Acquired Platelet Function Defects Research Articles

Evaluation of an automated platelet aggregation method for detection of congenital or acquired platelet function defects.

Light transmission aggregometry (LTA) is the most widely used laboratory method for an initial screening of patients with a suspected platelet function defect (PFD), and its use has also been proposed for assessing the efficacy of antiplatelet treatment (APT). An automated LTA method has been developed by Sysmex (Kobe, Japan) on a routine coagulation analyzer (CS-2400), together with a new research parameter called PAL (platelet aggregation level) to evaluate patients on APT. We evaluated the performance of CS-2400 compared to a stand-alone lumi-dual-aggregometer device in the diagnosis of PFD and in assessing the efficacy of APT. For these purposes, the study population was represented by a cohort of 23 patients with a previous diagnosis of PFD and a cohort of 28 patients on APT. Compared to healthy volunteers, patients with PFD showed a statistically significant reduction (p<0.05) in the maximal %light transmission, irrespective of the agonist used, both with the CS-2400 and the lumi-dual-aggregometer. As regards PFD patients, CS-2400 was effective in identifying the more severe defects, with a good sensibility and specificity, but less effective in identifying milder forms of PFD, such as platelet secretion defects. Patients on APT showed a statistically significant (p=0.001) reduced median %light transmission and PAL scores compared to healthy controls. Thanks to this LTA technology, CS-2400, a routine coagulation analyzer widely available in routine laboratories, could prove useful for initial assessment of patients with a suspected PFD. Moreover, the PAL scores were a fairly accurate reflection of the platelet response to APT.

Performance evaluation of the Anysis-200 platelet function analyzer in cardiac patients.

Platelet function analysis is crucial in assessing the hemostatic status to evaluate congenital and acquired platelet function defects. The Anysis-200 analyzer is a new automated lab-on-a-chip-based platelet function analyzer. We aimed to evaluate a new platelet function analyzing system, the Anysis-200 in comparison to the Platelet Function Analyzer (PFA)-200 in cardiac patients. Citrated blood was collected from 174 patients who visited the Department of Cardiology. The Anysis-200 consists of two kits, the microchips with collagen and epinephrine-coated membrane (C/EPI) or adenosine diphosphate-coated membrane (C/ADP). Platelet clogging in the Anysis-200 is measured by the blood migration distance obtained by a camera, which is compatible with the closure time in the PFA-200. We performed Anysis-200 and PFA-200 analyzers simultaneously and compared the results. The sensitivity and specificity of the Anysis-200 C/EPI kit in comparison to the PFA-200 C/EPI kit were 63.41% and 91.43%, respectively. Regarding the C/ADP kit, the sensitivity and specificity of the Anysis-200 were 58.97% and 74.29%, respectively. The agreement rate between the Anysis-200 and PFA-200 for C/EPI was 83.35% and 70.14% for C/ADP. The Anysis-200, which applies a novel method to detect platelet clogging, has shown moderate to fair agreement with the PFA-200. This test is potentially useful for screening cardiac patients with an abnormal platelet function.

Angiotensin 1-7 and Mas decrease thrombosis in Bdkrb2−/− mice by increasing NO and prostacyclin to reduce platelet spreading and glycoprotein VI activation

AbstractBradykinin B2 receptor–deleted mice (Bdkrb2−/−) have delayed carotid artery thrombosis times and prolonged tail bleeding time resulting from elevated angiotensin II (AngII) and angiotensin receptor 2 (AT2R) producing increased plasma nitric oxide (NO) and prostacyclin. Bdkrb2−/− also have elevated plasma angiotensin-(1-7) and messenger RNA and protein for its receptor Mas. Blockade of Mas with its antagonist A-779 in Bdkrb2−/− shortens thrombosis times (58 ± 4 minutes to 38 ± 4 minutes) and bleeding times (170 ± 13 seconds to 88 ± 8 seconds) and lowers plasma nitrate (22 ± 4 μM to 15 ± 5 μM), and 6-keto-PGF1α (259 ± 103 pg/mL to 132 ± 58 pg/mL). Bdkrb2−/− platelets express increased NO, guanosine 3′,5′-cyclic monophosphate, and cyclic adenosine monophosphate with reduced spreading on collagen, collagen peptide GFOGER, or fibrinogen. In vivo A-779 or combined L-NAME and nimesulide treatment corrects it. Bdkrb2−/− platelets have reduced collagen-related peptide–induced integrin α2bβ3 activation and P-selectin expression that are partially corrected by in vivo A-779, nimesulide, or L-NAME. Bone marrow transplantations show that the platelet phenotype and thrombosis time depends on the host rather than donor bone marrow progenitors. Transplantation of wild-type bone marrow into Bdkrb2−/− hosts produces platelets with a spreading defect and delayed thrombosis times. In Bdkrb2−/−, combined AT2R and Mas overexpression produce elevated plasma prostacyclin and NO leading to acquired platelet function defects and thrombosis delay.

Acquired Platelet Dysfunction in 109 Patients From a Tertiary Care Referral Hospital

Acquired platelet function defects (PFDs) remain poorly characterized, underrecognized, and therefore understudied. Clinical and laboratory records of 109 patients with acquired PFDs diagnosed over 5 years were analyzed. Screening studies (platelet count, prothrombin time, activated partial thromboplastin time, and thrombin time), template bleeding time, platelet factor 3 (PF-3) availability test, light-transmission aggregometry, and further testing as indicated were performed. 64 patients had mild and 26 had major bleeding. In all, 15 were referred for preoperative testing, whereas 4 had thrombotic events. Causes and associations of PFDs were drug-induced (34), idiopathic (34), hematopoietic neoplasms (15; myeloma 4, Waldenstrom macroglobulinemia 2, chronic myeloid leukemia 4, essential thrombocythaemia 3, and primary myelofibrosis and chronic lymphocytic leukemia 1 each), chronic liver disease (4), postcardiac surgery (2), uremia (2), and thalassemia major (7). Miscellaneous disorders comprised the rest. Acquired PFDs span a wide range of disease settings. Systematic, sequential laboratory testing identifies patterns of dysfunction, excludes inherited disorders, and streamlines management.

Erworbene Plättchenfunktionsstörungen

Given the high consumption of pharmacological agents in western societies, it is not surprising at all that drugs represent the most common cause of acquired platelet dysfunction. While acetylsalicylic acid, clopigogrel and integrin alphaIIbbeta3 (GPIIb-IIIa) receptor antagonists are well-known as prototypes of antiplatelet drugs, other widely used agents including non-steroidal anti-inflammatory drugs, antibiotics, serotonin reuptake inhibitors, and volume expanders can also impair platelet function and cause or aggravate haemorrhages. Besides pharmacological agents, certain clinical conditions are often associated with qualitative platelet disorders and bleeding diathesis. Consequently, in contrast to inherited platelet disorders, acquired platelet function defects are much more frequent in clinical practice and deserve special attention. Their pathogenesis is widespread and heterogeneous with various, sometimes overlapping abnormalities. Moreover, acquired platelet dysfunctions can occur at any age and range in severity from mild to life-threatening haemorrhages. Due to their heterogeneity, acquired platelet function disorders will be classified and discussed according to the underlying clinical setting or disease.

Flow-based assays for global assessment of hemostasis. Part 1: Biorheologic considerations.

Centre for Cardiovascular Sciences and MRC Centre for Immune Regulation, The Medical School, The University of Birmingham, Birmingham, UK; Department of Biomedical Engineering, University of Rochester , Rochester , USA; Department of Biochemistry, CARIM, University of Maastricht , Maastricht , The Netherlands; Dept of Physiology, McGill University, Montreal, Quebec,Canada/ affiliation with CYTORHEX Inc of Canada; Center for Molecular and Vascular Biology, University of Leuven , Leuven ; Belgium; KellSa s.a.s., Biella , Italy

Abnormal Platelet Function Is Common in Pediatric Congenital Cardiac Surgery Patients.

Background: Hemostasis in cardiac surgery patients requires functional platelets. Acquired platelet function defects are well recognized in high shear aortic lesions in adults and have been described in some congenital cardiac patients with ventricular septal defects (VSDs) and with pulmonary hypertension. Abnormal shear flow is characteristic of many congenital cardiac defects. We hypothesized that platelet function abnormalities might be common in this patient group. The Platelet Function Analyzer -100 (PFA-100) is commonly used to test for platelet function defects. Pediatric reference ranges are the same as adult. Prolongation of closure times to collagen/epinephrine are common in patients on aspirin and related antiplatelet agents, with prolongation to collagen/ADP being characteristic of many clinically significant platelet disorders (congenital and acquired vonWillebrand's disease, other platelet function defects).Methods: We used the PFA-100 to preoperatively screen pediatric patients aged 2 mos-18 years coming to surgical repair of cardiac lesions at our institution. All aortic valve surgery patients were screened as of July 2004, and all cardiac surgery cases as of Jan 2005. For analysis only patients with platelet counts of > 100 and hematocrits of > 28 were included. If PFA-100 closure times to collagen/epi were normal, collagen/ADP testing was not performed. For study purposes PFA-100 results were counted as abnormal only when closure times for collagen/ADP were prolonged beyond the 95% confidence intervals for normal controls. No special hematological interventions were ordered preoperatively on the basis of an abnormal PFA-100 alone.Results: PFA-100 results were available on 38 patients. 28 of 38 (74%) were abnormal, with underlying cardiac pathology strongly correlated with abnormal PFA-100 values (see table). 6 patients were on aspirin, discontinued preoperatively, and none on other antiplatelet agents. 3 of these 6 had normal PFAs to collagen/epi when tested. Although patient groups were not homogeneous, patients with abnormal PFA-100 results had higher overall intraoperative and postoperative red cell and platelet transfusion requirements on a cc/kg basis (55.3 vs 17.6 for RBCs p=.008 and 12.8 vs 6.5 for platelets p=.038). 24 hour post-operative chest tube drainage (cc/kg) did not differ between groups (23.2 vs 22.7 p=0.95). There were 2 reexplorations for hemorrage, both in patients with abnormal PFAs.Conclusions: Prevalence of platelet function abnormalities appears high in pediatric congential cardiac surgery patients. The etiology of these abnormalities is unclear and there may possibly be a correlation with aortic valve pathology and other high shear lesions. Patients with abnormal platelet function also had increased transfusion requirements. However it is unclear is this finding is related to the platelet function defect or to differences in patient age and complexity of surgery. Larger studies that better define the population at-risk for bleeding and the significance of abnormal platelet function are needed.Correlation of abnormal PFA-100 and cardiac lesion typeSurgical repair% AbnormalTotalL ventricular outflow tract and aortic valve100%9Tetralogy of Fallot100%4Other VSD repair100%4Coarctation of aorta100%2Right ventricular outflow tract and pulmonary artery stenosis86%7Operations for hypoplastic ventricles33%3AV septal defect50%2Isolated ASD closure0%4Other33%3Total38

Approach to the Assessment of Platelet Function: Comparison between Optical-based Platelet-rich Plasma and Impedance-based Whole Blood Platelet Aggregation Methods

Platelet aggregation studies play an important role in the assessment of hereditary and acquired platelet function defects. The first aggregation test introduced into laboratory practice used platelet-rich plasma (PRP) where aggregation was detected by an optical method. The assessment of platelet function using whole blood (WB) aggregation by an impedance method followed up nearly 20 years later. The WB impedance aggregation assay appears to be superior to the optical method because it 1) evaluates platelets in a physiologic milieu in the presence of red and white blood cells, which are known to modulate platelet function; 2) is faster; 3) has higher sensitivity; and 4) does not require centrifugation, thus avoiding injury to platelets and loss of giant thrombocytes. These two assays were compared. Clearly, the WB impedance aggregation methodology has many advantages over the optical PRP assay for the assessment of the hyperactive platelet syndrome and the effects of anti-platelet drugs.

Platelet function defects associated with hemorrhage or thrombosis

Platelet dysfunction, especially acquired forms, is a common cause of hemorrhage, especially when associated with trauma or surgery. Although the hereditary platelet function defects are generally quite rare, hereditary storage pool disease is common enough to be suspected in an individual, usually a child, with characteristic historical and clinical findings. The acquired platelet function defects, especially those resulting from drugs, are common and should promptly be suspected in patients developing easy and spontaneous bruising, mild-to-moderate mucosal membrane hemorrhage, or unexplained bleeding associated with trauma or surgery. The template bleeding time is generally useful as a screening test of platelet function, but a normal template bleeding time, in the face of a suggestive history, suggestive clinical findings, or in a patient frankly bleeding, is not reliable, and platelet aggregation or lumiaggregation should be done in appropriate clinical situations. Also, prolongation of the template bleeding time is an unreliable predictor of clinical bleeding propensity. The mainstay of therapy for almost all these defects, if bleeding is significant, is the liberal infusion of appropriate numbers of platelet concentrates. The acquired platelet function defects should also be managed by attempts to treat or control the underlying disease, if possible, and offending drugs or potentially offending drugs should immediately be stopped.

Acquired Platelet Function Defects

Platelet dysfunctions, especially acquired forms, are common causes of hemorrhage, especially when associated with trauma or surgery. Although the hereditary platelet function defects are generally quite rare, hereditary storage-pool disease is common enough to be suspected in an individual, usually a child, with characteristic historical and clinical findings. The acquired platelet function defects, especially those resulting from drugs, are very common and should promptly be suspected in patients developing easy and spontaneous bruising, mild to moderate mucosal membrane hemorrhage, or unexplained bleeding associated with trauma or surgery. The template bleeding time is generally useful as a screening test of platelet function, but a normal template bleeding time, in the face of a suggestive history, suggestive clinical findings, or in the patient frankly bleeding, is not reliable, and platelet aggregation or lumi-aggregation should be done in appropriate clinical situations. Also, prolongation of the template bleeding time is an unreliable predictor of clinical bleeding propensity. The mainstay of therapy for essentially all these defects, if bleeding is significant, is the liberal infusion of appropriate numbers of platelet concentrates. The acquired platelet function defects should also be managed by attempts to treat or control the underlying disease, if possible, and offending drugs or potentially offending drugs should immediately be stopped.

Platelet function defects: a clinical review.

Platelet dysfunction, especially acquired forms, are common causes of hemorrhage, especially in association with trauma and surgery. Although the hereditary platelet function defects are generally quite rare, hereditary storage pool disease is common enough to be suspected in an individual, usually a child, with characteristic historical and clinical findings. The acquired platelet function defects, especially those resulting from drugs, are very common and should promptly be suspected in patients developing easy and spontaneous bruising, mild to moderate mucosal membrane hemorrhage, or unexplained bleeding associated with trauma or surgery. The template bleeding time is generally useful as a screening test of platelet function, but a normal template bleeding time, in the presence of a suggestive history, suggestive clinical findings, or in the patient frankly bleeding, is not reliable and platelet aggregation or lumi-aggregation should be done in appropriate clinical situations. The mainstay of therapy for essentially all these defects, if bleeding is significant, is the liberal infusion of appropriate numbers of platelet concentrates. The acquired platelet function defects, of course, should also be managed by attempts to treat or control the underlying disease, if possible, and offending drugs or potentially offending drugs should promptly be discontinued.