Iron deficiency anemia as a risk factor for cerebral sinus venous thrombosis- a systematic review

Introduction: Cerebral sinus venous thrombosis (CSVT) is a rare but severe and potentially life-threatening neurological condition. Risk factors are manifold and include hereditary thrombophilia and systemic diseases as well as transient risk factors such as infections, trauma or neurosurgical interventions. Iron deficiency anemia (IDA) is repeatedly discussed as a risk factor for CSVT, but this assumption is mainly based on case reports. Recently published experimental data show a conclusive pathophysiology of hypercoagulability resulting from iron-restricted erythropoiesis. Specifically, the researchers found increased thrombus formation and -progression both in arterial and venous thromboses in rodents with dietary iron deficiency. Given the high prevalence of IDA in the general population and easily accessible and effective treatment options, a better understanding of its association with CSVT is of major clinical interest [1] [2] [3] [4].

Method: We systematically reviewed the literature evaluating the association of IDA and CSVT. We searched the Databases MEDLINE (PubMed) and Embase (Ovid) for available evidence up to May 30^th, 2024. We included original articles in English addressing the association of iron deficiency (ID), anemia or IDA and CSVT. We reviewed the data following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and analysed the clinical significance of the evidence according to the Cochrane Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. We registered the systematic review on PROSPERO as CRD42020205229 before starting the search.

Results: We identified 55 articles that met the inclusion criteria: four case-control-studies with 289 cases with CSVT and 3279 controls, 16 case-series and 35 case-reports. The available data from all included studies support the hypothesis of anemia being a risk factor for CSVT. Estimated risk-ratios of the case-control-studies included ranged from 1.1-4.4 in adults and 3.8-12 in children.

Conclusion: Currently available data consistently show an increased risk of CSVT in subjects with IDA. The data is generated mainly by case-control studies and case reports. We rate the evidence as low to moderate according to standardized guidelines as the effect of IDA on CSVT seems to be relevant but no randomized clinical studies are published. As the pediatric case-control studies included patients with CSVT and arterial ischemic stroke and the influence of IDA seems to be higher on CSVT than on AIS, these studies likely underestimated the effect of IDA. As untreated IDA has been associated with various adverse long-term effects and treatment is readily available and affordable, this association further highlights the importance of early diagnosis and management of IDA.

Conflict of Interest:

The authors state no conflicts of interest.

• References

• 1 Stolz E, Valdueza JM, Grebe M, Schlachetzki F, Schmitt E, Madlener K. et al. Anemia as a risk factor for cerebral venous thrombosis? An old hypothesis revisited. Results of a prospective study. J Neurol 2007; 254 (06) 729-34
• 2 Coutinho JM, Zuurbier SM, Gaartman AE, Dikstaal AA, Stam J, Middeldorp S. et al. Association Between Anemia and Cerebral Venous Thrombosis: Case-Control Study. Stroke. 2015; 46 (10) 2735-40 hers
• 3 Maguire JL, deVeber G, Parkin PC.. Association between iron-deficiency anemia and stroke in young children. Pediatrics. 2007
• 4 Azab SF, Abdelsalam SM, Saleh SH, Elbehedy RM, Lotfy SM, Esh AM. et al. Iron deficiency anemia as a risk factor for cerebrovascular events in early childhood: a case-control study. Ann Hematol 2014; 93 (04) 571-6

Publication History

Article published online:
13 February 2025