Cerebral Venous Sinus Thrombosis in Inflammatory Bowel Disease: A Review of Published Case Reports



 

Aishah Ibrahim Albakr, MD1; Noor AlMohish, MBBS1

Perm J 2021;25:21.031

https://doi.org/10.7812/TPP/21.031
E-pub: 06/02/2021

Cerebral venous sinus thrombosis (CVST) is a rare extraintestinal manifestation of inflammatory bowel disease (IBD), and the risk of poor clinical outcomes remains high in patients with delayed CVST diagnoses. This study aimed to highlight the need to recognize the critical nature of CVST complications in IBD and the challenges associated with managing concurrent conditions. We retrospectively reviewed previously reported cases of CVST in patients with IBD by searching the PubMed, Web of Science, and Google Scholar databases for articles published between 2013 and 2020. Our search identified 35 cases of IBD complicated by CVST. The mean patient age was 24.6 years (range, 31 months-47 years; men > women, ratio, 1.18:1). CVST was 3.8 times more common among patients with ulcerative colitis than among those with Crohn’s disease. Active IBD was reported in 91.4% of patients. The mean interval between IBD diagnosis and CVST occurrence was 3 years (range, 2 days-16 years). Headache was the most frequently reported symptom (85.7%), and involvement of multiple sinuses was reported in almost two-thirds of the patients. Corticosteroid therapy at the time of the CVST event was the most common prothrombotic risk factor, present in 57.14% of patients. The overall recovery rate after treatment was 77.14%; whereas the bleeding complication rate was 10%. This review provides essential information that can aid clinicians in making earlier diagnoses and promotes preventive strategies for CVST in patients with IBD. Given that CVST management can be challenging in these patients, a multidisciplinary approach is warranted.

INTRODUCTION

Inflammatory bowel disease (IBD)—which includes Crohn’s disease (CD), ulcerative colitis (UC), and unclassified IBD (IBD-U)—is characterized by both local (ie, intestinal) and systemic manifestations of chronic inflammation. Recently, there have been increases in the rate of IBD in developing countries, possibly as a result of westernization of dietary habits. Moreover, the highest incidence rates of IBD have been reported in northwestern Europe and North America.1,2

Extraintestinal manifestations of IBD are apparent in 5% to 50% of patients, with 29% of these manifestations occurring approximately 15 years after the initial diagnosis.2 Venous thromboembolism (VTE) is among the most critical extraintestinal manifestations, with a reported prevalence rate of 7.5% and a 1.7-fold increased risk among patients with IBD compared with the general population.3 Although patients with IBD develop cerebral venous sinus thromboses (CVST) at a younger age than those without IBD,4 the incidence of VTE is higher among older adults with IBD than among their younger counterparts.3-6 VTE events are also more frequent in patients with UC than in those with CD, and the risk is relatively higher in patients with active disease.3-6 Figure 1 summarizes the key prothrombotic factors in IBD patients.

tpj21031f1

Figure 1. Pathogenesis of inflammatory bowel disease (IBD)-associated venous thrombosis. Information adapted from the studies by Senchenkova et al71 and Scaldaferri et al.72 APC = activated protein C; EPCR = endothelial cell protein C receptor; IL-1B = interleukin 1-β; NO = nitric oxide; PAI-1 = plasminogen activator inhibitor 1; PAI-2 = plasminogen activator inhibitor 2; TF = tissue factor; TNF = tumor necrosis factor; tPA = tissue plasminogen activator; VEGF = vascular endothelial growth factor; VWF = von Willebrand factor.

The gap in knowledge that led to this review being conducted is not clear and must be stated.3-6 We have summarized the reported cases of IBD complicated by CVST, with a focus on demographic characteristics, risk factors, clinical aspects, disease management, and prognosis.

METHODS

Search Strategy and Statistical Analysis

We performed a literature search for manuscripts published between November 2012 and January 2020 using the following keywords: “inflammatory bowel disease, ulcerative colitis, and Crohn’s disease,” “cerebral venous sinus thrombosis,” “dural venous sinus thrombosis,” and “diagnosis and management of cerebral venous thrombosis.” We searched the Web of Science, PubMed, and Google Scholar databases to identify cases of IBD complicated by CVST in both adults and children. Google Translate (http://translate.google.co.uk/) was used for reports not written in English, and references were scanned using Google Electronic.

We obtained information related to patient demographics, risk factors, clinical features, IBD drugs, thrombosed veins, treatments, and outcomes. Missing data were recorded as not available. Descriptive statistics are presented in the text and tables using frequencies and means.

RESULTS

Demographic Data

We identified a total of 35 patients with IBD7-36 with neuroimaging-confirmed CVST (Table 1). The largest case series included 6 patients with IBD.16 Among the 35 patients identified, there were 16 women and 19 men, with a male-to-female ratio of 1.18:1. The mean age at CVST diagnosis was 24.6 years, with the youngest case having been reported in a 31-month-old boy with UC.34

Table 1. Case reports of patients with IBD who developed CVST

Study Disease IBD treatment Clinical features Thrombosed sinus Treatment Outcome
Dababneh et al (2014)7 UC, active Not mentioned Age/sex: 35 y/F DCV/SSS/TS/SS/IJV LMWH Complete recovery
Time from UC diagnosis to CVST onset: not mentioned
Presenting symptoms: altered LOC and headache
Menon et al (2013)8 UC, active Steroids, 5-aminosalicylic acid, and sulfasalazine Age/sex: 35 y/F SSS/TS LMWH followed by aspirin, AEDs Complete recovery
Time from UC diagnosis to CVST onset: 2 d
Presenting symptoms: headache and seizures
Mahmoud Reza et al (2013)9 UC, active Corticosteroid, mesalamine Age/sex: 11 y/M SSS Heparin and warfarin for 6 mo Complete recovery At the 6-mo follow-up, the patient had 2 UC exacerbations with a normal MRV
Time from CD diagnosis to CVST onset: 3 mo
Presenting symptoms: (pseudotumor cerebri) headache/photophobia, blurred vision, and repeated vomiting
Kosmidou et al (2013)10 CD, active Corticosteroids, adalimumab Age/sex: 44 y/F SSS Therapeutic dose of enoxaparin for 6 mo Complete recovery, normal MRV after 3 mo
Time from CD diagnosis to CVST onset: 5 y
Presenting symptoms: psychiatric manifestations
Jaqua et al (2013)11 UC, active Sulfasalazine, 6-mercaptopurine, and corticosteroids Age/sex: 22 y/M CVST/undetermined Enoxaparin followed by warfarin Complete recovery
Time from UC diagnosis to CVST onset: 3 y
Presenting symptoms: headache
Cojocaru et al(2014)13 UC, active Sulfasalazine, corticosteroids Age/sex: 32 y/M SSS/SS/TS LMWH, AEDs Complete recovery
Time from UC diagnosis to CVST onset: NA
Presenting symptoms: headache, generalized convulsive seizures, drowsiness, papilledema
Kwon et al (2014)14 CD, active Mercaptopurine Age/sex: 44 y/F SSS/TS/SS/IJV Heparin, local fibrinolysis, mechanical thrombectomy, warfarin Partial recovery
Time from CD diagnosis to CVST onset: NA
Presenting symptoms: headache/nausea/vomiting/photophobia
Patient course: clinical deterioration (decreased GCS)
Calcagno et al (2015)15 UC, active Corticosteroids, mesalamine Age/sex: 22 y/M Superficial vein and SS Heparin/warfarin Complete recovery
Time from UC diagnosis to CVST onset: NA
Presenting symptoms: headache and speech disturbances
DeFilippis et al (2015)16 Case series n = 6 4 UC/2 CD; all had active disease 4 patients on corticosteroids, 2 on CS and anti-TNF agents Age/sex: 3 M and 3 F; mean age: 18.7 y (10-34 y) The most common locations were SSS and SS, both occurring in 3 patients. Four patients had multiple cerebral thrombi involving both DCV and superficial veins All patients received heparin followed by warfarin for 6 mo Complete recovery: 3/6, 50%; minor deficit: 1/6, 16%; death: 2/6, 33%
Time from diagnosis to CVST onset: median duration of 3.5 y (0.5-16 y)
Presenting symptoms: headache or altered LOC
Shaikh et al (2015)12 UC, active Corticosteroid, mesalamine Age/sex: pre-teenage/M Vein of Galen and SS Combined use of Solitaire FR and Penumbra devices for EVT followed by LMWH Complete recovery
Time from UC diagnosis to CVST onset: 8 wk
Presenting symptoms: 2-d history of headache, confusion, bilateral leg weakness
Patient course: clinical deterioration (decreased GCS) over 2 d
Meher et al (2016)17 UC, remission Corticosteroid, 5-amino salicylic acid, and sulfasalazine Age/sex: 38 y/F TS/SS LMWH followed by warfarin, AED Complete recovery
The onset of CVST from CD diagnosis: 2 y
Presenting symptoms: headache/nausea/vomiting/photophobia/blurring of vision seizures altered LOC
Hashim et al. (2016)18 UC, active Corticosteroid mesalamine Age/sex: 35 y/M SSS LMWH followed by warfarin, AEDs Complete recovery
Time from UC diagnosis to CVST onset: 10 y
Presenting symptoms: headache/nausea/vomiting/seizures
Cho et al (2016)19 CD, active/ileo-colonic Infliximab Age/sex: 17 y/F Cortical veins, SSS, TS, IJV Heparin and rivaroxaban for 6 mo Resolution of the venous thrombosis with recanalization on MRV after 2 wk
Time from CD diagnosis to CVST onset: 4 y
Presenting symptoms: severe headache and vomiting
Taous et al. (2016)20 UC, active New onset Age/sex: 22 y/F TS/SS Anticoagulation Complete recovery
Time from UC diagnosis to CVST onset: CVST revealed UC diagnosis
Presenting symptoms: sudden-onset language dysfunction
Marusic et al (2017)21 UC, active Pulsed steroid therapy Age/sex: 15 y/M SSS/TS LMWH Complete recovery
Time from UC diagnosis to CVST onset: 2 y
Presenting symptoms: headache
Goh et al (2017)22 UC, active 6-mercaptopurine and steroids Age/sex: 47 y/M SSS Heparin and warfarin Complete recovery
Time from UC diagnosis to CVST onset: 5 mo
Presenting symptoms: seizures
Dallimore et al (2018)23 UC, active NA Age/sex: 25 y/F SSS/DCV Heparin Complete recovery
Time from UC diagnosis to CVST onset: NA
Presenting symptoms: seizures
Conners et al (2018)24 UC, active Infliximab Age/sex: 17 y/F SSS/TS/SS LMWH, AEDs Complete recovery
Time from UC diagnosis to CVST onset: NA
Presenting symptoms: headache/confusion/recurrent tonic-clonic seizures
Abdalla et al (2019)25 There are 2 references that begin with UC, active Mesalamine, 6-mercaptopurine/pulsed steroid therapy Age/sex: 27 y/M SSS Heparin and apixaban, AEDs Partial recovery/discharged to a rehabilitation facility
Time from UC diagnosis to CVST onset: NA
Presenting symptoms: acute-onset right-sided numbness and weakness/seizures/headache
Lee et al(2018)26 UC, active New onset Age/sex: 35 y/M SSS/TS Heparin and lifelong warfarin Complete recovery
Time from UC diagnosis to CVST onset: simultaneous diagnosis
Presenting symptoms: headache, decreased LOC, intermittent dystonic posture of the right arm, focal motor weakness
Mathew et al (2018)27 UC, active New onset Age/sex: 32 y/M SSS LMWH Complete recovery
Time from UC diagnosis to CVST onset: NA
Presenting symptoms: headache/seizures
Zhu et al (2019)28 CD, active, colonic disease Azathioprine Age/sex: 31 y/M SS Heparin and warfarin, AEDs Complete recovery
Time from CD diagnosis to CVST onset: 7 y
Presenting symptoms: headache/nausea/vomiting/seizures
Bouomrani et al (2019)29 CD, active ileal disease New onset Age/sex: 28 y/F TS Heparin and warfarin Complete recovery for 2 y
Time from CD diagnosis to CVST onset: simultaneous diagnosis
Presenting symptoms: headache/nausea/vomiting/blurred vision
Martín-Masot al. (2019)30 UC, postproctocolectomy Corticosteroids, azathioprine, mesalamine Age/sex: 5 y and 2 mo/M TS Heparin and warfarin, AEDs Complete recovery at the 3-y follow-up
Time from UC diagnosis to CVST onset: 3 y
Presenting symptoms: headache, monoparesis, focal and recurrent seizures
Deskur et al (2019)31 UC, active CS Age/sex: 25 y/M TS LMWH for 15 mo Complete recovery
Time from UC diagnosis to CVST onset: 2 y
Presenting symptoms: subacute headache for 2 mo, followed by severe headache associated with nausea
Stamp et al (2019)32 UC, active New onset Age/sex: 17 y/F SSS and SS LMWH (long-term), AEDs Complete recovery
Time from UC diagnosis to CVST onset: NA
Presenting symptoms: headache, seizures, altered LOC, and focal weakness
Stamp et al (2019)32 UC, active Azathioprine, infliximab Age/sex: 26 y/M SS/DVS LMWH, AEDs Bleeding per rectum after LMWH; partial recovery
Time from UC diagnosis to CVST onset: 2 mo
Presenting symptoms: seizures/altered LOC/motor weakness
Orfei et al (2019)33 IBD-U New onset Age/sex: 17 y/M TS/SS/IJV LMWH followed by warfarin, ventriculoperitoneal shunting Complete recovery
Time from IBD diagnosis to CVST onset: 18 mo
Presenting symptoms: headache, nausea, vomiting (delayed diagnosis for 3 wk)
Rivera-Suazo et al (2020)34 UC, active Corticosteroids, azathioprine, infliximab Age/sex: 2 y and 7 mo/M SSS LMWH, AEDs Active bleeding; complete recovery
Time from UC diagnosis to CVST onset: 15 mo
Presenting symptoms: seizures, motor weakness
Arsovska et al (2019)35 UC, active Sulfasalazine and azathioprine Age/sex: 19 y/F SSS LMWH for 6 mo because of melena, switched to warfarin, and then switched to rivaroxaban (lifelong), AEDs Partial recovery with mRS of 3; recurrent seizures 14 mo after CVST episode
Time from UC diagnosis to CVST onset: 1 y
Presenting symptoms: headache, motor weakness
Patient course: clinical deterioration for 3 wk (seizures, decreased GCS)
Liu et al (2020)36 UC, active New onset Age/sex: 12 y/F SSS superior mesenteric artery thrombosis LMWH, EVT followed by LMWH and warfarin Partial recovery
Time from UC diagnosis to CVST onset: simultaneous diagnosis
Presenting symptoms: seizures/left-sided weakness

AEDs = anti-epileptic drugs; CD = Crohn’s disease; CS = corticosteroid; CVST = cerebral venous sinus thrombosis; d = days; DCV = deep cerebral vein; DVS = deep vein system; EVT = endovascular treatment; F = female; GCS = Glasgow Coma Scale; IBD = inflammatory bowel disease; IBD-U = IBD-unclassified; IJV = internal jugular vein; LMWH = low-molecular weight heparin; LOC = level of consciousness; M = male; mo = months; mRS = modified Rankin score; MRV = magnetic resonance venography; NA = not available SS = sigmoid sinus; SSS = superior sagittal sinus; TNF = tumor necrosis factor; TS = transverse sinus; UC = ulcerative colitis; wk = weeks; y = years.

Possible Thrombotic Risk Factors in Patients With IBD

CVST risk factors other than IBD were reported in 23 patients (65.7%; Table 2). Anemia (hemoglobin < 12 mg/dL) was reported in 15 of 35 patients (42.8%)7-12,17-20,26,28,29,31,33-36 and represented the sole risk factor other than IBD in 5 of 15 patients (33.3%).7,8,19,20,29 Normocytic normochromic anemia was noted in 2 patients,17-29 whereas microcystic hypochromic anemia was noted in 1 patient.32 The other reports did not specify the type of anemia. Twenty patients (57.14%) were on corticosteroids at the time of the CVST event,9-13,15-18,21,22,25,28,30,31,33,34 and corticosteroid use represented the only risk factor for CVST in 6 of these patients.13,15,21,22,25-34 One patient was reported to have experienced multiple thrombotic episodes, including CVST, Budd–Chiari syndrome, and idiopathic thrombocytopenia.11 Two patients had a history of deep vein thrombosis.14-23 One patient was found to have superior mesenteric artery thrombosis during the CVST event,36 whereas another patient exhibited left radial artery occlusion.22 Two patients (5.7%) developed CVST events postoperatively: one experienced the event while on VTE prophylaxis,12 whereas the other was an adolescent who was not on prophylaxis and had multiple other risk factors (ie, homozygous methylene-tetra-hydro-folate reductase [MTHFR] gene C677T mutation, total parenteral nutrition, and immobility).30 Hormonal therapy (oral contraceptive pills16 or estradiol patches14) at the time of IBD exacerbation was reported in 2 patients with CD (5.7%).

Table 2. Risk factors for CVST in patients with IBD (n = 35)

Risk factor Number (%)
Corticosteroid therapy 20 (57.14)
Anemia 15 (42.8)
Previous thrombotic events 5 (14.2)
Inherited thrombophilia 4 (11.4)
High homocysteine level 2 (5.7)
Hormonal therapy 2 (5.7)
Postoperative status 2 (5.7)

CVST = cerebral venous sinus thrombosis; IBD = inflammatory bowel disease.

Inherited thrombogenic mutations were reported in 4 of 35 patients (11.4%). These included heterozygous factor V Leiden gene mutation,14 heterozygous MTHFR gene mutation,16 and homozygous MTHFR gene mutation each in 1 patient.30 One patient had multiple mutations that included a heterozygous MTHFR mutation, heterozygous factor XIII mutation, homozygous endothelial nitric oxide synthase (eNOS-786 T>C) mutation, heterozygous B-fibrinogen mutation, and heterozygous eNOS G894T and lymphotoxin A mutations.35 Laboratory investigations revealed hyperhomocysteinemia in 2 patients (5.7%).13,27 A thrombophilia screen was performed in 25 patients, revealing transient abnormalities of the coagulation system in 3 (12%)10,11,19 and persistently high antiphospholipid antibodies in 1 (4%).28

Clinical Presentation

UC was more common than CD (n = 27 vs n = 7). One patient had IBD-U.33 Active disease was present in 32 patients (91.4%), whereas 3 patients (8.5%) were in remission.17,30-33 In 20% of the patients, the CVST event had occurred at or before the time of IBD diagnosis.8,20-29,32-36 The mean interval between IBD diagnosis and a subsequent CVST event was 3 years (range, 2 days-16 years). Headache was the most common symptom (n = 30, 85.7%), followed by seizures (n = 17, 48.5%), focal neurologic disorder (n = 12, 34.2%), changes in mental status (n = 11, 31.4%), and symptoms of increased intracranial pressure, such as nausea, vomiting, and papilledema (n = 11, 31.4%). A severe symptomatic increase in intracranial pressure requiring ventriculoperitoneal shunting was reported in a 17-year-old male patient with IBD-U.33 One patient with CD exhibited agitation accompanied by anxiety attacks, thoughts of impending doom, paranoia, and insomnia in the absence of headache or other common symptoms.12

Location of the Thrombosed Sinus

The most common thrombosed sinus was the superior sagittal sinus (n = 25, 71.4%). Thromboses were observed in the transverse sinus, sigmoid sinus, and deep cerebral/cortical veins in 14 (40%), 15 (42.8%), and 5 patients (14.2%), respectively. Involvement of more than 1 sinus was reported in 23 patients (65.7%).

Treatment

All patients (100%) had received anticoagulation treatment with heparin or low-molecular weight heparin (LMWH) in the acute phase of CVST. Three patients underwent endovascular treatment (EVT) via thrombolysis or mechanical thrombectomy because of progressive clinical and radiologic deterioration refractory to anticoagulation therapy.12,14,36 Maintenance heparin or LMWH was used in 12 patients (34.2%).7,10,12,13,21,23,24,27,31,32,34 LMWH treatment was followed by warfarin administration in 18 patients (58.06%).9,11,15-18,22,26,28,29,30-33,36 One patient who was initially treated with warfarin was switched to rivaroxaban because of deterioration of the international normalized ratio (INR) after eating a green salad.35 Two patients were treated with LMWH followed by novel anticoagulants (apixaban25 and rivaroxaban19), whereas 1 patient was treated with LMWH followed by aspirin.8 In 1 case report, the type of anticoagulation therapy was not specified.22 Long-term anticoagulation therapy was given to 4 of 35 patients.26,31,32,35 Complete recovery was achieved in 27 patients (77.14%), whereas partial recovery was achieved in 6.14,16,25,32,35,36 Two patients died16: 1 died as a result of severe CVST and brain edema, whereas the other had recovered from CVST but died secondary to bowel perforation.16 Active bleeding after LMWH was reported in 3 patients whose therapy had been temporarily discontinued. All 3 patients stabilized and ultimately achieved complete recovery after resumption of treatment.32,34,35 Anti-epileptic drugs were administered to 17 patients with symptomatic seizures. One patient experienced recurrent seizures after 14 months of anti-epileptic drug treatment.35 No other cases of recurrence were reported.

DISCUSSION

This review of published case reports (Table 1) demonstrates that patients with IBD experiencing CVST tend to be young males, which is consistent with previous studies.37,38 However, we observed a younger age of onset than that reported in the review by Cognat et al37 (mean, 24.6 vs 30.7 years, respectively). One Danish study reported that young patients with IBD (< 20 years old) were at increased risk for developing VTE (hazard ratio, 6) compared with age- and sex-matched individuals without IBD.39 Nylund et al40 observed that children and adolescents (5-20 year old) with IBD were also at increased risk of venous thrombosis. Our analysis suggests that male patients with IBD were more often affected with CVST than their female counterparts, although the male-to-female ratio appeared nearly equal. This discrepancy is most likely explained by a higher percentage (40%) of patients under the age of 17 years, which is in turn associated with lower rates of pregnancy and hormonal therapy. Similarly, Acikgoz et al41 reported that CVST occurs in adolescents of both sexes, with IBD at equal rates.

In the International Study on Cerebral Vein and Dural Sinus Thrombosis, the presence of more than 1 risk factor was observed in 44% of the patients with CVST. Therefore, even when 1 risk factor has been identified, a complete workup should be performed to identify other potential factors.42 In this review, almost two-thirds of the patients had possible prothrombotic risk factors other than IBD at the time of the CVST event. Overall, the distribution of prothrombotic risk factors (Table 2) is relatively similar to that reported in a previous study.38 Our review verified the high risk of thrombosis in patients with active IBD (hazard ratio, 8.4),43,44 and we observed that most patients had active disease. In fact, active disease was the only risk factor in one-third of the patients with UC and CD at nearly rates; similar findings were reported by Katsanos et al.38 The risk of CVST is particularly high in patients with IBD after surgery, which is known to increase the risk of VTE by nearly 40-fold44; therefore, VTE prophylaxis has been recommended in surgical candidates.45 However, Kosmidou et al10 reported a case of superior sagittal thrombosis that occurred while the patient was on thromboprophylaxis after surgical treatment for a perianal abscess. This report contradicts the available evidence and suggests that VTE prophylaxis should not prevent clinicians from considering a diagnosis of CVST. Table 3 summarizes the recommendations for CVST prophylaxis in patients with IBD.

Table 3. Summary of recommendations for CVST prophylaxis in patients with IBD

Consideration Recommendation
Type of thromboprophylaxis If the bleeding risk is high or active bleeding is present, mechanical thromboprophylaxis using graduated compression stockings/intermittent pneumatic compression is recommended. If the bleeding risk is decreased, prophylactic anticoagulation therapy should be considered.45
CVST prophylaxis in hospitalized patients with IBD CVST prophylaxis is recommended for all hospitalized patients with severe disease and no contraindications to thromboprophylaxis.60,73-75
Hospitalized patients with reversible prothrombotic risk factors All reversible IBD- and patient-related risk factors should be managed appropriately, which includes: treating disease activity and its complications, adequate hydration, treating infections, vitamin supplementation in case of deficiency, early mobilization, cessation of smoking and oral contraceptive use, avoiding indwelling catheters, and treating other coexisting conditions such as anemia or antiphospholipid syndrome.45
Pregnant women with a history of CVST Prophylactic use of anticoagulation is recommended for women with a history of CVST during pregnancy or the postpartum period with no contraindications to prophylaxis.76
Patients with IBD undergoing major surgery Prophylactic use of anticoagulation is recommended.45,77

CVST = cerebral venous sinus thrombosis; IBD = inflammatory bowel disease.

Because most patients in this review had active disease, corticosteroid therapy was used in a large percentage of cases. Theoretically, corticosteroids exert an anti-inflammatory effect; however, some studies have reported that steroids increase the risk of thrombosis in patients with IBD. In a 2015 retrospective study of 15,000 adult patients with IBD, corticosteroid use contributed to an almost 5-fold increase in the risk of thrombotic events.46 As reported by a recent meta-analysis, patients with IBD who used corticosteroids exhibited a high risk of thrombotic risk (hazard ratio, 2.2), whereas biological therapy decreased this risk.46,47 The exact mechanism underlying these phenomena remains unclear, although they are thought to occur secondary to steroid inhibition of prostacyclin synthesis and fibrinolysis while stimulating the coagulation cascade.46,47 Anemia has been previously recognized as the most common risk factor for CVST in patients with IBD,38 in accordance with our results.

The prevalence of genetic mutations is similar in patients with IBD and the general population, and does not vary based on the presence of VTE.48,49 However, the presence of hereditary factors seems to increase the risk of VTE. In this review, only 11% of patients had hereditary thrombophilia. Although factor V Leiden mutations are well recognized as the most common hereditary forms of thrombophilia,48,49 MTHFR mutations were most frequent among the cases reviewed in the present study.

Routine screening for thrombophilia and autoimmune diseases is not recommended,50,51 because the findings of these examinations are nonspecific, especially in the acute phase of CVST, and have not been shown to influence the disease outcome.4,45,50 Our findings are consistent with those of previous studies, because only 1 of 25 patients who underwent thrombophilia screening exhibited persistent increases in antiphospholipid antibodies, leading to a diagnosis of antiphospholipid syndrome concurrent with IBD.26 Considering the systemic thrombotic effects of IBD, multiple potential sites should be considered in patients with CVST.11,22,36 Although hyperhomocysteinemia is not uncommon in patients with IBD, the association between hyperhomocysteinemia and thrombosis is yet to be fully established.52,53 In our literature review, we identified 2 cases in which hyperhomocysteinemia was the only risk factor other than IBD.13,27

In accordance with our findings, a previous study noted that the distribution of CVST symptoms appears to be similar in patients with and without IBD.37 The diagnosis may be easier when neurologic symptoms are associated with headaches, whereas the presence of isolated symptoms can result in delayed diagnosis. Kosmidou et al10 reported the case of a 44-year-old woman with CD who had psychiatric manifestations in the absence of headaches, which delayed the diagnosis by 3 weeks. Although the distribution of the thrombosed sinus in our review was similar to that noted in previous analyses,49 the rate of multisinus involvement was higher in our review than in previous reports (65% vs 50%, respectively).37,38

The presumed safety of heparin in patients with IBD experiencing CVST events is indirectly based on previous studies that have suggested that heparin exerts immunomodulatory and anti-inflammatory effects that can be beneficial in steroid-resistant IBD.54,55 Katsanos et al38 stated that heparin treatment for CVST leads to good neurologic outcomes and low mortality rates in patients with IBD. In a 2012 review of 54 studies, Cognat et al37 documented complete recovery and good outcomes in 84% (47/54) of the patients with IBD who had undergone full anticoagulation therapy. The most common treatment strategies in these cases included intravenous or subcutaneous LMWH followed by oral anticoagulant treatment (warfarin), with the goal of achieving an INR of 2 to 3 when the patient was relatively stable. Table 4 summarizes the management of CVST in patients with IBD.

Table 4. Summary of recommendations for CVST management in patients with IBD

Consideration Recommendation
Confirmed CVST diagnosis on CTV or MRV Start anticoagulation immediately with heparin at the therapeutic dosage, even in patients with ICH at baseline.38,51
Duration of anticoagulation therapy Oral anticoagulants (warfarin) for 6-12 mo are recommended to prevent the recurrence of CVST and other VTE events.38,51
In patients with active disease who have CVST, anticoagulation therapy is recommended for at least 3 mo after IBD remission.45
Patients with recurrent VTE or irreversible prothrombotic conditions may require lifelong anticoagulation therapy.38,51
EVT If the clinical condition deteriorates or ICP continues to increase despite anticoagulation, EVT is recommended.51
Managing seizures If the patient develops seizures, anti-epileptic drugs are recommended to prevent recurrent episodes.51
Patients with IBD experiencing CVST during pregnancy or the postpartum period Subcutaneous LMWH is recommended in patients with acute CVT.51
CVST in the pediatric age group (> 28 d old) Therapeutic anticoagulation followed by maintenance treatment (LMWHs/warfarin) for 3-6 mo.50

CTV = computed tomography venography; CVST = cerebral venous sinus thrombosis; CVT = cerebral venous thrombosis; EVT = endovascular treatment; IBD = inflammatory bowel disease; ICH = intracerebral hemorrhage; ICP = intracranial pressure; LMWH = low-molecular weight heparin; MRV = magnetic resonance venography; VTE = venous thromboembolism.

There are several important considerations when managing CVST in patients with IBD. First, commonly used regimens for IBD flare-ups have been associated with drug or food interactions. For example, steroid therapy is known to interact with warfarin. In 2 retrospective studies, steroids were found to increase the mean INR by 1.24 in patients on warfarin.56,57 The INR should be monitored closely, and the warfarin dose should be adjusted accordingly.58 Although there are no recommendations for the use of direct oral anticoagulants (DOACs) in patients with CVST,51 they have been used off-label by physicians to avoid food interactions with warfarin.59 In this review, CVST occurred in 3 patients with IBD who had been treated with DOACs as a result of difficulty in achieving the target INR.19,25,35 A second major consideration is active gastrointestinal bleeding. Hematochezia may occur at the time of the CVST event11 or after anticoagulation therapy, as previously noted in 3 cases.32,34,35 The treatment plan should be individualized, taking into consideration the clinical status and episode severity of each patient, and it often requires a multidisciplinary approach.60 Third, patients should be carefully monitored for active intracranial bleeding. Given the high mortality rate of untreated CVST and venous hemorrhages, continuation of anticoagulation therapy has been recommended.50,51 Finally, clinicians should monitor patients for warfarin resistance. Multiple bowel resections are not uncommon in patients with CD, and such resections may influence warfarin absorption because of loss of effective surface area. A higher dose of warfarin may be required because of possible short gut syndrome in patients with multiple resections.14

EVT should be considered when the patient’s clinical condition deteriorates despite anticoagulation therapy or when intracranial pressure continues to increase despite optimal management. Possible EVT approaches include direct thrombolytic therapy, mechanical thrombectomy, balloon angioplasty, and stenting.52,53 Despite reports of favorable clinical outcomes, no large-scale randomized controlled trials have provided evidence supporting the use of EVT in patients with CVST.61,62,63 EVT and on-site thrombolysis for the treatment of CVST have been documented in 7 patients with IBD,12,14,36,64-66 5 of whom achieved complete recovery with no reported mortality or bleeding-related complications.12,64-66 Thrombolytic agents are thought to be safer and more effective than heparin, because they are more rapidly metabolized and carry a lower risk of bleeding. Moreover, thrombolytics play an important role in improving venous flow and inhibiting thrombus progression.67,68

In this review, complete recovery was noted in most patients who had received treatment. This phenomenon may partly be due to improvements in diagnostic methods and CVST therapies since the publication of previous studies.69,70 The rate of complete recovery was comparable to that in the review by Katsanos et al.38 Despite major concerns regarding bleeding in patients with IBD, bleeding complications were observed in only 3 of the reviewed cases, and the events were controlled without complications in all patients.32,34,35 Other treatment options, including DOACs, aspirin, thrombolysis, and EVT have been associated with relatively promising results; however, because of the small number of reported cases, their safety and efficacy are yet to be definitively concluded.

CONCLUSION

Thrombosis is a well-recognized feature of IBD that can be related to the pathogenesis of the disease as well as the presence of prothrombotic risk factors. However, CVST events can be prevented, and awareness of IBD-related risk factors is essential for avoiding future occurrences. Future studies and trials should aim to investigate issues concerning CVST prophylaxis, including the need to extend thromboprophylaxis postdischarge, especially in ambulatory patients with IBD flare-ups. CVST should be suspected in all patients with IBD presenting with neurologic symptoms. Furthermore, the critical nature of CVST complications in IBD and the challenges associated with managing the concurrent conditions must be recognized. Given that anticoagulation therapy is both safe and effective, it is considered the mainstay treatment for CVST in patients with IBD. However, further studies are required to validate the safety and efficacy of DOACs and EVT in these patients.

Disclosure Statement

The author(s) have no conflicts of interest to disclose.

Funding

No source of funding.

Author Affiliations

1Department of Neurology, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia

Corresponding Author

Aishah Ibrahim Albakr, (abakr@iau.edu.sa)

Author Contributions

Aishah Ibrahim Albakr conceptualized the content and participated in the literature search, manuscript editing, and manuscript review. Noor AlMohish participated in the literature search and manuscript preparation.

References

1. Ng SC, Shi HY, Hamidi N, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: A systematic review of population-based studies. Lancet 2017 Dec;390:2769-78. DOI: https://doi.org/10.1016/S0140-6736(17)32448-0

2. Annese V. A review of extraintestinal manifestations and complications of inflammatory bowel disease. Saudi J Med Sci 2019 May-Aug;7(2):66-73. DOI: https://doi.org/10.4103/sjmms.sjmms_81_18

3. Cohen JB, Comer DM, Yabes JG, Ragni MV. Inflammatory bowel disease and thrombosis: A national inpatient sample study. TH Open 2020 Jan;4(1):e51-8. DOI: https://doi.org/10.1055/s-0040-1710506, PMID:32435723

4. Ferro JM, Canhão P, Stam J, Bousser MG, Barinagarrementeria F. Prognosis of cerebral vein and dural sinus thrombosis: Results of the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Stroke 2004 Mar;35(3):664-70. DOI: https://doi.org/10.1161/01.STR.0000117571.76197.26, PMID:14976332

5. Ando K, Fujiya M, Nomura Y, et al. The incidence and risk factors of venous thromboembolism in Japanese inpatients with inflammatory bowel disease: A retrospective cohort study. Intest Res 2018 Jul;16(3):416-25. DOI: https://doi.org/10.5217/ir.2018.16.3.416, PMID:30090041

6. Faye AS, Wen T, Ananthakrishnan AN, et al. Acute venous thromboembolism risk highest within 60 days after discharge from the hospital in patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol 2020 May;18(5):1133-41.e3. DOI: https://doi.org/10.1016/j.cgh.2019.07.028, PMID:31336196

7. Dababneh H, Guerrero WR, Moussavi M, Hussain M, Kirmani JF. Ulcerative colitis presenting with bilateral thalamic infarcts due to cerebral sinus thrombosis. J Vasc Interv Neurol 2014 Jun;7(2):27-8, PMID:25132908.

8. Menon B, Goyal R, Nihal L, Reddy R. Cerebral venous thrombosis in ulcerative colitis. J Neurosci Rural Pract 2013 Jan;4(1):84-6. DOI: https://doi.org/10.4103/0976-3147.105629, PMID:23546367

9. Mahmoud Reza A, Firozeh H, Houman A, Mehri NS. Pseudotumor cerebri in a case of ulcerative colitis with sagittal sinus thrombosis. Iran J Pediatr 2013 Feb;23(1):109-12, PMID:23549165.

10. Kosmidou M, Vagias I, Katsanos KH, Tsianos EV. Agitation as the only symptom of cerebral venous sinus thrombosis in a patient with Crohn’s disease. Ann Gastroenterol 2013 May;26(4):373, PMID:24714740.

11. Jaqua NT, Stratton A, Yaccobe L, Tahir U, Kenny P, Kerns T. A review of the literature on three extraintestinal complications of ulcerative colitis: An ulcerative colitis flare complicated by Budd-Chiari syndrome, cerebral venous thrombosis and idiopathic thrombocytopenia. Acta Gastroenterol Belg 2013 Sep;76(3):311-6, PMID:24261025.

12. Shaikh H, Pukenas BA, McIntosh A, Licht D, Hurst RW. Combined use of Solitaire FR and Penumbra devices for endovascular treatment of cerebral venous sinus thrombosis in a child. J NeuroIntervent Surg 2015 Mar;7(3):e10. DOI: https://doi.org/10.1136/neurintsurg-2013-011088.rep

13. Cojocaru IM, Cojocaru M, Sapira V, Ionescu A, Tacu N. Cerebrovascular complications in patients with inflammatory bowel disease. Rom J Intern Med 2014 Jan-Mar;52:39-44.

14. Kwon Y, Koene RJ, Cho Y. A case of cerebral venous sinus thrombosis associated with Crohn’s disease: Dilemma in management. Gastroenterol Rep (Oxf) 2016 May;4(2):154-7. DOI: https://doi.org/10.1093/gastro/gou079, PMID:25389155

15. Calcagno GP, Bagattini JC, Forster TA, Chiarella M, Cohen H. [Intracranial sinus venous thrombosis in ulcerative colitis. Report of one case]. Rev Med Chil 2015 Apr;143(4):520-4. DOI: https://doi.org/10.4067/S0034-98872015000400015, PMID:26204545

16. DeFilippis EM, Barfield E, Leifer D, et al. Cerebral venous thrombosis in inflammatory bowel disease. J Dig Dis 2015 Feb;16(2):104-8. DOI: https://doi.org/10.1111/1751-2980.12212, PMID:25395041

17. Meher LK, Dalai SP, Panda S, Hui PK, Nayak S. Unusual case of cerebral venous sinus thrombosis in patient with ulcerative colitis in remission. J Clin Diagn Res 2016 May;10(5):OD35-6. DOI: https://doi.org/10.7860/JCDR/2016/20105.7883, PMID:27437291

18. Hashim H, Khan M, Dar J, Alrukn S, Al Madani A. Cerebral sinus thrombosis: A rare but fatal complication of inflammatory bowel disease. J Neurol Stroke 2016 Mar;4:00136. DOI: https://doi.org/10.15406/jnsk.2016.04.00136

19. Cho YH, Chae MK, Cha JM, et al. Cerebral venous thrombosis in a patient with Crohn's disease. Intest Res 2016 Jan;14(1):96-101. DOI: https://doi.org/10.5217/ir.2016.14.1.96, PMID:26884741

20. Taous A, Berri MA, Lamsiah T, Zainoun B, Ziadi T, Rouimi A. Cerebral venous thrombosis revealing an ulcerative colitis. Pan Afr Med J 2016 Mar;23:120. DOI: https://doi.org/10.11604/pamj.2016.23.120.9186

21. Marusic E, Polic B, Runjic E, Ursic A, Lahman Doric M, Zitko V. Influenza-associated encephalopathy - case report. Eur J Paediatr Neurol 2017 Jun;21(Supp 1):e120. DOI: https://doi.org/10.1016/j.ejpn.2017.04.975

22. Goh IY, Saric S, Leschke P, McFarlane M, Jha PK. Thromboembolism in active ulcerative colitis. BMJ Case Rep 2017 Jun;2017:bcr-2016-218608. DOI: https://doi.org/10.1136/bcr-2016-218608.

23. Dallimore J, Bhatnagar R. Bleeding or clotting: An intracranial dilemma. BMJ Case Rep 2018 Feb;2018:bcr2017222781. DOI: https://doi.org/10.1136/bcr-2017-222781, PMID:29437804

24. Conners LM, Ahad R, Janda PH, Mudasir Z. Cerebral venous sinus thrombosis in a patient with ulcerative colitis flare. Case Rep Neurol Med 2018 Jan;2018:5798983. DOI: https://doi.org/10.1155/2018/5798983, PMID:29610691

25. Abdalla AO, Alluri D, Hassaballa M, Calvo L, Otaki F. A case of cerebral venous sinus thrombosis presenting during relapse of ulcerative colitis. Am J Case Rep 2019 Mar;20:419-22. DOI: https://doi.org/10.12659/AJCR.913429, PMID:30928992

26. Lee J, Hwang SW, Lee J, et al. A case of ulcerative colitis presenting with cerebral venous thrombosis. Intest Res 2018 Apr;16(2):306-11. DOI: https://doi.org/10.5217/ir.2018.16.2.306, PMID:29743845

27. Mathew S, Ravikanth R. Cerebral venous thrombosis in inflammatory bowel disease. CHRISMED J Health Res 2018 Jan;5:54-6. DOI: https://doi.org/10.4103/cjhr.cjhr_53_17

28. Zhu L, Cheng J, Gu P, et al. Therapeutic strategies of thromboembolic events in patients with inflammatory bowel diseases: Two case reports. Medicine (Baltimore) 2019 Mar;98(9):14622. DOI: https://doi.org/10.1097/MD.0000000000014622, PMID:30817579

29. Bouomrani S, Rgaïeg N, Guermazi M, Yahyaoui S. Cerebral vein thrombosis revealing Crohn’s disease. Radiol Diagn Imaging 2019 Apr;3. DOI: https://doi.org/10.15761/RDI.1000153.

30. Martín-Masot R, Ortiz Pérez P, Serrano Nieto J, et al. Central venous sinus thrombosis in a boy with acute severe ulcerative colitis. Front Pediatr 2019 Feb;7:19. DOI: https://doi.org/10.3389/fped.2019.00019

31. Deskur A, Zawada I, Błogowski W, Starzyńska T. Cerebral venous sinus thrombosis in a young patient with ulcerative colitis: A case report. Medicine (Baltimore) 2019 Oct;98(41):e17428. DOI: https://doi.org/10.1097/MD.0000000000017428, PMID:31593096

32. Stamp K, Pattinson A, Maliakal P, Nandakumar T, Sebastian S. Cerebral venous thrombosis as presenting manifestation of inflammatory bowel disease (IBD). GastroHep 2019 Jan;1(1):45-50. DOI: https://doi.org/10.1002/ygh2.325

33. Orfei M, Gasparetto M, Torrente F. Headache and inflammatory bowel disease: Think cerebral vein! BMJ Case Rep 2019 Jan;12(1):e227228. DOI: https://doi.org/10.1136/bcr-2018-227228, PMID:30700456

34. Rivera-Suazo Y, Arguello Calderon I, Vasquez-Frias R. Trombosis del seno venoso sagittal superior en paciente pediátrico con enfermedad inflamatoria intestinal: Reporte de caso. Revista De Gastroenterología De México 2020 Jul-Sep;85:346-66. DOI: https://doi.org/10.1016/j.rgmx.2019.07.007.

35. Arsovska A, Caliandro P, Caso V, et al. Cerebral venous sinus thrombosis in a 19 year old female with ulcerative colitis: Long term follow-up and review from the literature. Rad Hrvat Akad Znan Umjet 2019 Jul;537(46-47):48-54. DOI: https://doi.org/10.21857/94kl4cx2jm

36. Liu Y, Ren D, Zhou Q, Gao L. Cerebral sinovenous thrombosis in a child with ulcerative colitis: A case report. Medicine 2020 Jan;99:e18649. DOI: https://doi.org/10.1097/md.0000000000018649

37. Cognat E, Crassard I, Denier C, Vahedi K, Bousser MG. Cerebral venous thrombosis in inflammatory bowel diseases: Eight cases and literature review. Int J Stroke 2011 Dec;6(6):487-92. DOI: https://doi.org/10.1111/j.1747-4949.2011.00620.x, PMID:22017824

38. Katsanos AH, Katsanos KH, Kosmidou M, Giannopoulos S, Kyritsis AP, Tsianos EV. Cerebral sinus venous thrombosis in inflammatory bowel diseases. QJM 2013 May;106(5):401-13. DOI: https://doi.org/10.1093/qjmed/hcs229, PMID:23243293

39. Kappelman MD, Horvath-Puho E, Sandler RS, et al. Thromboembolic risk among Danish children and adults with inflammatory bowel diseases: A population-based nationwide study. Gut 2011 Jul;60(7):937-43. DOI: https://doi.org/10.1136/gut.2010.228585, PMID:21339206

40. Nylund CM, Goudie A, Garza JM, Crouch G, Denson LA. Venous thrombotic events in hospitalized children and adolescents with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2013 May;56(5):485-91. DOI: https://doi.org/10.1097/MPG.0b013e3182801e43, PMID:23232326

41. Acikgoz M, Guzel A, Aslan K, et al. A significant association in paediatric emergency department, cerebral sinovenous thrombosis and ulcerative colitis: A review of the literature. West Indian Med J 2016 Feb;64(5):1-25. DOI: https://doi.org/10.7727/wimj.2015.290.

42. Kaddourah O, Numan L, Jeepalyam S, Abughanimeh O, Ghanimeh MA, Abuamr K. Venous thromboembolism prophylaxis in inflammatory bowel disease flare-ups. Ann Gastroenterol 2019 Nov-Dec;32(6):578-83. DOI: https://doi.org/10.20524/aog.2019.0412, PMID:31700234

43. McCurdy JD, Israel A, Hasan M, et al. A clinical predictive model for post-hospitalisation venous thromboembolism in patients with inflammatory bowel disease. Aliment Pharmacol Ther 2019 Jun;49(12):1493-501. DOI: https://doi.org/10.1111/apt.15286, PMID:31066471

44. Kim TJ, Kong SM, Shin JB, et al. P196 risk of venous thromboembolism according to disease activity, hospitalisation, or surgry in inflammatory bowel disease: A nationwide cohort study. J Crohns Colitis 2019 Jan;13(Suppl_1):S189-90. DOI: https://doi.org/10.1093/ecco-jcc/jjy222.320

45. Nguyen GC, Bernstein CN, Bitton A, et al. Consensus statements on the risk, prevention, and treatment of venous thromboembolism in inflammatory bowel disease: Canadian Association of Gastroenterology. Gastroenterology 2014 Mar;146(3):835-e6.PMID:24462530 DOI: https://doi.org/10.1053/j.gastro.2014.01.042

46. Higgins PD, Skup M, Mulani PM, Lin J, Chao J. Increased risk of venous thromboembolic events with corticosteroid vs biologic therapy for inflammatory bowel disease. Clin Gastroenterol Hepatol 2015 Feb;13(2):316-21. DOI: https://doi.org/10.1016/j.cgh.2014.07.017, PMID:25038374

47. Sarlos P, Szemes K, Hegyi P, et al. Steroid but not biological therapy elevates the risk of venous thromboembolic events in inflammatory bowel disease: A meta-analysis. J Crohns Colitis 2018 Mar;12(4):489-98. DOI: https://doi.org/10.1093/ecco-jcc/jjx162, PMID:29220427

48. Tsiolakidou G, Koutroubakis IE. Thrombosis and inflammatory bowel disease-the role of genetic risk factors. World J Gastroenterol 2008 Jul;14(28):4440-4. DOI: https://doi.org/10.3748/wjg.14.4440, PMID:18680221

49. Papa A, Danese S, Grillo A, Gasbarrini G, Gasbarrini A. Review article: Inherited thrombophilia in inflammatory bowel disease. Am J Gastroenterol 2003 Jun;98(6):1247-51. DOI: https://doi.org/10.1111/j.1572-0241.2003.07491.x, PMID:12818264

50. Saposnik G, Barinagarrementeria F, Brown RD Jr, et al. Diagnosis and management of cerebral venous thrombosis: A statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011 Apr;42(4):1158-92. DOI: https://doi.org/10.1161/STR.0b013e31820a8364, PMID:21293023

51. Ferro JM, Bousser MG, Canhão P, et al. European Stroke Organization guideline for the diagnosis and treatment of cerebral venous thrombosis - endorsed by the European Academy of Neurology. Eur J Neurol 2017 Oct;24(10):1203-13. DOI: https://doi.org/10.1111/ene.13381, PMID:28833980

52. Erzin Y, Uzun H, Celik AF, Aydin S, Dirican A, Uzunismail H. Hyperhomocysteinemia in inflammatory bowel disease patients without past intestinal resections: Correlations with cobalamin, pyridoxine, folate concentrations, acute phase reactants, disease activity, and prior thromboembolic complications. J Clin Gastroenterol 2008 May-Jun;42(5):481-6. DOI: https://doi.org/10.1097/MCG.0b013e318046eab0, PMID:18344891

53. Vučković BA, van Rein N, Cannegieter SC, Rosendaal FR, Lijfering WM. Vitamin supplementation on the risk of venous thrombosis: Results from the MEGA case-control study. Am J Clin Nutr 2015 Mar;101(3):606-12. DOI: https://doi.org/10.3945/ajcn.114.095398, PMID:25733646

54. Zezos P, Papaioannou G, Nikolaidis N, et al. Low-molecular-weight heparin (enoxaparin) as adjuvant therapy in the treatment of active ulcerative colitis: A randomized, controlled, comparative study. Aliment Pharmacol Ther 2006 May;23(10):1443-53. DOI: https://doi.org/10.1111/j.1365-2036.2006.02870.x, PMID:16669959

55. Vrij AA, Jansen JM, Schoon EJ, Brüine AD, Hemker HC, Stockbrügger RW. Low molecular weight heparin treatment in steroid refractory ulcerative colitis: Clinical outcome and influence on mucosal capillary thrombi. Scand J Gastroenterol 2001 Jan;36(234):41-7. DOI: https://doi.org/10.1080/003655201753265091

56. Kalita J, Chandra S, Kumar B, Bansal V, Misra UK. Cerebral venous sinus thrombosis from a tertiary care teaching hospital in India. Neurol 2016 May;21(3):35-8. DOI: https://doi.org/10.1097/NRL.0000000000000079, PMID:27119274

57. Hazlewood KA, Fugate SE, Harrison DL. Effect of oral corticosteroids on chronic warfarin therapy. Ann Pharmacother 2006 Dec;40(12):2101-6. DOI: https://doi.org/10.1345/aph.1H418, PMID:17119104

58. Dowd MB, Vavra KA, Witt DM, Delate T, Martinez K. Empiric warfarin dose adjustment with prednisone therapy. A randomized, controlled trial. J Thromb Thrombolysis 2011 May;31(4):472-7. DOI: https://doi.org/10.1007/s11239-010-0535-8, PMID:21161329

59. van der Hulle T, Kooiman J, den Exter PL, Dekkers OM, Klok FA, Huisman MV. Effectiveness and safety of novel oral anticoagulants as compared with vitamin K antagonists in the treatment of acute symptomatic venous thromboembolism: A systematic review and meta-analysis. J Thromb Haemost 2013 Dec;12(3):320-8. DOI: https://doi.org/10.1111/jth.12485, PMID:24330006

60. Mowat C, Cole A, Windsor A, et al. Guidelines for the management of inflammatory bowel disease in adults. Gut 2011 May;60(5):571-607. DOI: https://doi.org/10.1136/gut.2010.224154, PMID:21464096

61. Lee SK, Mokin M, Hetts SW, et al. Current endovascular strategies for cerebral venous thrombosis: Report of the SNIS standards and guidelines committee. J Neurointerv Surg 2018 Aug;10(8):803-10. DOI: https://doi.org/10.1136/neurintsurg-2018-013973, PMID:29871990

62. Mortimer AM, Bradley MD, O’Leary S, Renowden SA. Endovascular treatment of children with cerebral venous sinus thrombosis: A case series. Pediatr Neurol 2013 Nov;49(5):305-12. DOI: https://doi.org/10.1016/j.pediatrneurol.2013.07.008, PMID:24139531

63. Liao CH, Liao NC, Chen WH, et al. Endovascular mechanical thrombectomy and on-site chemical thrombolysis for severe cerebral venous sinus thrombosis. Sci Rep 2020 Mar;10(1):4937. DOI: https://doi.org/10.1038/s41598-020-61884-5, PMID:32188921

64. Kothur K, Kaul S, Rammurthi S, Bandaru VC, Suryaprabha SA, Mrudula KR. Use of thrombolytic therapy in cerebral venous sinus thrombosis with ulcerative colitis. Ann Indian Acad Neurol 2012 Jan;15(1):35-8. DOI: https://doi.org/10.4103/0972-2327.93276, PMID:22412271

65. Tsujikawa T, Urabe M, Bamba H, et al. Haemorrhagic cerebral sinus thrombosis associated with ulcerative colitis: A case report of successful treatment by anticoagulant therapy. J Gastroenterol Hepatol 2000 Jun;15(6):688-92. DOI: https://doi.org/10.1046/j.1440-1746.2000.02190.x, PMID:10921427

66. Philips MF, Bagley LJ, Sinson GP, et al. Endovascular thrombolysis for symptomatic cerebral venous thrombosis. J Neurosurg 1999 Jan;90(1):65-71. DOI: https://doi.org/10.3171/jns.1999.90.1.0065, PMID:10413157

67. Wasay M, Bakshi R, Kojan S, Bobustuc G, Dubey N, Unwin DH. Nonrandomized comparison of local urokinase thrombolysis versus systemic heparin anticoagulation for superior sagittal sinus thrombosis. Stroke 2001 Oct;32(10):2310-7. DOI: https://doi.org/10.1161/hs1001.096192, PMID:11588319

68. Viegas LD, Stolz E, Canhão P, Ferro JM. Systemic thrombolysis for cerebral venous and dural sinus thrombosis: A systematic review. Cerebrovasc Dis 2014;37(1):43-50. DOI: https://doi.org/10.1159/000356840, PMID:24356180

69. Averback P. Primary cerebral venous thrombosis in young adults: The diverse manifestations of an underrecognized disease. Ann Neurol 1978 Jan;3(1):81-6. DOI: https://doi.org/10.1002/ana.410030112, PMID:655656

70. Chaun H, Beckman JH, Sparling TG. Cerbral venous thrombosis in ulcerative colitis and review of the literature. Can J Gastroenterol 1991 Aug;5(4):129-32. DOI: https://doi.org/10.1155/1991/848256

71. Senchenkova E, Seifert H, Granger DN. Hypercoagulability and platelet abnormalities in inflammatory bowel disease. Semin Thromb Hemost 2015 Sep;41(6):582-9. DOI: https://doi.org/10.1055/s-0035-1556590, PMID:26270113

72. Scaldaferri F, Lancellotti S, Pizzoferrato M, De Cristofaro R. Haemostatic system in inflammatory bowel diseases: New players in gut inflammation. World J Gastroenterol 2011 Feb;17(5):594-608. DOI: https://doi.org/10.3748/wjg.v17.i5.594, PMID:21350708

73. Kornbluth A, Sachar DB. Ulcerative colitis practice guidelines in adults: American College of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol 2010 Mar;105(3):501-24. DOI: https://doi.org/10.1038/ajg.2009.727, PMID:20068560

74. Van Assche G, Dignass A, Reinisch W, et al. The second European evidence-based Consensus on the diagnosis and management of Crohn's disease: Special situations. J Crohns Colitis 2010 Feb;4(1):63-101. DOI: https://doi.org/10.1016/j.crohns.2009.09.009, PMID:21122490

75. Van Assche G., Dignass A., Bokemeyer B., et al. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 3: Special situations. J Crohns Colitis 2013 Feb;7(1):1-33. DOI: https://doi.org/10.1016/j.crohns.2012.09.005

76. Royal College of Obstetricians and Gynaecologists. Reducing the risk of venous thromboembolism during pregnancy and the puerperium, Green-Top Guideline No. 37a. London: Royal College of Obstetricians and Gynaecologists; 2015. Accessed June 19, 2020. https://www.rcog.org.uk/globalassets/documents/guidelines/gtg-37a.pdf

77. McKechnie T, Wang J, Springer JE, Gross PL, Forbes S, Eskicioglu C. Extended thromboprophylaxis following colorectal surgery in patients with inflammatory bowel disease: A comprehensive systematic clinical review. Colorectal Dis 2020 Jun;22(6):663-78. DOI: https://doi.org/10.1111/codi.14853, PMID:31490000

Keywords: cerebral veins, inflammatory bowel disease, venous thrombosis

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