Platelet Survival In Patients Research Articles

Calprotectin Impairs Platelet Survival in Patients With Primary Antiphospholipid Syndrome.

While thrombosis and pregnancy loss are the best-known clinical features of antiphospholipid syndrome (APS), many patients also exhibit "extra-criteria" manifestations, such as thrombocytopenia. The mechanisms that drive APS thrombocytopenia are not completely understood, and no clinical biomarkers are available for predicting antiphospholipid antibody (aPL)-mediated thrombocytopenia. Calprotectin is a heterodimer of S100A8 and S100A9 that is abundant in the neutrophil cytoplasm and released upon proinflammatory neutrophil activation. Here, we sought to evaluate the presence, clinical associations, and potential mechanistic roles of circulating calprotectin in a cohort of primary APS and aPL-positive patients. Levels of circulating calprotectin were determined in plasma by the QUANTA Flash chemiluminescent assay. A viability dye-based platelet assay was used to assess the potential impact of calprotectin on aPL-mediated thrombocytopenia. Circulating calprotectin was measured in 112 patients with primary APS and 30 aPL-positive (without APS criteria manifestations or lupus) patients as compared to patients with lupus (without APS), patients with unprovoked venous thrombosis (without aPL), and healthy controls. Levels of calprotectin were higher in patients with primary APS and aPL-positive patients compared to healthy controls. After adjustment for age and sex, calprotectin level correlated positively with absolute neutrophil count (r=0.41, P < 0.001), positively with C-reactive protein level (r=0.34, P = 0.002), and negatively with platelet count (r = -0.24, P = 0.004). Mechanistically, we found that calprotectin provoked aPL-mediated thrombocytopenia by engaging platelet surface toll-like receptor 4 and activating the NLRP3-inflammasome, thereby reducing platelet viability in a caspase-1-dependent manner. These data suggest that calprotectin has the potential to be a functional biomarker and a new therapeutic target for APS thrombocytopenia.

Effects of Fish Oil Supplementation on Platelet Survival and ex Vivo Platelet Function in Hypercholesterolemic Patients

Little is known about the effects of dietary supplementation on platelet survival with low doses of n-3 and n-6 fatty acids in patients with hypercholesterolemia. The effects of a 6-week intervention with fish oil capsules (daily intake: 216 mg eicosapentaenoic acid, 140 mg docosahexaenoic acid, 390 mg gamma-linolenic acid, and 3480 mg linoleic acid) on in vivo platelet survival ( 111In-oxine labeled platelets) and on ex vivo markers of platelet activation were investigated in a placebo-controlled, double-blind study with 26 hypercholesterolemic patients. In vivo platelet survival increased in the fish oil group (T) from a mean of 159±14 hours to a mean of 164±12 hours p=0.025 , whereas it remained unchanged in the placebo (P) group (T vs. P; p=0.055). Ex vivo, thromboxane B 2 decreased from a mean of 225±16 to 212±21 ng/mL p=0.003 in T but did not change in P (T vs. P: p=0.002). Malondialdehyde formation was lowered significantly by fish oil supplementation from a mean of 5.49±1.03 to 5.12±1.05 nM/10 9 platelets, p=0.005, as compared with P (T vs. P; p=0.018). The trendwise decrease in 11-DH-thromboxane B 2 plasma levels was not significant nor was the increase in platelet sensitivity to prostaglandn I 2 by fish oil. Baseline platelet survival in patients with hyperlipoproteinemia type IIa was not different from those with hyperlipoproteinemia IIb and response to treatment in terms of platelet activation markers was not either. The changes in platelet activation parameters in T were associated with significant reductions in cholesterol (−2.9%), low density lipoprotein cholesterol (−3.5%), and triglycerides (−12.4%). Both ex vivo and in vivo platelet activation parameters exhibited signs of decreased activation by a 6-week diet supplemented with n-3 and n-6 fatty acids, which might be beneficial in reducing atherothrombotic risk, in patients with hyperlipoproteinemia type IIa and IIb.

EFFECT OF ISRADIPINE ON IN-VIVO PLATELET FUNCTION

In animal studies calcium channel blockers (CCB's) and especially isradipine, a second generation dihydropyridine, interrupt the sequence of events culminating in the formation of atherosclerotic lesions. The effect of 4 weeks isradipine treatment (5mg daily) on blood pressure and in-vivo platelet function (measured with 111Indium-oxine labeled autologous platelets) were investigated in a randomized, double-blind and placebo controlled trial in 40 patients with mild to moderate hypertension and scintigraphically diagnosed active atherosclerotic lesions of the carotid arteries. The average supine systolic/diastolic blood pressure was significantly reduced at the end of the treatment period in the isradipine group (group I; p<0.0001) but remained unchanged in the placebo group (group P). The heart rate was not significantly altered in either group. There were no serious side effects. The platelet uptake ratio (PUR) measured over the atherosclerotic region of the carotid artery on 4 consecutive days before and after treatment decreased significantly in group I from 1.20 to 1.15 (within groups: p<0.0001) but remained unchanged in group P. Platelet survival increased significantly in group I (mean 5.70 hours, lower quartile 4.50, upper quartile 4.50 hours, within groups: p<0.0001) and remained unchanged in group P. Isradipine has a beneficial effect on in-vivo platelet function as evidenced by a decreased platelet deposition on vascular lesion sites and an associated prolonged platelet survival in patients with hypertension and active atherosclerotic lesions. © 1997 Elsevier Science Ltd

Role of platelets in progressive glomerular diseases.

There is increasing evidence that platelets are involved in the pathogenesis of glomerulonephritis. Intraglomerular platelets or their degradation products are observed in biopsies from patients with lupus nephritis, mesangioproliferative, membranous or IgA nephropathy. Moreover shortened platelet survival in patients with various glomerular diseases has also been described. In models of experimental glomerulonephritis, platelets may participate in glomerular injury, together with other mediators, by complex mechanisms. As extensively documented, platelets release within the glomerulus vasoactive, chemotactic and mitogenic substance that interact with a number of soluble mediators generated by renal resident or inflammatory cells and contribute to amplify glomerular injury. Thus platelet-activating factor and other platelet secretory products, polycationic macromolecules, platelet factor 4 and beta-thromboglobulin, alter glomerular permeability to proteins and enhance immune-mediated glomerular injury. Platelet-derived factors, like platelet-derived growth factor (PDGF) and transforming growth factor beta (TGF beta) mediate renal disease progression in experimental and human glomerulonephritis via their chemotactic activity for infiltrating leucocytes and their effect of promoting extracellular matrix synthesis by resident renal cells. In these settings increased renal expression of PDGF and TGF beta has correlated with clinical features. Specific PDGF and TGF beta inhibitors ameliorated experimental glomerular disease. A wide variety of therapies to inhibit platelet function have been employed over the years, however the results of clinical studies are controversial and do not allow conclusions to be drawn about the efficacy of anti-platelet agents in progressive renal disease. Identification of specific platelet inhibitors or interventions specific for platelet secretory products and their target cells will be crucial for understanding the exact role of platelets and their products in glomerular disease.

Platelet Survival in Patients with Dilated Cardiomyopathy

Dilated cardiomyopathy is associated with thromboembolic complications, which correlate poorly, however, with a visible left ventricular thrombus. Therefore, this study was performed to assess whether an abnormality of platelet function in vivo can be detected in patients with dilated cardiomyopathy. Platelet survival was measured after autologous labeling with indium-111 oxine in 28 patients with dilated cardiomyopathy and angiographically normal coronary arteries (mean ejection fraction 21 +/- 9% [standard deviation], range 4 to 39%) and in nine patients with coronary artery disease and similar left ventricular dysfunction (mean ejection fraction 21 +/- 10%). Plasma levels of beta-thromboglobulin and platelet factor 4 were measured in patients with idiopathic cardiomyopathy (n = 15) and platelet scintigraphic images of the heart (n = 24) were obtained in subsets of both patient groups. Platelet survival was significantly and similarly shortened in patients with idiopathic and ischemic cardiomyopathy (67 +/- 34 and 55 +/- 24 h, respectively) compared to controls (209 +/- 9 h, n = 12; p less than 0.001). Of the two platelet-specific proteins, beta-thromboglobulin was increased in the patients compared with controls (42 +/- 17 versus 22 +/- 6 ng/ml, p less than 0.001). Platelet scintigraphy 24 h (n = 24) and/or 48 h (n = 9) after labeling showed a diffuse pattern of enhanced platelet uptake over the heart which varied in intensity among patients, but which was never seen in controls (n = 6). This increased platelet uptake was similar in patients with idiopathic and ischemic cardiomyopathy but did not correlate with either ejection fraction or cardiothoracic ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Platelet survival in patients with beta-thalassemia.

Thromboembolic events associated with significant morbidity and mortality have been observed in patients with beta-thalassemia major (TM). These include arterial as well as venous thrombosis and the development of early arteriosclerosis. To elucidate the possibility that TM patients may develop a hypercoagulable state we carried out a study of platelet kinetics on ten patients with TM and four patients with thalassemia intermedia (TI). Autologous platelets were labeled with indium-111-oxine, and the platelet lifespan (PLS) was determined. A significant shortening of PLS was observed in 13 out of 14 patients examined. The mean PLS (+/- 1 SD) in ten patients (8 TM, 2 TI) who underwent splenectomy was 107 +/- 36 hr (control splenectomized 248 + 51 hr) (P less than .001) and in four nonsplenectomized patients (2 TM, 2 TI) was 102 +/- 64 hr (control 224 + 23 hr) (P less than .01). The short PLS in addition to reported findings of increased circulating platelet aggregates and the decreased response of TM platelets to aggregating agents suggests in vivo platelet activation in thalassemic patients.

Platelet Survival in Patients with Angiographically Diseased and Normal Coronary Arteries

Platelets may contribute to the pathogenesis of atherosclerosis and to the complications of coronary artery disease. Therefore, platelet kinetics were studied in 69 patients with angiographically documented coronary artery disease and in 16 patients with a normal coronary angiogram. Platelet survival time was calculated from the decay of radioactivity after injection of 51Cr-labeled autologous platelets. None of the mathematical models used was able to discriminate between the two patients groups. No correlation existed between survival time and extent of the arterial disease. Patients with a high serum cholesterol did not exhibit an enhanced platelet consumption. Thus, these studies do not support the idea that turnover is enhanced in patients with coronary artery disease as compared to those with normal coronary arteries.

Indexes of intravascular hemolysis, quantification of coagulation factors, and platelet survival in patients with porcine heterograft valves

Ten patients with porcine heterograft valves who were not receiving anticoagulant agents were evaluated to determine the effect of the valve on red blood cell survival and on platelet activation and consumption as measured by (1) quantification of the coagulation mechanism, (2) platelet function studies, and (3) 51-chromium platelet survival time. There was no evidence of significant intravascular hemolysis as determined by the reticulocyte count, serum iron and iron binding capacity, serum bilirubin level, or lactic dehydrogenase activity. The coagulation profile and the platelet function studies were normal. No statistically significant difference was found in the platelet survival time in the 10 patients with porcine heterograft valves (half-life 3.2 +/- 0.8 days) and the 11 normal control subjects (half-life 3.6 +/- 0.6 days) (p greater than 0.2). The finding of a normal platelet survival time in patients with porcine heterograft valves is consistent with clinical experience indicating that this device is associated with a low incidence of systemic embolization, approximating 3% per year.

Platelet survival in patients treated with ticlopidine following reconstructive arterial surgery

Platelet survival in patients treated with ticlopidine following reconstructive arterial surgery

Aspirin, Dipyridamole and Platelet Survival in Patients with Diabetes Mellitus

1. Platelet survival in 27 insulin-dependent diabetic patients with severe retinopathy was studied in a double-blind cross-over trial using placebo, aspirin (990 mg/day) and a combination of dipyridamole (225 mg/day) with aspirin at two dosage levels (330 mg and 990 mg/day). 2. Twenty patients (group I) had 51Cr-labelled-platelet survival after treatment with placebo and the high-dose-aspirin/dipyridamole combination. The remaining seven patients (group II) had platelet-regeneration times measured after each of the four treatment periods. 3. Treatment of group I patients with the high-dose-aspirin/dipyridamole combination resulted in significant (P less than 0.001) prolongation of platelet survival from 7.3 +/- 0.2 (mean +/- SEM days to 8.4 +/- 0.1 days. 4. In group II patients, when compared with the mean placebo result of 7.2 +/- 0.2 days, the mean aspirin-labelled-platelet-regeneration time was significantly (P less than 0.01) longer only after high-dose-aspirin/dipyridamole (9.8 +/- 0.5 days) but not after low-dose-aspirin/dipyridamole (8.3 +/- 0.5 days) or aspirin alone (7.3 +/- 0.3 days). 5. These results suggest that it may be premature to consider reducing the dose of aspirin in aspirin/dipyridamole combinations below 1 g/day when used as antithrombotic therapy.

Platelet survival in patients with diabetes mellitus

Platelet survival in patients with diabetes mellitus

Platelet survival in patients with diabetes mellitus.

Platelet survival by 51chromium labeling was determined in six normal control subjects and in twelve patients with diabetes mellitus, before and after improved glucose control (mean HbA1c 10.5 +/- 2.2% and 7.1 +/- 1.8%, respectively). Mean platelet survival was 9.47 +/- 0.85 days for the normal subjects and 9.04 +/- 1.40 and 9.90 +/- 1.05 for the diabetic subjects in hyperglycemic and improved glycemic states, respectively. The differences between these values were not statistically significant. However, platelet survivals performed in three diabetic patients who had severe retinal disease requiring photocoagulation were significantly shortened compared with nonsmoking control subjects (P less than 0.05) or to patients without severe retinopathy (P less than 0.01). These observations imply that measurable changes in in vivo platelet survival occur after the development of small vessel disease. It remains to be determined whether abnormalities described for diabetic platelets in vitro or changes in in vivo platelet physiology contribute to the initiation or propagation of vascular disease in the hyperglycemic individual.

Platelet survival time and thromboembolism in patients with mitral valve prolapse.

Thromboembolism (TE) occurs in about 20% of patients with rheumatic mitral valve disease, and platelet survival time in these patients has correlated with TE. In patients with mitral valve prolapse, TE appears to occur very infrequently. Platelet survival (autologous labeling with chromium-51) was performed in 26 patients with mitral prolapse. Five patients had a history of stroke, as well as normal cerebrovascular arteriography and shortened platelet survival (average half-time +/- SEM 2.3 +/- 0.18 days; normal half-time 3.7 +/- 0.03 days; n = 26; p less than 0.01). Platelet survival was shortened in seven of 21 patients without TE (33%) (3.3 +/- 0.06 days; p less than 0.01 vs patients with TE). In 138 patients with rheumatic heart disease, platelet survival was shortened in 40 of 41 (98%) with a history of TE (2.3 +/- 0.08 days) and in 76 of 97 (78%) without TE (2.9 +/- 0.07 days; p less than 0.001 vs patients with TE). In patients with mitral prolapse, sulfinpyrazone increased platelet survival (2.4 +/- 0.16 to 2.7 +/- 0.19 days; n = 7; p less than 0.05). Our results suggest that platelet survival time is shortened in patients with mitral prolapse and rheumatic heart disease who have had TE. Of those without TE there is an increased frequency of shortened platelet survival in patients with rheumatic heart disease (78%) compared with those with mitral prolapse (33%), consistent with the infrequency of TE in mitral prolapse.

Platelet survival in patients with substitute heart valves

The hemodynamic benefits of replacing defective heart valves with prosthetic valves are compromised by thromboembolic complications. After replacement of artificial heart valves, platelets are destroyed by prosthetic heart valves, and consumed by interaction with prosthetic valves.It has been shown that patients with substitute heart valves have short platelet survival time, which can be lengthened after treatment with platelet inhibitor drugs as Dipyridamole. For this purpose we have given 450mg daily dosage of Dipyridamole in all patients with prosthetic valves.To determine the relation thromboembolism to the presence of substitute heart valves, kinetic studies of platelet were performed in 14 patients. Six patients had received mitral valve prostheses, 4 had aortic valve prostheses, and 4 had double artificial valves. In accordance with platelet survival half time, platelet survival was determined that it was normal or not. The normal platelet survival half time was 4.0±0.5 days (S. E. M.). Average platelet survival time in 4 patients with aortic artificial valves was 3.85±0.75 days (survival half-time±S. E. M.), in 6 patients with mitral artificial valves, 3.73±0.67 days, and in 4 patients with double prostheses, 3.71±0.74 days. In these patients average platelet survival was almost normal, because they were given Dipyridamole. Thromboembolism occurred in 3 of the 14 patients (21 percent). In this group, platelet survival was shortened in 2 of 3 patients and was normal in one. In these patients, kind of prostheses was Kay-Shiley valve. In spite of treatment with Dipyridamole, it was seen that platelet survival was shortened in 6 patients. In the case of non-thromboembolism episode, it was thought that platelet was destroyed by prothetic heart valves, or was reduced by platelet aggregation and adhesiveness. Therefore there was confirmed that platelet behavior changing factor needed furthermore. In the case of thromboembolism episode, it was thought that platelet was reduced by formation of clot at artificial heart valve and its surrounding. Therefore anticoagulant and fibrinolysin therapy, or artificial valve re-replacement needed in this case.

The Influence of Ascorbic Acid on Platelet Structure and Function

To determine the effect on platelet behavior of transient exposure of platelets to ascorbic acid, studies of platelet function and ultrastructure were done before exposure to ascorbic acid at pH 6.5, during exposure to pH 6.5, and after restoration of pH to pre-acidification levels. The effect of ascorbic acid (A.A.) was compared to that of HCl and citric acid (C.A.). ADP- and collagen-induced aggregation of normal platelets were significantly impaired by both A.A. and C.A. but were less affected by HCl. The release of 14C-serotonin was significantly reduced by each agent. The ultrastructure of normal platelets brought to pH 6.5 by A.A. was normal. After neutralization, there was marked dilatation of the open channel system and loss of the disc shape. When platelets were brought to pH 6.5 by A.A., then neutralized, the aggregates which formed after stimulation by ADP or collagen were smaller than normal, the platelets were less closely approximated, and degranulation was less complete. The data show that exposure of platelets to ascorbic acid for short intervals impairs their function when measured after restoration of pH to levels compatible with maximal responses. Platelet survival studies using autologous platelets labelled with 51Cr in the presence or absence of ascorbic acid showed that the recovery of normal platelets was unaffected by ascorbic acid, whereas recovery of platelets from patients with idiopathic thrombocytopenic purpura, idiopathic thrombocythemia, and alcohol-related thrombocytopenia was markedly reduced. The injury resulting from the use of ascorbic acid in preparing platelets for studies of platelet survival in patients with disorders affecting platelets may impair the recovery of the cells, resulting in artifactual changes in the survival studies.

Platelet survival in patients with prosthetic heart valves

Chromium-51 platelet survival studies were carried out in 20 patients with a prosthetic heart valve. Only 1 of 10 patients with a prosthetic mitral valve had a significantly shortened platelet survival time, and the mean value of 8.3 ± 0.96 (±1 standard deviation) days was not significantly different from that of normal control subjects (8.9 ± 0.75 days). Four of 10 patients with an aortic prosthesis had a shortened platelet survival time, and the mean value of 7.8 ± 0.10 days in this group differed significantly from the normal control value (P < 0.05). Treatment with aspirin did not appear to alter platelet survival but, when combined with Coumadin therapy, resulted in marked prolongation of bleeding time. Our results do not support the concept that thrombus formation on the prosthesis is the cause of the shortened platelet survival time since thrombus formation is more likely to occur in mitral than aortic prostheses. Reduced platelet survival time secondary to damage by the prosthesis, similar to the problem of hemolysis in red blood cells, is a more likely explanation.

Platelet survival in patients with substitute heart valves.

To determine the relation of thromboembolism to the presence of substitute heart valves platelet studies were performed in 55 patients. Average platelet survival was normal in patients with homograft valves and Beall prostheses, but was short in those with older prosthetic mitral valves. Short platelet survival time and the frequency of thromboembolism were significantly related. Thromboembolism had occurred in 62 per cent of patients with short survival but in only 9 per cent of those with normal survival, and average platelet survival was significantly shorter in 13 patients with thromboembolism than in 42 patients without thromboembolism. In postoperative patients with newer mitral valves, average platelet survival was abnormally short in those who had had thromboembolism before operation. Postoperative thromboembolism occurred in 30 per cent of these patients but in none of those without preoperative thromboembolism in whom meah platelet survival also was normal. Results demonstrate that platelet survival correlates with a history of thromboembolism in patients with substitute heart valves. (N Engl J Med 290:534–537, 1974)

Platelet survival in patients with rheumatic heart disease.

Platelet studies were carried out in patients with valvular heart disease to determine the correlation of results with thromboembolism. Platelet survival was normal in 11 patients with aortic stenosis, and no thromboembolism occurred. In 55 patients with mitral stenosis, average platelet survival was slightly shortened. In 29, thromboembolism had occurred, and mean platelet survival was abnormal and significantly shorter than in the 26 patients without thromboembolism. Of patients with thromboembolism, 93 per cent had short survival as compared to 31 per cent of those without thromboembolism. Thromboembolism had occurred in 83 per cent of patients with short platelet survival as compared to 10 per cent in those with normal platelet survival. The results demonstrate that short platelet survival differentiates patients with mitral-valve disease and a history of thromboembolism from those without thromboembolism. Such studies done prospectively may identify thromboembolism-prone patients in whom platelet-inhibitor therapy may prove useful. (N Engl J Med 290:537–539, 1974)

Platelet survival in patients with a Beall valve: Relation to low incidence of thromboembolism

Recent investigations demonstrating short platelet survival time in patients with prosthetic heart valves have suggested that platelets contribute to thromboembolism in this group. New prostheses have proved less thrombogenic than those previously employed, but platelet survival studies in patients with these valves are lacking. In this study, the Beall mitral prosthesis, known to be infrequently associated with thromboembolism, was used as a model, and platelet survival time and its relation to hemolysis, thrombosis and the surface area of the disc were determined in 9 patients. Platelet survival time was normal in 6 of 9 patients, and mean survival time (6.5 ± 0.29 days) did not differ significantly from normal (6.73 ± 0.21 days; P > 0.50). Platelet survival time was inversely related to increasing disc surface area but did not correlate with the presence or degree of hemolysis. The fact that platelet abnormalities were not demonstrable in patients with Beall valves may explain the low incidence of thromboembolism in this group. Platelet survival studies may be useful for determining the thrombogenic potential of valvular prostheses and for evaluating newer prosthetic materials and designs.

REDUCED PLATELET SURVIVAL IN PATIENTS WITH STARR-EDWARDS PROSTHESES.

REDUCED PLATELET SURVIVAL IN PATIENTS WITH STARR-EDWARDS PROSTHESES.