[Enoxaparin and tinzaparin in pediatrics: Impact of recommendation on prescription quality and anti-Xa levels]. / Énoxaparine et tinzaparine en pédiatrie : impact de recommandations sur la qualité des prescriptions et l'activité anti-Xa.

OBJECTIVES: A protocol has been written and distributed in May 2017 to all prescribers in a pediatric hospital to standardize and to secure the prescriptions of enoxaparin and tinzaparin considered as two high risk medications. The aim of this study is to evaluate the impact of the protocol on those prescriptions in a pediatric population. METHODS: This is a monocentric retrospective study comparing prescriptions of this two low-molecular-weight heparins for patients under 18 years old in 2016 and 2018, thus before and after the protocol redaction. RESULTS: In 2016, 2246 prescriptions of enoxaparin and tinzaparin were analyzed for 627 patients. Among them, 142 (22.6%) patients have had at least one anti-Xa level dosed. On the other hand, in 2018, 2061 prescriptions were written for 628 patients including 96 (15.3%) who have had at least one anti-Xa level dosed. The conformity rate of the first dose in IU/kg/administration of the first enoxaparin prescription goes from 36.3% before protocol to 52.1% after (P=0.03*). Concerning tinzaparin, the conformity rate goes from 69.2% to 83.3%. (P=0.19). The rate of first anti-Xa level in the range 0.4 to 1.2 IU/ml increase between 2016 and 2018 from 27.7% to 43.8% (P<0.001*). CONCLUSION: This protocol enabled to improve the quality of prescriptions in terms of: dosage written in IU/kg/administration, frequency of administration, dilution conformity, and result of the first anti-Xa level. Some efforts must be made in writing the dose in IU not in mg or ml.

[Neonatal renal venous thrombosis in 2008]. / Thrombose néonatale des veines rénales en 2008.

Venous thromboses are rare in childhood. In the neonatal period, these are mainly neonatal renal venous thromboses (NRVT). We propose a synthesis of the main recent reviews on NRVT published over the last 15 years. These studies reported the higher male prevalence, the predominance of left kidney vein involvement, the increasing incidence in premature newborns, and a high level of thrombophilia in screened newborns. The usual presentation of NRVT, which associates abdominal mass, macroscopic hematuria, and thrombocytopenia, has been progressively modified by these new epidemiological features. The abdominal Doppler ultrasound scan is widely used for diagnosis and must be systematically associated with a transfontanellar ultrasound to look for cerebral hemorrhage, which should be a contraindication for anticoagulation. Recent consensus recommends at least prophylactic heparin therapy in the majority of cases to prevent thrombus extension. Fibrinolysis should be reserved for bilateral thrombosis with systemic effects. Despite improvements in screening and care, mean-term and long-term sequellae such as kidney atrophia, moderate renal insufficiency, systemic hypertension, and relapses in case of thrombophilia are still frequent and severe. A systematic follow-up by pediatric nephrologists is recommended.

The decrease of fibrinogen is an early predictor of the severity of postpartum hemorrhage.

BACKGROUND: Postpartum hemorrhage (PPH) is a major source of maternal morbidity. OBJECTIVES: This study's objective was to determine whether changes in hemostasis markers during the course of PPH are predictive of its severity. PATIENTS AND METHODS: We enrolled 128 women with PPH requiring uterotonic prostaglandin E2 (sulprostone) infusion. Two groups were defined (severe and non-severe PPH) according to the outcome during the first 24 hours. According to our criteria, 50 of the 128 women had severe PPH. Serial coagulation tests were performed at enrollment (H0), and 1, 2, 4 and 24 hours thereafter. RESULTS: At H0, and through H4, women with severe PPH had significantly lower fibrinogen, factor V, antithrombin activity, protein C antigen, prolonged prothrombin time, and higher D-dimer and TAT complexes than women with non-severe PPH. In multivariate analysis, from H0 to H4, fibrinogen was the only marker associated with the occurrence of severe PPH. At H0, the risk for severe PPH was 2.63-fold higher for each 1 gL(-1) decrease of fibrinogen. The negative predictive value of a fibrinogen concentration >4 gL(-1) was 79% and the positive predictive value of a concentration

[Normal and abnormal cytological aspects of peripheral blood cells in neonates and young children]. / Aspect cytologique normal et pathologique du sang chez le nouveau-né et le jeune enfant.

Morphological alterations of blood cells are observed early in most hereditary disorders. Therefore, the cytological study of the blood cells is a must for the diagnosis of these disorders in neonates and children. Knowledge of the quantitative and qualitative physiological peculiarities of blood cells in neonates is mandatory for an accurate interpretation. In the present article, the main cytological characteristics of blood cells in healthy neonates and infants and their abnormalities associated with hereditary or acquired blood disorders are reviewed.

Effect of individual plasma lipoprotein(a) variations in vivo on its competition with plasminogen for fibrin and cell binding: An in vitro study using plasma from children with idiopathic nephrotic syndrome.

Simultaneous natural changes in lipoprotein(a) [Lp(a)] and plasminogen occur in the nephrotic syndrome and offer a unique opportunity to investigate their effects on plasminogen activation under conditions fashioned in vivo. Plasminogen, Lp(a), and apolipoprotein(a) in plasma were characterized, and their competitive binding to carboxy-terminal lysine residues of fibrin and cell membrane proteins was determined in nephrotic children during a flare-up of the disease (61 cases) and after 6 weeks (33 cases) and 6 months (42 cases) of remission. Low plasminogen concentrations (median 1.34 micromol/L, range 0.39 to 1.96 micromol/L) and high Lp(a) levels (median 0.27 g/L, range 0.07 to 2. 57 g/L) were detected at flare-up. These changes were associated with an increased Lp(a) binding ratio onto fibrin (3.13+/-0.48) and cells (1.53+/-0.24) compared with binding ratios of control children (1.31+/-0.19 and 1.05+/-0.07, respectively) with normal plasminogen and low Lp(a) (median 0.071 g/L). After 6 weeks and 6 months of remission, the values for net decrease in Lp(a) binding to fibrin were 1.7+/-0.22 (after 6 weeks) and 1.88+/-0.38 (after 6 months) and were correlated with low Lp(a) concentrations (median 0.2 g/L, range 0.07 to 0.8 g/L; and median 0.12 g/L, range 0.07 to 1.34 g/L) and inversely associated with increased plasminogen levels (median 1.82 micromol/L, range 1.4 to 2.1 micromol/L; and median 1.58 micromol/L, range 1.1 to 2.1 micromol/L). These studies provide the first quantitative evidence that binding of Lp(a) to lysine residues of fibrin and cell surfaces is directly related to circulating levels of both plasminogen and Lp(a) and that these glycoproteins may interact as competitive ligands for these biological surfaces in vivo. This mechanism may be of relevance to the atherothrombotic role of Lp(a), particularly in nephrotic patients.

Recombinant tissue-type plasminogen activator therapy of thrombosis in 16 neonates.

We report 16 cases of neonatal vascular thrombosis treated with the same protocol for recombinant tissue-type plasminogen activator infusion. Flow restoration was complete in seven patients, partial in seven, and absent in two. Safety was satisfactory provided contraindications were respected.

The molecular genetic basis of Glanzmann's thrombasthenia in a gypsy population in France: identification of a new mutation on the alpha IIb gene.

Glanzmann's thrombasthenia is a rare inherited bleeding disorder caused by a qualitative or quantitative defect of platelet alpha IIb beta 3. We describe here a new mutation that is the molecular genetic basis of Glanzmann's thrombasthenia in two gypsy families. Our investigation was focused on the alpha IIb gene as a result of biochemical and immunologic analysis of patients' platelets showing undetectable alpha IIb but residual beta 3 levels. The entire alpha IIb cDNA was polymerase chain reaction (PCR) amplified using patients platelet RNA. Sequence analysis showed an 8-bp deletion located at the 3' end of exon 15. This deletion causes a reading-frame shift leading to a premature stop codon and the synthesis of a severely truncated form of alpha IIb. Genomic DNA study showed a G-->A substitution, the Gypsy mutation, at the splice donor site of intron 15. This mutation results in an abnormal splicing occurring at an alternative donor site located 8 bp upstream from the mutation. Based on those results, an allele-specific PCR analysis was developed to allow a rapid identification of the mutation in patients and potential carriers of the gypsy community. This PCR analysis can also be used for genetic counseling and antenatal diagnosis.

[Characteristics of the fibrinolytic system in the newborn]. / Particularités du système fibrinolytique du nouveau-né.

Recent development of microassays and determination of age-specific normal ranges have shed new light on the components and functioning of the neonatal fibrinolytic system. Plasminogen and tissue plasminogen activator levels are low in neonates, who generate plasmin more slowly and in smaller amounts than adults. Quantitative and qualitative changes occur as the fibrinolytic system matures. This is also true of the coagulation system responsible for the production of thrombin, which is the target for plasmin. These data are essential to assess the risk of thrombosis in neonates and, if appropriate, to guide management decisions including selection of a thrombolytic agent, of the optimal dosage, and of the best laboratory tests for monitoring purposes. Ongoing studies are investigating the mechanisms involved in neonatal lysis of thrombin clots occurring naturally or as the result of thrombolytic therapy.