Long-term aspirin and clopidogrel response evaluated by light transmission aggregometry, VerifyNow, and thrombelastography in patients undergoing percutaneous coronary intervention.

BACKGROUND: A reduced response to aspirin and clopidogrel predicts ischemic events, but reliable tests are needed to identify low responders. We compared 3 platelet-function tests during long-term dual treatment with aspirin and clopidogrel. METHODS: Patients who underwent a percutaneous coronary intervention and were receiving a combination of 325 mg/day aspirin and 75 mg/day clopidogrel were followed for 1 year. Blood was sampled 5 times during this period for 3 tests: light transmission aggregometry (LTA) assay, with 5.0 micromol/L ADP or 1.0 mmol/L arachidonic acid (AA) used as an agonist; VerifyNow assay, with the P2Y(12) or aspirin cartridge (Accumetrics); and thrombelastography (TEG), stimulated by 2.0 micromol/L ADP or 1.0 mmol/L AA. RESULTS: Twenty-six of 33 patients completed all scheduled visits. A low response to clopidogrel was found in a few patients at variable frequencies and at different visits, depending on the method and criteria used. We found a moderate correlation between the LTA (ADP) and VerifyNow (P2Y(12) cartridge) results, but the TEG (ADP) results correlated poorly with the LTA and VerifyNow results. A low response to aspirin was found with the VerifyNow (aspirin cartridge) and TEG (AA) methods on 6 and 2 occasions, respectively, but not with the LTA (AA) method, except for 1 occasion caused by probable noncompliance. CONCLUSIONS: Detecting a low response to clopidogrel depends largely on the method used. Which method best predicts ischemic events remains uncertain. A low response to aspirin is rare with AA-dependent methods used at the chosen cutoffs. In some patients, the response to clopidogrel or aspirin may be classified differently at different times, even with the same method.

Platelet quality measured with dynamic light scattering correlates with transfusion outcome in hematologic malignancies.

BACKGROUND: A clinically meaningful test for platelet (PLT) quality could improve the transfusion management of patients. The aim of this pilot study was to determine whether a new measure of PLT quality and function based on dynamic light scattering (DLS) correlates with transfusion outcome. STUDY DESIGN AND METHODS: For a total of 160 transfusions, the pretransfusion, 1 hour posttransfusion, and 24-hour posttransfusion PLT counts were routinely measured in 49 patients (31 male, 18 female; age 46 +/- 15 years) with hematologic malignancies. The corrected count increments (CCIs) at 1 hour (PLT recovery) and 24 hours (PLT survival) were calculated and used as the transfusion outcome measures. The ThromboLUX score (LightIntegra Technology, Inc., Vancouver, BC, Canada; range, 0-40; cutoff, 12) and the PLT morphology score of the PLT concentrates were determined and compared to transfusion outcome. RESULTS: The CCIs and ThromboLUX scores were normally distributed and showed a strong correlation (n = 96, in the mixed regression model the adjusted coefficient is R = 0.6292, p < 0.0001), while other variables such as product type, age, and microscopic PLT morphology score were not correlated with transfusion outcome (p > 0.05). Importantly, 12 of 96 transfusions with poor PLT quality were clinically ineffective, that is, did not adequately increase the PLT counts in the recipients. One patient died after receiving three consecutive ineffective PLT transfusions with a low ThromboLUX score. CONCLUSION: In this pilot study, the ThromboLUX score strongly correlated with transfusion outcome (PLT recovery and survival) independent of clinical and product issues.

Diagnosing platelet delta-storage pool disease in children by flow cytometry.

Bleeding problems are symptomatic of platelet delta-storage pool diseases (SPDs) such as Hermansky-Pudlak syndrome. Although at present no cure is available for delta-SPD, early diagnosis is of great importance for prophylactic and supportive treatment. This study tested the usefulness of a flow cytometric assay for platelet serotonin in children. The assay was used to diagnose delta-SPD in a 10-year-old girl. Platelet serotonin levels were significantly lower in the patient than in all healthy control subjects (10 children and 10 adults). The serotonin results were supported by traditional tests, which are transmission electron microscopy of whole mounts and adenosine triphosphate release by lumi-aggregometry. The flow cytometric serotonin assay is a major improvement to current pediatric diagnostics. The advantages of this test are small sample volume of fresh or fixed/frozen platelets, availability of objective results within 2 hours of obtaining the blood sample, and automated analysis by flow cytometry.

Platelet serotonin levels support depression scores for women with postpartum depression.

OBJECTIVE: It is very challenging to make an unbiased diagnosis of psychiatric illness. Platelets have long been proposed as easily obtainable, neurological models of serotonergic neurons. This study examined whether a new measurement for platelet serotonin could aid in the diagnosis of postpartum depression and support the results from questionnaires. METHODS: Study participants included 11 patients with postpartum clinical depression according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, criteria. Blood was donated either at acute onset of depression before treatment (n = 5) or while patients were nonresponsive to paroxetine treatment (n = 8; 2 of these patients dropped out). A follow-up sample was donated approximately 8 weeks later during paroxetine treatment (n = 11). Platelet serotonin was determined with a new immunocytochemical assay and standard high-pressure liquid chromatography. Serotonin levels were compared with Hamilton Depression Rating Scale scores. RESULTS: Platelet serotonin levels in patients with depression before paroxetine treatment or nonresponsive to their initial paroxetine regimen were reduced to 50% of normal levels. Treatment-induced severe reduction of platelet-associated serotonin only occurred in responsive patients. Mean platelet serotonin levels were significantly lower in responders (17.3%, standard deviation [SD] 4%), compared with nonresponders (33.4%, SD 8%; p < 0.001). CONCLUSION: Platelet serotonin levels obtained with a new immunocytochemical test correlated well with results from depression scoring and might be useful as evidence-based support for questionnaires.

The influence of selective serotonin reuptake inhibitors on human platelet serotonin.

Clinical depression has been proposed to be an independent risk factor for cardiovascular disease. While it is suggested that selective serotonin reuptake inhibitors (SSRIs) reduce the risk of acute cardiovascular problems of depressed patients, the effect of SSRIs on platelets, the only blood cells committed to serotonin (5-HT) transport, remains largely unknown. The goal of this pilot study was to measure the 5-HT levels in platelets of untreated and SSRI-treated depressed patients and normal subjects and to determine whether the interaction of SSRIs with platelets can explain their possible cardiovascular benefit in patients with depression. Platelet 5-HT was determined by an immunocytochemical assay and high-pressure liquid chromatography with electrochemical detection (HPLC-ECD). In normal control subjects without cardiovascular disease, 78 +/- 8% of platelets were 5-HT-positive (n = 14). Depression caused a significant reduction in platelet 5-HT to 46 +/- 21% in untreated patients (n = 13) and 22 +/- 13% in SSRI-treated patients (n = 14). As a class, all selective serotonin reuptake inhibitors significantly reduced the 5-HT concentration in patient platelets. An inverse relationship of 5-HT level and dose of medication might be suggested. These results correlated well with 5-HT data from HPLC (r = 0.8509, p < 0.001). SSRIs did not affect platelet aggregation and dense granule release in response to thrombin, but significantly reduced ADP-induced platelet aggregation and dense granule release in both patient and normal control samples. The active inhibition of platelet aggregation by SSRIs might explain their cardiovascular benefit.