Increased enoxaparin dosing is required for obese children

Weight-based dosing for enoxaparin is recommended in the 2008 American College of Chest Physicians (ACCP) guidelines for venous thromboembolism (VTE) prophylaxis. Enoxaparin 0.5 mg/kg per dose administered subcutaneously every 12 hours is recommended for this indication in children. There is no established upper dosing limit of enoxaparin for prophylaxis in children, and the US Food and Drug Administration-approved enoxaparin dose for adults for VTE prophylaxis is 30 mg subcutaneously every 12 hours or 40 mg subcutaneously daily. Therefore, we assumed that the upper limit for children is 40 mg subcutaneously daily. We reviewed 3 cases of obese adolescent boys who required large doses of enoxaparin to achieve the ACCP-recommended anti-factor Xa range of 0.1 to 0.3 IU/mL for the prevention of VTE. All 3 patients required doses of enoxaparin that are higher than that recommended for adults for VTE prophylaxis: patient A (BMI: 105.9) required >0.28 mg/kg per dose, patient B (BMI: 95.7) required 0.15 mg/kg per dose, and patient C (BMI: 29.9) required 0.49 mg/kg per dose. The desired anti-factor Xa range was achieved when enoxaparin was administered every 12 hours in each patient with no reported episodes of VTE. One patient had minor bruising, but no other adverse events were noted. Because of the variability in dose requirements and unpredictability in patient responses demonstrated in our 3 adolescents, prospective studies are needed to provide definitive recommendations on dosing of enoxaparin for VTE prophylaxis in this subset of obese pediatric patients.     

The low molecular weight heparin dalteparin for prophylaxis and therapy of thrombosis in childhood: a report on 48 cases

We investigated the efficacy, safety and relation of dose to plasma anti-Xa activity of the low molecular weight heparin (LMWH) dalteparin in prophylaxis and therapy of arterial and venous thrombosis in pediatric patients. A total of 48 children were enrolled: 10 received dalteparin for prophylaxis (group I), 8 for reocclusion prophylaxis following successful thrombolysis (group II), 5 following failed thrombolysis (group III) and 23 for primary antithrombotic therapy (group IV). Two children were treated with dalteparin for pulmonary veno-occlusive disease (PVOD) and for primary pulmonary hypertension (PPH), respectively. Outcome: In group I no thrombo-embolic event occurred. In group II recanalization was maintained or improved, in group III vascular occlusion persisted under dalteparin. In group IV we saw complete recanalization in 7/23 (30%), partial recanalization in 7/23 (30%) and no recanalization in 9/23 (40%) cases. The child with PVOD had recanalization proven by lung biopsy; the clinical condition of the child with PPH also improved. Minor bleeding occurred in 2/48 (4%) children. For prophylaxis 95 - 52 (mean and SD) anti-Xa IU/kg BW, for therapy 129 - 43 (mean and SD) anti-Xa IU/kg BW proved effective. For both prophylaxis and therapy the required dose per kg BW was inversely related with age (r² = 0.64, P = 0.017; r² = 0.13, P = 0.013). Conclusion Dalteparin proved to be an effective and well tolerated drug for prophylaxis and therapy of thrombosis in pediatric patients. Dose requirement for effective treatment was higher in younger children and decreased with age.     

Portal vein thrombosis in a patient with severe haemophilia A and F V G1691A mutation during continuous infusion of F VIII after intramural jejunal bleeding - Successful thrombolysis under heparin therapy

We report on a 14-year-old boy with severe haemophilia A who developed a portal vein thrombosis during continuous infusion of F VIII. For treatment of a posttraumatic intramural jejunal haematoma with extension into the mesenterium the patient received continuous infusion (CI) of a high purity F VIII concentrate, starting with an initial bolus injection of 100 IU F VIII/kg bw and followed by 4-5 IU F VIII/kg bw/h i.v. F VIII plasma activity ranged between 47 and 88%. Resorption of the haematoma was proven by abdominal ultrasonic follow-ups. After 3 weeks of CI a thrombus formation in the portal vein was detected by ultrasound and confirmed by duplex ultrasound. Subsequent to diagnosis the patient was heparinised with unfractionated heparin (UFH 300-450 IU/kg/d i.v.). In order to induce further resorption of the haematoma, F VIII concentrate was given concomitantly (50 IU/kg bw twice daily) during the initial phase of treatment. After 14 days of anticoagulant therapy with UFH, the regimen was changed to low molecular weight heparin (LMWH; Fraxiparin 0.3™; 2850 IU anti-X activity/d s.c.; bw 60 kg). F VIII dosage was gradually reduced with advanced resorption of the haematoma and thereafter switched to prophylaxis (40 IU/kg bw 3 times weekly). Complete lysis of the thrombus was observed after 6 months of treatment with UFH and LMWH respectively without any further complications. Thereafter LMWH was discontinued. Thrombophilic screening revealed no abnormalities except heterozygous F V G1691A. Conclusion The coexistence of a common prothrombotic risk factor and haemophilia may cause severe complications, in particular if the bleeding disorder has to be corrected temporarily by administration of the concerning deficient agent.     

Fluctuations of anti-Xa concentrations during maintenance enoxaparin therapy for neonatal thrombosis

Aim: To evaluate fluctuations in anti‐Xa concentrations in infants treated with enoxaparin for thrombosis and describe clinical outcomes. Methods: A retrospective chart review was performed on infants treated with enoxaparin in the Neonatal Intensive Care Unit, and data on enoxaparin doses, anti‐Xa concentrations, clinical characteristics and outcomes were abstracted. Results: Our cohort (n = 26) had a median gestation of 36 (range, 23–41) weeks, birthweight of 2522 (510–3912) grams and 5‐min Apgar score of 8(4–9). Fifteen (57.7%) infants were males. Thromboses was diagnosed at a median age of 22 (range, 1–97) days; enoxaparin was initiated at 27.5 (range, 4–98) days at a mean (SD) dose of 1.4 (0.3) mg/kg every 12 h. Therapeutic anti‐Xa concentrations (0.5–1 U/mL) were achieved at a mean (SD) dose of 2.1 (0.6) mg/kg at 12.5 (12.2) days of treatment. Of the 143 anti‐Xa concentrations, 39 (27%) were within the therapeutic range. During maintenance therapy following initial therapeutic anti‐Xa concentration, 40% concentrations were therapeutic. Minor bleeding was noted in four infants and intracranial bleed in one infant; four infants died. During treatment, thrombocytopenia, renal and hepatic impairment during treatment were noted in 7, 2 and 4 infants, respectively. Clot resolution was observed in 21 (81%) infants. Conclusions: Anti‐Xa concentrations fluctuate during maintenance enoxaparin therapy, with therapeutic levels being achieved only sporadically in young infants. Despite this, enoxaparin appears efficacious in thrombosis resolution. Further studies on the impact of stringent control of concentrations on outcomes in this population are warranted.     

Low molecular heparin for treatment of venous thrombosis in two very low-birth-weight pre-term infants with genetic risk factors

We describe the use of low molecular weight heparin to treat venous thrombosis in two very low-birth-weight pre-term infants (GA: 30 and 27 weeks) both with genetic and acquired prothrombotic risk factors. Initially both infants were treated with unfractionated heparin. Since in one infant no effect on the thrombus size was observed and in the other infant there was an increase in size, the anticoagulation therapy was switched to subcutaneously injected low molecular heparin (Enoxaparin). During enoxaparin therapy the anti-Xa-level was carefully monitored and dosages were adjusted accordingly. Partial resolution of the thrombosis was achieved in both infants during enoxaparin therapy. No clot extension or recurrence of thrombosis occurred. An accidental overdose of Enoxaparin (100 times the required dosage) was administered to one infant without any consequences. Our data suggest that the use of low molecular weight heparin (Enoxaparin) for treatment of venous thrombosis in our two preterm infants was practical, safe and effective.     

Experience with intravenous enoxaparin in critically ill infants and children

OBJECTIVE: Subcutaneous administration of enoxaparin is often difficult in special populations, such as premature infants and critically ill children with severe edema. The difficulty achieving adequate anticoagulation in these patients has led to the employment of intravenous enoxaparin in some cases. However, little pharmacodynamic data are available for determining the appropriate dosing and monitoring (by anti-Factor Xa levels) of intravenous enoxaparin. The objective of this study is to report our experience with the use of intravenous enoxaparin in pediatric patients in the intensive care unit. DESIGN: Retrospective review of medical records. SETTING: Single institution pediatric intensive care unit. PATIENTS: All pediatric patients receiving intravenous enoxaparin in the pediatric intensive care unit at Children's Medical Center Dallas between April 1, 2005 and March 31, 2006 were identified using hospital pharmacy records. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Seven patients were identified as having received intravenous enoxaparin while in the intensive care unit. Higher anti-Xa levels were found at 1-2 hrs after administration of intravenous enoxaparin rather than at the 4-6 hrs documented with subcutaneous administration and these levels decreased substantially 6-8 hrs after an intravenous dose. Mean therapeutic dose for children <1 yr of age was 2.40 mg/kg/dose (+/-sd 0.58). For children > or =1 yr of age, the mean therapeutic dose was 1.11 mg/kg/dose (+/-sd 0.13). The mean prophylactic dose for the two children was 0.93 mg/kg/dose (+/-sd 0.43). CONCLUSIONS: Our data show that the pharmacodynamics of intravenous administration is different from subcutaneous administration and deserves further study.     

The use of low molecular weight heparin in pediatric patients: a prospective cohort study

OBJECTIVE: Low molecular weight heparins (LMWHs) offer several advantages over standard anticoagulant therapy (unfractionated heparin/warfarin) including predictable pharmacokinetics, minimal monitoring, and subcutaneous administration. Our objective was to determine the safety and efficacy of LMWHs in children. METHODS: A prospective cohort of children treated with the LMWH enoxaparin (Rhone Poulenc Rorer) was monitored at the Hospital for Sick Children, Toronto, Canada, from March 1994 until July 1997. RESULTS: There were 146 courses of LMWH administered for treatment and 31 courses for prophylaxis of thromboembolic events (TEs). Clinical resolution of TEs occurred in 94% of children receiving therapeutic doses of LMWH, and 96% of children receiving prophylactic doses of LMWH had no symptoms of recurrent or new TEs. Major bleeding occurred in 5% of children receiving therapeutic doses. Recurrent or new TEs occurred in 1% and 3% of children receiving therapeutic and prophylactic doses of LMWH, respectively. CONCLUSION: LMWH appears to be efficacious and safe for both management and prophylaxis of TEs. The results of this cohort study justify a randomized controlled trial comparing LMWH with standard therapy for the management of TEs in children.     

An assessment of published pediatric dosage guidelines for enoxaparin: a retrospective review

OBJECTIVE: To evaluate the ability of published dosage guidelines for enoxaparin to achieve therapeutic anticoagulation and to determine whether the routine monitoring of anti-Xa levels is still necessary at a tertiary care pediatric institution. METHODS: Consecutive charts and laboratory records were reviewed for all patients receiving treatment doses of enoxaparin for thrombosis in the authors institution over a 4-year period (1998-2002). RESULTS: Sixty-six percent (25/38) of the anti-Xa levels were within the recommended therapeutic range (0.5-1.0 [+/- 10%] U/mL) after two doses. The success rates of achieving therapeutic levels were 1/6, 2/3, 6/9, 10/11, and 6/9, for patients 2 months or younger, more than 2 months to 1 year, more than 1 year to 6 years, more than 6 years to 12 years, and more than 12 years of age, respectively. Patients with cardiac or renal disease were more likely to achieve high anti-Xa levels. Thirty-seven percent of patients reported adverse effects. The most common effects were injection site-related bruising and minor bleeding. One patient experienced a major bleed that was not life-threatening. CONCLUSIONS: Most patients achieved therapeutic anticoagulation when dosed according to the published guidelines. Children with cardiac conditions or renal insufficiency or those younger than 2 months were more likely to require dosage adjustments to achieve the therapeutic range. Routine monitoring of anti-Xa levels is still necessary in these patient populations, particularly when the early establishment of therapeutic anticoagulation may be critical. Enoxaparin appears to be well tolerated in the authors' patient population.     

肾病综合征并发颅内静脉窦血栓五例

目的 探讨肾病综合征患儿并发颅内静脉窦血栓的诊断,及应用尿激酶与低分子肝素等联合治疗效果.方法 采用尿激酶与低分子肝素等联合治疗.(1)尿激酶:初剂量2000～4000 U/(kg·d),首剂冲击量20 000～40 000 U在15～30 min内滴完,而后将余量用输液泵均匀地泵入,第2天起2000 U/(kg·d)用输液泵均匀地泵入,1个疗程3～7 d.治疗期间每周测定3次凝血酶时间(TT)、激活的部分凝血致活酶时间(APTT),应控制TT和APTT应小于2倍延长的范围内,特别注意有无出血情况.(2)低分子肝素:每次100～120 AXaIU/kg,每天1～2次,腹部皮下注射,2周1疗程.(3)抗血小板凝聚药物:长期口服双嘧达莫3～5 mg/(kg·d),每天2～3次,疗程3个月.结果 5例肾病综合征并发颅内静脉窦血栓,经过尿激酶、低分子肝素与双嘧达莫等联合治疗,1个月后患儿临床症状均消失;复查血浆黏度1个月恢复正常,部分凝血活酶时间、血浆凝血酶原时间、纤维蛋白原降解产物1～2个月后恢复至正常,头颅CT或MRI检查1～3个月后静脉血栓消失,示颅内静脉窦血栓完全再通;随访无复发病例.结论 早期应用尿激酶抗纤溶、低分子肝紊抗凝及抗血小板凝聚药物综合治疗,其溶栓疗效较好.对儿童肾病综合征并发颅内静脉窦血栓的早期诊断与防治具有一定的推广价值.     

Prophylaxis and therapy using liposomal amphotericin B (AmBisome) for invasive fungal infections in children undergoing organ or allogeneic bone-marrow transplantation

Sixty-one children with a median age of 6 years (range 1-16) were given prophylaxis/therapy for 78 courses of treatment with liposomal amphotericin (AmBisome) and were reviewed retrospectively. Thirty-six received allogeneic bone marrow, 22 a liver transplant, 2 kidneys and 1 a liver and kidney. AmBisome was given as prophylaxis in 30 episodes, as treatment for suspected invasive fungal infections (IFI) in 33 and for a verified IFI in 15. AmBisome prophylaxis was given for a median of 14 days in a dose of 1 mg/kg/day. The median dose of AmBisome was 2.1 mg/kg/day (range 0.9-5.0). The median duration of therapy was 10 days in children with suspected IFI and 20 days in children with verified IFI. The total dose ranged from 0.025 g up to a maximum of 3.95 g. Proven and probable side effects of AmBisome were a decrease in the level of serum potassium (30/78 cases), renal toxicity (22), an increase in the alkaline phosphatases (24), back pain (2), fever and abdominal pain (2), anaphylactic reaction (1), an increase in the bilirubin level (1), nausea (1), chest pain (1) and fever (1). Of 31 children with suspected IFI, fever disappeared in 21 (68%). In 14 verified or suspected IFI cases treated for 5 days or more, the clinical cure rate was 12 (86%). Eradication of fungi from a deep site was verified in 8/10 and the survival rate from 1 1/2 years to more than 7 years was 7/12 (58%). We conclude that AmBisome was well tolerated as prophylaxis and therapy in transplanted children, few acute toxic side effects were seen and the cure rate in verified IFI was high.     

A clinical audit of antithrombin concentrate use in a tertiary paediatric centre

Aim: The aim of this study was to investigate the clinical use of antithrombin concentrate (ATC) in children and specifically to determine the current practice of ATC administration, including dosing and indications for administration. Methods: A clinical audit was performed of patients treated with ATC during two 12‐month periods: 1 June 1999–1 June 2000 and 1 June 2009–1 June 2010. Results: Thirty‐seven patients whose age ranged from 1 day to 13.5 years (median 30 days) received a median of two doses (range 1–15) with a median dose of 40 units/kg (range 1–200 units). The majority (90%) of patients were located in the intensive care unit, and the major indication (76%) for use of the ATC was in the setting of unfractionated heparin (UFH) resistance. Post‐ATC administration, 32% of the doses given resulted in antithrombin levels reaching age‐specific normative levels. Of the patients administered ATC with the aim of optimising UFH therapy, 28% of patients had their UFH dose reduced without any measurement of UFH effect. Conclusions: This data provides the basis for future investigations of the specific biochemical changes accompanying ATC administration and the development of paediatric‐specific evidence‐based guidelines for ATC use.     

Limited Tolerance of Intensified Conditioning Regimens in Children Receiving Methotrexate/Cyclosporin A for Graft-Versus-Host Disease Prophylaxis

Twenty-one patients with a median age of 9 years (0.5-19) underwent intensifid myeloblative therapy: 1800 mg/m² etoposide (VP) was added to 120 mg/kg cyclophosphamide (CY) and 12 Gy fractionated total body irradiation (FTBI) or 12-16 mg/kg busulfan (BU) for treatment of acute lymphoblastic leukemia (11 patients), acute myeloid leukemia (8 patients), non-Hodgkin's lymphoma (1 patient), or myelodysplastic syndrome (1 patient). Severe liver toxicity occurred in 5 of 7 children (71 %) receiving short-term methotrexate (MTX) and additional cyclosporin A (CSA) for prophylaxis of graft versus-host disease (GVHD). Three of them died of subsequent acute renal failure on days 8, 13, and 34.

In contrast, acute severe organ toxicity occurred in only 1 of 14 children (7%) receiving the same intensified regimens who were autografted (7 pts) or received MTX alone for GVHD prophylaxis (7 pts). These observations suggest that GVHD prophylaxis with MTX and CSA may adversely influence the tolerance of intensified antileukemic regimens in children.     

Pulmonary embolism in children

Unlike in adults, pulmonary embolism (PE) is an infrequent event in children. It has a marked bimodal distribution during the paediatric years, occurring predominantly in neonates and adolescents. The most important predisposing factors to PE in children are the presence of a central venous line (CVL), infection, and congenital heart disease. Clinical signs of PE are non-specific in children or can be masked by underlying conditions. Diagnostic testing is necessary in children, especially with the lack of clinical prediction rules. Recommendations for tests are derived from adult studies with ventilation/perfusion (V/Q) scintigraphy being well established. There exists an increasing role for computerised tomography pulmonary angiography (CTPA) and magnetic resonance pulmonary angiography (MRPA). Thrombotic events in children are initially treated with unfractionated heparin (UFH) or low molecular weight heparin (LMWH). For the extended anticoagulant therapy LMWH or vitamin K antagonists can be used with duration of treatment recommendations extrapolated from adult data. Mortality rates for PE in children are reported to be around 10%, with death usually related to the underlying disease processes. Exact data about recurrence risk in children is unknown. Because of the difference in aetiology, presentation, diagnostic methods and treatment between adults and children further research is necessary to assess the validity of recommendations for children.     

Intensive chemotherapy for metastatic neuroblastoma: A southwest oncology group study

Thirty-three children with Evans stage IV neuroblastoma were treated with an intensive chemotherapy regimen reported by Helson to be highly effective. The purpose of the study was to determine whether the toxic regimen was manageable by different investigators and to increase the sample of patients. Remission induction therapy consisted of courses repeated every four weeks: Cyclophos-phamide (CTX) 80 mg/kg IV, with IV fluids and furosemide on days 1 and 2; vincristine (VCR) 0.03 mg/kg IV 12 hours after cyclophosphamide; trifluoro-methyl-2-deoxyridine (F3TdR) 45 mg/kg IV push, and papaverine (PAP) 45 mg/kg (12-hour infusion) under cardiac monitoring on days 3 and 4. Initially during maintenance, courses of therapy were reduced to two days. Because this was found to be ineffective therapy, the courses were extended to four days. Some of the patients who achieved response were removed from the protocol and placed on different maintenance therapy. Seventeen of 21 children newly diagnosed and 6/12 children previously treated for metastatic neuroblastoma achieved partial or complete remissions. Eight of 16 newly diagnosed patients achieving response are still alive, six without evidence of disease for periods of time ranging from 20 to 41 months. The median of the administered drug dosages was 100% of the recommended dosages. Seventy percent of the 229 courses given were initiated at correct interval. Therapy had to be delayed on the others because of toxicity. The value of the four-drug combination is limited because of side effects related to myelosuppression which resulted in severe complications and frequent hospitalizations.     

Nadroparin therapy in pediatric patients with venous thromboembolic disease

Low-molecular-weight heparins are increasingly used for treatment of pediatric venous thromboembolic disease (VTE). Pediatric data about therapeutic doses of nadroparin are not available. To evaluate pharmacodynamics and safety of therapeutic doses of nadroparin, consecutive patients (age 0 to 18 y) with objectively diagnosed VTE and treated with nadroparin were included in this single center study over a 12-year period. All patients started with 85.5 IU/kg of nadroparin twice daily. The target therapeutic range (TTR) was set at 0.5 to 1.0 anti-Xa IU/mL 4 hours postdose. Safety end points were major bleeding and therapy-related death. A total of 84 patients were enrolled, of whom 8 patients did not undergo measurement of anti-Xa levels. Fifty-four (71%) of 76 patients achieved TTR. The maintenance dose (mean+/-SE) was 448+/-42 IU/kg/d in neonates (<2 mo, n=6), 253+/-22 IU/kg/d in infants (2 mo to 1 y, n=10), 214+/-8 IU/kg/d in children (2 to 11 y, n=13), and 183+/-5 IU/kg/d in adolescents (12 to 18 y, n=25). Neonates required significantly more dose adjustments and time to achieve TTR than adolescents. No major bleeding or therapy-related death occurred. In summary, an age-dependent response to nadroparin exists in pediatric patients. Nadroparin therapy seems to be safe for treatment of pediatric VTE.     

Pharmacokinetics of amikacin in infants and pre-school children.

The pharmacokinetic properties of amikacin sulfate in infants and children aged from three weeks to 6 years were studied during treatment with doses of 7.5 mg/kg every 12 hours using standard assay methods and technique of two compartment open model kinetic analysis. Peak serum concentrations of amikacin were measured 30 or 60 min after the first intramuscular injection. These ranged from 11.8 microgram/ml to 23 microgram/ml in infants and from 9.0 microgram/ml to 29 microgram/ml in children. Five minutes after the first intravenous bolous injection they varied from 16 microgram/ml to 29.8 microgram/ml in infants and from 34 microgram/ml to 42 microgram/ml in children. Twelve hours after injection serum concentrations were less than 0.8 microgram/ml in all patients. Mean serum half-lives of amikacin in infants and children were 2.1 hours and 2.0 hours after intramuscular, and 2.2 and 2.0 hours after intravenous administration respectively. No evidence of accumulation was observed after four days treatment. The amount of antibiotic recovered within 12 hours from the urine in all patients ranged from 34.5 to 65% of an intramuscular dose, and from 45.8 to 63.3% of an intravenous dose. The dosage regime of 7.5 mg/kg body weight given every 12 hours should be safe and effective for the treatment of infections in the age groups studied.     

Low molecular weight heparin in the successful treatment of a spontaneous aortic thrombosis in a neonate

A successfully treated case of a spontaneous aortic thrombosis in a neonate is described as an illustration of the advantages of using low molecular weight heparin (LMWH) over unfractionated heparin (UFH) for anticoagulation therapy. A 5-day-old neonate presented with an abdominal aortic thrombosis detected by echocardiography. Intravenous UFH was commenced following thrombectomy. Poor venous access made monitoring the anticoagulation therapy problematic. Subcutaneous LMWH was substituted for UFH. It requires substantially less monitoring and no intravenous access, has fewer side effects, and allows for much earlier discharge from the hospital. Extensive investigation for a hypercoagulable state revealed no definite cause for the thrombus. The findings of homozygosity for a methylene tetrahydrofolate reductase (MTHFR) mutation and a mildly elevated homocysteine level are interesting but unlikely to account for the thrombotic event in this case. Anticoagulation with LMWH proved effective and more convenient than using UFH.     

A spontaneous intramural hematoma of the bowel presenting as obstruction in a child receiving low-molecular-weight heparin

Low-molecular-weight heparin (LMWH) is a safe and effective alternative to unfractionated heparin and coumadin in the treatment and prophylaxis of thrombosis in children. When compared with these more established anticoagulants, it is easier to achieve therapeutic levels and the incidence of hemorrhagic complications is equivalent or lower. In children there is less published experience than in adults, but the low frequency of significant bleeding appears to be similar. The authors describe a child on therapeutic doses of LMWH for a deep vein thrombosis who spontaneously developed an intramural hemorrhage in his small bowel, leading to infarction and a partial bowel resection.     

LOW MOLECULAR WEIGHT HEPARIN IN THE SUCCESSFUL TREATMENT OF A SPONTANEOUS AORTIC THROMBOSIS IN A NEONATE

A successfully treated case of a spontaneous aortic thrombosis in a neonate is described as an illustration of the advantages of using low molecular weight heparin (LMWH) over unfractionated heparin (UFH) for anticoagulation therapy. A 5-day-old neonate presented with an abdominal aortic thrombosis detected by echocardiography. Intravenous UFH was commenced following thrombectomy. Poor venous access made monitoring the anticoagulation therapy problematic. Subcutaneous LMWH was substituted for UFH. It requires substantially less monitoring and no intravenous access, has fewer side effects, and allows for much earlier discharge from the hospital. Extensive investigation for a hypercoagulable state revealed no definite cause for the thrombus. The findings of homozygosity for a methylene tetrahydrofolate reductase (MTHFR) mutation and a mildly elevated homocysteine level are interesting but unlikely to account for the thrombotic event in this case. Anticoagulation with LMWH proved effective and more convenient than using UFH.     

Efectos hemodinámicos del omeprazol por vía intravenosa en niños en estado crítico

IntroductionCritical patients usually have hemodynamic disturbances which may become worse by the administration of some drugs. Omeprazole is a drug used in the prophylaxis of the gastrointestinal bleeding in these patients, but its cardiovascular effects are unknown. The objective was to study the hemodynamic changes produced by intravenous omeprazole in critically ill children and to find out if there are differences between two different doses of omeprazole.Material and methodsA randomized prospective observational study was performed on 37 critically ill children aged from 1 month to 14 years of age who required prophylaxis for gastrointestinal bleeding. Of these, 19 received intravenous omeprazole 0.5 mg/kg every 12 hours, and 18 received intravenous omeprazole 1 mg/kg every 12 hours. Intravenous omeprazole was administered in 20 minutes by continuous infusion pump. Heart rate, systolic, diastolic and mean arterial blood pressure, central venous pressure and ECG were recorded at baseline, and at 15, 30, 60 and 120 minutes of the infusion.ResultsThere were no significant changes in the electrocardiogram, heart rate, blood pressure and central venous pressure. No patients required inotropic therapy modification. There were no differences between the two doses of omeprazole.ConclusionsIntravenous omeprazole administration of 0.5 mg/kg and 1 mg/kg is a hemodynamically safe drug in critically ill children.