Increased Incidence of Major Bleeding in Children Receiving Unfractionated Heparin for Clinical Management: A Prospective Cohort Study.

Abstract BACKGROUND: Unfractionated heparin (UFH) is one of the most frequently prescribed drugs in paediatric tertiary care centres and is used in a diverse group of disorders including cardiopulmonary bypass, extra corporeal membrane oxygenation, dialyses and maintenance of both venous and arterial catheter patency. Dosing of UFH in children is extrapolated from adults and is assessed by either a chromogenic Anti-Xa assay or a clot-based activated partial thromboplastin time (aPTT). The overall objective of the study was to assess safety of current standard of practice in the use of therapeutic UFH in children. Objective #1: The primary objective was to determine the incidence of bleeding and the incidence of recurrent thrombosis in children receiving UFH. Objective #2: To assess the monitoring UFH by assessing the relationship of the aPTT and Anti-Xa heparin levels to heparin dose. STUDY DESIGN: A prospective cohort study in nonselected children in a intensive care setting. The primary outcomes were major bleeding events and recurrent thrombosis. The secondary outcomes were assessing the APTT and Anti-Xa levels. Inclusion Criteria: Patients 〉 36 weeks gestation and 〈18 years of age requiring therapeutic doses of UFH. Exclusion Criteria: patients who received UFH for less than 1 day. Major bleeding was defined aprior as any of the following: CNS bleeding, retroperitoneal bleeding, and/or bleeding that results in stopping UFH infusion. RESULTS: Patient Population 39 patients were enrolled, 22 (56%) male, 32 (82%) < 1 year of age and 90% of which where cardiac patients. Major Bleeding events: 11/39 patients had a major bleeding event 28.2% (95% CI 15.0–44.9%). No patient had recurrent thrombosis. Relationship of aPPT and Anti-Xa to heparin dose; A total of 188 paired aPTTs and anti-Xa levels were performed. There was little correlation between aPTT and anti-Xa levels (r2=0.205) and APTT and UFH dose (r2=0.054). There was no relationship between anti-Xa levels and UFH dose (r2=0.0089). (Figure 1 and 2) Figure Figure CONCLUSIONS:. There is an unacceptably high rate of bleeding in children receiving UFH for clinical care. There is little or no relationship of aPPT and Anti-Xa to heparin dose. Clinical trials are needed to assess the appropriate use of UFH therapy in children.

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The relationship of primary health care use with persistence of insomnia: a prospective cohort study

BMC Family Practice ◽

10.1186/1471-2296-13-8 ◽

2012 ◽

Vol 13 (1) ◽

Cited By ~ 6

Author(s):

Richard A Hayward ◽

Kelvin P Jordan ◽

Peter Croft

Keyword(s):

Health Care ◽

Cohort Study ◽

Primary Health Care ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Health Care Use ◽

Primary Health ◽

Relationship Of ◽

The Relationship

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Relationship of Cigarette Smoking and Alcohol Consumption to Incidence of Systemic Lupus Erythematosus in a Prospective Cohort Study of Black Women

Arthritis Care & Research ◽

10.1002/acr.23703 ◽

2019 ◽

Vol 71 (5) ◽

pp. 671-677 ◽

Cited By ~ 5

Author(s):

Yvette C. Cozier ◽

Medha Barbhaiya ◽

Nelsy Castro‐Webb ◽

Carolyn Conte ◽

Sara K. Tedeschi ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Cohort Study ◽

Black Women ◽

Alcohol Consumption ◽

Cigarette Smoking ◽

Prospective Cohort Study ◽

Lupus Erythematosus ◽

Prospective Cohort ◽

Systemic Lupus ◽

Relationship Of

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Smoking is Associated with Increased Risk of Major Bleeding: A Prospective Cohort Study

Thrombosis and Haemostasis ◽

10.1055/s-0038-1675798 ◽

2018 ◽

Vol 119 (01) ◽

pp. 039-047

Author(s):

Anne Langsted ◽

Børge Nordestgaard

Keyword(s):

Cohort Study ◽

Prospective Cohort Study ◽

Major Bleeding ◽

Prospective Cohort ◽

Hazard Ratio ◽

General Population Study ◽

Smoking Intensity ◽

Increased Risk ◽

Former Smokers ◽

Never Smokers

Background Tobacco smoking represents the most preventable cause of several fatal and disabling diseases worldwide. Several ingredients in tobacco have been suspected to cause changes in the arterial wall leading to instability of blood vessels. The association of smoking with major bleeding is largely unexplored. We tested the hypothesis that smoking and high tobacco consumption are associated with increased risk of bleeding. Materials and Methods This is a prospective cohort study with a mean follow-up of 5.9 years including 99,359 individuals from the Copenhagen General Population Study, with a questionnaire including self-reported smoking status and information on smoking intensity in cigarettes per day and pack-years. In this study, 17,555 were current smokers, 40,182 former smokers and 41,622 were never smokers. Results Multivariable adjusted hazard ratios for current smokers versus never smokers were 1.49 (95% confidence interval [CI]: 1.38–1.61) for any major bleeding, 1.71 (1.37–2.13) for intracranial bleeding, 1.35 (1.14–1.60) for airway bleeding, 2.20 (1.84–2.62) for gastrointestinal bleeding and 1.39 (1.26–1.55) for urinary bleeding. Increased smoking intensity was also associated with increased risk of any major bleeding, where > 40 pack-years in current and former smokers compared with never smokers had a multivariable adjusted hazard ratio of 1.59 (95% CI: 1.45–1.73) (p for trend across four groups: < 0.001). Also, current smokers smoking > 20 cigarettes per day compared with former and never smokers had a corresponding hazard ratio of 1.67 (1.51–1.85) (p for trend across four groups: < 0.001). Conclusion Current smokers have an increased risk of any major bleeding as well as of intracranial, airway, gastrointestinal and urinary bleeding. Also, increased smoking intensity was associated with increased risk of major bleeding.

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Major bleeding events after endoscopic sphincterotomy and endoscopic papillary balloon dilatation in cirrhotic patients: A nationwide population-based cohort study

Advances in Digestive Medicine ◽

10.1002/aid2.12026 ◽

2017 ◽

Vol 4 (1) ◽

pp. 26-31

Author(s):

Chi-Chih Wang ◽

Ming-Chang Tsai ◽

Ming-Hseng Tseng ◽

Tzu-Wei Yang ◽

Yao-Tung Wang ◽

...

Keyword(s):

Cohort Study ◽

Major Bleeding ◽

Endoscopic Sphincterotomy ◽

Balloon Dilatation ◽

Population Based ◽

Bleeding Events ◽

Cirrhotic Patients ◽

Major Bleeding Events ◽

Endoscopic Papillary Balloon Dilatation

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Combination Of 4T’s Score and Rapid Gel Centrifugation Assay Excludes HIT In a Prospective Cohort Study

Blood ◽

10.1182/blood.v122.21.3535.3535 ◽

2013 ◽

Vol 122 (21) ◽

pp. 3535-3535 ◽

Cited By ~ 1

Author(s):

Lori Ann Linkins ◽

Shannon M. Bates ◽

Agnes Y.Y. Lee ◽

Theodore E. Warkentin

Keyword(s):

Cohort Study ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Research Funding ◽

Diagnostic Testing ◽

Prediction Rule ◽

Turnover Time ◽

Serotonin Release ◽

Diagnostic Strategy ◽

Bleeding Events

Abstract The diagnosis of heparin-Induced thrombocytopenia (HIT) is based on the presence of a compatible clinical picture combined with laboratory evidence of heparin-dependent, platelet-activating IgG antibodies. The 4T's Score is a clinical prediction rule that determines the likelihood that a patient has HIT before laboratory testing is performed. A rapid assay (H/PF4-PaGIA, Diamed, Switzerland) uses gel centrifugation to measure binding of antibodies to antigen-coated polystyrene beads (15 min turnover time). The purpose of this study is to evaluate the clinical utility of a diagnostic strategy which combines the 4T's Score with a H/PF4-PaGIA result to guide management of patients with suspected HIT while awaiting results of the serotonin-release assay (SRA). Methods Prospective cohort study of 538 consecutive adult patients with suspected HIT at 4 Canadian hospitals. Physicians completed a standardized 4T's Score sheet and the H/PF4-PaGIA was performed using fresh plasma in a central lab by technologists blinded to the 4T's Score (frozen plasma was used for 85 patients due to disruptions in worldwide availability of the assay.) The SRA and an in-house IgG anti-PF4/H enzyme-immunoassay (EIA) were performed on all patients by blinded technologists. Serologically-confirmed HIT (“HIT positive”) was defined as >50% serotonin release (mean) at three reaction conditions (0.1 U/mL heparin; 0.3 U/mL heparin; enoxaparin, 0.1 U/ml), as well as inhibition (<20% release or >50% inhibition) at 100 U/mL heparin and in the presence of Fc receptor-blocking monoclonal antibody, and a positive EIA. Thrombotic events, major bleeding events, and mortality were captured at day 30. Recommendations for management of patients while awaiting the SRA: patients with a Low 4T's Score (irrespective of H/PF4-PaGIA result) and patients with an Intermediate 4T's Score and negative H/PF4-PaGIA were to receive low-dose danaparoid or fondaparinux. Therapeutic-dose non-heparin anticoagulation was recommended for all patients with an Intermediate 4T's Score and positive H/PF4-PaGIA and for all patients with a High 4T's Score irrespective of H/PF4-PaGIA result. The primary outcome measure was the frequency of management failures defined as a patient with serologically-confirmed HIT who had one of the following combinations of diagnostic testing (a) Low 4T's Score and negative H/PF4-PaGIA; (b) Low 4T's Score and positive H/PF4-PaGIA or (c) Intermediate 4T's Score and negative H/PF4-PaGIA. Results 527 patients with mean age 66.5 yr (sd 15.4) were analyzed; 11 patients with missing diagnostic testing results were excluded. Clinical outcomes of the management of patients according to the diagnostic strategy will be reported separately. Results of diagnostic accuracy of the 4T's Score and H/PF4-PaGIA compared to the SRA are provided below. The prevalence of serologically-confirmed HIT in the study population was 6.5%. Two patients with indeterminate SRAs but IgG>1.0 were reported as HIT Positive. A negative H/PF4-PaGIA result reduced the probability of HIT based on the 4T's Score from 2.5% to 0.7% (95% CI: 0.1-2.6%) in the Low group, from 6.1% to 0% (95% CI: 0-2.7%) in the Intermediate group and from 35.7% to 0% (95% CI: 0-14.3%) in the High group. A positive H/PF4-PaGIA result increased the probability of HIT based on the 4T's Score to 15.4% (Low 4T's), 38.5% (intermediate 4T's) and 83.3% (High 4T's). The proportion of management failures was 1.5% (95% CI : 0.7%-3.0%). Of the 8 patients who were identified as management failures, 2 (Low 4T's) had a negative H/PF4-PaGIA. Out of 33 HIT Positive patients, 8 (24.2%) would have been missed based on a Low 4T's Score alone and 2 (6.1%) based on negative H/PF4-PaGIA alone. The combination of a Low or Intermediate 4T's Score and a negative H/PF4-PaGIA result had a negative predictive value for HIT of 99.5% (95% CI: 98.3-99.9). Conclusions The proportion of management failures was low (1.5%) and within acceptable limits (95% CI : 0.7%-3.0%). Combining the 4T's Score with the result of H/PF4-PaGIA excludes the diagnosis of HIT in the majority of patients with a Low or Intermediate probability for HIT and raises the likelihood of HIT in patients with a High probability. Disclosures: Linkins: BioRad DiaMed: PaGIA assays purchased at cost for study Other. Bates:BioRad Diamed: provided assays for study at cost Other. Lee:BioRad Diamed: provided assays for study at cost Other. Warkentin:GSK: Research Funding; WL Gore: Consultancy; Immucor GTI Diagnostics: Research Funding; Paringenix: Consultancy; Pfizer Canada: Honoraria; BioRad Diamed: provided assays for study at cost, provided assays for study at cost Other.

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Reversal of dabigatran-associated major bleeding with activated prothrombin concentrate: A prospective cohort study

Thrombosis Research ◽

10.1016/j.thromres.2017.02.010 ◽

2017 ◽

Vol 152 ◽

pp. 44-48 ◽

Cited By ~ 24

Author(s):

Sam Schulman ◽

B. Ritchie ◽

S. Nahirniak ◽

P.L. Gross ◽

M. Carrier ◽

...

Keyword(s):

Cohort Study ◽

Prospective Cohort Study ◽

Major Bleeding ◽

Prospective Cohort

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Evaluation of anticoagulation status for atrial fibrillation on early ischaemic stroke outcomes: a registry-based, prospective cohort study of acute stroke care in Surrey, UK

BMJ Open ◽

10.1136/bmjopen-2017-019122 ◽

2017 ◽

Vol 7 (12) ◽

pp. e019122 ◽

Cited By ~ 7

Author(s):

Thang S Han ◽

Christopher H Fry ◽

David Fluck ◽

Brendan Affley ◽

Giosue Gulli ◽

...

Keyword(s):

Atrial Fibrillation ◽

Cohort Study ◽

Ischaemic Stroke ◽

Scale Score ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Severe Stroke ◽

Increased Risk ◽

Relationship Of ◽

The Relationship

ObjectiveThe relationship of anticoagulation therapies with stroke severity and outcomes have been well documented in the literature. However, none of the previous research has reported the relationship of atrial fibrillation (AF)/anticoagulation therapies with urinary tract infection (UTI), pneumonia and length of stay in hyperacute stroke units (HASUs). The present study aimed to evaluate AF and anticoagulation status in relation to early outcomes in 1387 men (median age=75 years, IQR=65–83) and 1371 women (median age=83 years, IQR=74–89) admitted with acute ischaemic stroke to HASUs in Surrey between 2014 and 2016.MethodsWe conducted this registry-based, prospective cohort study using data from the Sentinel Stroke National Audit Programme. Association between AF anticoagulation status with severe stroke on arrival (National Institutes of Health Stroke Scale score ≥16), prolonged HASU stay (>3 weeks), UTI and pneumonia within 7 days of admission, severe disability on discharge (modified Rankin Scale score=4 and 5) and inpatient mortality was assessed by logistic regression, adjusted for age, sex, hypertension, congestive heart failure, diabetes and previous stroke.ResultsCompared with patients with stroke who are free from AF, those with AF without anticoagulation had an increased adjusted risk of having more severe stroke: 5.8% versus 14.0%, OR=2.4 (95% CI 1.6 to 3.6, P<0.001), prolonged HASU stay: 21.5% versus 32.0%, OR=1.4 (1.0–2.0, P=0.027), pneumonia: 8.2% versus 19.1%, OR=2.1 (1.4–2.9, P<0.001), more severe disability: 24.2% versus 40.4%, OR=1.6 (1.2–2.1, P=0.004) and mortality: 9.3% versus 21.7%, OR=1.9 (1.4–2.8, P<0.001), and AF patients with anticoagulation also had greater risk for having UTI: 8.6% versus 12.3%, OR=1.9 (1.2–3.0, P=0.004), pneumonia: 8.2% versus 11.5%, OR=1.6 (1.1–2.4, P=0.025) and mortality: 9.7% versus 21.7%, OR=1.9 (1.4–2.8, P<0.001). The median HASU stay for stroke patients with AF without anticoagulation was 10.6 days (IQR=2.8–26.4) compared with 5.8 days (IQR=2.3–17.5) for those free from AF (P<0.001).ConclusionsPatients with AF, particularly those without anticoagulation, are at increased risk of severe stroke, associated with prolonged HASU stay and increased risk of early infection, disability and mortality.

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