scholarly journals Differences in Clinical Presentation, Rate of Pulmonary Embolism, and Risk Factors Among Patients With Deep Vein Thrombosis in Unusual Sites

2019 ◽  
Vol 25 ◽  
pp. 107602961987255 ◽  
Author(s):  
Angelo Porfidia ◽  
Enrica Porceddu ◽  
Daniela Feliciani ◽  
Marzia Giordano ◽  
Fabiana Agostini ◽  
...  
Keyword(s):  
Risk Factors ◽  
Pulmonary Embolism ◽  
Deep Vein Thrombosis ◽  
University Hospital ◽  
Cerebral Vein ◽  
Jugular Vein Thrombosis ◽  
Unusual Site ◽  
Vein Thrombosis ◽  
Significant Difference ◽  
Deep Vein

Unusual site deep vein thrombosis (USDVT) is an uncommon form of venous thromboembolism with heterogeneous signs and symptoms, unknown rate of pulmonary embolism (PE), and poorly defined risk factors. We conducted a retrospective analysis of 107 consecutive cases of USDVTs, discharged from our University Hospital over a period of 2 years. Patients were classified based on the site of thrombosis and distinguished between patients with cerebral vein thrombosis, jugular vein thrombosis, thrombosis of the deep veins of the upper extremities, and abdominal vein thrombosis. We found statistically significant differences between groups in terms of age ( P < .0001) and gender distribution ( P < .05). We also found that the rate of symptomatic patients was significantly different between groups ( P < .0001). Another interesting finding was the significant difference between groups in terms of rate of PE ( P < .01). Finally, we found statistically significant differences between groups in terms of risk factors for thrombosis, in particular cancer ( P < .01). Unprovoked cases were differently distributed among groups ( P < .0001). This study highlights differences between patients with USDVT, which depend on the site of thrombosis, and provides data which might be useful in clinical practice.

P6461The long-term clinical comparisons of symptomatic patients of pulmonary embolism with and those without deep vein thrombosis: from the COMMAND VTE Registry

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
K Murata ◽  
Y Yamashita ◽  
T Morimoto ◽  
H Amano ◽  
T Takase ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Deep Vein Thrombosis ◽  
Acute Phase ◽  
Clinical Presentation ◽  
Vein Thrombosis ◽  
Significant Difference ◽  
Severe Clinical Presentation ◽  
Recurrent Vte ◽  
Deep Vein

Abstract Background Venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT), has significant morbidity and mortality. Acute PE, in particular, is fatal if we miss it, and symptomatic patients of PE sometimes have concomitant DVT. Purpose This study compared the risk of mortality in symptomatic patients of PE with and those without DVT in the long term. Methods The COMMAND VTE Registry is a multicenter registry enrolling consecutive 3027 patients with acute symptomatic VTE objectively confirmed by imaging examination or by autopsy among 29 centers in Japan between January 2010 and August 2014. Patients with both PE and DVT (N=1334) were regarded as PE patients, and the current study population consisted of 1715 PE patients and 1312 DVT patients. Results There were 1203 symptomatic patients of PE, including 381 without and 822 with DVT. In our cohort, the mean age was 67.9±14.9 years, 63% was female, 44% had hypertension, 12% diabetes mellitus, 5% history of VTE. There were 20% of active cancer. Baseline characteristics were well matched except for dyslipidemia (18% vs. 23%, p=0.021) and atrial fibrillation (8% vs. 5%, p=0.045). Patients without DVT had a more severe clinical presentation compared to those with DVT, including hypoxemia, shock and arrest. Moreover, Initial parenteral anticoagulation therapy in the acute phase was administered less frequently in patients without DVT (89% vs. 96%, P=0.0001). Two groups received thrombolysis (20% vs. 26%, P=0.18) and mechanical supports (Ventilator 14% vs. 5%, p<0.001, PCPS 5% vs. 3%, p<0.001, respectively). During follow-up, 93 (8%) patients experienced recurrent VTE events and 98 (8%) major bleeding events, and 323 (27%) patients died. The most frequent cause of death was cancer (11%). There were a significant differences in the cumulative incidences of all-cause death between the groups (32% vs. 24%, P=0.006), whereas there was significant difference in VTE-related death (13% vs. 4%, p<0.001). Estimated freedom rates from death for patients of PE without and those with DVT were as follows: 88% vs 99% at 10-day, 86% vs 95% at 1-month, 75% vs 83% at 1-year, and 64% vs 71% at 5-year, respectively. Landmark analysis Conclusions In symptomatic patients of PE, there was a difference in mortality between groups, but no difference in recurrent VTE. Patients without DVT had a more severe clinical presentation compared to those with DVT, and many VTE-related deaths in the acute phase. The one-month mortality rate differed statistically between groups, but there was no significant difference in long-term survival beyond one month. Most of deaths were due to underlying diseases, mainly cancer, and less commonly due to VTE in the long term. Acknowledgement/Funding Research Institute for Production Development, Mitsubishi Tanabe Pharma Corporation

scholarly journals Venous Thromboembolism in Denmark: Seasonality in Occurrence and Mortality

TH Open ◽  
2019 ◽  
Vol 03 (02) ◽  
pp. e171-e179 ◽  
Author(s):  
Nils Skajaa ◽  
Erzsébet Horváth-Puhó ◽  
Kasper Adelborg ◽  
Paolo Prandoni ◽  
Kenneth J. Rothman ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Deep Vein Thrombosis ◽  
Venous Thromboembolism ◽  
Seasonal Pattern ◽  
Cerebral Vein ◽  
Cerebral Vein Thrombosis ◽  
Splanchnic Vein Thrombosis ◽  
Vein Thrombosis ◽  
Winter Peak ◽  
Deep Vein

Background Many cardiovascular conditions exhibit seasonality in occurrence and mortality, but little is known about the seasonality of venous thromboembolism. Methods Using Danish registries, we identified all patients with deep vein thrombosis, pulmonary embolism, splanchnic vein thrombosis, cerebral vein thrombosis, and retinal vein thrombosis during 1977–2016. We tallied monthly deaths occurring within 90 days of the venous thromboembolism diagnosis. We estimated peak-to-trough ratios and timing of the peak of both diagnoses and deaths summed over all years of the study period. The departure from 1.0 of the peak-to-trough ratio measures the intensity of any seasonal pattern. Results We estimated a peak-to-trough ratio of 1.09 (95% confidence interval: 1.07–1.11) for deep vein thrombosis and 1.22 (1.19–1.24) for pulmonary embolism occurrence. The peak-to-trough ratios for splanchnic vein thrombosis, cerebral vein thrombosis, and retinal vein thrombosis occurrence were 1.10 (1.01–1.20), 1.19 (1.00–1.40), and 1.12 (1.07–1.17), respectively. The occurrence of all conditions peaked during winter or fall. In time trend analyses, the peak-to-trough ratio increased considerably for splanchnic vein thrombosis, cerebral vein thrombosis, and retinal vein thrombosis occurrence. In associated mortality, the peak-to-trough ratio for deep vein thrombosis was larger (1.15, 1.07–1.23) than that for pulmonary embolism (1.04, 1.01–1.08). Discussion Excess winter risks were modest, but more marked for pulmonary embolism occurrence than for deep vein thrombosis occurrence. The seasonal pattern intensified throughout the study period for splanchnic vein thrombosis, cerebral vein thrombosis, and retinal vein thrombosis. The winter peak in mortality following pulmonary embolism was smaller than that for deep vein thrombosis.

Deep Vein Thrombosis and Pulmonary Embolism: Awareness and Knowledge Gaps In the General Public

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4731-4731
Author(s):  
Jack E Ansell ◽  
Gregory A Maynard ◽  
Richard J Friedman ◽  
Elizabeth A Varga ◽  
Lisa L Fullam ◽  
...  
Keyword(s):  
Risk Factors ◽  
Pulmonary Embolism ◽  
Deep Vein Thrombosis ◽  
Medical Condition ◽  
Blood Clot ◽  
Public Awareness ◽  
The United States ◽  
Vein Thrombosis ◽  
Blood Clots ◽  
Deep Vein

Abstract Abstract 4731 Deep vein thrombosis (DVT) and pulmonary embolism (PE) impose a major public health burden in the United States, affecting an estimated 350,000 to 600,000 individuals and accounting for ~100,000 deaths in the United States each year, according to The Surgeon General's Call to Action (CTA) To Prevent Deep Vein Thrombosis and Pulmonary Embolism (2008). In response to this CTA, the National Blood Clot Alliance (NBCA), a national, community-based, non-profit organization dedicated to the prevention, diagnosis, and treatment of thrombosis and thrombophilia, conducted a survey to benchmark DVT/PE awareness among the general public. Little information about the public's knowledge of venous thromboembolism (VTE) is found in the literature, making this one of the most comprehensive, relatively large surveys of its kind. This DVT/PE awareness survey was conducted in November 2009, among a representative cross-section of 500 adults, >20 years, participating in online research panels. Among all respondents surveyed, just 21% said that they had heard of a medical condition called DVT (unaided), and, among this group (n=104), 86% correctly identified it as “deep vein thrombosis” on an aided checklist. Among those respondents who had not heard of a DVT or who had made an incorrect checklist selection (n=411), when DVT was identified for them as “deep vein thrombosis,” 29% then said they knew what it was. Among all respondents, just 16% said that they had heard of a medical condition called PE, and, among this group (n=80), 83% identified it correctly as “pulmonary embolism” on an aided checklist. Awareness of specific DVT risk factors and DVT/PE signs/symptoms was low. Results of this survey show that the medical lexicon poses substantial barriers: only 23% of all respondents reported to know what thrombophilia means and just 9% had heard of VTE. Conversely, 8 in 10 of all respondents said that they do know what a blood clot is, and virtually all respondents (98%) said that they believe blood clots can be life-threatening. The leading factors respondents said they believe are risks for causing blood clots included: family history of blood clots (73%), major trauma (71%), major surgery (69%), and being bedridden (68%), while <60% of respondents mentioned other risk factors, such as cancer, chemotherapy, pregnancy, hormone therapy and birth control pills, or age. The public health impact of DVT/PE is significant, while DVT/PE public awareness, including awareness of important DVT/PE risk factors and signs/symptoms, is disproportionately low. These survey data support recommendations in the Surgeon General's CTA, underscoring the urgent need for education, especially the use of simplified terms, to close gaps in DVT/PE public awareness/knowledge, and can help guide educational initiatives relative to DVT/PE that may contribute to decreased morbidity and mortality. Disclosures: Ansell: Bayer, Inc: Consultancy; Bristol Myers Squibb: Consultancy, Data Safety Monitoring Boards; Daiichi Sankyo: Consultancy; Boehringer Ingleheim: Consultancy; Ortho McNeil: Consultancy; Sanofi Aventis: Speakers Bureau. Brownstein:Ortho-McNeil, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc.: Data reported from project supported by Ortho-McNeil, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc.

scholarly journals Risk Factors for Deep Vein Thrombosis and Pulmonary Embolism

2000 ◽  
Vol 160 (6) ◽  
pp. 809 ◽  
Author(s):  
John A. Heit ◽  
Marc D. Silverstein ◽  
David N. Mohr ◽  
Tanya M. Petterson ◽  
W. Michael O'Fallon ◽  
...  
Keyword(s):  
Risk Factors ◽  
Pulmonary Embolism ◽  
Deep Vein Thrombosis ◽  
Vein Thrombosis ◽  
Deep Vein

scholarly journals Deep Vein Thrombosis, Demographic Characteristics and Risk Factors in Iran

2013 ◽  
Vol 2 (4) ◽  
pp. 135-140
Author(s):  
Shokoufeh Hajsadeghi ◽  
Scott Reza Jafarian Kerman ◽  
Rashin Joodat ◽  
Maral Hejratie ◽  
Helen Vaferi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Health Care ◽  
Deep Vein Thrombosis ◽  
Health Care Systems ◽  
Care Providers ◽  
Female Ratio ◽  
Vein Thrombosis ◽  
Significant Difference ◽  
Care Systems ◽  
Deep Vein

Background: Deep vein thrombosis (DVT) can be an ethnicity related disease and an important health issue for health-care systems. Thus, domestic recognition of risk factors and disease characteristics seem to be inevitable. This study was designed to evaluate the epidemiology, basic characteristics, and risk factors in patients with DVT.Materials and Methods: In this descriptive cross-sectional study, all patients with primary or final diagnosis of DVT, confirmed by Doppler ultrasound in a 5-year period were included. Demographic data and prognosis were extracted from medical files. To evaluate the outcome of the patients after discharge, a phone-call follow-up was performed for all available patients.Results: Three-hundred seventy-one DVT patients were included with 232/139 male to female ratio. The mean age was 55.72±20.01 years with significant difference between genders (p=0.006). Mean weight was 88.97±10.2 kg with no significant difference between genders (p=0.74). The most common affected veins were common femoral vein (257 cases, 69.2%), followed by Popliteal, iliac, axillary, and subclavian veins. No season preference was seen in DVT occurrence. One-year survival of the patients after discharge was 92.6% and two-year survival was 87.7%.Conclusion: By knowing local information about this disease, health-care providers can give accurate warnings and suggestions to prevent the probable thrombosis chances. As Iran lacked information about DVT characteristics, this study can be an epidemiologic guide for health-care systems and an opening path for future studies.

scholarly journals Incidence, risk factors and clinical course of pyogenic spondylodiscitis patients with pulmonary embolism

2021 ◽  
Author(s):  
Daniel Dubinski ◽  
Sae-Yeon Won ◽  
Fee Keil ◽  
Bedjan Behmanesh ◽  
Max Dosch ◽  
...  
Keyword(s):  
Risk Factors ◽  
Pulmonary Embolism ◽  
Deep Vein Thrombosis ◽  
Bed Rest ◽  
Blood Type ◽  
Vein Thrombosis ◽  
Pyogenic Spondylodiscitis ◽  
Increased Risk ◽  
Retrospective Clinical Study ◽  
Deep Vein

Abstract Purpose In patients with pyogenic spondylodiscitis, surgery is considered the treatment of choice to conduct proper debridement, stabilise the spine and avoid extended bed rest, which in turn is a risk factor for complications such as deep vein thrombosis and pulmonary embolism. Methods We conducted a retrospective clinical study with analysis of a group of 99 patients who had undergone treatment for pyogenic discitis at our institution between June 2012 and August 2017. Included parameters were age, sex, disease pattern, the presence of deep vein thrombosis, resuscitation, in-hospital mortality, present anticoagulation, preexisting comorbidities, tobacco abuse, body mass index, microbiological germ detection and laboratory results. Results Among the analysed cohort, 12% of the treated patients for pyogenic spondylodiscitis suffered from a radiologically confirmed pulmonary embolism. Coronary heart disease (p < 0.01), female sex (p < 0.01), anticoagulation at admission (p < 0.01) and non-O blood type (p < 0.001) were associated with development of pulmonary embolism. Pulmonary embolism was significantly associated with resuscitation (p < 0.005) and deep vein thrombosis (p < 0.001). Neurosurgery was not associated with increased risk for pulmonary embolism compared to conservative-treated patients (p > 0.05). Conclusion Surgery for pyogenic spondylodiscitis was not associated with an elevated risk of pulmonary embolism in our analysis. However, we describe several risk factors for pulmonary embolism in this vulnerable cohort. Prospective studies are necessary to improve prevention and postoperative management in patients with pyogenic spondylodiscitis.

Abstract TMP74: Stroke And Pulmonary Embolism, Clinical Features, Risk Factors And Outcome

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
jitphapa pongmoragot ◽  
Alejandro Rabinstein ◽  
Yongchai Nilanont ◽  
Daniel Selchen ◽  
Rick Swartz ◽  
...  
Keyword(s):  
Risk Factors ◽  
Pulmonary Embolism ◽  
Deep Vein Thrombosis ◽  
Length Of Stay ◽  
Predisposing Factors ◽  
P Value ◽  
Stroke Patients ◽  
Vein Thrombosis ◽  
History Of ◽  
Deep Vein

Introduction: Pulmonary embolism (PE) is an uncommon medical complication after stroke. Predisposing factors include deep vein thrombosis (DVT) in patients with hemiplegia or an underlying hypercoagulable state. However, little information is known regarding PE in stroke patients. Objective: We evaluated clinical characteristics, predisposing factors, and outcomes in stroke patients who developed PE. Methods: We included patients with an acute ischemic stroke (AIS) admitted to the participating institutions in the Registry of the Canadian Stroke Network between 2003 to 2008. Pulmonary embolism was diagnosed by nuclear imaging within 30 days of the stroke case index. Demographic data and clinical variables were collected. Logistic regression and survival analyses were completed to determine the association of risk factors with the outcomes of interest. Outcome Measures: primary outcome was death or disability at discharge defined as the modified Rankin scale >3. Secondary outcomes include admission to the Intensive Care Unit, disposition, and length of hospital stay, death at 3 months and at 1 year. Results: Among 11,287 patients with AIS, PE was found in 89 (0.78%) of patients. The development of PE was associated with higher risk of death in 30 days (25.8%vs 13.6%;p <0.001) and 1 year, (47.2% vs 24.6%;p <0.001). Disability was also more common in stroke patients with PE (85.4% vs 63.6% without PE; p <0.001). Mean length of stay was longer in stroke patients with PE (36 vs 16 days; p<0.001). Past medical history of cancer or deep vein thrombosis, history of cardiac arrest or deep vein thrombosis during admission were associated with PE. After adjustment, PE was associated with lower survival at 30 days (p value = 0.0012) and 1 year (p value < 0.0001) (Figures 1 & 2 represent survival function). Conclusions: In this large study, PE occurs in approximately 1% of AIS patients. PE was associated with higher disability, longer length of stay and lower short and long-term survival.

Deep Vein Thrombosis and Pulmonary Embolism: Awareness and Knowledge Gaps In the General Public and at-Risk Oncology Patients

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4740-4740
Author(s):  
Frederick R Rickles ◽  
Gregory A Maynard ◽  
Richard J Friedman ◽  
Alan P Brownstein ◽  
Elizabeth A Varga ◽  
...  
Keyword(s):  
Risk Factors ◽  
At Risk ◽  
Pulmonary Embolism ◽  
Deep Vein Thrombosis ◽  
General Public ◽  
Risk Patient ◽  
Oncology Patients ◽  
Vein Thrombosis ◽  
Increased Risk ◽  
Deep Vein

Abstract Abstract 4740 Deep vein thrombosis (DVT) and pulmonary embolism (PE) affect up to 600,000 individuals and account for ~100,000 deaths in the United States each year, according to The Surgeon General's Call to Action (CTA) To Prevent Deep Vein Thrombosis and Pulmonary Embolism (2008). Oncology patients, particularly those who are hospitalized or undergo chemotherapy, are at increased risk for DVT/PE. Mortality is greater among patients with cancer and venous thromboembolism (VTE) than among those with cancer alone. In response to the Surgeon General's CTA, the National Blood Clot Alliance (NBCA), a national, community-based, non-profit organization dedicated to the prevention, diagnosis, and treatment of thrombosis and thrombophilia, conducted a survey to benchmark DVT/PE awareness among the general public and several at-risk patient groups, including oncology patients. The literature contains little information about at-risk patient knowledge, and almost no information about general public knowledge of VTE, making this the first, large survey of both public and at-risk patient awareness of DVT/PE. The survey was conducted in November 2009, among a representative cross-section of 500 adults, >20 years, participating in online research panels. For comparison, the identical survey was conducted among a sample of 500 adults, >20 years, screened from an online research panel, who had received a cancer diagnosis or experienced recurrence of cancer within the past 6 months, or who were on active cancer treatment. Evaluations comparing survey responses provided by oncology patients who, in connection with their treatment, did require a hospital stay versus those who did not require a hospital stay showed no statistically significant differences in DVT/PE awareness between the two subgroups. Among all oncology patients surveyed, 24% said that they had heard of a medical condition called DVT, compared to 21% of the general public. Among all respondents who said that they knew what a DVT was (unaided) or who were able to correctly identify DVT on an aided checklist, 61% of oncology and 53% of national respondents said they could name DVT risk factors. The most frequently mentioned DVT risk factor was “sitting for a long time” among both the oncology (45%) and national (28%) samples. Among oncology patients who could name DVT risk factors (n=155), 8% named surgery, 1% named cancer treatment. Among national respondents who could name DVT risk factors (n=109), significantly more (79%) said they could name DVT signs/symptoms compared to oncology respondents (63%) who said the same. While not statistically significant, the national sample did show greater recognition of certain DVT signs/symptoms: skin redness/discoloration, 41% national, 21% oncology; leg swelling, 50% national, 31% oncology; and, leg pain, 37% national, 27% oncology. PE awareness was low among both groups, with 15% of all oncology and 16% of all national respondents saying that they had heard of PE. Of those who what said they knew what a PE was (unaided) or identified it correctly from an aided checklist, about one-third of both groups said they could name PE signs/symptoms, with “breathing difficulties” cited most frequently by oncology (69%) and national (73%) respondents. Significantly fewer oncology patients (28%) mentioned chest pain/tightness as a PE sign/symptom, compared to the national sample (57%). About 8 in 10 oncology and national respondents said that they did know what a blood clot is, and virtually all respondents (98%) recognized blood clots as life threatening. DVT/PE awareness/knowledge was low. Despite increased risk, oncology patients demonstrated no greater awareness of DVT/PE than the general public. DVT/PE education, utilizing interventions identified in the Surgeon General's DVT/PE CTA, should target the general public, with special emphasis on at-risk oncology patients to fill gaps relative to increased DVT/PE risks and signs/symptoms. Terms should be further simplified for future public awareness and patient education initiatives. Disclosures: Brownstein: Ortho-McNeil, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc.: Data reported from project supported by Ortho-McNeil, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc. Ansell:Bayer, Inc: Consultancy; Bristol Myers Squibb: Consultancy, Data Safety Monitoring Boards; Daiichi Sankyo: Consultancy; Boehringer Ingleheim: Consultancy; Ortho McNeil: Consultancy; Sanofi Aventis: Speakers Bureau.

scholarly journals Relative Impact of Risk Factors for Deep Vein Thrombosis and Pulmonary Embolism

2002 ◽  
Vol 162 (11) ◽  
pp. 1245 ◽  
Author(s):  
John A. Heit ◽  
W. Michael O'Fallon ◽  
Tanya M. Petterson ◽  
Christine M. Lohse ◽  
Marc D. Silverstein ◽  
...  
Keyword(s):  
Risk Factors ◽  
Pulmonary Embolism ◽  
Deep Vein Thrombosis ◽  
Relative Impact ◽  
Vein Thrombosis ◽  
Deep Vein

scholarly journals Which patients are at high risk of recurrent venous thromboembolism (deep vein thrombosis and pulmonary embolism)?

2020 ◽  
Vol 4 (21) ◽  
pp. 5595-5606
Author(s):  
Fionnuala Ní Áinle ◽  
Barry Kevane
Keyword(s):  
Risk Factors ◽  
Pulmonary Embolism ◽  
Deep Vein Thrombosis ◽  
Venous Thromboembolism ◽  
Recurrence Risk ◽  
Vein Thrombosis ◽  
Recurrent Venous Thromboembolism ◽  
Clinical Conditions ◽  
Deep Vein

Abstract Recurrent venous thromboembolism (VTE, or deep vein thrombosis and pulmonary embolism) is associated with mortality and long-term morbidity. The circumstances in which an index VTE event occurred are crucial when personalized VTE recurrence risk is assessed. Patients who experience a VTE event in the setting of a transient major risk factor (such as surgery associated with general anesthesia for &gt;30 minutes) are predicted to have a low VTE recurrence risk following discontinuation of anticoagulation, and limited-duration anticoagulation is generally recommended. In contrast, those patients whose VTE event occurred in the absence of risk factors or who have persistent risk factors have a higher VTE recurrence risk. Here, we review the literature surrounding VTE recurrence risk in a range of clinical conditions. We describe gender-specific risks, including VTE recurrence risk following hormone- and pregnancy-associated VTE events. Finally, we discuss how the competing impacts of VTE recurrence and bleeding have shaped international guideline recommendations.

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