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Biomedical subjects

Steven R Deitcher

Publications and source records attributed to Steven R Deitcher.

At least 37 records · Page 2Linked to original sources
PubMed2004

Goal-oriented thrombolytic therapy for venous thromboembolic disease.

The goal of a therapeutic intervention should be to positively impact a meaningful patient outcome. Too often, though, efficacy of a treatment is based on a surrogate endpoint. Thrombolytic therapy for venous thromboembolic disease is an example of a treatment whose success is primarily based on radiographic or echocardiographic endpoints and not endpoints such as symptom relief, functional capacity, quality of life, thrombosis recurrence, and survival. Thrombolysis for lower-extremity deep venous thrombosis does not reduce the incidence of pulmonary embolism, has unclear impact on the rates of post-thrombotic syndrome, and is associated with increased rates of major hemorrhage compared to conventional anticoagulation. Reserving thrombolysis for limb-threatening thrombosis especially in the young seems prudent. Currently available evidence does not support the routine use of thrombolytic therapy in patients with hemodynamically stable pulmonary embolism regardless of right ventricular function status. Risks, benefits, and alternative therapies must always be considered, and therapy must be guided by individual case circumstances and the best available scientific evidence.

Endpoint Determination↗
PubMed2003

Clinical utility of subcutaneous hirudins.

The clinical utility of subcutaneous hirudins is discussed. The term "hirudins" refers to a class of antithrombotic agents structurally derived from the medicinal leech salivary protein hirudin. Breakthroughs in biotechnology over the past 20 years have resulted in the development of recombinant versions of hirudin (r-hirudin). Lepirudin is one such r-hirudin that is identical to natural hirudin except for the substitution of leucine for isoleucine at the N-terminus and the elimination of a sulfate group on the tyrosine at position 63. Another r-hirudin, desirudin, is identical to hirudin except for a valine-valine in the N-terminus and the absence of the sulfate group on tyrosine at position 63. Both r-hirudins are bivalent and tightly bind to both the catalytic site and the exposite of thrombin to exert their inhibitory effects on thrombin. Unfractionated heparin (UF) and low-molecular-weight heparins (LMWHs) are widely used in medical and surgical patients to prevent and treat arterial and venous thrombotic events. Besides bleeding, the major adverse effect of heparins is heparin-induced thrombocytopenia (HIT). HIT is associated with a paradoxical hypercoagulable state and marked risk of clinical thrombosis. Management of HIT requires the immediate cessation of all heparin exposure, and the initiation of an alternative anticoagulant. Because r-hirudins are effective agents and do not cross-react with HIT-associated antibodies, they are excellent anticoagulants in patients with past or current HIT. Clinical trials have also demonstrated the efficacy and safety of subcutaneous (s.c.) r-hirudins compared to heparins in non-HIT settings. Results of these trials support the use of r-hirudin therapy in patients with HIT or at risk of developing HIT. Additionally, case reports have described safe and effective use of s.c. r-hirudin therapy in the outpatient setting in both HIT and non-HIT patients.

Antithrombins↗
PubMed2003

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.

Aged↗
PubMed2003

Calf deep venous thrombosis should be treated with anticoagulation.

A 50-year-old man with hypertension presents with a 2-day history of right calf swelling and pain. Venous duplex ultrasound reveals a right soleal vein thrombosis. He denies history of bleeding, renal disease, and symptoms suggestive of pulmonary embolism (PE). Physical examination is unrevealing except for calf tenderness, redness, warmth, and swelling. He is ambulatory. A decision is made to treat the calf deep venous thrombosis (DVT) with anticoagulation.

Anticoagulants↗
PubMed2003

Patients with inferior vena caval filters should receive chronic thromboprophylaxis.

A 32-year-old man with testicular carcinoma is diagnosed with an acute left leg deep venous thrombosis (DVT) during his fourth cycle of combination chemotherapy. Because of anticipated moderate to severe thrombocytopenia, anticoagulation is initially avoided and an inferior vena cava (IVC) filter is placed to prevent pulmonary embolism (PE). After completion of all chemotherapy he is deemed to be in remission and anticoagulation is begun. The optimal duration of anticoagulation in this patient is pondered.

Adult↗
PubMed2003

Estrogen-containing oral contraceptives are allowable in young women with factor V Leiden heterozygosity without a history of thrombosis.

An 18-year-old woman without significant past medical and surgical history presents to discuss the safety and efficacy of oral contraceptives. She is sexually active and currently relying on condoms alone for birth control. Her cousin had a deep venous thrombosis (DVT) following a pregnancy. As part of the family screening, this patient was identified as a factor V Leiden heterozygote. The risks and benefits of initiating oral contraceptives are discussed.

Adolescent↗
PubMed2003

Cancer-related deep venous thrombosis: clinical importance, treatment challenges, and management strategies.

Venous thromboembolic disease (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), is an underdiagnosed and underappreciated clinical problem in cancer patients that results in significant patient morbidity and mortality. Standard treatment practices, including the use of intravenous unfractionated heparin (UFH) for initial anticoagulation, the use of oral warfarin for chronic anticoagulation, and the prescription of only 3 to 6 months total therapy, may not be optimal in the setting of active cancer and ongoing anticancer therapy. Challenges of VTE management in cancer patients include heparin resistance because of excess circulating acute phase proteins, increased recurrence rates during warfarin therapy (target international normalized ratio 2 to 3), limited venous access to support therapeutic monitoring, and increased bleeding rates during anticoagulation. Bleeding during anticoagulation is of particular concern in patients with disease- or chemotherapy-related thrombocytopenia, central nervous system involvement with cancer, and recent surgical intervention. Low-molecular-weight heparins (LMWHs) have been shown to be equally effective and safe for initial anticoagulation compared with UFH and have gained popularity, especially in the setting of VTE in cancer. LMWHs have the advantage of less nonspecific protein binding, subcutaneous weight-based dosing without the need for monitoring in most cases, and less heparin-induced thrombocytopenia. Recent clinical trials have shown LMWHs are at least as effective as oral warfarin for long-term anticoagulation in cancer patients. Interest in LMWHs and several new classes of parenteral and oral anticoagulants extends beyond the primary and secondary prevention of VTE and includes antiangiogenesis, metastasis prevention, and survival prolongation.

Anticoagulants↗
PubMed2003

Prevention of thromboembolism after neurosurgery for brain and spinal tumors.

OBJECTIVE: Deep venous thrombosis (DVT) is a major cause of morbidity and mortality after surgery for primary and metastatic brain tumors. METHODS: We conducted a confidential survey of American neurosurgeons interested in tumor surgery to assess DVT risk awareness and thromboprophylaxis patterns. RESULTS: Of the 172 respondents, 108 (63%) underestimated the DVT risk after brain tumor surgery. After operating on patients who had brain or spinal tumors, 81.4 and 78.5% of respondents, respectively, reported using DVT prophylaxis. After performing brain tumor surgery, 76.2% of respondents reported using solely mechanical methods of prophylaxis "always" or "most of the time." CONCLUSION: American neurosurgeons tend to underestimate the risk of DVT associated with brain tumor surgery and to use mechanical thromboprophylaxis despite the availability of effective pharmacologic antithrombotics. A better appreciation of the risk of thrombosis, combined with clinical studies to address safety, may enhance the use of prophylaxis and the perceived safety of antithrombotics in this setting.

Anticoagulants↗
PubMed2003

Hypercoagulable state testing and malignancy screening following venous thromboembolic events.

Mounting interest in hypercoagulability, increased availability of hypercoagulable state test 'panels' and enhanced ability to identify abnormalities in tested patients have prompted widespread testing. Testing for acquired and inherited hypercoagulable states uncovers an abnormality in over 50% of patients presenting with an initial venous thromboembolic event (VTE) but may have minimal actual impact on management in most of these patients. Such laboratory screening should be reserved for patients in whom the results of individual tests will significantly impact the choice of anticoagulant agent, intensity of anticoagulant therapy, therapeutic monitoring, family screening, family planning, prognosis determination, and most of all duration of therapy. Testing 'just to know' is neither cost-effective nor clinically appropriate. The most important testing in patients following acute VTE may be age- and gender-specific cancer screening. Cancer screening following VTE seems most prudent in older individuals and in those with idiopathic VTE and no laboratory evidence for an inherited hypercoagulable state. Cancer screening should focus on identification of treatable cancers and those where diagnosis in an early stage favorably impacts patient survival. Extensive searches for occult malignancy employing whole-body computed tomography and serum tumor markers may identify more cancers but without affecting patient outcome. We advocate that physicians should focus their attention more on VTE prophylaxis and proper treatment and less on costly and, at times, invasive testing of questionable value.

Aged↗
PubMed2003

Diagnosis of venous thromboembolic disease in cancer patients.

Venous thromboembolic disease is a common but likely underdiagnosed condition in the cancer patient population. Timely and accurate diagnosis of venous thromboembolism is imperative due to the unacceptable morbidity and mortality associated with a misdiagnosis. Because diagnosis of the condition based on clinical grounds alone is unreliable, physicians should select an appropriate objective diagnostic test to confirm or refute their clinical impressions. Compression duplex ultrasound is the best initial imaging test for both suspected upper- and lower-extremity deep venous thrombosis. Magnetic resonance venography (MRV) is a valid alternative when ultrasound is inconclusive, but contrast venography remains the "gold standard." Suspected pulmonary embolism should be initially evaluated by helical (spiral) computed tomography (CT) or ventilation/perfusion lung scintigraphy, the former being preferred in cases of obvious pulmonary or pleural disease. Indeterminate studies should prompt performance of contrast pulmonary angiography. Inferior vena cava thrombosis is also best assessed by contrast venography, with MRV and CT reserved as alternative imaging modalities. Evidence to date suggests that D-dimer assays remain unreliable in excluding venous thromboembolism in cancer patients. A newer latex agglutination D-dimer assay may prove to be clinically useful in this setting.

Biomarkers↗
PubMed2002

Adenovirus encoding vascular endothelial growth factor-D induces tissue-specific vascular patterns in vivo.

The capacity of an adenovirus encoding the mature form of vascular endothelial growth factor (VEGF)-D, VEGF-D Delta N Delta C, to induce angiogenesis, lymphangiogenesis, or both was analyzed in 2 distinct in vivo models. We first demonstrated in vitro that VEGF-D Delta N Delta C encoded by the adenovirus (Ad-VEGF-D Delta N Delta C) is capable of inducing endothelial cell proliferation and migration and that the latter response is primarily mediated by VEGF receptor-2 (VEGFR-2). Second, we characterized a new in vivo model for assessing experimental angiogenesis, the rat cremaster muscle, which permits live videomicroscopy and quantitation of functional blood vessels. In this model, a proangiogenic effect of Ad-VEGF-D Delta N Delta C was evident as early as 5 days after injection. Immunohistochemical analysis of the cremaster muscle demonstrated that neovascularization induced by Ad-VEGF-D Delta N Delta C and by Ad-VEGF-A(165) (an adenovirus encoding the 165 isoform of VEGF-A) was composed primarily of laminin and VEGFR-2-positive vessels containing red blood cells, thus indicating a predominantly angiogenic response. In a skin model, Ad-VEGF-D Delta N Delta C induced angiogenesis and lymphangiogenesis, as indicated by staining with laminin, VEGFR-2, and VEGFR-3, whereas Ad-VEGF-A(165) stimulated the selective growth of blood vessels. These data suggest that the biologic effects of VEGF-D are tissue-specific and dependent on the abundance of blood vessels and lymphatics expressing the receptors for VEGF-D in a given tissue. The capacity of Ad-VEGF-D Delta N Delta C to induce endothelial cell proliferation, angiogenesis, and lymphangiogenesis demonstrates that its potential usefulness for the treatment of coronary artery disease, cerebral ischemia, peripheral vascular disease, restenosis, and tissue edema should be tested in preclinical models.

Adenoviridae↗
PubMed2002

Fosinopril versus amlodipine comparative treatments study: a randomized trial to assess effects on plasminogen activator inhibitor-1.

BACKGROUND: ACE inhibitors and calcium antagonists may modulate fibrinolysis. We conducted a randomized controlled trial to assess the effects of these drugs on plasminogen activator inhibitor-1 (PAI-1) antigen, an inhibitor of fibrinolysis. METHODS AND RESULTS: Participants with hypertension and type 2 diabetes mellitus (n=96, 51% black) were randomized after an initial 4 weeks of placebo to double-blind 20 or 40 mg fosinopril or 5 or 10 mg amlodipine daily for 4 weeks in a fixed-dose regimen. After 4 weeks of placebo washout, the patients received 4 weeks of crossover treatments. After treatment with placebo, systolic and diastolic blood pressure were 143+/-2 and 86+/-1 mm Hg and plasma PAI-1 was 43.4+/-2.3 ng/mL. Amlodipine achieved a greater systolic and diastolic blood pressure reduction than fosinopril (10 mm Hg versus 8 mm Hg, P=0.029, and 5 mm Hg versus 3 mm Hg, P=0.040, respectively) but tended to increase PAI-1, whereas fosinopril tended to decrease PAI-1 (5.4+/-3.6 versus -3.8+/-2.5 ng/mL, P=0.045). The PAI-1 changes depended on drug dose (6.5+/-6.1 and 3.4+/-3.9 ng/mL with amlodipine 10 and 5 mg, respectively, and -0.4+/-3.1 and -7.4+/-4.0 ng/mL with fosinopril 20 and 40 mg, respectively, P for trend 0.024). No significant differences between fosinopril and amlodipine were found for short-term changes in tissue plasminogen activator antigen, fibrinogen, C-reactive protein, and interleukin-6. The findings were similar in black and white participants. CONCLUSIONS: Short-term treatment with fosinopril significantly reduced PAI-1 compared with amlodipine in a dose-dependent fashion. This effect, which was independent of blood pressure reduction, may account for the improved clinical outcomes achieved with ACE inhibitors compared with calcium antagonists.

Amlodipine↗
PubMed2002

Interpretation of the international normalised ratio in patients with liver disease.

Wide acceptance of the international normalised ratio (INR) and thromboplastins with low international sensitivity indices (ISIs) has inadvertently led to the application of the INR to patients other than those on anticoagulation treatment. I examined the degree of factor deficiency for a given INR in patients with liver disease and controls receiving stable-dose warfarin. The degree of factor V and VII, but not prothrombin, deficiencies for a given INR were greater in liver patients than controls. The INR measured with a low-ISI thromboplastin can quantify the coagulation status of patients with liver disease, but should not be interpreted as having the same meaning as the INR in patients receiving warfarin.

Adult↗
PubMed2002

Safety and efficacy of alteplase for restoring function in occluded central venous catheters: results of the cardiovascular thrombolytic to open occluded lines trial.

PURPOSE: To evaluate the safety and efficacy of alteplase (TPA) for restoring function to occluded central venous catheters (CVCs). PATIENTS AND METHODS: The study design was a phase III, open-label, single-arm multicenter trial. Subjects with occluded, nondialysis CVCs were enrolled. All subjects received a 2-mg dose of TPA within the dysfunctional catheter lumen that was allowed to dwell for 30 to 120 minutes. Functionality was tested at 30 and 120 minutes. If the CVC remained obstructed at 120 minutes, a second 2-mg TPA dose was allowed to dwell for 30 to 120 minutes. The primary safety end point was the rate of intracranial hemorrhage (ICH) within 5 days of treatment, and serious adverse events were recorded up to 30 days. RESULTS: Nine hundred ninety-five patients received treatment (female, 562; male, 433; mean age, 50.7 years; range, 2 to 91 years). CVCs treated were as follows: single (26%), double (39%), or triple (6%) lumen catheters or ports (29%). The primary end point was 0% ICH within 5 days. There were no cases of death, major bleeding episodes, or embolic events attributable to treatment. Flow was successfully restored in 52% and 78% of CVCs at 30 and 120 minutes after one dose, and 84% and 87% at 30 and 120 minutes after a second dose, respectively. Restoration of flow was 86%, 93%, 90%, and 79%, for single, double, and triple lumen catheters and ports, respectively. Estimated 30-day catheter patency was 74%. CONCLUSION: A regimen of up to two 2-mg doses of TPA is safe and effective for the restoration of flow to occluded central venous catheters.

Adolescent↗
PubMed2002

Treatment of occluded central venous catheters with alteplase: results in 1,064 patients.

PURPOSE: Thrombosis of central venous access devices (CVADs) is a relatively frequent complication. Alteplase (tissue plasminogen activator) has been used to salvage dysfunctional devices. The purpose of this study was to analyze the safety and efficacy of alteplase after administration of a maximum of two 2-mg/2-mL doses to thrombosed CVADs. MATERIALS AND METHODS: A combined analysis was performed of two pivotal prospective phase-III clinical trials (Cardiovascular thrombolytic to Open Occluded Lines [COOL] Trials) involving 80 centers enrolling patients from November 1999 through December 2000. Patients 2 years of age or older (with body weights >10 kg) with dysfunctional nondialysis CVADs were eligible, including those with peripherally inserted central catheters, apheresis catheters, and ports. Alteplase (2 mg/2 mL) was instilled into the lumen of the central venous catheter and allowed to dwell for as long as 120 minutes. For patients with body weights of 10-30 kg, 110% of the internal lumen volume of alteplase (2 mg/2 mL) was administered. If the device was still occluded after a maximum of 120 minutes, a second alteplase dose was given and allowed to dwell for as long as 120 minutes. The primary efficacy endpoint was designated as restored function after a maximum of two doses. The primary safety endpoint was intracranial hemorrhage (ICH) within 5 days. RESULTS: A total of 1,064 patients (465 men, 599 women; mean age, 50.7 y; range, 2-91 y) with dysfunctional catheters were treated. After alteplase administration, function was restored in 798 patients (75.0%; 95% CI: 72.3%, 77.6%) after one dose and 905 (85.1%; 95% CI: 82.8%, 87.2%) after two doses. Efficacy rates were similar among catheter types (single-, double-, and triple-lumen catheters, and ports). Serious adverse events monitored within 30 days of treatment included ICH (0.0%), embolic events (0.0%), gastrointestinal bleeding (0.3%), thrombosis (0.3%), and sepsis (0.4%). One event (fever) was attributed to the study drug. Efficacy was independent of age, sex, body weight, and catheter type. CONCLUSION: A regimen of as many as two 2-mg doses of alteplase is safe and effective for restoring flow to occluded central venous access devices.

Adolescent↗
PubMed2002

Outpatient management of venous thromboembolic disease with subcutaneous lepirudin: a case report.

Outpatient treatment of deep venous thrombosis has gained widespread acceptance and is facilitated by the use of subcutaneous low molecular weight heparins (LMWH). We report two patients in whom subcutaneous lepirudin was used for long term anticoagulation after heart transplant or surgical pulmonary embolectomy because treatment with LMWH or warfarin was contraindicated, unsuccessful, or impractical. Neither bleeding complications nor recurrent thromboses developed. Subcutaneous lepirudin may be safely and effectively employed for the outpatient treatment of venous thrombosis in selected cases including patients with heparin-induced thrombocytopenia and in those who fail LMWH.

Adult↗