Biomedical subjects
Stephan Moll
Publications and source records attributed to Stephan Moll.
Phase II trial of alfimeprase, a novel-acting fibrin degradation agent, for occluded central venous access devices.
PURPOSE: Alfimeprase is a recombinantly produced, genetically modified variant of the metalloproteinase, fibrolase. Alfimeprase proteolytically cleaves fibrin, independent of plasminogen activation to plasmin, and directly dissolves thrombi. Based on the direct fibrin degradation effect of alfimeprase, rapid activity in patients with occluded central venous access devices (CVADs) was hypothesized. PATIENTS AND METHODS: We performed a phase II, randomized, double-blind, active-control, multicenter, dose-ranging study to compare the safety and efficacy of one or two instillations of three intraluminal doses of alfimeprase (0.3, 1.0, and 3.0 mg) and alteplase 2.0 mg in re-establishing patency to occluded CVADs in 55 adult patients. RESULTS: All three alfimeprase doses were more successful than alteplase during the first 15 and 30 minutes of treatment. The alfimeprase 3.0-mg dose resulted in 40%, 50%, and 60% patency restoration rates at 5, 15, and 30 minutes, respectively, compared with 0%, 0%, and 23% for alteplase. The difference at 15 minutes was highly significant (P = .0075). Alfimeprase 3.0 mg produced the highest patency rate at 120 minutes after the first (60%) and second (80%) doses. No major hemorrhagic or embolic events were reported. CONCLUSION: A single 1- or 3-mg dose of alfimeprase has the potential to restore function to occluded CVADs rapidly and safely, and to facilitate on-time infusion of vital therapies.
False-negative factor V Leiden genetic testing in a patient with recurrent deep venous thrombosis.
False-negative genetic testing of the factor V Leiden (fVL) mutation is unusual. We report a case of a young woman with a history of deep venous thrombosis tested for the fVL at four separate laboratories on four separate dates. Two laboratories reported the patient to be heterozygous for the fVL, while the other two reported no evidence of a mutation. Testing methods of the various laboratories were reviewed, and additional testing was performed on stored and newly drawn DNA samples, including sequencing of the fVL gene segment. The preponderance of evidence indicates the patient to be heterozygous for the fVL mutation. Dissection of data suggests that either sample misidentification or faulty allele specific amplification methods could have led to false-negative results in two laboratories. In one of the two laboratories, misinterpretation of results and clerical error could not be excluded. There is a need for standardization of optimized fVL genetic testing methods. Further education of ordering physicians on the limitations of genetic testing is necessary.
Transient drug-induced white blood cell aplasia.
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Thrombophilias--practical implications and testing caveats.
This review summarizes recent information about the major thrombophilic conditions, their clinical relevance, and practical aspects pertaining to testing for these thrombophilias, such as when to test and what assays are appropriate. Conditions covered include factor V Leiden, prothrombin 20210 mutation, proteins C and S, antithrombin, antiphospholipid antibodies, homocysteine, and methylene-tetrahydrofolate-reductase enzyme mutation. Additional comments focus on education of patients and educational resources for patients, such as the National Alliance for Thrombosis and Thrombophilia (www.nattinfo.org).
A cautionary tale: fatal outcome of methotrexate therapy given for management of ectopic pregnancy.
BACKGROUND: Medical therapy with methotrexate is a standard practice for the commonly encountered problem of ectopic pregnancy. Methotrexate is excreted predominantly by the kidney and should be used with extreme caution in renal insufficiency. All physicians who administer methotrexate must understand its mechanism of action, distribution, and elimination to minimize potential risks to the patient. CASE: A young, dialysis-dependent woman received a standard dose of methotrexate for an ectopic pregnancy. Prolonged methotrexate exposure resulted. The consequences-pancytopenia, desquamation, acute respiratory distress syndrome, and profound bowel ischemia-ultimately led to her death. CONCLUSION: Methotrexate, even at extremely low doses, can be fatal in patients with renal insufficiency. Alternative means of therapy should be sought for women with ectopic pregnancy and renal failure.
Antiphospholipid antibodies.
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Cardiology patient pages. Homocysteine and MTHFR mutations: relation to thrombosis and coronary artery disease.
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Identification, diagnosis and treatment of heparin-induced thrombocytopenia and thrombosis: a registry of prolonged heparin use and thrombocytopenia among hospitalized patients with and without cardiovascular disease. The Complication After Thrombocytopenia Caused by Heparin (CATCH) Registry steering committee.
BACKGROUND: Heparin-induced thrombocytopenia (HIT) is estimated to occur in 1-5% of all patients receiving heparin, and 25-50% of such cases develop heparin-induced thrombocytopenia with thrombosis (HITT) A conservative estimate based only on cardiovascular patients suggests that in the United States approximately 100,000 patients develop thrombocytopenia, and 25-50,000 develop HITT annually. Both HIT and HITT are associated with high morbidity and mortality and represent substantial worldwide public health concerns. REGISTRY DESIGN: The objective of the Complication After Thrombocytopenia Caused by Heparin (CATCH) Registry is to identify the incidence of HIT and/or HITT in patients treated with systemic heparin (unfractionated or low molecular weight heparin) in contemporary practice. Additional objectives include to: (1) provide a comprehensive database of patients with suspected HIT or HITT, (2) monitor and define clinical events, including thrombocytopenia, thrombosis, and mortality among patients treated with prolonged (> 96 hours) heparin, (3) describe the incidence and outcomes of HIT and HITT in patients who are treated with heparin and who develop thrombocytopenia in the Coronary Care Unit setting, and (4) document and characterize current diagnostic and therapeutic strategies of suspected HIT. The unblinded registry will record approximately 5,000 patients at 60-80 US hospitals with either prolonged systemic heparin administration or thrombocytopenia and those with suspected HIT or HITT. Enrollment began in the first quarter 2003 and was completed at the end of 2004. IMPLICATIONS: The registry will provide valuable insights to the incidence and consequences of HIT and HITT that will enable improvements in diagnosis and treatment.
Cardiology patient pages. Prothrombin 20210 mutation (factor II mutation).
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Diffuse infiltrative lymphocytosis syndrome.
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Cholesterol emboli associated with warfarin treatment.
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Percutaneous coronary intervention in a patient with immune thrombocytopenia purpura.
The appropriate regimen of platelet inhibitors that should be used in patients with immune thrombocytopenia purpura (ITP; formerly called idiopathic thrombocytopenic purpura) who are undergoing percutaneous coronary intervention is unclear. We report the case of a patient with ITP who underwent two separate coronary interventions. The first involved the use of aspirin and a cutting balloon to treat obstructive disease of the left circumflex. When the patient presented with restenosis, he received eptifibatide, clopidogrel, and an intracoronary stent. He is currently 16 months removed from his second procedure and remains physically active without any anginal symptoms. Percutaneous revascularization in patients with ITP remains a challenge and this therapeutic approach, while ultimately successful in the patient, requires further validation.
Extensive fibromuscular dysplasia in a patient with Parkinson disease.
The cause of fibromuscular dysplasia is not known. Ergot derivatives have been reported as a potential causative agent. The anti-Parkinson medication pergolide is an ergot derivative, but an association between fibromuscular dysplasia and this drug has not been previously reported.
Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism.
BACKGROUND: Standard therapy to prevent recurrent venous thromboembolism includes 3 to 12 months of treatment with full-dose warfarin with a target international normalized ratio (INR) between 2.0 and 3.0. However, for long-term management, no therapeutic agent has shown an acceptable benefit-to-risk ratio. METHODS: Patients with idiopathic venous thromboembolism who had received full-dose anticoagulation therapy for a median of 6.5 months were randomly assigned to placebo or low-intensity warfarin (target INR, 1.5 to 2.0). Participants were followed for recurrent venous thromboembolism, major hemorrhage, and death. RESULTS: The trial was terminated early after 508 patients had undergone randomization and had been followed for up to 4.3 years (mean, 2.1). Of 253 patients assigned to placebo, 37 had recurrent venous thromboembolism (7.2 per 100 person-years), as compared with 14 of 255 patients assigned to low-intensity warfarin (2.6 per 100 person-years), a risk reduction of 64 percent (hazard ratio, 0.36 [95 percent confidence interval, 0.19 to 0.67]; P<0.001). Risk reductions were similar for all subgroups, including those with and those without inherited thrombophilia. Major hemorrhage occurred in two patients assigned to placebo and five assigned to low-intensity warfarin (P=0.25). Eight patients in the placebo group and four in the group assigned to low-intensity warfarin died (P=0.26). Low-intensity warfarin was thus associated with a 48 percent reduction in the composite end point of recurrent venous thromboembolism, major hemorrhage, or death. According to per-protocol and as-treated analyses, the reduction in the risk of recurrent venous thromboembolism was between 76 and 81 percent. CONCLUSIONS: Long-term, low-intensity warfarin therapy is a highly effective method of preventing recurrent venous thromboembolism.
Catastrophic antiphospholipid antibody syndrome.
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