Search Results (261)

Background: Antiphospholipid syndrome (APS) is one of the highest risk factors for obstetric complications. This article contains a case report of a patient with obstetric APS who experienced fetal loss during their first pregnancy and experienced a successful second pregnancy upon treatment with acetylsalicylic acid (ASA), low-molecular-weight heparin (LMWH), and hydroxychloroquine (HCQ). We compare placental pathology in these two pregnancies and discuss the impact of antiphospholipid antibodies and clinical management on pregnancy outcomes. We also propose methods to monitor obstetric antiphospholipid syndrome (OAPS) patients during pregnancy. Methods: A 26-year-old woman presented with a history of stillbirth at 25 weeks of pregnancy due to placental insufficiency. Before pregnancy, she experienced symptoms suggestive of autoimmune disease (thrombocytopenia, recurrent mouth aphthous ulcers, and Raynaud’s phenomenon) but had no diagnosis. Placental dysfunction correlated with the high ratio of sFlt-1/PIGF (soluble fms-like tyrosine kinase 1 and the placental growth factors index). Laboratory tests revealed the presence of antinuclear antibodies (ANAs) and triple positivity for antiphospholipid antibodies (aPLs). Results: Following the initiation of treatment for OAPS and regular monitoring consistent with current guidelines, the patient conceived and successfully delivered a healthy child. Conclusions: Adequate therapy and close monitoring during pregnancy, including clinical observation, placental biomarkers and regular ultrasonography, may help to reduce the risks and increase chances for optimal pregnancy outcomes. Additionally, pathological examination and clinical collaboration are essential components in future pregnancy counseling and should be a part of multidisciplinary management. Full article

Background: The optimal anticoagulation strategy for obese patients with superficial vein thrombosis (SVT) remains unclear. This study evaluates the impact of obesity on anticoagulation patterns and clinical outcomes in patients with lower limb SVT. Methods: We conducted a prospective observational study including consecutive patients with SVT in a tertiary hospital from 2014 to 2024. Patients with SVT ≥ 5 cm in length and ≥3 cm from the saphenofemoral junction were included. Obese (BMI ≥ 30) and non-obese (BMI < 30) patients were compared. Patients were followed for one year. Outcomes were assessed at 90 and 365 days. The primary outcomes were venous thromboembolism (VTE) recurrence (SVT, deep vein thrombosis [DVT], or pulmonary embolism [PE]). The secondary outcomes were major bleeding and all-cause mortality. Results: Of 136 patients, 58 (42.6%) were obese. Both groups had similar baseline characteristics, except for younger age and higher smoking prevalence in obese patients. Most patients received anticoagulation (91.9%), primarily a prophylactic dose of low molecular weight heparin or a prophylactic dose of fondaparinux. No significant differences were found in VTE recurrence at 90 or 365 days (p = 0.505), and no major bleeding events occurred. Female sex was associated with a higher risk of VTE recurrence (OR 4.33, 95% CI 1.17–15.98, p = 0.028), but obesity did not influence outcomes. Conclusions: Obesity was not associated with increased VTE recurrence in patients with lower limb SVT. No major bleeding events were observed. These findings suggest that standard anticoagulation regimens may be appropriate for obese patients with SVT, but further studies are needed to confirm these results. Full article

Pulmonary embolism (PE) is an under-recognised yet serious complication in patients with acute ischaemic stroke (AIS), contributing significantly to morbidity and mortality. The interplay of traditional risk factors—such as immobility, endothelial dysfunction, and hypercoagulability—with AIS-specific conditions, including atrial fibrillation, malignancy, and reperfusion therapies, complicates both diagnosis and management. Despite available prophylactic strategies, including low-molecular-weight heparin and intermittent pneumatic compression, their use remains limited by bleeding concerns and a lack of tailored guidelines. This review synthesises the current evidence on the incidence, risk factors, pathophysiology, diagnostic approaches, and preventive strategies for PE in AIS, identifying critical gaps in risk stratification and clinical decision-making. We propose a novel mechanistic framework—the Brain–Lung Thromboinflammatory Axis Hypothesis—which posits that stroke-induced systemic inflammation, neutrophil extracellular trap (NET) formation, and pulmonary endothelial activation may drive in situ pulmonary thrombosis independent of deep vein thrombosis. This conceptual model highlights new diagnostic and therapeutic targets and underscores the need for stroke-specific VTE risk calculators, biomarker-guided prophylaxis, and prospective trials to optimise prevention and outcomes in this vulnerable population. Full article

Background and Objectives: Inherited thrombophilia (IT) increases the risk of adverse pregnancy outcomes, but the benefit of low-molecular-weight heparin (LMWH) prophylaxis remains debated. This study aimed evaluate the effect of LMWH by analyzing outcomes in women with IT who received LMWH versus those who did not and also compare pregnancy complication rates before and after inherited thrombophilia diagnosis. Materials and Methods: We conducted a retrospective case–control study including 276 pregnant women with inherited thrombophilia and prior pregnancy complications and 276 healthy pregnant controls on delivery. The main outcome was the incidence of complications: preterm rupture of membranes, oligohydramnios, fetal growth restriction, preterm delivery, stillbirth, HELLP syndrome, gestational hypertension, deep vein thrombosis, and recurrent pregnancy loss. The effect of LMWH was assessed by comparing complication rates among inherited thrombophilia patients who received therapy versus those who did not. Results: Women with IT were older, had higher BMI, delivered earlier, and had neonates with lower birth weight compared to controls. In current pregnancies, LMWH was associated with reduced rates of preterm delivery, fetal growth restriction, gestational hypertension, and recurrent pregnancy loss, especially in factor V Leiden carriers. LMWH had little effect on low-risk genotypes and was not independently associated with outcome reduction. Conclusions: LMWH prophylaxis should be reserved for high-risk women with IT. Routine use in all IT pregnancies is not justified and may cause unnecessary risks and costs. Early screening, risk stratification, and individualized care are essential to optimize outcomes. Full article

Background/Objectives: Venous thromboembolism (VTE) is a preventable cause of morbidity in the neurocritical ill patient population. There is ongoing debate regarding the optimal timing and choice of pharmacologic thromboprophylaxis (PTP) and how these decisions relate to balancing the risk of bleeding complications with the development of VTE. Our review assesses the available data to provide un updated perspective to clinicians. Methods: A literature search was performed in December 2024 in PubMed and EMBASE. We focused on the timing of PTP initiation and the comparison of enoxaparin (ENX) with unfractionated heparin (UFH) in patients with traumatic brain injury (TBI), intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), spinal or spinal cord injury (SCI), or requirement for neurosurgical intervention. Results: We included 90 articles spanning a total of 669,725 patients with injuries of interest within neurocritical care. The existing data largely signaled a benefit of early administration (<24–72 h) of PTP in VTE prevention, though some studies suggested increased risks of complications. Data to inform a preference for PTP agent was less robust, though a signal of benefit for enoxaparin is suggested for subsets of patients with acute brain injury such as TBI. The data quality is limited by the large body of retrospective studies, the heterogeneity of study populations, outcome definitions, study methodologies, and the lack of detailed reporting of relevant factors. Conclusions: Our review provides an updated assessment of the available data on PTP timing and choice in neurocritically ill patients with hemorrhages or surgical need, with a practice-focused overview for clinicians balancing VTE risk with bleeding risk. The data suggest that in most circumstances, early PTP appears safe and indicated, and that low-molecular weight heparin (LMWH) can be considered over UFH in certain subsets of patients. Still, data gaps and conflicting results highlight the need for patient-specific decision making and indicate that more robust research is warranted to inform optimal clinical practice. Full article

Heparin, a widely used polysaccharidic anticoagulant of animal origin, is associated with risks of contamination and adverse effects, notably bleeding and thrombocytopenia. These limitations have prompted interest in alternative sulfated polysaccharides with anticoagulant properties and improved safety profiles. This study explored the anticoagulant potential of two marine bacterial exopolysaccharides (EPS), infernan and diabolican. It assessed whether chemical modifications (depolymerization, oversulfation) could enhance their anticoagulant properties compared to unfractionated and low molecular weight heparins. Native EPS were depolymerized to generate different molecular weights and then chemically oversulfated to increase negative charge density. Anticoagulant activities were evaluated using clotting and thrombin generation assays (TGA). Molecular docking was performed to model interactions with antithrombin and heparin cofactor II. Only highly sulfated derivatives significantly prolonged activated partial thromboplastin time while showing negligible effect on thrombin time and anti-factor Xa activity. They present different structures, and their binding to antithrombin is not achieved via the classic pentasaccharide motif. In TGA, these derivatives inhibited thrombin formation at higher doses than heparin but induced a marked delay in clot generation. Docking analyses supported their ability to bind serpins, albeit with lower specificity than heparin. Their limited anti-Xa activity and non-animal origin position them as promising anticoagulant candidates. Full article

Background: Chronic kidney disease (CKD) and its advanced stage, end-stage renal disease (ESRD), affect millions worldwide and are associated with a paradoxical hemostatic imbalance—marked by both increased thrombotic and bleeding risks—which complicates anticoagulant use and demands clearer, evidence-based clinical guidance. Design: This study is a critical review synthesizing the current literature on anticoagulant therapy in CKD and ESRD, with emphasis on altered pharmacokinetics, clinical complications, and therapeutic adjustments. Data Sources: PubMed, Scopus, and Google Scholar were searched for articles discussing anticoagulation in CKD/ESRD, focusing on pharmacokinetics, clinical outcomes, and dosing recommendations. Study Selection: Studies examining the safety, efficacy, and pharmacokinetics of anticoagulants—including heparin, low-molecular-weight heparin (LMWH), warfarin, and direct oral anticoagulants (DOACs)—in CKD and ESRD populations were included. Data Extraction and Synthesis: Key findings were summarized to highlight the dose modifications, therapeutic considerations, and clinical challenges in managing anticoagulation in CKD/patients with ESRD. Emphasis was placed on balancing thrombotic and bleeding risks and identifying gaps in existing guidelines. Results: Patients with CKD and ESRD exhibit a paradoxical hypercoagulable state marked by platelet dysfunction, altered coagulation factors, and vascular endothelial damage. This condition increases the risk of thrombotic events, such as deep vein thrombosis (DVT) and pulmonary embolism (PE), while simultaneously elevating bleeding risks. Hemodialysis and CKD-associated variables further complicate the management of coagulation. Among anticoagulants, unfractionated heparin (UFH) is preferred due to its short half-life and adjustability based on activated partial thromboplastin time (aPTT). Low-molecular-weight heparins (LMWHs) offer predictable pharmacokinetics but require dose adjustments in CKD stages 4 and 5 due to reduced clearance. Warfarin necessitates careful dosing based on the estimated glomerular filtration rate (eGFR) to maintain an international normalized ratio (INR) ≤ 4, minimizing bleeding risks. Direct oral anticoagulants (DOACs), particularly Apixaban, are recommended for patients with eGFR < 15 mL/min or those on dialysis, although data on other DOACs in CKD remain limited. The lack of comprehensive guidelines for anticoagulant use in CKD and ESRD highlights the need for individualized, patient-centered approaches that account for comorbidities, genetics, and clinical context. Conclusions: Managing anticoagulation in CKD/ESRD is challenging due to complex coagulation profiles and altered pharmacokinetics. Judicious dosing, close monitoring, and patient-centered care are critical. High-quality randomized controlled trials are needed to establish clear guidelines and optimize therapy for this vulnerable population. Full article

Background: Although thromboembolic complications are recognized in the treatment of acute lymphoblastic leukemia (ALL), ischemic strokes are rare but severe events. These life-threatening complications not only pose an immediate risk but can also result in long-term neurological deficits, significantly impacting a patient’s quality of life. Identifying high-risk patients and implementing effective prophylaxis strategies are crucial for improving patient outcomes. In addition to strokes, these patients are also at risk of other embolic and thrombotic events, which can occur in up to 35% of patients. Despite this, there are still no clear guidelines for prophylactic management in pediatric patients treated for oncologic diseases. Results: Using the example of a 14-year-old male treated for ALL who suffered an ischemic stroke, we conducted a review of the literature on embolic and thrombotic events, neurological complications, methods of prevention, and ways to monitor and detect patients with an increased risk of such difficulties. We outlined our approach to the monitoring of prothrombotic factors, the interpretation of their levels, and the subsequent adjustment to prophylactic management based on these findings. As a result of this review, we reached two basic conclusions. First, thromboembolic episodes are not uncommon complications in pediatric patients and can cause long-lasting consequences, even after the cancer is cured. Secondly, despite such an urgent problem, clinicians are still struggling with the question of monitoring prothrombotic factors, the choice of drug, and the duration of prophylaxis. Their decisions depend on the experience of the treating center. Conclusions: The pediatric population being treated for malignant disease urgently requires the establishment of guidelines that standardize the management of thromboembolic events. Full article

Background: Shoulder arthroscopy is a common, minimally invasive surgery, but the resulting postoperative blood loss remains poorly understood. In this study, we quantified the intraoperative and postoperative blood loss, the hemoglobin (Hb) drop, and the effects of irrigation fluid retention, as well as the influence of solutions administered through infusions. Methods: A prospective observational study of 49 patients undergoing arthroscopic rotator cuff tear (RCT) repair was conducted. Their preoperative and postoperative Hb levels were measured, along with the intraoperative and postoperative blood loss. Irrigation fluid retention was analyzed, and multiple regression was used to assess the factors contributing to Hb drops. Results: The intraoperative blood loss amounted to 36.46 ± 20.34 mL, while the total blood loss reached 791.17 ± 280.96 mL, with 94.64% occurring postoperatively. The postoperative Hb drop (2.06 ± 0.74 g/dL) was significantly greater than the intraoperative Hb drop (0.11 ± 0.06 g/dL) (p < 0.001). An older age (p = 0.02) and male sex (p = 0.025) significantly predicted the postoperative Hb drop, while irrigation fluid retention and administration of crystalloids and colloids had no notable effects. Capsulotomy was associated with a small but significant increase in intraoperative blood loss (p < 0.01). Increased intraoperative blood loss correlated with greater irrigation fluid retention (r = 0.41, adjusted R2 = 0.152, p < 0.001). Conclusions: In shoulder arthroscopy, the postoperative blood loss and Hb drop are significantly greater than the intraoperative blood loss and Hb drop, as well as the fluid gain, emphasizing the need for careful monitoring, especially in high-risk patients. Future studies should investigate the potential impacts of low-molecular-weight heparin on postoperative bleeding after shoulder arthroscopy. Full article

Venous thromboembolic events (VTEs), especially in the form of portal vein thrombosis (PVT), are common complications of cirrhosis and are associated with significant morbidity. These patients can also be easily tipped toward bleeding because of deficiencies in procoagulant factors and pharmacokinetic and pharmacodynamic changes that occur during disease progression. Therefore, the understanding of how to use pharmacotherapy to treat VTE is a key to success in achieving VTE resolution without potentiating adverse bleeding events (AEs). Based on a review of the literature and the authors’ clinical experience, it was determined that unfractionated heparin (UFH), low molecular weight heparin (LMWH), fondaparinux, argatroban, warfarin, and direct oral anticoagulants all have evidence of use in patients with cirrhosis and VTE. However, the available literature is mostly limited to retrospective studies and case reports. There appears to be a paucity of prospective, randomized trials that compare the available pharmacotherapy at typical and adjusted doses. Overall, the decision as to the choice of agent and dose prescribed for anticoagulant therapy should include assessment on clot burden, bleeding risk, drug-drug/disease interactions, and the risk of presence of AEs. Full article

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, but their association with thrombosis presents significant clinical challenges. Patients with cancer already exhibit elevated risks for venous thromboembolism and arterial thrombosis, with treatment modalities like chemotherapy further exacerbating this risk. Emerging evidence suggests that ICIs contribute to thrombotic events through multifactorial mechanisms, including immune dysregulation, T cell activation, endothelial dysfunction, elevated tissue factor expression, and impaired fibrinolysis. Additional risk factors such as obesity, smoking, prior thrombotic events, and combination ICI therapy further increase thrombosis susceptibility. The literature reports varying incidence rates of ICI-associated thrombosis, with some studies indicating comparable risks to chemotherapy, while others highlight higher rates, particularly during the initial treatment phase. Management aligns with standard protocols for cancer-associated thrombosis, using low-molecular-weight heparin or direct oral anticoagulants, though optimal treatment duration and the role of prophylactic anticoagulation require further investigation. This review provides a comprehensive overview of the mechanisms, incidence rates, and clinical management strategies of ICI-associated thrombosis, emphasizing the importance of proactive risk assessment to optimize patient outcomes. Full article

Background: Adverse drug reactions have been reported as leading causes of morbidity and mortality. Unfractionated heparin- and low-molecular-weight heparin-induced hyperkalemia are side effects that have been reported in approximately 7 to 8% of heparin-treated patients. Algorithms, assessment tools, and decision aids are needed to assist in determining the causality of these adverse drug reactions. Aim: The aim of this study was to determine the number of case reports of hyperkalemia resulting from unfractionated heparin or low-molecular-weight heparin use by utilizing the Naranjo Adverse Drug Reaction Probability Scale. Methods: PubMed, International Pharmaceutical Abstracts, and the Cochrane Library were searched for relevant publications. Search terms and Boolean operators, including “hyperkalemia AND heparin”, “hyperkalemia AND low molecular weight heparin”, “heparin AND hypoaldosteronism”, and “low molecular weight heparin AND hypoaldosteronism”, were used. Searches were limited to case reports and human specimens. Results: A total of 29 case reports were identified, incorporating 38 patient cases. Of the 38 patient cases, 5 [4 involving unfractionated heparin and 1 involving low-molecular-weight heparin] (13.2%) utilized the Naranjo Adverse Drug Reaction Probability Scale to identify the possibility of an adverse drug reaction occurring due to exposure to unfractionated or low-molecular-weight heparin as probable. Conclusions: The available evidence suggests that clinicians’ use of the Naranjo Adverse Drug Reaction Probability Scale to determine the potential of hyperkalemia occurring due to exposure to unfractionated heparin and low-molecular-weight heparin is limited. Clinicians should be encouraged to utilize an objective monitoring tool to help standardize assessment of causality for all adverse drug reactions. Full article

Background/Objectives: This systematic review and meta-analysis aimed to determine the effectiveness of different aspirin dosages in preventing preeclampsia and its effect on other pregnancy-associated conditions. Methods: A comprehensive search of three databases (Pubmed, Embase, and Cochrane Library) was conducted for randomized controlled trials without time interval criteria, comparing aspirin at various doses with placebo or no specific preeclampsia prophylaxis. Eligible randomized controlled trials (RCTs) examined pregnant women receiving aspirin at any dose and time during their pregnancy, while the control group received a placebo, or placebo and a different dose of aspirin, or no specific preeclampsia prevention. No exclusion criteria were established regarding the population, study size, study site, or length of aspirin prophylaxis. Studies examining additional preventive medication (such as low-molecular-weight heparin) compared to aspirin without a placebo group were excluded. For all outcomes, the risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated. Meta-regression was performed to examine the relation between aspirin dosage and preeclampsia. Results: Based on the analysis of 31 studies involving 28,318 pregnancies and 20 studies involving 26,551 pregnancies, the early initiation of aspirin significantly reduced the overall incidence of preeclampsia (RR = 0.63, CI: 0.47–0.84) and perinatal death risk (RR = 0.82, CI: 0.72–0.93), respectively. Based on our meta-regression model, we could not establish a dose-dependent correlation between aspirin dosage and the risk of preeclampsia. Conclusions: Early-initiated aspirin prophylaxis is effective in preventing preeclampsia, without raising the incidence of placental abruption or increasing the amount of peripartum bleeding. No specific dose was superior to others; thus, further research should explore higher doses and focus on preterm preeclampsia, maternal–fetal complications, and bleeding. Full article

The primary challenges in the tissue engineering of small-diameter artificial blood vessels include inadequate mechanical properties and insufficient anticoagulation capabilities. To address these challenges, urea-pyrimidone (Upy)-based polyurethane elastomers (PIIU-B) were synthesized by incorporating quadruple hydrogen bonding within the polymer backbone. The synthesis process employed poly(L-lactide-ε-caprolactone) (PLCL) as the soft segment, while di-(isophorone diisocyanate)-Ureido pyrimidinone (IUI) and isophorone diisocyanate (IPDI) were utilized as the hard segment. The resulting PIIU-B small-diameter artificial blood vessel with a diameter of 4 mm was fabricated using the electrospinning technique, achieving an optimized IUI/IPDI composition ratio of 1:1. Enhanced by multiple hydrogen bonds, the vessels exhibited a robust elastic modulus of 12.45 MPa, an extracellular matrix (ECM)-mimetic nanofiber morphology, and a high porosity of 41.31%. Subsequently, the PIIU-B vessel underwent dual-functionalization with low-molecular-weight heparin and gelatin via ultraviolet (UV) crosslinking (designated as PIIU-B@LHep/Gel), which conferred superior biocompatibility and exceptional anticoagulation properties. The study revealed improved anti-platelet adhesion characteristics as well as a prolonged activated partial thromboplastin time (APTT) of 157.2 s and thrombin time (TT) of 64.2 s in vitro. Following a seven-day subcutaneous implantation, the PIIU-B@LHep/Gel vessel exhibited excellent biocompatibility, evidenced by complete integration with the surrounding peri-implant tissue, significant cell infiltration, and collagen formation in vivo. Consequently, polyurethane-based artificial blood vessels, reinforced by multiple hydrogen bonds and dual-functionalized with heparin and gelatin, present as promising candidates for vascular tissue engineering. Full article

Introduction: Severely ill COVID-19 patients receiving prophylactic-dose anticoagulation exhibit high rates of thrombosis and mortality. The escalation of anticoagulation also does not reduce mortality and has an uncertain impact on thrombosis rates. The reasons why escalated doses fail to outperform prophylactic doses in reducing risks of thrombosis and death in severely ill COVID-19 patients remain unclear. We hypothesized that escalated anticoagulation would not effectively prevent hypercoagulability and, consequently, would not reduce the risk of thrombosis and death in some severely ill patients. Methods: We conducted a prospective multicenter study that enrolled 3860 COVID-19 patients, including 1654 severely ill. They received different doses of low-molecular-weight or unfractionated heparin, and their blood coagulation was monitored with activated partial thromboplastin time, D-dimer, and Thrombodynamics. A primary outcome was hypercoagulability detected by Thrombodynamics. Blood samples were collected at the trough level of anticoagulation. Results: We found that escalated anticoagulation did not prevent hypercoagulability in 28.3% of severely ill patients at the trough level of the pharmacological activity. Severely ill patients with such hypercoagulability had higher levels of inflammation markers and better creatinine clearance compared to severely ill patients without it. Hypercoagulability detected by Thrombodynamics was associated with a 1.68-fold higher hazard rate for death and a 3.19-fold higher hazard rate for thrombosis. Elevated D-dimer levels were also associated with higher hazard rates for thrombosis and death, while shortened APTTs were not. The simultaneous use of Thrombodynamics and D-dimer data enhanced the accuracy for predicting thrombotic events and fatal outcomes in severely ill patients. Conclusions: Thrombodynamics reliably detects hypercoagulability in COVID-19 patients and can be used in conjunction with D-dimer to assess the risk of thrombosis and death in severely ill patients. The pharmacological effect of LMWH at the trough level might be too low to prevent thrombosis in some severely ill patients with severe inflammation and better creatinine clearance, even if escalated doses are used. Full article