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1.
MT in anticoagulated patients: Direct oral anticoagulants versus vitamin K antagonists.
L'Allinec, V, Sibon, I, Mazighi, M, Labreuche, J, Kyheng, M, Boissier, E, Roy, M, Gory, B, Dargazanli, C, Desal, H, et al
Neurology. 2020;(8):e842-e850
Abstract
Mechanical thrombectomy (MT) is one of the main treatments for acute ischemic stroke (AIS) in patients on effective anticoagulation. The use of direct oral anticoagulants (DOA) has increased, given their efficacy and safety profile compared to vitamin K antagonists (VKA). We compared procedural and clinical outcomes of MT in patients on DOA and VKA treatment before stroke onset. We analyzed 2 groups from the Endovascular Treatment in Ischemic Stroke prospective registry: patients on DOA and patients on VKA treated by MT without thrombolysis. Generalized linear mixed models including center as random effect were used to compare angiographic (rates of reperfusion at end of procedure, number of passes >2, procedural complications) and clinical (favorable and excellent outcome, 90-day all-cause mortality, and hemorrhagic complications) outcomes according to anticoagulation subgroups. Comparisons were adjusted for prespecified confounders (age, admission NIH Stroke Scale score) as well as for meaningful baseline between-group differences. Among 221 patients included, more DOA-treated patients (n = 115, 52%) achieved successful (modified Thrombolysis in Cerebral Infarction score [mTICI] 2b/3) or near complete (mTICI 2c/3) reperfusion at the procedure end than did VKA-treated patients, with an adjusted odds ratio (OR) for DOA vs VKA of 3.27 (95% confidence interval [CI], 1.40-7.65) and 2.00 (95% CI, 1.08-3.73), respectively. DOA-treated patients had a lower 90-day mortality risk with an adjusted OR of 0.47 (95% CI, 0.24-0.89) and a better excellent outcome OR of 2.40 (1.10-5.27). There was no significant between-group difference in hemorrhagic or procedural complications. The study highlights the benefits of DOA compared to VKA. Regarding mortality, excellent outcomes, and recanalization rate, DOA appears to provide a favorable setting for MT treatment in AIS.
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2.
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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3.
Decreased levels of procoagulant phospholipids in bleeding patients treated by vitamin K antagonists.
Mathieu, E, Van Dreden, P, Aulagnier, J, Grusse, M, Dreyfus, JF, François, D, Vasse, M
Thrombosis research. 2016;:36-40
Abstract
International Normalized Ratio (INR) is currently used to monitor vitamin K antagonist therapy, and the bleeding incidence becomes exponential for INR>4.5. Inversely, more than 50% of patients with a supratherapeutic INR are asymptomatic. Therefore it could be of interest to identify patients with a higher bleeding risk. Microparticles derived from different cell types express procoagulant phospholipids (PPL) which can be evaluated by a chronometric coagulation assay where a shortening of the clotting times is associated with increased levels of PPL. In a series of 174 consecutive patients referred to our Emergency Department with an INR>5, median level of PPL was significantly (p=0.004) lower (38.2s) in the 119 asymptomatic patients than in patients with nonmajor (43.6s, n=35) or major bleeding (46.6s, n=19), indicating higher levels of procoagulant phospholipids in asymptomatic patients. By receiver operating characteristic curve analysis, a cut-off of 43.5s discriminated patients with higher haemorrhagic risk (area under the curve=0.648). In contrast, thrombomodulin levels, quantified either by immunological or functional assays were not significantly different between both groups. In conclusion, evaluation of PPL could be of interest to define the haemorrhagic risk of VKA- treated patients.
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4.
[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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5.
The coagulopathy of liver disease: does vitamin K help?
Saja, MF, Abdo, AA, Sanai, FM, Shaikh, SA, Gader, AG
Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis. 2013;(1):10-7
Abstract
Vitamin K is frequently administered in cirrhotic patients to correct their coagulopathy, but evidence for such practice is lacking. We aimed to assess whether vitamin K administration increases the levels of the vitamin K-dependent factor VII (FVII), protein C, and protein S in patients with different stages of liver dysfunction. Eighty-nine patients were recruited into four groups: group 1 [hepatitis B virus (HBV) inactive carriers, n = 23]; group 2 [chronic HBV and hepatitis C virus (HCV) hepatitis, n = 21]; group 3 (cirrhosis, n = 24); group 4 (hepatocellular carcinoma, n = 21); and a healthy control group (n = 39). A single dose of 10 mg of vitamin K1 was administered subcutaneously to all patients. Prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen, FVII, protein C, total and free protein S, and proteins induced by vitamin K absence (PIVKA)-II (des-gamma-carboxy prothrombin) were measured at baseline and 72 h after vitamin K administration. There was progressive increment in baseline PIVKA-II, and decrements in fibrinogen, FVII, protein C, and protein S across study groups (P < 0.0001). Compared to baseline, vitamin K administration did not affect the measured parameters, whereas TT showed no reduction in any of the groups. Protein C levels declined in group 2, whereas FVII, total and free protein S did not increase in any group, for all parameters. Vitamin K therapy does not cause significant improvements in the majority of coagulation parameters and hence does not seem to be routinely indicated in patients with liver disease.
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6.
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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7.
Undercarboxylated osteocalcin concentration in postmenopausal women receiving hormone therapy daily and on alternate days.
Yasui, T, Uemura, H, Umino, Y, Yamada, M, Kuwahara, A, Matsuzaki, T, Maegawa, M, Furumoto, H, Miura, M, Irahara, M
Menopause (New York, N.Y.). 2006;(2):314-22
Abstract
OBJECTIVE Undercarboxylated osteocalcin (ucOC) is a sensitive marker of vitamin K status. The authors examined the difference in serum ucOC concentrations in postmenopausal women receiving hormone therapy (HT) daily and on alternate days, and assessed the association between ucOC and triglyceride concentrations, which are related to the transport of vitamin K. DESIGN Seventy-three postmenopausal women were recruited for this study. Thirty-seven women received 0.625 mg of conjugated equine estrogens (CEE) and 2.5 mg of medroxyprogesterone acetate (MPA) daily, and 36 women received 0.625 mg of CEE and 2.5 mg of MPA on alternate days. The concentrations of serum ucOC, bone turnover markers, lipid profiles, and hormones were measured before and after 12 months of HT. RESULTS The ucOC concentration in women taking HT daily was significantly (P < 0.01) lower than that in women taking HT on alternate days. Serum ucOC concentrations during HT showed a significant (P < 0.01) inverse correlation with estradiol concentrations during HT. Serum estradiol concentrations during HT showed a significant (P < 0.01) positive correlation with triglyceride concentrations during HT. Furthermore, ucOC concentrations during HT showed a significant (P < 0.05) inverse correlation with triglyceride concentrations in women receiving HT. CONCLUSIONS The effect of HT on alternate days on ucOC concentration was weaker than the effect of HT daily. In addition, ucOC concentration after 12 months of HT daily might be decreased due to the conversion of ucOC to carboxylated OC by the effect of vitamin K through increased triglyceride levels induced by oral CEE.
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8.
Abrupt versus gradual withdrawal of vitamin K antagonist treatment in patients with venous thromboembolic disease: assessment of hypercoagulability and clinical outcome.
de Groot, MR, Njo, TL, van Marwijk Kooy, M, Büller, HR
Clinical laboratory. 2000;(11-12):575-81
Abstract
BACKGROUND It is yet unclear whether vitamin K antagonist treatment should be stopped abruptly or gradually after an episode of venous thromboembolism. The mode of withdrawal might influence a potential development of a hypercoagulable state, which could influence the risk for recurrent disease. METHODS We prospectively studied 37 consecutive patients in whom acenocoumarol was discontinued either abrupt (18) or gradually (19) (2/3 and 1/3 of the initial dose for one week). Blood sampling was performed at various time points up to 18 days after complete withdrawal and was analysed for INR, prothrombin fragment F1 + 2 and D-dimer. All patients were clinically followed-up for the assessment of the association between hypercoagulability and occurrence of disease such as recurrent venous thromboembolism or malignancy. RESULTS An approximately fourfold increase was observed (median increase from 0.3 to 1.3 nmol/l) in the F1 + 2 levels after both abrupt and gradual withdrawal and in the D-dimer concentrations in the abrupt withdrawal group (0.10 to 0.44 mg/l), while those in whom acenocoumarol was discontinued gradually showed a less pronounced increase of the D-dimer levels (0.11 to 0.29 mg/L) (not significant). During follow-up one recurrent venous thromboembolic event occurred in each group, and a diagnosis of cancer was made four times. All these patients had the highest D-dimer concentrations measured in the entire study group. CONCLUSIONS This study indicates the potential for a hypercoagulable state after acenocoumarol discontinuation, which was not prevented by tapering the acenocoumarol dose. D-dimer, measured 2 to 3 weeks after acenocoumarol withdrawal, might be an important tool to identify patients at risk for recurrent venous thromboembolism and/or for the presence of an underlying malignancy.