Elevated Plasma D-dimer Levels Research Articles

Elevated preoperative plasma D-dimer level is an independent prognostic factor for pediatric patients with Wilms tumor.

Elevated plasma D-dimer levels are an unfavorable prognostic indicator for various tumors. However, its predictive value for prognosis in pediatric patients with Wilms tumor (WT) remains unknown. We aimed to investigate the clinical and prognostic value of preoperative plasma D-dimer levels and other clinicopathological characteristics in patients with favorable histology WT (FHWT). The clinical data of 74 children with FHWT from January 2010 to January 2022 were retrospectively analyzed. The clinicopathologic characteristics, preoperative laboratory parameter results, including D-dimer level, and follow-up data were collected. Based on the postoperative recovery status, the patients were divided into tumor-free survival and disease progression groups. The risk factors affecting disease progression in pediatric patients with WT and the impact of plasma D-dimer levels on overall survival (OS) were evaluated. Over a median follow-up of 33 months (range: 2-145 months), 56 patients survived without progression. Relapses and metastases occurred in 18 patients, of which four survived and 14 died. Higher preoperative plasma D-dimer levels (>0.865) (Odds ratio [OR] = 7.240, 95% confidence interval (CI) = 1.276-33.272, P = 0.011) and tumor rupture (OR = 19.984, 95% CI = 1.182-338.013, P = 0.038) were independent prognostic factors for disease progression. Additionally, patients with elevated D-dimer levels demonstrated a worse 5-year OS than those with low D-dimer levels (Hazard ratio (HR) =4.278, 95% CI = 1.074-17.035, P = 0.039). Elevated D-dimer levels are a prognostic factor for a poorer outcome in pediatric patients with WT and are expected to become a clinical biomarker for predicting the prognosis of WT.

Treatment strategies for patients with out-of-hospital cardiac arrest associated with traumatic brain injury: A case series

IntroductionCollapse after out-of-hospital cardiac arrest (OHCA) can cause severe traumatic brain injury (TBI). We aimed to investigate the clinical characteristics and treatment strategies for patients with OHCA and TBI. MethodsWe analyzed a consecutive cohort of patients with intrinsic OHCA retrospectively treated between January 2011 and December 2021 at a single critical care center, and presented a case series of seven patients. Patients with collapse-related TBI were examined for the causes and situations of cardiac arrest, laboratory data, radiological images, targeted temperature management (TTM), coronary angiography (CAG), percutaneous coronary intervention (PCI), and extracorporeal cardiopulmonary resuscitation (ECPR). ResultsOf the 197 patients with intrinsic OHCA, 7 (3.6%) had TBI (age range: 49–70 years; 6 men). All seven patients presented with ventricular fibrillation in the initial electrocardiograms, with four refractory cases treated with ECPR. All patients underwent CAG under heparinization, and four underwent PCI with antiplatelet administration. Initial head computed tomography indicated an intracranial hemorrhage (ICH) in three patients. ICH appeared or was exacerbated in six patients after CAG with or without PCI, except in one who underwent delayed PCI. All patients displayed elevated plasma D-dimer levels, and four underwent neurosurgical procedures. Four patients survived (three with cerebral performance category [CPC] 2, one with CPC 3) and three died; two had hypoxic-ischemic brain injury and one had severe TBI. ConclusionDelayed ICH occurred frequently. Individualized management is required based on the extent of brain and cardiac damage, including optimal TTM, PCI procedures, and antiplatelet medications. Early detection of ICH and emergency treatment are critical for multi-disciplinary collaboration.

Clinical Characteristics of Asymptomatic Thromboembolism in Psychiatric Inpatients: A Retrospective Study.

Venous thromboembolism (VTE) poses a significant threat to individuals' health, yet its correlation with mental disorders remains underappreciated. Here, we conducted a retrospective analysis to explore the characteristics of psychiatric patients presenting with VTE. We retrospectively analyzed psychiatric inpatients with elevated plasma D-dimer levels at the Mental Health Center, First Affiliated Hospital, Zhejiang University School of Medicine, from January 2014 to January 2022. The inclusion criteria comprised comprehensive demographic and clinical profiles, including laboratory and imaging findings. A cohort of 33 eligible patients was included, with plasma D-dimer levels ranging from 880 to 10,700 μg/L FEU. Significantly higher D-dimer levels were observed in patients diagnosed with severe mental disorders (SMD), such as schizophrenia and bipolar disorder, compared to those with mild mental disorders (MMD), including depression and anxiety disorders (p = 0.007). Furthermore, individuals receiving antipsychotic medications for less than one year exhibited elevated D-dimer levels compared to those on treatment for over one year (p = 0.005). However, normalization of D-dimer levels did not demonstrate a significant association with psychiatric diagnosis or treatment duration (p > 0.05). Our findings suggest that patients diagnosed with SMD or those undergoing antipsychotic treatment for less than one year may have elevated D-dimer levels, indicating a potential predisposition to VTE severity. This underscores the importance of recognizing VTE risk in individuals with severe mental disorders and warrants further investigation into the impact of antipsychotic treatment duration on thrombotic risk.

Elevated preoperative plasma D-dimer level was an independent prognostic factor for patients with PDAC after curative resection: a retrospective analysis.

In this study, the relationship between preoperative plasma D-dimer level and overall survival and recurrence free survival were evaluated in patients with curative resection of pancreatic ductal adenocarcinoma. Preoperative plasma D-dimer level of 573 patients with pancreatic ductal adenocarcinoma were collected. The univariate and multivariate Cox hazard models were used to identify independent variables associated with overall survival and recurrence free survival in this study. The Kaplan-Meier method was used to evaluate overall survival and recurrence free survival, and the differences between survival curves were analyzed using the Log-rank test. Continuous variables were presented as $\overline{x}\pm s$, parametric analysis was performed using t-test. Categorical variables were analyzed by means of the chi-square or Fisher's exact test. Based on the analysis for the whole study, the results showed that patients in the elevated plasma D-dimer levels had a tendency to have an elder mean age (58.69±8.32years vs. 63.05±8.44years, P<0.001), larger tumour size ≥4cm (P=0.006), advanced T stage (P=0.024), N stage (P=0.041), Tumor, Node and Metastasis (TNM) stage (P=0.029) and postoperative complications (P=0.042) was more likely occurred. Besides, according to the results of Cox multivariate analysis, elevated preoperative plasma D-dimer level was an independent prognostic factor not only for overall survival (Hazard Ratio (HR):1.430, 95% Confidence Interval (CI) (1.163-1.759), P=0.001) but also for recurrence free survival (HR:1.236, 95% CI (1.018-1.500), P=0.032). In our study, the elevated preoperative plasma D-dimer level may act as an independent prognostic factor for overall survival and recurrence free survival in patients with pancreatic ductal adenocarcinoma after curative resection. Pancreatic ductal adenocarcinoma patients with elevated preoperative plasma D-dimer level had a worse prognosis than those with normal plasma D-dimer level; and the elevated preoperative plasma D-dimer level may imply heavy tumour burden and provide supplementary information regarding disease status.

Clinicoepidemiological Profile of Patients with Chronic Urticaria and its Association with D-dimer Levels at a Tertiary Care Centre: A Prospective Cohort Study

Introduction: Chronic urticaria is a commonly encountered, long-standing skin condition that typically lasts for more than six weeks and has various underlying aetiologies, including chronic infections, infestations, immunological and non immunological causes, and physical factors. In some cases, it may be idiopathic. Recent studies have shown that the activation of the coagulation cascade is involved in the development of chronic urticaria. This involvement is reflected in plasma D-dimer levels, which are explored in the current study. Aim: To assess the epidemiological and clinical characteristics of urticaria and their association with D-dimer levels in a tertiary care centre. Materials and Methods: This prospective cohort study was conducted at Department of Dermatology, Great Eastern Medical School and Hospital, Srikakulam, Andhra Pradesh, India, from August 2022 to July 2023. The study included 100 chronic urticaria patients attending the dermatology Outpatient Department (OPD) to investigate various clinical types and their epidemiological factors. D-dimer levels were estimated using the latex-enhanced immunoturbidimetry assay method. The mean and range were calculated, and statistical analysis of various clinic-epidemiological characteristics was performed using Pearson’s Chi-square test. A p-value &lt;0.05 was considered statistically significant. Results: Among the 100 patients with chronic urticaria, 40 (40%) were males and 60 (60%) were females. The mean age of presentation was 30 years, and the mean duration was 20.5 months. Elevated plasma D-dimer levels were noted in 40 (40%) of the study population. Chronic Spontaneous Urticaria (CSU) constituted 92 (92%) of the cases, followed by Chronic Inducible Urticaria (CIU) with 4 (4%) cases and 4 (4%) cases with CSU+CIU. Angioedema was noted in 20 (20%) of the cases in the present study. Thyroid disorder was seen in 12 (12%) of the study population. The majority of patients (44%) had mild urticaria. The mean Urticaria Activity Score (UAS) score before treatment was 21.08. A statistically significant association was found between elevated plasma D-dimer levels and age range, duration of chronic urticaria, disease severity, angioedema, and response to antihistamines. The response to antihistamines was graded based on the UAS7 score calculated before and after treatment. Conclusion: The present study provides additional evidence to the existing literature by establishing an association between D-dimer levels and factors such as severity and angioedema. It also provides important insights into the relationship between age range, duration of chronic urticaria, and elevated plasma D-dimer levels by establishing statistical significance between these factors.

The prognostic and predictive value of plasma D-dimer in children with neuroblastoma: a 7-year retrospective analysis at a single institution.

Elevated plasma D-dimer level is a poor prognostic factor for many solid tumors. However, limited research has been conducted on D-dimer in children with neuroblastoma (NB), and its clinical significance remains unclear. The present study investigated the clinical and prognostic significance of D-dimer in pediatric NB patients. A retrospective analysis of all newly admitted NB patients was conducted from January 2014 to December 2020. Baseline clinicopathological features, preoperative laboratory parameters, and follow-up information were collected. Univariate and multivariate analyses were performed to determine the relationship between D-dimer level, clinical features, and the prognostic value. Among 266 patients, the median value of D-dimer was 2.98 ng/mL, of which 132 patients showed elevated D-dimer levels before surgery (>2.98 ng/mL). Univariate analysis revealed that elevated D-dimer was significantly associated with age, hemoglobin, neutrophil-to-lymphocyte ratio, neuron-specific enolase, 24-hour vanillylmandelic acid, overall survival, and so on (P < 0.05). Patients with elevated D-dimer levels had shorter median overall survival time when compared with normal D-dimer levels (P = 0.01). The prognosis was better in patients with normal D-dimer levels when combined with lower age, ganglioneuroblastoma tumor type, lower stage on International Neuroblastoma Staging System, low-risk group, and without bone metastasis or bone marrow metastasis. The continuous increase of D-dimer level after treatment indicated tumor recurrence or progression. A high D-dimer level is associated with low overall survival, and an elevated D-dimer level after treatment indicates tumor recurrence and progression. D-dimer can be used as one of the evaluation factors for NB treatment or prognosis.

Elevated plasma D-dimer levels in patients with anti-N-methyl-D-aspartate receptor encephalitis.

We aimed to explore the difference in coagulation function between healthy individuals and patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis and its relationship with disease severity. We retrospectively compared coagulation function in 161 patients with first-attack anti-NMDAR encephalitis and 178 healthy individuals. The association between D-dimer levels and disease severity was analyzed using binary logistic regression. Receiver operating characteristic (ROC) curves were used to analyze the predictive value of D-dimer levels for the severity of anti-NMDAR encephalitis. Compared to control individuals, patients with anti-NMDAR encephalitis had higher D-dimer levels (median 0.14 vs. 0.05 mg/L, p < 0.001), blood white blood cell (WBC) count (median 8.54 vs. 5.95 × 109/L, p < 0.001), and neutrophil count (median 6.14 vs. 3.1 × 109/L, p < 0.001). D-dimers (median 0.22 vs. 0.10 mg/L, p < 0.001), blood WBC count (median 9.70 vs. 7.70 × 109/L, p < 0.001), neutrophil count (median 7.50 vs. 4.80 × 109/L, p < 0.001), and C-reactive protein (median 2.61 vs. 1.50 mg/l, p = 0.017) were higher; however, eosinophils (median 0.02 vs. 0.06 × 109/L, p < 0.001), and blood calcium (median 2.26 vs. 2.31 mmol/L, p = 0.003) were lower in patients with severe forms of anti-NMDAR encephalitis than in those with mild to moderate forms, and were associated with initial modified Rankin Scale scores. Multivariate analysis showed that D-dimer levels were significantly associated with severity [odds ratio =2.631, 95% confidence interval (CI) = 1.018-6.802, p = 0.046]. The ROC curve was used to analyze the predictive value of D-dimer levels for disease severity. The area under the curve was 0.716 (95% CI = 0.64-0.80, p < 0.001), and the best cut-off value was D-dimer = 0.147 mg/L (sensitivity 0.651; specificity, 0.705). Serum D-dimer and neutrophil levels were independent predictors of disease severity in patients with first-attack anti-NMDAR encephalitis.

Elevated plasma D-dimer levels are associated with the poor prognosis of critically ill children.

BackgroundD-dimer has been shown as a valuable predictor for the prognosis of sepsis. But the prognostic association of an elevated D-dimer with adverse outcomes of all critical illnesses in pediatric intensive care unit (PICU) has received far less emphasis.MethodsThis was a single-center retrospective study, including 7,648 critical patients aged between 28 days and 18 years from the pediatric intensive care (PIC) database from 2010 to 2018. The primary outcome was the in-hospital mortality rate.ResultsHigher levels of D-dimer, INR, PT, APTT, and lower Fib were observed in the non-survivor group (all P < 0.001). D-dimer, INR, PT and APTT were independent risk factors for prognosis in critically ill children. There was the highest AUROC in D-dimer for predicting in-hospital mortality of critically ill patients compared with INR, PT, APTT, and Fib (D-dimer: 0.77 vs. INR: 0.73 vs. PT: 0.73 vs. APTT: 0.64 vs. Fib: 0.60). The cut-off value, sensitivity, and specificity of D-dimer were 1.53, 0.65, and 0.77, respectively. Subgroup analysis showed a stable evaluation effectiveness of D-dimer for predicting in-hospital mortality of critically ill patients in the age and gender groups.ConclusionsWe found poorer coagulation function in the non-survivors compared with the survivors. Among the coagulation indicators, D-dimer was most strongly associated with in-hospital mortality of unselected critically ill children.

Pulmonary Tuberculosis-Related Ischemic Stroke: A Retrospective Case Control Study.

ObjectiveThere have been only a few studies of ischemic stroke in patients with pulmonary tuberculosis (pTB). This study aimed to explore the clinical features and the underlying pathogenesis of pulmonary tuberculosis-related ischemic stroke (TBRIS).MethodsActive pulmonary tuberculosis patients with acute ischemic stroke (without conventional vascular risk factors) were recruited as the TBRIS group. Patients who solely had active pulmonary tuberculosis were recruited as the control group (pTB group). Clinical data were collected, and multiple logistic regression analysis was applied to analyze the independent risk factors for TBRIS.ResultsA total of 179 TBRIS patients and 179 pTB patients were enrolled. Most (56.42%) of the TBRIS patients experienced the ischemic stroke events within 3 months after the diagnosis of tuberculosis. The multiple logistic regression analysis revealed that an increased mean platelet volume; elevated plasma D-dimer, C-reactive protein, and serum ferritin levels; and an increased monocyte percentage were independent risk factors for TBRIS. The AUC of the identification model was 0.778, with a sensitivity of 70.30% and a specificity of 78.90%.ConclusionThe findings in the present study suggested that most of the TBRIS patients experienced ischemic stroke within 3 months after the diagnosis of tuberculosis. And the more intensive immune response to the tuberculosis infection in the TBRIS group contributed to the initiation of platelet activation and to the development of a hypercoagulable state, which were attributed to the pathogenesis of TBRIS. Index of TBRIS equaling to 0.3234 facilitates clinicians to identify the pTB patients who were at higher risk for TBRIS, and allow physicians to take further effective measures to prevent ischemic stroke in patients with pTB. However, our findings will need to be confirmed by further studies.

Preoperative incidence and risk factors of deep vein thrombosis in patients with an isolated patellar fracture

PurposeThis study aimed to investigate the incidence, location, and related factors of preoperative deep venous thrombosis (DVT) in patients with isolated patellar fractures.MethodsPatients with an isolated patellar fracture, admitted between January 2013 and December 2019 at our institution, were retrospectively analyzed. Upon admission, patients underwent routine Doppler ultrasound scanning (DUS) of the bilateral lower extremities to detect DVT; those with DVT were assigned to the case group and those without DVT to the control group. Patients in both groups did not perform preoperative off-bed weight-bearing exercises. Data on demographics, comorbidities, and laboratory test results upon admission were extracted. Variables were evaluated between the two groups using univariate analyses, and independent risk factors associated with DVT were identified by logistic regression analysis.ResultsDuring the study period, 827 patients were included, of whom 5.8% (48/827) were found to have preoperative DVT. In DVT patients, 85.4%(41/48) were injured, 8.3%(4/48) were not injured, and 6.3%(3/48) were lower limbs. Multivariate analysis showed that male (male vs. female, odds ratio, OR = 2.25), delayed from injury to DUS (in each day, OR = 1.29), and elevated plasma D-dimer level (> 0.5 µg/mL, OR = 2.47) were independent risk factors associated with DVT.ConclusionsDespite the low prevalence of DVT after an isolated patellar fracture, this study underscores the importance of identifying those with a high risk of DVT, especially those with multiple identifiable factors, and encourage the early targeted use of anti-thromboembolic agents to reduce DVT occurrence.

Pattern of Conventional Coagulation and Thromboelastographic Parameters in Patients with COVID-19 Diseases and Association of COVID-Associated Coagulopathy with Mortality in Intensive Care Unit.

Background:Knowledge of underlying pathophysiology of coagulopathy is evolving and the pattern of coagulation parameters in coronavirus disease 2019 (COVID-19)–associated diseases is still not very clear.Aims:In the present study, we aimed to find out the pattern and distribution of conventional coagulation parameters and thromboelastographic (TEG) parameters in COVID-19–associated coagulopathy (CAC) in survivors and nonsurvivors at 28 days.Setting and Design:The present prospective observational study was conducted at a tertiary care COVID-19 intensive care unit (ICU) facility from March 21, 2020, to July 15, 2021.Materials and Methods:Admission clinical and laboratory data (conventional coagulation, inflammatory and TEG parameters, and disease severity parameters) of 64 COVID-19 patients admitted to the ICU were collected. Patients were divided into two groups, i.e., survivors and nonsurvivors.Statistical Analysis:Data were compared between two groups, i.e., survivors versus no survivors on 28 days using Student's t-test/Mann–Whitney U-test or Chi-square test/Fisher's exact test.Results:Admission mean plasma fibrinogen levels (474.82 ± 167.41 mg.dL−1) and D-dimer were elevated (1.78 [0.66, 3.62] mg.mL−1) in the COVID-19 ICU patients. Overall, COVID-19 patients had mean lower normal platelet count (150 ± 50 × 103 cells.mm−3), with marginally elevated prothrombin time (16.25 ± 3.76 s) and activated partial thromboplastin time (38.22 ± 16.72 s). A 65.6% (42/64) TEG profile analysis showed a normal coagulation profile, and the rest 21.9% (14/64) and 12.5% (8/64) had hypercoagulable and hypocoagulable states, respectively. Plasma D-dimer level was markedly elevated in nonsurvivors compared to survivors (P < 0.05), while no other conventional coagulation parameters and TEG profile demonstrated statistically significant between the two groups.Conclusion:Markedly elevated plasma D-dimer level was observed in nonsurvivors of COVID-19 ICU patients. A large portion of COVID-19 ICU patients had a normal TEG profile. Conventional coagulation parameters and TEG profile were similar between survivors and nonsurvivors.

The association between preoperative plasma D-dimer levels and early postoperative outcomes in patients with esophageal cancer

Background: The present study aimed to evaluate the efficacy of plasma D-dimer levels in predicting early morbidity and mortality in patients with esophageal cancer. Methods: for this purpose, 60 patients who did surgery for middle- (n=35) and lower-thoracic esophageal cancer (n=25) were recruited. Then, preoperative plasma D-dimer levels were measured in a quantitative and qualitative manner and their relation with postoperative outcomes in each type of cancer was assessed for six months. Results: With regard to the middle-thoracic esophageal cancer, complications were observed in 14 cases and deaths were reported in six individuals. Considering the lower type, morbidity was found in 11 cases and mortality was seen in five patients. In both types of cancer, plasma D-dimer levels were significantly higher in patients with complications or deaths compared with those who were not. Sensitivity, specificity, as well as positive and negative predictive value (P/NPV) of plasma D-dimer levels were 90.91%, 78.57%, 76.92%, and 91.67% for diagnosing morbidity of the lower-thoracic esophageal cancer and 80%, 85%, 57.14, 94.44% for predicting mortality in this type of cancer. Moreover, the given values were equal to 71.43%, 76.19%, 66.67%, and 80% for diagnosing complications of the middle-thoracic esophageal cancer and 83.3%, 72.41%, 38.46%, 95.45% in predicting deaths induced by this type of cancer. Conclusion: It was concluded that elevated plasma D-dimer levels could be accompanied by adverse events and early poor postoperative outcomes for esophageal cancer.

Functional decline in hospitalized older patients with coronavirus disease 2019: a retrospective cohort study

BackgroundThis study aimed to determine the frequency of functional decline and to identify the factors related to a greater risk of functional decline among hospitalized older patients with coronavirus disease 2019 (COVID-19).MethodsWe reviewed the medical records of patients aged over 65 years who were admitted to a tertiary care hospital for COVID-19 over 1 year from February 2020. We evaluated the proportion of functional decline, which was defined as a decrease in the Barthel Index score from before the onset of COVID-19 to discharge. Multivariable logistic regression analyses were performed to evaluate the associations between the demographic and clinical characteristics of patients at admission and a greater risk of functional decline. Two sensitivity analyses with different inclusion criteria were performed: one in patients without very severe functional decline before the onset of COVID-19 (i.e., limited to those with Barthel Index score ≥ 25), and the other with a composite outcome of functional decline and death at discharge.ResultsThe study included 132 patients with COVID-19; of these, 72 (54.5%) developed functional decline. The severity of COVID-19 did not differ between patients with functional decline and those without (P = 0.698). Factors associated with a greater risk of functional decline included female sex (adjusted odds ratio [aOR], 3.14; 95% confidence interval [CI], 1.25 to 7.94), Barthel Index score < 100 before the onset of COVID-19 (aOR, 13.73; 95% CI, 3.29 to 57.25), and elevation of plasma D-dimer level on admission (aOR, 3.19; 95% CI, 1.12 to 9.07). The sensitivity analyses yielded similar results to those of the main analysis.ConclusionsOver half of the older patients who recovered from COVID-19 developed functional decline at discharge from a tertiary care hospital in Japan. Baseline activities of daily living impairment, female sex, and elevated plasma D-dimer levels at admission were associated with a greater risk of functional decline.

Elevated plasma D-dimer levels are associated with risk of future incident venous thromboembolism

BackgroundD-dimer, a global biomarker for activation of the coagulation and fibrinolysis systems, is useful in assessing individual risk of venous thromboembolism (VTE) recurrence. However, there is limited information on the association between D-dimer and risk of a first lifetime VTE event. ObjectivesTo investigate the association between plasma D-dimer levels and risk of future incident VTE. MethodsA population-based nested case-control study, comprising 414 VTE patients and 843 randomly selected age- and sex-matched controls, was derived from the Tromsø Study (1994–2007). D-dimer was measured in plasma samples collected at cohort baseline (1994–95). Odds ratios (ORs) for VTE with 95% confidence intervals (CIs) were estimated according to quartile cut-offs of D-dimer levels determined in controls. ResultsThe risk of VTE increased across quartiles of D-dimer levels (Ptrend = 0.014) in the age- and sex-adjusted model. Participants with plasma D-dimer levels in the highest quartile (≥152 ng/mL) had an OR for VTE of 1.65 (95% CI 1.14–2.40) compared with those in the lowest quartile (<94 ng/mL). The ORs were marginally attenuated after additional adjustment for body mass index (BMI) (OR 1.51, 95% CI 1.04–2.20) and C-reactive protein (CRP) (OR 1.34, 95% CI 0.90–1.98). Similar results were obtained for VTE subgroups, i.e. deep vein thrombosis, pulmonary embolism, and provoked/unprovoked events. ConclusionOur results indicate that elevated plasma D-dimer levels are associated with increased risk of incident VTE. However, the attenuation of risk estimates upon additional adjustment for BMI and CRP suggests that D-dimer partly reflects underlying conditions associated with obesity and an inflammatory state.

Cerebral Venous Thrombosis Developing after COVID-19 Vaccination: VITT, VATT, TTS, and More.

Despite the huge efforts globally underway for preventing or limiting the spread of severe acute respiratory coronavirus disease 2 (SARS-CoV-2), the coronavirus disease 2019 (COVID-19) pandemic outbreak appears still virtually unstoppable. As for many other infectious diseases, COVID-19 vaccination has now become crucial for limiting viral spread, especially for averting hospitalizations, need for intensive care, and fatal outcome. Nonetheless, as for other vaccines, COVID-19 vaccination is not completely free from side effects. Among the adverse events that have been reported after receiving COVID-19 vaccination, special emphasis has been given to an unexpected number of thrombocytopenic episodes with or without thrombotic complications, especially in recipients of adenovirus-based COVID-19 vaccines. Along with a specific clinical presentation, encompassing "atypical" thrombosis (especially cerebral venous [sinus] thrombosis, CVT) more prevalent in young female subjects, this new syndrome called vaccine-induced thrombocytopenia and thrombosis (VITT) is characterized by, and thereby diagnosed for, the presence of three paradigmatic laboratory abnormalities, i.e., low platelet count (<150 × 109/L), elevated plasma D-dimer levels (>0.5 mg/L), accompanied by a positive test for anti-PF4 (platelet factor 4) antibodies assayed with ELISA (enzyme-linked immunosorbent assay) techniques. Timely identification of these important abnormalities by both clinicians and laboratory professional is essential for early diagnosis and management of VITT, since the outcome of this condition may be fatal in half or even more of effected patients with severe disease. Therefore, this narrative review aims to review here the epidemiology, pathogenesis, clinical, and laboratory characteristics of VITT and other COVID-19 vaccine-associated thrombocytopenias.

Thromboinflammation Supports Complement Activation in Cancer Patients With COVID-19.

BackgroundCOVID-19 pathology is associated with exuberant inflammation, vascular damage, and activation of coagulation. In addition, complement activation has been described and is linked to disease pathology. However, few studies have been conducted in cancer patients.ObjectiveThis study examined complement activation in response to COVID-19 in the setting of cancer associated thromboinflammation.MethodsMarkers of complement activation (C3a, C5a, sC5b-9) and complement inhibitors (Factor H, C1-Inhibitor) were evaluated in plasma of cancer patients with (n=43) and without (n=43) COVID-19 and stratified based on elevated plasma D-dimer levels (>1.0 μg/ml FEU). Markers of vascular endothelial cell dysfunction and platelet activation (ICAM-1, thrombomodulin, P-selectin) as well as systemic inflammation (pentraxin-3, serum amyloid A, soluble urokinase plasminogen activator receptor) were analyzed to further evaluate the inflammatory response.ResultsIncreases in circulating markers of endothelial cell dysfunction, platelet activation, and systemic inflammation were noted in cancer patients with COVID-19. In contrast, complement activation increased in cancer patients with COVID-19 and elevated D-dimers. This was accompanied by decreased C1-Inhibitor levels in patients with D-dimers > 5 ug/ml FEU.ConclusionComplement activation in cancer patients with COVID-19 is significantly increased in the setting of thromboinflammation. These findings support a link between coagulation and complement cascades in the setting of inflammation.

The clinical significance of ultra-high D-dimer levels

ObjectivePlasma D-dimer levels >5000 ng/mL are encountered in a number of conditions other than venous thromboembolism (VTE). Recent studies have used plasma D-dimer levels as a prognostic indicator for coronavirus disease 2019 (COVID-19) infection. The implications of abnormal levels are less clear for patients diagnosed with COVID-19 with a baseline elevation in plasma D-dimer levels. In the present study, we reviewed the occurrence of plasma D-dimer levels >5000 ng/mL and investigated the clinical significance of this finding before the onset of the COVID-19 pandemic. MethodsInpatient records for a 4-year period were screened for laboratory results of plasma D-dimer levels >5000 ng/mL. The patient data were reviewed for the clinical identifiers commonly associated with elevated plasma D-dimer levels, including VTE, cancer, sepsis, pneumonia, other infection, bleeding, and trauma. The patients were then categorized into groups stratified by the plasma D-dimer level to allow for comparisons between the various clinical diagnoses. ResultsA total of 671 patients were included in the present study. VTE was the most common diagnosis for patients with a plasma D-dimer level >5000 ng/mL, followed by cancer and pneumonia. Multiple clinical diagnoses were present in 61% of the patients. No clear cause for the ultra-high plasma D-dimer level could be identified in 11.3% of the patients. Among the patients lacking a clinical diagnosis at discharge, mortality was 24% in the 5000- to 10,000-ng/mL group, 28.6% in the 10,000- to 15,000-ng/mL group, and 75% in the >15,000-ng/mL group. ConclusionsVTE, cancer, and pneumonia were frequently present when ultra-high plasma D-dimer levels were encountered, and mortality was high when the levels were >15,000 ng/mL. The results from our study from a pre–COVID-19 patient population suggest that ultra-high plasma D-dimer levels indicate the presence of severe underlying disease. This should be considered when using the plasma D-dimer level as a screening tool or prognostic indicator for COVID-19 infection.

The clinical significance of a shortened activated partial thromboplastin time in patients with connective tissue disease.

Connective tissue disease (CTD) patients have been reported to have an increased risk of venous thromboembolism (VTE). Deep venous thrombosis represents a potential emergency that may have a fatal outcome. The D-dimer test is the most widely accepted screening marker for VTE; however, elevation of the plasma D-dimer level without demonstrable thrombosis sometimes accompanies CTD activity itself, infection, and other conditions. Thus, the accuracy of a diagnosis of VTE based on a D-dimer test result is lower in CTD patients. The activated partial thromboplastin time (APTT) test is a very common and simple test. The medical records of 535 CTD patients were retrospectively investigated. The following data were extracted: APTT, D-dimer, thrombotic events, laboratory data, and systemic corticosteroid therapy. The rates of thrombotic events and VTE were significantly increased in patients with a shortened APTT (< 26s) (PSAPTT) in comparison to those without a shortened APTT (p = 0.004, 0.0009, respectively). The number of PSAPTTs was significantly increased in patients with VTE in comparison to those without VTE (p = 0.0009). In the diagnosis of VTE in CTD patients, the specificity and positive predictive value (PPV) of the D-dimer test were 71.6% and 83.8% and 12.7% and 19.4%, respectively. The combination of a shortened APTT and elevated plasma D-dimer level improved the specificity and PPV to 94.7% and 97.3% and to 25.0% and 36.4%, respectively. For the evaluation of possibility of accompanying VTE in CTD patients, APTT shortened was useful and should be evaluated with careful attention. • Regarding the specificity for diagnosing VTE in CTD patients, a shortened APTT showed a value (84.3%) comparable or superior to that of the D-dimer test. • The combination of a shortened APTT and elevated D-dimer level improved the specificity of the diagnosis of VTE in CTD patients to (94.7% or 97.3%) in comparison to the D-dimer test alone (71.6% or 83.8%). • The positive predictive value of the combination of a shortened APTT and plasma D-dimer elevation for the diagnosis of VTE in CTD patients increased to 25.0% or 36.4%. • In the management of CTD patients, physicians should pay attention when they encounter patients with a shortened APTT, as it may indicate VTE.

Preoperative plasma D-dimer independently predicts survival in patients with pancreatic ductal adenocarcinoma undergoing radical resection

BackgroundElevated plasma D-dimer levels have been reported as an unfavorable prognostic indicator in many solid tumors. However, there are limited relevant studies in pancreatic cancer patients following radical surgery, and the clinical significance remains controversial. The aim of this study was to investigate the clinical and prognostic significance of preoperative plasma D-dimer in patients with pancreatic ductal adenocarcinoma (PDAC) undergoing resection.MethodsA retrospective analysis was performed on all patients who consecutively underwent radical surgery for PDAC by laparotomy or robotic surgery from December 2011 to December 2018. Baseline clinicopathologic characteristics, preoperative laboratory parameters, and follow-up information were collected. Univariate and multivariate analyses were performed to analyze the prognostic value of preoperative plasma D-dimer.ResultsAmong 1351 patients, elevated preoperative plasma D-dimer levels (≥ 0.55 ng/mL) were found in 417 (30.9%) patients. Three hundred twelve (23.09%) underwent minimally invasive robotic pancreatectomy. The median overall survival (OS) of patients with elevated D-dimer levels was 6.3 months shorter than that of patients with normal D-dimer levels (15.0 months vs 21.3 months, p < 0.001). Multivariate analysis showed that elevated D-dimer levels independently predicted poorer OS (hazard ratio, 1.33; 95% confidence interval, 1.17-1.51, p < 0.001). Subgroup analysis demonstrated that D-dimer was a reliable prognostic factor in patients who underwent R0 resection. In addition, integration of D-dimer, carbohydrate antigen 19-9 (CA19-9), and NLR provided a better prognostic model for PDAC patients before operation.ConclusionAn elevated preoperative plasma D-dimer level was a reliable independent prognostic factor for OS in patients with PDAC undergoing resection. Combination of D-dimer, CA19-9, and NLR can enhance the prognostic accuracy before operation.

Prevalence of Preoperative Lower Extremity Deep Vein Thrombosis in Bilateral Calcaneal Fractures

There are no studies on epidemiologic characteristics of deep vein thrombosis (DVT), when specified at in patients with bilateral calcaneal fractures. This study aimed to address the preoperative DVT in bilateral calcaneal fractures. Between October 2014 and December 2018, adult patients presenting with bilateral calcaneal fractures and having preoperative Duplex ultrasound (DUS) of bilateral lower extremities for detection of DVT were included. Their medical data were collected, with regards to demographics, comorbidities, injury-related data and biomarkers. Baseline characteristics between patients with and without DVT were compared using bivariate tests. The further multivariate logistics regression analysis was conducted to identify independent factors associated with DVT. In total, 258 patients with bilateral calcaneal fractures were included, with 21 (8.1%) having preoperative DVT, diagnosed at 7.7 ± 4.2 days after injury. The prevalence rate of proximal DVT was 1.9% and of distal DVT was 6.2%. Thirty five thrombi were found, with 6 (17.1%) in proximal veins and 29 (82.9%) in distal veins. Nine patients had DVTs in multiple veins, and 2 patients had bilateral DVTs. The multivariate analyses showed history of allergy (odds ratio [OR] = 2.17), concurrent other fractures (OR = 4.53), prolonged time since injury (for each day, OR = 1.16), elevated plasma D-dimer level (≥1.73 vs <1.73 mg/L, OR = 3.74) and reduced albumin level (<34.2 g/L vs ≥34.2 g/L, OR = 2.92) were independent factors associated with DVT. Multiple factors were identified to be associated with DVT and greater consideration should be given to the use of pharmacologic prophylaxis in patients involving these factors, to reduce DVT occurrence.