Antibodies to prothrombin, factor V, and beta2-glycoprotein I and vascular access thrombosis.

We studied 88 hemodialysis patients for the presence of antibodies to human factor II (hFII), bovine factor V (bFV), and human beta2-glycoprotein 1 (beta2GPI). Forty-one patients had elevated anti-hFII antibodies, 17 had elevated anti-bFV antibodies, and 9 had elevated anti-beta2GPI antibodies. Fifty-two patients had elevated antibodies to one or more protein. Patients with PTFE grafts had elevated antibodies most frequently (21 [75%] vs. 20 fistulas [45%; p = 0.016 compared with PTFE] and 11 tunneled catheters [68.8%]). Twelve of 13 patients (92.3%) with PTFE grafts and thrombosis had elevated antibody levels, compared with 9 of 15 without thrombosis (60%; p = 0.049). The number of thromboses and mean thrombosis rates were significantly higher in PTFE patients with antibodies (1.24 vs. 0.14 thromboses, p < 0.01; 42.67 vs. 6.44 thromboses/100 patient years, p < 0.05). When analyzed individually, thrombotic complications occurred more frequently in patients with PTFE grafts and elevated anti-bFV antibodies (p = 0.016), but did not correlate with anti-hFII or anti-beta2GPI antibodies. Thrombotic complications did not correlate with elevated antibody levels in patients with AV fistulas or cuffed catheters. In conclusion, hemodialysis patients with PTFE grafts frequently have elevated antibodies to FII, FV, and beta2GPI, and the presence of elevated antibody levels to one or more of these proteins is associated with an increased thrombotic risk. Further studies are necessary to determine whether limiting exposure to bovine thrombin preparations will decrease the incidence of these antibodies and PTFE graft thrombosis.

Risk factors associated with thrombosis in patients with antiphospholipid antibodies.

OBJECTIVE: To define risk factors associated with thrombosis in patients with antiphospholipid antibodies (aPL). METHODS: Ninety-nine patients with aPL, most of whom had prior thrombosis, were evaluated for the presence of acquired and inherited thrombophilic states. Genomic testing was performed for factor V(R506Q), 3' prothrombin (PTG) and methylene tetrahydrofolate reductase (MTHFR) polymorphisms. Clinical records were reviewed for the presence of acquired risk factors (RF) for thrombosis and events associated with aPL. Univariate statistical analysis was performed using Fisher's exact testing. A neural network statistical model was also used to identify which thrombophilic risk factors were most important in development of arterial and venous thrombosis. RESULTS: For arterial thrombosis, hypertension, tobacco use, hyperlipidemia, and diabetes mellitus were the most important predictors of thrombosis. By contrast, tobacco use, the 3' PTG and factor V(R506Q) polymorphisms, and previous cardiac surgery were the most important predictors of venous thrombosis. CONCLUSION: In this hypothesis-generating retrospective study, acquired risk factors were most important in arterial thrombosis, while the presence of factor V(R506Q) and 3' PTG polymorphisms were more important in the development of venous thrombosis. These findings are being validated in an ongoing, prospective study.

Setting the record straight: physician networking is an effective strategy.

Case studies of 11 leading integrated delivery systems (IDSs) disclose that, despite the widespread perception that integrated health care--and particularly the acquisition of physician networks--is a failed strategy, integration can be a vibrant and effective strategy if approached properly. The successful case-study IDSs have certain attributes in common: many were founded by multispecialty clinics; they involve physicians in a partnership role with administrators; and the primary purpose of their physician networks is to offer patients convenience and broader access to the system, rather than simply to increase referrals to the hospital or to compete for capitation contracts. Moreover, all of the IDSs are actively pursuing measures to improve the financial performance of their physician networks, including closing marginal clinics, improving economies of scale, adding ancillary and specialty services, seeking administrative procedures, and enhancing information technology capabilities.

Factor VIII Arg2304 --> His binds to phosphatidylserine and is a functional cofactor in the factor X-ase complex.

Four factor VIII light chain constructs containing hemophilia A mutations at R2304 and R2307 were prepared and expressed in mammalian cells. These mutations are located in a putative phosphatidylserine binding site identified by peptide studies (spanning amino acids 2303-2332). The levels of all four mutants in conditioned medium were significantly less than wild type by immunoprecipitation and ELISA. R2304H and wild type factor VIII light chains were concentrated by cation exchange chromatography from medium. R2304H and wild type factor VIII light chains bound immobilized phosphatidylserine similarly. The reconstituted cofactor activity of R2304H factor VIII light chain was slightly greater than wild type factor VIII light chain. These results are consistent with the recently reported crystal structure of factor VIII C2 domain that suggests R2304H is not directly involved in phospholipid binding. The observed clinical phenotype is probably due to decreased circulating levels of a functional protein.

Immunologic impact and clinical outcomes after surgical exposure to bovine thrombin.

OBJECTIVE: To determine prospectively the immunologic response and adverse clinical events in surgical patients exposed to bovine thrombin during cardiac surgical procedures. SUMMARY BACKGROUND DATA: Topical bovine thrombin is used extensively as a hemostatic agent during cardiovascular surgery. Antibodies developing after exposure to bovine thrombin have been anecdotally associated with hemorrhagic complications. METHODS: One hundred fifty-one patients undergoing cardiac surgical procedures were prospectively recruited for this study before surgical exposure with topical bovine thrombin. Immunoassays were used to determine antibody levels against both bovine and human coagulation proteins before and after exposure to bovine thrombin. Alterations in coagulation assay parameters and adverse clinical events were followed in all patients enrolled in the study. RESULTS: Baseline elevated antibody levels to one or more bovine coagulation proteins were observed most frequently in patients with a prior history of a surgical procedure during which bovine thrombin is frequently used. More than 95% of patients developed a seropositive response to bovine coagulation proteins, and 51% manifested elevated antibody levels to the corresponding human coagulation proteins after bovine thrombin exposure. Postoperative coagulation abnormalities were more common in patients with antibodies to human coagulation proteins. Patients with multiple elevated antibody levels to bovine proteins before surgery were more likely to sustain an adverse clinical outcome after surgery. Using a logistic regression model, the adjusted odds ratio for sustaining an adverse event with multiple elevated antibody levels to bovine proteins before surgery was 5.40. CONCLUSIONS: Bovine thrombin preparations are highly immunogenic and appear to be associated with an increased risk for adverse clinical outcomes during subsequent surgical procedures. The clinical safety of these commonly used preparations needs to be reassessed, and reexposure to these agents should likely be avoided.

Intercalibration method for underwater three-dimensional mapping laser line scan systems.

I present a method to calibrate absolutely a new family of underwater bathymetric laser scanner systems that use a single target range. Depth is calculated by triangulation among the source, the receiver, and the instantaneous position of a single spot produced by a highly collimated laser beam scanned across the target. For calibration, the refractive index of seawater is used to modulate the triangulation parameters rather than use of different target ranges to calibrate for extended range operation. Exploitation of a unique triangulation configuration allows the receiver characteristics to be ignored initially so that the scanner parameters can be determined. This allows the accurate positioning of the laser spot so that the receiver, in turn, can be calibrated. This intercalibration method provides high-resolution parameterization of the source-receiver characteristics and their geometric layout within the system so that an absolute bathymetric calibration can be realized in situ. In addition, a theoretical model derived to develop the methodology can be used to characterize and optimize future designs.

The right strategy and perseverance can make an IDS profitable.

Results of a recent study of 11 leading integrated delivery systems (IDSs) belie the common perception that IDSs are incapable of turning a profit. The study determined that the primary factors driving the poor financial performance of IDSs are organizational complexity, payment reductions mandated by the Balanced Budget Act of 1997, and a general lack of foresight regarding financial problems when embarking on an integration strategy. By implementing a wide range of initiatives to stem losses and improve financial performance, several of the case-study IDSs have accomplished dramatic financial turnarounds over the past three years, and all have achieved consistently stronger financial performance.

Assessment of primary hemostasis by PFA-100 analysis in a tertiary care center.

We evaluated the utility of the PFA-100 platelet function analyzer in identifying disorders in platelet function and/or von Willebrand factor (vWF) in patients with various systemic disorders being followed at a tertiary care center. Closure times were determined with collagen/ ADP (CADP) and collagen/epinephrine (CEPI) cartridges for 305 patients, and abnormal results were further evaluated with platelet aggregometry and vWF analysis. Prolonged CADP and/or CEPI closure times were identified in 114 patients (37.3%), but most were isolated prolonged CEPI closure times predominantly due to aspirin therapy (79 patients). Prolonged CADP closure times were most frequently due to qualitative platelet defects and/or decreased vWF levels. Prolonged CADP closure times were encountered most frequently in patients with sickle cell disease and were associated with a decreased hematocrit. This study demonstrated that the PFA-100 analyzer can accurately assess vWF-dependent platelet function and detect other platelet defects under high shear stress in complex patient populations.

Antibodies to topical bovine thrombin correlate with access thrombosis.

Bovine thrombin is often used topically to promote hemostasis during vascular surgery, including dialysis-access placement. Patients frequently develop antibodies to bovine thrombin preparations, and some may develop antiphospholipid antibodies. We evaluated 88 hemodialysis patients for the presence of antibodies to topical bovine thrombin to determine if elevated antibody levels correlated with vascular access thrombosis. Twenty-seven patients (30.7%) had elevated antibody levels to topical bovine thrombin. More patients with elevated antibody levels had prior vascular access thrombosis than patients with normal antibody levels (13 of 27 versus 5 of 61 patients; P < 0.001). This difference was almost entirely the result of greater levels of thrombosis in patients with polytetrafluoroethylene (PTFE) grafts and elevated antibody levels. In these patients, 11 of 13 patients (84.6%) with elevated antibody levels had a previous thrombosis compared with 2 of 15 patients (13. 3%) with normal antibody levels (P < 0.001). Patients with elevated antibody levels and PTFE grafts also had more prior thromboses (1.92 +/- 1.60 versus 0.133 +/- 0.35 thromboses; P < 0.01) and a greater thrombosis rate (66.89 +/- 63.71 versus 4.65 +/- 12.05 thromboses/100 patient-years; P < 0.01) than patients with normal antibody levels. There were no differences in the frequency of myocardial infarction, coronary artery bypass, access age, presence of diabetes mellitus, platelet counts, anticardiolipin antibody, albumin, lactate dehydrogenase, or C-reactive protein levels. In conclusion, patients with PTFE grafts and elevated antibody levels to topical bovine thrombin had significantly more vascular access thrombosis.

The effect of weight-bearing on the radiographic measurement of the position of the femoral head after total hip arthroplasty.

BACKGROUND: In most radiographic studies of polyethylene wear, investigators have used routine annual radiographs made with the patient in the supine position in order to measure penetration by the femoral head into the polyethylene liner. However, researchers have begun to question the effect of weight-bearing on the position of the head within the acetabular cup and, consequently, the effect of weight-bearing on measurements of penetration by the head. The purpose of the current study was to determine the effect of weight-bearing on the two-dimensional radiographic position of the femoral head within the acetabular cup. METHODS: Thirty-seven patients (forty-seven hips) who had had a total hip arthroplasty had radiographs made at one of two separate institutions. A set of anteroposterior radiographs was made for each patient: one radiograph was made with the patient supine and one was made with the patient upright bearing full weight on the replaced hip. At one of the institutions, a third anteroposterior radiograph was made with the patient in the same upright position but not bearing weight on the replaced hip. All measurements of the two-dimensional position of the head were performed by a single observer with use of a previously published computerized measurement system. RESULTS: Data from both institutions revealed that measurements of the position of the head on radiographs made with the patient supine were strongly and significantly correlated with measurements of the position of the head on radiographs made with the patient bearing weight (r2>0.93, p<0.001 for both regressions). Examination of the differences between the measurements revealed no bias for one set of measurements to consistently underestimate or overestimate the values derived with use of the other method. Moreover, we found a nearly perfect relationship between the measurements of the position of the head on radiographs made with the patient standing and bearing weight and those on radiographs made with the patient standing but not bearing weight (r2 = 0.97, p<0.001, slope = 0.99, intercept = 0.02 millimeter). CONCLUSIONS: On the basis of these findings, there is no evidence that radiographs must be made with the patient bearing weight in order to accurately measure the position of the femoral head within the polyethylene liner.

Capital and medical groups. Key issues facing physicians and practice administrators.

More and more physician groups are considering taking a capital partner, whether a physician practice management company, a hospital or other organization. But physicians have questions about how partnership will affect their salary in the short and long run, whether it will affect practice overhead, quality of care and physician control. They also want to know what to do if the relationship doesn't work out. This article answers those questions and recommends that groups do a careful self-evaluation and scrutinize any potential partners before making a move.

Providing capital for physician group practices: new opportunities for hospitals.

As physician group practices grow and consolidate, they have an increasing interest in developing close capital partnerships to ensure access to capital. Yet as many healthcare organizations have sought to divest poorly performing acquired physician practices, physicians have seen their pool of potential capital partners shrink. Under these conditions, hospitals have a new opportunity to present themselves to physician group practices as attractive capital partners. To understand the nature of this opportunity, one needs to know why group practices seek capital, how groups approach their investment strategies, and what criteria they use to compare prospective capital partners. To build stronger relationships with physicians, hospitals should focus on turning around their poorly performing acquired physician practices and pursue strategies such as collaborating with physician practice management companies and developing new models for partnering with physicians (e.g., special purchase agreements and more advanced management services organizations).

Total hip arthroplasty with porous-coated prostheses fixed without cement in patients who are sixty-five years of age or older.

We reviewed the results of 212 total hip arthroplasties performed without cement in 203 unselected, consecutive patients who were sixty-five years of age or older. The outcome was known for 196 hips, thirty-seven of which had been followed until the death of the patient and 159 of which had been followed for a minimum of five years. A reoperation was done in 4 percent (seven) of the 196 hips. These reoperations included one revision because of loosening of the stem and five revisions of the cup. Three of the acetabular revisions were done because of fracture due to polyethylene wear; one, because of recurrent dislocation; and one, because of polyethylene wear and a fracture due to lysis. In the seventh reoperation, a cup and stem were exchanged because of infection. The probability that a hip prosthesis would survive twelve years without a reoperation was 0.92 (95 percent confidence interval, 0.85 to 0.99). We evaluated the clinical results for 152 patients who had not had a reoperation and had been followed for at least five years (mean, 8.5 years; range, five to fourteen years). Of these patients, thirteen (9 percent) had pain that limited activity: five (3 percent) had pain in the thigh (four patients) or groin (one patient), and eight (5 percent) had trochanteric pain and tenderness. One hundred and forty-four (95 percent) of the patients noted an improvement in overall function, and 149 (98 percent) reported satisfaction with the outcome. One hundred and thirty-five hips that were not revised were followed radiographically for at least five years (mean, 8.2 years; range, five to fourteen years). In this group, osteolysis was observed in three hips (2 percent); loosening of the cup, in three (2 percent); and loosening of the stem, in one (1 percent). Stress-shielding was seen on the two-year postoperative radiographs of forty-five (26 percent) of the 174 hips that were followed for at least that duration. The prevalence of osteolysis, loosening of a component, and reoperations was no greater in this subgroup than in the overall group. These results indicate that total hip arthroplasty without cement can be successful in older patients. This study also provides a reference for comparison with the results of total hip arthroplasty performed with cement and those of so-called hybrid total hip arthroplasty (an acetabular component fixed without cement and a femoral component fixed with cement) in patients who are sixty-five years of age or older.