Abstract:
INTRODUCTION:Severe thrombocytopenia (≤50×10(9) platelets/L) is often the consequence of hematological malignancies and intensive chemotherapy. The risk of clinically significant bleeding is increased in these patients, despite the use of prophylactic platelet transfusions. The fact that there is no clear correlation between the platelet count and the risk of hemorrhage, suggests that there are other contributing factors. The contribution of impairments in platelet and coagulant function remains poorly understood. AIM:In patients with chemotherapy-induced thrombocytopenia due to hematological malignancies, we evaluate platelet and coagulant functions and determine the effects of platelet transfusion. Ultimately, we can identify specific hemostatic factors that aid in the prediction of bleeding. MATERIALS AND METHODS:In total 58 patients were included and blood was collected before and, if indicated (≤10×10(9) platelets/L), 1 hour after transfusion with platelet concentrate. Platelet function was assessed using flow cytometry by determining: 1) integrin αIIbβ3 activation (PAC-1 antibody), 2) P-selectin expression (anti-P-selectin antibody), 3) phosphatidylserine exposure (Annexin-V) and 4) intracellular calcium (Fluo-4 AM). Factor levels were determined in plasma. Thrombus and fibrin formation was assessed by perfusion of whole blood over a collagen-tissue factor surface at a shear rate of 1,000 s-1. RESULTS:Platelets from the thrombocytopenic patients before transfusion showed markedly reduced integrin αIIbβ3 activation and P-selectin expression in response to thrombin, collagen-related peptide and ADP, compared to healthy donor platelets. Also, agonist-induced intracellular calcium fluxes were greatly reduced. However, calcium fluxes with thapsigargin, a SERCA pump inhibitor, were similar in patient and control platelets, suggesting a normal calcium store content in the patient platelets. Furthermore, phosphatidylserine exposure was increased in unstimulated patient platelets compared to control platelets (8.2 vs. 1.8%, p<0.0001). Coagulation factor levels were within the normal range, with the exception of von Willebrand factor and fibrinogen levels, which were elevated. Platelet transfusion partly recovered the platelet integrin αIIbβ3 activation and P-selectin expression induced by agonists. Platelet deposition (6.7 vs. 1.7%, p<0.0001) and fibrin formation (7.6 vs. 0.9%, p=0.0005) under flow conditions were substantially improved after platelet transfusion. CONCLUSIONS:Platelets from cancer patients undergoing chemotherapy appear to display impaired functional responses to activating stimuli. Platelet transfusion partly restores these functional defects, resulting in improved thrombus and fibrin formation.
journal_name
Thromb Resjournal_title
Thrombosis researchauthors
Baaten CC,Moenen FC,Henskens YM,Swieringa F,Wetzels R,van Oerle R,Ten Cate H,Beckers EA,Heemskerk JW,van der Meijden PEdoi
10.1016/S0049-3848(16)30125-6subject
Has Abstractpub_date
2016-04-01 00:00:00pages
S171eissn
0049-3848issn
1879-2472pii
S0049-3848(16)30125-6journal_volume
140 Suppl 1pub_type
杂志文章abstract::Diabetes mellitus (DM) is associated with platelet and leukocyte dysfunction. Previous observations with regard to insulin effects on platelet and leukocyte function are less than consistent. We thus investigated the effects of insulin on platelets and leukocytes, as well as on platelet-leukocyte interactions in whole...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/s0049-3848(02)00306-7
更新日期:2002-09-01 00:00:00
abstract:INTRODUCTION:Warfarin is the most widely used oral anticoagulant. It has been suggested that anticoagulation effect of warfarin is significantly associated with the polymorphism of certain genes, including Cytochrome P450 complex subunit 2C9 (CYP2C9), Vitamin K Epoxide Reductase Complex Subunit 1 (VKORC1), Gamma-Glutam...
journal_title:Thrombosis research
pub_type: 杂志文章,meta分析,评审
doi:10.1016/j.thromres.2009.10.017
更新日期:2010-04-01 00:00:00
abstract:INTRODUCTION:Available data on fibrin clot properties and fibrinolysis in hyperthyroidism and hypothyroidism are inconsistent. Our objective was to assess the impact of effective treatment of hyper- and hypothyroidism on fibrin clot characteristics. MATERIAL AND METHODS:In a case-control study, ex vivo plasma fibrin c...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2014.05.041
更新日期:2014-08-01 00:00:00
abstract::Activated platelets secrete different chemokines, among others CCL5, thereby triggering inflammatory cell recruitment into the vessel wall. Here, we investigated how CCL5 deficiency influences vascular remodeling processes. Experiments were performed in apolipoprotein E and CCL5 double deficient (ApoE(-/-)×CCL5(-/-)) ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2016.06.013
更新日期:2016-08-01 00:00:00
abstract::This study examined the effect of exercise on plasma fibrinogen concentrations with simultaneous measurements of plasma volume changes. Eight moderately active males aged 26.6+/-3.6 years (mean +/- SD) completed maximal (VO2max) and submaximal (75% VO2max for 30 minutes) exercise trials separated by 7 days. Venous blo...
journal_title:Thrombosis research
pub_type: 临床试验,杂志文章
doi:10.1016/s0049-3848(99)00140-1
更新日期:1999-12-15 00:00:00
abstract::An issue of great importance and continuing concern with regard to all products derived from human plasma is their safety from potential contaminants in the source material from which they are purified. Since viral contaminants are a major safety consideration with these products, a number of different methods, includ...
journal_title:Thrombosis research
pub_type: 杂志文章,评审
doi:10.1016/s0049-3848(02)00044-0
更新日期:2002-03-01 00:00:00
abstract::Numerous factors affect the response to vitamin K antagonists (VKA) including age, dietary vitamin K, other drugs, pharmacogenetics, and disease states. In antithrombotic guidelines, fever is mentioned as a factor that may increase response to VKA. The purpose of this article is to review the available evidence regard...
journal_title:Thrombosis research
pub_type: 杂志文章,评审
doi:10.1016/j.thromres.2014.10.015
更新日期:2015-01-01 00:00:00
abstract:INTRODUCTION:Pelvic deep vein thrombosis (DVT) is difficult to diagnose during pregnancy. In a two-center trial, we evaluated the agreement between ultrasonography and magnetic resonance imaging (MRI) in diagnosing the extent of DVT into the pelvic veins during pregnancy. MATERIALS AND METHODS:Pregnant women with prox...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2010.05.011
更新日期:2010-08-01 00:00:00
abstract::A 15 year-aged Japanese girl with a life long mild purpura was found as a variant type of thrombasthenia. Basic tests revealed prolonged bleeding time, border-line clot retraction, no coagulation defect, no giant platelets and mild thrombocytopenia (70,000-110,000/microliters). Neither ADP, epinephrine nor collagen ag...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(87)90146-0
更新日期:1987-08-01 00:00:00
abstract::Understanding the intracellular events triggered by antiphospholipid (aPL) antibodies in platelets and endothelial cells (ECs) is important in designing new modalities of targeted therapies for the treatment of thrombosis in Antiphospholipid Syndrome (APS). A recent study showed a significant increase in the expressio...
journal_title:Thrombosis research
pub_type: 杂志文章,评审
doi:10.1016/j.thromres.2004.06.031
更新日期:2004-01-01 00:00:00
abstract:BACKGROUND:Clopidogrel, cilostazol, and aspirin were compared in terms of efficacy and safety for primary prevention of stroke in peripheral artery disease (PAD) patients. METHODS:This retrospective cohort study analyzed data contained in the Taiwan National Health Insurance Bureau database for patients treated for PA...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2013.01.036
更新日期:2013-08-01 00:00:00
abstract::Extended half-life (EHL) products have shown robust efficacy in clinical trials, whilst allowing for less intense treatment regimens when compared with standard half-life products. Regimen optimisation with EHL products could lead to further improvements in bleeding rates, quality of life and reductions in treatment b...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2019.12.012
更新日期:2020-12-01 00:00:00
abstract::Bleeding is an important complication of heparin therapy. A number of low molecular weight heparin fractions produce less bleeding than standard heparin for an equivalent antithrombotic effect in experimental animals. Low molecular weight heparin fractions and fragments are produced by a number of different procedures...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(84)90265-2
更新日期:1984-09-15 00:00:00
abstract::The von Willebrand factor (vWF) is found in plasma and in platelets. The concentration and multimeric composition of the vWF in platelets of 160 patients with bleeding tendency were examined since very little is known about the platelet vWF. For quantitative analysis of the platelet vWF, a modified ELISA was establish...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(92)90212-s
更新日期:1992-03-01 00:00:00
abstract:OBJECTIVE:The diallelic glycoprotein IIIa polymorphism P1A1/A2 was attributed to be an inherited risk factor for coronary events. Whether this polymorphism affects response to aspirin in patients with coronary artery disease is not known. METHODS:We assessed thrombin generation (prothrombin fragment F1+2) in consecuti...
journal_title:Thrombosis research
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.thromres.2006.03.005
更新日期:2007-01-01 00:00:00
abstract::To investigate the effects of new drugs on the prevention of venous thrombosis, the Wessler stasis model is extensively employed usually in the rabbit. In this model, a hypercoagulable state is achieved by the administration of either heterologous serum (often human serum) or an activated coagulation factor followed b...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(96)00023-0
更新日期:1996-02-15 00:00:00
abstract::Individuals with more than one defect in the natural anticoagulant system exhibit an increased risk for thrombosis. We report on a family with two cases of combined protein C (PROC) and protein S (PROS) deficiency, five cases of isolated PROC deficiency Type I, and two cases of isolated PROS deficiency Type I. PROC an...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/s0049-3848(01)00232-8
更新日期:2001-07-01 00:00:00
abstract::We investigated on how to effectively administer orally factor VIII preparation to two patients with von Willebrand's disease as volunteers, and the following results were obtained: Bleeding time and aPTT were shortened, but no change of PT was observed. Factor VIII:C increased slightly, but no significant increase wa...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(85)90211-7
更新日期:1985-06-15 00:00:00
abstract::RS-5186, sodium 6-[2-[1-(1H)-imidazolyl]methyl-4,5-dihydrobenzo[b]thiophene]- carboxylate, inhibited platelet thromboxane A2 (TXA2) synthetase with IC50 values of 6 nM and 13 nM for human and rabbit microsomes, respectively. It had a selectivity for TXA2 synthetase 10(5)-fold greater than that for cyclooxygenase, PGI2...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(88)90116-8
更新日期:1988-09-01 00:00:00
abstract::Heparin with low affinity (LA-heparin) to antithrombin III (AT III) enhanced the rate of inactivation of thrombin by AT III. The enhancement of the rate was saturable with AT III and was proportional to the LA-heparin concentration. Although the rate-enhancement in the presence of LA-heparin decreased with increase in...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(86)90247-1
更新日期:1986-02-01 00:00:00
abstract::It has previously been observed that aspirin diminishes the increase in blood fibrinolytic activity during arm venous occlusion. We studied the duration of this inhibitory effect on fibrinolytic response during 20 minutes arm venous occlusion and its effect on fibrinolytic response during acute physical activity (stan...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(87)90282-9
更新日期:1987-04-15 00:00:00
abstract::The anticoagulant (U.S.P., APTT; "in vitro" and "in vivo") antithrombotic (aXa; Yin and Wessler and chromogenic), antilipemic (LPL) activities of heparin, heparin fractions and fragments, heparinoids, heparan sulfate and other sulfated glycosaminoglycans were compared with the activities of these compounds as antithro...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(85)90298-1
更新日期:1985-12-01 00:00:00
abstract:INTRODUCTION:Patients with stable coronary artery disease (CAD) are at risk of arterial thrombosis causing myocardial infarction. Detection of global haemostatic markers of hypercoagulability and hypofibrinolysis may be important for risk stratification and individualised treatment. We examined overall haemostatic pote...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2013.03.015
更新日期:2013-05-01 00:00:00
abstract:INTRODUCTION:Viscoelastometry enables rapid evaluation of coagulopathy in settings such as cardiac surgery but may be influenced by red cell concentration. METHODS:In order to study the effects of supra-physiological red cell concentrations on viscoelastometry, we compared ROTEM® viscoelastometry and plasma coagulatio...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2013.07.006
更新日期:2013-08-01 00:00:00
abstract::The effect of activated protein C (APC) on agonist-induced platelet activation and on thrombin generation after intrinsic (IA) and extrinsic (EA) activation of the coagulation system was studied by flow cytometry and by measuring levels of prothrombin fragment F1+2. In platelet activation studies blood drawn from heal...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/s0049-3848(97)00119-9
更新日期:1997-07-15 00:00:00
abstract:INTRODUCTION:Proteasome inhibitor bortezomib (PS-341) has been the first proteasome inhibitor that has entered clinical trials with its antiproliferative and proapoptotic effects in patients with multiple myeloma. Recent studies indicate that proteasome inhibitors can be useful in prevention of experimental arterial th...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2007.06.013
更新日期:2008-01-01 00:00:00
abstract::Previous studies indicated that human placental anticoagulant protein, a member of the lipocortin family, prolonged the clotting time of normal plasma when clotting was induced by brain thromboplastin or by kaolin in the presence of cephalin and calcium. Using a two-stage amidolytic assay to assess factor X activation...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(87)90402-6
更新日期:1987-11-15 00:00:00
abstract::Fractalkine/CX3CR1 pathway is considered a major modulator of atherosclerosis. In the present study, expression of CX3CR1 on PBMCs/monocytes of healthy individuals and coronary artery diseased patients was initially assessed by flow cytometry. Effects of pre-inflammatory cytokines interferon (INF)-gamma and tumor necr...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2007.04.005
更新日期:2007-01-01 00:00:00
abstract:INTRODUCTION:A fraction of fibrinogen molecules contain an alternatively spliced variant chain called gamma'. Plasma levels of this variant have been associated with both myocardial infarction and venous thrombosis. Because clot structure has been associated with cardiovascular risk, we examined the effect of gamma' ch...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2008.11.016
更新日期:2009-07-01 00:00:00
abstract::Epidemiological studies have shown that oral contraceptives increase the risk of thromboembolic disease in susceptible women however the mechanisms involved are unclear. We investigated whole blood platelet aggregation in 44 women randomly allocated to 6 cycles of treatment with either gestodene (75ug) or desogestrel ...
journal_title:Thrombosis research
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/0049-3848(96)00013-8
更新日期:1996-02-15 00:00:00