Rise In D-dimer Research Articles

#743 Clinical outcomes of patients hospitalized with the diagnosis of COVID-19 infection and undergoing hemodialysis: a single center experience

Abstract Background and Aims The main purpose of this study is to determine the effect of dialysis on the prognosis (admission to intensive care unit, intubation requirement, length of hospitalization, mortality) of patients with COVID-19 receiving hemodialysis treatment in our clinics. Another aim of this study is to examine the effect of the need for hemodialysis on COVID-19 prognosis in order to contribute to the data of our country. Method Cross-sectional study of 104 patients with hemodialysis and were diagnosed COVID-19 were conducted. In this study, patients were divided into three groups: (i) those with chronic renal failure (CRF) and receiving routine hemodialysis; (ii) those with chronic kidney disease (CKD) but needing urgent hemodialysis; and (iii) those who did not have a known kidney disease but needed urgent hemodialysis because of acute kidney injury (AKI) . The study was performed in accordance with the Declaration of Helsinki. The local ethical committee approved the study design (date: 21.03.2022; reference number: 133/13). Results When we evaluated the demographic, clinical and laboratory factors in our study, it was found that the factors affecting mortality were lymphopenia, emergency HD treatment under the presence of CKD, an increase in AST more than 2 times, the need for mechanical ventilation and high d-dimer (Table 1). Conclusion This case demonstrates that AKI associated with cytokine storm and developing multi-organ dysfunction situation is directly linked to mortality, particularly in patients with severe clinical condition. When the biochemical data of the patients were analysed, it was discovered that AST increase, lymphopenia, and d-dimer rise were directly found associated with increase mortality. In light of these observations, the above-mentioned biochemical laboratory values of the patients can be closely monitored, as can the clinical course of COVID-19 and renal-related mortality.

Evaluation of d-dimer as outcome biomarker in COVID-19 acute respiratory distress patients.

Acute respiratory distress syndrome is a significant complication in critical care patients. COVID-19 (C19)-associated severe respiratory failure is related to it, and d-dimer rise predicts a worse outcome. To investigate the association between d-dimer and the severity of this respiratory syndrome, we conducted a study in C19 intubated patients. A retrospective, single-center observational study was conducted with 64 C19 adult intubated patients. Strata of d-dimer results between patients was evaluated using survival analysis. Survival was higher in mild respiratory distress patients. D-dimer showed poor sensitivity and specificity in predicting respiratory failure severity. Risk assessment for death showed a higher prevalence of admission d-dimer results (HR 1.335; 95% CI 0.695-2.564). Our sample confidently represented the medical profile of C19 severe patients. Sepsis development in C19 is associated with the inflammatory storm in respiratory distress syndrome. As the receiver operating curves show, the increase in d-dimer results is consistent with inflammation rather than a prognostic biomarker. As expected, severe respiratory distress patients presented higher mortality. In summary, d-dimer results are not associated with the prognosis of C19 respiratory distress syndrome patients.

Common Coagulopathies Associated With COVID-19 Patients.

The coronavirus disease 2019 (COVID-19) outbreak, which first appeared in the Chinese province of Hubei city of Wuhan, has been spreading internationally since December 2019. The World Health Organization (WHO) declared the coronavirus illness from 2019 to be a pandemic on March 11, 2020. Patients hospitalised with severe coronavirus or comorbid conditions (like cardiovascular disease and obesity) are linked to a worse prognosis. The rise in D-dimer and its relationship to prognosis are the most often documented aberrations in coagulation/fibrinolysis in COVID-19. However, the D-dimer assessment's utility is not limitless. Since the coagulation/fibrinolytic state might occasionally change over a short period of time, routine exams are also advantageous in understanding the relevance of the inquiry. Both thrombotic and hemorrhagic diseases should be taken into consideration, despite the fact that the pathophysiology of disseminated intravascular coagulation (DIC) linked with coronavirus disease 19 differs significantly from that of septic disseminated intravascular coagulation. Coagulation as well as fibrinolysis indicators are used to make the diagnosis of COVID-19 thrombosis, which encompasses both macro- and micro-thrombosis. Compared to bacterial-sepsis-associated coagulopathy/DIC, COVID-19 has a lower prevalence of prolonged prothrombin time, activated partial thromboplastin time, and decreased antithrombin activity. However, the causes of coagulopathy remain poorly understood. Hypoxia, endothelial injury, dysregulated immunological responses mediated by inflammatory cytokines, and lymphocyte cell death are thought to be implicated. While blood loss tends to be rare, it is uncertain if COVID-19 suffers from thrombosis or whether the current recommendations for regular venous thromboembolic dose are appropriate. It is important to decide on the COVID-19 therapy phases. Antiviral therapy, cytokine storm therapy, and thrombosis therapy are the steps. Future advancements are predicted, such as a therapy that combines heparin and nafamostat.

ELEVATIONS OF PROCALCITONIN AND D-DIMER IN PATIENTS WITH COVID-19 CORRELATE WITH VENTILATOR-ASSOCIATED PNEUMONIA IN THE SETTING OF VENTILATOR-ASSOCIATED EVENTS AND SPUTUM PRODUCTION

TYPE: Abstract TOPIC: Critical Care PURPOSE: It is undetermined whether trending of inflammatory markers in mechanically-ventilated COVID-19 patients is useful in identifying ventilator-associated pneumonia (VAP). The goal of this study is to determine if initial intubation, ventilator-associated events (VAE), or sputum collection was associated with elevations in inflammatory markers, procalcitonin, or positive cultures. METHODS: 287 patients were enrolled in this retrospective study. Data was analyzed into three cohorts: initial intubation, VAE, and sputum collection. Within each group, markers associated with each inciting event were compared to admission values RESULTS: The VAE cohort exhibited differences in WBC (14.1 vs 7.2, p=0.006), d-dimer (4144 vs 881, p<0.001), and CRP (10.4 vs 16, p=0.049). There were no significant differences in procalcitonin and ferritin. The sputum collection cohort revealed differences in WBC (16.8 vs 7.7, p<0.001), procalcitonin (2.95 vs 0.65, p=0.01), and CRP (10.2 vs 15.8, p=0.047). There were no significant differences in FiO2, PEEP, d-dimer, or ferritin. The VAE cohort identified a cultured organism 83% of the time, the initial intubation cohort 35%, and sputum collection cohort 38%. CONCLUSIONS: VAE was associated with a rise in d-dimer, while sputum culture collection was associated with elevated procalcitonin. Interestingly, VAE is suggestive of VAP with an identified organism 83% of the time. Furthermore, d-dimer was associated with VAE and positive organism identification. CLINICAL IMPLICATIONS: This data suggests a role for trending d-dimer and procalcitonin for identification of VAP in setting of a VAE or sputum collection. DISCLOSURE: Nothing to declare. KEYWORD: procalcitonin

Trends and diagnostic value of D-dimer levels in patients hospitalized with coronavirus disease 2019

Coronavirus disease 2019 (COVID-19) has been associated with increased incidence of venous thromboembolic events (VTE) as well as mortality. D-dimer is a marker of fibrinolysis and has been used as a diagnostic and prognostic marker in VTE among other diseases. The purpose of our study is to describe outcomes from out center and to examine trends in D-dimer levels as it relates to VTE and mortality.Patients admitted with confirmed COVID-19 cases to Emory Healthcare from March 12, 2020 through April 6, 2020 with measured plasma D-dimer levels were included in our retrospective analysis. Relevant data about comorbidities, hospitalization course, laboratory results, and outcomes were analyzed.One hundred fifteen patients were included in our study. Mean age was 64 ± 15 years, 47 (41%) females and 84 (73%) African-American. Hypertension was present in 83 (72%) and diabetes in 60 (52%). Mean duration of hospitalization was 19 ± 11 days with 62 (54%) patients intubated (mean duration of 13 ± 8 days). VTE was diagnosed in 27 (23%) patients (mean time to diagnosis 14 ± 9 days). Median D-dimer within the first 7 days of hospitalization was higher (6450 vs. 1596 ng/mL, p < 0.001) in VTE cases compared to non-VTE cases, and was predictive of VTE (area under the curve [AUC] = 0.72, optimal threshold 2500 ng/mL) although not of mortality (AUC 0.55, P = .34). Change in D-dimer level (AUC = 0.72 P = .004) and rate of D-dimer rise (AUC = 0.75 P = .001) were also predictive of VTE, though neither predicted death (P > .05 for all). Within the first 7 days of hospitalization, peak D-dimer level of >2500 ng/mL and a rate of change exceeding 150 ng/mL/d were predictive of future diagnosis of VTE. Rise in D-dimer >2000 ng/mL within any 24 hour period through hospital day 10 had 75% sensitivity and 74% specificity for diagnosis of VTE.We found that both magnitude and rate of rise in d-dimer within the first 10 days of hospitalization are predictive of diagnosis of VTE but not mortality. These parameters may aid in identifying individuals with possible underlying VTE or at high risk for VTE, thereby guiding risk stratification and anticoagulation policies in COVID-19 patients.

Coagulopathy as a Prodrome of Cytokine Storm in COVID-19-Infected Patients.

Background: The rapid coronavirus disease 2019 (COVID-19) pandemic has hit hard on the world and causes panic since the virus causes serious infectious respiratory illness and easily leads to severe conditions such as immune system overactivation or cytokine storm. Due to the limited knowledge on the course of infection of this coronavirus and the lack of an effective treatment for this fatal disease, mortality remains high. The emergence of a cytokine storm in patients with a severe condition has been reported as the top reason of the death of patients with COVID-19 infection. However, the causative mechanism of cytokine storm remains elusive. Thus, we aim to observe the association of coagulopathy (D-dimer) with cytokine (i.e., IL-6) and CT imaging in COVID-19-infected patients.Methods: In this retrospective observational study, we systematically analyzed the comprehensive clinical laboratory data of COVID-19-positive patients in different illness groups of mild, moderate, and severe conditions according to the Chinese Clinical Guidance for COVID-19 Pneumonia Diagnosis and Treatment (7th edition). T tests and chi-square tests were used for two-group comparisons. One-way ANOVA was used for three-group comparisons. Pearson and Spearman correlation coefficients of the D-dimer level with IL-6 and CT imaging were computed at baseline. With regular liquid biopsy approach, D-dimer, IL-6, and neutrophil-to-lymphocyte ratio were recorded repeatedly with a time curve to investigate disease progression, along with CT imaging, and other indicators.Results: All the 64 patients were clinically evaluated and classified into three groups of mild (32 cases), moderate (23 cases), and severe (nine cases) conditions. The D-dimer level positively correlated with IL-6 (R = 0.5) at baseline when the COVID-19-infected patients were admitted. In addition, we observed that D-dimer rises earlier than the cytokine storm represented by IL-6 surge, which suggests that coagulopathy might act as a trigger to potentiate a cytokine storm.Conclusion: Integrated analysis revealed a positive correlation of coagulopathy with cytokine storm in COVID-19-infected patients; the D-dimer rises early, which indicates that coagulopathy acts as a prodrome of cytokine storm. Coagulopathy can be used to monitor early cytokine storm in COVID-19-infected patients.

Fibrinogen and D-dimer variances and anticoagulation recommendations in Covid-19: current literature review.

INTRODUCTION Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly described virus responsible for the outbreak of the coronavirus disease 2019 (Covid-19), named by the World Health Organization (WHO) in February/2020. Patients with Covid-19 have an incidence of acute respiratory distress syndrome (ARDS) of 15.9-29% and sepsis is observed in all deceased patients. Moreover, disseminated intravascular coagulation (DIC) is one of the major underlying causes of death among these patients. In patients with DIC, there is a decrease in fibrinogen and an increase in D-dimer levels. Some studies have shown that fibrinogen and one of its end products, D-dimer, might have a predictive value for mortality in patients with non-Covid sepsis secondary to complications of DIC. Therefore, anticoagulation, considering its mortality benefits in cases of non-Covid sepsis, may also have an important role in the treatment of Covid-19. METHODS We reviewed the literature of all studies published by April 2020 on patients infected with Covid-19. Our review was limited to D-dimer and fibrinogen changes and anticoagulation recommendations. RESULTS Anticoagulation therapy can be started following the DIC diagnosis in Covid-19 patients despite the bleeding risks. In addition, the current evidence suggests a routine use of anticoagulation, particularly in patients with higher D-dimer levels (> 3.0 μg/mL). CONCLUSION Covid-19 is a systemic, hypercoagulable disease requiring more studies concerning treatment. Aanticoagulation is still an issue to be studied, but D-dimer rise and disease severity are the indicative factors to start treatment as soon as possible.

Case of successful treatment of a high risk acute tele with hypothony in a patient with polymorbid pathology

The presented article features the management of a high-risk patient with polymorbid pathology: cancer, stroke and venous thromboembolism. In spite of anticoagulant therapy with heparin, unilateral deep vein thrombosis of the lower leg was complicated by a primary episode of verified acute bilateral pulmonary artery thromboembolism of high-risk with hypotension and bilateral infarct-pneumonia. After urgent diagnosis of PE had been made, the following management of the patient in the acute phase was suggested: timely modern replacement artificial ventilation of the lungs for eight days, vasopressor support for six days, anticoagulant therapy, fluid replenishment and effective in its results, enteral nutrition. The pattern of evolving pulmonary hypertension and acute right ventricular dysfunction, coagulation disorders was tracked down. Residual thrombosis proved to linger by detection of steep D-dimer rise on the ninth day of the acute period. The signs of thrombosis persisted despite anticoagulant therapy, with the simultaneous complete disappearance of blood clots according to computed tomography. That was accompanied by severe disorders of the heart rhythm recalcitrant to antiarrhythmic and electropulse therapy. Further treatment in the settings of a specialized center revealed occult extra routes of impulse conducting that justified necessity of catheter ablation. On the ninetieth day the patient was alive and stable. Presented approach of diagnostic and therapeutic steps proved to be effective.

Multimodality treatment of a massive cervicothoracic lymphatic-venous malformation in a 13-year-old boy

Abstract We report the multi-modality treatment of a massive cervicothoracic lymphatic-venous malformation (LVM) in a 13-year-old boy that was present at birth as a small cervical mass. At four years of age, sclerotherapy significantly reduced the size of the malformation but over subsequent years the mass increased dramatically in size and resulted in a consumptive coagulopathy and limited left shoulder function. Treatment with sildenafil was without effect. The consumptive coagulopathy improved with subcutaneous enoxaparin. A multi-disciplinary team excised part of the mass when he was 11 years old. After surgery, gradual enlargement of the mass and rise in d-dimer prompted treatment with sirolimus. Two sessions of sclerotherapy arrested enlargement of the mass. Multi-modality treatment resulted in a marked reduction of the LVM in the child. However, enlargement of the mass and further treatment is anticipated as a cure has not yet been found.

D-dimer: An Overview of Hemostasis and Fibrinolysis, Assays, and Clinical Applications.

D-dimer is the smallest fibrinolysis-specific degradation product found in the circulation. The origins, assays, and clinical use of D-dimer will be addressed. Hemostasis (platelet and vascular function, coagulation, fibrinolysis, hemostasis) is briefly reviewed. D-dimer assays are reviewed. The D-dimer is very sensitive to intravascular thrombus and may be markedly elevated in disseminated intravascular coagulation, acute aortic dissection, and pulmonary embolus. Because of its exquisite sensitivity, negative tests are useful in the exclusion venous thromboembolism. Elevations occur in normal pregnancy, rising two- to fourfold by delivery. D-dimer also rises with age, limiting its use in those >80 years old. There is a variable rise in D-dimer in active malignancy and indicates increased thrombosis risk in active disease. Elevated D-dimer following anticoagulation for a thrombotic event indicates increased risk of recurrent thrombosis. These and other issues are addressed.

Utility Of D-Dimer As a Marker For Differentiation Syndrome and Infections In Acute Promyelocytic Leukemia (APL)

BackgroundAcute Promyelocytic Leukemia is a highly curable malignancy with cure rates of greater than 90% in most co-operative group trials. However, population based studies indicate that the survival is much lower with up to 30% early deaths. The most common causes of early deaths are bleeding, differentiation syndrome and infection. Early identification and management of these three complications is essential if the outcomes are to be improved further. Bleeding in APL is secondary to disseminated intravascular coagulation (DIC) a peculiar complication of the disease and coagulation panel including d-dimer, fibrinogen levels, prothrombin time, activated partial thromboplastin time are commonly used as markers of DIC. There are presently no available tests to identify DS or infection early and are entirely clinical diagnoses. Here we report the importance of d-dimer levels as probable markers of DS or infection during induction treatment for APL. MethodsWe performed a retrospective chart review on forty one patients diagnosed with Acute Promyelocytic Leukemia and treated with ATRA from September 2005 – June 2013 from Georgia Regents University and those referred here from surrounding treatment centers. Data obtained included D-Dimer levels at diagnosis, daily d-dimer levels when available, dates of differentiation syndrome from start of treatment and dates of infectious complications when available which was obtained from progress notes and microbiology lab and radiology reports. Results41 consecutive APL patients were evaluated for this study. One patient refused treatment and 15 patients did not have coagulation labs (specifically d-dimer) done throughout the course of induction treatment and had to be excluded. Age range of all the patients treated was 21-75 years. There were seven deaths overall and 21 patients had some evidence of DS. The diagnosis of DS was made clinically as per standard guidelines. We included 25 patients in whom there were d-dimer levels done throughout the hospitalization in this study. In these 25 patients, all had an increase in d-dimer levels after an initial drop as the DIC is corrected. 6 patients did not have any complications. In 4 patients the rise in d-dimer was followed by infectious complications. In the other 15 patients, their hospitalization was complicated by DS. In these 15 patients, 6 had elevation in d-dimer prior (0-5 days) to development of DS. In 3 patients the DS developed followed shortly by an elevation in d-dimer. The correlation between d-dimer elevation and DS could not be clearly ascertained from the available documentation in the other 6 patients. ConclusionsAPL is a curable malignancy but early deaths leads to poor outcomes outside of clinical trials. Early identification of the complications of the disease and treatment will allow us to further improve the outcomes in the community. D-dimer is an acute phase reactant and is elevated in any inflammatory state. From our data, the elevation in d-dimers following an initial decrease after correction of coagulopathy secondary to DIC might be marker of differentiation syndrome and or infection. These two conditions are pro-inflammatory states and might explain the increase in d-dimers observed. A larger scale validation is essential to confirm this observation which then might lead to more prompt identification of the complications and ultimately improved outcomes. Disclosures:No relevant conflicts of interest to declare.

Difference in the D-dimer rise between women with singleton and multifetal pregnancies

IntroductionThe differences in the d-dimer rise between women with singleton and multifetal pregnancies have not been studied extensively. Materials and Methodsd-Dimer levels were determined in 1089 blood specimens from 1089 women in various stages of pregnancy, including 977 and 112 women with singleton and multifetal pregnancies, respectively. None of the 1089 women developed hypertension or clinical venous thromboembolism during pregnancy or in the postpartum period. ResultsThe d-dimer levels were significantly and positively correlated with gestational week at examination in women with singleton or multifetal pregnancies. The d-dimer levels (μg/ml, mean±SD [number of specimens]) determined at the 1st trimester did not differ significantly (0.81±0.82 [102] for singleton vs. 1.20±0.77 [7] for multifetal), but those at the 2nd (1.61±1.45 [216] vs. 2.62±2.26 [59]) and 3rd (2.37±2.22 [659] vs. 4.02±2.14 [46]) trimesters were significantly higher in women with multifetal than singleton pregnancies. The 90th percentile value was 4.31μg/ml for 1089 specimens. A significantly greater number of women exceeded 4.31μg/ml during the 2nd (16.9% vs. 5.6%, P=0.0043) and 3rd (34.8% vs. 10.6%, P<0.0001) trimesters among those with multifetal than with singleton pregnancies. ConclusionsThe degree of d-dimer rise in pregnancy was greater in women with multifetal than with singleton pregnancies.

Platelet count kinetics following interruption of antiretroviral treatment

To investigate the mechanisms of platelet kinetics in the Strategies for Management of Antiretroviral Therapy (SMART) study that demonstrated excess mortality with CD4 guided episodic antiretroviral therapy (ART) drug conservation compared with continuous treatment viral suppression. Follow-up analyses of stored plasma samples demonstrated increased activation of both inflammatory and coagulation pathways after stopping ART. SMART patients from sites that determined platelets routinely. Platelet counts were retrospectively collected from 2206 patients from visits at study entry, and during follow-up. D-dimer levels were measured at study entry, month 1, and 2. Platelet levels decreased in the drug conservation group following randomization, but remained stable in the viral suppression group [median (IQR) decline from study entry to month 4: -24 000/μl (-54 000 to 4000) vs. 3000 (-22 000 to 24 000), respectively, P < 0.0001)] and the rate of developing thrombocytopenia (<100 000/μl) was significantly higher in the drug conservation vs. the viral suppression arm (unadjusted drug conservation/viral suppression [HR (95%CI) = 1.8 (1.2-2.7)]. The decline in platelet count among drug conservation participants on fully suppressive ART correlated with the rise in D-dimer from study entry to either month 1 or 2 (r = -0.41; P = 0.02). Among drug conservation participants who resumed ART 74% recovered to their study entry platelet levels. Interrupting ART increases the risk of thrombocytopenia, but reinitiation of ART typically reverses it. Factors contributing to declines in platelets after interrupting ART may include activation of coagulation pathways or HIV-1 replication itself. The contribution of platelets in HIV-related procoagulant activity requires further study.

The predictive values of D-dimer for the early prognosis of the acute myocardial infarction (AMI): a review of 3134 AMI patients

To investigate whether D-dimer could be an early warning signal for patients with acute myocardial infarction (AMI), then may be helpful in risk assessment in emergency department. Three thousand one hundred and thirty-four emergency AMI cases admitted to the hospital from January 1, 2009 to December 31, 2010 were retrospectively reviewed, and their age, gender, past medical history, D-dimer, MB isoenzyme of creatine kinase (CK-MB), cardiac troponin I (cTnI), the precursor of the N-terminal pro-brain natriuretic peptide (NT-proBNP), electrocardiogram (ECG) before treatment, and the CK-MB, cTnI and echocardiography left ventricular ejection fraction (LVEF) 2 hours after the treatment of percutaneous coronary intervention (PCI) or thrombolytic drugs, whether died and time from onset to death were recorded. According to the results of multivariate logistic regression analysis, draw the receiver operating characteristic curve (ROC curve) and fitting curve, and analyzed the relativity between the D-dimer before the treatment and prognosis of myocardial infarction. Multivariate logistic regression analysis showed that age [odds ratio (OR)=1.109, 95% confidence interval (95%CI) 1.073 to 1.147, P=0.000], whether undergoing emergency PCI (OR=4.162, 95%CI 1.980 to 8.748, P=0.000), D-dimer before treatment (OR=1.001, 95%CI 1.000 to 1.002, P=0.001), the LVEF values (OR=0.946, 95%CI 0.928 to 0.964, P=0.000) and cTnI after 2 hours of treatment (OR=1.011, 95%CI 1.004 to 1.018, P=0.002) were correlated to 28-day death. The ROC curves showed that age [area under curve (AUC) 0.796, P=0.000], whether undergoing emergency PCI (AUC 0.704, P=0.000), D-dimer before treatment (AUC 0.797, P=0.000) were positively correlated with the 28-day death; the LVEF values (AUC 0.261, P=0.000) were negative correlated with the 28-day death. The fitting curve of D-dimer before treatment, the time from onset to death and the LVEF showed no linear correlation. D-dimer was correlated with the early prognosis of patients with myocardial infarction, but was not correlated with the time from onset to death. The rise in D-dimer at the early stage of AMI may be helpful to indicate the critical condition of the AMI patients.

THE REASEARCH INTO THE CLINICAL CHARACTERISTICS OF PERIPARTUM CARDIOMYOPATHY

THE REASEARCH INTO THE CLINICAL CHARACTERISTICS OF PERIPARTUM CARDIOMYOPATHY

P4-08-04: Preoperative Thrombin Pathway Activation Identifies Node Positive Patients in Early Breast Cancer.

Abstract Activation of the thrombin pathway (TP) is seen in 50% of cancers and plays a significant role in promoting metastasis. Cancer-induced TP activation is exacerbated by surgery, and this activation may be greater in the presence of metastases. Our aim was to determine if pre-operative plasma d-dimer, a marker of TP activation, correlated with the presence of LN metastases in early breast cancer. We also examined whether surgery-induced TP activation is affected by tumour-associated factors. Methods Plasma d-dimer was measured using automated ELISA pre-operatively and at days 1 and 42 following surgery in 103 prospectively recruited patients undergoing surgery for early breast cancer(87 invasive,13 DCIS). D-dimer values were log-transformed and correlated with LN metastases, tumour size and grade and hormone receptor status using parametric statistical tests. Results Median age was 68 years (range 46–82). Mean tumour size was 14.6 mm (range 7.5-40). Seventy invasive cancer patients had wide local excision(WLE) and sentinel node biopsy(SNB) and 17 had mastectomy(MX) +/− axillary clearance(ANC). Twenty-two patients had positive lymph nodes at primary surgery (MX 8,WLE 14). Of these 3(14%) were ER-ve and 19(86%) were ER+ve. Mean pre-operative d-dimer was higher (p&amp;lt;0.01) in LN positive (704ng/ml, 95% confidence interval, CI, 455–1088) versus LN node negative invasive cancers (443ng/ml, CI 304–627) or DCIS (366ng/ml, CI 284–471). D-dimer was also higher in patients with lymphovascular invasion (612ng/ml, CI 423–886) than in those without (454ng/ml, CI 385–534) and this approached significance (p=0.084). Post-operative d-dimer was higher (p&amp;lt;0.05) after MX compared to WLE at all timepoints. Following WLE + SNB for invasive cancer, post-operative d-dimer rose and was higher at day 1 and day 42 in LN positive vs LN negative and in ER negative versus ER positive cancers (see table). Repeated measures ANOVA analysis showed that the change in d-dimer over time was significantly different between subjects according to LN status (p=0.037) or ER status (p=0.015). Only one patient in the ER negative group had LN metastases. There was no association between pre or postoperative d-dimer and tumour size, tumour grade or PR status. Conclusion Pre-operative TP activation and the thrombotic response to surgery (as measured by d-dimer) is greater in the presence of LN metastases regardless of tumour size. ER negative cancers (7/8 of which were LN negative) also resulted in a greater d-dimer rise, suggesting a difference in the thrombotic response to surgery between different cancer phenotypes. Ongoing work will determine if peri-operative TP activation can act as an independent predictor of node status and cancer recurrence. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-08-04.

Changes in fibrin D-dimer, fibrinogen, and protein S during pregnancy

Background. Pregnancy is a hypercoagulable state with a 5- to 10- fold higher risk of venous thromboembolism. Existing reference intervals for fibrin D-dimer (D-dimer), functional fibrinogen (fibrinogen) and protein S, free antigen (protein S) are based on non-pregnant patients and reference intervals for pregnant patients are warranted. Objectives. The aim of the present study was to contribute to the establishment of reference intervals for D-dimer, fibrinogen and protein S during pregnancy and to discuss the use of the analyses during pregnancy. Methods. We included 55 healthy pregnant women in gestational week 11–17, with normal current pregnancy. Blood samples were collected in gestational weeks 11–17, 21–27 and 34–37. The three plasma parameters D-dimer, fibrinogen and protein S were analysed by STA-R Evolution®. Results. A significant rise in D-dimer was found from first to second trimester (p < 0.0001) and from second to third trimester (p < 0.0001). The level of fibrinogen rose significantly from second to third trimester (p < 0.0001). Protein S showed a statistically significant fall in the level from first to second trimester (p < 0.0001) and remained stable thereafter. Conclusion. Changes during pregnancy in plasma D-dimer, protein S and fibrinogen were confirmed. Further clinical studies are needed to clarify a clinical useful cut-off point for D-dimer in pregnancy. We suggest careful attention to a low peripartum fibrinogen, since it indicates an increased bleeding risk. We confirmed an earlier suggested lower cut-off point for protein S, during pregnancy.

Atherothrombosis and oxidative stress: the connection and correlation in diabetes

Background: Hyperglycaemia-induced depletion of reduced glutathione (GSH) causes erythrocyte oxidative stress (EOS), which leads to vascular events including exacerbation of thrombotic events evidenced by changes in D-dimer level. It would, therefore, appear that there is a complex link between GSH and D-dimer, which are part of an emerging array of biomarkers associated with diabetes. The objective of this study was to investigate evidence of correlation between levels of plasma D-dimer and erythrocyte GSH in diabetes disease progression.Subjects and methods: A cohort of 69 subjects were selected based on medical history plus clinical findings and equally divided into control, prediabetes and diabetes groups, matched for age and sex. Plasma D-dimer and erythrocyte reduced glutathione (GSH) were determined and separated into quartiles as a means of indicating disease severity. Statistical analysis was by Pearson's correlation coefficient.Results: Of the three groups, only the diabetes group showed any correlation between GSH and D-dimer. Of importance is that for increasing GSH, the second quartile range of GSH (xbar ± SD = 45 ± 22 mg/100ml) showed a statistically significant negative correlation for ranked D-dimer (xbar ± SD = 1055 ± 828 μg/l; r = −0.88; P < 0.02). The fourth quartile GSH range (xbar ± SD = 79 ± 40 mg/100 ml) showed a statistically significant positive correlation with D-dimer (xbar ± SD = 1055 ± 828 μg/l; r = 0.91; P < 0.02). Thus, within the diabetes group only, the increasing level of oxidative stress as measured by GSH first indicates a reduction in D-dimer followed by a rise in D-dimer, which led to the proposal of a two-part process of atherosclerosis that reconciles previous contradictory findings.Conclusions: This study provides not only evidence of a correlation between oxidative stress level and fibrinolysis in diabetes, but also an explanation of why previous studies have found both hypo- or hyperfibrinolysis associated with diabetes.

Non-overt disseminated intravascular coagulation in patients during treatment with antithymocyte globulin for unrelated allogeneic hematopoietic stem cell transplantation.

We assessed the effect of rabbit antithymocyte globulin manufactured by Fresenius (ATG-F) on the hemostatic system in patients (n=12) with various hematological malignancies undergoing hematopoietic stem cell transplantation (HSCT) from HLA-matched unrelated donors. For this purpose, we monitored different parameters of coagulation before, during and after the administration of ATG-F. As a control group, we recruited patients (n=10) undergoing HSCT from their HLA-identical siblings who did not receive ATG-F as part of their preparative regimens. At 24 and 48 h after ATG-F treatment had been initiated, we found a temporary rise in D-Dimer, tissue factor, soluble thrombomodulin and thrombin-antithrombin III complex levels and a significant decrease of platelet counts in patients treated with ATG-F as compared to the control group. No differences between the two groups could be detected with regard to global coagulation tests as well as the incidence of bleeding manifestations, thromboembolic complications or the development of vascular-occlusive-disease of the liver. This temporary state of a stressed but compensated coagulation system under ATG-F therapy can be addressed as nonovert disseminated intravascular coagulation (DIC). The effect was independent from the different conditioning regimens and eased off after cessation of ATG-F. We conclude that ATG-F can induce nonovert DIC in patients receiving antithymocyte globulin as part of their conditioning regimen for HSCT.