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Biomedical subjects

P Brill-Edwards

Publications and source records attributed to P Brill-Edwards.

At least 37 records · Page 2Linked to original sources
PubMed1994

Use of Hirulog in the prevention of venous thrombosis after major hip or knee surgery.

BACKGROUND: The study objective was to determine whether Hirulog, a direct thrombin inhibitor, has potential efficacy and safety in the prevention of deep vein thrombosis (DVT) in orthopedic patients. A phase 2 open-label, dose-escalating design was used to study 222 unselected patients undergoing major hip or knee surgery in tertiary-care, university-affiliated hospitals. METHODS AND RESULTS: Subcutaneous Hirulog was initiated postoperatively. Patients were evaluated for bleeding and symptomatic pulmonary embolism, and mandatory bilateral venography was performed before discharge. Dose escalations were made on the basis of observed rates of bleeding and venous thrombosis. There were five dosage regimens used: 0.3 mg/kg every 12 hours, 0.6 mg/kg every 12 hours, 1.0 mg/kg every 12 hours for 3 days followed by 0.6 mg/kg every 12 hours for up to 11 days, 1.0 mg/kg every 12 hours, and 1.0 mg/kg every 8 hours. One hundred seventy-seven patients who had technically adequate bilateral venography or objectively documented pulmonary embolism were included in the primary analysis of efficacy. The highest dosage regimen (1.0 mg/kg every 8 hours) provided the lowest rates of total DVT (17%) and proximal DVT (2%), both of which were significantly lower (P = .010 and P = .023, respectively) than the pooled rates of total (43%) and proximal (20%) DVT seen with the first four regimens. Bleeding rates were low (< 5%) with all regimens. CONCLUSIONS: This study demonstrates that 1.0 mg/kg Hirulog every 8 hours started postoperatively is potentially efficacious and safe for the prevention of DVT after major hip or knee surgery.

Aged↗
PubMed1994

Heparin therapy in pediatric patients: a prospective cohort study.

Current guidelines for heparin therapy in pediatric patients have been extrapolated from trials in adult patients without rigorous evaluation of efficacy and safety. We prospectively monitored consecutive pediatric patients receiving systemic doses of heparin over 10 mo at one institution using a predetermined nomogram to monitor maintenance therapy. Sixty-five consecutive children; 38 males and 27 females, received systemic doses of heparin. Thirty children had deep venous thrombosis and/or pulmonary embolism; 11 had arterial thrombi, most frequently after diagnostic angiography; and the remaining 24 received heparin prophylactically, for congenital heart disease. Twenty-nine (45%) of the 65 patients were less than 1 y of age and 22 (34%) were 10 y or older. Congenital heart disease was the predominant diagnosis under 1 y and deep venous thrombosis in older children. After a bolus dose of 50 U/kg, 39% of children (n = 30) achieved a minimal level activated partial thromboplastin time (APTT). Sixty-eight percent of children achieved a minimal level APTT by 24 h and 81% by 48 h. For all 65 children, APTT values were within the therapeutic range 43% of the time. APTT values outside the therapeutic range were twice as likely to be low as high. The average amount of heparin required to maintain therapeutic APTT values for children was 22 U/kg/h: 28 U/kg/h for infants < 1 y and 20 U/kg/h for the rest. Bleeding was rare (2%) and mild. Documented recurrent thrombotic disease was more common (7%) with associated morbidity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Establishing a therapeutic range for heparin therapy.

OBJECTIVE: To compare two methods of determining a therapeutic range of activated partial thromboplastin time (aPTT) results. DESIGN: Cohort studies. SETTING: Referral teaching hospital. PATIENTS: Inpatients who received unfractionated heparin intravenously for venous thromboembolic disease. MEASUREMENTS: A therapeutic range determined by aPTT ratios of 1.5 to 2.5 times the control value as compared with a therapeutic range determined by protamine titration heparin levels of 0.2 to 0.4 U/mL. RESULTS: For all aPTT reagents studied, a ratio of 1.5 times the control value is much less than a minimum protamine titration heparin level of 0.2 U/mL. Various manufacturers' aPTT reagents and reagent lots from the same manufacturer show considerable variation in response to heparin and therefore have different therapeutic ranges. CONCLUSIONS: A different dose of heparin would be required to produce an aPTT ratio of 1.5 times the control value, depending on the reagent used. Establishing a therapeutic range for aPTT results using protamine titration heparin levels of 0.2 to 0.4 U/mL as a reference standard is practical and compensates for the variable response of aPTT reagents to heparin.

Cohort Studies↗
PubMed1993

Increased thrombin generation and activity in patients with systemic lupus erythematosus and anticardiolipin antibodies: evidence for a prothrombotic state.

The objective of this study is to determine whether patients with systemic lupus erythematosus (SLE) and anticardiolipin antibodies (ACA) have biochemical evidence of an ongoing prothrombotic state. Using a cross-sectional analysis of a cohort design in an outpatient SLE clinic setting, 43 consecutive patients with SLE participated. Patients underwent clinical and laboratory evaluations on two separate occasions at least 3 months apart. As part of the clinical evaluation, the following were ascertained: (1) the ongoing use of warfarin therapy; (2) the presence of prior venous and arterial thromboembolic disease by history, critical review of objective tests, and examination for reflux in the deep veins of the legs as an indicator of venous thrombosis; and (3) disease-related activity by performing a lupus activity criteria count (LACC). As part of the laboratory evaluation, blood was taken on both occasions and assayed for prothrombin fragments (F1 + 2) and fibrinopeptide A (FPA), as indices of thrombin generation and activity, respectively, and ACA. For the analyses, patients were classified as ACA+ if the assay was abnormal on both occasions and ACA- if the assay was negative on both occasions or negative on one occasion and positive on the other. ACA+ patients had: (1) a significantly higher mean level of F1 + 2 (1.07 nmol/L) than ACA- patients (0.79 nmol/L; P = .02) and patients receiving warfarin (0.47 nmol/L; P = .009) and (2) a significantly higher mean level of FPA (1.01 nmol/L) than ACA- patients (0.45 nmol/L; P = .02). When patients with prior thromboembolism were excluded from the analysis, significant differences in the mean levels of F1 + 2 and FPA between ACA+ and ACA- patients were still seen, whereas when patients with prior thromboembolism and/or active disease were excluded from the analysis, a significant difference in the mean level of FPA and a nonsignificant trend in the mean level of F1 + 2 were seen. The results of this study support the hypothesis that the presence of ACA in SLE patients is associated with an ongoing prothrombotic state.

Adult↗
PubMed1993

The use of an indwelling Teflon catheter for subcutaneous heparin administration during pregnancy. A randomized crossover study.

BACKGROUND: The use of subcutaneous heparin, the therapy of choice for women requiring anticoagulant prophylaxis during pregnancy, is problematic because of the discomfort produced by repeated injections. An indwelling subcutaneous Teflon catheter that can be left in place for 1 week recently became available for use as an entry port for parenteral therapy. Since the use of this catheter has the potential to overcome some of the problems of long-term heparin therapy, we decided to compare this Teflon catheter with twice-daily subcutaneous injections in women requiring heparin during pregnancy. METHODS: In a randomized, multiple-crossover study, patients alternated every 2 weeks between having heparin administered through the indwelling Teflon catheter and receiving heparin via subcutaneous injections. After each 4-week cycle, patients completed a questionnaire designed to determine their preferred method of heparin administration. The side effects, doses, and anticoagulant activity of heparin with the two delivery systems were also compared. RESULTS: Twelve patients completed one to five 4-week cycles of heparin therapy. Ten of the patients selected the Teflon catheter as the preferred route of heparin administration (P = .04) and 11 patients reported that the catheter caused less pain and bruising than twice-daily subcutaneous injections (P < .01). Five patients developed urticarial reactions at the sites of heparin injections. These reactions tended to be more severe when the Teflon catheter was used, and two women discontinued using the catheter after the first cycle because of this complication. There were no differences in heparin dose requirements or achieved activated partial thromboplastin times between the two routes of heparin administration. CONCLUSIONS: Most pregnant women in our study preferred to have subcutaneous heparin administered through an indwelling Teflon catheter rather than by twice-daily injections. Heparin given through the Teflon catheter was bioavailable and caused less local bruising than twice-daily injections. Urticarial reactions to heparin tended to be more severe with the use of the Teflon catheter and resulted in the discontinuation of the device's use in two of 12 patients.

Adult↗
PubMed1992

Prevention of thrombus growth by antithrombin III-dependent and two direct thrombin inhibitors in rabbits: implications for antithrombotic therapy.

We compared the abilities of heparin and two direct thrombin inhibitors to prevent fibrin accretion onto pre-existing thrombi in rabbits. Inhibition of thrombus growth was measured as the ability of each test compound to inhibit the accretion of 125I-fibrin onto thrombi pre-formed in jugular veins of rabbits. When administered as a continuous infusion, the two direct (i.e. antithrombin III-independent) thrombin inhibitors, r-hirudin and a tripeptide, Ac(D)-Phe-Pro-bor-Arg (P-8714) inhibited fibrin accretion as effectively as heparin, but did so in doses which generated little systemic anticoagulation, as compared to the marked anticoagulation associated with the heparin effect. However, both r-hirudin and P-8714 were more effective when they were administered as a single bolus injection than as a continuous infusion. Under the former conditions, there was only a transient systemic anticoagulant effect. We conclude that direct or antithrombin III-independent thrombin inhibitors are more effective than heparin in preventing thrombus growth. The limited effect of heparin is likely due to fibrin impairing the ability of heparin/antithrombin III to inactivate thrombin.

Amino Acid Sequence↗
PubMed1992

Relationship of antiphospholipid antibodies to pregnancy loss in patients with systemic lupus erythematosus: a cross-sectional study.

To determine whether an association exists between the presence of antiphospholipid antibodies and pregnancy loss, a cross-sectional study was performed. Consecutive women who were referred to three outpatient rheumatology clinics and who had systemic lupus erythematosus (SLE) and a history of one or more pregnancies were evaluated. Patients were interviewed to determine outcomes of all previous pregnancies. Blood was taken on two separate occasions at least 3 months apart to test for the presence of the lupus anticoagulant and anticardiolipin antibodies; on both occasions, five tests of the lupus anticoagulant, with well-defined normal ranges, and an enzyme-linked immunosorbent assay to measure IgG anticardiolipin antibodies were performed. Patients were considered to be positive for the lupus anticoagulant if one or more tests was abnormal on both occasions and positive for anticardiolipin antibodies if the test was abnormal on both occasions. Forty-two women were studied. Statistically significant associations were shown between lupus anticoagulant positivity and previous pregnancy loss (odds ratio [OR], 4.8; 95% confidence intervals [CI], 1.0 to 23.6; P = .05) and between anticardiolipin antibody positivity and previous pregnancy loss (OR, 20.0; 95% CI, 1.3 to 97.0; P = .01). All seven women with multiple episodes of pregnancy loss were lupus anticoagulant positive and four of these were also anticardiolipin antibody positive. If patients who are transiently positive for lupus anticoagulant and/or anticardiolipin antibodies are considered to be test positive, the associations with pregnancy loss are no longer statistically significant. Within the group of lupus anticoagulant-positive patients, we observed stronger associations between the presence of six or more positive tests and pregnancy loss than between the presence of two to five positive tests and pregnancy loss. No single test for the lupus anticoagulant provides a statistically significant association with pregnancy loss. The results of our study show that by performing multiple lupus anticoagulant tests and by repeating testing for lupus anticoagulant and anticardiolipin antibodies on more than one occasion, significant associations between the presence of antiphospholipid antibodies and previous pregnancy loss can be shown in patients with SLE.

Abortion, Spontaneous↗
PubMed1992

Venous thrombosis during pregnancy: leg and trimester of presentation.

In order to determine the relative frequencies of left and right leg venous thrombosis during pregnancy and the frequencies of venous thrombosis during the three trimesters, a cohort study of 60 consecutive patients with a first episode of venous thrombosis during pregnancy was performed. Fifty-eight women had isolated left leg thrombosis, two patients had bilateral venous thrombosis and no patient had isolated right leg venous thrombosis. Thirteen patients had venous thrombosis during the first trimester (21.7%), 28 during the second trimester (46.7%) and 19 during the third trimester (31.7%). These findings indicate that patients with symptoms in the right leg rarely have venous thrombosis. Because leg pain and swelling occur most frequently during the third trimester but venous thrombosis is relatively equally distributed during all three trimesters, patients presenting earlier during pregnancy are more likely to have venous thrombosis than patients presenting later during pregnancy.

Female↗
PubMed1992

D-dimer and thrombin-antithrombin III complexes in patients with clinically suspected pulmonary embolism.

One hundred and fifty-six consecutive patients with clinically suspected pulmonary embolism (PE) had blood drawn to measure levels of D-dimer and thrombin-antithrombin (TAT) complexes and underwent ventilation/perfusion (V/Q) lung scanning and bilateral impedance plethysmography (IPG); pulmonary angiography was performed in 10 patients. Patients were classified as: PE-positive (positive pulmonary angiography or high probability lung scan or non-high probability lung scan and abnormal IPG) or, PE-negative (normal lung scan or normal pulmonary angiography) or PE-unlikely (non-high probability lung scan and normal serial IPG and absence of venous thromboembolism in follow-up). Thirty patients were classified as PE-positive, 64 as PE-negative and 62 patients as PE-unlikely. PE-positive patients were treated with anticoagulants, whereas PE-negative and PE-unlikely patients were not. PE-unlikely patients were followed for 3 months with repeat IPG and clinical evaluation for the occurrence of venous thromboembolism. The sensitivities, specificities, positive predictive values and negative predictive values of the D-dimer and TAT complex assays were calculated for patients classified as PE-positive and PE-negative. In addition, the prevalences of normal D-dimer and TAT complex assays were calculated for PE-unlikely patients. Cutoffs of 300 ng/ml for D-dimer and 3.5 micrograms/ml for TAT complexes provided sensitivities of 96% for both assays, negative predictive values of 97% for D-dimer and 96% for TAT complexes and specificities of 52% for D-dimer and 51% for TAT complexes. The specificities of the assays were higher in patients without comorbid conditions and in outpatients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Warfarin-induced skin necrosis in 2 patients with protein S deficiency: successful reinstatement of warfarin therapy.

Warfarin-induced skin necrosis is a rare but serious complication of oral anticoagulant therapy. This condition has been associated with protein C deficiency but only rarely reported in patients with a deficiency of protein S. We have managed 2 patients with a history of warfarin-induced skin necrosis who were diagnosed as being protein-S-deficient. Since both patients were candidates for long-term anticoagulant therapy we elected to reintroduce warfarin using a regimen designed to minimize the risk of recurrent skin necrosis. While they were therapeutically anticoagulated with heparin, warfarin was started at 1 mg/day and the dose was increased gradually. Heparin was not discontinued until the prothrombin times were in the therapeutic range for at least 72 h. Both patients tolerated the reinstitution of warfarin without difficulty and they have now been followed for over 2 years on oral anticoagulants without complication.

Adult↗
PubMed1992

Optimal therapeutic level of heparin therapy in patients with venous thrombosis.

BACKGROUND: Audits of heparin sodium therapy suggest that heparin administration is fraught with difficulty. The literature indicates that the current clinical practice of intuitive ordering of heparin results in inadequate therapy because of fear of bleeding. The importance of exceeding the lower limit of the therapeutic range has been strongly supported by findings of prospective clinical trials. Firm evidence indicates that failure to exceed the lower limit is associated with unacceptably high rates of recurrent venous thromboembolism. By comparison, evidence supporting the risk of exceeding the upper limit of the therapeutic range is weak. OBJECTIVES: The purposes of this study were (1) to validate prospectively an approach designed to minimize the proportion of patients receiving subtherapeutic doses of heparin and (2) to determine the effectiveness and safety of decreasing the heparin dosage infused on the basis of activated partial thromboplastin time (APTT) prolongation reflecting both heparin and warfarin sodium effects. METHODS: We performed a randomized double-blind study evaluating a prescriptive approach to heparin administration in patients receiving heparin or heparin with warfarin. Thromboembolic and bleeding complications were objectively documented. RESULTS: Only 1% and 2% of patients had subtherapeutic heparin levels for 24 hours or more in the heparin and combined groups, respectively. Recurrent venous thromboembolism occurred infrequently in both groups (7%). Sixty-nine (69%) of 99 patients receiving combined therapy had supratherapeutic values, compared with 24 (24%) of 100 receiving heparin; bleeding complications occurred in 9% and 12%, respectively. CONCLUSIONS: Our findings demonstrate that no association exists between supratherapeutic APTT responses and bleeding, which is in direct contrast to the observed association between subtherapeutic APTT responses and recurrent venous thromboembolism.

Double-Blind Method↗
PubMed1991

The relationship of antiphospholipid antibodies to thromboembolic disease in systemic lupus erythematosus: a cross-sectional study.

In order to determine whether an association exists between antiphospholipid antibodies (APLA) and thromboembolic events in patients with systemic lupus erythematosus (SLE), we performed a cross-sectional study of consecutive unselected SLE patients. The occurrence of previous thromboembolic events was determined by investigators blinded to the APLA status of the patients by critical review of objective tests that had been performed at the time of symptomatic presentation and by performing venous Doppler ultrasound of the legs to elicit venous reflux as an indication of previous venous thrombosis. The presence of APLA was determined by coagulation assays for the lupus anticoagulant (LA) using five tests with well-defined control ranges and by ELISA assay for anticardiolipin antibodies (ACLA). These tests were measured on two separate occasions. The results of the study demonstrate a statistically significant association between persistently abnormal ACLA assays and thromboembolic events and a non-significant trend between persistently abnormal LA and thromboembolic events. Transient abnormalities of LA and ACLA were less strongly associated with thromboembolic events. We conclude that in patients with SLE, there is a significant association between thromboembolism and APLA.

Autoantibodies↗
PubMed1991

Rapid anticoagulation using ancrod for heparin-induced thrombocytopenia.

In order to determine the efficacy and safety of ancrod, a rapid acting defibrinogenating drug, for patients with heparin-induced thrombocytopenia, 11 consecutive patients who required anticoagulant therapy because of venous thromboembolism and who developed acute heparin-induced thrombocytopenia or had a history of heparin-induced thrombocytopenia were treated with ancrod. Heparin therapy was discontinued (in patients receiving heparin) and ancrod started at a dose of 1 to 2 U/kg every 24 hours with subsequent daily doses adjusted to maintain fibrinogen levels between 0.5 and 1.0 g/L. Ancrod was continued until warfarin had become effective. The platelet count increased to more than 150 x 10(9)/L within 2 to 10 days in all thrombocytopenic patients. Two patients with a history of heparin-induced thrombocytopenia maintained normal platelet counts while receiving ancrod. Two patients had recurrent venous thrombosis while receiving warfarin, 10 days after ancrod was discontinued: one of these patients had metastatic pancreatic carcinoma and developed phlegmasia cerulea dolens and the other patient developed a venographically proven extension of her deep venous thrombosis. One patient suffered a bleeding episode into the thigh with a 16-g/L decrease in her hemoglobin level while receiving ancrod therapy. No other side effects were noted. Our experience indicates that ancrod therapy is a reasonable approach for patients with heparin-induced thrombocytopenia who require anticoagulant therapy.

Aged↗
PubMed1991

Subcutaneous heparin therapy during pregnancy: a need for concern at the time of delivery.

Subcutaneous heparin is the treatment of choice for women requiring anticoagulant therapy during pregnancy. However, heparin therapy presents a management problem at delivery because of its potential to cause a persistent anticoagulant effect and thus increase the risk of bleeding. In order to avoid therapeutic complications it has been our practice to have women either discontinue their heparin injections with the onset of labour or to terminate heparin injections 12 h prior to elective induction. To determine the safety of our anticoagulant protocol at delivery we reviewed consecutive patients treated with subcutaneous heparin therapy during pregnancy, at our centre. Over a 23 month period we found that six of 11 women receiving subcutaneous heparin during pregnancy delivered while their aPTT was prolonged. In addition, three women received intravenous protamine sulphate prior to delivery and in one patient major bleeding occurred during an emergency cesarean section. Those women who had elevated aPTTs at the time of delivery all gave birth within 28 h of their last injection of heparin. In order to avoid a prolonged aPTT at delivery, we have now adopted a more conservative approach to the management of subcutaneous heparin use at term. Subcutaneous heparin is discontinued 24 h prior to commencing an elective induction of labour.

Female↗
PubMed1991

Heparin and graduated compression stockings in patients undergoing fractured hip surgery.

Despite evidence that effective regimens are available for the prevention of venous thrombosis in fractured hip patients, many centers do not use prophylaxis. In order to evaluate the efficacy and safety of heparin and graduated compression stockings, we conducted a cohort study of 55 consecutive fractures hip patients treated postoperatively with heparin, 5,000 U every 12 h, and graduated compression stockings. The rates of venous thromboembolism and bleeding were compared with an historical cohort from Hamilton. Before discharge, 51 patients underwent bilateral venography. Deep venous thrombosis (DVT) occurred in 10 of the 51 patients (incidence of 20%); three had proximal DVT (incidence of proximal DVT was 6%). DVT was seen in 29 of the 63 control patients (incidence 46%); 19 had proximal DVT (incidence of proximal DVT was 30%). The differences in the rates of DVT and proximal DVT are statistically significant (p less than 0.01). Bleeding occurred in one patient in the treatment group (incidence 2%) and five patients in the control group (incidence 8%). This study confirms that therapy with heparin and graduated compression stockings is effective, inexpensive, and convenient for the prevention of venous thrombosis in fractured hip patients and is associated with a low bleeding risk.

Aged↗
PubMed1990

Heparin effect on bone density.

In order to provide estimates of the risks of symptomatic osteoporosis and reduced bone density in premenopausal women treated with long-term (greater than 1 month) heparin therapy, we evaluated a cohort of 61 consecutive premenopausal women previously treated with long-term heparin (cases) and a group of controls matched for age, parity and duration between the last pregnancy and evaluation. All patients underwent dual photon absorptiometry of the lumbar spine and single photon absorptiometry of the wrist and most cases underwent plain lateral radiography of the thoracolumbar spine in order to exclude silent fractures. Although none of the cases suffered symptomatic fractures (0 of 61, 95% confidence intervals 0.0 to 5.9%), there was a significantly greater proportion of cases than controls with bone density below our pre-defined levels. The long-term implications of our findings are uncertain but because it is possible that the reduction in bone density predisposes women to fractures, this potential risk should be considered when treating women with long-term heparin.

Adult↗
PubMed1990

Heparin for 5 days as compared with 10 days in the initial treatment of proximal venous thrombosis.

It is common practice to begin anticoagulant treatment of deep-vein thrombosis with a 10-day course of intravenous heparin, with warfarin added on day 5 to 10 and continued for several months. We performed a randomized, double-blind trial comparing a shorter course of continuous intravenous heparin (5 days, with warfarin sodium begun on the first day) with the conventional 10-day course of heparin (with warfarin sodium begun on the fifth day) in the initial treatment of 199 patients with acute proximal venous thrombosis documented by venography. The frequency of objectively documented recurrent venous thromboembolism was low and essentially the same in the two groups (7.1 percent in the short-course group vs. 7.0 percent in the long-course group). Because the observed difference between the groups was 0.1 percent in favor of the long-course group, it is unlikely (P less than 0.05) that a true difference in favor of this group would be greater than 7.5 percent; the difference could be as much as 7.3 percent in favor of the short-course group. Major bleeding episodes were infrequent, and the rate was similar in both groups. We conclude that a five-day course of heparin is as effective as a 10-day course in treating deep venous thrombosis. Furthermore, using the shorter course would permit earlier discharge from the hospital and thus offer substantial cost savings.

Acute Disease↗