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Blood Advances Jun 2024
Topics: Humans; Venous Thrombosis; Intracranial Thrombosis; Animals; Mice; Janus Kinases
PubMed: 38916898
DOI: 10.1182/bloodadvances.2024012977 -
Frontiers in Medicine 2024The COVID-19 pandemic related to SARS-CoV-2 virus was responsible for global pandemic. The severe form of the disease was linked to excessive activation of immune...
BACKGROUND
The COVID-19 pandemic related to SARS-CoV-2 virus was responsible for global pandemic. The severe form of the disease was linked to excessive activation of immune pathways together with a systemic cytokine storm response and thrombotic venous or arterial complications. Factors predicting severe outcomes including venous and/or pulmonary thrombosis (VT) and death were identified, but the prognostic role of their combination was not addressed extensively.
OBJECTIVES
We investigated the role of prognostic factors from the coagulation or inflammatory pathways to better understand the outcome of the disease.
METHODS
For this, we prospectively studied 167 SARS-CoV-2-positive patients from admission in intensive care units (ICU) or emergency departments from four academic hospitals over a 14-month period. Besides standard biology, we assessed serum concentrations of inflammatory markers, coagulation factors and peripheral blood cells immunophenotyping.
RESULTS
Thirty-nine patients (23.3%) developed VT and 30 patients (18%) died. By univariate analysis, C-reactive protein (CRP) level > 150 mg/L, interleukin-6 (IL-6) ≥ 20 pg/mL, D-dimers > 1,500 μg/L, ADAMTS13 activity ≤ 50%, Von.
CONCLUSION
A combination of coagulation and inflammatory markers can refine the prognostication of severe outcome in COVID-19, and could be useful for the initial evaluation of other types of viral infection.
PubMed: 38915768
DOI: 10.3389/fmed.2024.1399335 -
Journal of Vascular Surgery. Venous and... Jun 2024Surgical decompression via transaxillary first rib resection (TFRR) is often performed in patients presenting with venous thoracic outlet syndrome (VTOS). We aimed to...
OBJECTIVE
Surgical decompression via transaxillary first rib resection (TFRR) is often performed in patients presenting with venous thoracic outlet syndrome (VTOS). We aimed to evaluate the outcomes of TFRR based on chronicity of completely occluded axillo-subclavian veins in VTOS.
METHODS
We performed a retrospective institutional review of all patients who underwent TFRR for VTOS and had a completely occluded axillo-subclavian vein between 2003 to 2022. Patients were categorized into three groups based on the time of inciting VTOS event to TFRR acuity of their venous occlusion: <4 weeks, 4-12 weeks and >12 weeks. We evaluated the association of TFRR timing with one-year outcomes including patency and symptomatic improvement. We used Chi-square test to compare baseline characteristics and postoperative outcomes.
RESULTS
Overall, 103 patients underwent TFRR for VTOS with a completely occluded axillo-subclavian vein (median age 30.0 years, 42.7% female, 8.8% non-White), of which 28 patients had occlusion < 4 weeks, 36 patients had occlusion 4-12 weeks, and 39 patients had occlusion >12 weeks. Postoperative venogram performed 2-3 weeks after TFRR demonstrated that 78.6% in the <4 weeks group, 72.2% in the 4-12 weeks group and 61.5% in the >12 weeks group had some degree of recanalization (p=0.76). Postoperative balloon angioplasty was successfully performed in 60 patients with stenosed/occluded axillo-subclavian vein at the time of postoperative venogram. At 10-14-month followup, 79.2% in the <4 weeks group, 73.3% in the 4-12 weeks group, and 73.3% in the >12 weeks group had patent axillo-subclavian veins based on duplex ultrasound (p=0.86). Among patients who underwent postoperative balloon angioplasty, 80.0%, 85.0% and 100% in the <4 weeks, 4-12 weeks and >12 weeks groups respectively demonstrated patency at 10-14 months (p=0.31). Symptomatic improvement was reported in 95.7% in the < 4 weeks group, 96.7% in the 4-12 weeks group and 93.5% in the >12 weeks group (P=0.84).
CONCLUSION
TFRR offers excellent postoperative outcomes for symptomatic VTOS patients, even in cases of completely occluded axillo-subclavian veins, regardless of the chronicity of the occlusion. By 14 months, 95.2% of patients experienced symptomatic improvement, and 75% attained venous patency.
PubMed: 38914374
DOI: 10.1016/j.jvsv.2024.101925 -
Thrombosis and Haemostasis Jun 2024Venous thromboembolism (VTE) is predisposed by thrombotic mutations in patients with hereditary thrombophilia. Although prothrombin deficiencies caused by homozygous or...
BACKGROUND
Venous thromboembolism (VTE) is predisposed by thrombotic mutations in patients with hereditary thrombophilia. Although prothrombin deficiencies caused by homozygous or compound heterozygous mutations are associated with bleeding diathesis, rare cases have shown a correlation between heterozygous prothrombin mutations and thrombosis.
MATERIAL AND METHODS
We surveyed genetic variants involved in thrombosis and hemostasis in 347 patients with unprovoked VTE or having a positive family history of thrombosis. For patients identified with heterozygous prothrombin mutations, we conducted family investigations and performed thrombin generation test (TGT) to elucidate the thrombotic risk. Novel mutants were expressed and subjected to functional assays to clarify the underlying thrombotic mechanisms.
RESULTS
Heterozygous prothrombin mutations were identified in 3.5% of patients (12/347), including three novel mutations Phe382Ser, Phe382Leu and Asp597Tyr found in one patient each, as well as previously reported Arg541Trp mutation in four patients and Arg596Gln mutation in five patients. A total of 42 mutation carriers were identified within the 12 pedigrees, among whom 64.3% (27/42) had experienced thrombotic events. TGT results demonstrated hypercoagulability for carriers of the five mutations, with Arg596Gln showing the highest thrombin generation potential followed by Arg541Trp. The Phe382-associated mutations severely impaired thrombomodulin binding ability of thrombin, resulting in obviously reduced protein C (PC) activation. The Asp597Tyr mutation exhibited a mild reduction in both antithrombin inhibition and PC activation reactions.
CONCLUSIONS
The presence of heterozygous prothrombin mutations represents a potential genetic predisposition for VTE. All thrombosis associated mutations potentiate coagulation activity by either conferring antithrombin resistance and/or impairing PC pathway activity.
PubMed: 38914130
DOI: 10.1055/a-2350-8338 -
Seminars in Thrombosis and Hemostasis Jun 2024By integrating findings from comprehensive reviews, meta-analyses, and cutting-edge genetic studies, this article illuminates the significance of stress-induced...
By integrating findings from comprehensive reviews, meta-analyses, and cutting-edge genetic studies, this article illuminates the significance of stress-induced hypercoagulability in clinical medicine. In particular, the findings from numerous prospective cohort studies indicate that stress and hemostatic factors of a hypercoagulable state are associated with increased incident risk and poor prognosis for atherosclerotic cardiovascular disease and venous thromboembolism. Mendelian randomization studies suggest that these associations are partially causal. The review synthesizes extensive research on the link between acute and chronic stress and hypercoagulability, outlining a potential pathway from stress to thrombosis risk. Consistent with the allostatic load concept, acute stress-induced hypercoagulability, initially adaptive, can turn maladaptive under chronic stress or excessive acute stress, leading to arterial or venous thrombotic events. Individuals with predisposing factors, including atherosclerosis, thrombophilia, or immobilization, may exhibit an increased risk of thrombotic disease during stress. Contextual sociodemographic characteristics, the stress experience, and coping resources additionally modulate the extent of stress-induced hypercoagulability. Research into the neuroendocrine, cellular, and molecular bases reveals how stress influences platelet activation coagulation and fibrinolysis. The activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis, along with vagal withdrawal, and the effects of catecholamines, cortisol, and vasopressin, are the central mechanisms involved. Hemoconcentration, inflammation, endothelial dysfunction, and thrombopoiesis additionally contribute to stress-induced hypercoagulability. Further research is needed to prove a causal link between chronic stress and hypercoagulability. This includes exploring its implications for the prevention and management of thrombotic diseases in stressed individuals, with a focus on developing effective psychosocial and pharmacological interventions.
PubMed: 38914118
DOI: 10.1055/s-0044-1787660 -
International Ophthalmology Jun 2024Macular edema (ME) is a common complication following branch retinal vein occlusion (BRVO) and is also the main reason for visual impairment. This study aimed to compare... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
BACKGROUND
Macular edema (ME) is a common complication following branch retinal vein occlusion (BRVO) and is also the main reason for visual impairment. This study aimed to compare the efficacy and safety of intravitreal ranibizumab (IVR) or dexamethasone implant (IDI) monotherapy, as well as the combination of IVR and IDI injections, in patients with ME secondary to branch retinal vein occlusion (BRVO).
METHODS
This multicenter, prospective, and comparative study included 292 patients with unilateral ME involvement (total of 292 eyes) secondary to BRVO. The patients were randomly assigned to three groups and followed up for 12 months. Patients in group 1 (n = 96) were treated with 3-dose loading IVR injections followed by a pro re nata (PRN) regimen. Patients in group 2 (n = 98) received IVR combined with IDI injection, followed by IVR PRN regimen. Patients in group 3 (n = 98) were treated with IDI injection, followed by repeated IDI injection based on clinical necessity. Best corrected visual acuity (BCVA), central retinal thickness (CRT), complications, and frequency of injections were recorded and compared between the three groups.
RESULTS
At baseline, the three groups did not differ in age, gender, duration of ME, BCVA, IOP, and CRT (P > 0.05). Mean number of total injections per eye within 12 months were 7.1 ± 2.3 (range 4-9) in group 1, 3.7 ± 1.5 (range 2-6) in group 2, and 1.8 ± 0.4 (range 1-3) in group 3. There was a statistical difference in the number of injections between group 1 and group 2 (P = 0.037). Eyes in group 3 received fewer injections than those in group 2, but the difference was not statistically significant (P = 0.052). BCVA improvement and CRT reduction were achieved in all groups and there was no significant difference between the three groups at the end of the 12th month. However, IOP elevation and cataract progression were more frequent in group 3, especially in those patients who received repeated IDI injections.
CONCLUSION
Three therapeutic regimens had comparable efficacy in treating ME secondary to BRVO. Combination therapy had an advantage in maintaining good effect with fewer re-injections and complications.
TRIAL REGISTRATION INFORMATION
The study complied with the principles of the Declaration of Helsinki and was approved by Xi'an Aier Ancient City Eye Hospital, Xi'an Aier Eye Hospital, and Xianyang Aier Eye Hospital ethics committees (2022SF-367).
Topics: Humans; Retinal Vein Occlusion; Ranibizumab; Male; Female; Dexamethasone; Intravitreal Injections; Macular Edema; Prospective Studies; Drug Implants; Visual Acuity; Middle Aged; Angiogenesis Inhibitors; Glucocorticoids; Tomography, Optical Coherence; Treatment Outcome; Aged; Drug Therapy, Combination; Follow-Up Studies
PubMed: 38913192
DOI: 10.1007/s10792-024-03158-x -
International Medical Case Reports... 2024Although rare, cerebral venous sinus thrombosis (CVT) can result in significant neurological complications, particularly after childbirth. Early diagnosis poses a...
BACKGROUND
Although rare, cerebral venous sinus thrombosis (CVT) can result in significant neurological complications, particularly after childbirth. Early diagnosis poses a challenge due to symptom overlap with other conditions. Limited publications and underdiagnosis of CVT are prevalent in developing nations, notably in Ethiopia.
CASE
A 29-year-old mother, having given birth four times, presented to the emergency department in her second month postpartum with complaints of persistent headaches and blurred vision over three weeks. Additionally, she reported sudden weakness on her right side for one day. Despite previous treatments for migraine headaches, she was diagnosed with CVT after magnetic resonance imaging/venography revealed blockage in the right anastomotic vein and the posterior segment of the superior sagittal sinus. Treatment commenced with the anticoagulant enoxaparin. During hospitalization, she experienced one episode of generalized seizures, leading to transfer to the intensive care unit where phenytoin was added. Subsequent diagnosis of papilledema occurred. After a 16-day hospital stay, she was discharged with warfarin, phenytoin, and acetazolamide. Oral anticoagulation and other medications ceased after six months of treatment, considering the postpartum period as a temporary risk factor for CVT. The patient currently maintains good health and has resumed normal activities.
CONCLUSION
Maintaining a high index of suspicion for CVT during the postpartum period and promptly conducting imaging scans are crucial for early diagnosis. This approach can halt neurological decline and facilitate immediate recovery through early therapeutic interventions.
PubMed: 38911608
DOI: 10.2147/IMCRJ.S457170 -
Cureus May 2024A hemodialysis tunneled catheter is one option for vascular access used with hemodialysis patients; however, catheter complications such as thrombosis are still...
INTRODUCTION
A hemodialysis tunneled catheter is one option for vascular access used with hemodialysis patients; however, catheter complications such as thrombosis are still inevitable. To prevent thrombosis formation, a catheter-locking solution is instilled between dialysis sessions. Heparin is used as a default locking solution in our Hemodialysis Care Project centers, while a recombinant tissue plasminogen activator (rt-PA) such as alteplase is used to treat suspected catheter thrombosis. This study aimed to identify the clinical factors, catheter brands, and hemodialysis variables that influence the choice of use for alteplase versus heparin, for those patients with tunneled catheters, and reduce overprescribing of high-alert medication alteplase.
METHODS
A retrospective medical chart review study was conducted involving 230 patients with tunneled catheters; the first group of 133 patients used alteplase regularly three times a week, while the second group of 97 patients completed at least one year using the same catheter access with heparin lock only.
RESULTS
Multivariate logistic regression and logistic regression analysis showed a significant association (p < 0.05) between different variables. Results suggest that overweight and hyperlipidemia patients are more likely to use alteplase. Patients using brand-name catheters such as Hemostar/Vas-cath (BD, Franklin Lakes, NJ) are less likely to use heparin than those using Medcomp catheters (Medcomp, Yuma, AZ). In addition, patients having a history of angioplasty would be less likely to have heparin than no angioplasty. Moreover, if the patient's fluid removal were equal to or less than 2 kg, they would be more likely to use heparin and vice versa.
CONCLUSION
The study postulates that identified variables affect whether alteplase or heparin is used in hemodialysis tunneled catheters, and may be useful to increase awareness, improve practices, or judiciously control the use of alteplase within Saudi Arabia and globally.
PubMed: 38910780
DOI: 10.7759/cureus.60817 -
Cureus May 2024Dengue, commonly referred to as 'breakbone fever,' is a mosquito-borne arboviral infection transmitted by , featuring an average incubation period of approximately seven... (Review)
Review
Dengue, commonly referred to as 'breakbone fever,' is a mosquito-borne arboviral infection transmitted by , featuring an average incubation period of approximately seven days. Key cytokines such as interferon-gamma (IFN-γ), tumor necrosis factor (TNF)-α, and interleukin (IL)-10 are pivotal in the pathogenesis of dengue. Travelers are particularly susceptible to contracting dengue fever, with disease severity often associated with CD8+ T cell response. Without proper hospitalization during severe cases like dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS), mortality rates can escalate to 50%. Dengue fever can lead to various complications, including neurological manifestations such as encephalopathy, encephalitis, cerebral venous thrombosis, myelitis, posterior reversible encephalopathy syndrome, strokes (both ischemic and hemorrhagic), immune-mediated neurological syndromes (such as mononeuropathy, acute transverse myelitis, Guillain-Barre syndrome, and acute disseminated encephalomyelitis), and neuromuscular complications. Treatment protocols typically involve assessing disease activity using composite indices, pursuing treatment objectives, and administering intravenous fluids according to symptomatology. Given the absence of specific antiviral treatment for dengue, supportive care, particularly hydration, remains paramount during the early stages. It is crucial to recognize that dengue viruses may contribute to the development of neurological disorders, particularly in regions where dengue is endemic. Furthermore, there is a necessity for well-defined criteria for specific neurological complications. Primary prevention strategies primarily revolve around vector control measures, which play a critical role in curtailing the spread of dengue.
PubMed: 38910682
DOI: 10.7759/cureus.60961 -
Journal of Scleroderma and Related... Jun 2024Systemic sclerosis is a rare disease with a high mortality rate. It is a multisystem connective tissue disease due to endothelial autoimmune activation along with tissue...
Systemic sclerosis is a rare disease with a high mortality rate. It is a multisystem connective tissue disease due to endothelial autoimmune activation along with tissue and vascular fibrosis, inducing vasculopathy, with an angiogenesis wasting. The endothelial damage provokes platelet activation and immune cell adhesion. The detachment of endothelial cells leads to the interaction of platelets and collagen present in the exposed subendothelial layer. This provokes the activation of several coagulative factors, inducing a pro-thrombotic condition by thrombin generation, which converts fibrinogen into fibrin. Moreover, thrombin has other functions, such as the induction of hyperplasia in smooth muscle cells and fibroblasts, thereby favouring fibrosis. An increased risk of venous thromboembolism has been found in systemic sclerosis, whereas pulmonary hypertension may be due to the obstruction of small pulmonary arteries. Pulmonary veno-occlusive disease may also occur. Warfarin showed inconsistent results, while the outcomes of a randomised, placebo-controlled clinical trial on apixaban versus placebo are still awaited. A new anticoagulation strategy based on anti-factor XI drugs is being developed, with the aim of achieving optimal anticoagulation along with a low risk of bleeding. The molecule types under investigation in this category include monoclonal antibodies, small molecules, natural inhibitors, antisense oligonucleotides, and aptamers. Patients with systemic sclerosis may be ideal candidates for clinical trials planned to analyse the efficacy and safety of these molecules.
PubMed: 38910594
DOI: 10.1177/23971983241256250