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Abstract

Hematologic diseases are considered important contributors to cerebral venous sinus thrombosis (CVST) cases. This retrospective study aims to compare the difference of the clinical and radiological characters between CVST patients with and without hematologic diseases. Consecutive hospitalized CVST patients with hematologic disorders constituted the hematologic disorder group, while that without identifiable risk factors comprised the control group in this study. We systematically documented the various types of hematologic diseases associated with CVST, along with laboratory tests. Clinical manifestations, imaging findings, as well as treatment and prognosis, were recorded. A comparative analysis was conducted between the hematologic disorder group and the control group based on the aforementioned parameters. The final analysis included 97 CVST cases associated with hematologic diseases and 65 cases without any identified risk factors. The spectrum of hematologic diseases in our study ranged from iron-deficiency anemia to acute leukemia. Patients with hematologic disorder showed higher admission mRS, greater thrombotic burden, and higher incidence of stroke and cerebral hemorrhage (p < 0.05). The use of batroxobin significantly improved the prognosis of CVST caused by hematologic diseases, without causing major bleeding or death during the follow-up period. Patients with hematologic disorders who develop CVST tend to present with more severe conditions compared to those without identifiable risk factors. It is essential to conduct timely screening for CVST in patients with hematologic diseases who present with risk factors of thrombosis.

Keywords

hematologic diseases cerebral venous sinus thrombosis batroxobin stroke platelet

Introduction

Approximately 85% of patients with cerebral venous sinus thrombosis (CVST) have either a prothrombotic risk factor or a direct cause identified.¹ Except for thrombophilia, autoimmune diseases, infections, malignancies, severe dehydration, and trauma, hematologic disorders also may associate with development of CVST. These disorders,² range from mild conditions like iron-deficiency anemia to more severe, life-threatening conditions such as lymphoma.^3-5 However, our understanding of the spectrum of hematologic diseases associated with CVST remains incomplete.

Hematologic diseases often lead to abnormal synthesis or altered morphology of various blood cell types, which may play a crucial role in thrombus formation. Nevertheless, it is still unclear how these pathological changes in blood cells influence the characteristics, presentation, response to treatment, and prognosis of CVST in patients with hematologic disorders compared to those without such disorders.

This retrospective study aims to compare these differences in patients with CVST associated with hematologic diseases against those without, thereby providing a clearer understanding of how hematologic disorders may affect the clinical outcomes of CVST.

Method

Study Population

In this study, we focused on hospitalized patients due to the need for detailed and comprehensive hematological evaluations and imaging results. Eligible patients who were clinically suspected of having CVST and also had hematologic disease constituted the hematologic disorder group, while patients with CVST but without any identified risk factors formed the control group. All patients were consecutively enrolled in this real-world self-control study from July 2019 through August 2023 at Xuanwu Hospital, Capital Medical University, China, after providing informed consent. Upon admission, contrast-enhanced magnetic resonance venography (CE-MRV) and magnetic resonance black-blood thrombus imaging (MRBTI) were performed to identify patients with CVST. Inclusion in the hematologic disorder group required definitive diagnoses made by hematologists. Patients were further classified according to specific types of hematologic diseases. Key inclusion criteria for the study included individuals aged <80 years, confirmation of CVST through MRBTI, first-time occurrence of CVST, a confirmed diagnosis of hematologic disease, agreement to participate in follow-up, and no gender preference.

Exclusion criteria applied to individuals who were pregnant, had indications for or contraindications against contrast medium, experienced major bleeding, had diseases causing pachymeningeal enhancement (eg idiopathic intracranial hypertension or cerebrospinal fluid (CSF) hypovolemia), suffered from craniotomy, temporal arteritis, cavernous sinus dural arteriovenous fistula, iatrogenic causes (including intrathecal chemotherapy and shunt placement), neoplastic diseases, chronic subdural hematoma, and hypertrophic pachymeningitis, as determined through medical history and detailed tests including opening pressure (lateral decubitus) and CSF analysis. Conditions such as infections and autoimmune diseases can trigger systemic inflammatory responses, leading to platelet activation and influencing platelet reactivity.⁶ This activation may impact the severity and prognosis of CVST,⁷ potentially confounding the comparison between the hematologic disorder group and the control group in subsequent analyses. Therefore, patients with infections or autoimmune diseases were excluded to minimize these confounding effects. Additionally, patients were excluded if they had a poor prognosis unrelated to sinus thrombosis, defined as cases where the primary cause of poor outcomes stemmed from severe health conditions or comorbidities (such as advanced malignancies, multi-organ failure, or severe systemic infections), rather than from CVST itself. Patients who discontinued anticoagulation for any reason during the follow-up period were also excluded. The trial protocol was approved by appropriate regulatory and ethical authorities at the ethics committee of Xuanwu Hospital, Capital Medical University. Signed informed consent were obtained from the patients or their legally authorized representative.

All patients underwent standard anticoagulation therapy, with the option of endovascular treatment as deemed appropriate. Dabigatran was administered in the form of 150-mg capsules, taken twice daily. Rivaroxaban was provided as individual doses of 10-mg or 20-mg capsules, to be taken once daily. Warfarin was prescribed as 1-mg, 3-mg, or 5-mg tablets, taken once daily. Dosages of warfarin were adjusted as necessary to maintain a target international normalized ratio (INR) range of 2.0 to 3.0. The duration of anticoagulation varied depending on the presence of risk factors, with patients without risk factors receiving a six-month course and those with risk factors undergoing anticoagulation for an extended period. Patients with both hematologic disease and CVST received standard treatment for the specific hematologic disease.

Laboratory Examinations

Patients included in the study underwent comprehensive laboratory examinations, which encompassing complete blood counts (hemoglobin, white blood cells, platelets, neutrophils), inflammation markers (erythrocyte sedimentation rate, C-reactive protein), coagulation-related indicators (activated partial thromboplastin time, D-dimer, fibrinogen), thrombophilia-related markers (protein C/S, antithrombin III), immune-related markers (anti-phospholipid antibodies, anti-nuclear antibodies), thyroid function (thyroxine, thyroid globulin antibodies), and CSF analysis (white blood cells, blood cells, IgA, IgG). Based on these findings, patients with concomitant infections, autoimmune diseases, or pregnancy-related factors and other risk factors were excluded. Detailed records were maintained for hematological indicators, such as red blood cells, white blood cells, platelets, C-reactive protein, IL-6, as well as cerebrospinal fluid-related markers, including IgA and cerebrospinal fluid white blood cells. A comparative analysis of these indicators was performed between the hematologic disorder group and the control group.

Imaging Assistant Examination

Two blinded and independently experienced neurologists assessed all baseline and follow-up neuroimaging. MRBIT and CE-MRV were scrutinized to identify the presence and location of thrombosis. Cranial MRI and DWI were employed to detect the occurrence of stroke or cerebral hemorrhage. Additionally, the thrombus location in the enrolled patients was recorded, including the superior sagittal sinus, transverse sinuses, sigmoid sinuses, and internal jugular veins. The number of thrombotic venous sinuses documented as thrombosis burden. A comparative analysis was conducted between the control group and the hematologic disorder group for the number of affected venous sinuses, the incidence of stroke, and the occurrence of cerebral hemorrhage. Furthermore, within various subgroups of hematologic disorder patients, comparisons were made regarding the number of involved venous sinuses, the rates of cerebral hemorrhage, and the occurrence of stroke.

Follow up

A schematic illustration of the study design is depicted in Figure 1, delineating the participant flow throughout the study. Upon confirmation of CVST, all patients were administered standard anticoagulation therapy, which included rivaroxaban, dabigatran, or warfarin. In addition to anticoagulation, a subset of patients was administered 10 IU or 5 IU of batroxobin every other day, with doses adjusted based on fibrinogen levels and body weight. Patients eligible for thrombolysis or thrombectomy underwent interventional procedures within the designated time window, followed by routine administration of standard anticoagulant doses postoperatively.

Figure 1.

Flowchart of this study.

Scheduled follow-up visits were conducted at 6 months and at the end of 12 months. During these follow-up visits, comprehensive assessments were performed, primarily focusing on the evaluation of clinical symptoms. Clinical symptoms were measured using the modified Rankin Scale (mRS). Baseline mRS scores were recorded at admission and again during follow-up. An excellent functional outcome was defined as a reduction in mRS score from baseline.

Statistical Analysis

All data were checked for normality using the Shapiro-Wilk test, with a significance level set at 0.05. Additionally, Q-Q plots were used for visual assessment of normality. Based on the results, parametric or non-parametric tests were applied accordingly. Descriptive statistics were calculated for all data, all the values in the text and tables were presented as mean standard deviation (mean ± SD) and analyzed with Student t-test or ANOVA univariate test. Linear-regression analysis was used to compare baseline mRS, repeat mRS in each group. Binary logistic regression was used to analyzed influence factor of incidence of stroke and cerebral hemorrhage after adjusting for confounding factors such as age and gender. Other categorical variables were reported as numbers, and analyze by Chi-square test or Fisher exact test，Two-sided p-values of <0.05 were considered statistically significant. All statistical analyses were performed using the SPSS version 21.0 for Windows.

Result

Study Population and Clinical Features

Out of the 121 patients initially screened, 9 were excluded due to unclear diagnosis, 15 lacked specific blood data, 3 were excluded due to the absence of imaging data, 4 patients withdrew from the study due to life-threatening hematologic diseases, and the remaining patients were excluded for incomplete test results or refusal to sign the informed consent form. Ultimately, 97 patients were enrolled in the hematologic disorder group, and 65 patients were included in the control group.

Within the hematologic disorder group, the mean (SD) age was 40.19 (13.24) years, with 31 (32.0%) participants being male. In the control group, the mean (SD) age was 45.62 (16) years, and 32 (49.2%) participants were male. All participants underwent CE-MRV and MRBTI as required by the protocol.

Common clinical symptoms include headaches, visual impairment, vomiting, dizziness, and seizures. After adjusting for confounders, hematologic patients remained significantly more likely to experience headaches (p < 0.01) and seizures (p = 0.034) compared to CVT patients without identifiable risk factors. Table 1 summarizes the main baseline characteristics for the entire study population in both groups.

Table 1.

Demographic and Clinical Characteristics of CVST Patients with Hematologic Disorders and That Without any Risk Factors.

	Hematologic Group(n = 97)	Control Group(n = 65)	P Value
Gender(male)(n,%)	31 (32.0)	32(49.2)	0.033*
Age (mean ± SD)	40.19 ± 13.24	45.62 ± 16.00	0.037*
Clinical symptoms n,(%)
Headache (n,%)	89(91.8)	41(63.1)	<0.001*
Vomiting (n,%)	17(17.5)	8(12.3)	0.506
Visual impairment (n,%)	39(40.2)	20(30.8)	0.247
Dizziness (n,%)	10(10.3)	15(23.1)	0.044*
Seizures (n,%)	18(18.6)	4(6.2)	0.034*
Venous infarction (n,%)	27(27.8)	3(4.6)	0.001*
Cerebral hemorrhage (n,%)	13(13.4)	2(3.1)	0.028*
Location of thrombosis (n,%)
Left transverse sinus (n,%)	49(50.5)	37(56.9)	0.521
Left sigmoid sinus (n,%)	42(43.3)	22(33.8)	0.254
Right transverse sinus (n,%)	53(54.6)	26(40.0)	0.079
Right sigmoid sinus (n,%)	48(49.5)	17(26.2)	0.053
Superior sagittal sinus (n,%)	60(61.9)	17(26.2)	<0.001*
Inferior sagittal sinus (n,%)	3(3.1)	4(6.2)	0.440
Vein of Galen (n,%)	5(5.2)	1(1.5)	0.403
Straight sinus (n,%)	18(18.6)	5(5.2)	0.066
Left internal jugular vein (n,%)	18(18.6)	12(18.4)	1.000
Right internal jugular vein (n,%)	21(21.6)	10(15.3)	0.416
Cortical vein (n,%)	12(18.4)	5(5.2)	0.303
Hemoglobin (g/L)	124.74	139.65	0.001*
Platelet (L)	372.03	225.15	<0.001*
White blood cell (*10⁹)	6.93	6.15	0.069
IL-6 (pg/ml)	5.24	4.22	0.035*
C reactive protein (mg/L)	4.52	2.11	0.094
CSF-IgA (mg/dl)	0.37	0.38	0.653
Admission mRS(mean ± SD）	2.27 ± 1.46	2.36 ± 0.80	0.042*
Follow-up mRS(mean ± SD）	1.42 ± 1.59	1.06 ± 0.77	0.880

*p < 0.05 (ANOVA test or T student test).

Comparison in Hematologic Disease Cohort

Patients with hematologic disease were categorized into subgroups based on specific conditions: anemia group (26 patients with iron-deficiency anemia, 3 patients with aplastic anemia, 2 patients with autoimmune hemolytic anemia), myeloproliferative neoplasms(MPN) group(51 patients), thrombocytopenia group(7 patients), paroxysmal nocturnal hemoglobinuria(PNH) group(3 patients), and abnormal bone marrow proliferation group.

The myeloproliferative neoplasms group consisted of primary myelofibrosis(6 patients), essential thrombocythemia(40 patients), and polycythemia vera(5 patients). The abnormal bone marrow proliferation group included myelodysplastic syndromes(MDS)(2 patients), acute lymphoblastic leukemia(ALL)(1 patient), acute myeloid leukemia and (AML) (1 patient) and non-Hodgkin lymphoma(1 patient) (Figure 2).

Figure 2.

Hematologic disorders can lead to CVST.

In particular, patients with hematologic disorders frequently exhibit platelet and hemoglobin abnormalities. Adjusted regression analysis controlling for age and gender revealed that thrombosis burden is not significantly influenced by platelet and hemoglobin levels (all p > 0.05). However, adjusted regression analysis demonstrated that the incidence of stroke and cerebral hemorrhage remained significantly associated with platelet counts (p < 0.05), and admission mRS was still correlated with the occurrence of stroke and cerebral hemorrhage (p < 0.01).

In addition, patients with different hematologic diseases display notable differences in the incidence of stroke and cerebral hemorrhage (p = 0.019 and p = 0.006), with patients experiencing thrombocytopenia showing a higher susceptibility to cerebral hemorrhage. Due to the limited inclusion of patients with PNH, AML and ALL, our analysis focused on anemia, MPN, and thrombocytopenia, which represent the three most prevalent hematologic disorders in this cohort.

Anemia

Among the enrolled patients, the median hemoglobin level was 96.86 g/L, and the median platelet count was 247.14 g/L. Notably, four patients maintained a stable hemoglobin level at enrollment due to ongoing regular treatment. According to hemoglobin level, 16 patients were diagnosed with mild anemia, and 19 patients with moderate anemia; no cases of severe anemia were noted in this group. Additionally,14 cases exhibited an elevation in platelet count.

Eleven patients (50%) suffered a stroke, while four patients (18.18%) experienced cerebral hemorrhage. The median baseline mRS was 2.5 ± 2.91. Among the sixteen patients who underwent follow-up, the median MRS after follow-up was 1.94 ± 2.08. No deaths occurred during the follow-up period, but one patient experienced recurrent CVST.

Furthermore, during the analysis of the assistant examination, it was observed that the admission mRS increases with rising platelet levels (p < 0.01). However, there was no correlation between thrombosis burden and hemoglobin or platelet count. In the analysis of events affecting neurologic function, such as stroke and cerebral hemorrhage, an association was found between platelet level and the incidence of stroke (p = 0.044), while the occurrence of cerebral hemorrhage showed no significant correlation with platelet and hemoglobin levels (all p > 0.05).

Myeloproliferative Tumor

Fifty-seven patients were diagnosed with myeloproliferative neoplasms, with 24 patients (42.1%) being male and an average age of 40.32 ± 11.76 years. The median hemoglobin level was 141.43 g/L, and the median platelet count was 466.47 g/L. The median baseline MRS was 2.14 ± 1.39. Among the 37 patients who underwent follow-up, the median MRS after follow-up was 1.02 ± 1.04. No deaths were reported either; however, 4 patients experienced recurrent CVST. Additionally, it was observed that increased platelet levels is associated with more sever thrombosis burden (p = 0.035) and a higher baseline mRS (p = 0.031) respectively.

In particular, 10 patients (17.5%) experienced stroke, and 5 patients (8.8%) with cerebral hemorrhage. However, platelet and hemoglobin levels were found to have no influence on the occurrence of these adverse events.

It is noteworthy that among patients with primary thrombocytosis, 15 patients who underwent bone marrow aspiration showed a positive JAK2 gene. Patients with a positive JAK2 gene exhibited higher platelet levels than those without the gene (p < 0.01). Moreover, JAK2-positive patients had a higher mRS compared to those who are JAK2 negative(p < 0.01).

Thrombocytopenia

Seven patients were diagnosed with thrombocytopenia. Among them, four patients (57.14%) were male, with a median age of 43.29 ± 12.72. The median hemoglobin level was 130 g/L, and the median platelet count was 109.67 g/L. Three patients were diagnosed with immune thrombocytopenic purpura (ITP). The remaining 4 patients did not have a clearly identified etiology.

In this cohort, two patients experienced stroke, while three patients had cerebral hemorrhage. The median baseline mRS was 2.71 ± 1.57. Among the six patients who underwent follow-up, the median mRS was 1.50 ± 1.64, and no current CVST was reported. It is noteworthy that, the thrombosis burden, as well as the incidence rates of stroke and cerebral hemorrhage, are not associated with abnormal alterations in hemoglobin and platelet levels (p > 0.05).

Clinical Follow up

In the entire hematologic disorder cohort, the baseline mRS score was 2.28 ± 1.46 (1–5) at the time of enrollment, hemoglobin and platelet levels were unrelated to increase of baseline mRS after adjusting for gender and age(p > 0.05).

During the 12.71 ± 1.25 months of the follow-up period, a total of 67 patients completed the follow-up with a median mRS score of 1.42 (0–6). The average hemoglobin level was 129 mg/L, and the average platelet count was 364 mg/L at follow-up. All of them received standardized and long-term anticoagulation, besides, fifty patients received batroxobin. Despite all patients receiving specialized hematologic treatment, only 46 patients achieved optimal control of their hematologic disorders. No deaths were reported during the follow-up period, but 12 patients experienced recurrent CVST.

The follow-up mRS was unrelated to hemoglobin levels (p = 0.079) and platelet counts (p = 0.722) but was associated with the use of batroxobin (p = 0.033) after adjusting for confounding factors.

In addition, patients showed no significant alterations in hemoglobin, platelet, and white blood cell counts after batroxobin administration. Importantly, none of the patients who received batroxobin experienced major bleeding, even in the presence of hemorrhagic hematologic disorders.

Comparison Between Patients with Hematologic Disease and That Without Risk Factors on CVST

Firstly, significant differences were observed in age and gender between the two groups (all p < 0.05). Patients in the hematologic disease group had a lower average age (40.19 ± 13.24 vs 45.62 ± 16.00, p = 0.037) and a smaller proportion of male patients (32% vs 49.2%, p = 0.033). After adjusting for confounding factors such as age and gender, we found that patients with hematologic diseases were more likely to involve multiple venous sinuses in the formation of venous sinus thrombosis (3.30 ± 1.550 vs 2.32 ± 1.239, p = 0.000). However, no significant differences were observed in the preferred thrombosis locations such as transverse sinus and sigmoid sinus between the two groups (all p > 0.05). The number of patients with cortical venous thrombosis also showed no significant difference (p = 0.303). Notably, patients with hematologic diseases had a significantly higher incidence of superior sagittal sinus thrombosis compared to the control group (p < 0.001) (Table 1）.

Moreover, the admission mRS of patients with hematologic diseases was higher than that of the control group (p = 0.042, 2.27 ± 1.46 vs 2.36 ± 0.80). However, there was no significant difference in the follow-up mRS comparison (p = 0.880, 1.42 ± 1.59 vs.1.06 ± 0.77). The occurrence of stroke and cerebral hemorrhage were also significantly higher in patients with hematologic diseases than in those without risk factors (all p < 0.05).

In the results of laboratory examination, we found no significant differences in white blood cell count, C-reactive protein, and CSF IgA between patients with hematologic disorders and the control group (all p > 0.05). However, the average value of IL-6 in patients with hematologic diseases was 5.24 ± 3.45 pg/ml, while the average value of IL-6 in the control group was 4.22 ± 3.93 pg/ml, showing a significant difference between the two groups (p = 0.035).

Discussion

Our study highlights significant differences in the clinical characteristics, presentation, treatment response, and prognosis of patients with CVST who have concomitant hematologic disorders versus those without such conditions. In our cohort of patients with CVST and concomitant hematologic disorders, a diverse range of hematologic conditions was observed, including anemia, myeloproliferative neoplasms, MDS, thrombocytopenia, lymphoma, acute leukemia, and paroxysmal nocturnal hemoglobinuria. And these patients showed more severe clinical presentations and greater thrombosis burden compared to those without hematologic disorders. This suggests that hematologic disorders play a significant role in exacerbating the severity of CVST.

Factors Contributing to Higher mRS Scores in CVST Patients with Hematologic Disorders

Our study revealed a significantly higher mRS score in patients with CVST who also have hematologic disorders compared to those without relevant risk factors. We propose that this difference may arise from several factors. First, it may be related to a higher thrombus burden. Existing research has established a correlation between thrombus burden and disease severity.^8-10 Furthermore, our imaging findings confirm that patients with hematologic disorders exhibit a significantly greater thrombus burden than the control group.

Secondly, our cohort showed a higher incidence of superior sagittal sinus thrombosis among patients with hematologic disorders. The involvement of the superior sagittal sinus, a major cerebral venous sinus, is frequently associated with bilateral brain injury, which can lead to more severe clinical symptoms and poorer outcomes.¹¹ However, the underlying mechanisms for the increased risk of superior sagittal sinus involvement in CVST among patients with hematologic disorders remain unclear and warrant further investigation. Thirdly, prior studies have suggested that thrombosis in the superior sagittal sinus may increase the risk of stroke, contributing to neurological deficits.¹¹ Our findings corroborate this, as the incidence of stroke and cerebral hemorrhage was indeed higher in patients with hematologic disorders compared to the control group. Consequently, patients with hematologic disorders are more likely to experience neurological deficits, whereas many patients in the control group exhibit CVST without such deficits. This discrepancy may also account for the higher mRS scores observed in the hematologic disorder group.

However, there was no significant difference in mRS scores between the two groups at follow-up, suggesting that standardized anticoagulant therapy effectively mitigates long-term neurological outcomes in both groups.

Inflammation and Platelet Abnormalities in CVST Severity Among Hematologic Disorders

The study indicates that the greater severity of CVST and increased thrombosis burden in patients with hematologic disorders may be linked to inflammation and platelet abnormalities. Although laboratory findings showed no significant differences in white blood cell count, C-reactive protein levels, or cerebrospinal fluid IgA levels between the two groups, the IL-6 levels were significantly higher in the hematologic disorder group.

This finding aligns with previous research highlighting the contribution of inflammation to the pathogenesis of CVST,^12,13 also, elevated IL-6 levels may serve as a potential biomarker for more aggressive disease and poorer prognosis of CVST.⁷ These findings suggest that the inflammatory response may play a more prominent role in the greater severity of CVST observed in these patients. Additionally, this warrants further exploration of anti-inflammatory treatments as adjunctive therapy for these patients.

Current studies investigating the mechanisms of other hematologic disorders indicate that abnormalities in platelet function or quantity may be a widespread pathological phenomenon. In iron-deficiency anemia, reactive thrombocytosis is a common compensatory response to iron deficiency.^14,15 Additionally, iron-deficiency anemia may adversely affect endothelial function, leading to endothelial damage.¹⁵ This endothelial dysfunction can promote platelet adhesion and aggregation, further contributing to the risk of thrombus formation.¹⁶ In myeloproliferative disorders, patients frequently exhibit spontaneous platelet aggregation and leukocyte-mediated platelet activation, further promoting thrombus formation.^17,18 Notably, patients with JAK2 mutations show significantly increased platelet and leukocyte activity, correlating with higher thrombus burden and elevated mRS in our cohort.^19-23

Although cases of PNH were less frequent in our study, prior research has identified platelet activation as a significant contributor to the increased thrombotic risk associated with PNH.^24,25 Even in thrombocytopenic conditions such as immune ITP, patients exhibit a significantly elevated thrombotic risk despite lower platelet counts. This increase is attributed to platelet-derived microparticles, which induce platelet adhesion and aggregation through the release of adenosine diphosphate (ADP) and membrane phospholipids, leading to thrombus formation.^26,27

Overall, abnormalities in platelet function and quantity play a crucial role in patients with CVST related to hematologic disorders. Whether through increased platelet counts, enhanced aggregation, or the formation of platelet-derived microparticles, these abnormalities contribute to heightened thrombus formation and increased complexity of the disease (Figure 3). Therefore, we hypothesize that abnormalities in platelet function and quantity may be core factors leading to the exacerbation of disease severity and increased thrombus burden in CVST patients.

Figure 3.

Mechanism of CVST caused by different hematologic diseases.

Additionally, it is noteworthy that hematologic malignancies, such as AML, non-Hodgkin lymphoma, MDS, and ALL, are known to increase thrombotic risk. However, in our study, the frequency of bleeding events exceeded that of thromboembolic events in all malignancy cases except for non-Hodgkin lymphoma.²² This finding suggests a complex relationship between hematologic malignancies and hemostatic mechanisms, indicating the need for further research to explore these dynamics in greater depth.

Treatment Therapy of CVST Caused by Hematologic Disorders

In all patients with hematologic disorders, standard doses of anticoagulants were administered, with 50 patients receiving batroxobin and 14 patients undergoing thrombolysis or thrombectomy procedures. The majority of patients demonstrated favorable prognoses.

Patients with hematologic disorders, often characterized by abnormalities in blood cells such as reduced platelet or red blood cell counts, are managed cautiously with anticoagulant therapy. However, our study revealed that prognosis was not directly related to hemoglobin and platelet levels. In other words, the type of hematologic disorder did not appear to significantly impact the prognosis of CVST. The key factor influencing the prognosis of CVST appears to be the timely implementation of appropriate treatments. Therefore, timely initiation of CVST-specific treatments is essential for patients with both hematologic disorders and CVST.

Some studies have suggested that combining Batroxobin, a defibrinogenating agent, with anticoagulation may increase the risk of hemorrhage.²⁸ However, in our study, no Batroxobin-induced hemorrhage was observed, even in patients with lower platelet levels. Additionally, Batroxobin significantly affects blood cell counts (red blood cells, white blood cells, and platelets), suggesting that the prognosis of patients with hematologic disorders was not adversely impacted. Therefore, the combination of Batroxobin and anticoagulation appears to be a safe option for patients with both CVST and hematologic disorders. Batroxobin primarily accelerates recanalization in CVST by reducing fibrinogen levels and promoting thrombolysis, without significantly affecting platelets or blood cells.²⁸

Limitation

This study has several limitations. First, as a single-center, retrospective study, our data collection may be subject to selection bias and various uncontrolled factors. Additionally, we were unable to fully control for all potential confounding factors, including baseline health status, medication histories, and physiological differences among patients. These uncontrolled variables could have affected the observed associations between hematologic disorders and CVST severity, potentially leading to biased estimations of thrombotic burden, incidence of complications like stroke or hemorrhage, and functional outcomes measured by the mRS. For instance, patients with more severe underlying health conditions or those on certain medications may be predisposed to worse CVST outcomes, independent of their hematologic status. Consequently, these confounders could compromise the accuracy and generalizability of our findings. Future studies should aim to use larger, multi-center cohorts with rigorous confounder control to better isolate the specific impact of hematologic disorders on CVST progression and prognosis. Second, the limited number of patients with specific hematologic disorders, such as ALL, restricted our ability to thoroughly analyze differences in the severity of CVST among various hematologic conditions. Third, we did not do conduct a detailed analysis of CVST recanalization during follow-up period, leaving the relationship between the severity of hematologic disorders and the rate of recanalization unclear. Further prospective studies are necessary to address these gaps and provide a more comprehensive understanding of these associations.

Conclusion

Hematologic disorders, including iron-deficiency anemia and primary thrombocytosis, acute leukemia, lymphoma, and paroxysmal nocturnal hemoglobinuria, may be linked to the development of CVST. Notably, patients with CVST and hematologic disorders frequently exhibit more severe clinical manifestations and greater thrombosis burden compared to those without identifiable risk factors. Future research should explore targeted therapies that address these specific blood abnormalities may help improve outcomes in this patient population.

Footnotes

Abbreviations

Authors’ Contributions

Xiangqian Huang and Mengqi Wang wrote the first draft of the manuscript; Ran Meng and Xunming Ji contributed to imaging assessments; Ran Meng and Yuchuan Ding wrote sections of the manuscript and contributed to manuscript revision.

Availability of Data and Materials

All data generated or analysed during this study are included in this published article.

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Ethics Approval and Consent to Participate

This research was conducted according to institutional and national policies. Written informed consent was obtained from all individual or guardian participants. Ethical approval was waived by the Research Ethics Committee of Xuanwu Hospital, Beijing, China in view of the retrospective nature of the study and all the procedures being performed were part of the routine care, and this study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the the National Natural Science Foundation of China [grant numbers 82171297, 82101390] and Changsha Natural Science Foundation [grant number kq2202498].

ORCID iD

Ran Meng

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The Impact of Hematologic Disorders on the Severity of Cerebral Venous Sinus Thrombosis: A Comparative Study

Abstract

Keywords

Introduction

Method

Study Population

Laboratory Examinations

Imaging Assistant Examination

Follow up

Statistical Analysis

Result

Study Population and Clinical Features

Comparison in Hematologic Disease Cohort

Anemia

Myeloproliferative Tumor

Thrombocytopenia

Clinical Follow up

Comparison Between Patients with Hematologic Disease and That Without Risk Factors on CVST

Discussion

Factors Contributing to Higher mRS Scores in CVST Patients with Hematologic Disorders

Inflammation and Platelet Abnormalities in CVST Severity Among Hematologic Disorders

Treatment Therapy of CVST Caused by Hematologic Disorders

Limitation

Conclusion

Footnotes

Abbreviations

Authors’ Contributions

Availability of Data and Materials

Declaration of Conflicting Interests

Ethics Approval and Consent to Participate

Funding

ORCID iD

References