Karen F. Marcoe

Platelet aggregometry can accurately predict failure of externally supported knitted Dacron femoropopliteal bypass grafts

PURPOSE Our purpose was to evaluate whether a method for quantification of platelet aggregability will predict failure of knitted Dacron femoropopliteal bypass grafts. METHODS A numerically derived platelet aggregation (PA) score, based on the aggregation pattern and platelet count, was determined in the 40 patients available for platelet analysis who underwent 53 femoropopliteal bypass grafts with preclotted, 6 mm, externally supported knitted Dacron grafts from 1981 to 1991 (mean follow-up 50 months). The preoperative score was found to remain stable after surgery, enabling the use of postoperative values when preoperative values were not available. The PA score was available in 19 patients (23 grafts) before surgery and 23 patients (30 grafts) after surgery. The following factors were analyzed for predicting graft failure by the Cox proportional hazards regression model: PA score, age, gender, history of smoking, coronary artery disease, hypertension, hyperlipidemia, cerebrovascular disease, diabetes, claudication versus limb salvage, site of the distal anastomosis, previous ipsilateral bypass, and state of the runoff as determined by preoperative angiography. RESULTS Of the studied risk factors, the value of the PA score was the most significant predictor of graft closure (p < 0.0001). An increase of 10 units was associated with an increased relative risk of 2.02. Throughout the follow-up period, 15 of 16 grafts remained patent in patients with a PA score of 15 or less, but only 2 grafts out of 17 remained patent in patients with a PA score of 30 or greater. CONCLUSIONS These data suggest that the PA score is a potential risk factor for failure of femoropopliteal bypass with externally supported knitted Dacron grafts.

Aspirin therapy in small-caliber arterial prostheses: Long-term experimental observations*

To study the therapeutic effects of 3 mg/kg aspirin given at the time of surgery and postoperatively, Dacron carotid grafts with an internal diameter of 4 mm and a length of 6 cm were implanted bilaterally in mongrel dogs. Sixteen control grafts in eight subjects and 20 grafts in 10 subjects treated with aspirin were followed by serial angiograms until consecutive studies showed stable patency rates in both groups. Platelet aggregations, malondialdehyde production, serum salicylate levels, and thromboxane A2 and prostacyclin secretion (measured as thromboxane B2 and 6-keto-prostaglandin F1 alpha) were monitored prior to and throughout the experiment. Surface mapping, indium-111 uptake, factor VIII-related antigen staining, and scanning and transmission electron microscopy were performed on the grafts at sacrifice. This study demonstrates a protective effect on the early patency of small-caliber prostheses in the canine model with daily oral aspirin administration. The degree and duration of this effect depends on the preoperative baseline ratio of thromboxane to prostacyclin in each subject.

Glutaraldehyde preparation of coronary artery bypass bioprostheses

A method for glutaraldehyde (GA) fixation of canine carotid arteries has been developed for the preparation of small caliber biologic prostheses for coronary artery bypass. The biologic grafts were preserved by a static inflation technique that proved to be more advantageous than the standard stenting method. The most suitable static inflation pressure was found to be 120 mm Hg. By means of colorimetric measurements the minimal tanning time and the amount of GA required for complete fixation for canine vascular tissue were established. Stabilization of the vessel collagen and confirmation of GA-collagen cross-linking were verified by evaluation of the elastic properties and shrinkage temperature of the grafts. Stress-strain measurements were evaluated to determine the number of cross-links introduced in the vascular tissue by GA. This number was shown to be proportional to the inflation pressure. Ethyl alcohol was chosen as the storage solution because it maintained the best physical, chemical, and histologic characteristics of the grafts. Biological evaluations were performed with carotid implants that were examined following acute low flow studies and implantations up to 112 days. All implantations have yielded 100% patencies.

Citric Acid Enhances the Antithrombotic Effect of Aspirin in Many Aspirin-Resistant Subjects

This study had three objectives: (1) to determine the frequency of high platelet aggregators in a consecutive series of 268 apparently healthy volunteers who presented to our Center; (2) to assess the inhibitory effect of aspirin (ASA) on these high aggregators; (3) to determine, in a double-blind trial, whether or not the addition of citric acid (CTA) to ASA would increase its inhibitory effect in subjects who had a suboptimal response to aspirin alone. A platelet aggregation-scoring methodology developed for turbidimetric platelet aggregometry was used to quantify baseline aggregation and medicinal effects. We define a high aggregator as one whose unmedicated PA score is ≥30. We define the response of a high aggregator to ASA as poor if the medicated PA score stays at ≥30. We found that 58 of 268 apparently healthy unmedicated volunteers (22%) had PA scores ≥30. and that 27 of these (47%) had a poor response to 325 mg ASA, with an average drop in their PA scores from 49.5 ± 13.1 to 41.1 ± 8.6 (16%). Twenty-five of these 27 people were enrolled in the double-Mind study comparing the effect of ASA and ASA + CTA on platelet aggregability. Of these high aggregators who had a poor response to ASA, 12 of 25 (50%) had a good response to 162.5 mg of ASA plus 162.5 mg of CTA, with an average drop of their PA scores from 46.7 ± 13.2 to 22.0 ± 5.2 (53%). CTA alone had no effect on the PA score, which was similar to the control placebo. Our data suggest that a 1:1 combination of ASA and CTA may offer significantly greater protection agairtst arterial thrombotic events than ASA alone in subjects who respond poorly to ASA. Key Words: Platelet aggregation—Antithrombotic medication—Thrombosis.

Ticlopidine, Alka-Seltzer, or a combination of citric acid with aspirin: effects on platelet aggregation in individuals with an insufficient response to aspirin alone.

Aspirin (ASA) does not effectively lower platelet aggregation in all people. The platelet aggregation (PA) score is an easily used clinical method for measuring the effect in individuals of antiplatelet medications. Fifteen apparently healthy subjects (2 men and 13 women), selected for their resistance to ASAs antiaggregation effect, completed a se quential trial of ticlopidine, Alka-Seltzer®, and ASA + citric acid (CTA). Ticlopidine was the strongest aggregation inhibitor and the ASA + CTA combination was more inhibitory than Alka-Seltzer. It was determined that measuring antiaggregation effects of a particular agent in an individual prior to usage would optimize treatment. The PA score methodology provides a means for testing patients prior to antiplatelet therapy for prevention and treatment of the thrombotic complications of vascular disease.

The Effect of Hematopoietic Growth Factors on Platelet Aggregability

We compared the in vitro effect of thrombopoietin (TPO) on platelet aggregation to other hematopoietic growth factors (HGFs): granulocyte colony stimulating factor (G- CSF), granulocyte macrophage colony stimulating factor (GM- CSF), interleukin-3 (IL-3), interleukin-6 (IL-6), and erythro poietin (EPO). The platelet aggregation response of the venous blood of eight volunteers with differing aggregation patterns was characterized by a platelet aggregation (PA) score that provided numerical assessment of an individuals platelet ag gregation tendency to adenosine diphosphate (ADP). The method for analysis of the data included constructing regres sion lines for each participants PA score versus the HGF con centration (range of 0.5 nG/mL to 100 nG/mL) and calculating the regression coefficients for the slope and the Y axis inter cept. We demonstrated that the proposed method resulted in accurate assessment of the HGF effect or lack of it on the platelet aggregation response. Within the concentration range evaluated, the influence of IL-6 and G-CSF on platelet aggrega bility was insignificant and the effects of GM-CSF and IL-3 were almost undetectable. In contrast, the potentiating effect of TPO on platelet activation was dose dependent with significant enhancement for all responder types. The concentrations of TPO utilized in our in vitro experiments were in pathophysi ological range, indicating that its impact on platelet aggregation may have clinical relevance, and that monitoring platelet func tion in conjunction with TPO treatment might be advisable. Investigation of the possible synergistic effect of HGF combi nations is warranted.

Identification of Potential Predisposition to Clinical Atherosclerosis: A Clinical Concept Based on Integration of Significant Blood Parameters with Platelet Aggregation Scores

We sought to develop a predictive method, based on the integration of blood parameters found to be significantly associated with thrombosis and progression of atherosclerosis, that would be more accurate than primary reliance on elevation of separate risk factors. The study involved 1,034 male subjects. Lipid profiles and fibrinogen levels were determined for 123 men with documented clinical atherosclerosis and 123 apparently healthy volunteers. There were significant differences between these groups for fibrinogen, triglycerides, and HDL cholesterol. An algebraic expression was then developed which combined normalized values of fibrinogen, HDL cholesterol, and triglycerides with platelet count and aggregation data to yield a numerical value, the clinical atheroscterosis predisposition (CAP) factor. We then tested this CAP factor with a validation group of 788 men, 372 of whom were patients with documented clinical atherosclerosis; the rest were apparently healthy. A 3-year prospective evaluation was done for 72 of the 123 apparently healthy volunteers. The CAP factor was 90% indicative of patient status for the 372 men with documented complications of atherosclerosis and appeared to predict severe coronary disease in the 3-year prospective evaluation. This initial study suggests that integrated analysis of thrombotic factors in white males. provides a useful estimate of an individuals risk for subsequent development of clinical atherosclerosis. Key Words: Atherosclerosis-Prevention and control-Blood-Platelets-Cholesterol-Triglycerides--Fibrinogen.