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European Review For Medical and... May 2018Several adipokines secreted by adipose tissue have an anti-thrombotic and anti-atherosclerotic function. Recently identified adipokine progranulin was found to play a...
OBJECTIVE
Several adipokines secreted by adipose tissue have an anti-thrombotic and anti-atherosclerotic function. Recently identified adipokine progranulin was found to play a protective role in atherosclerosis. Bearing in mind the central role of platelets in inflammation and atherosclerosis, we aimed, in this study, to examine the effect of progranulin on platelet function and coagulation profile in rats.
MATERIALS AND METHODS
Healthy male albino Wistar rats weighing (250-300 g) were divided into 4 groups. Three groups were given increasing doses of progranulin (0.001 µg, 0.01 µg, and 0.1 µg) intraperitoneally, while the control group received phosphate-buffered saline (PBS). Bleeding time, prothrombin time, activated partial thromboplastin time and platelet aggregation responses to adenosine diphosphate and arachidonic acid were assessed.
RESULTS
Administration of progranulin resulted in a significant inhibition of platelet aggregation in response to both adenosine diphosphate, and arachidonic acid. Bleeding time, prothrombin time and activated partial thromboplastin time were significantly prolonged in all groups that received progranulin, in particular, the 0.1 µg dose, in comparison to the control group.
CONCLUSIONS
This preliminary data is first suggesting that the antiplatelet and anticoagulant action of progranulin could have a physiological protective function against thrombotic disorders associated with obesity and atherosclerosis. However, these results merit further exploration.
Topics: Adenosine Diphosphate; Animals; Arachidonic Acid; Bleeding Time; Hemostasis; Humans; Male; Partial Thromboplastin Time; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Progranulins; Prothrombin Time; Rats
PubMed: 29863272
DOI: 10.26355/eurrev_201805_15087 -
Renal Failure Nov 2020The risk of bleeding has led to screening of the primary hemostasis before renal biopsy. A bleeding time test (BT) is considered standard practice, but reliance on this... (Comparative Study)
Comparative Study
The risk of bleeding has led to screening of the primary hemostasis before renal biopsy. A bleeding time test (BT) is considered standard practice, but reliance on this test is controversial and its benefits remain questionable. A possible alternative is thromboelastography (TEG). However, data regarding TEG in patients with renal dysfunction is limited. To determine TEG abnormalities and their consequences in patients who underwent a native kidney biopsy. A retrospective study of 417 consecutive percutaneous native renal biopsies performed in our Center. If serum creatinine >1.5 mg/dL, the patient underwent either a BT test (period A, January 2015-31 December 2016) or TEG (period B, January 2017-August 2018). In patients with prolonged BT, or an abnormal low maximal amplitude (MA) parameter of TEG, or suspected clinical uremic thrombopathy, the use of desmopressin acetate (DDAVP) was considered. Most biopsies (90.6%) were done by the same dedicated radiologist. Fifty-one patients had a BT test, which was normal in all tested patients. Seventy-one patients underwent TEG, and it was abnormal in 34 of them, most patients had combined abnormalities. The only parameter related to abnormal TEG was older age (Odds Ratio 1.21 [95% CI 1.09-2.38] = 0.04 for abnormal Kinetics; OR 1.37 (1.05-1.96) = 0.037 for abnormal MA). Twenty-six patients (6.23%) had bleeding complications. Risk of bleeding was significantly related to age (1.4 [1.11-7.48] = 0.04), systolic blood pressure (1.85 [1.258-9.65] = 0.02), and serum creatinine (1.21 [1.06-3.134] = 0.048). TEG abnormalities in patients with renal dysfunction are variable and fail to predict bleeding during kidney biopsy. The decision to administer DDAVP as a preventive measure during these procedures should be based on clinical judgment only.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biopsy; Bleeding Time; Clinical Decision-Making; Deamino Arginine Vasopressin; Female; Hemostatics; Humans; Kidney; Kidney Diseases; Male; Middle Aged; Point-of-Care Testing; Postoperative Hemorrhage; Retrospective Studies; Risk Assessment; Thrombelastography; Ultrasonography, Interventional; Young Adult
PubMed: 31842662
DOI: 10.1080/0886022X.2019.1700805 -
British Medical Journal (Clinical... Jul 1985
Topics: Bleeding Time; Blood Platelet Disorders; Humans; Platelet Count; Platelet Function Tests
PubMed: 3926099
DOI: 10.1136/bmj.291.6488.91 -
Journal of Hepatology Dec 2011Patients with cirrhosis can have abnormalities in laboratory tests reflecting changes in primary haemostasis, including bleeding time, platelet function tests, markers... (Review)
Review
Patients with cirrhosis can have abnormalities in laboratory tests reflecting changes in primary haemostasis, including bleeding time, platelet function tests, markers of platelet activation, and platelet count. Such changes have been considered particularly relevant in the bleeding complications that occur in cirrhosis. However, several studies have shown that routine diagnostic tests, such as platelet count, bleeding time, PFA-100, thromboelastography are not clinically useful to stratify bleeding risk in patients with cirrhosis. Moreover, treatments used to increase platelet count or to modulate platelet function could potentially do harm. Consequently the optimal management of bleeding complications is still a matter of discussion. Moreover, in the last two decades there has been an increased recognition that not only bleeding but also thrombosis complicates the clinical course of cirrhosis. Thus, we performed a literature search looking at publications studying both qualitative and quantitative aspects of platelet function to verify which primary haemostasis defects occur in cirrhosis. In addition, we evaluated the contribution of qualitative and quantitative aspects of platelet function to the clinical outcome in cirrhosis and their therapeutic management according to the data available in the literature. From the detailed analysis of the literature, it appears clear that primary haemostasis may not be defective in cirrhosis, and a low platelet count should not necessarily be considered as an automatic index of an increased risk of bleeding. Conversely, caution should be observed in patients with severe thrombocytopenia where its correction is advised if bleeding occurs and before invasive diagnostic and therapeutic procedures.
Topics: Bleeding Time; Blood Platelets; Hemorrhage; Hemostasis; Hemostatic Disorders; Humans; Liver Cirrhosis; Models, Biological; Platelet Activation; Platelet Aggregation; Platelet Transfusion; Splenectomy; Thrombocytopenia; Thrombopoietin
PubMed: 21718668
DOI: 10.1016/j.jhep.2011.06.008 -
Transfusion Feb 2021Cold storage of platelets (PLTs) has the potential advantage of prolonging storage time while reducing posttransfusion infection given the decreased likelihood of...
BACKGROUND
Cold storage of platelets (PLTs) has the potential advantage of prolonging storage time while reducing posttransfusion infection given the decreased likelihood of bacterial outgrowth during storage and possibly beneficial effects in treating bleeding patients. However, cold storage reduces PLT survival through the induction of complex storage lesions, which are more accentuated when storage is prolonged.
STUDY DESIGN AND METHODS
Whole blood-derived PLT-rich plasma concentrates from seven PLT pools (n = 5 donors per pool). PLT additive solution was added (67%/33% plasma) and the product was split into 50-mL bags. Split units were stored in the presence or absence of 1 mM of N-acetylcysteine (NAC) under agitation for up to 14 days at room temperature or in the cold and were analyzed for PLT activation, fibrinogen-dependent spreading, microparticle formation, mitochondrial respiratory activity, reactive oxygen species (ROS) generation, as well as in vivo survival and bleeding time correction in immunodeficient mice.
RESULTS
Cold storage of PLTs for 7 days or longer induces significant PLT activation, cytoskeletal damage, impaired fibrinogen spreading, enhances mitochondrial metabolic decoupling and ROS generation, and increases macrophage-dependent phagocytosis and macrophage-independent clearance. Addition of NAC prevents PLT clearance and allows a correction of the prolonged bleeding time in thrombocytopenic, aspirin-treated, immunodeficient mice.
CONCLUSIONS
Long-term cold storage induces mitochondrial uncoupling and increased proton leak and ROS generation. The resulting ROS is a crucial contributor to the increased macrophage-dependent and -independent clearance of functional PLTs and can be prevented by the antioxidant NAC in a magnesium-containing additive solution.
Topics: Acetylcysteine; Animals; Antioxidants; Aspirin; Bleeding Time; Blood Platelets; Blood Preservation; Cell Shape; Cold Temperature; Fibrinogen; Humans; Macrophages; Mice; Mice, Inbred NOD; Mice, SCID; Mitochondria; Oxygen Consumption; Phagocytosis; Platelet Activation; Platelet Transfusion; Platelet-Rich Plasma; Reactive Oxygen Species; Thrombocytopenia
PubMed: 33247486
DOI: 10.1111/trf.16200 -
Clinical and Applied... 2012In patients with chronic kidney disease (CKD) predisposition to bleeding is frequently seen due to disturbances in platelet adhesion and aggregation. Various tests have... (Clinical Trial)
Clinical Trial Comparative Study
INTRODUCTION
In patients with chronic kidney disease (CKD) predisposition to bleeding is frequently seen due to disturbances in platelet adhesion and aggregation. Various tests have been utilized to evaluate the disturbance of hemostasis in end-stage renal disease patients. In this trial; we evaluated skin bleeding time in patients admitted to our hospital with uremic symptoms and having hemodialysis (HD) for the first time. We also examined the effects of HD and uremia on this test and investigated its effectiveness in predicting the hemorrhagic complications before implementation of invasive procedures in uremic patients.
MATERIAL-METHOD
Twenty nine patients (13 men,16 women; mean age 59.7 ± 18.1) with CKD who presented with symptoms of uremia and treated with HD for the first time were enrolled in this trial. The skin bleeding time were measured before initiation of first hemodialysis and after the second hemodialysis session.
RESULTS
The skin bleeding time after the second dialysis was significantly shorter when compared to pre-dialysis values (p < 0.05). Correlation analysis between the skin bleeding time and urea, creatinine, hemoglobin, platelet, and bicarbonate showed no correlation.
CONCLUSIONS
Skin bleeding time could reveal the uremic platelet dysfunction and beneficial effect of dialysis in the patients who presented with uremic symptoms and treated with HD for the first time. We suggest that skin bleeding time may be an appropriate test for the evaluation of hemostasis disturbance in uremic patients and prediction of the bleeding risk before invasive procedures.
Topics: Adult; Aged; Bicarbonates; Bleeding Time; Blood Platelet Disorders; Blood Platelets; Clinical Trials as Topic; Creatinine; Female; Hematocrit; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Skin; Urea; Uremia
PubMed: 22327827
DOI: 10.1177/1076029611427438 -
British Journal of Clinical Pharmacology May 2008From case reports it has become clear that selective serotonin reuptake inhibitors (SSRIs) can cause bleeding disorders. The causative mechanism is as yet unknown....
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
From case reports it has become clear that selective serotonin reuptake inhibitors (SSRIs) can cause bleeding disorders. The causative mechanism is as yet unknown. Several publications have described the relationship between the serotonin transporter genotype and the prevalence of certain diseases such as depression, but few have focused on the relationship with side-effects of antidepressive drugs such as SSRIs.
WHAT THIS STUDY ADDS
This study suggests that the association between SSRI therapy and prolonged bleeding time may not be related to the polymorphism of the serotonin transporter (5-HTTLPR) investigated.
AIMS
Selective serotonin reuptake inhibitors (SSRIs), such as paroxetine, are associated with an increased risk of bleeding disorders, probably due to decreased platelet serotonin levels. Polymorphisms in the serotonin transporter gene (5-HTT) may influence the risk of SSRI-induced bleedings. The aim of this study was to investigate whether and to what extent the serotonin transporter polymorphism increases the bleeding time in paroxetine users.
METHODS
A prospective study, using routinely collected hospital and pharmacy data, was conducted among 43 patients between 18 and 70 years old and on >4 weeks of paroxetine therapy. The genotype for the serotonin transporter (5-HTTLPR), trough paroxetine levels, platelet function analyser (PFA)-closure time (collagen/epinephrine) and a complete blood count were assessed.
RESULTS
No significant difference was seen between the SS, SL, LL genotypes of the serotonin transporter and the PFA-closure time. None of the covariates had a significant influence on the association between the serotonin transporter polymorphism and the PFA-closure time. Age and von Willebrand factor showed the largest contribution, but not significant. No difference was seen between the PFA-closure time and the frequency of bruising and spontaneous bleedings between patients with at least one S allele and with the LL genotype.
CONCLUSION
Our prospective study does not support the assumption that paroxetine can cause a prolonged PFA-closure time during paroxetine therapy due to a serotonin transporter polymorphism. Old age, use of platelet inhibitors and a history of gastrointestinal bleeding remain the focus for SSRI-induced bleeding complications.
Topics: Adolescent; Adult; Aged; Bleeding Time; Blood Platelets; Depressive Disorder; Female; Genotype; Humans; Male; Middle Aged; Paroxetine; Polymorphism, Genetic; Prospective Studies; Serotonin Plasma Membrane Transport Proteins; Selective Serotonin Reuptake Inhibitors
PubMed: 18279474
DOI: 10.1111/j.1365-2125.2008.03098.x -
American Journal of Hematology Apr 2003Acquired von Willebrand's disease or syndrome (AVWS) is a rare bleeding disorder distinguished from congenital von Willebrand's disease by age at presentation and... (Review)
Review
Acquired von Willebrand's disease or syndrome (AVWS) is a rare bleeding disorder distinguished from congenital von Willebrand's disease by age at presentation and absence of personal and family history of bleeding disorders. We report on 22 patients with AVWS seen over 25 years. Mean age at diagnosis was 61.3 years (range 38-86 years); most patients had a spontaneous or a post-operative hemorrhage at presentation. Gastrointestinal bleeding and epistaxis were the most common spontaneous symptoms. Bleeding time was prolonged in most patients, associated with marked reductions in plasma von Willebrand factor antigen and ristocetin cofactor activity. Plasma VWF multimer distribution was normal (type 1 pattern) in 5 patients, indeterminate (no multimers detectable) in 6 patients (type 3 pattern), and abnormal (decreased higher-molecular-weight multimers, type 2 pattern) in 11 patients. None of 17 patients tested had an inhibitor of ristocetin cofactor activity. An underlying malignant or benign hematologic disease was found in 18 patients, and 1 patient had Crohn's disease. Desmopressin was effective in only half the patients so treated, but all patients responded to treatment with VWF-containing concentrates. Resolution of AVWS occurred with therapy of lymphoma (1 patient) and chronic lymphocytic leukemia (1 patient). Sixteen patients were alive at last follow-up; no deaths were related to bleeding. AVWS may be more prevalent than has been appreciated; we estimate up to 0.04%. Awareness of the existence of AVWS is essential for diagnosis and appropriate management. Therapy of associated diseases may improve the bleeding disorder.
Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antibody Specificity; Autoantibodies; Autoimmune Diseases; Bleeding Time; Crohn Disease; Deamino Arginine Vasopressin; Female; Hematologic Diseases; Hematologic Neoplasms; Humans; Male; Middle Aged; Minnesota; Paraproteins; Postoperative Hemorrhage; Retrospective Studies; von Willebrand Diseases; von Willebrand Factor
PubMed: 12666134
DOI: 10.1002/ajh.10298 -
Amino Acids Mar 2013It has been demonstrated that a wide variety of white blood cells and macrophages (i.e. Kupffer cells, alveolar and peritoneal macrophages and neutrophils) contain...
It has been demonstrated that a wide variety of white blood cells and macrophages (i.e. Kupffer cells, alveolar and peritoneal macrophages and neutrophils) contain glycine-gated chloride channels. Binding of glycine on the receptor stimulates Cl(-) influx causing membrane hyperpolarization that prevents agonist-induced influx of calcium. Since platelet-aggregation is calcium-dependent, this study was designed to test the hypothesis that glycine would inhibit platelet aggregation. Rats were fed diets rich of glycine for 5 days, while controls received isonitrogenous valine. The bleeding time and ADP- and collagen-induced platelet aggregation were measured. Dietary glycine significantly increased bleeding time about twofold compared to valine-treated controls. Furthermore, the amplitude of platelet aggregation stimulated with ADP or collagen was significantly decreased in whole blood drawn from rats fed 2.5 or 5 % dietary glycine by over 50 %. Addition of glycine in vitro (1-10 mM) also blunted rat platelet aggregation in a dose-dependent manner. Strychnine, a glycine receptor antagonist, abrogated the inhibitory effect of glycine on platelet-aggregation in vitro suggesting the glycine works via a glycine receptor. Glycine also blunted aggregation of human platelets. Further, the glycine receptor was detected in both rat and human platelets by western blotting. Based on these data, it is concluded that glycine prevents aggregation of platelets in a dose-dependent manner via mechanisms involving a glycine receptor.
Topics: Animals; Bleeding Time; Blood Platelets; Down-Regulation; Female; Glycine; Humans; Platelet Aggregation; Rats; Rats, Sprague-Dawley; Receptors, Glycine
PubMed: 23135224
DOI: 10.1007/s00726-012-1422-8 -
Blood Jun 1991
Review
Topics: Bleeding Time; Blood Platelet Disorders; Cardiac Surgical Procedures; Hemorrhage; Humans; Intraoperative Complications; Prospective Studies; Thrombocytopenia
PubMed: 2043759
DOI: No ID Found