish whether the net benefit was unequivocally positive, we expanded the range of plausible values by 20% for each of the four nonquantitative domains in which there were serious limitations. Results: We present how we applied these methods to examples of open radical cystectomy and laparoscopic partial nephrectomy. In high-VTE risk laparoscopic partial nephrectomy patients and high-and medium-VTE risk open radical cystectomy patients, results proved robust to expanded certainty intervals, justifying rating up quality of evidence. In low -risk patients, the results were not robust, and rating up was therefore not appropriate. Conclusion: This work represents the first empirical application in a decision -making context of the previously suggested concept of certainty ranges and should stimulate further exploration of the associated theoretical and practical issues. (C) 2018 Elsevier Inc. All rights reserved.
  • Lemma, Aurora N.; Tolonen, Matti; Vikatmaa, Pirkka; Mentula, Panu; Vikatmaa, Leena; Kantonen, Ilkka; Leppäniemi, Ari; Sallinen, Ville (2019)
    Objectives: Despite modern advances in diagnosis and treatment, acute arterial mesenteric ischaemia (AMI) remains a high mortality disease. One of the key modifiable factors in AMI is the first door to operation time, but the factors attributing to this parameter are largely unknown. The aim of this study was to evaluate the factors affecting delay, with special focus on the pathways to treatment. Methods: This was a single academic centre retrospective study. Patients undergoing intervention for AMI caused by thrombosis or embolism of the superior mesenteric artery between 2006 and 2015 were identified from electronic patient records. Patients not eligible for intervention or with chronic, subacute onset, colonic only, venous, or non-occlusive mesenteric ischaemia were excluded. Patients were divided into two groups according to the first speciality examining the patient (surgical emergency room [SER], surgeon examining the patient first or non-surgical emergency room [non-SER], internist examining the patient first). The primary endpoint was first door to operation time and secondary endpoints were length of stay and 90 day mortality. Results: Eighty-one patients with AMI were included. Fifty patients (62%) died during the first 30 days and 53 (65%) within 90 days. Presenting first in non-SER (vs. SER) was independently associated with a first door to operation time of over 12 h (OR 3.7 [95% CI 1.3-10.2], median time 15.2 h [IQR 10.9-21.2] vs. 10.1 h [IQR 6.9-18.5], respectively, p = .025). The length of stay was shorter (median 6.5 days [4.0-10.3] vs. 10.8 days [7.0-22.3], p = .045) and 90 day mortality was lower in the SER group (50.0% vs. 74.5%, p = .025). Conclusions: The first specialty that the patient encounters seems to be crucial for both delayed management and early survival of AMI. Developing fast/direct pathways to a unit with both gastrointestinal and vascular surgeons offers the possibility of improving the outcome of AMI.
  • HoT-PE Investigators; Barco, Stefano; Schmidtmann, Irene; Ageno, Walter; Harjola, Veli-Pekka; Lankeit, Mareike (2020)
    Aims To investigate the efficacy and safety of early transition from hospital to ambulatory treatment in low-risk acute PE, using the oral factor Xa inhibitor rivaroxaban. Methods and results We conducted a prospective multicentre single-arm investigator initiated and academically sponsored management trial in patients with acute low-risk PE (EudraCT Identifier 2013-001657-28). Eligibility criteria included absence of (i) haemodynamic instability, (ii) right ventricular dysfunction or intracardiac thrombi, and (iii) serious comorbidities. Up to two nights of hospital stay were permitted. Rivaroxaban was given at the approved dose for PE for >= 3 months. The primary outcome was symptomatic recurrent venous thromboembolism (VTE) or PE-related death within 3 months of enrolment. An interim analysis was planned after the first 525 patients, with prespecified early termination of the study if the null hypothesis could be rejected at the level of alpha = 0.004 ( Conclusion Early discharge and home treatment with rivaroxaban is effective and safe in carefully selected patients with acute low-risk PE. The results of the present trial support the selection of appropriate patients for ambulatory treatment of PE.
  • Laine, Outi; Joutsi-Korhonen, Lotta; Lassila, Riitta; Huhtala, Heini; Vaheri, Antti; Makela, Satu; Mustonen, Jukka (2016)
    We evaluated the mechanisms of thrombocytopenia and procoagulant changes in relation with clinical variables in a cohort of patients with acute hantavirus disease. Blood samples of 33 prospectively recruited, consecutive, hospitalized patients with acute Puumala virus-induced hemorrhagic fever with renal syndrome (HFRS) were collected acutely and at the recovery visit (control). Serum thrombopoietin (TPO) and activity of plasma microparticles (MPs) from various cell sources were measured with enzyme-linked immunosorbent assay-based methods. The results were related to data on platelet indices and functions, coagulation variables, and clinical disease. Serum TPO was nearly 4-fold higher acutely compared with the control (median 207pg/mL, range 56-1258pg/mL vs. median 58 pg/mL, range 11-241pg/mL, P Upregulated TPO together with high MPV and IPF% confirm active thrombopoiesis, but do not predict severity of HFRS. Simultaneously, elevated prothrombin fragments and D-dimer suggest increased consumption of platelets in patients with severe AKI. Activity of platelet-derived MPs in HFRS should be studied with flow cytometry in a larger cohort of patients.
  • Mattila, Nora; Seppänen, Hanna; Mustonen, Harri; Przybyla, Beata; Haglund, Caj; Lassila, Riitta (2018)
    Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer often diagnosed late. Earlier detection is urgently needed. Pancreatic ductal adenocarcinoma is known to associate with increased coagulation activity. We studied whether preoperative coagulation biomarkers are useful in distinguishing PDAC from a benign tumor, intraductal papillary mucinous neoplasm (IPMN) in this observational study. We analyzed standard clinical and coagulation variables in patients operated during 2010 and 2015 at Helsinki University Hospital. Pancreatic ductal adenocarcinoma with preoperative coagulation variables available and no neoadjuvant treatment or other active cancer was observed in 80 patients (stage I-III in 67 and IV in 13) and IPMN in 18 patients. Fibrinogen, factor VIII (FVIII), carbohydrate antigen (CA) 19-9, albumin, alkaline phosphatase, and conjugated bilirubin were higher in both stages I to III and IV PDAC compared to IPMN (P <.05). Factor VIII was highest in stage IV (P <.05). Combining these variables in a panel increased sensitivity and specificity for PDAC. In receiver operating characteristic analysis, the area under the curve (95% confidence interval) was 0.95 (0.90-1.00) for the panel, compared to 0.80 (0.71-0.88) for CA 19-9 alone (P <.01). In conclusion, PDAC was associated with increased fibrinogen and FVIII. Combining these coagulation biomarkers with CA 19-9, albumin, and alkaline phosphatase improves diagnostic accuracy.
  • Galambosi, Päivi; Hiilesmaa, Vilho; Ulander, Veli-Matti; Laitinen, Leena; Tiitinen, Aila; Kaaja, Risto (2016)
    Introduction: In contrast to unfractionated heparin (UFH), use of low-molecular weight heparin (LMWH) during pregnancy has not been reported to be associated with a significant decrease in bone mineral density (BMD). The aim of this study was to investigate whether long-term use of LMWH during pregnancy is associated with subsequent decrease in BMD or with increased number of osteoporotic fractures. Materials and methods: In this observational cohort study BMD was measured by dual energy X-ray absorptiometry (DEXA) 4-7 years after the last delivery in 152 women. Ninety-two women had prolonged LMWH-exposure during pregnancy - 75 as prophylaxis and 17 as treatment for venous thromboembolic event (VTE). Dalteparin and enoxaparin were the LMWH-preparations used. Sixty women without LMWH-exposure served as controls. A questionnaire about lifestyle factors and medical history was filled out by the subjects. Results: Lumbar spine BMD in the LMWH users was lower than that in the controls both in the prophylactic group (1.22 g/cm(2) vs. 1.27 g/cm(2); p=0.03), and in the treatment group (1.20 g/cm(2) vs. 1.27 g/cm(2); p= 0.07). BMD in femoral neck did not differ between the LMWH-users and controls. However, after adjusting for potential confounding factors, LMWH-exposure did not remain associated with decreased BMD in lumbar spine. Use of contraceptive pills was positively associated with BMD in lumbar spine. Incidence of osteopenia was 13% in the LMWH-group and 8% in the control-group, (p= 0.4). No osteoporosis or osteoporotic fractures were found. Conclusions: Prolonged use of LMWH during pregnancy was not associated with subsequent decrease in BMD, osteopenia, osteoporosis, or osteoporotic fractures. (C) 2016 Elsevier Ltd. All rights reserved.
  • Kinnunen, Pete T. T.; Murtola, Teemu J.; Talala, Kirsi; Taari, Kimmo; Tammela, Teuvo L. J.; Auvinen, Anssi (2017)
    Background: Venous thromboembolic events (VTE) are common in cancer patients and associated with higher mortality. In vivo thrombosis and anticoagulation might be involved in tumor growth and progression. We studied the association of warfarin and other anticoagulant use as antithrombotic medication and prostate cancer (PCa) death in men with the disease. Methods: The study included 6,537 men diagnosed with PCa during 1995-2009. Information on anticoagulant use was obtained from a national reimbursement registry. Cox regression with adjustment for age, PCa risk group, primary therapy and use of other medication was performed to compare risk of PCa death between warfarin users with 1) men using other types of anticoagulants and 2) non-users of anticoagulants. Medication use was analyzed as a time-dependent variable to minimize immortal time bias. Results: In total, 728 men died from PCa during a median follow-up of 9 years. Compared to anticoagulant nonusers, post-diagnostic use of warfarin was associated with an increased risk of PCa death (overall HR 1.47, 95% CI 1. 13-1.93). However, this was limited to low-dose, low-intensity use. Otherwise, the risk was similar to anticoagulant non-users. Additionally, we found no risk difference between warfarin and other types of anticoagulants. Pre-diagnostic use of warfarin was not associated with the risk of PCa death. Conclusions: We found no reduction in risk of PCa death associated with warfarin use. Conversely, the risk was increased in short-term use, which is probably explained by a higher risk of thrombotic events prompting warfarin use in patients with terminal PCa.
  • Putaala, Jukka; Nieminen, Tuomo (2018)
  • Gasecka, Aleksandra; Nieuwland, Rienk; Budnik, Monika; Dignat-George, Francoise; Eyileten, Ceren; Harrison, Paul; Lacroix, Romaric; Leroyer, Aurelie; Opolski, Grzegorz; Pluta, Kinga; van der Pol, Edwin; Postula, Marek; Siljander, Pia; Siller-Matula, Jolanta M.; Filipiak, Krzysztof J. (2020)
    Background Platelet P2Y12 antagonist ticagrelor reduces mortality after acute myocardial infarction (AMI) compared to clopidogrel, but the underlying mechanism is unknown. Because activated platelets, leukocytes, and endothelial cells release proinflammatory and prothrombotic extracellular vesicles (EVs), we hypothesized that the release of EVs is more efficiently inhibited by ticagrelor compared to clopidogrel. Objectives We compared EV concentrations and EV procoagulant activity in plasma of patients after AMI treated with ticagrelor or clopidogrel. Methods After percutaneous coronary intervention, 60 patients with first AMI were randomized to ticagrelor or clopidogrel. Flow cytometry was used to determine concentrations of EVs from activated platelets (CD61(+), CD62p(+)), fibrinogen(+), phosphatidylserine (PS+), leukocytes (CD45(+)), endothelial cells (CD31(+), 146(+)), and erythrocytes (CD235a(+)) in plasma at randomization, after 72 hours and 6 months of treatment. A fibrin generation test was used to determine EV procoagulant activity. Results Concentrations of platelet, fibrinogen(+), PS+, leukocyte, and erythrocyte EVs increased 6 months after AMI compared to the acute phase of AMI (P = .17). Conclusions Ticagrelor attenuates the increase of EV concentrations in plasma after acute myocardial infarction compared to clopidogrel. The ongoing release of EVs despite antiplatelet therapy might explain recurrent thrombotic events after AMI and worse clinical outcomes on clopidogrel compared to ticagrelor.
  • Karjalainen, Pasi P.; Niemela, Matti; Laine, Mika; Airaksinen, Juhani K. E.; Ylitalo, Antti; Nammas, Wail (2017)
    Stent underexpansion is associated with worse outcome after stent implantation. Whether post-dilation (PD) improves outcome in patients with acute coronary syndrome (ACS) remains unclear. We performed post hoc analysis of outcome in patients from the BASE ACS (A prospective randomized comparison of titanium-nitride-oxide-coated bioactive stents with everolimus-eluting stents in acute coronary syndrome) trial who underwent PD versus those who did not. The BASE ACS trial randomized 827 patients (1:1) with ACS to receive either titanium-nitride-oxide coated bioactive stents or everolimus-eluting stents. The primary end point was major adverse cardiac events (MACE): a composite of cardiac death, nonfatal myocardial infarction (MI), or ischemia-driven target lesion revascularization. Follow-up was planned at 12 months and yearly thereafter for up to 7 years. Of 827 patients enrolled in the BASE ACS trial, 357 (43.2%) underwent PD. Median follow-up duration was 5 years. Patients who, underwent PD had less frequent nonfatal MI events at long-term follow-up, compared with those who did not (4.5% vs 8.5%, respectively, p = 0.02). The rates of MACE (15.7% vs 15.1%, respectively, p = 0.81), and the other endpoints, were not significantly different (p >0.5 for all). The results were consistent in propensity score matched analysis (270 pairs). In patients treated with bioactive stents, those who underwent PD had a trend for a fewer nonfatal MI events (p = 0.076). Comparably, in patients treated with everofimus-eluting stents, MACE and all the individual end points were comparable (p >0.5 for all). In conclusion, patients treated with early percutaneous coronary intervention for ACS who underwent PD had less frequent nonfatal MI events at long-term follow-up, compared with those who did not; MACE rates were not significantly different. (C) 2016 Elsevier Inc. All rights reserved.
  • Ratasvuori, Maire; Lassila, Riitta; Laitinen, Minna (2016)
    Introduction and aim: Venous thromboembolism (VTE) is a severe complication associated both with major orthopaedic surgery and cancer. However, survival and postoperative complications of skeletal metastases despite their thrombogenic potential, have received little attention in both the clinical management and research setting. This single-centre observational cohort study aimed to evaluate the incidence and impact of VTE in association with cancer surgery targeted to the management of fractures secondary to skeletal metastases. Methods: Data were collected retrospectively from the medical database. We included consecutive 306 patients operated for 343 non-spinal skeletal metastases during a 15-year period (1999-2014). The incidence of VTE and its risk factors were assessed using binary logistic regression analysis. Kaplan-Meier and Cox regression analyses were used to evaluate variables affecting survival. Results: The rate of symptomatic VTE was 10% (30/306) during the 3-month postoperative period, while 79% received thromboprophylaxis. Fatal pulmonary embolism (PE) rate was high, 3.3% (10/306) after surgery. Intraoperative oxygen saturation drop, pulmonary metastases and intramedullary nailing were independent risk factors for VTE. Indicators of decreased survival were lung cancer, intramedullary nailing, multiple skeletal and pulmonary metastases, anaemia, leukocytosis, and PE. Conclusion: Relationship between fractures secondary to skeletal metastases and VTE needs further clinical attention. Whether the survival of patients with fractures secondary to skeletal metastases can be improved by targeted thromboprophylactic means should be studied further. (C) 2016 Elsevier Ltd. All rights reserved.
  • Bates, Shannon M.; Alonso-Coello, Pablo; Tikkinen, Kari A. O.; Ebrahim, Shanil; Lopes, Luciane Cruz; McDonald, Sarah D.; Zhou, Qi; Akl, Elie A.; Neumann, Ignacio; Jacobsen, Anne Flem; Zhang, Yuqing; Santamara, Amparo; Annichino-Bizzacchi, Joyce Maria; Sandset, Per Morten; Bitar, Wael; Eckman, Mark H.; Guyatt, Gordon H. (2016)
    Background: Pregnant women with prior venous thromboembolism (VTE) are at risk of recurrence. Prophylaxis with low molecular weight heparin (LWMH) reduces that risk but is inconvenient, costly, and may be associated with increased risks of obstetrical bleeding. The views of pregnant women, crucial when making prophylaxis recommendations, are currently unknown. Methods: Cross-sectional international multicenter study. We included women with a history of VTE who were either pregnant or planning pregnancy. We provided information regarding risk of VTE recurrence with and without LMWH and determined participant's willingness to receive LMWH prophylaxis through direct choice exercises, preference-elicitation (utilities) for health states (e.g. burden of LMWH prophylaxis), and a probability trade-off exercise. Results: Of 123 women, more women at high risk than those at low risk of recurrence (86.4% vs. 60.0%; p=0.003) chose to use LMWH. The median threshold reduction in VTE at which women were willing to accept use of LMWH, given a 16% risk of VTE without prophylaxis, was 3% (interquartile range: 1 to 6). Participants' evaluation of the relevant health states varied widely and was unrelated to their direct choices to use or not use LMWH. Conclusions: Although the majority of women with a previous VTE, pregnant or planning pregnancy choose to take LMWH during pregnancy, a minority -and in low risk women, a large minority-do not. Our results highlight the need for individualized shared decision-making (SDM) in the clinical encounter, and for guideline panels to make weak recommendations in favor of LMWH that make clear the need for SDM. (C) 2015 Elsevier Ltd. All rights reserved.