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Reversible crystallization of argatroban after subcutaneous application in pigs.

Lopez M, Nowak G

Thrombosis · 2012 · PMID 22988498 · Full text

Argatroban is a thrombin inhibitor used as anticoagulant in patients with heparin-induced thrombocytopenia. It is usually administered as an intravenous bolus followed by infusion. Nevertheless, its pharmacokinetics afte... Argatroban is a thrombin inhibitor used as anticoagulant in patients with heparin-induced thrombocytopenia. It is usually administered as an intravenous bolus followed by infusion. Nevertheless, its pharmacokinetics after subcutaneous administration is unknown. The aim of this study was to assess the pharmacokinetics of two different formulations of argatroban in pigs after subcutaneous administration. Antithrombotic activity in plasma was determined by ecarin chromogenic assay. To visualize the formation of crystals, argatroban was administered to rats into the subcutaneous tissue exposed after removing the skin, and the injection site was photographed at different times. After subcutaneous administration of a sorbitol/ethanol formulation of argatroban in pigs was observed a slow absorption phase was followed by long-lasting levels of this inhibitor. C(max) and AUC((0-24)) showed dose-dependent increases, while elimination half-life and t(max) value did not change significantly with dose. In contrast, saline-dissolved argatroban showed a faster absorption phase followed by a shorter elimination half-life. Argatroban dissolved in sorbitol/ethanol leads to long-lasting plasma levels due to the formation and permanent dissolution of a crystalline depot at the injection place. This represents a simple way to deliver argatroban continuously over an extended period which can be beneficial for prophylaxis or treatment of chronic coagulations disorders.

Actual situation of thromboembolic prophylaxis in obesity surgery: data of quality assurance in bariatric surgery in Germany.

Stroh C, Luderer D, Weiner R … +7 more , Horbach T, Ludwig K, Benedix F, Wolff S, Knoll C, Lippert H, Manger T

Thrombosis · 2012 · PMID 22848807 · Full text

Background. Evidence-based data on optimal approach for prophylaxis of deep venous thrombosis (VTE) and pulmonary embolism (PE) in bariatric operations is discussed. Using antithrombotic prophylaxis weight adjusted the r... Background. Evidence-based data on optimal approach for prophylaxis of deep venous thrombosis (VTE) and pulmonary embolism (PE) in bariatric operations is discussed. Using antithrombotic prophylaxis weight adjusted the risk of VTE and its complications have to be balanced with the increased bleeding risk. Methods. Since 2005 the current situation for bariatric surgery has been examined by quality assurance study in Germany. As a prospective multicenter observational study, data on the type, regimen, and time course of VTE prophylaxis were documented. The incidences of clinically diagnosed VTE or PE were derived during the in-hospital course and follow up. Results. Overall, 11,835 bariatric procedures were performed between January 2005 and December 2010. Most performed procedures were 2730 gastric banding (GB); 4901 Roux-en-Y-gastric bypass (RYGBP) procedures, and 3026 sleeve gastrectomies (SG). Study collective includes 72.5% (mean BMI 48.1 kg/m(2)) female and 27.5% (mean BMI 50.5 kg/m(2)) male patients. Incidence of VTE was 0.06% and of PE 0.08%. Conclusion. VTE prophylaxis regimen depends on BMI and the type of procedure. Despite the low incidence of VTE and PE there is a lack of evidence. Therefore, prospective randomized studies are necessary to determine the optimal VTE prophylaxis for bariatric surgical patients.

Factor V-Leiden Mutation: A Common Risk Factor for Venous Thrombosis among Lebanese Patients.

Kreidy R

Thrombosis · 2012 · PMID 22737581 · Full text

Aim. Lebanon exhibits one of the highest prevalences of factor V-Leiden (FVL) in the world (14.4%). The aim of this study is to evaluate the incidence of FVL mutation among Lebanese patients with lower extremity venous t... Aim. Lebanon exhibits one of the highest prevalences of factor V-Leiden (FVL) in the world (14.4%). The aim of this study is to evaluate the incidence of FVL mutation among Lebanese patients with lower extremity venous thrombosis. Material and Methods. From January 2003 to January 2011, 283 consecutive Lebanese patients, diagnosed with deep venous thrombosis (DVT) by duplex scan, were retrospectively reviewed. FVL mutation was tested among patients with conditions highly suggestive of hypercoagulation states (65 patients). Results. FVL mutation was detected among 56.9% of patients, 68.6% of patients younger than 50 years, and 43.4% of patients older than 50 years (P = 0.041). FVL mutation was commonly reported in young adults, in patients with pregnancy, estrogen drugs, recurrent DVT, and resistance to anticoagulation. Conclusion. The high rate of FVL mutation observed among Lebanese patients with venous thrombosis is related to the high prevalence of this mutation in the Lebanese population. Thrombophilia screening should be tailored to accommodate a population's risk factor. In countries with high prevalence of FVL, this mutation should be screened among patients younger than 50 years and patients with situations highly suggestive of hypercoagulation states.

Factor v leiden and inflammation.

Perez-Pujol S, Aras O, Escolar G

Thrombosis · 2012 · PMID 22666576 · Full text

Factor V Leiden, is a variant of human factor V (FV), also known as proaccelerin, which leads to a hypercoagulable state. Along these years, factor V Leiden (FVL) has been studied from the pathophysiologic point of view,... Factor V Leiden, is a variant of human factor V (FV), also known as proaccelerin, which leads to a hypercoagulable state. Along these years, factor V Leiden (FVL) has been studied from the pathophysiologic point of view, and research has been focused on finding clinical approaches for the management of the FVL associated to a trombophilic state. Less attention has been paid about the possible role of FVL in inflammatory conditions known to be present in different disorders such as uremia, cirrhosis, liver transplantation, depression as well as sepsis, infection or, inflammatory bowel disease (IBD). Whether platelet FVL will increase the activation of coagulation and/or in which proportion is able to determine the final outcome in the previously mentioned inflammatory conditions is a subject that remains uncertain. This paper will review the association of FVL with inflammation. Specifically, it will analyze the important role of the endothelium and the contribution of other inflammatory components involved at both the immune and vascular levels. This paper will also try to emphasize the importance of being a FVL carrier in associations to diseases where a chronic inflammation occurs, and how this condition may be determinant in the progression and outcome of a specific clinic situation.

Pathological perspective of drug-eluting stent thrombosis.

Inoue K

Thrombosis · 2012 · PMID 22666575 · Full text

Although very late stent thrombosis (VLST) after drug-eluting stent (DES) implantation remains a major concern, the precise mechanisms have not been clarified. An association between late acquired incomplete stent apposi... Although very late stent thrombosis (VLST) after drug-eluting stent (DES) implantation remains a major concern, the precise mechanisms have not been clarified. An association between late acquired incomplete stent apposition (ISA) and VLST of DES has been suggested by several intravascular ultrasound studies demonstrating very high prevalence of ISA in the setting of VLST. To clarify the pathological mechanisms of VLST, we investigated vascular responses of coronary arteries of VLST cases after DES implantation.

Everolimus-Eluting versus Paclitaxel-Eluting Stents in Percutaneous Coronary Intervention: Meta-Analysis of Randomized Trials.

Alazzoni A, Al-Saleh A, Jolly SS

Thrombosis · 2012 · PMID 22655192 · Full text

Background. Individual randomized trials have suggested that everolimus-eluting stents may have improved clinical outcomes compared to paclitaxel-eluting stents, but individual trials are underpowered to examine outcomes... Background. Individual randomized trials have suggested that everolimus-eluting stents may have improved clinical outcomes compared to paclitaxel-eluting stents, but individual trials are underpowered to examine outcomes such as mortality and very late stent thrombosis. Methods. Medline, Cochrane, and conference proceedings were searched for randomized trials comparing everolimus versus paclitaxel-eluting stents for percutaneous coronary intervention. Results. 6792 patients were included from 4 randomized controlled trials. Stent thrombosis was reduced with everolimus stents versus paclitaxel stents (0.7% versus 2.3%; OR: 0.32; CI: 0.20-0.51; P < 0.00001). The reductions in stent thrombosis were observed in (i) early stent thrombosis (within 30 days) (0.2% versus 0.9%; OR: 0.24; P = 0.0005), (ii) late (day 31-365) (0.2% versus 0.6%; OR: 0.32; P = 0.01), and (iii) very late stent thrombosis (>365 days) (0.2% versus 0.8%; OR: 0.34; P = 0.009). The rates of cardiovascular mortality were 1.2% in everolimus group and 1.6% in paclitaxel group (OR: 0.85; P = 0.43). Patients receiving everolimus-eluting stents had significantly lower myocardial infarction events and target vessel revascularization as compared to paclitaxel-eluting stents. Interpretation. Everolimus compared to paclitaxel-eluting stents reduced the incidence of early, late, and very late stent thrombosis as well as target vessel revascularization.

Dabigatran for stroke prevention in nonvalvular atrial fibrillation: answers to challenging "real-world" questions.

Ferreira J, Ferreira D, Viana-Baptista M … +3 more , Bettencourt P, Cernadas R, Crespo F

Thrombosis · 2012 · PMID 22645678 · Full text

Dabigatran etexilate is a novel, oral, reversible, direct thrombin inhibitor that constitutes a major breakthrough for stroke prevention in patients with nonvalvular atrial fibrillation (AF). Dabigatran was the first new... Dabigatran etexilate is a novel, oral, reversible, direct thrombin inhibitor that constitutes a major breakthrough for stroke prevention in patients with nonvalvular atrial fibrillation (AF). Dabigatran was the first new oral anticoagulant approved in Europe and became available in Portugal, for stroke prevention in nonvalvular AF, earlier than in most European countries. This paper is the joint effort of a panel of experts from different specialties and provides information on the use of dabigatran, in anticipation of the challenges that will come with increased usage.

Stent thrombosis: incidence, predictors and new technologies.

Buchanan GL, Basavarajaiah S, Chieffo A

Thrombosis · 2012 · PMID 22577541 · Full text

Some concerns have been raised regarding the risk of late and very late stent thrombosis (ST) following drug-eluting stent implantation. Despite remaining an uncommon complication of percutaneous coronary intervention, w... Some concerns have been raised regarding the risk of late and very late stent thrombosis (ST) following drug-eluting stent implantation. Despite remaining an uncommon complication of percutaneous coronary intervention, when ST occurs, it can be catastrophic to the individual, commonly presenting as acute ST elevation myocardial infarction or sudden cardiac death. The incidence and predictors of ST have been reported in the literature and the role of dual antiplatelet therapies in the avoidance of such a complication remains vital. Ongoing studies are assessing the role of these therapies including platelet reactivity testing, genetic testing and optimum duration of therapy. In addition, newer polymer-free and bioabsorbable stents are under investigation in the quest to potentially minimise the risk of ST.

Lack of Association between Recurrent Pregnancy Loss and Inherited Thrombophilia in a Group of Colombian Patients.

Cardona H, Castañeda SA, Cardona Maya W … +7 more , Alvarez L, Gómez J, Gómez J, Torres J, Tobón L, Bedoya G, Cadavid AP

Thrombosis · 2012 · PMID 22577540 · Full text

Studies have shown an association between recurrent pregnancy loss and inherited thrombophilia in Caucasian populations, but there is insufficient knowledge concerning triethnic populations such as the Colombian. The aim... Studies have shown an association between recurrent pregnancy loss and inherited thrombophilia in Caucasian populations, but there is insufficient knowledge concerning triethnic populations such as the Colombian. The aim of this study was to evaluate whether inherited thrombophilia is associated with recurrent pregnancy loss. Methods. We conducted a case-control study of 93 patients with recurrent pregnancy loss (cases) and 206 healthy multiparous women (controls) in a Colombian subpopulation. Three single nucleotide polymorphisms (SNPs) markers of the inherited thrombophilias factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T were genotyped by PCR-RFLP. Activated protein C resistance and plasma levels of antithrombin, protein C, and protein S were also measured. Results. The frequency of thrombophilia-associated SNPs, activated protein C resistance, and anticoagulant protein deficiencies, was low overall, except for the methylenetetrahydrofolate reductase C677T SNP. The differences between patients and controls had no statistical significance. Conclusion. Our study confirms the low prevalence of inherited thrombophilias in non-Caucasian populations and it is unlikely that the tested thrombophilias play a role in the pathogenesis of recurrent pregnancy loss in this Colombian population.

Evaluation of RANKL/OPG Serum Concentration Ratio as a New Biomarker for Coronary Artery Calcification: A Pilot Study.

Mohammadpour AH, Shamsara J, Nazemi S … +3 more , Ghadirzadeh S, Shahsavand S, Ramezani M

Thrombosis · 2012 · PMID 22577539 · Full text

Objective. There is a strong need for biomarkers to identify patients at risk for future cardiovascular events related with progressive atherosclerotic disease. Osteoprotegerin (OPG) protects the skeleton from excessive... Objective. There is a strong need for biomarkers to identify patients at risk for future cardiovascular events related with progressive atherosclerotic disease. Osteoprotegerin (OPG) protects the skeleton from excessive bone resorption by binding to receptor activator of nuclear factor-κB ligand (RANKL) and preventing it from binding to its receptor, receptor activator of nuclear factor-κB. However, conflicting results have been obtained about association of serum level of OPG or RANKL with coronary artery disease (CAD). Based on their role in inflammation and matrix degradation and the fact that atherosclerotic plaque formation is an inflammatory process, we hypothesized that RANKL : OPG ratio could be a better biomarker for CAD. Methods. In this cross-sectional study, the correlation between RANKL : OPG ratio serum concentration and coronary artery calcification (CAC) in 50 patients with ischemic coronary disease has been investigated. We used ELISA method for measuring RANKL and OPG serum concentrations. Results. There was a significant correlation between RANKL : OPG serum concentration ratio and CAC in our study population (P = 0.01). Conclusion. Our results suggested that RANKL : OPG ratio concentration has a potential of being used as a marker for coronary artery disease.

Anticoagulant and antiplatelet therapy in patients with atrial fibrillation and coronary artery disease.

Mischke K, Knackstedt C, Marx N

Thrombosis · 2012 · PMID 22577538 · Full text

Anticoagulation represents the mainstay of therapy for most patients with atrial fibrillation. Patients on oral anticoagulation often require concomitant antiplatelet therapy, mostly because of coronary artery disease. A... Anticoagulation represents the mainstay of therapy for most patients with atrial fibrillation. Patients on oral anticoagulation often require concomitant antiplatelet therapy, mostly because of coronary artery disease. After coronary stent implantation, dual antiplatelet therapy is necessary. However, the combination of oral anticoagulation and antiplatelet therapy increases the bleeding risk. Risk scores such as the CHA(2)DS(2)-Vasc score and the HAS-BLED score help to identify both bleeding and stroke risk in individual patients. The guidelines of the European Society of Cardiology provide a rather detailed recommendation for patients on oral anticoagulation after coronary stent implantation. However, robust evidence is lacking for some of the recommendations, and especially for new oral anticoagulants and new antiplatelets few or no data are available. This review addresses some of the critical points of the guidelines and discusses potential advantages of new anticoagulants in patients with atrial fibrillation after stent implantation.

Cerebral vein thrombosis misdiagnosed and mismanaged.

Sasidharan PK

Thrombosis · 2012 · PMID 22567255 · Full text

Cerebral venous thrombosis (CVT) should be considered in the differential diagnosis of all unexplained CNS disorders of sudden onset. Etiological factors are often subclinical forms of several common thrombophilic states... Cerebral venous thrombosis (CVT) should be considered in the differential diagnosis of all unexplained CNS disorders of sudden onset. Etiological factors are often subclinical forms of several common thrombophilic states occurring together, rather than the typical inherited and rare causes. Diagnosis is missed because of the heterogeneity in clinical presentation and etiological factors. In several patients with the so called idiopathic CVT nutritional deficiencies and lifestyle issues are more important factors in pathogenesis, rather than single rarer causes. High index of suspicion is the key to diagnosis. Clinical skill has to be fine tuned to diagnose the problem and to identify all the etiological factors. Radiology is essential for diagnosis but relying on radiology alone will lead to missing several cases and even erroneous diagnosis. It is inappropriate to proceed prematurely to laboratory investigations, forgetting proper clinical evaluation by studying diet, lifestyle, and environment of the patients. Success in managing lies in identifying all the contributory causes and correcting all of them giving excellent outcome almost always. Clinical observations based on case series and sharing of such information alone are the means to arrive at a consensus in diagnosis and management.

Experimental Validation of Methods for Prophylaxis against Deep Venous Thrombosis: A Review and Proposal.

Agutter PS, Malone PC, Silver IA

Thrombosis · 2012 · PMID 22567254 · Full text

The experimental procedure by which the valve cusp hypoxia (VCH) hypothesis of the etiology of deep venous thrombosis (DVT) was confirmed lends itself to testing of methods of prophylaxis. Similar animal experiments coul... The experimental procedure by which the valve cusp hypoxia (VCH) hypothesis of the etiology of deep venous thrombosis (DVT) was confirmed lends itself to testing of methods of prophylaxis. Similar animal experiments could end the present exclusive reliance on statistical analysis of data from large patient cohorts to evaluate prophylactic regimes. The reduction of need for such (usually retrospective) analyses could enable rationally-based clinical trials of prophylactic methods to be conducted more rapidly, and the success of such trials would lead to decreased incidences of DVT-related mortality and morbidity. This paper reviews the VCH hypothesis ("VCH thesis", following its corroboration) and its implications for understanding DVT and its sequelae, and outlines the experimental protocol for testing prophylactic methods. The advantages and limitations of the protocol are briefly discussed.

The role of dermcidin isoform 2: a two-faceted atherosclerotic risk factor for coronary artery disease and the effect of acetyl salicylic Acid on it.

Ghosh R, Maji UK, Bhattacharya R … +1 more , Sinha AK

Thrombosis · 2012 · PMID 22448321 · Full text

Hypertension and diabetes mellitus are considered to be two major atherosclerotic risk factors for coronary artery disease (CAD). A stress-induced protein identified to be dermcidin isoform 2 of Mr. 11 kDa from blood pla... Hypertension and diabetes mellitus are considered to be two major atherosclerotic risk factors for coronary artery disease (CAD). A stress-induced protein identified to be dermcidin isoform 2 of Mr. 11 kDa from blood plasma of hypertensive persons when injected (0.1 μM) in rabbits increased the systolic pressure by 77% and diastolic pressure by 45% over the controls within 2 h. Ingestion of acetyl salicylic acid (150 mg/70 kg) by these subjects reduced systolic (130 mm Hg) and diastolic pressures (80 mm Hg) with reduction of plasma dermcidin level to normal ranges (9 nM). The protein was found to be a potent activator of platelet cyclooxygenase and inhibited insulin synthesis. Aspirin was found to reduce hypertension by reduction of plasma dermcidin level, neutralized the effect of cyclooxygenase, and restored the pancreatic insulin synthesis through NO synthesis. These results indicated that dermcidin could be a novel atherosclerotic risk factor for its hypertensive and diabetogenic effects.

The avantgarde carbostent in patients scheduled for undelayable noncardiac surgery.

Briguori C, Visconti G, De Micco F … +1 more , Focaccio A

Thrombosis · 2012 · PMID 22448320 · Full text

Background. Treatment of patients who need coronary revascularization before undelayable non-cardiac surgery is challenging. Methods. We assessed the safety and efficacy of percutaneous coronary interventions (PCI) using... Background. Treatment of patients who need coronary revascularization before undelayable non-cardiac surgery is challenging. Methods. We assessed the safety and efficacy of percutaneous coronary interventions (PCI) using the Avantgarde( TM) Carbostent (CID, Italy) in patients undergoing PCI before undelayable non-cardiac surgery. The Multiplate analyzer point-of-care was used to assess residual platelet reactivity. One major cardiac events (MACE, defined as death, myocardial infarction, and stent thrombosis and major bleeding) were assessed. Results. 42 consecutive patients were analyzed. Total stent length ≥25 mm was observed in 16 (37%) patients. Multivessel stenting was performed in 11 (31.5%) patients. Clopidogrel was interrupted 5 days before surgery in 35 patients, whereas it was stopped the day of the surgery in 7 patients. Surgery was performed after 27 ± 9 (7-42) days from PCI. MACE occurred in one patient (2.4%; 95% confidence interval: 0.01-13%), who had fatal acute myocardial infarction 3 days after abdominal aortic aneurysm surgery and 12 days after stent implantation. No case of major bleeding in the postoperative phase was observed. Conclusions. The present pilot study suggests that, although at least 10-14 days of dual antiplatelet therapy remain mandatory, the Avantgarde( TM) stent seems to have a role in patients requiring undelayable surgery.

Aspirin prophylaxis for the prevention of thrombosis: expectations and limitations.

Rao GH, Fareed J

Thrombosis · 2012 · PMID 22448319 · Full text

Platelets play a very important role in the pathogenesis of acute vascular events leading to thrombosis of the coronary and cerebral arteries. Blockage of these arteries leading to regional ischemia of heart and brain ti... Platelets play a very important role in the pathogenesis of acute vascular events leading to thrombosis of the coronary and cerebral arteries. Blockage of these arteries leading to regional ischemia of heart and brain tissues precipitate heart attacks and stroke. Acetyl salicylic acid (Aspirin) has been the drug of choice for over half a century for the primary and secondary prophylaxis of thrombotic events. In spite of its extensive use as an antiplatelet drug for the prevention of vascular thrombosis, there is considerable concern about the degree of protection it offers, to patients under aspirin therapy. In this paper, we explain the phenomenon of aspirin resistance, discuss the limitations of aspirin therapy, and suggest methods to monitor "at-risk" individuals. Ability to monitor and determine at risk patients will provide opportunities for the clinicians to customize antiplatelet therapies.

Evaluating the Role of Compression Stockings in Preventing Post thrombotic Syndrome: A Review of the Literature.

Kanaan AO, Lepage JE, Djazayeri S … +1 more , Donovan JL

Thrombosis · 2012 · PMID 22315680 · Full text

Background. Postthrombotic syndrome (PTS) is a burdensome and costly complication of deep vein thrombosis (DVT). Up to 50% of patients with DVT will develop the disease within two years following the diagnosis of acute D... Background. Postthrombotic syndrome (PTS) is a burdensome and costly complication of deep vein thrombosis (DVT). Up to 50% of patients with DVT will develop the disease within two years following the diagnosis of acute DVT. Various risk factors for developing PTS have been identified and different modalities have been used to prevent its development. Compression stockings have been studied for the prevention of PTS in patients diagnosed with proximal DVT. Methods. MEDLINE and EMBASE databases were searched to identify relevant original articles. Results. Several trials including two metaanalyses have examined the role of compression stockings for the prevention of PTS. Although most trials showed significant reduction in the development of PTS with the use of compression stockings, limitations in study design prevent the generalizability of the data. Two studies supported an individualized tailored duration especially in patients at low risk for developing the syndrome. A randomized double-blind placebo-controlled trial involving 800 patients is currently ongoing and may confirm the results of older studies. Conclusions. Clinical trials support the use of compression stockings in patients diagnosed with proximal DVT for the prevention of PTS.

Paradoxical effect of aspirin.

Doutremepuich C, Aguejouf O, Desplat V … +1 more , Eizayaga FX

Thrombosis · 2012 · PMID 22292117 · Full text

Low-dose aspirin is an important therapeutic option in the secondary prevention of myocardial infarction (MI) and ischemic stroke, basedon its unique cost-effectiveness and widespread availability. In addition, based on... Low-dose aspirin is an important therapeutic option in the secondary prevention of myocardial infarction (MI) and ischemic stroke, basedon its unique cost-effectiveness and widespread availability. In addition, based on the results of a number of large studies, aspirin is also widely used in the primary prevention of MI. This paper provides an update of the available data to offer greater clarity regarding the risks of aspirin with respect to hemorrhagic stroke. In the secondary prevention of cardiovascular, cerebrovascular, and ischemic events, the evidence supports that the benefits of aspirin treatment significantly outweigh the risk of a major hemorrhage. When considering whether aspirin is appropriate, the absolute therapeutic cardiovascular benefits of aspirin must be balanced with the possible risks associated with its use, being hemorrhagic stroke. Regarding these clinical facts, normal, COX 1 -/-, and COX 2 -/- mice were treated with a wide range of doses of aspirin and studied by induced hemorrhagic time. The results outlined three major conclusions: high doses of aspirin induce hemorrhage, while low doses of aspirin do not. In the absence of COX 1, ultra low doses of aspirin produce an antihemorrhagic effect not observed with intermediate doses. The absence of COX 2 induced a hemorrhagic effect that needs further research, probably originated in compensatory phenomena.

Variability in the responsiveness to low-dose aspirin: pharmacological and disease-related mechanisms.

Rocca B, Petrucci G

Thrombosis · 2012 · PMID 22288010 · Full text

The main pharmacological aspects of pharmacodynamics (PD) and pharmacokinetics (PK) of aspirin as antiplatelet agent were unravelled between the late sixties and the eighties, and low-dose aspirin given once daily has be... The main pharmacological aspects of pharmacodynamics (PD) and pharmacokinetics (PK) of aspirin as antiplatelet agent were unravelled between the late sixties and the eighties, and low-dose aspirin given once daily has been shown to be a mainstay in the current treatment and prevention of cardiovascular disorders. Nevertheless, several PD and PK aspects of aspirin in selected clinical conditions have recently emerged and deserve future clinical attention. In 1994, the term "aspirin resistance" was used for the first time, but, until now, no consensus exists on definition, standardized assay, underlying mechanisms, clinical impact, and possible efficacy of alternative therapeutic interventions. At variance with an undefined aspirin-resistant status, in the last 5 years, the concept of variability in response to aspirin due to specific pathophysiological mechanisms and based on PK and/or PD of the drug has emerged. This growing evidence highlights the existence and possible clinical relevance of an interindividual variability of pharmacological aspirin response and calls for new, large studies to test new low-dose aspirin-based regimens which may ameliorate platelet acetylation, reduce variability in drug responsiveness, and improve clinical efficacy on selected populations.

Rheolytic Thrombectomy with or without Adjunctive Indwelling Pharmacolysis in Patients Presenting with Acute Pulmonary Embolism Presenting with Right Heart Strain and/or Pulseless Electrical Activity.

Hubbard J, Saad WE, Sabri SS … +4 more , Turba UC, Angle JF, Park AW, Matsumoto AH

Thrombosis · 2011 · PMID 22254138 · Full text

Purpose. To evaluate the safety and efficacy of the Possis rheolytic thrombectomy with or without indwelling catheter-directed pharmacolysis for the treatment of massive pulmonary embolus in patients presenting with righ... Purpose. To evaluate the safety and efficacy of the Possis rheolytic thrombectomy with or without indwelling catheter-directed pharmacolysis for the treatment of massive pulmonary embolus in patients presenting with right heart strain and/or a pulseless electrical activity (PEA). Materials and Methods. Retrospective review of patients undergoing pulmonary pharmacolysis was performed (07/2004-06/2009). Pre- and posttreatment Miller index scoring weres calculated and compared. Patients were evaluated for tPA doses, ICU stay, hospital stay, and survival by Kaplan-Meier analysis. Results. 11 patients with massive PE were found, with 10/11 presenting with a Miller score of >17 (range: 16-27, mean: 23.2). CTPA and/or echocardiographic evidence of right heart strain was found in 10/11 patients. 3 (27%) patients presented with a PEA event. Two (18%) patients had a contraindication to pharmacolysis and were treated with mechanical thrombectomy alone. The intraprocedural mortality was 9% (n = 1/11). Of the 10 patients who survived the initial treatment, 7 patients underwent standard mechanical thrombectomy initially, while 5 received power pulse spray mechanical thrombectomy. Eight of these 10 patients underwent adjunctive indwelling catheter-directed thrombolysis. The mean catheter-directed infusion duration was 18 hours (range of 12-26 hours). The average intraprocedural, infusion, and total doses of tPA were 7 mg, 19.7 mg, and 26.7 mg, respectively. There was a 91% (10/11) technical success rate. The failure was the single mortality. Average reduction in Miller score was 9.5 or 41% (P = 0.009), obstructive index of 6.4 or 47% (P = 0.03), and perfusion index of 2.7 or 28% (P = 0.05). Average ICU and hospital stay were 7.4 days (range 2-27 days) and 21.3 days (range 6-60 days), respectively. Intent to treat survival was 90% at 6, 12, and 18 months. Conclusion. Rheolytic thrombectomy with or without adjunctive catheter-directed thrombolysis provides a safe and effective method for treatment of acute PE in patients who present with right heart strain and/or a PEA event.
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