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Biomedical subjects

M Andrew

Publications and source records attributed to M Andrew.

At least 127 records · Page 7Linked to original sources
PubMed1994

Oral anticoagulation therapy in pediatric patients: a prospective study.

There are no validated guidelines for administering or monitoring oral anticoagulant therapy in pediatric patients. A pediatric thromboembolism program at the Hospital for Sick Children, Toronto, prospectively monitored consecutive children requiring warfarin over an 18 month period. A uniform protocol was followed and dose adjustments based upon international normalized ratios (INRs). One hundred and fifteen consecutive children; 68 males and 47 females, received warfarin. The age distribution was: <1y (19); 1-5 ys (33); 6-10 ys (20); 11-18 ys (43). Warfarin was used for secondary prevention of venous thromboembolism (n = 56) and primary prevention of thromboembolism (n = 59). Underlying disorders included: congenital heart disease (CHD) without mechanical valves (MV) (49); CHD with MV (18); cancer (8); longterm total parenteral nutrition (7); renal disorders (10); other (23). Treatment length was considered as short term (3-6 mths) n = 37 (32%); longterm (> 6 mths) n = 38 (33%); and life-long n = 40 (35%) of children. While receiving warfarin, 95 children received concurrent longterm treatment with other drugs: 1 drug (28); 2 drugs (27); 3 drugs (21); 4 or more drugs (19). The amounts of warfarin/kg required to achieve INRs of 2 to 3 decreased with increasing age. Children <1 year of age required 0.32 +/- 0.05 mg/kg whereas children 11-18 yrs required 0.09 +/- 0.01 mg/kg; P < 0.001. Monitoring warfarin required an average of 4.0 measurements per month and 1.5 dose changes per month. Changes in warfarin doses were primarily precipitated by drugs, intermittent illness, and changes in diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1994

Thrombin regulation in congenital heart disease after cardiopulmonary bypass operations.

Children with cyanotic congenital heart disease who undergo operation with cardiopulmonary bypass are at increased risk of thromboembolic or hemorrhagic complications, or both. Regulation of thrombin, a key enzyme in coagulation, is essential in preventing these complications. We therefore examined the in vitro capacity of plasma from 15 children with cyanotic congenital heart disease to generate thrombin and to inhibit 125I-thrombin before and after cardiopulmonary bypass. We also assessed whether thrombin had been generated in vivo by assaying levels of fibrinogen, thrombin-antithrombin III complexes, and D-dimer. Plasma levels of the thrombin inhibitors, antithrombin III, alpha-2-macroglobulin, and heparin cofactor II were also measured. Thrombin regulation was normal before operation. After cardiopulmonary bypass, the in vitro capacity to generate thrombin decreased by 50%, and this was primarily a result of hemodilution (31%). Similar postoperative decreases were noted in the levels of antithrombin III, heparin cofactor II, and alpha-2-macroglobulin (26% to 45%). However, the total in vitro plasma thrombin inhibitory capacity decreased by only 13%. Levels of thrombin-antithrombin III and D-dimer increased after operation, indicating that thrombin had been generated and inhibited in vivo. Clinically, there were no thromboembolic complications although six patients required replacement therapy for excessive small-vessel bleeding. In conclusion, thrombin regulation is significantly altered after cardiopulmonary bypass. Although thrombin is generated in vivo, the total residual capacity to do so is impaired because of hemodilution. Despite a concomitant decrease in thrombin inhibitor levels, the total residual in vitro capacity of plasma to inhibit thrombin is relatively spared. This suggests that after cardiopulmonary bypass the risk of hemorrhagic complications after an additional hemostatic challenge is relatively greater than the risk of thrombotic complications. This might be reflected in the predominance of hemorrhagic complications in our patients.

Adolescent↗
PubMed1993

Heparin therapy during cardiopulmonary bypass in children requires ongoing quality control.

Heparin therapy for children undergoing cardiopulmonary bypass (CPB) is monitored in the operating room by automated whole blood activated clotting times (ACT). For many years our institution used Hemochron (HC) ACT machines but changed to HemoTec (HT) ACT machines because they required a smaller blood sample and provided results in duplicate. When HemoTec ACT machines were introduced at our institution, the surgical team was concerned that increased amounts of heparin were being administered to our patients during CPB. This study was conducted to investigate the potential mechanisms responsible for these clinical observations. First, we compared ACT values on ex vivo blood samples from 20 consecutive pediatric patients (6 samples each) during CPB. The HC ACT values were significantly and systematically increased over HT ACT values (HC: 750 +/- 40 vs HT: 418 +/- 26, Mean +/- SEM, p < 0.01). 94% of all HC ACT values were above 450 s compared to only 27% of HT ACT values. If HT ACT values had been used for patient monitoring, all patients would have received more heparin to achieve ACT values above 450 s. The two machines reported similar ACT values when heparin was added in vitro to whole blood (0.1-5.0 units/ml), (HC: Y = 98X + 104, r2 = 0.93 HT: Y = 82X + 109, r2 = 0.94). Heparin concentrations in our patients following a bolus of 300 U/kg of heparin, but prior to CPB were 3.2 +/- 0.07 units/ml. Following the initiation of CPB, heparin concentrations decreased to 1.3 +/- 0.05, reflecting, in part hemodilution by the pump prime (1 U of heparin/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Plasma dermatan sulfate proteoglycan in a patient on chronic hemodialysis.

A 68-year-old man on chronic hemodialysis for 6 years, presented with a spontaneous psoas muscle hemorrhage. Investigations showed intermittently elevated activated partial-thromboplastin time and thrombin time. Preliminary investigations suggested a heparin-like inhibitor in the patient's plasma, but no anti-Xa activity could be detected. Investigation of the ability of patient plasma to inhibit exogenous thrombin showed that most thrombin was inhibited by heparin cofactor II, in contrast to normal plasma in which most thrombin was inhibited by antithrombin III. Treatment of plasma with glycosaminoglycan-degrading enzymes suggested the presence of dermatan sulfate (DS) in patient plasma. This was confirmed in a heparin cofactor II-dependent antithrombin assay for DS that showed anticoagulant equivalent to 2.2 +/- 0.3 micrograms/mL (mean +/- SD) of porcine mucosal DS. Of this activity, approximately 90% was sensitive to enzymes that degrade DS. The glycosaminoglycan containing fraction of plasma was isolated and subjected to gel chromatography. Anticoagulant activity eluted from Sephadex G-100 (Pharmacia, Montreal, Quebec, Canada) as two peaks with Kav of 0.10 and 0.45. After treatment with base, the Kav of the higher molecular weight species was increased to 0.55. This activity was completely sensitive to enzymes that degrade DS. Thus, the active DS was present as a proteoglycan. The lower molecular weight material was not sensitive to enzymes that degrade DS or heparan sulfate and it was active in the heparin cofactor II-dependent antithrombin assay but not in an antithrombin III-dependent antithrombin assay. This activity was not degraded by heating. Subsequently, measurement of DS activity was performed in plasmas obtained from eight other patients on hemodialysis before administration of heparin that showed that all patients had DS activity present that varied from 0.05 to 0.4 microgram/mL. No enzyme-resistant activity could be shown in these patients. In summary, a circulating anticoagulant with properties of DS is present in patients requiring hemodialysis.

Aged↗
PubMed1993

Pharmacy personnel and fever: a study on perception, self-care and information to customers.

To study the fever perception and self-care of pharmacy personnel as well as the information given to customers about the management of fever problems, a random sample of 152 Norwegian pharmacists and 150 pharmacy technicians were interviewed, in 1989, by a national opinion poll company. One-third thought that body temperatures between 39.0 degrees C and 40.5 degrees C could be life-threatening. Of all respondents 24% (33% of technicians, 16% of pharmacists) assumed body temperatures to be rising when sweating accompanied fever. In cases of common cold or influenza accompanied by fever 56% of the personnel would use antipyretics. 7% Of the staff (14% of technicians, 1% of pharmacists) believed penicillin to be effective against viral infections. Antipyretic drug preferences were consistent, but a wide range of perceptions was revealed, in particular with respect to start of antipyretic therapy and seeking medical care for children. Undergraduate and postgraduate education of pharmacy personnel should aim more at satisfying the demand for information of the general public and focus more on the symptomatic treatment of fever and minor illness in general. Pharmacists in charge have a special responsibility in counselling their assistants.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1993

[Do we need new guidelines on iron supplementation during pregnancy?].

Studies have shown that the present official Norwegian recommendations on iron supplementation during pregnancy are not followed. A meeting was arranged in February 1993 to discuss the need to change the recommendations. The article describes the conclusions of the panel. It was proposed that the iron status of the pregnant woman, determined as serum ferritin concentration, should be measured early (before the 15th week of gestation) and iron supplement should be given as selective prophylaxis based on the serum ferritin level. The Directorate of Public Health has been asked to issue new recommendations.

Female↗
PubMed1993

[Pregnancy and iron supplementation--are the official guidelines followed?].

In the present study we have examined to what extent the national recommendations concerning iron supplements during pregnancy are being followed. 222 women in childbed were interviewed within one week after delivery concerning their intake of iron and other dietary supplements. We found that no more than 1/4 of the women were using iron supplements according to the national recommendations and that the advice given by doctors, midwives or public health nurses varied considerably. 70% of the women were recommended to take iron supplement, but no more than 66% of them were given specific advice as to which iron preparation they should take, or in what doses. The specific advice that was given varied. 93% of the women who were advised to take iron supplement followed this advice. More women took low-dose iron preparations, while more doctors recommended high-dose preparations. Only 30% of the women thought that iron supplement is vital for all pregnant women. We also found that many of the women (59%) took one or more dietary supplements, alone or in addition to iron.

Female↗
PubMed1993

Do coagulation screening tests detect increased generation of thrombin and plasmin in sick newborn infants?

BACKGROUND: Disseminated intravascular coagulation (DIC) is usually diagnosed in sick infants who have prolonged clotting times, depletion of platelets and coagulation factors, and elevated levels of fibrin derivatives. However, the diagnostic accuracy of abnormal coagulation profiles in neonates at risk of DIC has been uncertain. Since DIC is characterized by activation of both the coagulation and fibrinolytic systems, the objective of this study was to determine whether coagulation screening tests correctly identify infants with biochemical evidence of increased thrombin and plasmin generation. METHODS: Non-surgical patients in a tertiary care nursery who were sick enough to require an indwelling arterial catheter for monitoring purposes, were enrolled in a prospective cohort study. Blood samples for thrombin/antithrombin III (TAT) complexes and the plasmin-derived fibrinopeptide B beta 1-42 were drawn 36 to 72 h after birth from a free-flowing arterial line. Platelet counts, D-Dimer levels, plasma fibrinogen concentrations and prothrombin times, expressed as International Normalized Ratios or INR, were measured at the same time. RESULTS: One hundred patients were studied. Fifty-seven infants had elevated levels of TAT (> or = 4 micrograms/l) and B beta 1-42 (> or = 4 nmol/l). The sensitivities of platelets < 150 x 10(9)/l, D-Dimer > 500 ng/ml, fibrinogen < 1.5 g/l, and INR > 1.5 were 39%, 30%, 12%, and 11%, respectively. Corresponding specificities were 88%, 91%, 98%, and 95%. CONCLUSIONS: Abnormal coagulation screens in sick newborn infants strongly support a diagnosis of DIC. However, normal screens do not exclude activation of the coagulation and fibrinolytic systems.

Antithrombin III↗
PubMed1993

An antithrombin III assay based on factor Xa inhibition provides a more reliable test to identify congenital antithrombin III deficiency than an assay based on thrombin inhibition.

OBJECTIVES: To determine whether functional antithrombin III (AT-III) levels measured by a factor Xa inhibition (AT-III-Xa) assay identifies AT-III deficient individuals more reliably than functional AT-III levels measured by a thrombin inhibition (AT-III-IIa) assay. STUDY DESIGN: Cross-sectional study. PATIENT POPULATION: Sixty-seven members of a large family with type 2 AT-III deficiency. INTERVENTION: DNA analysis was used as the reference diagnostic standard for AT-III status and subjects were classified as AT-III deficient or non deficient according to these results. Functional AT-III levels were measured in all subjects using: 1) a chromogenic substrate for thrombin and added human thrombin (AT-III-IIa), and 2) a chromogenic substrate for factor Xa and added bovine factor Xa (AT-III-Xa). Functional heparin cofactor II (HC-II) levels were measured using a commercially available kit. The proportions of 125I-alpha-thrombin complexed to AT-III and HC-II were measured by polyacrylamide gel electrophoresis and autoradiography. RESULTS: Thirty-one (46%) individuals were classified as AT-III deficient and 36 (54%) as AT-III non deficient. AT-III-Xa assay measured a significantly lower mean AT-III value and a narrower range for individuals classified as AT-III deficient than the AT-III-IIa assay. Using the AT-III-IIa assay, six subjects had borderline AT-III levels compared to none with the AT-III-Xa assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

A comparative study of heel-stick devices for infant blood collection.

OBJECTIVE: To evaluate two heel-stick devices by comparing the volume of blood collected, blood sampling time, amount of hemolysis, pain inflicted during the procedure, and extent of bruising. DESIGN: Randomized trial. SETTING: Primary care center in a tertiary-level perinatal hospital. PARTICIPANTS: Forty healthy, full-term newborns with a postnatal age of greater than 24 hours. Newborns were fed no more than 1 1/2 hours before blood sample collection and fulfilled the requirement for routine phenylketonuria and thyroid screening. INTERVENTIONS: Newborns were allocated to a single stab with either an automated incision or a lancet puncture device. MEASUREMENTS/MAIN RESULTS: The total volume of blood and blood sampling time were significantly better with the automated incision device (P < .001). Hemolysis was also reduced with the automated incision device (P < .03). Plasma hemoglobin levels were below 1.0 g/L in all samples obtained with the automated incision device and in 71% of samples obtained with the lancet device. There were no differences in the extent of bruising or in pain symptoms manifested by mean increases in heart rate and percentage of time crying during the procedure. CONCLUSIONS: The larger volume of blood obtained within a shorter period for blood collection and reduced hemolysis with the automated incision device make it a preferred instrument for neonatal blood collection.

Birth Weight↗
PubMed1993

A prospective, randomized trial of high-dose intravenous immune globulin G therapy, oral prednisone therapy, and no therapy in childhood acute immune thrombocytopenic purpura.

Fifty-three children, aged 7 months to 14.4 years and with typical acute immune thrombocytopenic purpura and platelet counts < or = 20 10(9)/L, were randomly assigned to receive intravenously administered immune globulin G (IVIG), 1 gm/kg per day for 2 consecutive days (n = 19); orally administered prednisone, starting at a dose of 4 mg/kg per day, with tapering and discontinuation of corticosteroids by day 21 (n = 18); or no therapy (n = 16). Both IVIG and prednisone resulted in significantly fewer days with platelet counts < or = 20 x 10(9)/L in comparison with no therapy (median, 1 and 2 days vs 4 days; corresponding ranges, 1 to 20 and 1 to 11 days vs 1 to 132 days; p < 0.01). Reversal of clinically important thrombocytopenia assessed by the number of days taken to achieve a platelet count of > or = 50 x 10(9)/L was significantly faster in children randomly assigned to receive IVIG (median, 2 days; range, 1 to 34 days) than in those receiving prednisone (median, 4 days; range, 2 to 13 days; p < 0.001) or no therapy (median, 16 days; range, 2 to 132 days; p < 0.001). Because the risk of intracranial hemorrhage in children with acute immune thrombocytopenic purpura is highest in the group with severe thrombocytopenia, and appears to be restricted to children with platelet counts < or = 20 x 10(9)/L, these results support the use of IVIG or high doses of prednisone as initial therapy in children with acute immune thrombocytopenic purpura and severe thrombocytopenia (platelet counts < or = 20 x 10(9)/L).

Administration, Oral↗
PubMed1993

A randomized, controlled trial of platelet transfusions in thrombocytopenic premature infants.

A multicenter prospective, randomized controlled trial was conducted to determine whether early use of platelet concentrates would reduce the incidence or extension of intracranial hemorrhage or both in sick preterm infants with thrombocytopenia. The effects on bleeding as reflected by the amount of blood product support administered and a shortened bleeding time were assessed as secondary outcomes. Premature infants with a platelet count < 150 x 10(9)/L within the first 72 hours of life were randomly assigned to receive either conventional therapy or conventional therapy plus platelet concentrates (10 ml/kg). The platelet count was maintained < 150 x 10(9)/L until day 7 of life by one to three platelet transfusions. In 22 (28%) of the 78 treated infants and 19 (26%) of the 74 control infants, either a new intracranial hemorrhage developed or an already-present one became more extensive (p = 0.73). Similar numbers of infants had each grade of intracranial hemorrhage on both initial and follow-up ultrasonography. Similar numbers of infants received fresh frozen plasma and packed red blood cells, but treated infants received less of both. The bleeding time was prolonged in the treated group before the infusion of platelet concentrates but subsequently shortened (mean difference, 79.0; 95% confidence interval, 73.1 to 84.9). Subanalysis of the control group showed that infants with platelet counts < 60 x 10(9)/L (n = 21) on at least one occasion received more fresh frozen plasma and packed red blood cells than did those with platelet counts > 60 x 10(9)/L.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Component Transfusion↗
PubMed1993

Standardization of prothrombin times in newborn infants.

The prothrombin time (PT) for patients receiving warfarin varies widely, reflecting the heterogeneity of thromboplastin reagents. The International Committee on Thrombosis and Haemostasis recommends that PT values for these patients be expressed as international normalized ratios. This study showed that thromboplastin reagents also significantly influence PT values in neonatal plasma and that expressing PT values as international normalized ratios decreases this variability.

Adult↗
PubMed1993

Heparin-induced thrombocytopenia and thrombosis: clinical and laboratory studies.

Heparin-induced thrombocytopenia is one of the most common and important immunological complications of drug therapy. Most patients with heparin-induced thrombocytopenia have isolated thrombocytopenia, which by itself seldom causes serious morbidity. However, a small proportion of patients also develop an acute arterial thrombotic episode which can be fatal. It remains uncertain why some patients have only isolated thrombocytopenia, whereas others have thrombotic complications. In this report we describe 53 patients with heparin-induced thrombocytopenia in whom the diagnosis was confirmed using the platelet 14C-serotonin release assay. The intent of the study was to look for laboratory or clinical characteristics that could be used to predict which patients will have the less serious thrombocytopenia and which patients will have thrombocytopenia plus thrombotic complications. The laboratory markers included AT-III, protein C, protein S and heparin cofactor II. No serological result identified whether a patient was at risk of having isolated thrombocytopenia or an acute thrombotic event. However, during the acute thrombocytopenic episode, there was evidence of global activation of the coagulation cascade as evidenced by reductions in the level of protein C, heparin cofactor II and antithrombin III. Following resolution of the thrombocytopenia, these inhibitory factors returned to normal indicating that the thrombotic complications were not caused by a familial deficiency. We did observe a highly significant association (P < 0.001) between concomitant cardiovascular complications and the occurrence of an arterial thrombosis in patients with heparin-induced thrombocytopenia. Recent surgery of any type was strongly associated with venous thrombi (P < 0.001). Our data suggest that heparin-induced thrombocytopenia is a procoagulant disorder with thrombosis tending to occur at sites of pre-existing pathology.

Acute Disease↗
PubMed1993

Overtight nappy precipitating thrombosis in antithrombin III deficiency.

An antithrombin III deficient infant presented with iliac vein thrombosis, apparently precipitated by an overtight nappy. Venous thrombosis is unusual, both in normal and in antithrombin III deficient children, but children with venous thrombosis should have their natural anticoagulants assayed and obvious risk factors avoided.

Antithrombin III Deficiency↗