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Select utilization of obese donors in living donor liver transplantation: implications for the donor pool.

Living donor liver transplantation evolved in response to donor shortage. Current guidelines recommend potential living donors (LD) have a body mass index (BMI) <30. With the current obesity epidemic, locating nonobese LD is difficult. From September 1999 to August 2003, 68 LD with normal liver function test (LFTs) and without significant comorbidities underwent donor hepatectomy at our center. Post-operative complications were collected, including wound infection, pneumonia, hernia, fever, ileus, biliary leak, biliary stricture, thrombosis, bleeding, hepatic dysfunction, thrombocytopenia, deep venous thrombosis, pulmonary embolism, difficult to control pain, depression and anxiety. Complication rates for LD with BMI >30 (n = 16) and BMI <30 (n = 52) were compared. The incidence of wound infection increased with BMI, 4% for nonobese and 25% for obese LD (p = 0.024). There were no statistically significant differences for all other complications. No LD died. Recipient survival was 100% with obese LD and 80% with nonobese LD (p = 0.1). Select donors with a BMI >30 may undergo donor hepatectomy with acceptable morbidity and excellent recipient results. Updating current guidelines to include select LD with BMI >30 has the potential to safely increase the donor pool.

Adolescent↗

Effect of danazol on the biochemical abnormality of inherited antithrombin III deficiency.

Seven members of a family affected by hereditary antithrombin III deficiency were identified. The disorder was associated with recurrent spontaneous episodes of phlebitis, deep venous thrombosis, and pulmonary embolism in middle age. Danazol, a 17-alkyl derivative of ethinyl testosterone, which has been used to treat other antiprotease deficiency states, was assessed in the management of two men with antithrombin deficiency. In a dose of 600 mg a day danazol appeared to correct the antithrombin deficiency. This drug may provide a useful adjunct to anticoagulant treatment, particularly before surgery.

Adult↗

Current issues in anticoagulation.

Anticoagulation therapy with unfractionated heparin, low-molecular-weight heparins and oral vitamin K antagonists is currently the mainstay of treatment and prevention of thromboembolic disorders (such as deep vein thrombosis, pulmonary embolism and stroke prevention in patients with atrial fibrillation). Although these therapies have proven benefits, they also have important limitations that result in their underuse in routine clinical practice. Consequently, many patients identified by guidelines as requiring anticoagulant therapy receive no or inadequate treatment. Heparins require parenteral administration and pose the risk of heparin-induced thrombocytopenia. Vitamin K antagonists have a narrow separation of antithrombotic and haemorrhagic effects and numerous food and drug-drug interactions, and require frequent coagulation monitoring and dose adjustment to ensure effective antithrombotic protection while minimizing the risk of bleeding complications. In response to these limitations, several new anticoagulants have recently been developed, including selective factor Xa inhibitors such as fondaparinux and ximelagatran, the first oral agent in the new class of direct thrombin inhibitors and the first new oral anticoagulant for almost 60 years. Ximelagatran possesses many of the properties of an ideal agent for anticoagulation therapy. With its oral formulation, consistent and predictable pharmacological profile and no coagulation monitoring, ximelagatran has the potential to increase the use and duration of anticoagulation treatment in thromboembolic disorders and to reduce the burden associated with long-term management.

Anticoagulants↗

Use of intravenous tranexamic acid to reduce allogeneic blood transfusion in total hip and knee arthroplasty: a meta-analysis.

Total hip or knee arthroplasty is associated with significant blood loss. Techniques such as the use of antifibrinolytics or desmopressin, or normovolaemic haemodilution have been used to reduce the need for allogeneic blood transfusion. Tranexamic acid has been used to reduce blood loss and transfusion requirement for total hip and knee arthroplasty, with variable results. This meta-analysis aims to evaluate whether intravenous tranexamic acid, when compared with placebo, reduces blood loss and transfusion requirement in total hip and knee joint replacement surgery and whether it might increase the risk of thromboembolic complications. The literature search was based on MEDLINE, EMBASE, Cochrane Controlled Trials Register, and information from the pharmaceutical company that produces tranexamic acid (Pharmacia-Upjohn). We identified 15 clinical trials and 12 were considered suitable for detailed data extraction. Tranexamic acid reduces the proportion of patients requiring allogeneic blood transfusion (OR 0.16, 95% CI: 0.09-0.26), total amount of blood loss (WMD 460 ml, 95% CI: 274-626 ml), and the total number of units of allogeneic blood transfused (WMD 0.85 unit, 95% CI: 0.36-1.33). Tranexamic acid does not increase the risk of thromboembolic complications such as deep vein thrombosis, pulmonary embolism, thrombotic cerebral vascular accident, or myocardial infarction (OR 0.98, 95% CI: 0.45-2.12). Intravenous tranexamic acid appears effective and safe in reducing allogeneic blood transfusion and blood loss in total hip and knee arthroplasty.

Antifibrinolytic Agents↗

Hemorrhagic complications in patients treated with anticoagulant doses of a low molecular weight heparin (enoxaparin) in routine hospital practice.

Low molecular weight heparins (LMWHs) are a rapidly growing class of anticoagulant drug. Their efficacy has been demonstrated in several clinical settings where they are rapidly becoming the anticoagulant of choice. Controlled clinical studies in patients with deep vein thrombosis, pulmonary embolism, and unstable angina have documented that the frequency of major hemorrhage is 0.5-4%. The purpose of the study was to determine the frequency of minor and major hemorrhage occurring in patients receiving anticoagulant doses of an LMWH (enoxaparin) during routine clinical practice. A prospective, observational study of consecutive patients receiving enoxaparin 1 mg/kg twice daily for at least 24 hours in five internal medicine wards of a university teaching hospital was performed. Five hundred forty-nine patients were studied. The mean age was 67.5+/-15.5 years and the mean duration of enoxaparin therapy was 3.8+/-1.5 days. Hemorrhage was documented in a total of 94 patients (17.3%). Major hemorrhage occurred in 14 patients (2.6%), injection-site hemorrhage occurred in 55 patients (10%), and minor hemorrhage (noninjection site) was documented in 25 patients (4.7%). There were two deaths attributed to hemorrhage. Patients with major hemorrhage were older than patients with minor or no hemorrhage (75.5+/-10.4 versus 66.8+/-15.2 years; p=0.03) and occurred in patients receiving enoxaparin for a longer period (5.14+/-3.8 days) than those with minor (4+/-2.5 days) or no hemorrhage (2.9+/-2.1 days). Major hemorrhage was significantly associated with impaired renal function, chronic liver disease, and concomitant treatment with warfarin or a proton pump inhibitor. Enoxaparin used in anticoagulant doses in unselected medical patients is not associated with more major hemorrhagic complications than observed in controlled clinical trials. Major hemorrhage may be more likely in older patients, in patients with chronic liver disease and impaired renal function, in patients receiving prolonged enoxaparin therapy, and in patients receiving warfarin or proton pump inhibitors.

Age Factors↗

Obstetric complications in patients with hereditary thrombophilia identified using the LCx microparticle enzyme immunoassay: a controlled study of 5,000 patients.

Factor V Leiden (FVL) and prothrombin (PT) G20210A mutations are associated with increased risk of deep venous thrombosis, pulmonary embolism, and obstetric complications. The development of inexpensive and reliable screening methods will assist in defining subpopulations of patients at risk who should undergo testing. We used a method, developed by Abbott Laboratories (Abbott Park, IL), to study 5,000 pregnant women and evaluated the association of obstetric complications with the presence of the FVL and PT G20210A mutations. We found a statistically significant association between FVL and stillbirth. There were also trends toward an association between FVL and placental abruption and between PT G20210A and intrauterine growth retardation. In addition, an association may exist between PT G20210A and preterm delivery for white women. All other parameters studied, including miscarriage and preeclampsia, did not show a statistically significant association with FVL or PT G20210A. These results confirm the association between genetic thrombophilia and selected obstetric complications.

Boston↗

The role of diabetes mellitus in the higher prevalence of tuberculosis among Hispanics.

OBJECTIVES: This research studied the relative contribution of diabetes mellitus to the increased prevalence of tuberculosis in Hispanics. METHODS: A case-control study was conducted involving all 5290 discharges from civilian hospitals in California during 1991 who had a diagnosis of tuberculosis, and 37,366 control subjects who had a primary discharge diagnosis of deep venous thrombosis, pulmonary embolism, or acute appendicitis. Risk of tuberculosis was estimated as the odds ratio (OR) across race/ethnicity, with adjustment for other factors. RESULTS: Diabetes mellitus was found to be an independent risk factor for tuberculosis. The association of diabetes and tuberculosis was higher among Hispanics (adjusted OR [ORadj] = 2.95: 95% confidence interval [CI] = 2.61, 3.33) than among non-Hispanic Whites (ORadj = 1.31: 95% CI = 1.19. 1.45): among non-Hispanic Blacks, diabetes was not found to be associated with tuberculosis (ORadj = 0.93: 95% CI = 0.78, 1.09). Among Hispanics aged 25 to 54, the estimated risk of tuberculosis attributable to diabetes (25.2%) was equivalent to that attributable to HIV infection (25.5%). CONCLUSIONS: Diabetes mellitus remains a significant risk factor for tuberculosis in the United States. The association is especially notable in middle-aged Hispanics.

Adult↗

Primary pulmonary hypertension.

Primary pulmonary hypertension (PPH) is a condition characterized by sustained elevation of pulmonary artery pressure (PAP) without demonstrable cause. The most common symptom at presentation is dyspnea. Other complaints include fatigue, chest pain, syncope, leg edema, and palpitations. Right heart catheterization is diagnostic, showing a mean PAP >25 mmHg at rest and >30 mmHg during exercise, with a normal pulmonary capillary wedge pressure. In the National Institutes of Health-PPH registry, the median survival period was 2.8 years. Treatment is aimed at lowering PAP, increasing cardiac output, and decreasing in situ thrombosis. Vasodilators have been used with some success in the treatment of PPH. They include prostacyclin, calcium-channel blockers, nitric oxide and adenosine. Anticoagulation has also been advised for the prevention of deep vein thrombosis, pulmonary embolism, and in situ thromboses of the lungs. New drug treatments under investigation include L-arginine, plasma endothelin-I, and bosentan. Use of oxygen, digoxin, and diuretics for symptomatic relief have also been recommended. Patients with severe PPH refractory to medical management should be considered for surgery.

Female↗

[Drug hypersensitive syndrome caused by fluindione].

BACKGROUND: Fluindione (Previscan) is an oral anticoagulant prescribed in relay to heparin therapy for deep venous thrombosis, pulmonary embolism... The main complications with oral anticoagulants are bleeding. However, severe immuno-allergic complications, especially acute hepatitis, acute renal failure and acute bone marrow failure, have been described with phenindione therapy. OBSERVATIONS: The authors report herein the first five cases of drug-induced hypersensitivity syndrome due to fluindione. Clinical signs included erythroderma and severe systemic manifestations which occurred within 3 to 8 weeks after introducing the molecule. Sex ratio was four males for one female; their ages ranged from 53 to 84 years. Clinical signs included erythroderma (with photosensitivity in two patients), lymphadenopathy and fever evoking severe sepsis. In our observations, marked eosinophilia (5 cases), lymphocytosis, atypical lymphocytes (4 cases), hepatic cytolysis (4 cases), associated in 2 cases with hepatic cholestasis, and pulmonary signs were noted. Cutaneous eruption healed in about 3 to 6 weeks after withdrawal of the drug. In two cases, systemic steroids were required for the severity of systemic manifestations. Long after the acute episode and when steroids were stopped, patch testing with fluindione was still positive. DISCUSSION: To date, acute and/or severe skin diseases due to fluindione, associated or not with multisystemic involvement, have never been reported. This molecule is the most commonly used for the treatment of thromboembolic diseases. Patch testing is easy to perform and can help physicians find the responsible molecule. Moreover, skin manifestations are present only in 87 p. 100 of drug-induced hypersensitivity syndromes. Acute hepatitis and acute renal failure might be drug-induced hypersensitivity syndromes without cutaneous manifestations.

Aged↗

[Falls in the elderly: analysis of potential risk based on observations in 1994-2001].

In medicine a fall is commonly construed as a sudden and totally accidental loss of postural balance, be that whilst walking or pursuing any other physical activities, in result of which a victim falls directly onto the ground, floor, or any other low-sited surface area. Frequency of falls in the elderly breaks down into 33% in the outpatients, 20% in the hospitalised patients and 45% in the nursing home residents. Data regarding the actual frequency of falls often misrepresent the facts, as most falls do not result in severe complications, although frequently enough facilitate development of post-fall syndrome and in due course in manifest deterioration of patients' overall mobility, thus making them even more prone to prospective falls. Around 10-15% of falls results in serious, life-threatening trauma. Immobilisation of a patient in the wake of a serious fall brings about a potential threat of venous thrombosis, pulmonary embolism, dehydration, muscular contracture and bed sores. Consequently, more frequent and prolonged hospitalisation is required, whereas a patient becomes steadily more care-dependent. By far the most frequent consequences of falls are bone fractures (50%), the ones sustained within the upper femoral bone area considered the most serious. Mortality resultant from post-fall complications tends to increase significantly with every decade of age. In full consideration of the above issues the present study aimed to assess the potential risk of accidental falls in the elderly, and therefore the falls sustained by 571 residents (aged 68-93 years) of two nursing homes in Krakow throughout 1994-2001 were subject to detailed analysis. The data yielded comprehensive information on the accompanying circumstances (i.e. specific location, timing, prevalent situation) within each one of the studied groups, thus facilitating development of the appropriate preventive measures. Studies comprehensively addressing the issue of accidental falls in the elderly and the attendant medical care costs sustained by the public health system are still very scarce in Poland, although the problem definitely merits further studies and an in-depth investigation, especially in consideration of the on-going restructuring within the country's medical service sector.

Accidental Falls↗

Venous thromboembolic prophylaxis following total hip arthroplasty: a North American perspective.

Patients undergoing total hip arthroplasty are at risk for venous thromboembolic disease, including deep venous thrombosis, pulmonary embolism, and postphlebitic syndrome. The incidence of these complications has declined as a result of recent advances in surgical procedures, early postoperative patient mobilization, and prophylactic alternatives. This paper reviews the benefits and disadvantages of current mechanical and pharmacologic thromboprophylactic alternatives, as well as the prophylactic effects of different anesthesia techniques and of presurgical autologous blood donation. The pharmacologic agents that are widely used in North America today include aspirin, warfarin, and low-molecular-weight heparins. The low-molecular-weight heparins-enoxaparin and dalteparin-have recently gained increasing acceptance among orthopedic surgeons. The effectiveness and safety of extending prophylaxis beyond the time of hospital discharge are also discussed. It is concluded that the optimal thromboprophylactic regimen is one that is customized, adjusted according to each patient's risk factors and other characteristics.

Anesthesia↗

Correlation of antifactor Xa concentrations with renal function in patients on enoxaparin.

Enoxaparin is a low molecular weight heparin (LMWH) that has been shown to be effective in deep vein thrombosis, pulmonary embolism, and unstable angina. Because renal function plays an important role in the clearance of LMWH, the authors sought to investigate the effect of renal function on enoxaparin. This prospective multiple-dose study evaluated 18 patients with varying degrees of renal function initiated on enoxaparin 1 mg/kg subcutaneously every 12 hours. Peak blood levels of anti-Xa concentrations were obtained 4 +/- 0.5 hours postdose after receiving at least three doses of enoxaparin. The median antifactor Xa levels were higher in patients with creatinine clearance (CLCr) < or = 30 mL/min compared to CLCr > or = 31 mL/min (1.34 IU/mL vs. 0.91 IU/mL, respectively, p < 0.05). A linear correlation was established between creatinine clearance and anti-Xa concentrations (p < 0.0005). On the basis of the data, the authors believe that a dose adjustment is necessary in patients receiving repeated doses of enoxaparin with CLCr < or = 30 mL/min.

Aged↗