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Biomedical subjects

K Kottke-Marchant

Publications and source records attributed to K Kottke-Marchant.

53 records · Page 3Linked to original sources

Low factor XIIIA levels are associated with increased blood loss after coronary artery bypass grafting.

Current hematologic approaches to minimize postoperative bleeding have focused principally on antifibrinolytic agents. To explore whether a need might exist to promote clot stabilization independent of steps that might be taken to prevent lysis, we followed levels of the functional A-chain of factor XIII (fibrin stabilizing factor) immunologically in 19 patients undergoing coronary artery bypass grafting. The levels of factor XIIIA together with alterations in fibrinogen were followed at five stages of operation: (1) initial catheter placement (control), (2) heparinization, (3) initiation of cardiopulmonary bypass, (4) discontinuation of cardiopulmonary bypass, and (5) heparin neutralization with protamine sulfate. Significant (p < 0.05) inverse correlations were observed between postoperative chest-tube drainage volumes and levels of XIIIA at stages 1 through 3, and borderline associations (p < 0.1) were observed for stages 4 and 5. Pronounced losses of factor XIIIA accompanied initiation of cardiopulmonary bypass, when levels fell to 43% +/- 12% (standard deviation) of the control value, significantly below the 59% +/- 9% of the control value expected from hemodilution. By comparison, fibrinogen concentrations fell only to the extent attributable to hemodilution, unaccompanied by substantial degradation as indicated by electrophoretic, functional, and immunologic assays. There was a reversible heparin-induced precipitation of fibrin complexes and fibrinogen dimers from the blood on initiation of hypothermia, but these components returned to the circulation on restoration of normothermia. This precipitation was unrelated to losses of factor XIIIA. The findings warrant inference that XIIIA supplementation in deficient states should be considered as an adjunct to other therapies for postoperative bleeding.

Adult↗

Laboratory diagnosis of hemorrhagic and thrombotic disorders.

The study of hemostasis is a rapidly expanding field. Not only are new disorders being elucidated almost monthly, but also new proteins and interrelationships between known proteins are being reported continuously. These factors make the study of hemostatic disorders at once both exhilarating and challenging. New analysis techniques, such as chromogenic assays, ELISA assays, and molecular techniques, have advanced the study of hemostasis from the early days of tilt tube-based clotting tests. Further advancement in test automation will provide detailed analytic capabilities to smaller laboratories in the future. Additionally, continued advances in genetic testing will eventually allow us a detailed molecular view of a patient's hemostatic system previously unthinkable. This review has attempted to synthesize a very broad range of hemostatic physiology, laboratory testing, and pathologic disorders into a brief synopsis. Many details have unfortunately been excluded, but it is hoped that the nucleus of information presented on the recognition and diagnosis of hemostatic disorders will be valuable in the evaluation of patients with both simple and complex bleeding and thrombotic disorders.

Blood Coagulation Disorders↗

Immobilization of high-affinity heparin oligosaccharides to radiofrequency plasma-modified polyethylene.

Oligosaccharides of heparin with high affinity for antithrombin III (ATIII) have been immobilized onto surface-modified NHLBI Primary Reference low density polyethylene (PE). PE was modified by radiofrequency plasma polymerized (< 150 nm thick) films derived from N-vinyl-2-pyrrolidone (PPNVP) or allyl alcohol (PPAA), and coupled by chemical derivatization to either 3-aminopropyltriethoxysilane or amino-terminated poly(ethylene oxide). High affinity heparin oligosaccharides (HA-heparin, anti-factor Xa activity of 592 +/- 120 IU/mg) prepared by partial deaminative cleavage of commercial crude heparin and fractionated by agarose-ATIII affinity chromatography, were immobilized to surface-modified PE by reductive amination. The anticoagulant activity, as determined by a chromogenic assay for the inhibition of factor Xa, was estimated to be 30-70 mIU/cm2, with binding estimated to be 56-119 ng/cm2. The highest activity was obtained for the HA-heparin immobilized to PE modified by PPNVP with a PEO spacer. Visual confirmation of ATIII binding to immobilized HA-heparin was demonstrated by a gold-labeled double antibody method with imaging by SEM.

1-Propanol↗

Effect of Buckberg cardioplegia and peripheral cardiopulmonary bypass on infarct size in the closed chest dog.

OBJECTIVES: To simulate a human catheterization laboratory setting of controlled reperfusion during myocardial infarction, regional infusion of commercially available Buckberg cardioplegic solution and peripheral vented bypass were administered in the closed chest dog. BACKGROUND: Studies in open-chest dogs have demonstrated a significant reduction in infarct size and improvement in regional wall motion with a similar controlled reperfusion method using infusion of substrate-enriched (Buckberg) cardioplegic solution during cardiopulmonary bypass coupled with left ventricular venting. METHODS: After 100 or 180 min of balloon occlusion of the proximal left anterior descending artery, controlled reperfusion was performed with cardioplegic infusion and vented bypass. Dogs matched for occlusion time underwent balloon deflation without bypass or cardioplegia (uncontrolled reperfusion groups). Microspheres were used to quantify coronary ischemia during balloon inflation. All four groups (n = 8 to 9 per group) were followed up at 1 week to determine regional wall motion and infarct size. RESULTS: Qualitative echocardiographic analysis demonstrated no significant difference among groups in recovery of regional wall motion at 1 week; however, wall motion improved significantly in all groups between the ischemia and 1-week recovery periods. The histologic infarct size compared with the area at risk for dogs with uncontrolled versus controlled reperfusion, respectively, was 17.9 +/- 10.5% versus 31.9 +/- 8.3% (p < 0.05) for dogs with 100 min of occlusion and 40.1 +/- 11.7% versus 46.2 +/- 8.4% (p = NS) for dogs with 180 min of occlusion. A greater rate-pressure product in the dogs with controlled reperfusion after 100 min of occlusion (p < 0.05) may explain the larger infarct size observed for that group. CONCLUSIONS: These results demonstrate that regional infusion of substrate-enriched cardioplegic solution in combination with peripheral vented bypass does not further reduce infarct size after prolonged ischemia in the closed chest dog (compared with uncontrolled reperfusion).

Animals↗

The immobilization of glucose oxidase onto radio-frequency plasma-modified poly(etherurethaneurea).

Glucose oxidase was covalently immobilized onto a radio-frequency plasma-modified poly(etherurethaneurea). Thin (90-100 nm) plasma-polymerized N-vinyl-2-pyrrolidone films were deposited onto poly(etherurethaneurea) films. Active sites for the immobilization were obtained via reduction with aqueous sodium borohydride and activation with 1-cyano-4-dimethylaminopyridinium tetrafluoroborate. Modified poly(etherurethaneurea) films were assayed for binding and activity of the immobilized glucose oxidase layer. The results of a modified radioimmunoassay and an 'immunochemical stain' indicated that washing in 900 ml of continuously stirred 2% sodium dodecyl sulfate, 2% Triton X-100, and 20 mM sodium phosphate, pH 7.0, for 24 h each at 4 degrees C was necessary to remove physically adsorbed glucose oxidase from the solid supports. An amperometric activity determination in 9 ml of well-stirred 20 mM sodium phosphate-0.1 M sodium chloride, pH 7.4, gave a qualitative demonstration of the activity of the immobilized enzyme on 18.75 cm2 of modified poly(etherurethaneurea) film. A colorometric activity determination using the coupled reaction with o-dianisidine and peroxidase indicated that glucose oxidase covalently immobilized on approximately 2.4 cm2 of modified poly(etherurethaneurea) film had an activity approximately equal to that of 13.4 nM glucose oxidase in 50 mM sodium acetate, pH 5.1, with a specific activity of approximately 32.0 U/mg at pH 5.1 and room temperature.

Biocompatible Materials↗

Early brain metastases in endometrial carcinoma.

Endometrial carcinoma is the most common invasive neoplasm of the female genital tract. Yet, intracranial metastases are rare and usually associated with widespread disease. We report three patients with endometrial carcinoma and early brain metastases, two with unsuspected endometrial carcinoma presenting with neurologic symptoms and one who developed neurologic symptoms on the day of hysterectomy. Histologically, one tumor was a clear cell carcinoma and two were endometrial adenocarcinoma. In tumors with a mixture of nuclear grades, the most undifferentiated portion metastasized. Two tumors displayed vascular invasion and deep myometrial invasion. Only one had positive estrogen receptors. Intracranial metastases can occur early in the course of endometrial carcinoma. They are associated with aggressive high-grade neoplasms with deep myometrial and vascular invasion.

Adenocarcinoma, Papillary↗

Endomyocardial biopsy. Pathologic findings in cardiac transplant recipients.

With the advent of cyclosporin therapy, cardiac transplantation has become an effective procedure in treating selected patients with end-stage myocardial diseases. Because cyclosporin masks the clinical symptoms of rejection, the endomyocardial biopsy has become the "gold standard" for grading allograft rejection. Many classification systems for grading rejection have been proposed, largely based on the original work of Billingham. Comparisons among these schemes, useful for the evaluation of results from different centers, might be facilitated by adoption of the concept of stable versus unstable acute rejection. Many questions remain regarding the mechanism of acute rejection, the diagnosis of chronic rejection by endomyocardial biopsy, the effects of therapy, and the pathogenesis of endocardial lymphocytic infiltrates, to name a few. However, the recently developed techniques of in situ hybridization and propagation of lymphocytes from endomyocardial biopsies in conjunction with immunohistochemistry and electron microscopy may bring us to a new level of sophistication in understanding the pathology of cardiac transplantation.

Acute Disease↗

Localized fibrous tumor (localized fibrous mesothelioma) of the liver.

A case of localized fibrous tumor (LFT) (localized fibrous mesothelioma) of the liver in an 83-year-old woman is presented. The tumor was 15 x 9 x 8 cm and was confined to the left lateral segment of the liver. Occasional mitotic figures (MF) (2 to 3 per 50 high-power fields [HPF]) were present. Strong, diffuse vimentin positivity was demonstrated by immunohistochemistry. Immunoreactivity for cytokeratins (AE1-3), epithelial membrane antigen (EMA), desmin, and desmosomal proteins (desmoplakin I + II) was absent. Electron microscopic examination showed a mesenchymal appearance of the majority of neoplastic cells, with a few ultrastructural features suggestive of mesothelial differentiation. These findings supported a submesothelial origin of the tumor. After a partial hepatectomy with total gross and microscopic removal of the tumor, the patient was alive without recurrence at 2 years, 5 months later. A review of the English literature showed six additional cases that are probably similar. Currently, all tumors have been clinically benign, although follow-up information has been limited.

Aged↗

Effect of albumin coating on the in vitro blood compatibility of Dacron arterial prostheses.

A recirculating in vitro perfusion system was used to assess the effect of albumin precoating on the thrombogenicity of Dacron vascular grafts. A complete analysis of platelet activation was carried out, involving platelet count, release, adhesion and aggregation. Fibrin formation was assessed by measuring fibrinogen levels and fibrinopeptide A production; leucocyte interaction was analysed by measuring total leucocyte count as well as an analysis of cell adhesion to the surface by scanning electron microscopy. The platelet count decreased progressively with perfusion time for Dacron until by 30 min, it had declined to 69% +/- 2% of baseline. The platelet count did not, however, change significantly from baseline when albumin-coated Dacron was tested. Release of platelet factor 4 and beta-thromboglobulin at 180 min for Dacron was 37.8 +/- 29.8 times and 66.9 +/- 18.2 times baseline, respectively, while albumin coating caused significantly less (P less than 0.03) platelet release. Albumin coating diminished coagulation activation and fibrinopeptide A formation. The total leucocyte concentration decreased significantly for Dacron by 180 min, while that for albumin-coated Dacron did not change significantly from baseline levels. Albumin coating produced a film-like covering over the Dacron. For Dacron, there were numerous leucocytes and platelets adherent to the surface, whilst cellular deposition was minimal upon the albumin-coated surface. Thus, albumin coating improved the short-term blood compatibility of Dacron by all of the methods employed in this study.

Albumins↗

Endomyocardial lymphocytic infiltrates in cardiac transplant recipients. Incidence and characterization.

The incidence, morphology, and immunoreactivity of endomyocardial lymphocytic infiltrates (ELIs) were studied to define the lesion more precisely, gain insight into its cause, and elucidate a possible relationship between ELIs and other lymphoproliferative lesions known to be associated with cyclosporine treatment of transplant recipients. We found ELIs in 166 (14.4%) of 1152 biopsy specimens from cyclosporine-treated patients with cardiac transplants, with 78.6% of those patients having at least one ELI. The ELIs ranged in size from 0.007 to 1.89 mm2 and were predominantly T-lymphocyte infiltrates with foci of polyclonal B lymphocytes (follicular center type). Macrophages and plasma cells were located at the interface between the ELI and myocardium. The infiltrate extended into the myocardium in approximately 50% of cases and was associated with severe, local myocyte injury. The morphologic and immunohistochemical appearance was distinct from that of acute rejection and consistent with an early lymphoproliferative lesion of the type associated with Epstein-Barr virus and cyclosporine therapy.

Biopsy↗

Comparison of whole-blood cyclosporine levels and the frequency of endomyocardial lymphocytic infiltrates (the Quilty lesion) in cardiac transplantation.

Endomyocardial lymphocytic infiltrates (ELI), or "Quilty" lesions are morphologically and immunohistochemically distinct and are thought to be due in part to Cyclosporine therapy. In order to evaluate the relationship of ELI to CsA therapy, we compared the whole-blood CsA levels (WBCsA) with the frequency of ELI in our cardiac transplant patients. From January 1, 1987 to January 1, 1988, 364 concurrent endomyocardial biopsies and WBCsA were performed on 43 cardiac transplant patients. All biopsies were evaluated for acute rejection. ELI were recognized as well-circumscribed, flat or pedunculated lesions within the endomyocardium composed of mature T lymphocytes with pockets of B lymphocytes and occasional macrophages and plasma cells. All WBCsA were trough levels and were determined by high-pressure liquid chromatography. Results were evaluated using a logistic regression model for clustered data. ELI were observed in 17.9% (65/364) biopsies, and 60.5% (26/43) of patients had at least one ELI during the study period. The mean WBCsA was 155.2 ng/ml (SD = 62.9) in the ELI-positive group, and 190.2 ng/ml (SD = 97.0) in the ELI-negative group. Applying the regression model revealed a statistically significant negative correlation between WBCsA and the presence of ELI (P = 0.033)--that is, a lower WBCsA was associated with an increased probability of ELI. The frequency of clinically significant rejection was lower in the ELI-positive biopsies, and this correlation approached statistical significant (P = 0.053). These data suggest that ELI are unrelated to increased WBCsA and may represent an idiosyncratic reaction to CsA, or be related to factors other than CsA therapy.

Adolescent↗

Vascular graft-associated complement activation and leukocyte adhesion in an artificial circulation.

Complement-associated leukocyte adhesion appears to be a consistent in vitro and in vivo finding for many types of polymers; however, very little work has been done on the interaction of leukocytes with vascular graft materials. An in vitro perfusion system was used to study complement and leukocyte activation associated with the following vascular graft materials when tested with human blood: expanded polytetrafluoroethylene (ePTFE), crimped Dacron Bionit (DB) and preclotted Dacron Bionit. A decrease in the total leukocyte concentration with perfusion time was seen for all materials tested, and paralleled leukocyte adhesion to the graft surface as observed by scanning electron microscopy. The most dramatic decrease in leukocyte concentration was observed for the interaction of heparinized whole blood with Dacron. This was due to a selective decrease in neutrophils and monocytes, and was correlated with an increase in both leukocyte adhesiveness and complement activation, as measured by C5a elevation. Inhibiting complement activation by use of the anticoagulant, sodium citrate, curtailed Dacron-induced leukocyte adhesion. Little leukocyte or complement activation was observed for ePTFE or the silicone rubber control regardless of the anticoagulant used.

Adult↗

The platelet reactivity of vascular graft prostheses: an in vitro model to test the effect of preclotting.

An in vitro perfusion system was used to study the platelet reactivity of the following vascular graft materials when tested with human blood: expanded polytetrafluoroethylene (ePTFE), crimped Dacron Bionit (DB) and preclotted Dacron Bionit (DB/PC). These materials were simultaneously compared to silicone rubber (SR) using an identical perfusion circuit with the same donor's blood. All vascular graft materials tested in this in vitro perfusion system caused some degree of platelet activation as shown by a decrease in platelet count, an increase in platelet factor 3 activity, elevation of plasma levels of both platelet factor 4 and beta-thromboglobulin and decreased platelet aggregability. The observed platelet activation was striking for Dacron and especially preclotted Dacron, with ePTFE showing low levels of platelet activation. Platelet activation by Dacron was initially rapid and then levelled off, whereas the platelet activation with preclotted Dacron began more slowly, but reached much greater levels after three hours of in vitro perfusion.

Blood Coagulation↗

The effect of heparin vs. citrate on the interaction of platelets with vascular graft materials.

Heparin is known to affect platelet function in vitro, but little is known about the effect of heparin on the interaction of platelets with polymer surfaces in general, and vascular graft materials in particular. For this reason, the effect of heparin vs. citrate anticoagulation on the interaction of platelets with the vascular graft materials expanded polytetrafluoroethylene (ePTFE), Dacron Bionit (DB) and preclotted Dacron Bionit (DB/PC) was studied in a recirculating, in vitro perfusion system. Platelet activation, as shown by a decrease in platelet count, an increase in platelet release and a decrease in platelet aggregation, was observed for all vascular graft materials tested using heparin and was greater for Dacron and preclotted Dacron than for ePTFE. Significant differences between heparin and citrate anticoagulation were seen for platelet release, platelet aggregation and the relative ranking of material platelet-reactivity. However, the trends and time course of platelet activation were similar with both heparin and citrate for the materials tested.

Adult↗

Hemostatic profiles of HeartMate ventricular assist device recipients.

Candidates for ventricular assist devices often have hepatic dysfunction and concomitant coagulation abnormalities. Factors II, V, VII, XI, plasminogen, fibrinopeptide A (FpA), and D-dimers were measured in 19 HeartMate (ThermoCardiosystems, Inc., Woburn, MA) patients before device implantation; at 6 hr, 24 hr, and 2 weeks postimplantation; and before explantation. Ten patients had entry hepatic dysfunction (total bilirubin > 2 mg/dl; aspartate and alanine aminotransferases > 60 U/L); nine had normal hepatic function. All except one patient received perioperative aprotinin; all received only aspirin and dipyridamole after surgery. At preimplant, both patient groups had subnormal factor II, V, VII, XI, and plasminogen with elevated FpA and D-dimer. By 2 weeks postimplant, these factor levels had normalized, except for FpA and D-dimer levels, which suggest ongoing remodeling of fibrin deposits on the device surfaces. No statistically significant differences in the assayed hemostatic markers were observed between the two patient groups. Clinically, 15/19 (79%) patients survived to cardiac transplantation; 3/19 (16%) patients required reoperation for early bleeding. All three had low factor VII and XI; two of three also had hepatic dysfunction and subnormal levels of factor II and V. Most patients with entry hepatic dysfunction improve after device implantation; all four deaths were in patients with persistent hepatic dysfunction despite circulatory support.

Blood Coagulation Factors↗

The preoperative bleeding time test: assessing its clinical usefulness.

The bleeding time test can aid in the diagnostic evaluation of patients with clinical hemorrhagic disorders or a history of bleeding. However, its low positive predictive value in predicting perioperative bleeding should force one to abandon it as a routine preoperative screening test.

Bleeding Time↗