Incidence of thrombosis in children with tunneled central venous access devices versus peripherally inserted central catheters (PICCs)

Introduction

The recent proliferation of deep vein thrombosis in children has been attributed to the increased use of central venous catheters, specifically tunneled lines and peripherally inserted central catheters. A formal comparison of the incidence rate for deep vein thrombosis between tunneled lines and peripherally inserted central catheters has not been undertaken.

Methods

Children < 18 years of age who were admitted to Children’s Hospital Los Angeles from July, 2005 to July, 2012 were eligible for inclusion. Data were extracted from the hospital discharge database which includes data on all procedures and up to 20 diagnoses per admission. Diagnoses and procedures were identified by International Classification of Disease, Ninth Revision coding. Patients were excluded if they received more than one central line. Data collected included type of central line, deep vein thrombosis event, and underlying medical illnesses classified according to chronic complex conditions.

Results

Over the seven year study period there was an overall rate of 73 deep vein thromboses per 10,000 hospital discharges. Of the 6915 eligible subjects, 181 had a deep vein thrombosis for an overall incidence rate of 2.6%. There were 152 thrombi (2.6%) in subjects with peripherally inserted central catheters and 29 thrombi (3.1%) in subjects with tunneled lines [OR = .83 (0.55, 1.29), p = 0.38].

Conclusion

Despite the relative ease and simplicity of use of peripherally inserted central catheters leading to a substantial rise in their use, this study demonstrates that such lines pose a substantial risk for venous thrombosis and no difference in incidence was detected between such lines and tunneled lines.     

Who are at risk for thromboembolism after arthroplasty? A systematic review and meta-analysis

Background

Thromboembolism, including deep venous thrombosis and pulmonary embolism, is a grave threat to patients undergoing total joint replacement. Using a systematic review and meta-analysis we asked whether gene mutations or polymorphisms could be risk factors for thrombosis after arthroplasty.

Methods

We performed a comprehensive search of Medline, PubMed, Embase, Cochrane databases, China National Knowledge Infrastructure (CNKI), and Google Scholar, and identified 19 studies detailing genetic investigations of patients with thromboembolism following joint replacement.

Results

Our meta-analyses included 5149 patients who underwent arthroplasty surgery. Significant associations with venous thromboembolism were identified for factor G1691A (odds ratio (OR) 1.41, 95% confidence interval (CI) 1.03 - 1.94, p = 0.03), prothrombin G20210A (OR 2.16, 95% CI, 1.27- 3.69, p = 0.005), and MTHFR/C677T/TT (OR 2.36, 95% CI 1.03 - 5.42, p = 0.04) in Caucasian populations. No significant gene mutation was identified in Asian populations.

Conclusion

This study suggests a way to identify patients scheduled for arthroplasty who are at higher risk of thrombosis, enabling individualized treatment.     

Cerebral venous thrombosis and myeloproliferative neoplasms: Results from two large databases

Introduction

Myeloproliferative neoplasms (MPNs) include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Patients with MPNs are prone to develop arterial and venous thrombosis either at diagnosis or during follow-up; in particular splancnic vein is strongly associated with MPN. Conversely, presence of MPN is uncommon in patients with deep vein thrombosis of the lower extremities and with pulmonary embolism. Only few studies with conflicting results have evaluated the prevalence of an underlying MPN in patients with cerebral venous thrombosis (CVT), and limited evidence exists on the incidence of CVT in patients with established MPN.

Methods

We assessed the frequency of MPNs in a series of 706 patients with cerebral vein thrombosis (CVT) and the frequency of CVT in a cohort of 2,143 MPNs patients.

Results

Twenty-seven CVT patients (3.8%) were diagnosed with MPN: 9 before CVT (1.3%), 4 concomitantly (0.6%), and 14 after CVT (2.0%). Nine CVT cases (0.4%) were diagnosed in the MPN cohort, with a slightly higher frequency in PV (five of 735, 0.7%) than in ET (three of 964, 0.3%) and in PMF (one of 444, 0.2%).

Conclusion

Considering the analyses of these databases jointly, the results obtained suggest a weak association between CVT and MPNs and ultimately suggest that a thorough investigation looking for an underlying MPN may not be warranted in all the patients with CVT without overt myeloproliferative features.     

Haplotypes of TAFI gene and the risk of cerebral venous thrombosis - a case-control study

Introduction

Cerebral venous thrombosis (CVT) is an uncommon disease with some differences compared to other-site thrombosis, including a higher frequency in young people, female sex and oral contraceptive users. Thrombin-activatable fibrinolysis inhibitor (TAFI) is a regulator of fibrinolysis, whose levels are genetically controlled and its increase is associated to thrombosis. Our objective was to investigate in a case-control study the association between CVT and TAFI single nucleotide polymorphisms (SNPs) and its haplotypes in comparison to other-site venous thrombosis and controls.

Materials and Methods

Seventy two patients with CVT were compared to 143 individuals with no history of thromboembolic events (control group) and to 128 patients with deep vein thrombosis in the limbs and/or pulmonary embolism (venous thromboembolism-VTE group). SNPs were genotyped by restriction fragment length polymorphism or allele-specific PCR for F2 20210G > A, F5 1691G > A, TAFI (-1053C > T, -438G > A, 505G > A, 1040C > T and + 1542C > G).

Results

The GTC haplotype for TAFI 505G > A/1040C > T/+ 1542C > G SNPs was associated with an increased risk of CVT compared to controls [odds ratio (OR) 2.67, 95% confidence interval (CI): 1.13 - 6.34) and VTE group (OR 2.51, 95%CI: 1.07 - 8.06). The CVT risk became even more pronounced when evaluating unprovoked or hormone-related thrombosis cases: CVT compared to controls (OR 3.24, 95%CI: 1.19 - 8.82) and VTE group (OR 4.32, 95%CI: 1.27 - 14.63).

Conclusions

Our data indicate that the GTC haplotype for TAFI 505G > A/1040C > T/+ 1542C > G SNPs increased the risk of CVT in comparison to controls and VTE cases. Further studies are required to confirm our findings.     

Subarachnoid and intra-cerebral hemorrhage in young adults: Rare and underdiagnosed

Objectives

Convexity subarachnoid and intra-cerebral hemorrhages, in patients aged < 50 years, are always a diagnostic challenge. This condition is characterized by acute headaches with or without neurological symptoms and/or seizures, and by the radiological demonstration of subarachnoid and/or intra-cerebral hemorrhages and, more rarely, by the association of ischemic events.

Patients and methods

In a prospective series of 30 consecutive patients (median age 31 years; 22 women) with a subarachnoid and intra-cerebral hemorrhages, 19 were diagnosed with reversible cerebral vasoconstriction syndrome (RCVS), 7 with cerebral venous sinus thrombosis (CVST), and 4 with a bleeding mycotic aneurysm (MA).

Results

RCVS appeared spontaneously in 16 patients and was related to the postpartum period in three cases. Subarachnoid hemorrhage (SAH) was demonstrated in 24 patients as follows: 18 cases were in cortical areas, 4 were in the polygon of Willis, one was inter-hemispheric, and one was inter-hemispheric/intra-cerebral. A convexity pure intra-cerebral hemorrhage (ICH) was recorded in 6 cases. Among the 7 patients suffering from CVST, the superior sagittal sinus was involved in 4 cases, the transverse sinuses (TS) in 2, and the TS plus sigmoid sinus (SS) in one.

Conclusion

The three most common causes in this series were RCVS, followed by CVST and bleeding from MA. Because of atypical clinical or radiological presentations, this large spectrum of etiologies can cause diagnostic difficulties. Therefore, careful analysis is needed to ensure correct and prompt diagnosis and to avoid any dangerous delays in management.     

High prevalence of recurrent thrombosis in subsets of cancer patients with isolated gonadal vein thrombosis: A single center retrospective study

Purpose

Cancer patients are a high-risk population for venous thromboembolism (VTE); the natural history of gonadal vein thrombosis (GVT) occurring in cancer patients is not well described in the medical literature.

Methods

Utilizing a software program the computerized tomographic scan reports of patients at a single cancer center from January 1, 2004 to June 30, 2011 were searched for the term GVT. Patients included in this analysis had a diagnosis of cancer, an isolated GVT (i.e. no evidence of thrombosis at another site), no symptoms referable to the GVT, and at least six months of follow-up information. All subsequent recurrent VTE events were confirmed by imaging studies.

Results

196 cancer patients with GVT were identified. The majority of patients in this analysis had metastatic disease (118, 61.2%) as well as active cancer (167, 85.2%). Twenty patients (10.8%) developed recurrent VTE (median follow-up 14.5 months); median time to recurrent VTEs was 5.5 months (range 0–19 months). When considering only patients with without a recent history of gynecologic surgery, VTE recurrence rates were 14.3%. Active cancer was the only risk factor significantly associated with recurrent VTE (P = 0.047).

Conclusions

Based upon the patient’s risk factors for VTE, treatment of an incidentally detected GVT in cancer patients with anticoagulation, as per guidelines for other VTE sites, may be indicated in certain high risk subgroups, especially those patients with active cancer who have not had prior pelvic surgery.     

Efficacy of postoperative anticoagulation therapy with enoxaparin for portal vein thrombosis after hepatic resection in patients with liver cancer

Backgrounds

Enoxaparin, low-molecular-weight heparin, has become a routine thromboprophylaxis in general surgery.

Study design

A retrospective cohort study was performed in 281 patients who underwent hepatic resections for liver cancers from 2011 to 2013. These patients were divided into two groups; an enoxaparin (-) group (n = 228) and an enoxaparin (+) group (n = 53). Short-term surgical results including venous thromboembolism (VTE) and portal vein thrombosis (PVT) were compared.

Results

In the enoxaparin (+) group, the patients’ age (65 vs. 69 years; p = 0.01) and BMI (22.9 vs. 24.4; p < 0.01) were significantly higher. According to the symptomatic VTE, symptomatic pulmonary embolism occurred in one patient (0.4%) in the enoxaparin (-) group, but the complication rate was not significantly different (p = 0.63). The complication rate of PVT was significantly lower in the enoxaparin (+) group (10 vs. 2%; p = 0.04). The independent risk factors for PVT were an operation time ≥ 300 minutes (Odds ratio 6.66) and non-treatment with enoxaparin (Odds ratio 2.49).

Conclusions

Postoperative anticoagulant therapy with enoxaparin could prevent PVT in patients who underwent hepatic resection for liver cancers.     

Association of F11 polymorphism rs2289252 with deep vein thrombosis and related phenotypes in population of Latvia

Introduction

Deep vein thrombosis (DVT) has a strong inherited predisposition that is partly explained by the strong genetic risk factors such as mutations in factor V, prothrombin, antithrombin III, protein C and S genes. Only recently the first GWAS have been performed on DVT resulting in discovery of novel genetic variants, however, the information on the common polymorphisms predisposing to the risk of DVT is still scarce.

Materials and Methods

Here we selected six SNPs (rs5361 in SELE, rs2066865 in FGG, rs2227589 in SERPINC1, rs1613662 in GP6, rs13146272 in CYP4V2, rs2289252 in F11) reported to be associated with venous thrombosis conditions and studied the association of these common variants in selected case (n = 177) and control (n = 235) groups from population of Latvia. Genotyping was performed using TaqMan hybridization probe SNP genotyping assay.

Results

Patients with DVT had a significantly higher frequency of F11 rs2289252 polymorphism (p = 0.001; OR [95%CI] = 1.61 [1.20-2.14]). When stratified by recurrence of DVT the tendency was observed that the same SNP had higher OR value in group of DVT patients with repeated episodes of DVT compared to patients with single DVT episode (p = 0.009; OR [95%CI] = 2.27[1.22-4.21] and p = 0.009; OR [95%CI] = 1.52[1.11-2.08] respectively), but due to limited group of cases this finding should be replicated.

Conclusion

We conclude that F11 gene variant rs2289252 contribute to inherited forms of DVT incidence and correlation of other analysed SNPs should be explored in populations with greater sample size and associated with various thrombosis related traits.     

Two years outcome of isolated distal deep vein thrombosis

Background

Isolated distal deep vein thrombosis (IDDVT) is frequently found in symptomatic outpatients, but its long term outcome is still uncertain.

Aims

To assess IDDVT long term outcome and the impact of IDDVT characteristics on outcome.

Methods

In a prospective, single center study we enrolled symptomatic outpatients in whom IDDVT was detected by whole-leg compression ultrasonography. Patients with provoked IDDVT were treated with low molecular weight heparins (LMWH) for 30 days while those with unprovoked IDDVT received with vitamin K antagonists (VKA) for three months. The primary end-point was the rate of the composite of pulmonary embolism (PE), proximal deep vein thrombosis (DVT), and IDDVT recurrence/extension during 24 month follow-up.

Results

90 patients (age 61 ± 18, male 48.9%) were enrolled. Risk factors for thrombosis were reduced mobility (34.4%), obesity (25.3%), surgery (15.6%), and previous DVT (15.6%) and cancer in 8 patients (8.9%). Eighty-eight patients were treated (56 with LMWH and 32 with VKA). During follow-up (median 24 ± 2 months), 17 events were recorded, which included 3 PE (two in cancer patients), 4 proximal DVTs (one in cancer patient) and 10 IDDVT. Male sex (HR 4.73 CI95%: 1.55-14.5; p = 0.006) and cancer (HR 5.47 CI95%: 1.76-17.6; p = 0.003) were associated with a higher risk of complications, whereas IDDVT anatomical characteristics, anticoagulant therapy type, and provoked IDDVT were not.

Conclusions

The risk of recurrent venous thromboembolism after IDDVT may be relevant in male patients or in patients with active cancer. Larger studies are needed to address this issue.     

Anti-thrombosis effect of LRRFIP1 shRNA lentivirus in a mouse model of deep vein thrombosis

Introduction

Deep vein thrombosis (DVT) is one of the common complications of orthopedic surgery. Low molecular weight heparin (LMWH) is a usually used agent for DVT, but it would increase the risk of bleeding. LRRFIP1 has been shown to play an important role in the formation of thrombosis. Therefore, we investigated the effect of LRRFIP1 shRNA lentivirus on DVT in mice.

Materials and Methods

Lentiviral Vectors carrying LRRFIP1 shRNA were constructed and transfected into cultured mouse bone marrow cells (BMCs). Male ICR mice were irradiated with a single dose of 9.5 Gy and then were injected with different agents through the tail vein. Stasis venous thrombosis was induced by inferior vena cava (IVC) ligation. Mice were sacrificed on the 1st, 3rd and 7th day post operation and the thrombi were removed, blotted the excess blood on it with filter paper and immediately weighed. P-selectin and d-Dimer were determined by enzyme-linked immunosorbent assay (ELISA).

Results

LRRFIP1 shRNA significantly suppressed the expression of LRRFIP1 in the thrombi. In contrast, low molecular weight heparin (LMWH) and negative shRNA exhibited little effect on the expression of LRRFIP1. LRRFIP1 shRNA, LMWH and negative shRNA inhibited the thrombus formation in vivo significantly. The plasma P-selectin and d-Dimer levels were significantly increased after IVC ligation. LRRFIP1 shRNA significantly decreased the plasma P-selectin and d-Dimer levels. However, LMWH and negative shRNA showed little effects on the levels of plasma P-selectin and d-Dimer.

Conclusion

LRRFIP1 shRNA might represent a promising prevention strategy for DVT.     

Molecular basis and thrombotic manifestations of antithrombin deficiency in 15 unrelated Chinese patients

Introduction

Antithrombin (AT) deficiency is associated with an increasing risk of thrombosis.

Materials and methods

15 unrelated patients with AT deficiency defined by thrombophilic assays were recruited and detailed clinical information about patients, focusing on the personal and family history of thromboembolism (TE), were recorded. Mutation analysis was performed by direct sequencing of an AT gene (SERPINC1) in the patients and their family members.

Results

A total of 15 heterozygous causative mutations, each being identified in one family, were identified. Five mutations (33.3%) were reported here for the first time, including three null mutations (Ser36X, Lys70X and Try307X) and two missense mutations (Phe123Cys and Leu340Phe) probably impairing the structural integrity and stability of protein based on the AT structural analysis. Of the 15 patients, 33.3% (5/15) had additional risk factors and only one patient presented with additional genetic alteration causing an early onset of thrombosis. Fourteen patients (93.9%) suffered from multisite recurrent thrombotic episodes after a first episode of thrombosis. 93.3% of the patients experienced deep vein thrombosis (DVT) and 40.0% presented with mesenteric venous thrombosis (MVT). In addition, both venous and arterial thrombosis was present in two unrelated patients. 51.0% subjects with AT deficiency in the 15 unrelated pedigrees experienced TE events.

Conclusions

Prophylactic anticoagulation may be suggested in AT-deficient patients to avoid the recurrent and multisite thrombosis. The association of primary MVT and AT deficiency is highlighted.     

Individual propensity for thrombosis: comparison of venous and arterial circulations

Introduction

The pathogenesis of venous thrombosis has been attributed to complex interaction between environmental and inherited variables. A basal predisposition for venous thrombophilia independent of environmental variables has not been previously defined experimentally. Both to address the existence of an individual propensity to venous thrombosis and to establish an animal model in which variables governing this propensity could be tested, we provoked venous thrombi in a cohort of pigs of uniform size and age. We furthermore sought to determine whether the thrombotic propensity in the venous circulation is associated with similar propensity for arterial thrombosis.

Materials and methods

Bilateral iliac venous stents were deployed and 2 h later, thrombi were harvested and weighed. The thrombotic response was compared to carotid arterial thrombi generated by crush injury within the same pig. Venous and arterial thrombus platelet deposition were measured by scintillation detection of autologous ¹¹¹In-platelet content.

Results

In a cohort of 27 pigs, venous thrombus weights and platelet content varied over greater trrhan 10-fold range from least to greatest responders. There was strong intra-individual correlation of thrombus platelet deposition (r = 0.86; p = 0.008) and thrombus weights (r = 0.68; p = 0.015) between stented iliac vein pairs. Venous thrombosis correlated with whole blood platelet counts but not carotid platelet-rich thrombus formation.

Conclusions

The wide variation in venous thrombotic response to a standardized injury appears to represent an intrinsic propensity of the individual. The poor correlation with arterial thrombosis implies unique mechanisms responsible for this propensity in arteries and veins.     

Matrix metalloproteinase-9 deletion is associated with decreased mid-term vein wall fibrosis in experimental stasis DVT

Introduction

Post thrombotic syndrome therapy is primarily palliative, and the associated vein wall inflammatory mechanisms are unclear. Vein wall fibrotic injury following deep venous thrombosis (VT) is associated with elevated matrix metalloproteinases (MMPs). Whether and by what mechanism MMP9 directly contributes to vein wall remodeling after VT is unknown.

Methods

WT and MMP9 -/- mice underwent stasis VT by ligation of the inferior vena cava (IVC) and tissue was harvested at 2, 8, and 21 days. Assessment of thrombus size, and gene, protein and structural vein wall determinations were done.

Results

VT resolution was increased in MMP9-/- mice as compared with controls at 21d only. The primary phenotypic fibrotic vein wall differences occurred at 8d post VT, with significantly less vein wall collagen content as assessed by Picosirius red staining in MMP9 -/- mice as compared with WT. Increased monocytic vein wall influx with less IL-1b and TGFb was found in MMP9 -/- vein walls as compared with WT. Corresponding levels of PAI-1 were increased in MMP9 -/- compared with WT, and no difference in FSP-1 + cells as compared with controls.

Conclusions

In stasis VT, MMP9 modulates midterm vein wall collagen content, with an altered local inflammatory and profibrotic environment, likely directed by monocytes. Thus, MMP9 plays a role in both vein wall responses as well as late thrombus resolution.     

Thrombosis of the inferior vena cava and malignant disease

Background

Inferior vena cava thrombosis (IVCT) is a rare event, and studies detailing its underlying aetiologies are scarce.

Methods

One hundred and forty-one IVCT patients (57% females, median age 47 years) were analysed with a focus on malignancy-related thrombosis and compared with 141 age- and sex-matched control patients with isolated lower-extremity deep vein thrombosis.

Results

Malignancies were more prevalent among IVCT patients compared with the control group (39% vs. 7.8%; P < 0.001). Malignancy-related IVCT more frequently involved the suprarenal and hepatic segments of the IVC and extended more often to the right atrium than IVCT did in non-cancer patients. Among IVCT patients with malignancies, renal cell carcinoma (38%) and other malignancies of the genitourinary tract (25%) were the most common tumours. Analysis of the underlying pathological mechanisms of malignancy-related thrombosis identified external compression of the IVC by tumour masses in 9 cases (16%), and progression of malignancy into the IVC (so-called “tumour thrombosis”) in 24 cases (44%). The remaining 22 cases (40%) were attributed to malignancy-related hypercoagulability and the presence of additional venous thromboembolism risk factors, such as previous surgery, immobilisation, or chemotherapy.

Conclusions

Malignancies substantially contribute to the risk of thrombosis involving the IVC. Tumour invasion, especially in cases of renal cell cancer and malignancy-related hypercoagulability are major triggering factors for thrombogenesis.     

Time-dependent hardening of blood clots quantitatively measured in vivo with shear-wave ultrasound imaging in a rabbit model of venous thrombosis

Objective

Provide in vivo blood clot hardening evolution with ultrasound using supersonic imaging of shear waves.

Methods

We conducted a prospective study in flow stasis-induced venous thrombosis within jugular veins of white female New Zealand rabbits. Blood clot elasticity was noninvasively measured in vivo using the Young's modulus (in kilopascals), on a 2-hour and a 2-week periods after thrombus induction. Monitoring was followed by a necropsy and ex vivo mechanical characterization to validate the existence and elasticity of explanted thrombi.

Results

Stagnant blood in the region of interest underwent clotting and progressive hardening with thrombus aging. The mean Young's moduli varied from 1.0 ± 0.6 kPa (at 10 min) to 5.3 ± 1.6 kPa (at 2 hours), then to 25.0 ± 6.8 kPa (at 14 days) post-surgery. Mean ex vivo moduli of 6.2 ± 0.7 kPa at 2 hours and 29.0 ± 2.4 kPa at 2 weeks agreed with in vivo measures.

Conclusions

Supersonic imaging of shear waves provides consistent quantitative non-invasive elasticity measurements not available with standard compression ultrasound imaging for diagnosing and following venous thromboembolism. This information translatable to humans could aid in determining whether continued anticoagulant treatment is necessary, especially in the setting of unprovoked venous thromboembolism.     

Chronic cerebrospinal venous insufficiency in multiple sclerosis: A sonographer-blinded case-control study

Objectives

To evaluate the presence of chronic cerebrospinal venous insufficiency (CCSVI) and cerebral venous anomalies in a consecutive series of patients with multiple sclerosis (MS), other neurologic diseases (NEU) and healthy controls (HC).

Methods

A consecutive series of 80 MS patients, 41 HC and 26 NEU cases underwent a transcranial and extracranial echo-color Doppler (ECD) evaluation of cerebrospinal venous return in a sonographer-blinded fashion. According to the original Dr. Zamboni's protocol, CCSVI was diagnosed in presence of ≥2 ECD venous criteria.

Results

We did not observe any association between CCSVI and MS. CCSVI was detected in 17.5% of MS cases, 7.3% of HC and 11.5% of NEU patients (p = 0.333). The prevalence of internal jugular vein stenosis (IJV) and the proportion of patients with any positive ECD criterion differed significantly among groups, being higher in MS cases versus HC (67.5% and 76.2% versus 48.8% and 41.5%, respectively; p = 0.005 and p = 0.006). No relationship between CCSVI and MS type and severity was evidenced.

Conclusions

The present study argues against a positive link between CCSVI and MS risk or severity. Interestingly, a weak association between venous ECD anomalies (in particular IJV stenosis) and MS was observed in our population. This finding should be interpreted with caution due to the possible confounders and needs to be confirmed in large controlled studies.     

Influence of coronary artery disease-associated genetic variants on risk of venous thromboembolism

Introduction

We investigated whether genetic variations robustly associated with coronary artery disease are also associated with risk of venous thromboembolism in a well-defined, female case–control study (n = 2753) from Sweden.

Materials and Methods

39 single nucleotide polymorphisms in 32 loci associated with coronary artery disease in genome-wide association studies were identified in a literature search and genotyped in the ThromboEmbolism Hormone Study (TEHS). Association with venous thromboembolism was assessed by logistic regression.

Results

Only rs579459 in the ABO locus demonstrated a significant association with VTE. A tentative association between ANRIL and VTE in the discovery analysis failed to replicate in a meta-analysis of 4 independent cohorts (total n = 7181).

Conclusions

It appears that only the ABO locus is a shared risk factor for coronary artery disease and VTE.     

Clinical differences between acute CVST and non-thrombotic CVSS

Background

Cerebral venous sinus thrombosis (CVST) is a rare stroke subtype, which has many overlapping symptoms with non-thrombotic cerebral venous sinus stenosis (CVSS) in the acute phase. Despite these similarities, their therapeutic regimens and outcomes are entirely different, and treatment delay is life-threatening. This study aims to address their clinical differences to help promote proper patient care.

Methods

34 cases of CVST and 34 cases of non-thrombotic CVSS diagnosed with digital subtraction angiography (DSA) in the acute phase (symptoms onset within 7 days) were consecutively enrolled in this prospective non-randomized and controlled study. Differences between CVST and CVSS in their clinical manifestation, plasma biomarkers, and MR or DSA imaging were compared.

Results

CVST and CVSS overlap in many ways, but differ in their respective medical histories and neurological deficits. However, 20.6% of CVST and 64.7% of CVSS occur without a definitive medical history, and 70.6% of CVST and 64.7% of CVSS occur without focal neurologic deficits. In the acute phase of CVST, d-dimer and fibrinogen are found to be abnormally elevated in 94.1% and 73.5% of cases, respectively. In the CVSS group, d-dimer and fibrinogen are only elevated in 17.6% and 5.9% of cases, respectively (binary logistic regressions test, all P < 0.001). In the CVST group, the predominant features in MRI/MRV and DSA imaging include local brain lesions, flow void signal loss, non-visualization, and a local filling defect sign at the involved sinus. Conversely, in the CVSS group, imaging revealed symmetrically small bilateral ventricles and the spread of cerebral edema in MRI/MRV. DSA imaging in the CVSS group revealed external compression and a narrow sinus with disproportionate venous engorgement. Despite these findings, positive imaging only appears in a minority of patients in the two groups during the acute phase ( Table 4).

Conclusions

DSA may be beneficial to diagnose CVST in ambiguous patients suspected to have either CVST or CVSS. Clinically useful biomarkers (d-dimer and fibrinogen) may predict CVST in the emergency room in the ambiguous patients with or without equivocal MRI/MRV imaging.     

Thyroid function,activated protein C resistance and the risk of venous thrombosis in users of hormonal contraceptives

Introduction

Use of combined hormonal contraceptives is associated with a three- to eight-fold increased risk of venous thrombosis compared with non-use. The thrombotic risk depends on the estrogen dose as well as the progestogen type. Use of hormonal contraceptives leads to resistance to activated protein C (APC), which may serve as marker for the risk of venous thrombosis. Hyperthyroidism is also associated with an increased risk of venous thrombosis, due to increased free Thyroxine (FT4) levels which cause a hypercoagulable state.

Materials and methods

The objective of this study was to evaluate the effects of hormonal contraceptives on levels of FT4, thyroid stimulating hormone (TSH) and thyroxine binding globulin (TBG), and to investigate the effects on APC resistance per contraceptive group. We measured FT4, TBG and TSH levels and APC resistance in 231 users of oral contraceptives.

Results

Users of the most thrombogenic hormonal contraceptives, i.e. containing desogestrel, cyproterone acetate or drospirenone, had higher TBG levels than users of less thrombogenic hormonal contraceptives, i.e. the levonorgestrel-containing intrauterine device. TSH levels were not significantly elevated and FT4 levels did not change. TBG levels were also associated with APC resistance.

Conclusion

Use of hormonal contraceptives lead to elevated TBG levels, slightly elevated TSH levels and unchanged FT4 levels without causing a hyperthyroid state. Thus, the increased thrombotic risk during the use of hormonal contraceptives cannot be explained by a hyperthyroid state caused by use of these hormonal contraceptives.