Discrepancies between two D-dimer assays and impact on clinical decisions; a retrospective analysis of samples tested in community and hospital-based laboratories in Auckland.

AIM: In patients with suspected venous thromboembolism, an elevated D-dimer level provides an important branch-point in the management pathway. This study compared two D-dimer assays, INNOVANCE® DDimer (Innovance) and STA®-Liatest® D-Di Plus (Liatest), to assess potential impact on clinical management. METHOD: Reflecting current practice in Waitemata, Auckland, we compared paired samples from 805 patients referred to hospital following a community D-dimer test. Samples were determined to be positive or negative using a 500µg/L fibrinogen equivalent units (FEU), and age-adjusted cut-offs. RESULTS: In the Innovance assay, 2% of samples had a result <500µg/L FEU. In contrast, by Liatest, 18% were below 500µg/L. This positive bias of Innovance was amplified with use of age-adjusted cut-offs; 23% of samples with an elevated Innovance result showed a normal result by Liatest. On average, the Innovance values were 22% higher than Liatest. Results suggestive of interference from heterophile antibodies were seen in 6% of sample-pairs. CONCLUSION: Innovance D-dimer test yielded higher values than Liatest and experienced interference from suspected heterophile antibodies. Discrepancies in nearly a quarter of patients may be leading to substantial under or over investigation, inefficient use of resources and clinical confusion.

Unreliability of Serum- or Plasma-based Assays of D-dimer or Fibrin (Fibrinogen) Degradation Product for Diagnosing Periprosthetic Joint Infection: A Prospective Parallel Study.

OBJECTIVE: The ability of D-dimer to diagnose periprosthetic joint infection (PJI) before revision hip or knee arthroplasty is still controversial, and the differences in diagnostic ability between serum- or plasma-based assays of D-dimer and fibrin (fibrinogen) degradation product (FDP) are uncertain. The prospective parallel study was performed to determine the ability of D-dimer to diagnose PJI before revision hip or knee arthroplasty, and the differences in diagnostic ability between serum- or plasma-based assays of D-dimer and FDP. METHODS: Patients undergoing knee or hip arthroplasty at our institution were prospectively enrolled into the following groups: those without inflammatory diseases who were undergoing primary arthroplasty ("Prim" group), those with inflammatory arthritis who were undergoing primary arthroplasty ("Prim/Inflam"), those undergoing revision arthroplasty because of aseptic failure ("Rev/Asept"), or those undergoing revision arthroplasty because of PJI ("Rev/PJI"). The ability of preoperative levels of D-dimer or FDP in serum or plasma to diagnose PJI in each group was assessed using areas under receiver operating characteristic curves (AUCs) and other diagnostic performance indicators. The diagnostic performance of these assays was compared with that of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). RESULTS: In the final analysis, Prim included 42 patients; Prim/Inflam, 40; Rev./Asept, 62; and Rev./PJI, 47. D-dimer assays led to AUCs of 0.635 in serum and 0.573 in plasma, compared to 0.593 and 0.607 for FDP. Even in combination with CRP or ESR, these assays failed to perform as well as the combination of CRP and ESR for diagnosing PJI. CONCLUSION: Levels of D-dimer or FDP in serum or plasma, whether used alone or together with CRP or ESR, are unreliable for diagnosing PJI before revision arthroplasty.

Phenotypes of Disseminated Intravascular Coagulation.

Two phenotypes of disseminated intravascular coagulation (DIC) are systematically reviewed. DIC is classified into thrombotic and fibrinolytic phenotypes characterized by thrombosis and hemorrhage, respectively. Major pathology of DIC with thrombotic phenotype is the activation of coagulation, insufficient anticoagulation with endothelial injury, and plasminogen activator inhibitor-1-mediated inhibition of fibrinolysis, leading to microvascular fibrin thrombosis and organ dysfunction. DIC with fibrinolytic phenotype is defined as massive thrombin generation commonly observed in any type of DIC, combined with systemic pathologic hyperfibrinogenolysis caused by underlying disorder that results in severe bleeding due to excessive plasmin formation. Three major pathomechanisms of systemic hyperfibrinogenolysis have been considered: (1) acceleration of tissue-type plasminogen activator (t-PA) release from hypoxic endothelial cells and t-PA-rich storage pools, (2) enhancement of the conversion of plasminogen to plasmin due to specific proteins and receptors that are expressed on cancer cells and endothelial cells, and (3) alternative pathways of fibrinolysis. DIC with fibrinolytic phenotype can be diagnosed by DIC diagnosis followed by the recognition of systemic pathologic hyperfibrin(ogen)olysis. Low fibrinogen levels, high fibrinogen and fibrin degradation products (FDPs), and the FDP/D-dimer ratio are important for the diagnosis of systemic pathologic hyperfibrin(ogen)olysis. Currently, evidence-based treatment strategies for DIC with fibrinolytic phenotypes are lacking. Tranexamic acid appears to be one of the few methods to be effective in the treatment of systemic pathologic hyperfibrin(ogen)olysis. International cooperation for the elucidation of pathomechanisms, establishment of diagnostic criteria, and treatment strategies for DIC with fibrinolytic phenotype are urgent issues in the field of thrombosis and hemostasis.

Coagulation parameters correlate to venous thromboembolism occurrence during the perioperative period in patients with spinal fractures.

BACKGROUND: Venous thromboembolism (VTE) is one of the leading causes of mortality in hospitalized patients. However, whether the coagulation-related parameters of the hospitalized patients could be used to predict the occurrence of VTE in patients with spinal injury surgery remained unclear. METHOD: The patients with spinal fractures who met the inclusion and exclusion criteria were enrolled to be analyzed using a retrospective analysis approach. The association of risk factors of enrolled patients and operations to VTE occurrence were analyzed. The activated partial thromboplastin time, prothrombin time, thrombin time, D-dimer (D-D), fibrinogen (FIB) and fibrinogen degradation products (FDP) were detected. ROC and HR analysis were applied to evaluate the correlation of coagulation-related parameters and other parameters to VTE occurrence. RESULT: The indicators of D-D, FIB and FDP were significantly elevated in VTE patients compared to non-VTE patients. The multivariate analysis of OR showed that six risk factors, including age ≥ 60, spinal cord injury, postoperative bedtime over 5 days, plasma D-dimer ≥ 0.54 mg/L, plasma fibrinogen ≥ 3.75 g/L and plasma FDP ≥ 5.19 mg/L, were positively correlated to VTE. CONCLUSION: The six risk factors, including D-D, FIB, FDP, age ≥ 60, spinal cord injury, and postoperative bedtime over 5 days, could be used to predict the occurrence of VTE.

Increased D-dimer and fibrin degradation product levels as potential indicators for evaluating infection-related acute urticaria: a case-case-control study.

About 20% of world population suffer from acute urticaria at some stage in their lives. Recent studies showed coagulation dysfunction in chronic urticaria. The involvement of coagulation changes in acute urticaria remains unclear. Fifty-eight acute urticaria patients were enrolled in this study and divided into two groups (referred to throughout as infection-related and infection-unrelated acute urticaria). The routine laboratory parameters including coagulation tests between the two groups were compared. The correlation between coagulation tests and CRP at acute phase was also assessed. Dynamic change of routine coagulation test results at acute phase and resolving phase was compared. The potential performance of coagulation for infection indication was tested. We found D-dimer, fibrin degradation product (FDP), and fibrinogen (Fg) increased in the acute phase of infection-related acute urticaria patients. D-dimer, FDP, Fg, and APTT are positively correlated with CRP in the acute phase. D-dimer and FDP decreased in the resolving phase of infection-related acute urticaria patients. Higher D-dimer (> 0.48 mg/L) and FDP (> 3.84 mg/L) may indicate infection-related acute urticaria. In conclusion, in acute urticaria with low venous thromboembolism risk, D-dimer level and dynamic change can be potentially used for the infection-related clinical practice management.

Immunohistochemical evaluation of fibrin/fibrinogen, d-dimers, and intravascular thrombosis in brains of dogs with meningoencephalitis of unknown origin.

Granulomatous meningoencephalitis (GME) and necrotizing encephalitides (NE) are the most common immune-mediated inflammatory diseases of the central nervous system in dogs. Activation of the fibrinolytic system in multiple sclerosis, a similar immune-mediated disease affecting the central nervous system in humans, seems to be related to disease progression. The aim of this study was to identify fibrin/fibrinogen and D-dimer deposition, as well as presence of intravascular thrombosis (IVT) in brains of dogs with a diagnosis of GME or NE. Immunohistochemical studies using antibodies against fibrin/fibrinogen and D-dimers were performed. Statistical analyses were performed to determine whether there were differences in the presence and location of fibrin/fibrinogen, D-dimers deposits, and IVT between GME and NE. Samples from sixty-four dogs were included in the study: 32 with a diagnosis of GME and 32 with a diagnosis of NE. Fibrin/fibrinogen depositions were detected in all samples and d-dimers were detected in 43/64 samples. IVT was present in 29/64 samples, with a significantly higher score in samples from dogs with NE than in samples from dogs with GME (P = 0.001). These data support hemostatic system activation in both diseases, especially NE. This finding might be related to the origin of the necrotic lesions seen in NE, which could represent chronic ischemic lesions. Further studies are needed to investigate the association between vascular lesions and the histopathological differences between GME and NE and the hemostatic system as a potential therapeutic target.

D-dimer testing: A narrative review.

D-dimer containing species are soluble fibrin degradation products derived from plasmin-mediated degradation of cross-linked fibrin, i.e., 'D-dimer'. D-dimer can hence be considered a biomarker of in vivo activation of both coagulation and fibrinolysis, the leading clinical application in daily practice of which is ruling out venous thromboembolism (VTE). D-dimer has been further evaluated for assessing the risk of VTE recurrence and helping define optimal duration of anticoagulation treatment in VTE, for diagnosing disseminated intravascular coagulation (DIC), and for screening those at enhanced risk of VTE. D-dimer assays should however be performed as intended by regulatory agencies, as their use outside these indications might make them a laboratory-developed test (LDT). This narrative review is aimed at: (1) reviewing the definition of D-dimer, (2) discussing preanalytical variables affecting D-dimer measurement, (3) reviewing and comparing the assays performance and some postanalytical variables (e.g., different units and age-adjusted cutoffs), and (4) discussing the interest of D-dimer measurement across different clinical settings, including pregnancy, cancer, and coronavirus disease 2019 (COVID-19).

Predictive value of D-dimer and fibrinogen degradation product for splanchnic vein thrombosis in patients with severe acute pancreatitis: a single-center retrospective study.

BACKGROUND AND AIM: Early diagnosis of splanchnic vein thrombosis (SVT) after severe acute pancreatitis (SAP) remains difficult because of its insidious onset. Common serum markers for thrombosis such as D-dimer (D-D) have lost their diagnostic value due to their elevation in non-thrombotic patients with SAP. The aim of this study is to predict SVT after SAP using common serum indicators of thrombosis by establishing a new cut-off value. METHODS: 177 SAP patients were included in a retrospective cohort study from September 2019 to September 2021. Patient demographics, dynamic changes of coagulation and fibrinolysis indicators were collected. Univariate analyses and binary logistic regression analyses were applied to assess potential risk factors for the development of SVT in SAP patients. A receiver operating characteristic (ROC) curve was generated to assess the predictive value of independent risk factors. Moreover, clinical complications and outcomes were compared between two groups. RESULTS: Among 177 SAP patients, 32 (18.1%) developed SVT. The most common cause of SAP was biliary (49.8%), followed by hypertriglyceridemia (21.5%). Multivariate logistic regression analyses showed that D-D (OR, 1.135; 95%CI, 1.043-1.236; p = 0.003) and fibrinogen degradation product (FDP) (OR, 1.037; 95%CI, 1.015-1.060; p = 0.001) were independent risk factors for SVT development in patients with SAP. The area under ROC curve for D-D was 0.891 (p = 0.003, sensitivity= 95.3%, specificity = 74.1%) at a cut-off value of 6.475, and the area under ROC curve for FDP was 0.858 (p = 0.001, sensitivity = 89.4%, specificity = 72.4%) at a cut-off value of 23.155. CONCLUSION: D-D and FDP are significant independent risk factors with high predictive value for SVT in patients with SAP.

Plasma D-Dimer Is Noninferior to Serum C-Reactive Protein in the Diagnosis of Periprosthetic Joint Infection.

BACKGROUND: No single test has demonstrated absolute accuracy in the diagnosis of periprosthetic joint infection (PJI). Serological markers are often used as screening tools in the workup of patients with suspected PJI. This study aimed to determine the diagnostic utility of plasma D-dimer for PJI in a variety of clinical scenarios. METHODS: This prospective study enrolled 502 patients undergoing revision hip or knee arthroplasty. PJI was defined per a modified version of the 2018 International Consensus Meeting (ICM) criteria. Plasma D-dimer, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and fibrinogen were measured preoperatively. Receiver operating characteristic curves were used to assess the utility of each biomarker in the diagnosis of PJI. Pairwise comparison with Bonferroni correction was performed to determine whether the differences in areas under the curve (AUCs) between the markers were significant. RESULTS: Of the 412 patients included, 317 (76.9%) did not have an infection (aseptic group) and 95 (23.1%) had an infection (PJI group). All 4 serological markers, D-dimer (AUC, 0.860; sensitivity, 81.3%; specificity, 81.7%), CRP (AUC, 0.862; sensitivity, 90.4%; specificity, 70.0%), ESR (AUC, 0.833; sensitivity, 73.9%; specificity, 85.2%), and fibrinogen (AUC, 0.798; sensitivity, 74.7%; specificity, 75.4%), demonstrated comparable accuracy for the diagnosis of PJI (all p > 0.05). When examining the performance of the different inflammatory markers in diagnosing infection caused by indolent organisms, D-dimer demonstrated the highest sensitivity at 93.8%. CONCLUSIONS: We found that plasma D-dimer was noninferior to serum CRP and ESR in the diagnosis of PJI and may be a useful adjunct when screening patients undergoing revision total joint arthroplasty. LEVEL OF EVIDENCE: Diagnostic Level II . See Instructions for Authors for a complete description of levels of evidence.

Fibrin monomer complex as a potential thrombosis marker related to venous thromboembolism risk in pregnant women.

BACKGROUND: Pregnancy is a risk factor for venous thromboembolism (VTE) due to increased coagulation factor activity and decreased protein S activity. However, thrombosis markers for predicting VTE in pregnancy remain controversial. This study aimed to investigate the relationship between VTE risk and thrombosis markers in pregnant women and to identify markers related to VTE risk. METHODS: Archived plasma samples from 107 pregnant women were used in this study, and the concentrations of D-dimer, fibrin monomer complex (FMC), plasmin-plasmin inhibitor complex, prothrombin time, activated partial thromboplastin time, and fibrinogen were measured. VTE risk was scored according to the Royal College of Obstetricians and Gynaecologists green-top guidelines and the patients were divided into low- or high-risk groups. RESULTS: The median (range) of risk score for deep vein thrombosis was 2 (0-8), and we defined the high-risk group included those with a score of ≧3. D-dimer and FMC concentrations were significantly higher in the high-risk group than in the low-risk group (D-dimer 4.5 vs 2.6 µg/mL, p = 0.008; FMC 14.6 vs 3.4 µg/mL, p < 0.001). Although D-dimer concentration significantly increased with gestational age (Spearman's correlation coefficient [rs] = 0.317, p < 0.001), FMC concentration did not (rs = -0.081, p = 0.409). The area under the receiver operating characteristic curve values of D-dimer, FMC, and both D-dimer and FMC for the high-risk group were 0.656, 0.713, and 0.738, respectively. CONCLUSIONS: FMC may be a thrombosis marker related to VTE risk in pregnancy and is potentially preferable over D-dimer concentrations.

An interaction between the inflammatory condition and the hypercoagulable condition occurs in primary Sjögren syndrome.

This study aimed to assess the D-dimer level in patients with primary Sjögren syndrome (pSS), uncover its relationship with clinical symptoms, and appraise its predictive value in discriminating disease activity. The laboratory parameters of 101 consecutive patients with pSS and 101 healthy controls were analyzed and compared. Patients were divided into two subgroups according to their D-dimer levels, for the comparison of clinical features. Pearson's correlations were used to measure the relationships between D-dimer levels and other variables. The area under the curve (AUC) was calculated to predict disease activity. The erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hsCRP) level, and D-dimer level were each higher in patients with pSS than in healthy controls. Compared with the low-D-dimer-level patients, those with elevated D-dimer levels exhibited higher ESRs (p < 0.0001) and higher levels of hsCRP (p < 0.0001), fibrinogen (p < 0.0001), and immunoglobulin A (p = 0.002). Cases with elevated D-dimer levels were prone to be more severe, based on ESSDAI evaluation (p < 0.0001). Patients with higher D-dimer levels had more articular involvement (p < 0.0001), which was significantly correlated with both the ESR (r = 0.21, p = 0.03) and hsCRP level (r = 0.56, p = 0.001). The D-dimer level may help to discriminate low disease activity from moderate/high disease activity (AUC = 0.754). The D-dimer level was correlated positively with both the ESR and hsCRP level in patients with pSS. The ESR and levels of hsCRP, fibrinogen, and disease activity were higher in the elevated D-dimer level group. The D-dimer level was demonstrated to have predictive value in differentiating pSS disease activity. Key Points •D-Dimer was higher in patients with pSS. •D-Dimer may help for predicting the disease activity in patients with pSS.

D-dimer: old dogmas, new (COVID-19) tricks.

D-dimer is a fibrin degradation product encompassing multiple cross-linked D domains and/or E domains present in the original fibrinogen molecule, whose generation is only theoretically possible when hemostasis and fibrinolysis pathways are concomitantly activated. D-dimer measurement has now become a pillar in the diagnosis/exclusion and prognostication of venous thromboembolism (VTE) and disseminated intravascular coagulation (DIC), when incorporated into validated clinical algorithms and especially using age-adjusted diagnostic thresholds. Although emerging evidence is also supporting its use for predicting the duration of anticoagulant therapy in certain categories of patients, the spectrum of clinical applications is constantly expanding beyond traditional thrombotic pathologies to the diagnosis of acute aortic dissection, acute intestinal ischemia and cerebral venous thrombosis among others, embracing also clinical management of coronavirus disease 2019 (COVID-19). Recent findings attest that D-dimer elevations are commonplace in patients with severe acute respiratory syndrome (SARS-CoV-2) infection (especially in those with thrombosis), its value predicts the clinical severity (up to death) of COVID-19 and remains more frequently increased in COVID-19 patients with post-discharge clinical sequelae. Further, D-dimer-based anticoagulant escalation may be associated with a lower risk of death in patients with severe SARS-CoV-2 infection and, finally, D-dimer elevation post-COVID-19 vaccination mirrors an increased risk of developing vaccine-induced thrombocytopenia and thrombosis (VITT).

Dabigatran etexilate is efficacious in consumptive coagulopathy and pain associated with venous malformations.

OBJECTIVE: Consumptive coagulopathy treatment and pain management are crucial for patients with venous malformations (VMs). Dabigatran etexilate, a non-vitamin K antagonist oral anticoagulant, has known advantages compared with low-molecular-weight heparin and vitamin K antagonists, including oral administration, a more consistent pharmacokinetics/pharmacodynamics profile, a better safety profile, and no need for coagulation surveillance. In the present study, we tested the efficacy and safety of dabigatran etexilate for consumptive coagulopathy treatment and pain management for patients with VMs. METHODS: To investigate the efficacy and safety of dabigatran etexilate in treating localized intravascular coagulation (LIC) associated with VM, we retrospectively collected data for 19 outpatients with VM and LIC, who had been treated with dabigatran etexilate from September 2019 to June 2021. The patients provided oral informed consent and underwent biologic blood testing, routine examinations, and determination of coagulation function before and after treatment. The dosage of dabigatran etexilate was 110 mg twice daily for adults and 55 mg twice daily for children. RESULTS: All 19 patients had benefited from dabigatran etexilate treatment with coagulation improvement and pain relief. Pain had improved in all 16 evaluable patients. The fibrinogen and D-dimer levels had improved in 18 of 19 patients. The fibrin degradation product level had improved in 10 of 14 patients. None of patients reported lesion regression, appearance changes, or improvement in mobility. No significant differences were found in the D-dimer, fibrinogen, and fibrin degradation product levels between the short-term (<10 days) and long-term (≥10 days) use of the medication. Dabigatran etexilate was well tolerated by all patients. No bleeding event had occurred during follow-up. CONCLUSIONS: The results of our study have confirmed the efficacy and safety of dabigatran etexilate in treating pain and LIC in patients with VMs. Dabigatran etexilate is a suitable choice preoperatively to modify coagulation function and pain in patients with VMs.

A Retrospective Case-Control Study on the Diagnostic Values of Hemostatic Markers in Hypertensive Disorder of Pregnancy.

OBJECTIVE: The purpose of this study was to evaluate the diagnostic performance of the following hemostatic markers in hypertensive disorder of pregnancy (HDP): tissue-type plasminogen activator and inhibitor-1 complex (tPAI-C), thrombomodulin, thrombin-antithrombin complex, plasmin inhibitor-plasmin complex, D-dimer, and fibrinogen degradation products. METHODS: A total of 311 individuals diagnosed with HDP and 187 healthy controls (HC) of matched gestational age were admitted, including 175 subjects with gestational hypertension, 94 with mild preeclampsia, and 42 with severe preeclampsia. RESULTS: Compared with those of the HC group, the plasma concentrations of all the hemostatic markers continuously increased with the clinical severity of the hypertensive disorder, regardless of their statistical significance. In the receiver operating characteristic analysis, tPAI-C displayed the best discrimination performance. CONCLUSION: The tPAI-C level was consistently and significantly elevated across the different HDP groups when compared with the HC group, suggesting aggravated fibrinolysis disorder increasing with the severity of the HDP.

The diagnostic and prognostic value of D-dimer in different types of aortic dissection.

OBJECTIVE: To evaluate the serum D-dimer level and its diagnostic and prognostic predictive value in patients with different types of aortic dissection. METHODS: Eighty-four aortic dissection patients who were diagnosed clinically in our hospital from January 2017 to January 2021 were selected for the study. All patients were divided into Stanford type A (39 cases) and Stanford type B (45 cases) groups. The serum D-dimer level was detected at 1 h, 6 h, 12 h, 24 h, and 72 h after admission to the hospital, and its expression level with different types of aortic dissection was analyzed. The relationship between D-dimer and the prognosis of patients was also analyzed. RESULTS: The serum D-dimer levels of patients in group A were significantly higher than those in group B at 6 h, 12 h, 24 h, and 72 h after admission, and the differences were statistically significant. In group A, 16 patients died, and 23 patients survived, while in group B, 18 patients died, and 27 patients survived. The serum D-dimer level of the dead and surviving patients in group A was significantly higher than that of group B, and the serum D-dimer level of dead patients in groups A and B was significantly higher than that of surviving patients. For diagnostic value, the AUC was 0.89, sensitivity was 76.92%, specificity was 90.00% in group A, and the AUC was 0.82, sensitivity was 71.11%, and specificity was 85.00% in group B. For the prognostic predicted value, the AUC was 0.74 in group A, while the AUC was 0.69 in group B. CONCLUSIONS: D-dimer has different serum levels in different types of aortic dissection patients, with higher levels in Stanford A. Serum D-dimer levels may be used as a better biomarker to diagnose the two types of aortic dissection and play an important role in patient prognostic prediction, especially Stanford type A.

D-dimer Thresholds to Exclude Pulmonary Embolism among COVID-19 Patients in the Emergency Department: Derivation with Independent Validation.

OBJECTIVE: To derive and validate a D-dimer cutoff for ruling out pulmonary embolism (PE) in COVID-19 patients presenting to the emergency department (ED). METHODS: A retrospective cohort study was performed in an integrated healthcare system including 22 adult ED's between March 1, 2020, and January 31, 2021. Results were validated among patients enrolled in the RECOVER Registry, representing data from 154 ED's from 26 US states. Consecutive ED patients with laboratory confirmed COVID-19, a D-dimer performed within 48 h of ED arrival, and with objectively confirmed PE were compared to those without PE. After identifying a D-dimer threshold at which the 95% confidence lower bound of the negative predictive value for PE was higher than 98% in the derivation cohort, it was validated using RECOVER registry data. RESULTS: Among 3978 patients with a D-dimer result, 3583 with confirmed COVID-19 infection were included in the derivation cohort. Overall, PE incidence was 4.1% and a D-dimer cutoff of <2 µ/mL (2000 ng/mL) was associated with a NPV of 98.5% (95% CI = 98.0%-98.9%). In the validation cohort of 13,091 patients with a D-dimer, 7748 had confirmed COVID-19 infection, and the PE incidence was 1.14%. A D-dimer cutoff of <2 µ/mL was associated with a NPV of 99.5% (95% CI = 99.3%-99.7%). CONCLUSION: A D-dimer cutoff of <2 µ/ml was associated with a high negative predictive value for PE among patients with COVID-19. However, the resultant sensitivity for PE result at that threshold without pre-test probability assessment would be considered clinically unsafe.

Lipoprotein(a) during COVID-19 hospitalization: Thrombosis, inflammation, and mortality.

BACKGROUND AND AIMS: High levels of lipoprotein(a) could worsen the outcome of COVID-19 due to prothrombotic and proinflammatory properties of lipoprotein(a). We tested the hypotheses that during COVID-19 hospitalization i) increased thrombotic activity and inflammation are associated with lipoprotein(a) levels, and ii) lipoprotein(a) levels are associated with rate of hospital death and discharge. METHODS: We studied 211 patients admitted to Copenhagen University Hospital in 2020 with COVID-19, that is, prior to any vaccination. Thrombotic activity was marked by elevated D-dimer while inflammation was marked by elevated interleukin-6, C-reactive protein, and procalcitonin. Patients were followed until death (N = 36) or discharge (N = 175). RESULTS: A 2-fold higher D-dimer was associated with 14% (95%CI: 8.1-20%) higher lipoprotein(a). Conversely, 2-fold higher interleukin-6, C-reactive protein, and procalcitonin were associated with respectively 4.3% (0.62-7.8%), 5.7% (0.15-5.2%), and 8.7% (5.2-12%) lower lipoprotein(a). For hospital death, the multivariable adjusted hazard ratio per 2-fold higher lipoprotein(a) was 1.26 (95%CI:0.91-1.73). Corresponding hazard ratios per 2-fold higher biomarker were 0.93 (0.75-1.16) for D-dimer, 1.42 (1.17-1.73) for interleukin-6, 1.44 (0.95-2.17) for C-reactive protein, and 1.44 (1.20-1.73) for procalcitonin. For hospital discharge, the multivariable adjusted hazard ratio per 2-fold higher lipoprotein(a) was 0.91 (95%CI:0.79-1.06). Corresponding hazard ratios per 2-fold higher biomarker were 0.86 (0.75-0.98) for D-dimer, 0.84 (0.76-0.92) for interleukin-6, 0.80 (0.71-0.90) for C-reactive protein, and 0.76 (0.67-0.88) for procalcitonin. CONCLUSIONS: In COVID-19 patients, thrombotic activity marked by elevated D-dimer was associated with higher lipoprotein(a) while elevated inflammatory biomarkers of interleukin-6, C-reactive protein, and procalcitonin were associated with lower lipoprotein(a); however, elevated lipoprotein(a) was not associated with rate of hospital death or discharge.

[Application value of D-dimer in preoperative diagnosis of low toxic infectious nonunion].

OBJECTIVE: To evaluate the value of D-dimer and common hematological indexes in the preoperative diagnosis of low toxicity infectious bone nonunion. METHODS: Total of 116 cases of bone nonunion from June 2015 to January 2020 were analyzed retrospectively, including 91 males and 25 females;the age ranged from 18 to 65 years old with an average of(45.3±11.2) years old. According to the diagnostic criteria, 116 cases were divided into low toxicity infectious bone nonunion group(31 cases) and aseptic bone nonunion group(85 cases). D-dimer, total leukocyte count, C-reactive protein and erythrocyte sedimentation rate(ESR) were measured at admission, and the differences between two groups were compared. The diagnostic accuracy, sensitivity and specificity were analyzed through the subject working characteristic curve and the area under the curve. RESULTS: All patients were followed up for 12 to 24 months with an average of (11.5±4.3) months. D-dimer, total leukocyte count, C-reactive protein and ESR in low toxicity infectious bone nonunion group were higher than those in aseptic bone nonunion group(P<0.05);compared with other hematological indexes, the area under the curve of D-dimer was the highest, which is 0.826, and the best cut-off value of D-dimer was 1.57 g/L. The sensitivity and specificity of preoperative diagnosis of low toxicity infectious bone nonunion were 78.3% and 84.2%. CONCLUSION: The preoperative diagnostic value of D-dimer in low toxicity infectious bone nonunion is better than other inflammatory indexes. The combination of D-dimer and other inflammatory indexes is conducive to the early diagnosis of low toxicity infectious bone nonunion and the evaluation of the condition.