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Biomedical subjects

A J Reininger

Publications and source records attributed to A J Reininger.

25 records · Page 2Linked to original sources
PubMed1994

Platelet response to vascular surgery--a preliminary study on the effect of aspirin and heparin.

Patients with peripheral arterial disease (PAD) demonstrate high cardiovascular mortality, which is further increased after arterial reconstruction. Enhanced platelet reactivity has been postulated for these patients. The effect of surgery and of periprocedural aspirin and heparin therapy on platelet reactivity was assessed with the Stagnation Point Flow Adhesio-Aggregometer (SPAA). The platelet adhesivity and aggregability of 44 PAD patients was quantitated perioperatively. Aspirin was administered during the entire course, low molecular weight heparin (LMWH) preoperatively and as of the fourth postoperative (pOP) day and unfractionated heparin (UH) upon surgery and three days thereafter. A group of 15 aspirin-free general surgical patients receiving LMWH and with no evidence of PAD served as controls. Plasma fibrinogen levels and platelet count were determined. The heparin-induced platelet activation (HIPA) assay for detection of heparin-associated thrombocytopenia (HAT) antibodies was also performed. Baseline values of SPAA-measured platelet reactivity (p < 0.001) and plasma fibrinogen (p < 0.01) were higher for patients as compared to controls and increased markedly after surgery. In the PAD group maximum platelet activation and fibrinogen levels coincided with a marked drop in platelet count and were concomitant to administration of unfractionated heparin. Thereby, a drop in platelet count of > 30% was observed in 25 patients (57%). The HIPA test verified HAT antibodies in 3 (12%) of these patients, two of which suffered postoperative thrombosis. In the control group significant pOP increases were noted only for plasma fibrinogen. Changes in platelet count and reactivity were minimal and nonsignificant. No thrombosis occurred and no HAT antibodies were detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Flow mediated fibrin thrombus formation in an endothelium-lined model of arterial branching.

In vivo arterial thrombosis occurs preferentially at curvatures and branchings, i.e. regions of flow separation and recirculation where blood is retained orders of magnitude longer than within straight vessel sections. To examine the effect of such disturbed flow on endothelial thromboresistance glass T-branchings lined with endothelial cells from human umbilical cord veins (HUVEC) were perfused with buffered fibrinogen solution (3mg/ml). The flow was adjusted to form a large recirculation zone and flow conditions were determined beforehand by means of flow visualization via dye injection as well as by laser ultramicroscope anemometry. Thrombus formation, which was registered on-line by video and evaluated planimetrically, was induced by injection of thrombin at concentrations ranging from 0.3 to 2.0 units/ml. Fibrin thrombus growth always began within the flow niche at the point of flow separation and extended downstream along the wall and into the vessel lumen finally occluding up to 80% of the lumen. Light and electron microscopy revealed that overall thrombus form as well as the orientation of single fibrin fibers were correlated strictly to the prevailing streamlines. Despite the integrity of the endothelial lining fibrin thrombus formation occurred. The fibrin fibers closely contacted the endothelial surface. These results indicate that recirculation zones promote fibrin thrombus formation sufficient to obstruct the vessel lumen and that intact endothelium alone is insufficient in preventing adhesion of fibrin to its surface.

Arteries↗
PubMed1994

Effects of magnesium on platelet aggregation and adhesion. Magnesium modulates surface expression of glycoproteins on platelets in vitro and ex vivo.

Magnesium deficiency and its association with platelet hyperreactivity has been well recognised in a variety of diseases including myocardial infarction, preeclampsia, and diabetes. In order to investigate potential effects of intravenous Mg2+ supplementation, platelet function was studied by measurements of in vitro bleeding time (BT) and of fibrinogen (Fg)-mediated aggregation of washed platelets. In addition, the effect of Mg2+ on platelet adhesion onto immobilised Fg, on Fg binding to activated platelets, and on surface expression of GMP-140 or GP53 was evaluated. Mg2+ (4 mM) prolonged in vitro BT by 30% and inhibited Fg-mediated aggregation significantly, independent of the agonist used to initiate platelet aggregation (ADP, collagen, epinephrine, thrombin, phorbol ester). Adhesion of resting platelets to immobilised Fg was reduced by 50% in the presence of 2 mM Mg2+. Moreover, Mg2+ reduced Fg binding to ADP- or collagen-stimulated platelets as well as surface expression of GMP-140 with an IC50 of approximately 3 mM. Intravenous administration of Mg2+ to healthy volunteers inhibited both ADP-induced platelet aggregation (p < 0.05) by 40% and binding of Fg or surface expression of GMP-140 by 30% (p < 0.05). Thus, pharmacological concentrations of Mg2+ effectively inhibit platelet function in vitro and ex vivo.

Bleeding Time↗
PubMed1994

[Increased pre- and postoperative thrombocyte activity in vascular surgery patients].

To determine the effect of vascular surgery on platelet function, a perioperative investigation of 37 patients with peripheral arterial disease (PAD) was performed using the Stagnation Point Adhesio-Aggregometer (SPAA). The SPAA provides well defined flow conditions. By means of dark field microscopy platelet microthrombus formation can be directly observed and measured continuously. Mathematical evaluation of resulting growth curves renders the constants for adhesion and aggregation, Kpw and Kpp, respectively. The PAD patients were divided into 2 groups: diabetics (n = 9) and nondiabetics (n = 28), and were examined perioperatively at regular intervals (average: n = 8). Preoperatively all patients received aspirin and low molecular weight heparin (LMWH). As of surgery and up to the third postoperative day all patients received unfractionated heparin (UH), at which time LMWH was resumed. Plasma fibrinogen concentration was also determined. Data obtained preoperatively were compared to those of 40 healthy volunteers (without medications). In the present study a significant increase (p < 0.001) in platelet reactivity was verified in PAD patients in spite of aspirin and LMWH administration. As of the first and up to the 8th day after surgery, a marked increase in platelet adhesivity and aggregability as well as plasma fibrinogen concentration and a concomitant decrease in platelet count was observed. Maximum values were obtained during intravenous administration of UH. Thrombocytopenia (< 150,000/ml) was observed in 12 patients. The hypercoagulability response to vascular surgery observed in the present study occurred in spite of therapy with aspirin and heparin. Our findings indicate the need for further improvement in conventional therapy and the SPAA as a useful tool in monitoring the effectiveness of current as well as of future inhibitors of platelet function.

Adult↗
PubMedDate not supplied

Quantitative analysis of platelet function using stagnation point flow aggregometry. First clinical results.

BACKGROUND: The clinical consequences of atherosclerosis result from vascular occlusion. The central role of platelet-vessel wall interaction in the initiation and perpetuation of this process is well established. Individual analysis and quantification of two major platelet functions underlying atherosclerosis and thrombosis, i.e. adhesion (platelet-wall interaction) and aggregation (platelet-platelet interaction), would contribute significantly towards elucidation of the mechanisms involved and therefore towards optimization of prophylaxis and therapy. The Stagnation-Point-Flow-Adhesio-Aggregometer (SPAA), in which such an evaluation of platelet function is possible, was thus standardized and its clinical reproducibility and predictive power assessed. METHODS: Using the SPAA, a morphometric separation of adhesion and aggregation is obtained via dark field micrographs of platelet microthrombi formed during stagnation point flow of platelet rich plasma (PRP). Quantification is achieved via biomathematical evaluation of simultaneously obtained growth curves, whereby the degree of adhesivity and aggregability is reflected in the respective growth rate constants Kpw (%) and Kpp (%). Experiments with the PRP of 36 healthy volunteers were performed and the results compared to those obtained for 32 patients exhibiting angiographically verified peripheral arterial disease (PAD). RESULTS: The control group exhibited values (Kpw) ranging from 0.40% to 1.10% (average Kpw: 0.71 +/- 0.21%). Differences in average Kpw value between the control subgroup over and that under 45 years of age were absent. A spontaneous platelet aggregation was not observed in the controls (Kpp = 0%). The overall intraindividual Kpw variation in 18 volunteers examined 3 times or more ranged from a minimum of 3% to a maximum of 20% of respective Kpw value. The patients were divided into two subgroups: diabetics and nondiabetics. The nondiabetic group demonstrated an average Kpw of 1.56%. In addition, a spontaneous aggregation was observed in 50% of all experiments (average Kpp = 1.42%). The diabetic group exhibited the highest average adhesion value (Kpw = 1.94%) occurrence of spontaneous aggregation in all experiments (Kpp = 2.10%). CONCLUSION: The consistency in adhesion values obtained among the controls as well as the minimal intraindividual variance observed, demonstrates the reproducibility of the method. The statistically significant increase (p < 0.001) in adhesivity of patients as compared to controls, as well as the common occurrence of spontaneous aggregation can therefore be considered a pathologic platelet response reflecting the severity of the disease. Results obtained verify the presence of circulating hyperreactive platelets in PAD patient and indicate the predictive power of the method. Thus the SPAA may be of considerable aid in improving thrombosis prophylaxis and therapy.

Arteriosclerosis↗