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PubMed2002

Comparison of in vitro closure time (PFA-100) with whole blood electrical aggregometry and platelet surface antigen expression in healthy volunteers.

It was the aim of this study to compare in vitro closure time (PFA-100), reflecting platelet-related primary hemostasis, to more platelet-specific tests like whole blood electrical aggregometry and platelet surface antigen expression in healthy volunteers. In vitro closure time was measured using a PFA-100. Platelet surface antigen expression (CD63, CD62-P, CD42b, CD36, CD31) was determined in accordance with the consensus protocol for flow-cytometric characterisation of platelet function. Platelet aggregometry was performed using a whole blood electrical aggregometer (ADP and arachidonic acid as agonists). Analysis of the obtained data revealed only a few significant correlations between the different platelet function tests used. This finding can be explained by the various aspects of platelet function being focused by these tests in different extents. Whenever platelet function is analysed, the investigator should be aware of the specific and limited evidence of the method used. For screening purposes, it may be useful to introduce a platelet function index, referring to basal platelet activity, platelet adhesion and platelet aggregation at low and high shear stress forces.

Antigens, CD↗
PubMed2003

The influence of induced hypothermia for hemostatic function on temperature-adjusted measurements in rabbits.

UNLABELLED: In hypothermic patients, a tendency to bleed may be observed even when hemostatic tests seem to be normal. Coagulation and platelet function tests are usually performed at 37 degrees C. We investigated the influence of induced hypothermia on temperature-adjusted hemostasis function testing using Sonoclot Analyzer (Sonoclot) and Thromboelastography (TEG). Anesthesia was induced and maintained with IV ketamine and fentanyl on 15 male New-Zealand White rabbits. A water blanket was used to induce hypothermia to 30 degrees C and to rewarm to 37 degrees C. Blood samples were obtained at four points: before hypothermia, at 34 degrees C, at 30 degrees C, and after rewarming. Standard coagulation tests were performed at 37 degrees C (C method), and simultaneously, real temperature hemostasis function tests (R method) were run. In Sonoclot(R), activated clotting time and time to peak increased and clot rate decreased significantly at 30 degrees C in the R method compared with those in the C method. In TEG(R), reaction time and clot formation time were prolonged and clot formation rate was diminished at 30 degrees C in the R method compared with those in the C method. Induced hypothermia delayed the coagulation cascade and reduced platelet function. During hypothermia, hemostatic measurements should be performed at real temperature to avoid overestimating patient hemostatic function based on results measured at the standard 37 degrees C. IMPLICATIONS: We investigated the influence of induced hypothermia on temperature-adjusted hemostasis function tests in rabbits using Sonoclot Analyzer and Thromboelastography. Induced hypothermia delayed the coagulation cascade and reduced platelet function. The conventional coagulation tests performed at 37 degrees C failed to detect these hypothermia-induced degradations in hemostasis performance.

Anesthesia↗
PubMed2001

Clinical application of procedural platelet monitoring during percutaneous coronary intervention among patients at increased bleeding risk.

The goal of platelet function testing in the catheterization laboratory is to provide information about the platelet contributions to the risk of thrombotic or hemorrhagic events and optimization of anti-platelet therapy for percutaneous interventions. We present several illustrative cases in which platelet monitoring with the Rapid Platelet Function Assay (RPFA, Accumetrics) was used to guide dosing of a glycoprotein (GP) IIb/IIIa inhibitor for coronary and peripheral intervention among patients at increased bleeding risk.

Abciximab↗
PubMed1999

Can the Platelet Function Analyzer (PFA)-100 test substitute for the template bleeding time in routine clinical practice?

The bleeding time (BT) is widely used in clinical medicine as a screening test of platelet function, although its deficiencies in such a role are well recognized. The Platelet Function Analyzer (PFA)-100 measures the ability of platelets activated in a high-shear environment to occlude an aperture in a membrane treated with collagen and epinephrine (CEPI) or collagen and ADP (CADP). The time taken for flow across the membrane to stop (closure time) is recorded. This study compared the PFA-100 with the BT as a screening test of platelet dysfunction in 113 hospital inpatients. The PFA-100 test was performed initially using the CEPI cartridge; CADP tests were performed on those with abnormal (> 163 s) CEPI closure times. Whole blood platelet aggregation studies and chart review were performed on patients in whom the BT and PFA-100 results did not agree.Abnormal bleeding times and PFA-100 results were obtained in 20.4% and 35.4% of patients, respectively. The results of BT and PFA-100 agreed in 74.3% of patients. Of the 29 patients in whom the BT and PFA-100 results were discordant, whole blood platelet aggregation studies supported the PFA-100 result in 25 (86.2%). The PFA-100 was more sensitive to aspirin-induced platelet dysfunction and was more rapidly and cheaply performed than the BT. Since the PFA-100 test reflects platelet function better than the BT, we conclude that this test could replace the BT as a first-line screening test for platelet dysfunction in clinical practice.

Journal Article↗
PubMed2005

Duration of increased bleeding tendency after cessation of aspirin therapy.

BACKGROUND: Aspirin has a significant effect on hemostasis, so it is often recommended that patients taking aspirin discontinue treatment before elective surgery. While off aspirin, these patients may be at risk of thrombosis. The optimum period of time that aspirin should be withheld is controversial. The aim of this study was to establish the duration of the antihemostatic effect of prolonged aspirin therapy. STUDY DESIGN: In a prospective study, 51 healthy volunteers were randomly assigned into 3 groups, each receiving an identical tablet for 14 days. One group received a placebo tablet; individuals in the other two groups received either 75 mg or 300 mg of aspirin once a day. Template bleeding times and specific platelet function testing (using the PFA-100; Dade Behring) were carried out on subjects before therapy and again after its completion until they returned to baseline. RESULTS: Thirty-eight volunteers complied sufficiently with the protocol to provide useful results. All bleeding times normalized within 96 hours and all platelet function tests within 144 hours after stopping aspirin. There was no demonstrable hemostatic defect in any volunteer persisting by or beyond the sixth day after treatment cessation. There was no apparent difference in duration of effect between those taking either 75 mg or 300 mg of aspirin. CONCLUSIONS: This study uses sensitive measures of platelet function to demonstrate the duration of increased bleeding tendency after withdrawal of aspirin therapy. It supports discontinuation of aspirin therapy 5 days before elective surgery (with the operation being performed on the sixth day).

Adult↗
PubMed1992

[A new preoperative evaluation of platelet aggregation--Part II].

With the new platelet function test which we reported in the first paper, the platelet aggregation was evaluated in 50 patients, and the comparison with the results of bleeding time was made in 20 cases. There was no statistical correlation between the bleeding time and the platelet aggregation. The bleeding time has been considered as an indicator of platelet function and is included in a preoperative check list. However, its result depends on the amount of platelets and the endothelial factor, and the reliability of bleeding time on platelet function is considered small, especially in patients medicated with antiplatelet drugs. For such patients, the platelet aggregation test is essential. The present study demonstrated that the patient belonging to grade-1 were resistant to hemostasis during the operation. Taking into the surgical and anesthetic depression on the platelet function into consideration, the patients below grade-2 are risky for the surgery.

Adult↗
PubMed2006

Evaluation of platelet function in aspirin treated patients with CAD.

BACKGROUND: Studies of platelet function in the acute coronary syndrome (ACS) have revealed both increased and unchanged platelet activation. To obtain a better understanding of platelet function in coronary artery disease in the setting of aspirin therapy, we performed platelet functional testing in patients with ACS and compared results to patients without CAD. METHODS: We measured platelet aggregation and activation in response to ADP and epinephrine in 80 age and gender matched hospitalized patients (40 with ACS, 40 with non-cardiac chest pain (NCCP)). All subjects received ASA (81-325 mg). Platelet aggregation was performed using standard light transmission in platelet-rich plasma and activation was measured via flow cytometric analyses. We also studied platelet function under high shear rates measured by the platelet function analyzer (PFA-100). RESULTS: ASA effect was found to be present in all subjects by blunted platelet aggregation in response to arachidonic acid. Patients with ACS showed significantly higher levels of platelet aggregation to epinephrine compared to patients with NCCP (p = 0.001). Other measures of platelet function including ADP aggregation, Pselectin, activated glycoprotein IIb/IIIa expression, and PFA-100 were unchanged between the two groups. CONCLUSIONS: We have found conflicting results of platelet functional testing in ACS. Specifically aspirin therapy in patients with ACS is effective in suppressing the platelet release response and is effective in the partial suppression of platelet aggregation; however, it appears that ACS patients have increased platelet aggregation to adrenergic stimuli when compared to age and gender matched controls without CAD despite the use of aspirin. In some studies, because ACS patients have an accentuated response to adrenergic stimuli this might be interpreted as aspirin resistance. Our study suggests that depending on the assay used to determine aspirin resistance, not all patients with this label are resistant to the biological effects of aspirin but they may have higher than normal baseline platelet sensitivity to adrenergic stimuli.

Aged↗
PubMed1985

[Evaluation of principal risk factors, hemorheological and blood coagulation characteristics in arteriosclerosis obliterans in the elderly].

The main risk factors, whole blood filterability, platelet function tests and blood coagulation tests have been evaluated in 68 non-diabetic patients with atherosclerosis obliterans of the lower limbs (stages II and III of Fontaine classification), 34 of geriatric age and 34 of middle age, and in 44 healthy controls of middle age. No different prevalence of risk factors has been found among vasculopathic patients of both ages; platelet function tests and blood coagulation tests are overlapping in the two groups of vasculopathic patients, but they are altered in comparison to healthy controls, whereas whole blood filterability is decreased in both groups of atherosclerotic patients, but mostly in elderly subjects, in whom a therapeutic approach with hemorheological drugs seems more suitable.

Adult↗
PubMed1999

Evaluation of platelet function with the PFA-100 system in patients with congenital defects of platelet secretion.

The template bleeding time is still the screening test for defects of platelet function, although it is an invasive and poorly reproducible technique. The PFA-100 measures platelet function at high shear. Whole blood is aspirated through a capillary to an aperture of a membrane coated with platelet agonists. The system measures the time required to obtain occlusion of the aperture by a platelet plug (closure time). We measured the closure times in the PFA-100 system and the bleeding time in seven patients with delta-storage pool deficiency, 10 patients with "primary secretion defect" (not due to abnormalities of platelet granules or the arachidonate pathway), and 40 controls. Measurements were repeated I and 4 hours after intravenous infusion of desmopressin in six delta-storage pool deficiency and eight primary secretion defect patients. Baseline bleeding time and closure times with the collagen/epinephrine cartridge were longer in delta-storage pool deficiency and primary secretion defect patients than in controls. In contrast, closure times with the collagen/adenosine diphosphate cartridge were normal in both delta-storage pool deficiency and primary secretion defect patients. Treatment with desmopressin increased the plasma von Willebrand Factor levels, shortened the prolonged bleeding time, shortened the closure times with the collagen/adenosine diphosphate cartridge, and normalized the closure times with the collagen/ epinephrine cartridge. Therefore, the PFA-100 test may be a less invasive alternative to the bleeding time in the diagnosis and therapeutic monitoring of patients with platelet secretion defects. The collagen/epinephrine cartridge is more sensitive than the collagen/adenosine diphosphate cartridge to defects of platelet secretion.

Adult↗
PubMed1988

Effects of a fish oil concentrate in patients with hypercholesterolemia.

The effects of a fish oil supplement on lipid and lipoprotein levels, platelet function, and vital signs were investigated in 31 hypercholesterolemic patients. Thirteen patients took 5 g of encapsulated fish oil per day and 18 patients took 5 g of encapsulated safflower oil "placebo" per day for 28 days. Diet and exercise patterns were kept as constant as possible during the study. The fish oil group had significant increases in several lipid/lipoprotein values at the end of the treatment, including an increase of total cholesterol of 14% (P = 0.0001), LDL of 16% (P = 0.003), HDL of 13% (P = 0.015) and HDL2 of 36% (P = 0.009). The triglyceride level fell 24%, a nonsignificant change (P = 0.217). The ratios of total cholesterol/HDL and LDL/HDL were increased at the end of fish oil treatment, and returned to baseline 30 days after fish oil was stopped. The placebo group had no significant changes in any of the lipid/lipoprotein values. Neither the fish oil nor the placebo group had significant changes in vital signs or platelet function tests (bleeding time, thromboxane B2, platelet factor 4 and beta-thromboglobulin) during the study. These results suggest that fish oil supplements may have an adverse effect on lipid/lipoprotein values in hypercholesterolemic patients.

Adolescent↗
PubMed1996

[Lupus anticoagulants in patients with systemic lupus erythematosus].

Lupus anticoagulants (LA) and anticardiolipin antibodies (aCL) are known as thrombosis-related antiphospholipid antibodies. LA is not as well characterized as aCL, and the relation between LA and aCL is not clarified. Since standardized method for the detection of LA has not been established, we measured LA activities in outpatients with SLE by using two different methods (KCT and dRVVT), and analyzed the characteristics of LA in SLE. LA was detected in 29.8% of all samples (14.3% in both methods, 15.5% in one method). IgG-aCL and IgM-aCL was detected in 38% and 20%, respectively, of all LA positive samples. Though a good correlation was observed between LA activities and IgG-aCL levels, a considerable number of LA positive samples were negative for aCL. This indicated the presence of factors with LA activity other than aCL. On the contrary there was also a high percentage of LA negative samples with positive aCL (42.4% in IgG-aCL, 47.4% in IgM-aCL), suggesting the presence of aCL with poor or low LA activity. These findings showed the heterogeneity of antiphospholipid antibodies both in LA and in aCL. The platelet function tests showed increased platelet adhesiveness and normal platelet aggregation in LA positive patients with SLE even in the inactive phase. The serum levels of factors such as protein C, protein S, antithrombin III and thrombomodulin were within normal range. Clinical features such as hemolytic anemia, thrombosis and abortion were more frequently observed in LA positive population than in LA negative population. The clinical features tend to be different between patients with dRVVT-LA and those with KCT-LA, though not significant. Because of the heterogeneity in LA, a combination of more than two different methods including dRVVT was recommended for the detection and the evaluation of LA.

Adult↗
PubMedDate not supplied

Platelet count and platelet function in patients with angina pectoris (before and after a cycloergometric exercise test).

Platelet count and platelet function (circulating platelet aggregates, retention by glass beads and aggregation) were studied under basal conditions and after a cycloergometric exercise test in 10 subjects with stable angina pectoris and 10 normal subjects. There were no baseline differences between patients and controls in any of the tests of platelet function, nor did the values change after the exercise test. There was, however, a significant increase in the number of circulating platelets after the test in angina patients. Possible reasons for this phenomenon are discussed, with emphasis on the role of catecholamine hypersecretion induced by the physical exercise.

Adult↗
PubMed1998

PFA-100 system: a new method for assessment of platelet dysfunction.

The PFA-100 system is a platelet function analyzer designed to measure platelet-related primary hemostasis. The instrument uses two disposable cartridges: a collagen/epinephrine (CEPI) and a collagen/ADP (CADP) cartridge. Previous experience has shown that CEPI cartridges detect qualitative platelet defects, including acetylsalicylic acid (ASA)-induced abnormalities, while CADP cartridges detect only thrombocytopathies and not ASA use. In this seven-center trial, 206 healthy subjects and 176 persons with various platelet-related defects, including 127 ASA users, were studied. The platelet function status was determined by a platelet function test panel. Comparisons were made as to how well the defects were identified by the PFA-100 system and by platelet aggregometry. The reference intervals for both cartridges, testing the 206 healthy subjects, were similar to values described in smaller studies in the literature [mean closure time (CT) 132 s for CEPI and 93 s for CADP]. The use of different lot numbers of cartridges or duplicate versus singleton testing revealed no differences. Compared with the platelet function status, the PFA-100 system had a clinical sensitivity of 94.9% and a specificity of 88.8%. For aggregometry, a sensitivity of 94.3% and a specificity of 88.3% were obtained. These values are based on all 382 specimens. A separate analysis of sensitivity by type of platelet defect, ASA use versus congenital thrombocytopathies, revealed for the PFA-100 system a 94.5% sensitivity in identifying ASA users and a 95.9% sensitivity in identifying the other defects. For aggregometry, the values were 100% for ASA users and 79.6% for congenital defects. Analysis of concordance between the PFA-100 system and aggregometry revealed no difference in clinical sensitivity and specificity between the systems (p > 0.9999). The overall agreement was 87.5%, with a Kappa index of 0.751. The two tests are thus equivalent in their ability to identify normal and abnormal platelet defects. Testing 126 subjects who took 325 mg ASA revealed that the PFA-100 system (CEPI) was able to detect 71.7% of ASA-induced defects with a positive predictive value of 97.8%. The overall clinical accuracy of the system, calculated from the area under the ROC curve, was 0.977. The data suggest that the PFA-100 system is highly accurate in discriminating normal from abnormal platelet function. The ease of operation of the instrument makes it a useful tool to use in screening patients for platelet-related hemostasis defects.

Adolescent↗
PubMedDate not supplied

Hemostatic profile in neonatal septicemia.

Hemostatic profile was studied in 25 full term non-asphyxiated neonates with blood culture-proven septicemia. Observations were compared with that of 25 healthy, non-asphyxiated, full term, birth weight and age-matched controls. Detailed coagulation tests & platelet studies were done in each of the 50 neonates by standard techniques. Hemostatic defects occurred in 96% of the septicemic neonates and none in the control group irrespective of the occurrence of clinical bleeding. The coagulation tests were deranged in 805 and platelet function tests in 92% of patients. These tests were significantly deranged in septicemic neonates as compared to control group.

Anti-Bacterial Agents↗
PubMed2006

Mechanism of the antithrombotic effect of dietary diacylglycerol in atherogenic mice.

INTRODUCTION: We have shown earlier that diacylglycerol (DAG) but not triacylglycerol (TAG) inhibited thrombus formation. The aim of the present study was to investigate the mechanism of this antithrombotic effect of DAG. MATERIALS AND METHODS: Four different diets, the (1) Western-style high-fat diet (HFD) containing 20% lipid and 0.05% cholesterol (w/w), (2) TAG-rich and (3) DAG-rich HFDs containing 20% lipid and 0.05% cholesterol, but all lipid replaced by TAG or DAG oil with very similar fatty acid composition and the (4) Japanese-style low-fat diet (LFD) containing 7% oil but no cholesterol were given to apolipoprotein E and low-density lipoprotein (LDL) receptor double-deficient mice. Atherogenicity was assessed by morphology, mapping the whole aorta and measuring the total area of lipid-stained lesions. Endothelial function was measured by the flow-mediated vasodilation test. Platelet reactivity was assessed from native blood sample by a shear-induced platelet function test (hemostatometry). Serum lipoprotein profile was measured by HPLC. RESULTS: Both the Western-style and the TAG-rich HFDs have accelerated atherosclerosis. In contrast, DAG-rich HFD inhibited the atherosclerotic process to an extent comparable with the Japanese-style LFD. There was no significant difference in platelet and coagulant activity between the studied diet groups. DAG-rich but not the TAG-rich HFD significantly suppressed serum LDL cholesterol level. CONCLUSIONS: The present findings suggest that the mechanism of antithrombotic and anti-atherogenic effect of DAG may involve the protection of the vascular endothelium from injury and lowered serum LDL cholesterol.

Animals↗