Analysis of coagulation factors in angioedema/urticaria: increased values of D-dimer and fibrinogen in isolated angioedema.

INTRODUCTION: Recent research has shown that blood coagulation and the extrinsic coagulation cascade are involved in the pathogenesis of chronic spontaneous urticaria (CSU), but little is known about the coagulation factors in angioedema. METHODS: This study included 58 participants: 29 patients with chronic angioedema (14 with isolated angioedema and 15 with angioedema with wheals) and 29 healthy controls (HCs). We compared the values of coagulation factors in patients with isolated angioedema to those with wheals. Plasma levels of D-dimer, fibrinogen, and factor VII were measured by enzyme-linked immunosorbent assay (ELISA) for all participants. RESULTS: Significantly higher D-dimer (p = 0.016; ε² = 0.381) and fibrinogen (p = 0.044; ε² = 0.331) levels were recorded in patients with angioedema (both groups) than in the HCs, with higher levels for angioedema with wheals. Factor VII and fibrinogen levels did not differ significantly between the groups with angioedema, but coagulation factors were more often elevated in both angioedema groups than in HCs. CONCLUSIONS: One characteristic of angioedema is an elevated blood coagulation potential, which may help produce fibrin and may be important in controlling angioedema attacks.

Development of a chemiluminescence assay for tissue plasminogen activator inhibitor complex and its applicability to gastric cancer.

BACKGROUND: Venous thromboembolism (VTE), is a noteworthy complication in individuals with gastric cancer, but the current diagnosis and treatment methods lack accuracy. In this study, we developed a t-PAIC chemiluminescence kit and employed chemiluminescence to detect the tissue plasminogen activator inhibitor complex (t-PAIC), thrombin-antithrombin III complex (TAT), plasmin-α2-plasmin inhibitor complex (PIC) and thrombomodulin (TM), combined with D-dimer and fibrin degradation products (FDP), to investigate their diagnostic potential for venous thrombosis in gastric cancer patients. The study assessed variations in six indicators among gastric cancer patients at different stages. RESULTS: The t-PAIC reagent showed LOD is 1.2 ng/mL and a linear factor R greater than 0.99. The reagents demonstrated accurate results, with all accuracy deviations being within 5%. The intra-batch and inter-batch CVs for the t-PAIC reagent were both within 8%. The correlation coefficient R between this method and Sysmex was 0.979. Gastric cancer patients exhibited elevated levels of TAT, PIC, TM, D-D, FDP compared to the healthy population, while no significant difference was observed in t-PAIC. In the staging of gastric cancer, patients in III-IV stages exhibit higher levels of the six markers compared to those in I-II stages. The ROC curve indicates an enhancement in sensitivity and specificity of the combined diagnosis of four or six indicators. CONCLUSION: Our chemiluminescence assay performs comparably to Sysmex's method and at a reduced cost. The use of multiple markers, including t-PAIC, TM, TAT, PIC, D-D, and FDP, is superior to the use of single markers for diagnosing VTE in patients with malignant tumors. Gastric cancer patients should be screened for the six markers to facilitate proactive prophylaxis, determine the most appropriate treatment timing, ameliorate their prognosis, decrease the occurrence of venous thrombosis and mortality, and extend their survival.

A nomogram to predict mortality in patients with severe fever with thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is an acute infectious disease caused by a novel Bunyavirus infection with low population immunity and high mortality rate. Lacking specific therapies, the treatment measures vary with the severity of the disease, therefore, a case control study involved 394 SFTS patients was taken to determine risk factors for mortality. Comparative clinical data from the first 24 h after admission was collected through the electronic medical record system. Independent risk factors for death of SFTS were identified through univariate and multivariate binary logistic regression analyses. The results of the logistic regression were visualized using a nomogram which was created by downloading RMS package in the R program. In our study, four independent mortality risk factors were identified: advanced age(mean 70.45 ± 7.76 years), MODS, elevated APTT, and D-dimer. The AUC of the nomogram was 0.873 (0.832, 0.915), and the model passes the calibration test namely Unreliability test with P = 0.958, showing that the model's predictive ability is excellent. The nomogram to determine the risk of death in SFTS efficiently provide a basis for clinical decision-making for treatment.

New Diagnostic Tools for Pulmonary Embolism Detection.

The presentation of pulmonary embolism (PE) varies from asymptomatic to life-threatening, and management involves multiple specialists. Timely diagnosis of PE is based on clinical presentation, D-dimer testing, and computed tomography pulmonary angiogram (CTPA), and assessment by a Pulmonary Embolism Response Team (PERT) is critical to management. Artificial intelligence (AI) technology plays a key role in the PE workflow with automated detection and flagging of suspected PE in CTPA imaging. HIPAA-compliant communication features of mobile and web-based applications may facilitate PERT workflow with immediate access to imaging, team activation, and real-time information sharing and collaboration. In this review, we describe contemporary diagnostic tools, specifically AI, that are important in the triage and diagnosis of PE.

Massage for rehabilitation after total knee arthroplasty: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: This study aimed to evaluate the effectiveness of massage for postoperative rehabilitation after total knee arthroplasty (TKA). DATA SOURCES: The PubMed, Web of Science, EMBASE, Cochrane Library, and China National Knowledge Infrastructure (CNKI) databases were systematically searched from inception to May 2024. STUDY SELECTION: Any randomized controlled trials on the use of massage for postoperative TKA rehabilitation were included. DATA EXTRACTION: A meta-analysis of outcomes, including postoperative pain, knee range of motion (ROM), postoperative D-dimer levels, and length of hospital stay, was performed. The Cochrane Risk of Bias Assessment Tool was used to assess the risk of bias, and the data for each included study were extracted independently by two researchers. DATA SYNTHESIS: Eleven randomized controlled clinical trials with 940 subjects were included. The results showed that compared with the control group, the massage group experienced more significant pain relief on the 7th, 14th and 21st days after the operation. Moreover, the improvement in knee ROM was more pronounced on postoperative days 7 and 14. In addition, the massage group reported fewer adverse events. However, there was no statistically significant difference in the reduction in postoperative D-dimer levels between the patients and controls. Subgroup analysis revealed that massage shortened the length of hospital stay for postoperative patients in China but not significantly for patients in other regions. Nevertheless, the heterogeneity of the studies was large. CONCLUSIONS: Increased massage treatment was more effective at alleviating pain and improving knee ROM in early post-TKA patients. However, massage did not perform better in reducing D-dimer levels in patients after TKA. Based on the current evidence, massage can be used as an adjunctive treatment for rehabilitation after TKA.

[Impact of anemia on incidence of perioperative lower limb deep vein thrombosis in patients undergoing total hip arthroplasty].

Objective: To explore the impact of anemia on the incidence of perioperative lower limb deep vein thrombosis (DVT) in patients undergoing total hip arthroplasty (THA). Methods: A retrospective analysis was conducted on clinical data of 1 916 non-fracture patients who underwent THA between September 2015 and December 2021, meeting the selection criteria. Among them, there were 811 male and 1 105 female patients, aged between 18 and 94 years with an average of 59.2 years. Among the patients, 213 were diagnosed with anemia, while 1 703 were not. Preoperative DVT was observed in 55 patients, while 1 861 patients did not have DVT preoperatively (of which 75 patients developed new-onset DVT postoperatively). Univariate analysis was performed on variables including age, gender, body mass index (BMI), diabetes, hypertension, history of tumors, history of thrombosis, history of smoking, revision surgery, preoperative D-dimer positivity (≥0.5 mg/L), presence of anemia, operation time, intraoperative blood loss, transfusion requirement, and pre- and post-operative levels of red blood cells, hemoglobin, hematocrit, and platelets. Furthermore, logistic regression was utilized for multivariate analysis to identify risk factors associated with DVT formation. Results: Univariate analysis showed that age, gender, hypertension, revision surgery, preoperative levels of red blood cells, preoperative hemoglobin, preoperative D-dimer positivity, and anemia were influencing factors for preoperative DVT ( P<0.05). Further logistic regression analysis indicated that age (>60 years old), female, preoperative D-dimer positivity, and anemia were risk factors for preoperative DVT ( P<0.05). Univariate analysis also revealed that age, female, revision surgery, preoperative D-dimer positivity, anemia, transfusion requirement, postoperative level of red blood cells, and postoperative hemoglobin level were influencing factors for postoperative new-onset DVT ( P<0.05). Further logistic regression analysis indicated that age (>60 years old), female, and revision surgery were risk factors for postoperative new-onset DVT ( P<0.05). Conclusion: The incidence of anemia is higher among patients with preoperative DVT for THA, and anemia is an independent risk factor for preoperative DVT occurrence in THA. While anemia may not be an independent risk factor for THA postoperative new-onset DVT, the incidence of anemia is higher among patients with postoperative new-onset DVT.

Upcoming evidence in clinical practice of two-stage revision arthroplasty for prosthetic joint infection.

Total joint arthroplasty is the recommended treatment for patients with end-stage osteoarthritis, as it reduces disability and pain and restores joint function. However, prosthetic joint infection is a serious complication of this procedure, with the two-stage exchange being the most common treatment method. While there is consensus on diagnosing prosthetic joint infection, there is a lack of agreement on the parameters that can guide the surgeon in performing definitive reimplantation in a two-stage procedure. One approach that has been suggested to improve the accuracy of microbiologic investigations before definitive reimplantation is to observe a holiday period from antibiotic therapy to improve the accuracy of cultures from periprosthetic tissues, but these cultures report some degree of aspecificity. Therefore, several pieces of evidence highlight that performing reimplantation using continuous antibiotic therapy should be considered a safe and effective approach, leading to higher cure rates and a shorter period of disability. Dosage of C-reactive protein (CRP), erythrocyte sedimentation rate (ERS) and D-dimer are helpful in diagnosing prosthetic joint infection, but only D-dimer has shown sufficient accuracy in predicting the risk of infection recurrence after a two-stage procedure. Synovial fluid analysis before reimplantation has been shown to be the most accurate in predicting recurrence, and new cutoff values for leukocyte count and neutrophil percentage have shown a useful predictive rule to identify patients at risk of unfavourable outcome. A new scoring system based on a numerical score calculated from the beta coefficient derived through multivariate analysis of D-dimer levels, synovial fluid leukocytes and relative neutrophils percentage has demonstrated high accuracy when it comes to guiding the second step of two-stage procedure. In conclusion, reimplantation may be a suitable option for patients who are on continuous therapy without local symptoms, and with CRP and ERS within the normal range, with low synovial fluid leukocytes (< 952/mL) and a low relative neutrophil percentage (< 52%) and D-dimer below 1100 µg/mL. A numerical score derived from analysing these three parameters can serve as a valuable tool in determining the feasibility of reimplantation in these patients.

[Successful treatment of high-risk pulmonary embolism with low-dose anticoagulation: a case report].

Reperfusion is considered as the cornerstone of the treatment of high-risk pulmonary embolism (PE). However, when thrombolysis is contraindicated and surgery or interventional therapy is not available, the treatment of high-risk PE becomes very difficult. To our knowledge, there are no reports of successful treatment of high-risk PE with low-dose anticoagulation. On November 30, 2021, a 56-year-old male patient with subarachnoid hemorrhage was admitted to the emergency department of the First Affiliated Hospital of Chongqing Medical University. On the second day of admission, the patient suddenly went into shock during aneurysm clipping. After implementing D-dimer, markers of myocardial injury, echocardiography and computed tomography pulmonary angiography, a high-risk PE was diagnosed. Due to the contraindication of thrombolysis and the refusal of endovascular treatment, he was eventually cured with low-dose anticoagulation combined with vasopressors.

Risk factors associated with pulmonary hypertension in patients with active tuberculosis and tuberculous destroyed lung: a retrospective study.

Pulmonary tuberculosis (TB) can result in irreversible damage and lead to tuberculous destructive lung (TDL), a severe chronic lung disease that is associated with a high mortality rate. Additionally, pulmonary hypertension (PH) is a hemodynamic disorder that can be caused by lung diseases. The objective of this study is to investigate the risk factors associated with PH in active TB patients diagnosed with TDL. We conducted a retrospective review of the medical records of 237 patients who were diagnosed with TDL, active pulmonary tuberculosis, and underwent echocardiography at the Third People' Hospital of Shenzhen from January 1, 2016, to June 30, 2023. Univariate and multivariate logistic regression analyses were performed to identify factors that correlated with the development of pulmonary hypertension. Univariate and multivariate logistic regression analyses revealed that several factors were associated with an increased risk of pulmonary hypertension (PH) in individuals with tuberculosis destroyed lung (TDL). These factors included age (OR = 1.055), dyspnea (OR = 10.728), D-dimer (OR = 1.27), PaCO2 (OR = 1.040), number of destroyed lung lobes (OR = 5.584), bronchiectasis (OR = 3.205), and chronic pleuritis (OR = 2.841). When age, D-dimer, PaCO2, and number of destroyed lung lobes were combined, the predictive value for PH in patients with TDL was found to be 80.6% (95% CI 0.739-0.873),with a sensitivity of 76.6% and specificity of 73.2%. Advanced age, elevated D-dimer levels, hypercapnia, and severe lung damage were strongly correlated with the onset of PH in individuals with active pulmonary tuberculosis (PTB) and TDL. Furthermore, a model incorporating age, D-dimer, PaCO2, and the number of destroyed lung lobes might be valuable in predicting the occurrence of PH in patients with active PTB and TDL.

The prognostic value of prognostic nutritional index and renal function indicators for mortality prediction in severe COVID-19 elderly patients: A retrospective study.

Identifying prognostic factors in elderly patients with severe coronavirus disease 2019 (COVID-19) is crucial for clinical management. Recent evidence suggests malnutrition and renal dysfunction are associated with poor outcome. This study aimed to develop a prognostic model incorporating prognostic nutritional index (PNI), estimated glomerular filtration rate (eGFR), and other parameters to predict mortality risk. This retrospective analysis included 155 elderly patients with severe COVID-19. Clinical data and outcomes were collected. Logistic regression analyzed independent mortality predictors. A joint predictor "L" incorporating PNI, eGFR, D-dimer, and lactate dehydrogenase (LDH) was developed and internally validated using bootstrapping. Decreased PNI (OR = 1.103, 95% CI: 0.78-1.169), decreased eGFR (OR = 0.964, 95% CI: 0.937-0.992), elevated D-dimer (OR = 1.001, 95% CI: 1.000-1.004), and LDH (OR = 1.005, 95% CI: 1.001-1.008) were independent mortality risk factors (all P < .05). The joint predictor "L" showed good discrimination (area under the curve [AUC] = 0.863) and calibration. The bootstrapped area under the curve was 0.858, confirming model stability. A combination of PNI, eGFR, D-dimer, and LDH provides useful prognostic information to identify elderly patients with severe COVID-19 at highest mortality risk for early intervention. Further external validation is warranted.

Identification of early coagulation changes associated with survival outcomes post severe burns from multiple perspectives.

Coagulation alterations manifest early after severe burns and are closely linked to mortality outcomes. Nevertheless, the precise characterization of coagulation changes associated with early mortality remains elusive. We examined alterations in indicators linked to mortality outcomes at both the transcriptomic and clinical characteristic levels. At the transcriptomic level, we pinpointed 28 differentially expressed coagulation-related genes (DECRGs) following burn injuries and endeavored to validate their causal relationships through Mendelian randomization. DECRGs tied to survival exhibit a significant association with neutrophil function, wherein the expression of CYP4F2 and P2RX1 serves as robust predictors of fatal outcomes. In terms of clinical indicators, early levels of D-dimer and alterations in serum calcium show a strong correlation with mortality outcomes. Coagulation depletion and fibrinolytic activation, stemming from the hyperactivation of coagulation pathways post-severe burns, are strongly linked to patient mortality. Monitoring these early coagulation markers with predictive value can effectively identify individuals necessitating priority critical care.

Significance of serum protein electrophoresis in the diagnosis of Tsukayama type IV periprosthetic joint infection.

Objectives: To investigate the efficacy of serum protein electrophoresis (SPE) in the diagnosis of periprosthetic joint infection (PJI) after hip and knee arthroplasty. Methods: The medical records of patients undergoing hip and knee arthroplasty at a class A tertiary hospital between August 2013 and January 2021 were retrospectively investigated. A total of 179 patients were included and divided into two groups: 66 patients in the PJI group and 113 patients in the aseptic loosening (AL) group. Serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), D-dimer, Fibrinogen, Serum albumin and the proportion of serum protein in SPE were compared between the two groups. The diagnostic sensitivity and specificity were determined using the receiver operating characteristic (ROC) curve, and the diagnostic value was compared using the area under the ROC curve (AUC). Results: There was no significant difference in age, sex and body mass index (BMI) between PJI group and AL group (P>0.05), but there was significant difference in the ratio of hip to knee (X2 = 22.043, P<0.001). The CRP, ESR, D-dimer, Fibrinogen and the proportion of α1 globulin band in PJI group was 22.99(10.55,40.58) mg/L, 37.00(23.00,61.70) mm/h, 790.00(500.00,1500.00) ng/ml, 4.84(3.81,5.55) g/L and 5.80(5.00,7.73) % which was higher than that in AL group [1.89(0.50,4.12) mg/L, U=7.984, P<0.001; 10.10(7.00,16.90) mm/h, U=8.095, P<0.001; 570.00(372.50,780.00) ng/ml, U=3.448, P<0.001; 2.84(2.45,3.43) g/L, U=8.053, P<0.001 and 4.20(3.90,4.80) %, U=8.154, P<0.001]. The Serum albumin and the proportion of Albumin band in PJI group was 36.10(33.10,39.00) g/L and 49.00(44.95,52.20) % which was lower than that in AL group [38.10(34.00,41.10) g/L, U=-2.383, P=0.017 and 54.40(51.55,56.70) %, U=-6.162, P<0.001]. The proportion of In PJI group, the AUC of proportion of α1 globulin was 0.8654, which was equivalent to CRP (0.8698), ESR (0.8680) and outperformed that of fibrinogen (0.8025). Conclusions: Elevated proportion of α1 globulin in SPE presented with good diagnostic value for Tsukayama type IV PJI, and its accuracy was comparable to those of ESR and CRP. And α1 globulin can assist with CRP and ESR to determining the timing of second-stage revision.

"Ultrastructural changes of platelets in COVID-19 and chronic viral hepatitis patients ".

Platelet-viral interactions are evolving as a new concern. Coagulation disorder is a major consequence of the COVID-19 infection. In chronic hepatitis virus infections, defect in coagulation factors, thrombocytopenia and platelet function abnormalities are common. A SARS-CoV-2 infection on top of chronic viral hepatitis infection can be common in areas where viral hepatitis is endemic. Here, we investigate the platelet ultrastructural changes and estimate the serum platelet factor-4 (PF-4), ferritin, CRP, and D-dimer in COVID-19 patients (n = 60), COVID-19 patients with associated chronic viral hepatitis (n = 20), and healthy subjects (n = 20). Ultrastructural changes were demonstrated in all test groups, denoting platelet activation. In chronic viral hepatitis patients, Platelet ultrastrustural apoptotic changes were also seen. Significantly high levels of PF-4 were confirmed in moderate and severe COVID-19 patients (P.value <0.001), with a cut off value of 17 ng/ml for predicting disease severity. A positive correlation of PF-4 with the level of serum ferritin, CRP, and D-dimer (p value < 0.001) was noted, while negatively correlated with platelet count and platelet granule count (p value < 0.001). In our study, chronic viral hepatitis patients presented mild COVID-19 signs, and their PF-4 level was comparable with the subgroup of mild COVID-19 infection. The platelet's critical role in COVID-19 coagulopathy and chronic viral hepatitis is evidenced by the ultrastructural changes and the high levels of PF4. Moreover, a dual viral infection poses a substantial burden on the platelets, necessitating close monitoring of the patient's coagulation profile.

Occurrence and significance of elevated D-dimer levels in different types of osteomyelitis: a clinical study.

OBJECTIVE: Plasma D-dimer levels >0.5 mg/L are encountered in various conditions besides venous thromboembolism (VTE). Recent studies use them as a prognostic indicator for systemic and inflammatory diseases. The clinical significance of abnormal levels is unclear in osteomyelitis patients with baseline elevation. Our study reviews the occurrence and significance of >0.5 mg/L D-dimer levels in different types of osteomyelitis. PATIENTS AND METHODS: This study involved 125 individuals, out of which 94 were male and 31 were female. The patients were divided into two groups based on the results of bacterial culture testing. Group A comprised those who tested positive for bacterial culture, while group B included those who tested negative. Out of 68 samples tested, 56% were found to have Staphylococcus aureus. All 125 patients underwent blood testing, which included measuring the D-dimer levels, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), and MHR monocyte to high-density lipoprotein cholesterol (HDL-C) ratio in different types of osteomyelitis. The statistical analysis of these tests was carried out. RESULTS: Although there were no significant differences in white blood cell (WBC) count, Neutrophil count, Lymphocyte count, or erythrocyte sedimentation rate (ESR) as well as the NLR, PLR, LMR, MHR, HDL-C ratio. The C-reactive protein (CRP) levels were significantly higher in group A (26.13±50.30) than in group B (10.76±18.70) (p<0.05). D-dimer levels were elevated in 40.8% of patients with bacterial culture-positive osteomyelitis, negative culture osteomyelitis, implants with fractures, and no trauma osteomyelitis. No correlation was found between the increase in D-dimer levels and the presence of bacterial culture or implant-related osteomyelitis in patients. CONCLUSIONS: No significant correlation was found between D-dimers and osteomyelitis, including positive bacterial cultures, implant-related osteomyelitis, or osteomyelitis without trauma. However, 40% of the patients had higher D-dimer levels.

A new surface plasmon resonance-based immunoassay for rapid and sensitive quantification of D-dimer in human plasma for thrombus screening.

D-dimer is a protein fragment generated during the fibrin breakdown by plasmin, and it serves as a mature biomarker for diagnosing thrombotic disorders. A novel immunoassay method based on surface plasmon resonance (SPR) has been developed, validated, and successfully applied for the quantification of D-dimer in human plasma with high sensitivity and rapidity. In this methodological study, we investigated the activity and stability of the SPR biosensor, sample pre-processing, washing conditions, intra-day and inter-day precision and accuracy and detection parameters, including a limit of detection of 8.3 ng/mL, a detection range spanning from 31.25 to 4000 ng/mL, and a detection time of 20 min. We compared D-dimer plasma concentration determination results using SPR with a classical latex-enhanced immunoturbidimetric immunoassay in 29 healthy individuals and thrombotic patients, and both methods exhibited consistency. Furthermore, we propose a hypothesis about the relationship between the concentration of D-dimer and its molecular weight. With an increase in the D-dimer concentration in plasma, the D-dimer approaches its simplest form (190 kDa).

Coagulation activity and thrombotic risk following high-volume endurance exercise in recreationally active cyclists.

Despite the prognostic effect of physical activity, acute bouts of high-volume endurance exercise can induce cardiac stress and postexercise hypercoagulation associated with increased thrombotic risk. The aim of this study was to explore the effect of high-volume endurance exercise on coagulation and thrombotic activity in recreational cyclists. Thirty-four recreational cyclists completed 4.8 ± 0.3 h of cycling at 45 ± 5% of maximal power output on a bicycle ergometer. Intravenous blood samples were collected preexercise, immediately postexercise, 24 and 48 h postexercise, and analyzed for brain natriuretic peptide (BNP), cardiac troponin (cTn), C-reactive protein (CRP), D-dimer, thrombin-antithrombin (TAT) complex, tissue factor (TF), tissue factor pathway inhibitor (TFPI), and TF-to-TFPI ratio (TF:TFPI). An increase in cTn was observed postexercise (P < 0.001). CRP concentrations were increased at 24 and 48 h postexercise compared with preexercise concentrations (P ≤ 0.001). TF was elevated at 24 h postexercise (P < 0.031) and TFPI was higher immediately postexercise (P < 0.044) compared with all other time points. TF:TFPI was increased at 24 and 48 h postexercise compared with preexercise (P < 0.025). TAT complex was reduced at 48 h postexercise compared with preexercise (P = 0.015), D-dimer was higher immediately postexercise compared with all other time points (P ≤ 0.013). No significant differences were observed in BNP (P > 0.05). High-volume endurance cycling induced markers of cardiac stress among recreational cyclists. However, plasma coagulation and fibrinolytic activity suggest no increase in thrombotic risk after high-volume endurance exercise.NEW & NOTEWORTHY In this study, a high-volume endurance exercise protocol induced markers of cardiac stress and altered plasma coagulation and fibrinolytic activity for up to 48 h in recreationally active cyclists. However, analysis of coagulation biomarkers indicates no increase in thrombotic risk when appropriate hydration and rest protocols are implemented.

D-dimer and risk of venous thromboembolism recurrence: Comparison of two studies with similar designs but different laboratory and clinical results.

BACKGROUND: D-dimer testing may help deciding the duration of anticoagulation in subjects at high risk of venous thromboembolism (VTE) recurrence. Two management studies on this issue have been published (DULCIS in 2014 and APIDULCIS in 2022). They had similar designs but had important different results. Aim of this article is to compare their results. METHODS: Both studies were finalized to extend anticoagulation [with vitamin K anticoagulants (VKAs) in DULCIS or apixaban 2.5 mg BID (kindly provided by BMS-Pfizer Collaboration) in APIDULCIS] only in patients with positive D-dimer results. RESULTS: More D-dimer assays resulted positive in APIDULCIS than in DULCIS (61.1 % vs 47.7 %, respectively; p < 0.0001). While only 4 (0.5 %) refused low dose apixaban in APIDULCIS, the 22.6 % of patients with positive D-dimer refused to resume VKAs in DULCIS; their rates of recurrence were 187 and 8.8 per 100 person-years, respectively (incidence rate ratio [IRR]: 21.2). The incidence of bleeding was low in those receiving apixaban vs those who resumed VKAs (0.4 vs 2.3 per 100 person-years, respectively; IRR 0.17;). While the recurrence rate was low and similar in the studies in subjects who resumed anticoagulation, it was significantly higher in APIDULCIS than in DULCIS in those who stopped anticoagulation for negative D-dimer (5.6 vs 3.0 per 100 person-years, respectively; IRR 1.9). CONCLUSION: The low dose Apixaban for extended VTE treatment is effective and safe, and well accepted by patients. Why subjects who stopped anticoagulation for negative D-dimer had a higher recurrence rate in APIDULCIS than in DULCIS remains to be explained.

Reference Value Fibrin Monomer in Healthy Children: A Cross-Sectional Study.

The objective of this study is to determine the fibrin monomer reference intervals in healthy children. This cross-sectional study was conducted in the Hematology Department at Vietnam National Children's Hospital (April 2023 to March 2024). Children without prior history of clotting disorders or anticoagulants use hospitalized in preparation for orthopedic surgery or inguinal hernia surgery were enrolled in the study. The fibrin monomer test method was the quantitative fibrin monomer test on the STA-R system (Diagnostica Stago™, France). Eighty-six children (58 males and 28 females) were enrolled in the study. The median (interquartile range, 2.5th-97.5th) fibrin monomer value of the study subjects was 2.56 (0.11-5.93) µg/mL, with no statistically significant difference in fibrin monomer values among the age groups of 1 month to 3 years, 3 years to 13 years, and 13 years to 18 years. This is the first study conducted in Vietnam to determine reference values of fibrin monomer in children. This information can help in the diagnosis and treatment of early hypercoagulation stage and disseminated intravascular coagulation in children.

Incidence of deep venous thrombosis in patients with hemophilia undergoing bilateral simultaneous total knee arthroplasty: a retrospective cohort study.

BACKGROUND: Hemophilic arthropathy usually affects the knees bilaterally. In order to reduce costs and improve rehabilitation, bilateral simultaneous total knee arthroplasty (TKA) can be performed. However, pharmacological prophylaxis for deep venous thrombosis (DVT) remains controversial in patients with severe hemophilia. The purpose of this study was to establish the incidence of DVT in severe hemophilia A patients undergoing bilateral simultaneous TKA without pharmacological thromboprophylaxis. METHODS: Consecutive patients with severe hemophilia A undergoing bilateral simultaneous TKA at a single center between January 2015 and December 2020 were retrospectively reviewed. All patients received a modified coagulation factor substitution regimen. Tranexamic acid (TXA) was used for hemostasis in all patients during surgery. All patients followed a standardized postoperative protocol with routine mechanical thromboprophylaxis, and none received anticoagulation. D-dimer was measured preoperatively, on the day of the operation and on postoperative days 1, 7 and 14. Ultrasound (US) of the lower extremities was performed before (within 3 days of hospitalization) and after surgery (days 3 and 14) to detect asymptomatic DVT. Patients were followed up until 2 years after surgery for the development of symptomatic DVT or pulmonary embolism (PE). RESULTS: 38 male patients with severe hemophilia A underwent 76 simultaneous TKAs. Mean (± standard deviation) age at the time of operation was 41.7 (± 17.1) years. Overall, 47.3% of patients had D-dimer concentrations above the threshold 10 µg/mL on day 7 and 39.5% on day 14. However, none of the patients had DVT detected on postoperative US, nor developed symptomatic DVT or PE during the 2-year follow-up. CONCLUSIONS: The risk of DVT in patients with severe hemophilia A after bilateral simultaneous TKA is relatively low, and routine pharmacological thromboprophylaxis may not be needed.