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Biomedical subjects

S Z Goldhaber

Publications and source records attributed to S Z Goldhaber.

At least 19 recordsLinked to original sources
PubMed2006

Hormonal factors and risk of recurrent venous thrombosis: the prevention of recurrent venous thromboembolism trial.

BACKGROUND: In some but not all studies, men with venous thrombosis had a higher risk of recurrence than women. Information on women with initial hormone-related thrombosis is scant. OBJECTIVE: We assessed the incidence of recurrent thrombosis by gender, and among women using exogenous hormones or pregnant/postpartum at the time of index thrombosis. PATIENTS/METHODS: A total of 508 men and women with one or more previous venous thrombosis episodes were observed while participating in a randomized trial of low-intensity warfarin or placebo for 2.1 years. Index thrombosis events during treatment with postmenopausal hormones, oral contraceptives, or during pregnancy, or the puerperium were considered to be hormone-related events. RESULTS: Among 268 men the 3-year probability of recurrent thrombosis was 18.4% (95% confidence intervals; CI 12.3-24.4). Among 109 women without hormone-related thrombosis, the rate was 15.0% (95% CI 6.3-23.8). Among 129 women with hormone-related thrombosis, the rate was 5.0% (95% CI 1.1-8.9). Adjusting for other risk factors and treatment assignment, women had a 39% lower thrombosis recurrence risk than men: hazard ratio (HR) 0.61 (95% CI 0.34-1.08). Women with hormone-related thrombosis had a 58% lower risk than men: HR 0.42 (95% CI 0.19-0.97); and a 46% lower recurrence risk than other women; HR 0.54 (95% CI 0.19-1.54). Women without hormone-related index events had a recurrence rate similar to men; HR 0.83 (95% CI 0.42-1.66). CONCLUSIONS: In this trial population, women had a lower risk of recurrent venous thrombosis than men. This difference was explained by a low risk of recurrence among women with hormone-related index thrombosis.

Aged↗
PubMed2006

D-dimer, factor VIII coagulant activity, low-intensity warfarin and the risk of recurrent venous thromboembolism.

BACKGROUND: Elevated plasma D-dimer and factor VIII coagulant activity (FVIIIc) may be associated with the risk of recurrent venous thromboembolism (VTE). OBJECTIVES: To evaluate D-dimer and FVIIIc as risk factors for recurrent VTE and assess the efficacy of extended low-intensity warfarin (target International Normalized Ratio 1.5-2.0) in preventing recurrence by biomarker level. PATIENTS AND METHODS: In the Prevention of Recurrent Venous Thromboembolism trial, 508 idiopathic VTE patients treated for > or = 3 months with full-intensity warfarin, and who had stopped warfarin for 7 weeks on average, were randomized to low-intensity warfarin or placebo and followed for 2.1 years for recurrent VTE. Prerandomization blood samples were analysed for D-dimer and FVIIIc. RESULTS: One-third of participants had elevated baseline D-dimer (> or = 500 ng mL(-1)) and one-fourth, elevated FVIIIc (> or = 150 IU dL(-1)). Adjusting for other risk factors, the hazard ratios (HRs) for recurrent VTE with elevated D-dimer or FVIIIc were 2.0 [95% confidence interval (CI) 1.2-3.4] and 1.5 (95% CI 0.8-2.8), respectively. The association of elevated D-dimer with recurrence was larger among patients with one prior VTE (HR 3.2, 95% CI 1.3-8.0) than in patients with more than one event (HR 1.4, 95% CI 0.7-2.2). For patients with one prior VTE on placebo, the annual recurrence incidence was 10.9% with elevated D-dimer and 2.9% with normal values. Low-intensity warfarin was equally effective in recurrence risk reduction in those with normal or elevated biomarkers. CONCLUSIONS: Among patients with idiopathic VTE, measurement of D-dimer, but not FVIIIc, might be useful for risk stratification. The efficacy of extended low-intensity warfarin therapy did not vary by biomarker level.

Adult↗
PubMed2002

Modern treatment of pulmonary embolism.

Modern treatment of acute pulmonary embolism requires rapid and accurate diagnosis followed by risk stratification to devise an optimal management strategy. Patients at low risk have good outcomes simply with intensive anticoagulation treatment. Higher-risk patients may require more aggressive intervention with thrombolysis or embolectomy. Clinical risk factors for an adverse outcome include increasing age, cancer, congestive heart failure, systemic arterial hypotension, chronic obstructive pulmonary disease and right ventricular dysfunction. A promising approach is the Geneva Prognostic Score, which is based upon a rapid clinical assessment. On physical examination, signs of right ventricular failure, including distended jugular veins and a right-sided S3 gallop, should be looked for. The electrocardiogram may show evidence of right ventricular strain with a new right bundle branch block or T wave inversion in leads V1-V4. The troponin level may be elevated as a marker of cardiac injury and right ventricular microinfarction, even in the absence of coronary artery disease. The most useful imaging marker of high risk is the presence of moderate or severe right ventricular dilatation and hypokinesis on the echocardiogram, especially with progressively worsening right ventricular function despite intensive anticoagulation treatment. Patients at high risk should be considered for thrombolytic therapy or embolectomy rather than management with anticoagulation therapy alone. Special care must be taken to avoid thrombolytic therapy among patients who might be susceptible to intracranial haemorrhage. Intracranial haemorrhage reached a surprisingly high rate of 3.0% in the International Cooperative Pulmonary Embolism Registry of 2,454 prospectively evaluated acute pulmonary embolism patients at 52 hospitals in seven countries. An alternative approach to patients at high risk is a catheter-based or open surgical embolectomy. It is crucial to refer these patients as quickly as possible, rather than delaying intervention until cardiogenic shock has ensued. Fortunately the current tools for risk stratification provide an "early window" for prognostication and can help the coordination of a definitive treatment plan with optimal results.

Acute Disease↗
PubMed2002

Rationale and design of a clinical trial of a low-molecular-weight heparin in preventing clinically important venous thromboembolism in medical patients: the prospective evaluation of dalteparin efficacy for prevention of venous thromboembolism in immobilized patients trial (the PREVENT study).

The utility of low-molecular-weight heparin (LMWH) in the prophylaxis of venous thromboembolic disease has been examined using the surrogate endpoint of venographically identified thrombi. The largest portion of these thrombi were asymptomatic calf-vein thrombi. The clinical relevance of this observation is a matter of debate. The present study is designed to evaluate the impact of an LMWH on clinically important endpoints. The current study is a randomized, prospective, double-blinded, multicenter, multinational, controlled clinical trial comparing dalteparin with placebo in moderately high-risk hospitalized medical patients. A total of 3300 patients will be randomized to receive either 5,000 IU per day of dalteparin or placebo for 14 days. Patients will undergo appropriate evaluation for any symptomatic episodes and all patients will undergo a bilateral compression ultrasound (CUS) on day 21 to search for asymptomatic proximal thrombi. The primary endpoint is the combination of objectively confirmed symptomatic deep vein thrombi (DVT), fatal or non-fatal pulmonary emboli, all proximal DVT, and sudden death. This study will be the first study to examine clinically important endpoints in evaluating the effect of a LMWH in hospitalized medical patients. This study also is the first study to use CUS rather than venography in concordance with contemporary medical practice. This trial is thus designed to address this important question in a clinically relevant manner.

Adult↗
PubMed2001

Unsolved issues in the treatment of pulmonary embolism.

The three most controversial and unsolved issues in the treatment of pulmonary embolism (PE) are: (1) the role of thrombolysis, (2) the role of low molecular weight heparin and length of hospital stay, and (3) the optimal duration of anticoagulation. The trend is to use thrombolysis more frequently, to administer low molecular weight heparin and shorten the hospitalization duration in low-risk patients, and to give prolonged courses of anticoagulation with warfarin. PE thrombolysis appears most beneficial in patients at high risk of adverse clinical outcomes in whom the potential hazards of bleeding can be justified by the danger of conservative management with anticoagulation alone. With respect to utilizing low molecular weight heparin as a way of shortening the duration of hospitalization, there are no data to warrant this approach. The current FDA mandate for symptomatic PE patients is to administer intravenous unfractionated heparin administered as a bridge to therapeutic warfarin. Finally, the optimal duration of anticoagulation following acute PE remains mired in controversy. Despite the high rate of recurrent venous thrombosis after discontinuation of anticoagulation, there are currently insufficient data to recommend indefinite warfarin therapy.

Anticoagulants↗
PubMed2001

Balloon pulmonary angioplasty for treatment of chronic thromboembolic pulmonary hypertension.

BACKGROUND: Although pulmonary thromboendarterectomy is increasingly successful for the definitive treatment of chronic thromboembolic pulmonary hypertension (CTEPH), not all patients have surgically accessible disease. Others are poor surgical candidates because of comorbid illness. Therefore, for selected patients, we defined and implemented an alternative interventional strategy of balloon pulmonary angioplasty (BPA). METHODS AND RESULTS: Eighteen patients (mean age, 51.8 years; range, 14 to 75 years) with CTEPH underwent BPA; they averaged 2.6 procedures (range, 1 to 5) and 6 dilations (range, 1 to 12). Selection of pulmonary artery segments for dilation required (1) complete occlusion, (2) filling defects, or (3) signs of intravascular webs. After an average of 36 months of follow-up (range, 0.5 to 66 months), the average New York Heart Association class improved from 3.3 to 1.8 (P:<0.001), and 6-minute walking distances increased from 209 to 497 yards (P:<0.0001). Pulmonary artery mean pressures decreased from 43.0+/-12.1 to 33. 7+/-10.2 mm Hg (P:=0.007). Eleven patients developed reperfusion pulmonary edema; 3 required mechanical ventilation. CONCLUSIONS: BPA reduces pulmonary artery hypertension in patients with CTEPH and is associated with long-term improvement in New York Heart Association class and 6-minute walking distances. BPA is a promising interventional technique that warrants randomized comparison with medical therapy in CTEPH patients who are not surgical candidates.

Adolescent↗
PubMed2001

G20210A mutation in the prothrombin gene and the risk of recurrent venous thromboembolism.

OBJECTIVES: The study was done to determine whether the G20210A mutation in the prothrombin gene increases the risk of recurrent venous thromboembolism (VTE), both alone and in combination with factor V Leiden. BACKGROUND: Several inherited defects of coagulation are associated with increased risk of first VTE, including a recently identified G20210A mutation in the prothrombin gene. However, whether the presence of this mutation confers an increased risk of recurrent venous thromboembolism is controversial. METHODS: A total of 218 men with incident venous thromboembolism were genotyped for the prothrombin mutation and for factor V Leiden and were followed prospectively for recurrent VTE over a follow-up period of 7.3 years. RESULTS: A total of 29 men (13.3%) suffered recurrent VTE. Five of the 14 carriers of the prothrombin mutation developed recurrent VTE (35.7%; incidence rate = 8.70 per 100 person-years), while 24 of 204 individuals who did not carry the prothrombin mutation developed recurrent VTE (11.8%; incidence rate = 1.76 per 100 person-years). Thus, presence of the G20210A mutation was associated with an approximate fivefold increased risk for recurrent VTE (crude relative risk [RR] 4.93; 95% confidence interval [CI] 1.9-12.9; p = 0.001; age-, smoking-, and body mass index-adjusted RR 5.28; 95% CI 2.0-14.0; p = 0.001). In these data, recurrence rates were similar among those with an isolated mutation in the prothrombin gene (18.2%) as compared to those with an isolated factor V Leiden mutation (19.2%). However, all three study participants who carried both mutations (100%) suffered a recurrent event during follow-up. CONCLUSIONS: In a prospective evaluation of 218 men, the presence ofprothrombin mutation was associated with a significantly increased risk of recurrent VTE, particularly among those who co-inherited factor V Leiden.

Adult↗
PubMed2001

Isolated calf vein thrombosis: comparison of MR venography and conventional venography after initial sonography in symptomatic patients.

RATIONALE AND OBJECTIVES: The authors performed this study to compare magnetic resonance (MR) venography and conventional venography in the diagnosis of deep venous thrombosis (DVT) in the calf after sonography. MATERIALS AND METHODS: Sonography was performed in 595 patients who were suspected of having lower-extremity DVT. Patients with positive above-knee duplex sonograms, allergy to iodinated contrast material, renal insufficiency, or cardiac pacemakers and patients who were obese were excluded. The remaining 73 patients were asked to undergo MR venography and conventional venography. All studies were to be performed within 48 hours of the clinical diagnosis and according to standard clinical practice. Images were interpreted by radiologists who were blinded to the results of other modalities. Two separate analyses were performed: one in which conventional venography was used as the standard of reference, and one in which the presence of at least two positive studies for thrombus was considered diagnostic. RESULTS: Although 36 patients agreed to participate in the study, only 14 underwent MR venography and conventional venography within 48 hours of the clinical diagnosis. With use of any two positive studies for confirmation, acute DVT was diagnosed in three patients. Conventional venography depicted two of the three cases, whereas sonography and MR venography each depicted all three. The findings were concordant in only five of the 14 patients. CONCLUSION: Moderate discrepancy among modalities was demonstrated. This suggests radiologists should undertake comparisons among these three modalities for the detection of calf DVT. In patients with a high clinical suspicion, a second modality may be useful if the initial study is negative.

Adult↗
PubMed2001

Epidemiology of pulmonary embolism.

The diagnosis of venous thromboembolism (VTE) has notoriously been challenging because the disease often has no specific clinical presentation, can at times be completely asymptomatic, and can masquerade as other illnesses. To further complicate matters, the rules for coding VTE in the presence of other illnesses changed in 1983 so that among patients who died of VTE and other causes, VTE was omitted from the coding. The International Cooperative Pulmonary Embolism Registry enrolled 2454 consecutive pulmonary embolism (PE) patients from 52 participating hospitals in 7 countries. The aim was to establish the 3-month all-cause mortality rate and to identify factors associated with death. Three-month follow-up was completed in 98% of the patients. The all-cause mortality rate was 11.4% during the first 2 weeks after diagnosis and 17.4% at 3 months. Especially troubling among survivors was the high rate of recurrent VTE after anticoagulation was discontinued. Age is a potent risk factor for the development of VTE. The two most common genetic mutations that predispose to VTE are the factor V Leiden and the prothrombin gene. VTE can be precipitated by oral contraceptives, pregnancy, or hormone replacement therapy.

Contraceptives, Oral, Hormonal↗
PubMed2001

Thrombolytic therapy in pulmonary embolism.

Successfully utilized contemporary pulmonary embolism (PE) thrombolysis reverses right heart failure rapidly and safely. This therapeutic approach may lower mortality from PE and reduce morbidity from chronic pulmonary hypertension. PE thrombolysis remains a debatable indication because large clinical trials using survival as an endpoint have not been carried out. Instead, thrombolysis trials have been undertaken with surrogate endpoints such as reduction in clot burden, reduction in pulmonary arterial pressure, and improvement in right ventricular function. Currently, the only contemporary thrombolytic regimen for PE that is approved by the Food and Drug Administration is recombinant tissue plasminogen activator, in a dose of 100 mg/2 h. New thrombolytic agents under development for PE include reteplase, saruplase, and recombinant staphylokinase. Future clinical trials will require multicenter collaboration and focus on clinically relevant endpoints such as reduction of mortality and recurrent venous thromboembolism, under particular consideration of the risk of intracranial hemorrhage that ranges between about 1.7% in clinical trials up to approximately 3.0% in a large registry.

Anticoagulants↗
PubMed2001

Rescue percutaneous coronary intervention immediately following coronary artery bypass grafting.

Perioperative graft failure after coronary artery bypass graft (CABG) can result in acute myocardial infarction with dire clinical consequences. We report a case of rescue percutaneous coronary intervention immediately after unsuccessful CABG. This approach salvaged the patient from cardiogenic shock and should be recognized as a viable alternative to immediate reoperation for certain patients.

Aged↗
PubMed2001

Cost implications of low molecular weight heparins as prophylaxis following total hip and knee replacement.

Deep venous thrombosis (DVT) and pulmonary embolism (PE) are serious and costly complications of total hip and knee replacement surgery. The risk of these complications is significantly reduced by prophylaxis. Low molecular weight heparins (LMWH) are being used for this indication with increased frequency. The objective of this study was to assess the cost implications of LMWH for the prevention of symptomatic DVT and PE complications following total hip and knee replacement surgery. The study design was cost analysis based on utilization and the costs of medical resources for prophylaxis and treatment of DVT/PE. A retrospective hospital data set was used to assess symptomatic DVT/PE complication rates and medical resource utilization in patients receiving warfarin, other, and no prophylaxis. The results of a clinical trial were used to estimate relative reductions in risk of symptomatic DVT/PE due to prophylaxis with LMWH. The 7721 total hip and knee replacement patients analyzed were admitted in 1992 in 57 acute-care non-federal hospitals. The measurements were of incremental costs or charges expected to be saved as a result of using LMWH prophylaxis instead of warfarin prophylaxis. Prophylaxis using LMWH rather than warfarin reduces the expected total costs (charges) of treatment by $50 ($193), not including the pharmaceutical costs associated with prophylaxis. The cost reduction in favor of LMWH was sensitive to several factors, including blood monitoring costs and DVT/PE complication rates. Where a reduction of one day in hospital stay could be realized from LMWH's early onset of action, the cost (charges) reduction increased to $226 ($624). In conclusion, LMWH has the potential to offer several short- and long-term cost advantages compared with warfarin, mostly due to lower test costs associated with prophylaxis and reduced complication rates.

Adult↗
PubMed2001

Thrombolysis in pulmonary embolism: a debatable indication.

Successfully utilized contemporary pulmonary embolism thrombolysis reverses right heart failure rapidly and safely. This therapeutic approach may lower mortality from pulmonary embolism and reduce morbidity from chronic pulmonary hypertension. Pulmonary embolism thrombolysis remains a debatable indication because large clinical trials using survival as an endpoint have not been carried out. Instead, thrombolysis trials have been undertaken with surrogate endpoints such as reduction in clot burden, reduction in pulmonary arterial pressure, and improvement in right ventricular function. In an era where hundreds of thousands of myocardial infarction patients have participated in thrombolysis trials that focus on survival as the principal endpoint, the much smaller trials of PE thrombolysis have not been sufficiently definitive to achieve a consensus. Pharmaceutical companies have not considered this area of investigation to be a good return on investment, because PE is a much less common problem than acute coronary syndromes. No government funding agency has targeted PE thrombolysis as a priority for clinical research. Currently, the only contemporary thrombolytic regimen for pulmonary embolism that is approved by the Food and Drug Administration is tissue plasminogen activator, in a dose of 100 mg/2 h. New thrombolytic agents under development for pulmonary embolism include reteplase, saruplase, and recombinant staphylokinase. Future clinical trials will require multicenter collaboration and focus on clinically relevant endpoints such as reduction of mortality and recurrent venous thromboembolism.

Clinical Trials as Topic↗
PubMed2000

Diagnosis of deep venous thrombosis.

Although deep venous thrombosis (DVT) is often considered an elusive disease that is difficult to recognize clinically, important clinical clues and properly ordered imaging tests can reliably detect or exclude this condition. This article will provide a practical approach to recognizing clinical settings in which DVT should be suspected, suggesting a focused history and physical examination and outlining optimal strategies for test ordering. This information will help ensure that patients with DVT are identified rapidly and, conversely, that those without DVT will receive reassurance or specific treatment for the medical problem that mimics it. Once DVT is suspected, a workup can proceed rapidly and accurately to resolve the diagnostic issue.

Humans↗