What Causes Inr Readings to Be High in Afib Patients

Introduction

Because of the increasing age of the full general population and significant improvements in imaging techniques, the number of patients with unruptured and often incidental intracranial aneurysms is increasing.¹ Management of these patients is controversial and 1 of the major challenges facing neurosurgeons today because the instance fatality charge per unit of aneurysmal subarachnoid hemorrhage (aSAH) remains high.^1–iv Although prevention of rupture with surgical or endovascular handling is considered to be the most effective approach, handling-related risks and complications remain a significant trouble.¹ To make a calculated assessment most the lifetime gamble of rupture compared with the chance of handling, information technology is of paramount importance to understand the natural history of unruptured intracranial aneurysms and its related take a chance factors. Although several aneurysm and patient-related risk factors for aSAH have been identified, such as hypertension and smoking, the natural history of unruptured intracranial aneurysms has yet to exist clearly defined.^v–8

Equally the use of anticoagulation therapy for atrial fibrillation, mechanical centre valves, and other indications is apace increasing with an aging population, neurosurgeons should be enlightened of the concomitant risks of this treatment. Recent population-based studies accept reported contradictory findings virtually the association between anticoagulant therapy and SAH risk.^9–12 Even so, these reports did non include or specify the number of aSAH and were express because of a depression number of patients on anticoagulant therapy,¹² lack of inclusion of important misreckoning factors, such as smoking and alcohol use,^ix the use of standardized diagnosis codes with possible misclassification and lower diagnostic validity equally a result, and the use of command groups consisting of the general population without intracranial aneurysms. Moreover, only 1 written report included international normalized ratio (INR) values, albeit limited to patients on anticoagulation therapy.^x Given the widespread apply of anticoagulant therapy and the potential fatal consequences of aSAH, nosotros conducted a large instance-command study investigating the magnitude and direction of the clan between anticoagulation apply, INR values, and the hazard of aSAH.

Methods

The data that back up the findings of this study are available from the corresponding writer on reasonable request. The medical records of 4696 patients who were diagnosed with an intracranial aneurysm betwixt 1990 and 2016 at the Brigham and Women's Hospital and Massachusetts Full general Hospital and who were either on no anticoagulant therapy or on warfarin at the fourth dimension of diagnosis were reviewed. This study has been canonical by our institutional review board and considered minimal run a risk. Patient consent was, therefore, waived by the board. Patients were identified prospectively on clinical presentation (2007–2016) and retrospectively using natural linguistic communication processing in conjunction with the Partners Healthcare Inquiry Patients Data Registry, which includes 4.2 one thousand thousand patients who have received care from Brigham and Women'southward Hospital and Massachusetts General Hospital (1990–2013).^thirteen International Classification of Diseases Ninth Revision (ICD-9) and Current Procedural Terminology (CPT) codes were used to obtain an initial prepare of potential aneurysm patients from the Research Patients Data Registry, and natural language processing was then used together with codified features to train a classification algorithm which classified 5589 patients as having aneurysm with a positive predictive value of 0.91. Of the 5589 patients, 727 were likewise seen on clinical presentation from 2007 to 2013 with prospectively collected data. Four hundred and seventy-four additional patients who were seen on clinical presentation from 2013 to 2016 were included with prospectively collected data. The medical records and imaging studies of the 6063 patients were reviewed in detail (Drs Can and Du) to identify 4696 patients with definite saccular aneurysms and who were on no anticoagulant therapy or on warfarin. Patients on depression–molecular weight heparin were excluded. Of the 4696 patients, 1198 were obtained prospectively. The results of the imaging studies, including intracranial aneurysm site and size, were recorded. Patients with possible infundibula or nondefinitive diagnoses of aneurysms, feeding artery aneurysms associated with arteriovenous malformations, fusiform, or dissecting aneurysms, and those lacking clinical notes or radiographic images were excluded from the present report. In addition, patients who received handling of their aneurysm(due south) earlier presentation were too excluded from the present study. Patients who presented with an aSAH were categorized as harboring a ruptured aneurysm.

Patient demographics (historic period, sex, and race), comorbidities (hypertension, coronary artery disease, myocardial infarction, and atrial fibrillation), number and maximum size of intracranial aneurysms, family history of aneurysms or family history of SAH, and electric current tobacco and alcohol use were obtained. The diagnosis of aSAH was confirmed with a computed tomographic scan, cerebrospinal fluid assay, or intraoperatively by a neurosurgeon. In addition, nosotros collected detailed information about anticoagulant use, type of anticoagulant, indication, and INR values at the time of diagnosis of the intracranial aneurysms. A adventure factor was causeless to exist absent if nosotros found no documentation of its presence. INR values were obtained at the time of diagnosis for ruptured aneurysms and within a twelvemonth of diagnosis for unruptured aneurysms. For patients whose initial INR at the time of diagnosis were obtained while heparinized and falsely elevated, the next available INR later on the fractional thromboplastin time had normalized was used. Patients were classified as anticoagulant users if they were on anticoagulants at the time of diagnosis. Four patients had been on anticoagulants earlier diagnosis and had discontinued their anticoagulation at least 2 months before diagnosis. These patients were classified as nonanticoagulant users. We obtained clinical notes with anticoagulation details past using the following search terms: anticoagulate, anticoagulated, anticoagulation, anticoagulation, anticoagulant, anticoagulant, anticoagulants, antithrombotic, antithrombotic, coumadin, coumarin, warfarin, heparin, molecular, vitamin K antagonist, unfractioned, argatroban, acova, dalteparin, fragmin, bivalirudin, angiomax, angiox, lepirudin, refludan, fondaparinux, arixtra, idraparinux, acenocoumarol, lovenox, enoxaparin, aggrastat, tirofiban, integrilin, and eptifibatide. These clinical notes were subsequently manually reviewed. Patients who were on low–molecular-weight heparin were excluded as that does non affect the INR values.

Differences in baseline characteristics betwixt patients with anticoagulant therapy and without anticoagulant therapy were evaluated using Student t tests for continuous variables and Pearson χⁱⁱ examination for categorical variables. Univariable and multivariable logistic regression models were implemented to test for effects because of anticoagulant apply and INR values, with a backward emptying procedure to place pregnant confounders. Cutoff P values of 0.1 were used to select the initial prepare of variables to exist included in the initial multivariable model for backward elimination, with the exception of current anticoagulant use because this was one of the variables of involvement. Adjusted odds ratios (OR) with 95% CIs were calculated, and P<0.05 was considered significant. Interaction terms between INR and anticoagulant utilize were included. Marginal effects of anticoagulant use on rupture adventure stratified past INR values were calculated. To command for differences in baseline characteristics, inverse probability weighting using propensity scores was applied. Covariate balance was tested after inverse probability weighting using a χ² test. Missing values were accounted for past using multiple imputation with chained equations, and inferential statistics were obtained from 40 imputed datasets. Sensitivity analyses using subgroups consisting of complete cases (ie, without missing data) just, anticoagulation users only, and nonanticoagulation users only were also performed. All statistical analyses were performed using the Stata statistical software packet (version 14, StataCorp Higher Station, TX).

Results

Summary statistics of patient demographics and characteristics stratified by anticoagulant use are shown in Table 1. A full of 4696 patients with 6403 aneurysms were included, of which 1300 (27.seven%) patients presented with a ruptured aneurysm. In general, patients on anticoagulant therapy were significantly older, less often electric current smokers, and more frequently diagnosed with hypertension, coronary avenue disease, myocardial infarction, and atrial fibrillation. In addition, INR values were significantly higher in anticoagulated patients.

Table 1. Patient Characteristics Stratified by Anticoagulant Employ

Variables	All North=4696	Missing	Anticoagulant Group Due north=131*	Nonanticoagulant Group N=4565	P Value
Ruptured aneurysm (%)	1300 (27.7)	0	27 (20.6)	1273 (27.9)	0.07
Female (%)	3662 (78.0)	0	96 (73.3)	3566 (78.i)	0.19
White race (%)	3734 (79.5)	0	108 (82.four)	3628 (79.4)	0.40
Black race (%)	290 (six.2)	0	vi (four.6)	284 (six.2)	0.45
Hispanic race (%)	270 (5.vii)	0	5 (3.8)	265 (5.8)	0.33
Asian race (%)	107 (2.3)	0	1 (0.8)	106 (2.iii)	0.25
Other/unknown race (%)	295 (half-dozen.3)	0	11 (8.4)	284 (6.ii)	0.31
Age at diagnosis (SD)	55.6 (thirteen.vii)	0	65.8 (12.5)	55.3 (13.6)	<0.01
Hypertension (%)	2150 (45.8)	0	74 (56.5)	2076 (45.5)	0.01
Coronary artery disease (%)	252 (five.4)	0	18 (thirteen.7)	234 (5.one)	<0.01
Myocardial infarction (%)	193 (iv.1)	0	13 (nine.9)	180 (3.9)	<0.01
Atrial fibrillation (%)	140 (3.0)	0	47 (35.9)	93 (two.0)	<0.01
Size of largest aneurysm (SD)	6.9 (four.8)	92	half-dozen.iii (4.0)	6.9 (4.8)	0.17
Number of aneurysms (SD)	1.iv (0.eight)	0	1.3 (0.7)	1.4 (0.8)	0.52
Family history aneurysms (%)	788 (sixteen.8)	0	18 (13.7)	770 (16.ix)	0.35
Family unit history SAH (%)	456 (nine.7)	0	8 (6.ane)	448 (9.eight)	0.16
Current tobacco use (%)	1396 (30.4)	105	22 (17.1)	1374 (thirty.8)	<0.01
Current alcohol utilize (%)	2030 (46.seven)	347	53 (42.4)	1977 (46.8)	0.33
International normalized ratio at fourth dimension of diagnosis (SD)	1.09 (0.27)	1230	2.05 (0.9)	i.05 (0.1)	<0.01

Covariance residue was optimized with inverse probability weighting using propensity scores. The results of the unweighted and weighted multivariable analyses are shown in Table ii. V out of 10 variables had a standardized mean difference of 10% or higher, indicating possible misreckoning before inverse probability weighting. This number decreased to 2 later on weighting (Table 3). In the weighted multivariable analysis, current alcohol utilize (OR, one.89; 95% CI, 1.ten–3.24) and college INR values at the fourth dimension of diagnosis among nonanticoagulant users (OR, 28.sixteen; 95% CI, 12.44–63.77) were significantly associated with aSAH. The interaction term between anticoagulant use and INR indicates the additional furnishings of INR in patients who were anticoagulated compared with those who were not. The OR of the interaction term was <1 (equivalent to a negative coefficient) and indicates a decreased take a chance of rupture in anticoagulated patients for a given INR. To examine the effects of this interaction for specific INRs, the marginal effect was calculated. Nosotros found that in anticoagulant users, the marginal effects of anticoagulant therapy on rupture risk were negative and meaning for INR one.ii and higher (Effigy i). Although the size of some coefficients changed slightly, the direction and significance of most coefficients remained the aforementioned in the sensitivity assay using complete cases merely, with the exception of tobacco use which became significant and alcohol utilize which lost significance (Tabular array I in the online-only Data Supplement). In the subgroup analysis of patients not on anticoagulation, INR values were too associated with a higher take chances of rupture at presentation (Table II in the online-but Data Supplement). The cause for elevated INR in nonanticoagulated patients included liver disease, bleeding disorder, and vitamin K deficiency (Tabular array III in the online-only Data Supplement). In the subgroup analysis of anticoagulated patients, there was a like trend for INR although it did not reach statistical significance (Table Ii in the online-only Data Supplement). Effigy ii shows the proportion of ruptured aneurysms stratified co-ordinate to INR values among anticoagulant users and nonusers. The ORs and significance levels for INR in the weighted models were similar to the unweighted models (Table 2; Table I in the online-only Data Supplement).

Table 2. Unweighted and Weighted Multivariable Logistic Regression for Rupture Status in All Patients (N=4696)

Characteristics	Univariable Unweighted		Multivariable Unweighted		Multivariable Weighted
	OR (95% CI)	P Value	OR (95% CI)	P Value	OR (95% CI)	P Value
Female	0.64 (0.55–0.74)	<0.01	0.72 (0.62–0.84)	<0.01	0.75 (0.46–1.24)	0.27
Black race (vs white race)	1.92 (1.l–2.45)	<0.01	one.97 (1.52–ii.56)	<0.01	1.64 (0.65–four.15)	0.29
Hispanic race (vs white race)	0.32 (1.01–one.72)	0.04	1.36 (ane.03–1.lxxx)	0.03	0.71 (0.34–1.48)	0.36
Asian race (vs white race)	1.86 (1.25–2.76)	<0.01	ane.99 (1.31–iii.01)	<0.01	ane.52 (0.75–iii.08)	0.25
Other/unknown race (vs white race)	0.32 (1.02–1.71)	0.03	1.45 (1.11–1.89)	<0.01	2.53 (0.81–7.86)	0.xi
Age at diagnosis	0.98 (0.97–0.98)	<0.01	0.99 (0.98–0.99)	<0.01	0.99 (0.98–1.01)	0.43
Hypertension	1.11 (0.98–i.26)	0.10	…	…	…	…
Coronary avenue illness	0.70 (0.51–0.95)	0.02	0.75 (0.55–1.04)	0.09	1.xx (0.63–2.29)	0.57
Myocardial infarction	0.86 (0.62–1.twenty)	0.37	…	…	…	…
Atrial fibrillation	0.97 (0.67–1.42)	0.89	…	…	…	…
Size of largest aneurysm	1.01 (0.99–1.02)	0.38	…	…	…	…
Number of aneurysms	1.02 (0.94–1.11)	0.lx	…	…	…	…
Family history aneurysms	0.60 (0.fifty–0.73)	<0.01	0.56 (0.46–0.68)	<0.01	0.74 (0.35–1.57)	0.43
Family history subarachnoid hemorrhage	0.60 (0.47–0.76)	<0.01	…	…	…	…
Current tobacco utilise (vs not current)	2.01 (1.75–2.30)	<0.01	i.95 (ane.69–two.25)	<0.01	ane.65 (0.99–2.75)	0.05
Current alcohol use (vs not current)	1.36 (1.xix–1.56)	<0.01	1.34 (1.16–1.54)	<0.01	1.89 (i.10–3.24)	0.02
Electric current anticoagulant therapy (vs not current)*	0.67 (0.44–ane.03)	0.07	8.23 (two.05–33.07)	<0.01	xix.59 (3.11–123.20)	<0.01
INR at time of diagnosis†	1.sixty (1.24–2.07)	<0.01	22.78 (ten.85–47.81)	<0.01	28.16 (12.44–63.77)	<0.01
Interaction term between anticoagulant use and INR	0.92 (0.76–1.ten)	0.36	0.07 (0.03–0.17)	<0.01	0.04 (0.01–0.11)	<0.01

Tabular array 3. Standardized Hateful Deviation of Covariables Before and After Weighting

Covariables	Unweighted	Weighted
Female	−0.11	0.05
Black race (vs white race)	−0.07	0.02
Hispanic race (vs white race)	−0.09	−0.006
Asian race (vs white race)	−0.13	−0.11
Other/unknown race (vs white race)	0.08	0.07
Historic period at diagnosis	0.81	0.03
Coronary avenue illness	0.thirty	−0.03
Family history aneurysms	−0.09	−0.07
Current tobacco use (vs not electric current)	−0.32	−0.09
Current alcohol apply (vs not current)	−0.08	−0.18

• Download effigy
• Download PowerPoint

Figure i. The marginal furnishings of anticoagulant employ on rupture run a risk stratified by international normalized ratio levels. *Significant. Error confined represent 95% CI.

• Download figure
• Download PowerPoint

Figure 2. Proportion of ruptured aneurysms stratified by international normalized ratio-values amid (A) anticoagulant users and (B) nonanticoagulant users.

Give-and-take

We evaluated whether anticoagulation therapy and elevated INR values in patients with intracranial aneurysms were associated with rupture. Our primary finding is that elevated INR is significantly associated with ruptured aneurysms, even when adjusted for a wide variety of confounders. Interestingly, the effects of INR seem to be ameliorated by anticoagulant use at INR levels of ane.2 and college.

Whether the use of anticoagulants influences the risk of SAH has been the focus of a limited number of population-based studies with inconsistent results.^{9–12,xiv,15} In a registry-based Danish study using prescription data, a pregnant association between anticoagulation therapy and SAH could non exist establish.¹² However, simply ix patients with SAH were current users of vitamin M antagonists, important confounders such as smoking and alcohol employ were lacking, and inclusion of patients based on diagnosis codes could accept led to misclassification of SAH cases. In contrast, in a subsequent Dutch population-based study, vitamin K antagonists were significantly associated with SAH (OR, ii.46; 95% CI, one.04–five.82).¹¹ The most recent population-based study on this topic showed no association between anticoagulant use and SAH (<one month: OR, ane.85; 95% CI, 0.97–3.51 and >3 years: OR, i.24, 95% CI, 0.86–1.77).⁹ All the same, in all 3 studies, INR values were non available, preventing the authors from drawing firm conclusions on coagulation condition and the gamble of aSAH because noncompliance in anticoagulant users could bias the results. García-Rodríguez et al¹⁰ recently demonstrated that warfarin use was associated with an increased run a risk of SAH compared with no therapy (OR, 1.67; 95% CI, 1.15–ii.43), with a nonsignificant association with INR values of >3 (OR, two.64; 95% CI, 0.95–7.35). Even so, INR values of just 24 SAH patients on anticoagulation therapy were included. In contrast, nosotros included the INR values of both anticoagulant users and nonusers because high INR values could besides exist caused by liver illness, bleeding disorders, and dietary vitamin K deficiency. Moreover, their control group consisted of subjects with an unknown incidence of unruptured aneurysms, in contrast to our study. 1 of the major limitations of all previously mentioned population-based registries are misclassification bias and information bias, both on the level of event and exposure, considering of the use of diagnosis codes and subsequent decreased accurateness in diagnosis.¹¹

Previous studies reported an increased risk of intracerebral hemorrhage in anticoagulant users.¹⁶ In improver, intracerebral hemorrhage associated with oral anticoagulant employ was highly associated with bloodshed risk because of early hematoma growth.^17,eighteen In contrast, we recently showed in a nationwide study that anticoagulant use was not associated with differential mortality or complication rates later aSAH.¹⁹ Our current results betoken that anticoagulants, past decreasing the furnishings of increased INR values, may be protective confronting intracranial aneurysm rupture at a given INR value. This protective upshot could exist because of boosted pharmacodynamic characteristics of oral anticoagulants beyond the inhibition of vitamin G–dependent coagulation factors, such as possible immunomodulatory backdrop.^twenty Indeed, it has been shown that anticoagulation with warfarin downregulates inflammation by inhibition of IL-6 (interleukin-6) production and TNF (tumor necrosis gene)-induced I-κβ phosphorylation and consequent inflammatory bespeak transduction.^21,22 Because vascular inflammation, specifically TNF-mediated inflammation, is idea to play a central role in intracranial aneurysm pathogenesis,^23,24 the anti-inflammatory furnishings of warfarin may provide the caption for its ameliorating effects on INR tiptop and subsequent aneurysm rupture, every bit shown in our study. However, it is too possible that the patients with elevated INR merely who were non anticoagulated may have involvement of other parts of the coagulation pathway beyond what is detectable by INR and be more susceptible to aneurysm rupture equally a result.²⁵

The main strengths of our report are the big sample size, the presence of a large control group with unruptured intracranial aneurysms, and the use of a high-quality, homogeneous database, including INR values for anticoagulant users and nonusers. The main limitation of our report includes the retrospective design for a portion of the patients. It is possible that the decreased association between the furnishings of INR in anticoagulated patients and aneurysm rupture is noncausal but because of the increased use of intracranial imaging in anticoagulated patients leading to the increased discovery of unruptured aneurysms. However, propensity score weighting was used to control for selection bias. The subgroup assay of anticoagulated patients showed a trend in the association of elevated INR with aneurysm rupture. The lack of statistical significance may be considering of bereft ability because of the small sample size of that subgroup.

With an increasing number of unruptured intracranial aneurysms beingness diagnosed every twelvemonth, specifically in an older population with poly-pharmacy and comorbidities, such as atrial fibrillation and valvular diseases, the present study addresses a clinically relevant question for the clinician. In deciding on the optimal management of unruptured intracranial aneurysms in patients with elevated INR values, the treating physician must understand the effect of anticoagulation therapy and elevated INR values on the natural history of unruptured intracranial aneurysms. Our results advocate caution with anticoagulant prescriptions in this vulnerable but growing patient population.

Summary

In conclusion, we found that elevated INR values are significantly associated with an increased adventure of aSAH in patients with unruptured intracranial aneurysms and that the effects may exist moderated past anticoagulation therapy. Time to come randomized control trials are needed to confirm these findings.

Sources of Funding

This study was supported by Partners Personalized Medicine (Dr Du), the National Institutes of Health (U54 HG007963: Drs Cai and White potato, U01 HG008685: Dr Murphy, and R01 HG009174: Dr Spud), and Patient-Centered Outcomes Research Institute (282364.5077585.0007, Dr Murphy).

Footnotes

References

• i. van Gijn J, Rinkel GJ. Subarachnoid haemorrhage: diagnosis, causes and management. Brain . 2001; 124(pt 2):249–278.CrossrefMedlineGoogle Scholar
• 2. Hop JW, Rinkel GJ, Algra A, van Gijn J. Changes in functional outcome and quality of life in patients and caregivers after aneurysmal subarachnoid hemorrhage. J Neurosurg . 2001; 95:957–963. doi: 10.3171/jns.2001.95.half-dozen.0957CrossrefMedlineGoogle Scholar
• 3. Hijdra A, Braakman R, van Gijn J, Vermeulen Grand, van Crevel H. Aneurysmal subarachnoid hemorrhage. Complications and issue in a infirmary population. Stroke . 1987; eighteen:1061–1067.LinkGoogle Scholar
• 4. Hijdra A, van Gijn J, Nagelkerke NJ, Vermeulen M, van Crevel H. Prediction of delayed cerebral ischemia, rebleeding, and outcome after aneurysmal subarachnoid hemorrhage. Stroke . 1988; nineteen:1250–1256.CrossrefMedlineGoogle Scholar
• 5. Taylor CL, Yuan Z, Selman WR, Ratcheson RA, Rimm AA. Cerebral arterial aneurysm formation and rupture in xx,767 elderly patients: hypertension and other hazard factors. J Neurosurg . 1995; 83:812–819. doi: 10.3171/jns.1995.83.5.0812CrossrefMedlineGoogle Scholar
• 6. Weir BK, Kongable GL, Kassell NF, Schultz JR, Truskowski LL, Sigrest A. Cigarette smoking as a cause of aneurysmal subarachnoid hemorrhage and take chances for vasospasm: a report of the Cooperative Aneurysm Study. J Neurosurg . 1998; 89:405–411. doi: 10.3171/jns.1998.89.3.0405CrossrefMedlineGoogle Scholar
• 7. Tin can A, Castro VM, Ozdemir YH, Dagen South, Yu S, Dligach D, et al. . Clan of intracranial aneurysm rupture with smoking elapsing, intensity, and cessation. Neurology . 2017; 89:1408–1415. doi: x.1212/WNL.0000000000004419CrossrefMedlineGoogle Scholar
• 8. Can A, Castro VM, Ozdemir YH, Dagen South, Dligach D, Finan S, et al. . Alcohol consumption and aneurysmal subarachnoid hemorrhage. Transl Stroke Res . 2018; nine:xiii–19. doi: 10.1007/s12975-017-0557-zCrossrefMedlineGoogle Scholar
• 9. Pottegård A, García Rodríguez LA, Poulsen FR, Hallas J, Gaist D. Antithrombotic drugs and subarachnoid haemorrhage run a risk. A nationwide case-control study in Denmark. Thromb Haemost . 2015; 114:1064–1075. doi: ten.1160/TH15-04-0316CrossrefMedlineGoogle Scholar
• 10. García-Rodríguez LA, Gaist D, Morton J, Cookson C, González-Pérez A. Antithrombotic drugs and take a chance of hemorrhagic stroke in the general population. Neurology . 2013; 81:566–574. doi: 10.1212/WNL.0b013e31829e6ffaCrossrefMedlineGoogle Scholar
• xi. Risselada R, Straatman H, van Kooten F, Dippel DW, van der Lugt A, Niessen WJ, et al. . Platelet aggregation inhibitors, vitamin K antagonists and risk of subarachnoid hemorrhage. J Thromb Haemost . 2011; 9:517–523. doi: 10.1111/j.1538-7836.2010.04170.xCrossrefMedlineGoogle Scholar
• 12. Olsen G, Johansen MB, Christensen Southward, Sørensen HT. Use of vitamin M antagonists and take a chance of subarachnoid haemorrhage: a population-based case-command study. Eur J Intern Med . 2010; 21:297–300. doi: x.1016/j.ejim.2010.04.009CrossrefMedlineGoogle Scholar
• 13. Castro VM, Dligach D, Finan Southward, Yu S, Can A, Abd-El-Barr Chiliad, et al. . Large-scale identification of patients with cerebral aneurysms using tongue processing. Neurology . 2017; 88:164–168. doi: x.1212/WNL.0000000000003490CrossrefMedlineGoogle Scholar
• 14. Tarlov N, Norbash AM, Nguyen TN. The safety of anticoagulation in patients with intracranial aneurysms. J Neurointerv Surg . 2013; 5:405–409. doi: 10.1136/neurintsurg-2012-010359CrossrefMedlineGoogle Scholar
• 15. Garbe E, Kreisel SH, Behr Due south. Risk of subarachnoid hemorrhage and early instance fatality associated with outpatient antithrombotic drug use. Stroke . 2013; 44:2422–2426. doi: ten.1161/STROKEAHA.111.000811LinkGoogle Scholar
• 16. Flaherty ML, Kissela B, Woo D, Kleindorfer D, Alwell K, Sekar P, et al. . The increasing incidence of anticoagulant-associated intracerebral hemorrhage. Neurology . 2007; 68:116–121. doi: ten.1212/01.wnl.0000250340.05202.8bCrossrefMedlineGoogle Scholar
• 17. Hart RG, Boop BS, Anderson DC. Oral anticoagulants and intracranial hemorrhage. Facts and hypotheses. Stroke . 1995; 26:1471–1477.CrossrefMedlineGoogle Scholar
• 18. Steiner T, Rosand J, Diringer M. Intracerebral hemorrhage associated with oral anticoagulant therapy: current practices and unresolved questions. Stroke . 2006; 37:256–262. doi: 10.1161/01.STR.0000196989.09900.f8LinkGoogle Scholar
• 19. Dasenbrock HH, Yan SC, Gross BA, Guttieres D, Gormley WB, Frerichs KU, et al. . The impact of aspirin and anticoagulant usage on outcomes after aneurysmal subarachnoid hemorrhage: a Nationwide Inpatient Sample analysis. J Neurosurg . 2017; 126:537–547. doi: 10.3171/2015.12.JNS151107CrossrefMedlineGoogle Scholar
• twenty. Eichbaum FW, Slemer O, Zyngier SB. Anti-inflammatory consequence of warfarin and vitamin K1. Naunyn Schmiedebergs Curvation Pharmacol . 1979; 307:185–190.CrossrefMedlineGoogle Scholar
• 21. Kater AP, Peppelenbosch MP, Brandjes DP, Lumbantobing M. Dichotomal effect of the coumadin derivative warfarin on inflammatory signal transduction. Clin Diagn Lab Immunol . 2002; nine:1396–1397.MedlineGoogle Scholar
• 22. Maclean PS, Tait RC, Rumley A, McMahon Advertizement, Lowe GD. Anticoagulation with warfarin downregulates inflammation. J Thromb Haemost . 2003; ane:1838–1839.CrossrefMedlineGoogle Scholar
• 23. Jayaraman T, Berenstein Five, Li 10, Mayer J, Silane M, Shin YS, et al. . Tumor necrosis cistron alpha is a key modulator of inflammation in cerebral aneurysms. Neurosurgery . 2005; 57:558–564; discussion 558.CrossrefMedlineGoogle Scholar
• 24. Jayaraman T, Paget A, Shin YS, Li Ten, Mayer J, Chaudhry H, et al. . TNF-alpha-mediated inflammation in cerebral aneurysms: a potential link to growth and rupture. Vasc Health Risk Manag . 2008; 4:805–817.CrossrefMedlineGoogle Scholar
• 25. Kamal AH, Tefferi A, Pruthi RK. How to interpret and pursue an aberrant prothrombin time, activated partial thromboplastin time, and bleeding time in adults. Mayo Clin Proc . 2007; 82:864–873. doi: 10.4065/82.vii.864CrossrefMedlineGoogle Scholar

yuegary2001.blogspot.com

Source: https://www.ahajournals.org/doi/10.1161/STROKEAHA.118.022412

Share this post