Unfractionated heparin dosing requirements in the presence of inflammation during the first six months of life.

BACKGROUND: Critically ill neonates with inflammation secondary to SIRS or sepsis often develop an acquired pro-thrombotic state. Unfractionated heparin (UFH) is commonly prescribed in this population, but these subjects often remain sub-therapeutic or require very high doses of UFH to achieve and sustain therapeutic anti-Xa activity. This is due, in part, to the unique pharmacokinetics/dynamics of this population but may also be influenced by the degree of inflammation. OBJECTIVE: To evaluate UFH dosing requirements in neonates and infants <6 months of age with variable degrees of systemic inflammation. Clinical outcomes of bleeding and clotting will also be examined. SUBJECTS/METHODS: A retrospective chart review was performed in infants <6 months of age treated with intravenous UFH for at least 24 h with intent to reach a goal anti-Xa of 0.3-0.7 U/mL at Children's Hospital Colorado between October 2008 and August 2014. Subjects were divided into two groups, based on their ability to achieve and maintain anti-Xa concentrations between 0.3 and 0.7 U/mL. The relationship between UFH dose (U/kg/h) and inflammatory status (using pediatric age-specific definitions for SIRS, sepsis, severe sepsis, or septic shock) was examined. RESULTS: Seventy-three subjects were included in the analysis. Twenty-three subjects (mean age = 41.2 days ±â€¯standard deviation [SD] 52.3) achieved therapeutic anti-Xa concentrations while fifty subjects (mean age = 43.4 days ±â€¯SD 53) did not. The median UFH dose needed in subjects who achieved goal anti-Xa concentrations in the absence of SIRS or sepsis criteria was 24.5 U/kg/h (interquartile range [IQR] = 23.6-25.9) while the median dose of UFH in subjects who achieved goal anti-Xa level in the setting of infection, SIRS, or sepsis of any type was 36.1 U/kg/h (IQR = 34-43.5) (p < 0.0001). In subjects who maintained therapeutic anticoagulation, there was a direct relationship between UFH dose and the severity of inflammation as determined by pediatric SIRS/sepsis criteria. CONCLUSIONS: Maintenance of therapeutic UFH levels remains a challenge in infants, especially in those with concomitant inflammatory processes. Infection, SIRS, and sepsis of any type were collectively associated with a 32% increase in unfractionated heparin dose required to achieve and maintain therapeutic anti-Xa serum concentrations.

Peri-procedural bridging with low molecular weight heparin in patients receiving warfarin for venous thromboembolism: a pediatric experience.

INTRODUCTION: The incidence of venous thromboembolism (VTE) in children appears to be increasing, and warfarin remains one of the few standard anticoagulants used for secondary VTE prevention. When invasive procedures are required in adults with high TE risk who are receiving warfarin, low-molecular weight heparin (LMWH) bridging is recommended, based mainly upon observational evidence; in children, no such studies have been published. We sought to determine the risks of recurrent TE (both VTE and arterial TE [ATE]) and major bleeding with peri-procedural LMWH bridging in children receiving warfarin for VTE. METHODS: Children (age≤21years of age at the time of bridge) receiving warfarin for VTE and undergoing a standardized clinical care protocol for peri-procedural LMWH bridging were enrolled and followed in an institution-based prospective inception cohort study at Children's Hospital Colorado between March 2006 and February 2012. Outcomes were assessed at 30days post-procedure, and followed International Society on Thrombosis and Haemostasis guidelines. RESULTS: Seventeen children comprised the cohort, with a total of 23 bridging episodes. Median age at bridging episode was 17.5years (range, 12 to 21years). In 22% of bridging episodes, indication was for major surgery. Median duration of LMWH administration prior to procedure was 6days (range, 4-10days); median duration off anticoagulation peri-procedurally was 1.5days (range: 1-2days). The risks of major bleeding, recurrent VTE, and ATE at 30days post-procedure were 4.3% (1/23), 0% and 0%, respectively. CONCLUSIONS: This study provides important preliminary data on safety and efficacy of perioperative LMWH bridging for adolescent VTE patients receiving warfarin. Larger collaborative pediatric studies are warranted to substantiate these findings and to investigate prognostic factors of bleeding and recurrent TE in this setting.

[Sample survey of persons insured in statutory health insurance institutions in Hessen--concept and realisation of person-related data base]. / Versichertenstichprobe AOK Hessen/KV Hessen -- Konzeption und Umsetzung einer personenbezogenen Datenbasis aus der Gesetzlichen Krankenversicherung.

Statutory health insurance data are being increasingly used for secondary data research. Longitudinal data can be prepared for research in health care, epidemiology or demand planning, in particular through the person-related nature of the data which is a precondition for the creation of inter-sector and inter-period data sets. This application possibility was introduced in a method study "person-related sampling of statutory health insurance data" and is now translated into practice on a larger scale for the first time in the regional sample "Versichertenstichprobe AOK Hessen/KV Hessen". For the collection and use of these data, model procedures were designed which take account of organisational (data access, contractual agreement, advisory board), technical (sampling, collection and storage of data) and confidentiality (data protection concept, pseudonymisation) aspects. The insured person-related sample may thus serve as a basis for the data pool planned for the national health system (Social Security Regulation 303 a-SGB V).