Biomedical subjects

P Brill-Edwards

Publications and source records attributed to P Brill-Edwards.

At least 19 recordsLinked to original sources

PubMed1996

Evaluation of a soluble fibrin assay in patients with suspected pulmonary embolism.

In order to determine the clinical utility of an enzyme immunoassay (EIA) for soluble fibrin in patients with suspected pulmonary embolism (PE), 195 unselected patients with suspected PE underwent blood sampling for measurement of plasma levels of soluble fibrin, and objective testing for PE. A soluble fibrin result of < or = 0.75 micrograms/ml showed a sensitivity of 100% for PE and a specificity of 12.8%, whereas a soluble fibrin result of < or = 1.35 micrograms/ml showed a sensitivity of 90.3% and a specificity of 49.4% for PE. The soluble fibrin assay has potential clinical utility in excluding PE.

Adolescent↗

PubMed1996

The effects of long-term heparin therapy during pregnancy on bone density. A prospective matched cohort study.

We performed a prospective matched cohort study to investigate the effects of long-term (> 1 month) heparin therapy on lumbar spine bone density. Twenty-five women who received heparin during pregnancy, and 25 matched controls underwent dual photon absorptiometry of the lumbar spine in the post-partum period. Zero of 25 heparin-treated patients developed fractures. Heparin-treated patients had a 0.082 g/cm2 lower bone density compared to untreated controls, which is clinically and statistically significant (p = 0.0077). There were 6 matched pairs in which only the heparin-treated patient had a bone density below 1.0 g/cm2, compared to only one pair in which only the control patient had a bone density below this level (p = 0.089). The correlation coefficients of the difference in bone density in each matched pair, and the duration of heparin therapy, the mean daily dose, and the total dose of heparin were 0.042, - 0.015, and 0.021, respectively; none of these values is statistically significant. We conclude: 1) long-term heparin therapy was associated with a significant reduction in bone density, although fractures are uncommon, 2) there was no significant correlation between lumbar bone density and the dose or duration of heparin.

Absorptiometry, Photon↗

PubMed1995

Antiphospholipid antibodies and venous thromboembolism.

The clinical relevance of antiphospholipid antibodies (APLA) in patients without systemic lupus erythematosus who have venous thromboembolism (VTE) in unknown. Limited evidence suggests that there is an association between the presence of APLA and both initial and recurrent episodes of VTE and that patients with APLA and VTE are resistant to warfarin therapy. Unselected patients with a first episode of clinically suspected deep vein thrombosis or pulmonary embolism were evaluated with objective tests for VTE and with laboratory tests for APLA; the latter included tests for the lupus anticoagulant (LA) and anticardiolipin antibodies (ACLA). Patients with VTE were treated with anticoagulant therapy and observed during and after discontinuation of anticoagulants for symptomatic recurrence of VTE. There was a strong association between LA and VTE (odds ratio, 9.4; 95% confidence interval [CI], 2.1 to 46.2) and 9 to 65 (14%; 95% CI, 7% to 25%) patients with VTE had LA. There was no association between the presence of ACLA and VTE (odds ratio, 0.7; 95%CI, 0.3 to 1.7) because of the high frequency of positive ACLA assays in patients without VTE. None of the 16 patients with VTE and APLA developed recurrent VTE while receiving warfarin therapy. There was no difference in rates of recurrent VTE in patients with or without APLA after anticoagulant therapy was discontinued. The strong association between LA and VTE suggests that testing for LA in patients with VTE is useful. The measurement of ACLA in patients with VTE has no clinical usefulness because the results are abnormal in a high proportion of patients without VTE. Although the presence of APLA in patients with VTE was not associated with resistance to a conventional intensity of warfarin or an increased risk of recurrent VTE after discontinuation of warfarin, a larger study should address these issues in a subgroup of patients with VTE and LA.

Adolescent↗

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↗

PubMed1995

Acquired free protein S deficiency is associated with antiphospholipid antibodies and increased thrombin generation in patients with systemic lupus erythematosus.

In order to determine whether there is a relationship between acquired free protein S deficiency and increased thrombin generation, we performed a cross-sectional study of patients with systemic lupus erythematosus (SLE). Plasma samples were assayed for free protein S and were correlated to levels of prothrombin fragments (F1 + 2); an elevated level of F1 + 2 was used as a surrogate marker for a prothrombotic state. Assays for anticardiolipin antibodies (ACA) and lupus anticoagulant (LA) were performed on two separate blood samples taken at least 3 months apart in order to detect the presence of antiphospholipid antibodies. Of the 36 subjects, 9 had reduced free protein S levels compared to 0 of 21 controls (P = 0.01) and the mean free protein S level was significantly lower in the SLE population than in controls (0.30 +/- 0.08 U/mL versus 0.43 +/- 0.10 U/mL, P < 0.001). Of the 24 subjects with antiphospholipid antibodies, 9 had reduced free protein S levels, compared to 0 of 12 subjects without antiphospholipid antibodies (P = .01). The mean F1 + 2 level was significantly higher in study subjects with reduced free protein S levels than in those with normal free protein S levels (1.22 +/- 0.50 nmol/L versus 0.78 +/- 0.27 nmol/L, P = 0.05). This study confirms an association between antiphospholipid antibodies and reduced free protein S levels and demonstrates that patients with SLE and acquired free protein S deficiency generate more thrombin than patients with SLE and normal free protein S levels. Further studies are needed to determine whether the thrombotic diathesis associated with the presence of antiphospholipid antibodies is directly caused by the concomitant presence of acquired free protein S deficiency.

Adult↗

PubMed1995

Application of a novel and rapid whole blood assay for D-dimer in patients with clinically suspected pulmonary embolism.

STUDY OBJECTIVE: To determine the clinical utility of a novel whole blood assay for D-dimer (SimpliRED) in patients with clinically suspected pulmonary embolism (PE). DESIGN: Prospective cohort. PATIENTS: Eighty-six consecutive patients with clinically suspected PE. INTERVENTION: All patients had the SimpliRED D-dimer assay performed and underwent ventilation/perfusion (V/Q) lung scanning and bilateral impedance plethysmography (IPG); pulmonary angiography was performed in two patients. Patients were classified as: 1) PE-positive; positive pulmonary angiography or high probability V/Q scan or non-high probability V/Q scan and either abnormal IPG (either at presentation or upon serial testing and confirmed by contrast venography) or symptomatic thromboembolic event within three months of presentation or 2) PE-negative; normal V/Q scan or normal pulmonary angiography or non-high probability V/Q scan and normal serial IPG and absence of symptomatic venous thromboembolism within three months of follow up. Sixteen (19%) patients were classified as PE-positive and 70 (81%) patients were classified as PE-negative. MEASUREMENTS AND RESULT: The sensitivities, specificities, positive predictive values, and negative predictive values of the D-dimer assay were calculated for all patients and for the subgroup of patients without comorbid conditions that independently can cause elevated D-dimer levels. The D-dimer showed a sensitivity of 94%, a negative predictive value of 98%, a specificity of 66%, and a positive predictive value of 38%. In the subgroup of patients without comorbid conditions, the specificity increased to 98% and the positive predictive value to 83%, but because only six patients had an abnormal D-dimer level, the 95% confidence interval on the observed positive predictive value is wide (36-100%). CONCLUSIONS: This study demonstrates that the SimpliRED D-dimer assay, which can be performed and interpreted at the bedside within five minutes, has potential clinical utility as an exclusionary test in patients with clinically suspected PE. The assay should be evaluated in large clinical management studies.

Adolescent↗

PubMed1995

Evaluation of a soluble fibrin assay in patients with suspected deep vein thrombosis.

BACKGROUND: The objective of this study was to determine the clinical utility of an enzyme immunoassay (EIA) for soluble fibrin in patients with clinically suspected deep vein thrombosis (DVT). METHODS AND RESULTS: 101 unselected patients with clinically suspected DVT underwent blood sampling for measurement of plasma levels of soluble fibrin, and objective testing for DVT. According to results of the objective tests, patients were classified as DVT-positive (n = 34) or DVT-negative (n = 67). Using different cut-points of soluble fibrin results, the sensitivities, specificities, positive and negative predictive values of the soluble fibrin assay were calculated. A soluble fibrin result of < or = 0.75 mg/ml showed a sensitivity and negative predictive value of 100%, and a specificity of 17.9% for DVT, a soluble fibrin result of < or = 1.40 mg/ml showed a sensitivity of 91.2% and a negative predictive value of 93.6%, and a specificity of 65.7% for DVT, whereas a soluble fibrin result of < or = 8.0 mg/ml showed a specificity and positive predictive value of 100% for DVT. CONCLUSIONS: This study demonstrates that the soluble fibrin assay used in the study has potential clinical utility as a diagnostic test in patients with clinically suspected DVT and supports further evaluation of this assay.

Evaluation Studies as Topic↗

PubMed1995

Pre-operative plasma levels of thrombin-antithrombin III complexes correlate with the development of venous thrombosis after major hip or knee surgery.

STUDY OBJECTIVE: To determine whether levels of thrombin-antithrombin III (TAT) in plasma, taken two weeks pre-operatively, predict the development of deep vein thrombosis (DVT) in patients undergoing major hip or knee surgery. DESIGN: Prospective cohort. SETTING: Tertiary-care referral centre, university-affiliated hospital. PATIENTS: Ninety eight consecutive patients undergoing elective hip or knee surgery. INTERVENTION: All eligible consenting patients were seen in a preoperative clinic two weeks prior to surgery and had blood taken for measurement of plasma TAT level. After surgery, they received a combination of unfractionated heparin 5000 Units 12-hourly subcutaneously, and antiembolism stockings (TEDS), as prophylaxis against DVT. Contrast venography was performed prior to discharge, and according to the results, patients were classified as having proximal (popliteal and/or more proximal) DVT (n = 12), calf DVT (n = 7) or no DVT (n = 79). MEASUREMENTS AND RESULTS: The mean TAT level was significantly higher in patients who developed DVT (5.7 micrograms/l) than in those who did not (4.1 micrograms/l), p = 0.035. Using cut-points of 3.5 and 5.5 micrograms/l for the TAT level, patients could be categorized as high, intermediate, and low risk for the development of DVT. The proportion of patients with TAT levels of > or = 3.5 micrograms/l who developed calf or proximal DVT was significantly higher than the proportion of patients with TAT levels of < 3.5 micrograms/l who developed calf or proximal DVT (p = 0.02). The proportion of patients with TAT levels > 5.5 micrograms/l who developed proximal DVT was significantly higher than the proportion of patients with TAT levels of < or = 5.5 micrograms/l who developed proximal DVT (p = 0.03). CONCLUSIONS: This study demonstrates that pre-operative TAT levels correlate with the risk of developing DVT after major orthopedic surgery. Further studies are needed to determine the reason(s) for this observation and whether rational recommendations about prophylaxis and screening for DVT can be made based on the results of a preoperative TAT level.

Adult↗

PubMed1994

Reevaluation of the sensitivity of impedance plethysmography for the detection of proximal deep vein thrombosis.

BACKGROUND: To reevaluate the sensitivity of impedance plethysmography (IPG) for proximal deep vein thrombosis (DVT) and to establish a relationship between the location and size of thrombi and the results of IPG. DESIGN: Prospective cohort study. METHODS: One hundred thirty-two consecutive patients with clinically suspected DVT underwent IPG testing and most (n = 118) underwent contrast-enhanced venography; in 14 patients, venous ultrasonography was performed and demonstrated definitive proximal DVT in which the size and extent of the thrombus could be delineated. All patients with dubious or normal ultrasound results underwent contrast-enhanced venography. All tests were performed and test results were interpreted without knowledge of the results of the other tests. Patients were considered to have proximal DVT if this was demonstrated on venography or ultrasound, calf DVT if this was demonstrated on venography, or no DVT if venography yielded normal findings. The sensitivity and specificity of IPG for DVT were calculated. RESULTS: Of the 132 patients, 40 (30%) had proximal DVT, seven (5%) had calf DVT, and 85 (64%) had no DVT. The sensitivity of IPG for proximal DVT was 65% and the specificity was 93%. Of the proximal vein thrombi, IPG detected three (23%) of 13 that involved the popliteal vein but not the superficial femoral vein and 23 (85%) of 27 proximal vein thrombi that involved the superficial femoral vein. CONCLUSIONS: Our study demonstrated that the sensitivity of IPG for proximal DVT at our center is only 65%, a figure that is much lower than those reported in earlier studies from our institution. We hypothesize that because of a change in referral practice, an increased proportion of patients with less severe symptoms are now referred to our center than in the past. These patients have thrombi that are smaller, less likely to be occlusive, and therefore less likely to yield abnormal IPG findings.

Adult↗

PubMed1994

A noninvasive strategy for the treatment of patients with suspected pulmonary embolism.

BACKGROUND: Pulmonary embolism has historically presented a formidable diagnostic problem because of the nonspecificity of the clinical findings associated with this disorder and the diagnostic uncertainties and challenges presented by both ventilation-perfusion lung scanning and pulmonary angiography. We have reported previously that serial noninvasive leg testing provides a practical noninvasive alternative to pulmonary angiography in patients with non-high probability (nondiagnostic) lung scans and adequate cardiorespiratory reserve. We have reevaluated this observation prospectively to (1) confirm or refute our original observation in an independent cohort and (2) to increase the numbers sufficiently to provide narrow confidence limits for the observed outcomes. METHODS: A prospective comparative study in 1564 consecutive patients with suspected pulmonary embolism who underwent ventilation-perfusion lung scanning and objective testing for proximal-vein thrombosis. RESULTS: On long-term follow-up of 627 patients with the following characteristics: (1) abnormal, nondiagnostic lung scans, (2) not taking anticoagulant therapy, and (3) serial noninvasive test results negative for proximal-vein thrombosis, only 12 patients (1.9%; 95% confidence limits, 0.8% to 3.0%) had venous thromboembolism. By comparison, venous thromboembolism on follow-up occurred in four (0.7%) of 586 patients (95% confidence limits, 0.02% to 1.3%) with normal lung scans in whom anticoagulant therapy was withheld and in eight (5.5%) of 145 patients (95% confidence limits, 1.8% to 9.2%) with high probability lung scans who received anticoagulant therapy. CONCLUSIONS: Our findings indicate that the clinician has a practical noninvasive strategy in patients with adequate cardiorespiratory reserve and nondiagnostic lung scans that (1) avoids pulmonary angiography, (2) identifies patients with proximal-vein thrombosis who require treatment, and (3) avoids the need for treatment and further investigation in the majority of patients.

Adolescent↗

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↗