Anticoagulation For Cerebral Venous Thrombosis Research Articles

Anti-inflammatory Effect of Batroxobin Combined With Anticoagulation in Patients With Cerebral Venous Thrombosis.

Inflammation is pivotal in the pathogenesis and development of cerebral venous thrombosis (CVT). Herein, we aimed to assess the anti-inflammatory effects of batroxobin combined with anticoagulation in CVT. Participants were categorized into the batroxobin group (batroxobin combined with anticoagulation) and the control group (anticoagulation only). Regression analysis was employed to explore the association between the number of episodes of batroxobin administration and the fluctuation of inflammatory indicators, as well as the proportion of patients with inflammatory indicators that were reduced after batroxobin use. Twenty-three cases (age: 39.9 ± 13.8 years, female: 39.1%) in the batroxobin group and 36 cases (40.3 ± 9.6 years, 52.8%) in the control group were analyzed. Compared to the control group, batroxobin combined with anticoagulation significantly decreased fibrinogen (P < .001), platelet-lymphocyte ratio (PLR) (P = .016) and systemic immune-inflammation index (SII) (P = .008), and increased the proportion of the patients with lower fibrinogen (P < .001), neutrophil-lymphocyte ratio (NLR) (P = .005), PLR (P = .026), and SII (P = .006). Linear analysis showed that as the number of episodes of batroxobin administration increased, the fibrinogen (P < .001), the PLR (P = .001), and the SII (P = .020) significantly decreased. Logistic regression analysis showed as the number of episodes of batroxobin administration increased, the ratio of the patients with decreased NLR (P = .008) and PLR (P = .015), as well as SII (P = .013), significantly increased. Batroxobin could decrease NLR, PLR, and SII in CVT. The effect was related to the number of episodes of batroxobin administration. Besides reducing fibrinogen and indirect thrombolysis effects, this may be another critical benefit of batroxobin for CVT.

Timing and Predictors of Recanalization After Anticoagulation in Cerebral Venous Thrombosis.

Vessel recanalization after cerebral venous thrombosis (CVT) is associated with favorable outcomes and lower mortality. Several studies examined the timing and predictors of recanalization after CVT with mixed results. We aimed to investigate predictors and timing of recanalization after CVT. We used data from the multicenter, international AntiCoagulaTION in the Treatment of Cerebral Venous Thrombosis (ACTION-CVT) study of consecutive patients with CVT from January 2015 to December 2020. Our analysis included patients that had undergone repeat venous neuroimaging more than 30 days after initiation of anticoagulation treatment. Prespecified variables were included in univariate and multivariable analyses to identify independent predictors of failure to recanalize. Among the 551 patients (mean age, 44.4±16.2 years, 66.2% women) that met inclusion criteria, 486 (88.2%) had complete or partial, and 65 (11.8%) had no recanalization. The median time to first follow-up imaging study was 110 days (interquartile range, 60-187). In multivariable analysis, older age (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.03-1.07), male sex (OR, 0.44; 95% CI, 0.24-0.80), and lack of parenchymal changes on baseline imaging (OR, 0.53; 95% CI, 0.29-0.96) were associated with no recanalization. The majority of improvement in recanalization (71.1%) occurred before 3 months from initial diagnosis. A high percentage of complete recanalization (59.0%) took place within the first 3 months after CVT diagnosis. Older age, male sex, and lack of parenchymal changes were associated with no recanalization after CVT. The majority recanalization occurred early in the disease course suggesting limited further recanalization with anticoagulation beyond 3 months. Large prospective studies are needed to confirm our findings.

Long-term Anticoagulation with Apixaban in Patients with Cerebral Venous Thrombosis.

Introduction: Cerebral venous thrombosis (CVT) is a life-threatening neurological condition. There is limited evidence for the use of direct oral anticoagulants (DOAC) for long-term anticoagulation in this patient population. We report a case series of patients treated with apixaban and their clinical course. Methods: This was a retrospective cohort study. Patients diagnosed with CVT in a defined time period at our institution were screened for long-term anticoagulation and patients who were treated with apixaban were included in this study. Results: A total of nine patients were included in this study. The mean age was 36 years and 56% of the patients included were women. All received initial anticoagulation with unfractionated heparin (UFH) infusion for at least twenty-four hours, except for one patient who had anti-thrombin III deficiency and was treated with argatroban infusion. For long-term anticoagulation, 56% of patients received apixaban 10 mg twice daily for the first five to seven days followed by 5 mg twice daily, while the remaining 44% were transitioned from IV anticoagulation to apixaban 5 mg twice daily. There were no adverse events reported, except for one patient who developed anemia after 7 months of treatment and required a blood transfusion. Complete recanalization was achieved in 78% while 22% had partial recanalization. Follow-up time ranged from six to twenty-three months. Conclusion: The use of apixaban for long-term anticoagulation in CVT resulted in recanalization in all of the patients in this case series without any major side effects. This case series adds to the emerging studies demonstrating the utility of apixaban for CVT.

Endovascular Therapy for Cerebral Vein Thrombosis: A Propensity-Matched Analysis of Anticoagulation in the Treatment of Cerebral Venous Thrombosis.

Endovascular treatment (EVT) for cerebral vein thrombosis (CVT) has not been proven to be more effective than anticoagulation based on recent results of the Thrombolysis or Anticoagulation for Cerebral Venous Thrombosis (TO-ACT) randomized clinical trial. To compare outcomes of EVT vs medical management in CVT. We compared EVT vs medical management in a retrospective multinational cohort of consecutive patients with CVT across 4 countries (USA, Italy, Switzerland, and New Zealand) and 27 sites (2015-2020), using propensity score matching (PSM) and inverse probability treatment weighting (IPTW), and meta-analyzed these results with the TO-ACT trial. The primary outcome was excellent functional outcome (modified Rankin Scale [mRS] 0-1) at 90 days. Of the 987 patients, the mean age was 45.7 ± 16.9 years and 79 (8%) underwent EVT. With PSM (n = 124), there were no major differences in clinical or imaging features between groups other than a higher proportion of female patients receiving EVT (81% vs 65%, P = .04). There was no difference in the primary outcome with PSM (odds ratio [OR] 1.48, 95% CI, 0.55-3.96) or IPTW (OR 1.02, 95% CI, 0.34-3.06). EVT was associated with a higher 90-day shift in modified Rankin Scale (OR 2.00, 95% CI, 1.01-3.98) and mortality with IPTW (OR 4.60, 95% CI, 1.10-19.23) but no other differences in secondary outcomes with PSM or IPTW. A meta-analysis of primary and secondary outcomes from TO-ACT and PSM patients from anticoagulation in the treatment of cerebral venous thrombosis also showed no significant association with EVT in primary or secondary outcomes. In this large observational cohort, there was no evidence of benefit with EVT for CVT. These findings corroborate the results from the TO-ACT trial.

Effect of Endovascular Treatment With Medical Management vs Standard Care on Severe Cerebral Venous Thrombosis

To date, only uncontrolled studies have evaluated the efficacy and safety of endovascular treatment (EVT) in patients with cerebral venous thrombosis (CVT), leading to the lack of recommendations on EVT for CVT. To evaluate the efficacy and safety of EVT in patients with a severe form of CVT. TO-ACT (Thrombolysis or Anticoagulation for Cerebral Venous Thrombosis) was a multicenter, open-label, blinded end point, randomized clinical trial conducted in 8 hospitals in 3 countries (the Netherlands, China, and Portugal). Patients were recruited from September 2011 to October 2016, and follow-up began in March 2012 and was completed in December 2017. Adult patients with radiologically confirmed CVT who had at least 1 risk factor for a poor outcome (mental status disorder, coma state, intracerebral hemorrhage, or thrombosis of the deep venous system) were included. Data were analyzed according to the intention-to-treat principle from March 2018 to February 2019. The trial was halted after the first interim analysis for reasons of futility. Patients were randomized to receive either EVT with standard medical care (intervention group) or guideline-based standard medical care only (control group). The EVT consisted of mechanical thrombectomy, local intrasinus application of alteplase or urokinase, or a combination of both strategies. Patients in the intervention group underwent EVT as soon as possible but no later than 24 hours after randomization. Primary end point was the proportion of patients with a good outcome at 12 months (recovered without a disability; modified Rankin Scale [mRS] score of 0-1). Secondary end points were the proportion of patients with an mRS score of 0 to 1 at 6 months and an mRS score of 0 to 2 at 6 and 12 months, outcome on the mRS across the ordinal continuum at 12 months, recanalization rate, and surgical interventions in relation to CVT. Safety end points included symptomatic intracranial hemorrhage. Of the 67 patients enrolled and randomized, 33 (49%) were randomized to the intervention group and 34 (51%) were randomized to the control group. Patients in the intervention group vs those in the control group were slightly older (median [interquartile range (IQR)] age, 43 [33-50] years vs 38 [23-48] years) and comprised fewer women (23 women [70%] vs 27 women [79%]). The median (IQR) baseline National Institutes of Health Stroke Scale score was 12 (7-20) in the EVT group and 12 (5-20) in the standard care group. At the 12-month follow-up, 22 intervention patients (67%) had an mRS score of 0 to 1 compared with 23 control patients (68%) (relative risk ratio, 0.99; 95% CI, 0.71-1.38). Mortality was not statistically significantly higher in the EVT group (12% [n = 4] vs 3% [n = 1]; P = .20). The frequency of symptomatic intracerebral hemorrhage was not statistically significantly lower in the intervention group (3% [n = 1] vs 9% [n = 3]; P = .61). The TO-ACT trial showed that EVT with standard medical care did not appear to improve functional outcome of patients with CVT. Given the small sample size, the possibility exists that future studies will demonstrate better recovery rates after EVT for this patient population. ClinicalTrials.gov Identifier: NCT01204333.

Efficacy and risks of anticoagulation for cerebral venous thrombosis.

Cerebral venous thrombosis (CVT) is a rare but life-threatening disease. Timely and proper treatments are the keys in saving patients' life and preventing from permanent neurological deficits. We performed this network meta-analysis to evaluate the role of anticoagulation in CVT, especially for the patients accompanied with hemorrhagic stroke. PubMed, Embase, Web of Science, Cochrane Database, and Chinese Biomedical (CBM) databases were searched comprehensively to select eligible articles (up to 30 June 2017). Network meta-analysis was performed based on classical frequency statistics. Around 14 studies comprising 1135 cases were included. Overall analysis showed that low-molecular weight heparin (LMWH) and unfractionated heparin (UFH) were more effective (LMWH vs placebo: OR 4.76, 95%CI: 2.56-8.33; UFH vs placebo: OR 4.12, 95%CI: 2.17-8.33), and safe (LMWH vs placebo: OR 0.22, 95%CI: 0.069-0.65; UFH vs placebo: OR 0.28, 95%CI: 0.058-0.99) than placebo in the management of CVT. Besides, LMWH showed more advantages than UFH; As for the patients accompanied with hemorrhagic stroke, LMWH and UFH were also better than placebo (efficacy: LMWH vs placebo: OR 20, 95%CI: 5.56-100; UFH vs placebo: OR 12.5, 95%CI: 3.7-33.3; safety: LMWH vs placebo: OR 0.18, 95%CI: 0.04-0.77; UFH vs placebo: OR 0.16, 95%CI: 0.04-0.6) in the management of CVT. In addition, LMWH was more effective than UFH for the patients accompanied with hemorrhagic stroke. Anticoagulant treatment with heparin is safe and beneficial for patients with CVT, even for those accompanied with hemorrhagic stroke. Besides, LMWH is better than UFH in the management of CVT.

Abstract WP180: Recanalization Predicts Prognosis After Cerebral Venous Thrombosis: A Systematic Review and Meta-analysis

Background: Guidelines recommend a 3-12 month duration of anticoagulation for cerebral venous thrombosis (CVT) and a repeat venogram at 3-6 months to assess recanalization. However, the relationship between recanalization and prognosis is not well defined. We performed a systematic review and meta-analysis to clarify the association between venous recanalization and prognosis in CVT. Methods: We performed a literature search to identify all published studies that evaluated recanalization and prognosis in adult patients with a diagnosis of CVT treated with anticoagulation. Studies were identified using MEDLINE and EMBASE databases (1946 - 2017). Recanalization was ascertained by repeat venogram (CT, MR or conventional) and degree of recanalization was characterized as complete, partial or absent. Prognosis was defined using the modified Rankin Scale (mRS, 0-1 = excellent outcome). Results: We found 675 articles and conference abstracts. Thirty-five were appropriate for full-text review and 11 had information regarding recanalization and clinical outcome, accounting for 450 subjects in total. All but one study had clinical and neuro-imaging reassessments within 12 months. Eighty-five percent had complete or partial recanalization within one year. Eighty-seven percent had an excellent outcome (mRS 0-1). As compared with complete or partial recanalization, those with no recanalization had a significantly increased odds of an mRS of 2-6 (OR 3.3, 95% CI 1.5 - 7.2, p=0.003). There was no significant difference in odds of worse prognosis for those with partial recanalization versus full recanaliation. No recanalization also carried a higher odds of CVT recurrence (OR 7.2, 95% CI 1.5 - 33, p=0.01) and chronic headache (OR 3.8, 95% CI 1.6 - 9.0, p=0.002). Conclusion: Absence of recanalization is associated with a poorer prognosis in CVT patients. There does not appear to be a dose-response relationship with regards to degree of recanalization (partial versus complete) and prognosis.

Low molecular weight heparin versus unfractionated heparin in the management of cerebral venous thrombosis: A systematic review and meta-analysis.

IntroductionThere are two main choices of anti-coagulation in cerebral venous thrombosis: Unfractionated heparin versus low molecular weight heparin. A consensus is yet to be reached regarding which agent is optimal. Therefore the aim of this systematic review and meta-analysis was to identify which agent is most effective in treating CVT.MethodsDatabases Pubmed (MEDLINE), Google Scholar and hand-picked references from papers of interest were reviewed. Studies comparing the use of low molecular weight heparin and unfractionated heparin in adult patients with a confirmed diagnosis of cerebral vein thrombosis were selected. Data was recorded for patient mortality, functional outcome and haemorrhagic complications of therapy.ResultsA total of 2761 papers were identified, 74 abstracts were screened, with 5 papers being read in full text and three studies suitable for final inclusion. A total of 179 patients were in the LMWH group and 352 patients were in the UH group. Mortality and functional outcome trended towards favouring LMWH with OR [95% CI] of 0.51 [0.23, 1.10], p = 0.09 and 0.79 [0.49, 1.26] p = 0.32 respectively. There was no difference in extra-cranial haemorrhage rates between either agent with a OR [95% CI] of 1.00 [0.29, 3.52] p = 0.99.ConclusionTrends towards improved mortality and improved functional outcomes were seen in patients treated with LMWH. No result reached statistical significance due to low numbers of studies available for inclusion. There is a need for further large scale randomized trials to definitively investigate the potential benefits of LMWH in the treatment of CVT.

Antithrombotic Strategy in Cerebral Venous Thrombosis: Differences Between Neurologist and Hematologist Respondents in a Canadian Survey.

Patterns of practice for management of cerebral venous thrombosis in Canada are unknown. We surveyed Canadian neurologists and hematologists regarding anticoagulation in cerebral venous thrombosis. The response rate was 28%, with 27 neurologists and 20 hematologists responding. We found that choice of first-line initial anticoagulation differed significantly between neurologists and hematologists, with 89% of neurologists favouring unfractionated heparin and hematologists' preference split between unfractionated heparin (50%) and low-molecular-weight heparin (50%). Differences in patterns of practice likely reflect clinical equipoise.

Stroke : Highlights of Selected Articles

<i>Stroke</i> : Highlights of Selected Articles

Response to Letter Regarding Article, “Anticoagulants for Cerebral Venous Thrombosis: Harmful to Patients?”

I thank Dr Stam1 for the letter rebutting my analysis of anticoagulants for cerebral venous thrombosis (CVT).2 Dr Stam’s letter did not dispute my criticism of the meta-analysis of anticoagulants for CVT randomized controlled trials in the Cochrane Database of Systematic Reviews that he coauthored.3 This meta-analysis included a randomized controlled trial by Einhaupl and colleagues that reported 3 of 10 deaths in the placebo group and 0 of 10 deaths with full-dose heparin. However, the stillbirth of a 38-week-gestation fetus attributed to heparin was not counted as a death in the anticoagulated group. In addition, a placebo group patient that died was heparinized after a clinical diagnosis of pulmonary infarction, and still the death counted in the placebo group. We have learned since the early 1980s, when this trial was conducted, that …

Letter by Fuentes and Díez-Tejedor Regarding Article, “Anticoagulants for Cerebral Venous Thrombosis: Harmful to Patients?”

We have read with interest the recently published article by Cundiff1 in the section Comments and Opinions of Stroke that raised an important question: do we really have enough evidence to support the safety of anticoagulants for cerebral venous thrombosis (CVT)? Current guidelines recommend initial anticoagulation with adjusted-dose intravenous unfractionated heparin or weight-based low molecular weight heparin in full anticoagulant doses, followed by vitamin K antagonists, regardless of the presence of intracranial hemorrhage (ICH), with a level of evidence B.2 However, this recommendation mainly lays on the results of a Cochrane review3 that include data from 2 small randomized trials involving a total of 79 patients. One of them could not demonstrate a statistically significant effect of subcutaneous nadroparin and the other, evaluating the …

Letter by Stam Regarding Article, “Anticoagulants for Cerebral Venous Thrombosis: Harmful to Patients?”

In an opinion piece published recently in this journal, Dr Cundiff1 tries to convince the readers that anticoagulants may be not effective and even harmful to patients with cerebral venous thrombosis (CVT). By doing so, he holds a minority opinion against current practice and published guidelines. Therefore, his methods and arguments deserve close scrutiny. Although presented as an opinion statement, the article has all characteristics of a systematic review: the author went at great lengths to identify all studies of CVT, published from 1991 to 2013, which reported anticoagulants treatment and clinical outcomes. Not surprisingly in a rare disease like CVT, most of these studies are case series. From the 39 studies identified, only 6 are randomized trials. In these 39 studies, 2211 patients were treated with full-dose heparin, of whom …

Letter by Cundiff Regarding Editorial, “Cerebral Venous Thrombosis: Another Heparin Controversy”

My opinion piece in Stroke challenged the evidence basis for anticoagulant drug treatment for cerebral venous thrombosis (CVT).1 Thanks to Dr Selim2 for his rebuttal. Based on my systematic review of the limited available evidence divulged by CVT study authors in published articles and personal e-mails, my article detailed the case against anticoagulants: Dr Selim2 concedes that “the efficacy of anticoagulation in CVT has not been unequivocally proven.” However, he provides justification for anticoagulants based on the theory that they can prevent CVT propagation and thereby prevent ICHs. Although full-dose heparin has …

Cerebral Venous Thrombosis

See related article, p 298. Results from clinical studies and advances in radiological diagnosis during the past 20 years have significantly altered the management of patients with cerebral venous thrombosis (CVT), with resultant improvement in overall prognosis and decreased mortality. Although the efficacy of anticoagulation in CVT has not been unequivocally proven, it is widely used as the mainstay therapy. There is a pathophysiological rationale to recommend the use of anticoagulation in CVT. Occlusion of cerebral venous system impairs blood outflow from the brain, resulting in increased intracranial and capillary pressure and subsequently intracerebral hemorrhage (ICH). The use of anticoagulation can theoretically prevent thrombus propagation, facilitate recanalization of the occluded venous sinus, and improve venous outflow. Scattered case reports and series in the literature described the successful use of heparin in CVT since the 1940s.1,2 In the early 1990s, Einhaupl et al3 performed the first randomized controlled study: 20 patients with CVT were randomized to a placebo versus heparin. Patients treated with heparin showed significant improvement; all of the heparin-treated patients survived, and 80% had a complete clinical recovery after 3 months. No new cases of ICH occurred after initiation of heparin. Einhaupl et al3 also reported their retrospective experience in 43 patients with CVT with ICH; 27 patients were treated with intravenous heparin after the ICH. Of these, 15% of patients died compared with 69% of patients who did not receive heparin, and …

Fatal intracranial hemorrhage after anticoagulation in cerebral venous thrombosis

Fatal intracranial hemorrhage after anticoagulation in cerebral venous thrombosis

Thrombolysis or anticoagulation for cerebral venous thrombosis (TO-ACT trial)

Background: Endovascular thrombolysis (ET), with or without mechanical clot removal, may be beneficial for a subgroup of patients with cerebral venous sinus thrombosis (CVT), who have a poor prognosis despite treatment with heparin. Published experience with ET is promising, but only based on case series.

Local Thrombolysis for Severe Cerebral Venous Sinus Thrombosis

Local Thrombolysis for Severe Cerebral Venous Sinus ThrombosisJan Stam, Susanna M. Zuurbier and Jonathan M. CoutinhoAudio Available | Share

Thrombolysis or Anticoagulation for Cerebral Venous Thrombosis: Rationale and Design of the TO-ACT Trial

Endovascular thrombolysis, with or without mechanical clot removal, may be beneficial for a subgroup of patients with cerebral venous sinus thrombosis (CVT) who have a poor prognosis despite treatment with heparin. Published experience with endovascular thrombolysis is promising but only based on case series and not on controlled trials. The objective of the Thrombolysis or Anticoagulation for Cerebral Venous Thrombosis (TO-ACT) trial is to determine if endovascular thrombolysis improves the functional outcome of patients with a severe form of CVT. The TO-A C T trial is a multicenter, prospective, randomized, open-label, blinded endpoint trial. Patients are eligible if they have a radiologically proven CVT, a high probability of poor outcome (defined by presence of one or more of the following risk factors: mental status disorder, coma, intracranial hemorrhagic lesion, or thrombosis of the deep cerebral venous system), and if the responsible physician is uncertain if endovascular thrombolysis or standard anticoagulant treatment is better. One hundred sixty-four patients (82 in each treatment arm) will be included to detect a 50% relative reduction (from 40% to 20%) of poor outcomes. Patients will be randomized to receive either endovascular thrombolysis or standard therapy (therapeutic doses of heparin). Endovascular thrombolysis is composed of local application of rt-plasminogen activator (PA) or urokinase within the thrombosed sinuses, mechanical thrombosuction, or a combination of both. Patients randomized to endovascular thrombolysis will be treated with heparin before and after the interventional procedure, according to international guidelines. The primary endpoint is the modified Rankin score (mRS) at 12 months, with a score ≥2 defined as poor outcome. Secondary outcomes are six-months mRS, mortality, and recanalization rate. Major intracranial and extracranial hemorrhagic complications within one-week after the intervention are the principal safety outcomes. Results will be analyzed according to the 'intention-to-treat' principle. Blinded assessors not involved in the treatment of the patient will assess endpoints with standardized questionnaires.

Safety of anticoagulation for cerebral venous thrombosis associated with intracerebral hematoma.

Intracerebral hemorrhage (ICH) occurs in 25 to 50% of cases of cerebral venous thrombosis (CVT).1,2⇓ Although there is increasing evidence that treatment with heparin remains safe and is appropriate in patients with hemorrhagic venous infarction,1,2⇓ some uncertainties remain about the use of anticoagulation for CVT in the presence of large intracerebral hemorrhages or hemorrhages located in the temporal lobe.3 The size of intracerebral hemorrhage (ICH) in CVT can range from trivial to massive. However, indication of the volume of ICH has been rare in previously published studies of CVT.3,4⇓ When CVT is treated with combined intrathrombus tissue plasminogen activator (tPA) and IV heparin, the risk of recurrent ICH is greater for patients with large ICH compared with those with small or subtle hemorrhages.4 It is not known whether treatment with IV heparin alone is associated with a similar increase in hemorrhage risk for patients with large ICH. We present a series of patients with CVT that …