Platelet Aggregation Score Research Articles

Ramucirumab in second‑line advanced colorectal cancer therapy: A study on therapeutic outcomes and hepatic sinusoidal platelet aggregation.

The present study investigated the role of ramucirumab (RAM) in treating liver metastases (LMs) as a second-line or salvage treatment in patients with advanced CRC. Of the 36 patients, 21 (58%) received RAM plus folinic acid, fluorouracil and irinotecan (FOLFIRI) as second-line treatment, whereas 15 (42%) received it in a salvage setting. The median overall survival time was 23 months [95% confidence interval (CI), 12-34 months] for those in the second-line treatment group and 8 months (95% CI, 5-19 months) for those in the salvage treatment group. Of the 36 patients, 14 (39%) underwent surgical resection of LMs during chemotherapy. A total of 6 patients underwent surgical resection for LMs for the first time during second-line RAM plus FOLFIRI (RAM-LM); of the remaining 8 patients, 6 underwent resection of LMs during first-line bevacizumab (BEV)-based chemotherapy (BEV-LM). Immunohistochemical analysis of CD42b showed that the platelet aggregation score (CD42b score), which ranges from 0 (absence of deposition) to 3 (presence of linear deposition), tended to decrease with the increasing duration of treatment with both RAM and BEV. Although there was no significant difference in the mean duration of anti-VEGF antibody treatment between the BEV-LM and RAM-LM groups, the median CD42b score was higher in the RAM-LM group (median CD42b score, 3; range, 0-3) compared with that in the BEV-LM group (median CD42b score, 1; range, 0-3; P=0.01), suggesting that RAM induces a different degree of platelet aggregation in liver sinusoids compared to BEV.

Relationship between Vascular Resistance and Sympathetic Nerve Fiber Density in Arterial Vessels in Children With Sleep Disordered Breathing.

BackgroundSleep disordered breathing in children is associated with increased blood flow velocity and sympathetic overactivity. Sympathetic overactivity results in peripheral vasoconstriction and reduced systemic vascular compliance, which increases blood flow velocity during systole. Augmented blood flow velocity is recognized to promote vascular remodeling. Importantly, increased vascular sympathetic nerve fiber density and innervation in early life plays a key role in the development of early‐onset hypertension in animal models. Examination of sympathetic nerve fiber density of the tonsillar arteries in children undergoing adenotonsillectomy for Sleep disordered breathing will address this question in humans.Methods and ResultsThirteen children scheduled for adenotonsillectomy to treat sleep disordered breathing underwent pupillometry, polysomnography, flow‐mediated dilation, resting brachial artery blood flow velocity (velocity time integral), and platelet aggregation. The dorsal lingual artery (tonsil) was stained and immunofluorescence techniques used to determine sympathetic nerve fiber density. Sympathetic nerve fiber density was correlated with increased resting velocity time integral (r=0.63; P<0.05) and a lower Neuronal Pupillary Index (r=−0.71, P<0.01), as well as a slower mean pupillary constriction velocity (mean, r=−0.64; P<0.05). A faster resting velocity time integral was associated with a slower peak pupillary constriction velocity (r=−0.77; P<0.01) and higher platelet aggregation to collagen antigen (r=0.64; P<0.05). Slower mean and peak pupillary constriction velocity were associated with higher platelet aggregation scores (P<0.05; P<0.01, respectively).ConclusionsThese results indicate that sympathetic activity is associated with change in both the function and structure of systemic vasculature in children with sleep disordered breathing.

Changes in haematology measurements with the Sysmex XT-2000iV during storage of feline blood sampled in EDTA or EDTA plus CTAD.

In veterinary medicine a complete blood cell count (CBC) cannot always be performed within 24 h as usually recommended, particularly for specimens shipped to a reference laboratory. This raises the question of the stability of the variables, especially in ethylenediamine tetra-acetic acid (EDTA) feline blood specimens, known to be prone to in vitro platelet aggregation. Citrate, theophylline, adenosine and dipyridamole (CTAD) has been reported to limit platelet aggregation in feline blood specimens. The aim of this study was to measure the stability of the haematological variables and the platelet aggregation score in EDTA and EDTA plus CTAD (EDCT) feline blood specimens during 48 h of storage at room temperature. Forty-six feline EDTA and EDCT blood specimens were analysed with a Sysmex XT-2000iV analyser, and the platelet count and score of platelet aggregation were estimated immediately and after 24 and 48 h of storage. A significant increase in mean corpuscular volume, haematocrit, reticulocyte and eosinophil counts, and a significant decrease in mean corpuscular haemoglobin concentration and monocyte count were observed. Haemoglobin, mean corpuscular haemoglobin, and red blood cell, white blood cell, neutrophil and lymphocyte counts remained stable. Changes in reticulocyte indexes with time (low fluorescence ratio, medium fluorescence ratio, high fluorescence ratio and immature reticulocyte fraction) were not significant. Changes were generally more pronounced in EDTA than in EDCT. Platelet aggregation decreased markedly in initially highly aggregated EDTA specimens, and increased slightly in initially non- or mildly-aggregated EDTA or EDCT specimens. Platelet counts increased and decreased, or remained stable, respectively. CTAD can reduce storage-induced changes of the haematological variables in feline samples, thus improving the reliability of a CBC and limiting clinical misinterpretations.

Comparison of platelet clumping and complete blood count results with Sysmex XT-2000iV in feline blood sampled on EDTA or EDTA plus CTAD (citrate, theophylline, adenosine and dipyridamole)

False thrombocytopenia may result from platelet aggregation, especially in feline ethylenediamine tetra-acetic acid (EDTA) blood specimens. Citrate, theophylline, adenosine and dipyridamole (CTAD) was added to 46 feline EDTA specimens to test its anti-aggregation action. Platelet aggregation was estimated from blood films and a complete blood count was performed with a Sysmex XT-2000iV analyser. Platelet aggregation score was >2 in 11/46 EDTA tubes and only in one EDTA+CTAD specimen. The platelet count was higher in all CTAD-supplemented tubes except one, medians measured by cytometry being 225.5 × 10(9)/l and 249.0 × 10(9)/l in EDTA and EDTA+CTAD, respectively (P = 0.007). Adding CTAD had statistically and analytically significant but moderate effects on other blood variables, the most intense variations being observed for reticulocytes (about 3% higher in EDTA specimens) and reticulocyte indexes. Addition of CTAD to EDTA when sampling feline blood is a useful option to reduce platelet clumping.

Impaired Blood Rheology in Critically Ill Patients in an Intensive Care Unit

Critically ill patients are at increased risk of thromboembolic complications. Japanese patients admitted to the intensive care unit of Gunma University Hospital were divided into critically ill (high score) and moderately ill (low score) groups according to mean Acute Physiology and Chronic Health Evaluation (APACHE) II score. White blood cell count, potassium, creatinine, immunoglobulin G and blood passage time, measured using the microchannel method, were significantly higher and the platelet aggregation score and platelet count were significantly lower in the high-score group than in the low-score group, but other haemorheological parameters did not differ significantly between the two groups. White blood cell count, potassium, creatinine, APACHE II score and levels of immunoglobulins G, A and M were positively correlated with blood passage time in all patients. Critically ill patients had impaired blood rheology, which could result from increased white blood cell count, potassium, creatinine and immunoglobulins and may be associated with the pathophysiology of the thromboembolic process.

Administration of granulocyte colony-stimulating factor enhances endothelialization and microvessel formation in small-caliber synthetic vascular grafts

Objective: The purpose of this study was to determine whether systemic administration of granulocyte colony-stimulating factor (G-CSF) would promote endothelialization for small-caliber Dacron vascular grafts. Methods: We implanted 4-mm preclotted Dacron grafts in both carotids of 12 dogs. For a fair comparison, all dogs had a comparable platelet aggregation profile with platelet aggregation scores less than 30. Five dogs served as controls, and the others were given 7-day subcutaneous injections of G-CSF (10 μg/kg per day), starting on the seventh postoperative day. The effect of G-CSF was evaluated by white blood cell count, which showed a 3.7-fold (± 2.7-fold) increase at the end of treatment. Grafts were harvested at 4 weeks. All G-CSF grafts were patent, and one control occluded. Endothelial-like cell coverage averaged 80.8% on G-CSF grafts, but only 35.6% for control grafts (P <.0004). With the exclusion of the anastomotic pannus healing factor, the difference in endothelial-like cell coverage was even greater (68.5% vs 9.8%; P <.0001). Immunocytochemical staining and electron microscopy studies demonstrated endothelial cells. Light microscopy also showed that there were more microvessels on and in the G-CSF grafts than in the control grafts. This study suggests that G-CSF can enhance early endothelialization of small-caliber vascular grafts. Further studies to determine the proper dosage and timing are needed before clinical application can be recommended. (J Vasc Surg 2000;32:116-23.)

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 individual's platelet ag gregation tendency to adenosine diphosphate (ADP). The method for analysis of the data included constructing regres sion lines for each participant's 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.

High Concentrations of Thrombopoietin Activate Platelets In Vitro

Thrombopoietin (TPO), the ligand for the proto- oncogene c-mpl, has been cloned and expressed from both human and murine sources. Thrombopoietin increases platelet counts when given in vivo and acts on progenitor cells to in crease their proliferation and maturation into megakaryocytes. The effects of TPO on mature platelets were investigated by evaluating platelet aggregation and platelet activation- dependent antigen expression. Platelet aggregation score, a quantitative representation of aggregation, showed potentiation of response to ADP-induced aggregation but no direct agonist response to TPO alone. Soluble c-mpl blocked the effect of TPO on the platelet aggregation score. Flow cytometry showed that TPO at concentrations &gt;250 U/ml (50 ng/ml) caused a minority population of platelets to express the activation mark ers CD62, CD63 and activated glycoprotein IIb/IIIa. While stem cell factor and interleukins-3 and -6 did not affect platelet activation antigen expression, interleukin-11 increased CD62 expression on platelets in vitro. The effects of TPO on antigenic expression and aggregability were partially inhibited in vitro by preincubation with aspirin. We conclude that high concentra tions of TPO promote platelet activation antigen expression on a proportion of platelets and potentiate platelet aggregability to ADP in vitro by a process that is partially inhibited by aspirin.

Apparent Blood Stream Origin of Endothelial and Smooth Muscle Cells in the Neointima of Long, Impervious Carotid-Femoral Grafts in the Dog

The purpose of this study was to determine whether endothelial and smooth muscle cells originating from the blood stream contribute to the endothelialization of impervious, small-caliber, long Dacron grafts used as extraanatomical bypasses in dogs. We implanted silicone-rubber-coated, permanently impervious grafts 64 to 77 cm long and 6 mm in diameter, made of externally supported knitted Dacron as unilateral carotid-femoral bypasses with distal femoral arteriovenous fistulae in 10 dogs for 3 months; sides were alternated between cases. Subjects received 162 mg/day of aspirin, and its effectiveness on platelet aggregation (PA) was evaluated and expressed as a PA score. Graft healing was studied by stereomicroscopy with silver nitrate staining, by light microscopy with hematoxylin-eosin and immunocytochemical staining for endothelial and smooth muscle cells, and by scanning and transmission electron microscopy. Five grafts were patent for 3 months and could be included in the healing study; the five occluded grafts thrombosed within 14 days. Although there was no transinterstitial tissue ingrowth from perigraft tissues into the impervious Dacron grafts, scattered islands of endothelial cells were conclusively demonstrated on graft flow surfaces 3 months after implantation. Average endothelial-like cell coverage of the flow surfaces was 15.6% +/- 3.8%, and alpha-actin-positive smooth muscle cells and microvessels were found beneath some of the endothelial islands. These findings suggest that blood stream-derived endothelial and smooth muscle cells play a role in the healing of the inner wall of Dacron grafts in the dog.

Modified Technique for Measuring Platelet Aggregation

The turbidimetric method of Bom is the current approach for assessing the aggregation behavior of platelets. It has been of modest practical value, due to difficulty in standardizing laboratory techniques for plasma preparation and inadequate quantification of the aggregation process. We report a new technique of sedimented platelet rich plasma (SPRP) preparation that reduces the irregularities caused by factors associated with procuring and preparing blood samples and permits a more flexible protocol for laboratory practice. We quantified results with a platelet aggregation score, which is calculated by multiplying the ratio of the height of the initial wave of aggregation to the maximum height of the aggregation pattern by the total area under the aggregation curve and by the ratio of the whole blood platelet count and the number of platelets in the sample. Comparative analysis of platelet aggregation scores (n = 95) obtained with both plasma preparation techniques using a paired t test demonstrated no statistical differences ( t = 1.368, p = 0.174). To demonstrate the application of this modified method to evaluation of antiplatelet agents, the effects of aspirin and aspirin combined with citric acid on platelet aggregation were studied in vitro. The antiaggregatory effect of aspirin combined with citric acid was dependent on the pH and on their molar ratio, and was greater than the effect of aspirin alone. The SPRP protocol with platelet aggregation scoring methodology could be a valid alternative for measurement of the platelets' propensity to aggregate and the effect of antithrombotic treatments. Key Words: Platelet aggregation— Aspirin—Citric acid.

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 individual's risk for subsequent development of clinical atherosclerosis. Key Words: Atherosclerosis-Prevention and control-Blood-Platelets-Cholesterol-Triglycerides--Fibrinogen.

Effect of differential shear stress on platelet aggregation, surface thrombosis, and endothelialization of bilateral carotid-femoral grafts in the dog.

The purpose of this study was to determine the effects of increased shear stress on the aggregability of platelets as they traverse a long, small-caliber (6 mm) Dacron graft in the dog and on the surface thrombosis and endothelialization of such a graft. Each of nine dogs received bilateral carotid-femoral artery grafts, approximately 75 cm long, for 3 months; one graft of each pair had a distal femoral arteriovenous fistula to produce a higher shear rate than the contralateral graft. Platelet aggregation scores were determined on blood withdrawn from the external jugular vein and from the proximal and distal ends of the grafts in each animal. Graft flow rates, which were used in the computation of shear stress, and luminal pressure gradients through grafts were measured during surgery and specimen retrieval. Specimens were studied with light microscopy after hematoxylin and eosin and immunocytochemical staining and by scanning electron and transmission electron microscopy to evaluate the nature, composition, and thickness of the flow surface lining, as well as the transmural healing. Two high-shear stress and two low-shear stress grafts occluded unilaterally; five dogs had bilaterally patent grafts, allowing comparative analyses. All subjects had low platelet aggregability with aspirin. Platelet aggregation scores taken from proximal and distal ends of the grafts were not significantly different. The high-shear stress grafts had significantly more endothelial-like cell coverage (p < 0.0371) than the low-shear stress grafts, less flow-surface thrombus (p < 0.0056), and a thinner surface lining (p < 0.0029), on both the neointima and pseudointima. In subjects with low platelet aggregation scores, long Dacron grafts do not elevate platelet aggregability of blood flowing through them. High-shear stress grafts have less flow surface thrombus, more endothelialization, and a thinner surface lining than do low-shear stress grafts.

The Platelet Aggregation Score and Its Correlation to β- Thromboglobulin and Platelet Factor 4 Levels

We describe a new method of interpreting platelet aggregometry results and its correlation to platelet secretory protein levels. We studied 123 healthy male volunteers, 37-85 years of age. The aggregation response to 2.5 μM ADP was measured in a standardized platelet suspension (SPS) prepared from platelet-rich plasma. Turbidimetic measurements included amplitude of the primary aggregation wave (Amp1), maximum aggregation amplitude (Amax), and area under the aggregation curve (Sagg). A platelet aggregation (PA) score was calculated as ( Amp1 /Amax) ·Sagg ·(whole-blood platelet count/SPS platelet count). β-Thromboglobulin (β-TG)and . platelet factor 4 (PF4) levels were measured by radioimmunoassay. The PA score correlated significantly (p &lt; 0.0001) with β-TG ( r = 0.86) and PF4 ( r = 0.87). It was concluded that the PA score correlates closely with individual subjects' propensities to platelet activation, as reflected by plasma β-TG and PF4 levels. Key Words: Platelets-Platelet aggregometry-Platelet secretory proteins.

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.

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

Our purpose was to evaluate whether a method for quantification of platelet aggregability will predict failure of knitted Dacron femoropopliteal bypass grafts. 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. 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. These data suggest that the PA score is a potential risk factor for failure of femoropopliteal bypass with externally supported knitted Dacron grafts.