PubMed Health⌕ Search

Biomedical subjects

M P Massicotte

Publications and source records attributed to M P Massicotte.

At least 19 recordsLinked to original sources
PubMed2004

Neonatal thrombosis and its treatment.

Thromboembolic disease (TE) has been described as the new epidemic of tertiary paediatrics, and no where is this more evident than in the neonatal population. As survival of premature and sick newborns has improved, the frequency of complications associated with intensive supportive therapy and monitoring has increased. Clinically significant thrombosis is emerging as one of the more common complications associated with improved neonatal outcome. The long-term implications of neonatal thrombosis are only just being realised. This systematic review will consider the epidemiology, diagnostic strategies, and outcome for both arterial and venous TE in neonates. The role of inherited thrombophilic abnormalities, and the evidence for anticoagulation therapy will also be considered. The lack of high level evidence in determining optimum therapy is obvious. Further research regarding diagnostic strategies, and optimal therapies is urgently needed.

Catheterization, Peripheral↗
PubMed2003

Use of low molecular mass heparin (enoxaparin) in newborn infants: a prospective cohort study of 62 patients.

OBJECTIVE: To detail low molecular mass heparin (enoxaparin) use in the first few months of life. DESIGN: Prospective, consecutive cohort of unselected newborn infants. METHODS: Newborn infants were divided into groups by gestational age, underlying condition, hepatic and renal function, thrombocytopenia, and prothrombin time (PT/INR). Groups were analysed with respect to many aspects of enoxaparin treatment using multivariate methods. RESULTS: Sixty two newborn infants received enoxaparin representing 5.39 treatment years. Thromboembolic events (TEs) occurred predominantly in the lower and upper venous system in the presence of indwelling catheters (69%). Preterm infants required longer than full term infants to achieve an anti-(factor Xa) level in the target range (six versus two days). Preterm infants required higher doses of enoxaparin than full term infants to maintain anti-(factor Xa) levels in the target range (2.1 v 1.7 mg/kg/12 h). Infants with congenital heart disease (CHD) required less enoxaparin than those without CHD to maintain an anti-(factor Xa) level in the target range (1.7 v 2.1 mg/kg/12 h). Impaired renal and liver function influenced the number of dose changes needed (three versus one a month). Complete or partial resolution of TE was accomplished in 59% of newborn infants. Four infants developed major bleeds (1.2% per patient year). Recurrent TE and clot extension occurred in three infants (0.9% per patient year). CONCLUSIONS: Preterm infants are more difficult to treat with enoxaparin than full term infants. Enoxaparin appears to be an alternative to treatment with standard heparin or no treatment.

Anticoagulants↗
PubMed2003

Thromboembolism in paediatric lupus patients.

Paediatric patients with systemic lupus erythematosus (SLE) and antiphospholipid antibodies (aPL), specifically lupus anticoagulants (LAC) are at high risk of developing thromboembolic events (TE). Our objectives were to determine the prevalence of TE in paediatric SLE patients with LAC and to determine if anticoagulation was effective to decrease morbidity, and prevent recurrent TE. We reviewed data on 149 paediatric SLE patients treated over 10 years. In all, 24 patients (16%) were LAC positive, and 21 TE occurred in 13 of these LAC positive patients (54% incidence of TE in LAC positive patients). The events were cerebral venous thrombosis (9), arterial stroke (3), deep venous thrombosis (4), pulmonary embolism (2), other venous event (1) and other arterial events (2). The median duration between SLE diagnosis and first TE was 15.2 months (range 0-62), and the median age at first TE was 15.1 years (range 11.4-18.4). Long-term anticoagulation was prescribed, and eight patients (62%) were transferred to adult care on lifelong oral warfarin; four (31%) remain under our care on lifelong warfarin, and one patient died of causes unrelated to her TE. No patient has been identified with deficiencies of protein C, protein S or antithrombin III. One patient is heterozygous for Factor V Leiden, and one is heterozygous for both the Prothrombin 20210A mutation and the MTHFR (methylene tetrahydrofolate reductase) mutation. Four patients had recurrent TE (31%), and three were not anticoagulated at the time of their second event. One patient had two recurrences on therapeutic anticoagulation. Thromboembolic events are prevalent in the LAC positive paediatric SLE population, and consideration for lifelong anticoagulation must occur after an initial TE.

Adolescent↗
PubMed2001

Venous thromboembolism in pediatrics.

Venous thromboembolism (VTE) in pediatrics is quickly becoming a well-recognized cause of significant morbidity and mortality in children. Most children diagnosed with VTE have a serious underlying primary illness such as cancer, chronic total parenteral nutrition (TPN) dependency, or congenital heart disease. Infants and adolescents are most at risk of developing VTE, and the most significant risk factor is the presence of a central venous line (CVL). The incidence of VTE varies widely with study design and the diagnostic test used to detect thrombosis. Venography remains the gold standard diagnostic test, although ultrasound is increasingly used due to its noninvasive nature, despite concern regarding the sensitivity in upper system VTE. The treatment of uncomplicated VTE in children consists primarily of unfractionated heparin (UFH) initially, followed by oral anticoagulation or low molecular weight heparin (LMWH) for 3 months. LMWH offers many advantages over UFH due to the longer half-life, increased bioavailability, and ease of administration and monitoring in children. Acute complications of VTE in children are numerous and include pulmonary embolism (PE), chylothorax, and superior vena cava syndrome. Long-term morbidity includes recurrent VTE, postthrombotic syndrome, repeat general anesthetics for CVL placement, and eventual destruction of the upper venous system in children with repeat CVL-related VTE. Death from VTE is rare and is primarily due to PE.

Anticoagulants↗
PubMed2001

The use of alteplase to restore patency of central venous lines in pediatric patients: a cohort study.

We evaluated the efficacy and safety of alteplase to restore central venous line (CVL) patency in a consecutive cohort study. A uniform, weight-dependent protocol for alteplase administration was established prospectively. For children < or =10 kg, a dose of 0.5 mg was used; for children >10 kg, doses of 1 to 2 mg were used. The alteplase remained instilled for 1 to 4 hours or overnight. Retrospective data accrual found that 25 children received alteplase for a total of 34 courses; 29 (85%) of the 34 courses of alteplase completely restored CVL patency. Alteplase appears to be a safe and effective thrombolytic agent for CVL patency restoration in children.

Catheterization, Central Venous↗
PubMed2000

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.

Adolescent↗
PubMed2000

Outcome of pediatric thromboembolic disease: a report from the Canadian Childhood Thrombophilia Registry.

The outcome for children with deep vein thrombosis (DVT) and pulmonary embolism (PE) is unknown. An understanding of morbidity and mortality of DVT/PE is crucial to the development of rational treatment protocols. The Canadian Childhood Thrombophilia Registry has followed 405 children aged 1 mo to 18 y with DVT/PE for a mean of 2.86 y (range, 2 wk to 6 y) to assess outcome. The all-cause mortality was 65 of 405 children (16%). Mortality directly attributable to DVT/PE occurred in nine children (2.2%), all of whom had central venous line-associated thrombosis. Morbidity was substantial, with 33 children (8.1%) having recurrent thrombosis, and 50 children (12.4%) having postphlebitic syndrome. Recurrent thrombosis and postphlebitic syndrome were more common in older children, although deaths occurred equally in all age groups. The incidence of recurrent thrombosis and postphlebitic syndrome are likely underestimated because of difficulties in diagnosis, especially in younger children. The significant mortality and morbidity found in our study supports the need for international multicenter randomized clinical trials to determine optimal prophylactic and therapeutic treatment for children with DVT/PE.

Adolescent↗
PubMed1999

A randomized trial comparing 5-mg and 10-mg warfarin loading doses.

BACKGROUND: Warfarin sodium therapy is usually initiated with a loading dose to reduce the time required to elevate the international normalized ratio (INR). Warfarin loading doses are associated with early overanticoagulation and the development of a potential hypercoagulable state; they also may not hasten achieving an INR value between 2.0 and 3.0. This study was designed to prospectively confirm our observation that a 5-mg warfarin sodium loading dose is as effective as a 10-mg loading dose in achieving a therapeutic INR for 2 consecutive days on days 3 and 4 or 4 and 5 of therapy. METHODS: Fifty-three patients initiating warfarin therapy with a target INR of 2.0 to 3.0 were randomly allocated to receive an initial dose of 5 or 10 mg of warfarin. Subsequent doses were based on dosing algorithms. The INR was measured daily for 5 days. The primary end point of the study was the proportion of patients whose INR values were between 2.0 and 3.0 on 2 consecutive daily determinations on days 3, 4, or 5 of the study and whose INR did not exceed 3.0 at any point during the study. RESULTS: Five (24%) of 21 patients in the 10-mg group and 21 (66%) of 32 patients in the 5-mg group achieved the primary end point (relative risk 2.22, 95% confidence interval 1.30-3.70 [P < .003]). A trend toward less overanticoagulation was seen in the 5-mg warfarin group. CONCLUSION: A 10-mg loading dose of warfarin is unlikely to be more effective than a 5-mg loading dose in achieving an INR of 2.0 to 3.0 by day 4 or 5 of therapy.

Aged↗
PubMed1998

Prothrombotic disorders in infants and children with cerebral thromboembolism.

BACKGROUND: To our knowledge, the contribution of prothrombotic conditions to cerebral thromboembolism has never been prospectively studied in a large series of pediatric patients. METHODS: The Hospital for Sick Children, Toronto, Ontario, established a program in January 1992 to diagnose and treat children (term newborn to 18 years old) with arterial ischemic stroke or sinovenous thrombosis. The routine evaluation for prothrombotic conditions included plasminogen, antithrombin, protein C, free protein S, activated protein C resistance, IgG and IgM anticardiolipin antibody, and lupus anticoagulant. We analyzed samples taken within 2 years of the event. We report results on patients seen from January 1, 1992, to January 1, 1997. RESULTS: Ninety-two patients (47 males and 45 females) entered the program during the study interval. Patients ranged from newborn to 18 years in age. Arterial ischemic stroke occurred in 78% of patients while sinovenous thrombosis occurred in 22%. All were tested for prothrombotic disorders. One or more abnormal results were present in 35 (38%) of the 92 patients. The majority (21/35) had multiple abnormal test results. The abnormal test results were anticardiolipin antibody (33%), plasminogen (9.5%), activated protein C resistance (9%), protein C (7%), antithrombin (12.5%), lupus anticoagulant (8%), and free protein S (11.5%). Male sex predicted the presence of prothrombotic abnormalities (relative risk, 1.7; 95% confidence interval, 1.2-2.5), but stroke type (relative risk, 0.8; 95% confidence interval, 0.7-1.1), age group, and presence of other risk factors did not predict abnormal testing. CONCLUSIONS: A significant proportion (38%) of children with cerebral thromboembolism had evidence of prothrombotic conditions. In particular, there was a predominance of children with anticardiolipin antibody (33%). These data support a recommendation that children with cerebral thromboembolism be evaluated for prothrombotic disorders.

Adolescent↗
PubMed1998

Central venous catheter related thrombosis in children: analysis of the Canadian Registry of Venous Thromboembolic Complications.

BACKGROUND: Central venous lines (CVLs) are frequently associated with deep venous thrombosis (DVT) in children; however, little is known about the epidemiologic characteristics or outcome of CVL-related DVT. METHODS: The Canadian Childhood Thrombophilia Registry monitored 244 consecutive patients with objectively diagnosed CVL-related DVT for a median duration of 24 months (range 3 months to 7 years). RESULTS: The incidence of CVL-related DVT was 3.5 per 10,000 hospital admissions. CVL-related DVTs were more frequent in the upper venous system. Ultrasonography or echocardiography were the most commonly used diagnostic tests (n = 183 patients). Venograms were performed on 82 (34%) patients. A variety of therapies were used. Thirty-nine children had pulmonary emboli, but most were not investigated for pulmonary emboli. Nine (3.7%) children died as a consequence of their thromboembolic disease. Recurrent DVT occurred in 16 (6.5%) children, and postphlebitic syndrome occurred in 23 (9.5%) children. CONCLUSION: Currently no uniform guidelines exist for the prevention and management of CVL-related DVT in children. The frequency and clinical consequences of CVL-related DVTs justify controlled trials of primary prophylaxis in children requiring central venous access.

Adolescent↗
PubMed1998

Guidelines for antithrombotic therapy in pediatric patients.

Because of the relatively low incidence of TEs in children, the diagnostic and therapeutic approaches used are largely extrapolated from guidelines for adults. Features that differ in children compared with adults include underlying disorders, high incidence of CVL-related DVT in the upper venous system, and response to SH, warfarin, and thrombolytic agents. There is a paucity of information on the risk/benefit ratio of the therapeutic interventions and long-term outcome. Clinical trials are urgently needed to clarify optimal management for pediatric patients with TEs.

Causality↗
PubMed1998

Homozygous protein C deficiency: description of a new mutation and successful treatment with low molecular weight heparin.

We present a kindred with a new mutation of the protein C gene, in which the proband had an unusual clinical presentation. The relationship between warfarin induced skin necrosis and level of anticoagulation was investigated. The pharmacokinetics of protein C concentrate was assessed to determine frequency of replacement therapy. The clinical and biochemical efficacy of therapy with low molecular weight heparin (LMWH) was assessed. The effect of long-term LMWH on bone density in the growing child was monitored using whole body densitometry. Warfarin therapy required an INR of greater than 3.5 to avoid skin necrosis. If protein C replacement was to be used, doses of 100 U/kg/day would have been required to maintain protein C levels consistently at or above 0.20 U/ml. While receiving prophylactic therapy with LMWH for almost 3 years, there were no episodes of recurrent thrombosis, no skin necrosis and no bleeding. Biochemical markers of in vivo thrombin generation were suppressed and within the normal range. Bone density continued to increase at the normal rate throughout the treatment period. LMWH is an effective form of long-term therapy for homozygous protein C deficient patients with measurable protein C levels.

Adult↗
PubMed1997

Comparison of 5-mg and 10-mg loading doses in initiation of warfarin therapy.

BACKGROUND: Loading doses of warfarin that are larger than those used for maintenance therapy are widely used in clinical practice, but they have never been prospectively evaluated. OBJECTIVE: To compare the effect of 5- and 10-mg loading doses of warfarin on laboratory markers of warfarin's anticoagulant effect. DESIGN: Randomized clinical trial. SETTING: Tertiary care teaching hospital. PATIENTS: 49 patients seen over a 5-month period with a target international normalized ratio (INR) of 2.0 to 3.0. INTERVENTION: Patients were randomly assigned to receive an initial dose of 5 or 10 mg of warfarin. Subsequent doses of warfarin were administered on the basis of dosing nomograms. MEASUREMENTS: INRs and levels of factors II, VII, IX, and X and protein C were measured daily for 5 days. RESULTS: 11 of 25 patients in the 10-mg group (44% [95% CI, 34% to 54%]) and 2 of 24 patients in the 5-mg group (8% [CI, 3% to 14%]) had INRs greater than 2.0 at 36 hours (P = 0.005), at which time the factor VII levels were 27% (CI, 18% to 36%) in the 10-mg group and 54% (CI, 43% to 65%) in the 5-mg group (P < 0.001). In contrast, factor II levels were 74% (CI, 67% to 81%) in the 10-mg group and 82% (CI, 73% to 93%) in the 5-mg group (P > 0.2). At 60 hours, 9 of 25 patients in the 10-mg group (36% [CI, 17% to 54%]) and no patients in the 5-mg group had INRs greater than 3.0. At 84 hours, 15 of 24 patients in the 10-mg group (63% [CI, 43% to 81%]) and 19 of 24 patients in the 5-mg group (79% [CI, 62% to 95%]) had INRs between 2.0 and 3.0. Four patients in the 10-mg group and 1 patient in the 5-mg group received vitamin K for excessive prolongation of the INR. CONCLUSIONS: A 5-mg loading dose of warfarin produces less excess anticoagulation than does a 10-mg loading dose; the smaller dose also avoids the development of a potential hypercoagulable state caused by precipitous decreases in levels of protein C during the first 36 hours of warfarin therapy.

Anticoagulants↗
PubMed1995

A novel and rapid whole-blood assay for D-dimer in patients with clinically suspected deep vein thrombosis.

BACKGROUND: The clinical utility of using a novel whole blood assay for D-dimer (SimpliRED), alone or in combination with impedance plethysmography (IPG), was investigated in a two-center, prospective cohort study of 214 consecutive patients with clinically suspected deep vein thrombosis (DVT). METHODS AND RESULTS: All patients underwent the SimpliRED D-dimer assay, contrast venography, and IPG. According to the results of venography, 43 patients had proximal DVT (popliteal and/or more proximal veins), 10 had isolated calf DVT, and 161 had DVT ruled out. The D-dimer had a sensitivity of 93% for proximal DVT and of 70% for calf DVT, an overall specificity of 77%, and a negative predictive value of 98% for proximal DVT. The sensitivity and specificity of IPG for proximal DVT were 67% and 96%, respectively. When analyzed in combination with the IPG results, it was determined that (1) the combination of a negative D-dimer and a normal IPG had a negative predictive value of 97% for all DVT and of 99% for proximal DVT and occurred in 58% of patients (likelihood ratio, 0.1) and (2) the combination of a positive D-dimer and an abnormal IPG had a positive predictive value of 93% for any DVT and of 90% for proximal DVT and occurred in 14% of patients (likelihood ratio, 42.6). When the D-dimer and IPG results were discordant, it was not possible to exclude or diagnose DVT reliably; discordant results occurred in 28% of patients. CONCLUSIONS: The SimpliRED D-dimer assay, which can be performed and interpreted at the bedside within 5 minutes, has great potential in patients with clinically suspected DVT, especially for ruling out DVT, and is complementary to IPG. The assay should be evaluated in large clinical management studies.

Agglutination Tests↗