Antithrombotic and thrombolytic therapy for valvular disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.

BACKGROUND: Antithrombotic therapy in valvular disease is important to mitigate thromboembolism, but the hemorrhagic risk imposed must be considered. METHODS: The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. RESULTS: In rheumatic mitral disease, we recommend vitamin K antagonist (VKA) therapy when the left atrial diameter is > 55 mm (Grade 2C) or when complicated by left atrial thrombus (Grade 1A). In candidates for percutaneous mitral valvotomy with left atrial thrombus, we recommend VKA therapy until thrombus resolution, and we recommend abandoning valvotomy if the thrombus fails to resolve (Grade 1A). In patients with patent foramen ovale (PFO) and stroke or transient ischemic attack, we recommend initial aspirin therapy (Grade 1B) and suggest substitution of VKA if recurrence (Grade 2C). In patients with cryptogenic stroke and DVT and a PFO, we recommend VKA therapy for 3 months (Grade 1B) and consideration of PFO closure (Grade 2C). We recommend against the use of anticoagulant (Grade 1C) and antiplatelet therapy (Grade 1B) for native valve endocarditis. We suggest holding VKA therapy until the patient is stabilized without neurologic complications for infective endocarditis of a prosthetic valve (Grade 2C). In the first 3 months after bioprosthetic valve implantation, we recommend aspirin for aortic valves (Grade 2C), the addition of clopidogrel to aspirin if the aortic valve is transcatheter (Grade 2C), and VKA therapy with a target international normalized ratio (INR) of 2.5 for mitral valves (Grade 2C). After 3 months, we suggest aspirin therapy (Grade 2C). We recommend early bridging of mechanical valve patients to VKA therapy with unfractionated heparin (DVT dosing) or low-molecular-weight heparin (Grade 2C). We recommend long-term VKA therapy for all mechanical valves (Grade 1B): target INR 2.5 for aortic (Grade 1B) and 3.0 for mitral or double valve (Grade 2C). In patients with mechanical valves at low bleeding risk, we suggest the addition of low-dose aspirin (50-100 mg/d) (Grade 1B). In valve repair patients, we suggest aspirin therapy (Grade 2C). In patients with thrombosed prosthetic valve, we recommend fibrinolysis for right-sided valves and left-sided valves with thrombus area < 0.8 cm(2) (Grade 2C). For patients with left-sided prosthetic valve thrombosis and thrombus area ≥ 0.8 cm(2), we recommend early surgery (Grade 2C). CONCLUSIONS: These antithrombotic guidelines provide recommendations based on the optimal balance of thrombotic and hemorrhagic risk.

Does Ibuprofen increase neonatal hyperbilirubinemia?

OBJECTIVE: The aim of this study was to investigate whether ibuprofen exposure was associated with increased hyperbilirubinemia in preterm infants. METHODS: Since 2000, ibuprofen has been administered to all infants at <30 weeks of gestation who are admitted to our unit, to prevent patent ductus arteriosus. We retrospectively compared data for 418 infants subjected to ibuprofen prophylaxis (2000-2007) and 288 infants not exposed to ibuprofen (1993-1999). RESULTS: The ibuprofen group had a significantly higher peak total serum bilirubin level (9.0 +/- 2.5 mg/dL vs 7.3 +/- 3.3 mg/dL), more need for phototherapy (398 infants [95%] vs 254 infants [87.6%]), and a longer phototherapy duration (94.3 +/- 43.6 hours vs 87.2 +/- 38.6 hours). Groups did not differ with respect to gestational age, birth weight, gender ratio, glucose-6-phosphate dehydrogenase deficiency incidence, or hypoalbuminemia (<2.5 g/dL) incidence. Hemolytic isoimmunization was diagnosed with similar incidences (no-ibuprofen group: 7 of 288 infants; ibuprofen group: 8 of 418 infants). The rates of exchange-transfusion also were similar between the groups (no-ibuprofen group: 14 infants [4.8%]; ibuprofen group: 19 infants [4.5%]). CONCLUSIONS: Ibuprofen administration was associated with higher peak total serum bilirubin levels, and the more-pronounced hyperbilirubinemia led to longer phototherapy. The potential role of competition between ibuprofen and bilirubin in the hepatic glucuronidation pathway is discussed.

Total serum bilirubin levels during cyclooxygenase inhibitor treatment for patent ductus arteriosus in preterm infants.

AIM: To determine whether ibuprofen use in VLBW infants is associated with increased serum bilirubin levels and impaired neurodevelopmental outcome at 2 years of age compared to indomethacin. METHODS: We retrospectively evaluated bilirubin data and outcome parameters of 178 VLBW infants treated with COX inhibitors for a haemodynamically relevant patent ductus arteriosus (PDA) between 1998 and 2003 in a single institution. In our department ibuprofen replaced indomethacin for PDA treatment in 2001, while clinical and echocardiographic criteria for the indication of PDA invention have remained unchanged. RESULTS: Ibuprofen and indomethacin therapy groups did not differ in their baseline clinical profile. Peak serum bilirubin concentration was 10.2 mg/dL in the ibuprofen group and 8.6 mg/dL in the indomethacin group (p < 0.01), while phototherapy duration did not differ. At 2 years of age neurodevelopmental outcome was similar in both groups. In a single case analysis, four cases of adverse neurodevelopmental outcome despite inconspicuous clinical course were identified in the ibuprofen group. CONCLUSION: In VLBW infants with PDA, ibuprofen treatment was associated with higher bilirubin levels than indomethacin.

Parenteral amino acid and metabolic acidosis in premature infants.

BACKGROUND: Aggressive parenteral nutrition (PN) including amino acids is recommended for low-birth-weight infants to prevent energy and protein deficit. Their impact on acid-base homeostasis has not been examined. METHODS: We investigated the impact of dose and duration of parenteral amino acids, with cysteine, on acid-base parameters in 122 low-birth-weight infants. Premature infants 24 hours), or 3 g/kg/d for a short (5 hour), extended (24 hour), or prolonged (3-5 days) duration were included in the study. Data were obtained at age 0-3 days (n = 43) or, when clinically stable, age 3-5 days (n = 49). Data from 30 infants, matched for birth weight and gestational age, receiving PN during the first 5 days after birth were also obtained. Acidosis was defined as pH <7.25. RESULTS: Acidosis was evident in all infants between 2 and 5 days after birth. Infants with large patent ductus arteriosus (PDA) exhibited significantly (p < .05) lower pH early, had higher blood urea nitrogen levels (26 +/- 9 vs 18 + 8 mg/dL; p < .05), and had greater weight loss ( approximately 17% of birth weight) when compared with infants without PDA. Gestational age, weight loss, and patent ductus arteriosus accounted for 65% of variance in acidosis. CONCLUSIONS: Low-birth-weight infants develop metabolic acidosis between 2 and 5 days after birth, irrespective of dose and duration of parenteral amino acid administration. Careful management of parenteral fluids and comorbidities may lower the incidence of acidosis and promote protein accretion.

Phototherapy and plasma immunoreactive prostaglandin A values. Its effect in premature infants.

Plasma immunoreactive prostaglandin A (iPGA) values were determined for 14 premature infants before and after 48 hours of phototherapy and in a control group of six age-matched premature infants. At 4 to 8 days of life, the infants who had received phototherapy for 48 hours had significantly lower iPGA values compared with controls. At 2 to 3 days of life, four infants with a clinically apparent patent ductus arteriosus were found to have significantly elevated iPGA values compared with controls. After 48 hours of phototherapy, these infants likewise had a significant decrease in iPGA values compared with controls; in all four infants, the ductus closed spontaneously. Phototherapy is an effective method for decreasing plasma iPGA values in premature infants.