Biomedical subjects
S H Goodnight
Publications and source records attributed to S H Goodnight.
Factors V Leiden and the prothrombin gene mutation: two common genetic defects associated with thrombosis.
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College of American Pathologists Conference XXXI on laboratory monitoring of anticoagulant therapy: the clinical use and laboratory monitoring of low-molecular-weight heparin, danaparoid, hirudin and related compounds, and argatroban.
OBJECTIVE: To review the role of the laboratory in monitoring therapy with low-molecular-weight heparin, danaparoid, hirudin, and argatroban, as reflected in the medical literature and the consensus opinion of recognized experts in the field. DATA SOURCES: Review of the medical literature and current clinical practice by a panel of 6 international experts in the field of anticoagulant therapy. DATA EXTRACTION AND SYNTHESIS: The experts made an extensive review of the published literature and prepared a draft manuscript, which included preliminary recommendations. The draft manuscript was circulated to participants in the College of American Pathologists Conference XXXI on Laboratory Monitoring of Anticoagulant Therapy prior to the conference. The manuscript and recommendations were then presented at the Conference for discussion. Recommendations were accepted if a consensus of the 26 experts attending the Conference was reached. The results of the discussion were used to revise the manuscript into its final form. CONCLUSIONS: This report reviews the mechanism of action and potential uses of these newer anticoagulant agents. General guidelines for monitoring these agents and 9 specific recommendations for laboratory monitoring of low-molecular-weight heparin and danaparoid are provided, along with citation of the appropriate supporting literature. Issues for which a consensus was not reached at the Conference are also discussed.
Acute promyelocytic leukaemia in the all trans retinoic acid era.
Bleeding diathesis is a common complication of acute promyelocyctic leukaemia (APL). Multiple haemostatic defects are found in most patients with APL, which often worsen following cytoreductive chemotherapy. Besides thrombocytopenia, most patients develop disseminated intravascular coagulation, systemic fibrinolysis or both. A major aim in treating haemostatic defects of APL is to prevent death or disability from bleeding until chemotherapy clears the malignant promyelocytes from the blood and bone marrow. The therapeutic options are discussed in this review and practical guidelines for treatment are outlined.
Prospective comparison of infrainguinal bypass grafting in patients with and without antiphospholipid antibodies.
PURPOSE: The antiphospholipid antibodies (APL)-anticardiolipin antibodies (ACL) and lupus anticoagulant (LA)-are widely believed to be associated with decreased lower extremity bypass graft patency rates. To date, no prospective cohort study has confirmed this assumption. A prospective comparison of the result of infrainguinal revascularization procedures performed since 1990 in patients with and without APL forms the basis of this report. METHODS: Patients who underwent elective infrainguinal bypass procedures from 1990 to 1994 were evaluated for hypercoagulable states (ACL, LA, protein C, protein S, and antithrombin III). Patient data were prospectively entered in a computerized vascular registry, and postoperative follow-up was maintained for life. Graft patency, limb salvage, and patient survival rates were calculated by life-table methods. RESULTS: Three hundred twenty-seven lower extremity bypass grafting procedures were performed in 262 patients. APLs were present in 83 patients (32%); 70 patients (84%) had ACLs only, 11 patients (13%) had LA only, and two patients (3%) had both ACLs and LA. There was no significant difference between APL-positive and APL-negative patients with respect to demographics, associated medical conditions, indication for operations, and type of procedures performed. More patients who had APLs had warfarin treatment after surgery (43% vs 24%, p = 0.002). Life table 4-year primary patency rates showed minimal difference (APL-positive, 43%; APL-negative, 59%; p = 0.087), and no significant difference was noted in assisted primary patency rates (APL positive, 72%; APL negative, 73%; p = NS), limb salvage rates (APL positive, 79%; APL negative, 88%; p = NS), and patient survival rates (APL positive, 67%; APL negative, 66%; p = NS). CONCLUSIONS: APLs were found in a surprising one third of the patients who underwent leg bypass grafting procedures. The majority of APLs identified were ACLs (87%). There was minimal difference in graft primary patency rates, and no difference in assisted primary patency, limb salvage, and survival rates between patients with and without APLs who underwent leg bypass grafting procedures. The extreme morbidity rate associated with APLs in previous reports is not confirmed by this prospective study. APLs should not be regarded as a contraindication to indicated leg bypass grafting procedures.
Invasive line placement in critically ill patients: do hemostatic defects matter?
BACKGROUND: Blood components are often given prophylactically before the placement of invasive lines in patients with coagulation defects. Little, however, is known about the epidemiology of defects in these patients. The purpose of this study is to ascertain what proportion of intensive care patients who receive invasive lines have hemostatic defects, what actions are taken by physicians to correct these abnormalities before invasive line insertion, and what the incidence is of bleeding complications after invasive line placement. STUDY DESIGN AND METHODS: Charts were retrospectively reviewed for 490 intensive care patients in whom 938 arterial, pulmonary artery, and central venous lines were placed. RESULTS: At least one defect in hemostasis was documented for 388 patients (41%) before line placement, with 253 (27%) of these patients evidencing severe abnormalities. Seventeen percent of patients had no preprocedure laboratory evaluation. Trauma patients showed the highest numbers of abnormalities in hemostatic testing, but medical patients had more-severe defects. The occurrence of isolated abnormal laboratory values did not predict bleeding, but a score derived from a consideration of multiple defects did. Correction of the abnormalities was attempted in 37 percent of patients with hemostatic defects. Sixteen patients had bleeding complications, but only two had complications that were life-threatening. None of the complications were fatal. CONCLUSION: Invasive lines are used frequently in patients with hemostatic defects, often without any attempt to correct the abnormalities. Nevertheless, rates of hemorrhage are low and appear to be closely related to the level of experience of the physician rather than to defects in hemostasis. These findings suggest that the use of blood components for preprocedure correction of hemostatic defects is not necessary, except in those patients who have the most severe hemostatic abnormalities.
Aspirin therapy for cardiovascular disease.
Aspirin is a widely used and effective antithrombotic agent. Recent studies suggest that aspirin's anti-inflammatory effects are mediated via inhibition of an inducible isoform of cyclooxygenase in inflammatory cells (COX-2) and through blockade of the nuclear transcription factor, NF-kappa B. The optimal dose of aspirin for most clinical situations is 75 to 325 mg/d, but debate continues as to whether higher doses are needed to prevent cerebral ischemia. Aspirin is very effective for inhibition of platelet-mediated thrombosis at sites of vascular injury but does not reduce restenosis after coronary angioplasty or carotid endarterectomy, nor does it prevent a first stroke. Combined therapy with warfarin and aspirin has been shown to limit systemic embolic in high-risk patients with artificial heart valves, but at the cost of increased bleeding. A new aspirin derivative is currently being developed that appears to stimulate platelet nitric oxide release, inhibit thrombin-induced platelet aggregation, and lower gastric toxicity.
Molecular detection of a common mutation in coagulation factor V causing thrombosis via hereditary resistance to activated protein C.
More than half of all patients with familial or recurring venous thrombosis have hereditary resistance to activated protein C (HRAPC) as the result of specific missense mutation in the gene for coagulation factor V. Because the mutant factor Va (with an Arg to Gln substitution at codon 506) cannot be cleaved and inactivated by activated protein C, carriers of this mutation are at significantly increased risk of venous thrombosis. We have recently introduced a direct polymerase chain reaction (PCR)-based clinical diagnostic test for the factor V codon 506 mutation based on the destruction of an Mnl I restriction site by the causative nucleotide substitution. To assess the accuracy of this PCR-based assay, we compared a functional clotting time test for HRAPC with the direct mutation test. Of 47 patients dually tested, only five had discrepant values for the functional test versus the DNA test. Either of these two complementary assays is useful for the accurate diagnosis of HRAPC. The DNA-based test is, however, specifically recommended for evaluation of anticoagulated patients or patients with borderline functional tests and confirmation of genotype in HRAPC families. In an additional analysis of 287 normal individuals, we found an extremely high prevalence of the mutated codon 506 allele-- approximately 4% in each of two different populations. The absence of disease in the majority of heterozygous carriers suggests that symptomatic thrombosis requires the simultaneous presence of both a mutated factor V protein and additional synergistic factors.
Therapeutic use of n-3 fatty acids for vascular disease and thrombosis.
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Predisposition to thrombosis by a factor V mutation causing hereditary resistance to activated protein C.
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Antiplatelet therapy with aspirin: from clinical trials to practice.
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Antiphospholipid antibodies in vascular surgery patients. A cross-sectional study.
BACKGROUND: Autoantibodies to phospholipid (aPL) have been associated with vascular thromboses in cerebral, coronary, and peripheral venous and arterial sites. To date, no large cross-sectional study has examined the incidence of occurrence of aPL in patients with peripheral arterial disease. METHODS: A cross-sectional study was performed with patients admitted for vascular surgery procedures to treat peripheral arterial disease for 23 months between January 1, 1990 and November 1, 1991. Consecutive patients were evaluated for the presence of aPL. Medical records for each patient were reviewed in detail, and historic, operative, and postoperative parameters were tabulated for relationship to the presence of aPL. RESULTS: Two hundred thirty-four patients underwent complete testing for aPL. All patients were receiving chronic aspirin therapy. This represented 86% of admissions. Antiphospholipid antibodies were detected in 60 patients (26%). No differences in age, sex, operation performed, or postoperative outcome were found between patients with and without aPL. However, patients with aPL were 1.8 times more likely to have undergone previous lower extremity (LE) vascular surgery than patients without aPL (95% confidence interval = 1.0 - 3.6, p = 0.047). Patients with aPL and previous LE vascular surgery were 5.6 times more likely to have had occlusion of that procedure than patients without aPL (95% confidence interval = 1.9 - 16.8, p = 0.03). The occluded previous LE procedures had a shorter duration of patency before occlusion in patients with aPL than in those without (mean duration of patency 17 months vs. 50 months, p < 0.003). Patients with occluded previous LE procedures and aPL were 4 times more likely to be female (95% C.I. = 1.4 - 11.3, p = 0.018). CONCLUSIONS: The incidence of aPL in vascular surgery patients is substantial. Vascular surgery patients with aPL are more likely to have failure of previous LE bypass procedures and to be female and the bypass failure occurs significantly more rapidly than in patients without aPL. Based on these data, testing of vascular surgery patients for aPL and investigation of alternative antithrombotic treatment regimens in patients with aPL appears warranted.
Antiphospholipid antibodies and thrombosis.
Antiphospholipid antibodies (eg, anticardiolipin antibodies or the lupus anticoagulant) are a fascinating set of autoantibodies that have been linked to venous and arterial thrombosis, immune-mediated thrombocytopenia, and recurrent pregnancy loss. This review high-lights recent advances in the immunology of antiphospholipid antibodies and their target antigens, potential mechanisms of thrombosis and thrombocytopenia, and new methods for laboratory identification of these antibodies. Clinical syndromes associated with antiphospholipid antibodies are also covered, including ischemic neurological disorders, cardiac lesions, venous thromboembolism, and pregnancy loss. In each instance, recommendations for therapy are discussed.
Disseminated intravascular coagulation in cadaveric organ donors. Incidence and effect on renal transplantation.
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Interruption of vascular thrombus formation and vascular lesion formation by dietary n-3 fatty acids in fish oil in nonhuman primates.
BACKGROUND: Because of discrepant claims regarding the relative biological effects of n-3 fatty acids (n-3FAs), we have concurrently measured the effects of dietary n-3FAs on blood and vascular lipid composition, hemostatic function, blood thrombotic responses, vascular thrombus formation, and vascular lesion formation in baboons. METHODS AND RESULTS: Dietary n-3FAs displaced n-6FAs in plasma, platelets, blood vessels, and corresponding urinary eicosanoid metabolites (p < 0.01 in all cases) within weeks after initiation of a semipurified diet containing 1 g/kg per day n-3FA-ethyl ester concentrate (composed of two thirds eicosapentanoic acid and one third docosahexanoic acid). Coincidentally, platelet hemostatic function became minimally impaired (template bleeding times prolonged from 4.3 +/- 0.5 minutes to 7.6 +/- 1.3 minutes, p = 0.039); concentrations of collagen producing half-maximal platelet aggregation increased (from 6.4 +/- 2.1 to 8.5 +/- 2.5 micrograms/mL, p = 0.045); and tissue factor expression by endotoxin-stimulated blood monocytes fell (from 6.5 +/- 1.2 to 1.7 +/- 0.14 mU/10(6) cells, p < 0.005). Dietary n-3FAs decreased deposition of platelets onto thrombogenic segments of Dacron vascular graft incorporated into chronic exteriorized femoral arteriovenous (AV) shunts, a thrombotic process resistant to the effects of both aspirin and heparin (111In-labeled platelet deposition decreased from 14.1 +/- 1.4 x 10(9) platelets/5-cm segment at 40-60 minutes with occlusion to 7.5 +/- 0.8 x 10(9) platelets/5-cm segment without occlusion; p < 0.001). Platelet deposition onto segments of endarterectomized homologous normal aorta in the AV shunts of n-3FA-treated animals was similarly reduced (from 4.4 +/- 0.9 to 1.8 +/- 0.4 x 10(9) platelets; p < 0.01). Dietary n-3FAs interrupted vascular thrombus formation at sites of surgical carotid endarterectomy (platelet deposition, 1.5 +/- 0.4 versus 4.4 +/- 1.0 x 10(9) platelets in untreated controls; p < 0.001). Moreover, endarterectomized aortic segments (EASs) from n-3FA-treated donors exhibited little capacity to induce thrombus formation when tested in the AV shunts of control recipient animals (0.24 +/- 0.10 versus 4.4 +/- 0.90 x 10(9) platelets). However, in the converse crossover experiments, EASs from control animals actively accumulated platelets when studied in the AV shunts of n-3FA-treated animals (1.8 +/- 0.4 x 10(9) platelets; p < 0.01 versus n-3FA-treated EASs in shunts of normal animals). Dietary n-3FAs also abolished vascular lesion formation at sites of carotid endarterectomy 6 weeks after surgery (cross-sectional area of neointima 0.048 +/- 0.031 mm2 compared with 0.428 +/- 0.104 mm2 in control arteries; p = 0.010). CONCLUSIONS: In nonhuman primates, dietary n-3FAs in high doses eliminate both vascular thrombus formation and vascular lesion formation after mechanical vascular injury while largely sparing hemostatic function and modestly reducing blood thrombotic responses. These effects are attributed to selective n-3FA-dependent alterations in cellular membrane functions.
The hypercoagulable states: diagnosis and management.
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Antiplatelet therapy--Part I.
We summarize current information about aspirin and other antiplatelet drugs in patients with cardiac and vascular disease. For each indication, we briefly summarize the rationale for the use of antiplatelet therapy and describe the findings of relevant clinical trials. We propose recommendations for the use of these agents in clinical practice. Part I covers the use of antiplatelet therapy for the primary and secondary prevention of myocardial infarction, coronary thrombolysis, unstable and chronic stable angina, and coronary artery-saphenous vein bypass grafts. In part II we review the use of antiplatelet agents in coronary angioplasty, atrial fibrillation, artificial cardiac valves, stroke, and peripheral vascular disease.
Antiplatelet therapy--Part II.
We summarize current information about aspirin and other antiplatelet drugs in patients with cardiac and vascular disease. For each indication, we briefly summarize the rationale for the use of antiplatelet therapy and describe the findings of relevant clinical trials. We propose recommendations for the use of these agents in clinical practice. In Part 2, we discuss the use of antiplatelet agents in coronary angioplasty, atrial fibrillation, artificial cardiac valves, stroke, and peripheral vascular disease. In Part 1, we reviewed the use of antiplatelet therapy for the primary and secondary prevention of myocardial infarction, in conjunction with coronary thrombolysis, in patients with unstable and chronic stable angina, and following coronary artery-saphenous vein bypass grafting.