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Viscoelastic properties of plasma fibrin clots are similar in patients on rivaroxaban and vitamin K antagonists.
Kopytek, M, Zabczyk, M, Natorska, J, Siudut, J, Malinowski, KP, Ptaszek, P, Glajcar, A, Goralczyk, T, Undas, A
Journal of physiology and pharmacology : an official journal of the Polish Physiological Society. 2019;(1)
Abstract
Unfavorable fibrin clot features have been observed in patients with venous thromboembolism (VTE). We investigated whether rivaroxaban, a direct factor Xa inhibitor, and vitamin K antagonists (VKAs) can improve plasma clot viscoelastic properties. We studied four age- and sex-matched groups: 25 healthy controls, 15 VTE patients taking rivaroxaban 20 mg/day (blood concentration, 145 (67 - 217) ng/ml), 15 VTE patients taking VKA (INR: 2 - 3), and 15 VTE patients who stopped oral anticoagulant therapy (OAT). Using a hybrid rheometier the storage (G') and loss (G") moduli were evaluated in citrated plasma after addition of 5 pmol/l tissue factor. Fiber thickness within clots was assessed using scanning electron microscopy. Higher G' but not G" was observed for VTE patients taking rivaroxaban (+34%; post hoc, P = 0.029) compared to controls. As reflected by lower G' and G", patients taking rivaroxaban (-19% and -30%; post hoc, P = 0.0013 and P < 0.0001, respectively) formed less stiff and viscous clots compared to VTE patients after OAT withdrawal, also after adjustment for fibrinogen. VTE patients treated with rivaroxaban and VKA had similar clot viscoelastic properties (post hoc, P = 0.85 for G' and P = 0.29 for G"). G' and G" correlated with plasma rivaroxaban concentrations (r = -0.67, P = 0.005 and r = -0.59, P = 0.021, respectively), and the time from the last dose of rivaroxaban intake (r = 0.59, P = 0.02 and r = 0.58, P = 0.022, respectively). G' and G" showed no association with INR in patients on VKAs. G' or G" were not associated with fibrin diameter on scanning electron microscopy images in either group. Our preliminary study shows that both rivaroxaban and VKA improve clot viscoelastic properties in VTE patients, which might contribute to their antithrombotic effects. G' and G" may reflect specific clot physical features, beyond key plasma clot characteristics, which highlights benefits from comprehensive plasma clot analysis in patients with thrombotic diseases.
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Impact of periprocedural anticoagulation strategy on the incidence of new-onset silent cerebral events after radiofrequency catheter ablation of atrial fibrillation.
Müller, P, Halbfass, P, Szöllösi, A, Dietrich, JW, Fochler, F, Nentwich, K, Roos, M, Krug, J, Schmitt, R, Mügge, A, et al
Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing. 2016;(3):203-11
Abstract
BACKGROUND Silent cerebral events (SCEs) have been observed on diffusion-weighted cerebral magnetic resonance imaging (MRI) in a substantial number of asymptomatic patients after atrial fibrillation (AF) ablation procedures. The purpose of this study was to investigate if periprocedural oral anticoagulation (OAC) management affects the incidence of new-onset SCE after radiofrequency catheter ablation (RFCA) of AF. METHODS AND RESULTS One hundred ninety-two consecutive patients (64 ± 10.1 years, 38.5 % women) with symptomatic paroxysmal (n = 80, 41.7 %) or persistent AF undergoing RFCA of AF were prospectively enrolled. Periprocedural anticoagulation strategies were defined as uninterrupted use of novel oral anticoagulants (NOACs) (group I, n = 64), interrupted use of NOACs (group II, n = 42), continuation of vitamin K antagonist (VKA) with an international normalized ratio (INR) between 2.0 and 3.0 (group III, n = 43), and VKA discontinuation bridged with low molecular weight heparin (group IV, n = 43). Cerebral MRI was performed 1 to 2 days after RFCA for detection of new SCE. Overall, new SCEs were detected in 41 patients (21.4 %) after AF ablation. New SCEs were detected in 12.5 % in group I, 35.7 % in group II, 18.6 % in group III, and 23.3 % in group IV (p < 0.05). Multivariable logistic regression analysis revealed persistent AF and discontinuation of periprocedural OAC (group II and IV) to be independent predictors for the development of SCE. No relevant complications were identified. CONCLUSIONS Periprocedural continuation of NOAC as well as continuation of VKA seems to be safe and significantly reduce the occurrence of SCE after AF ablation.
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[Frequency of use of oral vitamin K antagonists in patients with atrial fibrillation and cognitive function disturbances].
Gorzelak, P, Zyzak, S, Krewko, Ł, Mozdzan, M, Broncel, M
Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego. 2014;(215):302-6
Abstract
UNLABELLED The incidence of atrial fibrillation (AF) and of thromboembolic complications increases along with age. This is also the case for cognitive function disturbances; therefore their occurrence in patients (pts) with AF may hamper control of anticoagulant therapy and maintenance of therapeutic INR values. The aim of the study was to evaluate the effect of cognitive function disturbances on implementation and monitoring of the treatment with oral vitamin K antagonists (VKA) in patients with AF. The relationship between the level of cognitive function disturbances and the severity of experienced AF symptoms was defined. MATERIAL AND METHODS The analysis included a group of 93 pts (41 males, 52 females, mean age: 76.8) with a diagnosis of AF and with indications for anticoagulation treatment with VKAs (CHA2DS2VASc > or = 2, HAS-BLED < 3), referred to the Clinic of Internal Diseases and Clinical Pharmacology of the Medical University of Lodz. In a group of pts (n = 46) treated chronically with VKAs, mean INR values at admission to the hospital were calculated and the number of results falling within the therapeutic range of 2-3, by the severity of cognitive disturbances, was analyzed. Cognitive abilities were assessed with the Mini Mental State Examination Scale (MMSE) (MMSE-Mini-mental state examination). The EHRA (European Heart Rhythm Association) classification was used to assess AF-related complaints. RESULTS The 93 studied subjects were divided into 3 groups: group I with normal cognitive function (MMSE = 24-27) - n = 35; group II with disturbances of cognitive function without dementia (MMSE = 24-26) - n = 35 and group III with dementia (MMSE < 24) - n = 23.66% of pts with normal MMSE result were referred to the hospital because AF-related symptoms and in the group of patients with MMSE < 24 these symptoms were the cause of hospitalization in 23% of pts. Despite the fact that all patients had indications for VKAs, this treatment was not started in 40%, 51.4% and 65% of pts in group I, II and III, respectively. At admission to the hospital, therapeutic level INR values were found only in 34.8% of AF pts. 49% of pts were treated with VKAs in total. In group II, a high percentage of patients (43%) treated with aspirin was found in spite of high thromboembolic risk and no contraindications to VKAs. About 23% of pts with a normal MMSE result and 14% of pts in group II experienced AF-related symptoms preventing them from normal functioning and performing daily activities (EHRA IV). Nobody in group III reported severe AF-related symptoms. CONCLUSIONS Along with the advancing age, there is an increase of the incidence of persistent and fixed atrial fibrillation, of the risk of thromboembolic complications and of the severity of cognitive function disturbances. Treatment with oral vitamin K antagonists was implemented much less frequently among patients with atrial fibrillation and cognitive function disturbances, as compared to the patients with normal cognitive function. The MMSE test should be routinely performed in patients with atrial fibrillation to monitor the efficacy and safety of the treatment with oral vitamin K antagonists properly. In patients with disturbances of cognitive function, significantly lower reportability of AF-related complaints was shown, as compared to individuals without these disturbances. Patients with normal MMSE result were referred to the hospital because AF-related symptoms, in the group of patients with MMSE < 23 the main reason for hospitalization was the severity of the symptoms heart failure. ECG should be a routine test performed in elderly patients with cognitive function disturbances or with dementia to detect atrial fibrillation.
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Decreased procoagulant phospholipids in patients treated by vitamin K antagonists.
Rousseau, A, Woodhams, B, Paunet-Bobo, M, Van Dreden, P, Bigot, D, Leclerc, S, Lenormand, B, Vasse, M
Thrombosis research. 2012;(3):491-4
Abstract
INTRODUCTION The stimulation of cells by thrombin is associated with the release of microparticles (MPs) from cell membranes. These MPs can express procoagulant activity. As vitamin K antagonists (VKA) decrease the generation of thrombin, we compared plasma procoagulant phospholipids (PPL) levels in patients with a previous history of venous thrombosis who were being treated with VKA and compared them with an untreated group. MATERIALS AND METHODS Plasma PPL were measured using a factor Xa-based coagulation assay. sGPV, a marker of platelet activation by thrombin, was measured by ELISA. Platelet MPs were also evaluated using standard flow cytometric techniques. Ninety-six VKA-treated patients and 80 patients not undergoing VKA therapy were tested and the results compared. RESULTS PPL activity was significantly reduced (p<0.0001) in VKA-treated patients compared with the untreated group. PPL were correlated with platelet and white blood cell count and with sGPV levels in the untreated group, but not in VKA-treated patients. PPL were correlated with fibrinogen levels in both groups, but not with C-reactive protein. Polymorphonuclear neutrophils (PMN) were significantly lower (p=0.01) in VKA-treated patients than in untreated patients. CONCLUSION The difference between PPL levels in VKA-treated patients and patients without treatment could be related to the decrease in PMN count. It remains to be established if this decrease of PPL is directly related to the capacity of activated PMN to generate MPs, or indirectly by reducing the amount of pro-inflammatory cytokines or reactive oxygen species produced by PMN.
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[Effects of normal saline for maintenance of arterial lines of surgical patients].
Han, SS, Park, JE, Kim, NE, Kang, HJ
Journal of Korean Academy of Nursing. 2012;(6):791-8
Abstract
PURPOSE The purpose of this study was to analyze the effectiveness of saline solution vs. heparinized-saline for maintenance of arterial lines and to detect changes in platelet and aPTT as physiological indexes. METHODS In this nonequivalent control group, non-synchronized, double-blind study the effects of heparinized and saline solution on the maintenance of arterial lines were compared. Fifty five patients received the heparinized solution and fifty nine patients received the saline solution. All patients who had surgery in K-university hospital between September and December 2011 were eligible for participation in the study. RESULTS There was no statistically significant difference between the saline and the heparin group in the maintenance time of the arterial lines or the number of irrigations. There was no statistically significant difference between the groups in changes in the number of platelets and aPTT for interaction between the groups and time intervals. CONCLUSION The results indicate that saline solution can be used as an irrigation solution for the maintenance of arterial lines of adult surgical patients, rather than heparinized-saline, in view of potential risk factors in the use of heparin.
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Emergency reversal of anticoagulation: the real use of prothrombin complex concentrates: a prospective multicenter two year French study from 2006 to 2008.
Desmettre, T, Dubart, AE, Capellier, G, Fanara, B, Puyraveau, M, Kepka, S, Coquart, J, Sheppard, F, Tazarourte, K
Thrombosis research. 2012;(3):e178-83
Abstract
INTRODUCTION Prothrombin complex concentrate (PCC) for reversal of vitamin K antagonist (VKA) is the main therapeutic option in cases of life-threatening bleeding. Clinical use of PCC is poorly documented. METHODS We prospectively assessed PCC use in four French emergency departments during a two year period 2006-2008 before publication of French Guidelines. An appropriate treatment was defined when PCC was recommended, with a dose of PCC above or equal to 20 UI/kg, with vitamin K and with an assessment of international normalized ratio (INR) after PCC. Time of diagnosis and PCC administration were collected, as INR values, thromboembolic events within seven days, hospital mortality. RESULTS 256 patients received PCC for reversal of OAT. PCC was mainly prescribed for major intracerebral (ICH) or gastrointestinal hemorrhage. An appropriate treatment was observed in 26% of patients. Intra-hospital mortality for major bleeding was 33% for ICH and 26% for non-ICH major bleeding. A PCC dose>20 UI/kg was able to reach an INR<1.5 in 65% of patients. For major hemorrhages (70%), time between patient arrival and treatment delivery exceeded three hours in half of cases. Control of INR was omitted in 20% of patients. No patients presented a thromboembolic event. CONCLUSION A suitable treatment was administered in 26% of patients. A PCC dose of 20-30 IU/kg seems adequate in most cases to reverse VKA activity, but both higher and lower doses achieve similar effects. Considerable progress is required to improve PCC administration and control of treatment efficacy, and to shorten time to diagnosis.
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[Clinical observation on compound danshen for thalidomide-related venous thromboembolism prophylaxis].
Yin, QS, Wei, XD, Song, YP
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi. 2011;(2):134-5
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The effect of LMWH (Nadroparin) on tumor progression.
Nagy, Z, Turcsik, V, Blaskó, G
Pathology oncology research : POR. 2009;(4):689-92
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Abstract
Recent clinical studies on patients with malignancies, who were treated with UHF and LMWHs raised the possibility, that these agents may possess an inhibitory effect on tumor progression. Further studies supported that this effect is independent from the anticoagulant and antithrombotic action. In this retrospective study oncological patients with an increased risk for thromboembolism were choosen, who received prophylactic treatment with an LMWH (nadroparin) at least for 6 months. Comparing with the control group, in some subgroups (T3 and T4, as well as M1) the LMWH-treated patients showed a significantly increased survival.
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Increased efficiency of hemodialysis with citrate dialysate: a prospective controlled study.
Kossmann, RJ, Gonzales, A, Callan, R, Ahmad, S
Clinical journal of the American Society of Nephrology : CJASN. 2009;(9):1459-64
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Abstract
BACKGROUND AND OBJECTIVES A bicarbonate dialysate acidified with citrate (CD) has been reported to have local anticoagulant effect. This study examines the effect of CD on dialysis efficiency, measured as eKt/Vurea, and predialysis concentrations of BUN, creatinine, phosphate, and beta-2 microglobulin in chronic dialysis units. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS Three outpatient chronic hemodialysis units with 142 patients were switched to CD for 6 mo. Using each patient's prior 6 mo on regular bicarbonate dialysate acidified by acetate (AD) as control, eKt/Vurea was compared with that of CD. Follow-up data for 7 mo after the study were collected from about one-half of the participants remaining on CD and the others returned to AD. RESULTS eKt/Vurea, increased (P < 0.0001) from pre-CD value of 1.51 +/- 0.01 to 1.57 +/- 0.01 with CD. During CD use beta-2 microglobulin levels declined (P = 0.0001) from 28.1 +/- 10.0 to 25.9 +/- 10.0. Similarly, the concentrations of BUN, creatinine, and phosphate also decreased on CD (P < 0.008). In the poststudy period, eKt/Vurea for the patients staying on CD remained unchanged at 1.60 +/- 0.17 versus 1.59 +/- 0.18 (P = NS), whereas in those returning to AD the eKt/Vurea decreased from 1.55 +/- 0.20 to 1.52 +/- 0.17 (P < 0.0001). CONCLUSIONS Data suggest that CD use is associated with increased solute removal.
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A protocol for the rapid normalization of INR in trauma patients with intracranial hemorrhage on prescribed warfarin therapy.
Kalina, M, Tinkoff, G, Gbadebo, A, Veneri, P, Fulda, G
The American surgeon. 2008;(9):858-61
Abstract
Trauma patients on prescribed warfarin therapy sustaining intracranial hemorrhage can be difficult to manage. Rapid normalization of coagulopathy is imperative to operative intervention and may affect outcomes. To identify and expedite warfarin reversal, we designed a protocol to administer a prothrombin complex concentrate. A Proplex T protocol was instituted in May 2004. It dictated that trauma patients with an International Normalized Ratio (INR) greater than 1.5, history of prescribed warfarin therapy, and intracranial hemorrhage on CT scan receive a prothrombin complex concentrate for reversal of their coagulopathy. Neither the protocol nor the factor concentrate was validated for use in this subset of trauma patients; therefore, adherence to the protocol and use of the factor concentrate was not mandatory. Patients not administered the prothrombin complex concentrate received vitamin K and fresh-frozen plasma. The protocol resulted in an increased number of patients receiving Proplex T (54.3% vs 35.4%, P = 0.047). Protocol patients had improved times to normalization of INR (331.3 vs 737.8 minutes, P = 0.048), number of patients with reversal of coagulopathy (73.2% vs 50.9%, P = 0.026), and time to operative intervention (222.6 vs 351.3 minutes, P = 0.045) compared with control subjects. There were no differences in intensive care unit (ICU) days, hospital days, or mortality. The Proplex T protocol increased the number of patients who received prothrombin complex concentrate, provided rapid normalization of INR, and improved time to operative intervention.