Levels Of Fibrin Degradation Products Research Articles

ADAMTS-13: A Prognostic Biomarker for Portal Vein Thrombosis in Japanese Patients with Liver Cirrhosis.

Portal vein thrombosis (PVT), one of the most prevalent hepatic vascular conditions in patients with liver cirrhosis (LC), is associated with high mortality rates. An imbalance between a disintegrin-like metalloproteinase with thrombospondin type-1 motifs 13 (ADAMTS-13) enzyme and von Willebrand factor (VWF) is responsible for hypercoagulability, including spontaneous thrombus formation in blood vessels. Herein, we aimed to identify potential prognostic and diagnostic biomarkers in Japanese patients with LC and PVT. In total, 345 patients were divided into two groups: 40 patients who developed PVT (PVT group) and 305 who did not develop PVT (NPVT group). Among the 345 patients with LC, 81% (279/345) were deemed ineligible due to the presence of preventive comorbidities, active or recent malignancies, and organ dysfunction. The remaining 66 patients were divided into two groups: the PVT group (n = 33) and the NPVT group (n = 33). Plasma ADAMTS-13 activity (ADAMTS-13:AC) and the vWF antigen (VWF:Ag) were measured using enzyme-linked immunosorbent assays. Contrast-enhanced, three-dimensional helical computed tomography (CT) was used to detect and characterize PVT. ADAMTS-13:AC was significantly lower in the PVT group than in the NPVT group. No significant differences in plasma vWF:Ag or liver stiffness were observed between the two groups. ADAMTS-13:AC of <18.8 was an independent risk factor for PVT on multivariate analyses (odds ratio: 1.67, 95% confidence interval: 1.21-3.00, p < 0.002). The receiver operating characteristic analysis of ADAMTS-13:AC revealed an area under the curve of 0.913 in PVT detection. Patients with PVT having ADAMTS-13:AC ≥18.8 (n = 17) had higher albumin levels and better prognoses than those with ADAMTS-13:AC <18.8 (n = 16). No significant correlations of ADAMTS-13:AC levels with either fibrin degradation product or D-dimer levels were observed. ADAMTS-13:AC levels could be potential diagnostic and prognostic biomarkers for PVT in Japanese patients with LC.

Tumor Lysis Syndrome in a Patient with BRAFV600E Mutated Colon Cancer Treated with Cetuximab and Encorafenib.

Tumor lysis syndrome (TLS) is a fatal complication associated with chemotherapy. We herein report a case of TLS in a 73-year-old woman with metastatic BRAFV600E mutated colon cancer after she received combined treatment with cetuximab and encorafenib. The serum uric acid, urea nitrogen, and creatinine levels were elevated on day four of the first cycle. The fibrin degradation product (FDP) and D-dimer levels were also high. Diuresis and rasburicase were initiated for TLS, and the laboratory data all normalized on day 8. Thus, the possibility of TLS being induced by targeted drugs in patients with solid tumors, including colorectal cancer, must not be overlooked.

Hematological disorders as a complication of COVID-19

Background. Coronavirus disease (COVID-19) can affect the blood and hemostasis systems and lead to complications that require intensive care. The aim is to detect such common complications by studying literary sources and clinical experience. Materials and methods. The search for relevant literature was conducted in PubMed, and in the other databases such as Science Direct, Google Scholar, Scopus and Web of Science. The literature search was done using the keywords “COVID-19”, “SARS-CoV-2” in combination with “coagulation dysfunction”, “coagulopathy”, “hematological manifestations”, “hematological parameters”, “deep vein thrombosis”, “pulmonary embolism”, “arterial thrombosis”, “D-dimer”, “fibrinogen”, “lymphopenia”, “thrombocytopenia”. Results. COVID-19-associated coagulopathy is characterized by high levels of D-dimer and fibrin degradation products in blood plasma, changes in prothrombin time, activated partial thromboplastin time, fibrinogen, and platelet count. Endothelial dysfunction caused by coronavirus leads to an increased risk of thrombotic complications, both in venous and arterial systems, additionally to the existing higher risk of thrombosis in the intensive care unit. The venous thromboembolism frequency among unvaccinated hospitalized patients and during ultrasound screening is significantly higher. Coronavirus disease can lead to arterial thrombosis in areas such as the aorta, kidneys, cerebral and peripheral arteries. COVID-19 can cause enhanced-fibrinolytic-type disseminated intravascular coagulation or limited thrombotic microangiopathy. According to research, patients with severe COVID-19 usually had leukocytosis, lymphopenia, and an elevated neutrophil-to-lymphocyte ratio. Thrombocytopenia is observed not only during the acute coronavirus disease, but also in the post-COVID-19 period. Both thrombosis and bleeding can occur in patients undergoing extracorporeal membrane oxygenation. Conclusions. A high level of D-dimer, a prolongation of prothrombin time, an increase or a quick decrease in fibrinogen level, lymphopenia, neutrophilia, and an increase in the neutrophil-to-lymphocyte ratio are considered prognostic factors for the severity of coronavirus disease. Deep vein thrombosis and pulmonary embolism are the most common thrombotic events in patients with COVID-19. Arterial thrombosis occurs more often in the cerebral arteries and arteries of the extremities.

Elevated markers of early fibrinolysis disorder as predictors of poor 90-day prognosis in patients with aneurysmal subarachnoid hemorrhage: A large prospective cohort study

ObjectivesEarly fibrinolysis disorder exists in aneurysmal subarachnoid hemorrhage (aSAH). We aimed to investigate the association of markers of early fibrinolysis disorder with poor 90-day prognosis in patients with aSAH. Materials and MethodsA total of 693 consecutive aSAH patients from April 2020 to December 2022 were selected from the Long-term Prognosis of Emergency Aneurysmal Subarachnoid Hemorrhage (LongTEAM) trial. Poor 90-day prognosis was defined as a modified Rankin Scale 3-6 at 90 days after discharge. D-dimer (DD) and Fibrin degradation product (FDP) levels on admission were used to assess fibrinolysis disorder and patients were classified according to their quartiles. Multivariable logistic regression analysis was used to determine the association. ResultsOf 693 patients included, 131 (18.9%) had poor 90-day prognosis. Patients in the highest quartile of DD and FDP levels had higher risk of poor 90-day prognosis than those in the first quartile (DD: adjusted odds ratio [aOR]=2.22, 95% confidence interval [CI], 1.13-4.36, p = 0.021; FDP: aOR=2.87, 95% CI, 1.48-5.58, p = 0.002), after adjusting for potential risk factors. Meanwhile, a linear dose-response relationship between DD and FDP and poor 90-day prognosis was found. Subgroup analysis showed that DD and FDP were consistently associated with poor 90-day prognosis across subgroups, and no intergroup interaction was found. Interestingly, the associations of DD and FDP with poor 90-day prognosis were more significant in low-grade aSAH patients. ConclusionsElevated markers of early fibrinolysis disorder, including DD and FDP on admission, were associated with poor 90-day prognosis in aSAH patients.

Fibrinogen Fragment X Mediates Endothelial Barrier Disruption via Suppression of VE-Cadherin

IntroductionMajor traumatic injury is associated with early hemorrhage-related and late-stage deaths due to multiple organ failure (MOF). While improvements to hemostatic resuscitation have significantly reduced hemorrhage-related deaths, the incidence of MOF among trauma patients remains high. Dysregulation of vascular endothelial cell (EC) barrier function is a central mechanism in the development of MOF; however, the mechanistic triggers remain unknown. Accelerated fibrinolysis occurs in a majority of trauma patients, resulting in high circulating levels of fibrin(ogen) degradation products, such as fragment X. To date, the relationship between fragment X and EC dysregulation and barrier disruption is unknown. The goal of this study was to determine the effects of fragment X on EC barrier integrity and expression of paracellular junctional proteins that regulate barrier function. MethodsHuman lung microvascular endothelial cells (HLMVECs) were treated with increasing concentrations of fragment X (1, 10, and 100 μg/mL), and barrier function was monitored using the xCELLigence live-cell monitoring system. Quantitative PCR (qPCR) was performed to measure changes in EC expression of 84 genes. Immunofluorescent (IF) cytostaining was performed to validate qPCR findings. ResultsFragment X treatment significantly increased endothelial permeability over time (P < 0.05). There was also a significant reduction in VE-cadherin mRNA expression in fragment X-treated HLMVECs compared to control (P = 0.01), which was confirmed by IF staining. ConclusionsFragment X may induce EC hyperpermeability by reducing VE-cadherin expression. This suggests that a targeted approach to disrupting EC-fragment X interactions could mitigate EC barrier disruption, organ edema, and MOF associated with major trauma.

Early identification of lung cancer patients with venous thromboembolism: development and validation of a risk prediction model

IntroductionVenous thromboembolism(VTE) is a leading cause of death in patients with lung cancer. Furthermore, hospitalization of patients with advanced lung cancer for VTE treatment represents a major economic burden on the national public health resources. Therefore, we performed this prospective study to identify clinical biomarkers for the early identification of VTE in lung cancer patients.MethodsThis prospective study enrolled 158 patients with confirmed lung cancer, including 27 who were diagnosed with VTE within six months of the follow-up after lung cancer diagnosis. Multivariate logistic regression analysis was used to evaluate the diagnostic performancese of all the relevant clinical features and laboratory indicators in identifying lung cancer patients with a higher risk of VTE. A novel risk prediction model was constructed consisting of five clinical variables with the best diagnostic performances and was validated using the receiver operation characteristic(ROC) curves. The diagnostic performances of the new risk prediction model was also compared with the Khorana risk score (KRS) and the Padua risk score (PRS).ResultsThe VTE group of lung cancer patients (n = 27) showed significantly higher serum levels of fibrin degradation products (FDP), D-dimer, thrombomodulin (TM), thrombin-antithrombin-complex (TAT), α2-plasmin inhibitor-plasmin Complex (PIC), and tissue plasminogen activator-plasminogen activator inhibitor complex (t-PAIC) compared to those in the non-VTE group (n = 131). ROC curve analyses showed that the diagnostic efficacy of the new VTE risk prediction model with TM ≥ 9.75 TU/ml, TAT ≥ 2.25ng/ml, t-PAIC ≥ 7.35ng/ml, history of VTE, and ECOG PS score ≥ 2 was superior than the KRS and the PRS in the early identification of lung cancer patients with a higher risk of VTE.ConclusionsThe new risk prediction model showed significantly high diagnostic efficacy in the early identification of lung cancer patients with a high risk of VTE. The diagnostic efficacy of the new risk prediction model was higher than the KRS and the PRS in this cohort of lung cancer patients.

Imaging and clinical predictors of acute constipation in patients with acute ischemic stroke.

Constipation symptoms are highly prevalent in acute ischemic stroke, but the clinical and neuroimaging predictors are unknown. This study aimed to identify lesions and clinical features associated with acute constipation. Data from patients with acute ischemic stroke registered in a hospital-based stroke registry between January 2018 and December 2019 were analyzed. Clinical, laboratory, and imaging features were examined for associations with acute constipation. Using the topographic lesion on diffusion-weighted images, multivariate support vector regression-based lesion-symptom mapping (SVR-LSM) was conducted and compared between the non-constipation and acute constipation groups. A total of 256 patients (mean age 67 years, men: 64%) were included. Acute constipation was noted in 81 patients (32%). Initial stroke severity, represented by initial National Institutes of Health and Stroke Scale (NIHSS) scores, was associated with acute constipation. Laboratory parameters, including fibrin degradation products (FDP), fibrinogen, D-dimer, lipoprotein (a), and free fatty acid levels, also showed statistically significant differences between the non-constipation and constipation groups. FDP, D-dimer, and free fatty acid levels were independently associated with acute constipation in the logistic regression model after adjusting for initial NIHSS scores and potassium levels. SVR-LSM revealed that bilateral lesions in the precentral gyrus, insula, opercular part of the inferior frontal gyrus, the inferior parietal lobule, and lesions in the right middle frontal gyrus were significantly associated with acute constipation. The results were consistent after controlling for the initial NIHSS scores and poststroke potassium levels. When cardioembolic stroke subjects were excluded, the right insular and prefrontal cortex lesions lost their association with acute constipation. Acute constipation symptoms after acute ischemic stroke are mainly related to bilateral lesions in the insula, precentral gyrus, postcentral gyrus, and inferior parietal lobule. Clinically important predictors of acute constipation include initial neurological severity and thromboembolic markers of stroke.

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 (> 0.48mg/L) and FDP (> 3.84mg/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.

Differences in coagulation-relevant parameters: Comparing cryoprecipitate and a human fibrinogen concentrate.

Variable fibrinogen content within cryoprecipitate makes accurate dosing challenging in patients with coagulopathic bleeding, in addition to pathogen transmission risks associated with its administration. Purified and standardized human fibrinogen concentrates (HFCs) represent reliable alternatives. Full cryoprecipitate characterization is required to inform selection of an appropriate fibrinogen source for supplementation therapy. Extended biochemical comparison of pooled cryoprecipitate and HFC (Fibryga, Octapharma) was performed using commercially available assays to determine levels of variability in cryoprecipitate and HFC. In addition to standard procoagulant factors, measurements included activities of platelet-derived microparticles (PMPs) and plasminogen, and levels of fibrin degradation products. Cryoprecipitate contains lower fibrinogen levels than HFC (4.83 vs.19.73 g/L; p<0.001), translating to approximately half the amount of fibrinogen per standard cryoprecipitate dose (two pools, pre-pooled from five donations each) vs. HFC (2.14 vs. 3.95 g; p<0.001). Factor XIII (FXIII) levels were also lower in cryoprecipitate vs. HFC (192.17 vs. 328.33 IU/dL; p = 0.002). Levels of procoagulants in cryoprecipitate, such as von Willebrand Factor (VWF) and factor VIII (FVIII), were highly variable, as was PMP activity. A standard cryoprecipitate dose contains significantly higher levels of measured plasminogen and D-dimer fragments than a standard HFC dose. The tested HFC is a more reliable fibrinogen and FXIII source for accurate dosing compared with cryoprecipitate. Cryoprecipitate appears considerably less predictable for bleeding management due to wide variation in pro- and anticoagulation factors, the presence of PMPs, and the potential to elevate VWF and FVIII to prothrombotic levels.

Retinochoroidal Manifestation of Toxoplasmosis in a Young Patient

We report the case of a 15-year-old young girl, with retinochoroidal manifestation of toxoplasmosis, without vitritis. Serology for Toxoplasma gondii was positive (IgG positive /IgM negative), but PCR for Toxoplasma gondii in peripheral blood samples was negative. Blood tests including complete hemogram (total leukocyte, red blood cell and platelet count) except for hemoglobin, coagulogram (APTT, INR, and fibrin degradation product level) and routine blood biochemistry (serum urea, creatinine, and random blood sugar) were within normal limits. The serum levels of triglycerides, low density lipoproteins, high-density lipoproteins and calcium were within normal limits. Direct ophthalmoscopy of the right eye revealed a well-demarcated circular atrophic pigmented scar of about four disc diameters involving the macula. We did not initiate any therapy, because the process appeared to be active anymore. In our case demonstrate of retinochoroidal manifestation of toxoplasmosis by routine fundus examination in a young patient with uncharacteristic complaints.

Clinical analysis of 11 cases of pregnancy with aortic dissection

Objective: To investigate the treatment and maternal and fetal outcomes of pregnant women with aortic dissection (AD). Methods: The clinical data of 11 pregnant women with AD treated at the First Affiliated Hospital of Air Force Military Medical University from January 1st, 2011 to August 1st, 2022 were collected, and their clinical characteristics, treatment plans and maternal and fetal outcomes were analyzed retrospectively. Results: (1) Clinical characteristics: the age of onset of 11 pregnant women with AD was (30±5) years old, and the week of pregnancy of onset was (31.4±8.0) weeks. Clinical manifestations: the main symptoms were sudden onset of chest and back pain or low back pain. Type of AD: 8 cases of Stanford type A, and 3 cases of type B. The aortic width was (42±11) mm. Diagnostic methods: the diagnosis of AD was confirmed by transthoracic echocardiography (TTE), computed tomography angiography (CTA) or enhanced CT examination, among which 4 cases were confirmed by CTA examination, 4 cases by TTE examination, and 3 cases by enhanced CT examination. Laboratory results: white blood cell count was (15.4±8.7) ×109/L, neutrophil count was (13.5±8.5) ×109/L, the median D-dimer level was 2.7 mg/L (2.1-9.2 mg/L), and the median fibrin degradation products level was 12.0 mg/L (5.4-36.1 mg/L). (2) Treatments: all 11 patients were admitted to hospital in emergency. Before operation, the departments of cardiac surgery, obstetrics, pediatrics and anesthesiology cooperated to develop individualized treatment plan. Aortic surgery was performed in 11 pregnant women with AD. In 6 of them, pregnancy termination was performed at the same time as aortic surgery, and aortic surgery was performed after cesarean section. Four cases of pregnancy termination and aortic operation were performed by stages, including aortic operation after cesarean section in 2 cases, and cesarean section after aortic operation in 2 cases. One case (12+6 weeks of gestation) had spontaneous abortion on the day after aortic surgery. The gestational age of the 11 patients on pregnancy termination was (32.9±7.4) weeks. Aorta surgical methods: 7 patients received under extracorporeal circulation ascending aorta replacement ± aortic valve replacement ± coronary artery transplantation (or coronary artery bypass transplantation)± left and right coronary Cabrol + total arch replacement (or aortic arch replacement)± stent implantation, 1 patient received under extracorporeal circulation aortic root replacement, and 3 patients underwent aortic endoluminal isolation. (3) Maternal and fetal outcomes: among the 11 pregnant women with AD, 9 (9/11) survived, 2 (2/11) died with lower limb ischemia before the onset of the disease. A total of 10 newborns were born in 9 pregnant women after delivery (1 of them was twins), and the 2 cases were spontaneous abortion after aortic surgery in the first trimester (12+6 weeks) and fetal death after hysterotomy in the second trimester (26+3 weeks), respectively. Among the 10 surviving neonates, 3 were full-term infants and 7 were premature infants. The birth weight of newborn was (2 651±784) g. Respiratory distress syndrome was found in 6 cases. The newborns were followed up for (5.6±3.6) years after birth, and the infants developed well during the follow-up period. Conclusions: Pregnancy complicated with AD is dangerous, and chest and back pain is the main clinical manifestation of this disease. With early identification and selection of appropriate diagnostic methods, multidisciplinary diagnosis and treatment, mother and children could obtain good outcomes.

Hypercoagulability in women with adenomyosis who experience heavy menstrual bleeding

ObjectivesTo investigate whether there is any difference in coagulability between patients with adenomyosis-associated heavy menstrual bleeding (ADM-HMB) and women without adenomyosis. Methods and materialsSeventy-two premenopausal patients with histologically diagnosed adenomyosis, but free of metabolic or hematological diseases, who experienced either moderate/heavy menses (MHB) or excessive (EXB) menstrual blood loss (MBL) based on their amount of MBL (>60mL but ≤100mL vs. >100mL) were recruited. Additionally, 50 patients without adenomyosis were also recruited. Their demographic, clinical and coagulation information were collected. All recruited subjects had platelet count, prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (aPTT), and plasma fibrinogen and D-dimer levels. AMD-HMB patients also had data on anti-thrombin activity and fibrin degradation products (FDPs). ResultsADM-HMB patients had significantly higher platelet count, fibrinogen and D-dimer levels but shorter PT and aPTT as compared with women without adenomyosis. Within the ADM-HMB patients, patients who complained of EXB had significantly higher plasma D-dimer and FDP levels but shorter aPTT and lower fibrinogen levels than those who complained of MHB. ConclusionThese data strongly suggest that ADM-HMB women are in a hypercoagulable state as compared with women without adenomyosis, especially in those complained of excessive MBL. Our findings suggest that precautionary or even prophylactic measures may be advised to reduce the risk of thrombotic events in ADM-HMB patients, especially those with excessive MBL. In addition, our data suggest that anti-thrombotic/anti-coagulation therapies may hold therapeutic potentials.

Гормональная контрацепция в аспекте влияния на систему гемостаза

Aim: to study the hemostasis indicators in female patients with hyperandrogenism (HA) and menstrual disorders (MDs) during combined oral contraceptive (COC) intake, depending on the presence of undifferentiated connective tissue displasia (UCTD). Patients and Methods: the study results of 28 female patients with HA and MDs were divided into 2 groups: group 1 — 22 patients (mean age 22.1±3.2 years) with UCTD, group 2 — 6 patients (mean age 20.5±1.8 years) without UCTD. The content of hormones in the blood (on the 2nd–3rd day of the menstrual period), the parameters of hemostasis before and after 1 month of COCs intake, and the level of homocysteine were determined in all patients. Results: the analysis revealed an increase in the levels of platelet activation markers, coagulation link and fibrinolysis. During COCs intake, an increase in the fibrinogen content was noted in patients of both groups, which, however, did not exceed the reference values. During the correlation analysis, it was found that in groups 1 and 2, the parameters of the fibrinogen baseline, D-dimer and the corresponding indicators after 1 month of COCs intake had a strong correlation with each other (r=0.845, r=0.864). However, group 1 had higher levels of fibrinogen and fibrin degradation products (D-dimer) (p&lt;0.0001) versus those in group 2. The study on the trend of prothrombin time (PTT) and activated partial thromboplastin time (APTT) during COCs intake in female patients with HA and UCTD revealed an acceleration of indicators (p&lt;0.01) versus those before COCs intake. At the same time, the change in blood clotting markers was not realized by episodes of thrombosis in any of the patients. Conclusion: patients with UCTD had changes that characterized the activation of thrombogenesis. When planning hormonal contraception, it is necessary to single out a group of female patients with HA and signs of UCTD as the most vulnerable in relation to an increased risk of thrombogenic events. KEYWORDS: hyperandrogenism, combined oral contraceptive, thrombosis, connective tissue dysplasia, hyperhomocysteinemia. FOR CITATION: Kudinova E.G. Hormonal contraception in terms of effect on the hemostasis system. Russian Journal of Woman and Child Health. 2023;6(2):130–137 (in Russ.). DOI: 10.32364/2618-8430-2023-6-2-130-137.

The indicators for early blood transfusion in patients with placental abruption with intrauterine fetal death: a retrospective review

BackgroundPlacental abruption (PA) with intrauterine fetal death (IUFD) is associated with a high risk of postpartum hemorrhage (PPH) resulting from severe disseminated intravascular coagulation (DIC). Therefore, blood products that are sufficient for coagulation factor replacement must be prepared, and delivery should occur at referral medical institutions that are equipped with sufficient blood products and emergency transfusion protocols. We retrospectively reviewed the records of patients with PA and IUFD (PA-IUFD) to identify possible factors that may indicate the need for early blood transfusion and investigated whether the Japanese scoring system for PPH can be applied in such cases.MethodsWe used a database of 16,058 pregnant patients who delivered at Yokohama City University Medical Center between January 2000 and February 2016. Thirty-three patients were diagnosed with PA-IUFD before delivery and categorized into two groups–blood transfusion and non-transfusion–to compare the maternal characteristics and pregnancy outcomes.ResultsIn patients with PA-IUFD, the transfusion group exhibited significantly more blood loss; lower fibrinogen levels and platelet counts; higher levels of fibrin degradation products (FDP), D-dimer, and prothrombin time; and a tendency for tachycardia on admission, compared to the non-transfusion group. Many patients in the transfusion group had normal fibrinogen levels on admission but later displayed markedly decreased fibrinogen levels. The Japan Society of Obstetrics and Gynecology (JSOG) DIC score was significantly higher in the transfusion than in the non-transfusion group.ConclusionsIn PA-IUFD, the fibrinogen level, platelet count, D-dimer, FDP, heart rate, and JSOG DIC score on admission may indicate the need for blood transfusion. However, even with normal fibrinogen levels on admission, continuous monitoring is indispensable for identifying progressive fibrinogen reductions in patients with PA-IUFD.

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

ObjectiveConsumptive 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. MethodsTo 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. ResultsAll 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. ConclusionsThe 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.

Kidney Histopathology Features of Suspected Intra-Kidney Venous Thromboembolism in Patients with Primary Glomerulonephritis

Introduction: Renal vein thromboembolism is a severe complication of nephrotic syndrome. Small thrombus in the intra-kidney venous system cannot be recognized by ultrasonography. The current study was to investigate the kidney pathological features of intra-kidney venous thrombus and their values in clinical practice. Methods: Kidney pathological features of glomerular capillary dilatation and congestion, peritubular capillary dilatation and congestion, and intraglomerular neutrophil infiltration were screened and scored during kidney biopsy information interpretation. Eighty-four consecutive patients with these features and primary glomerulonephritis were analyzed, comparing to another 84 control patients without these features who were matched according to the pathological types of glomerulonephritis. Results: In the patients with pathological features of suspected intra-kidney venous thrombus, the levels of proteinuria (5.2 vs. 3.2 g/24 h, p = 0.005), serum creatinine (80.9 vs. 71.2 μmol/L, p < 0.001), platelet count (274.0 vs. 254.5 ×10⁹/L, p = 0.020), D-dimer (0.2 vs. 0.2 mg/L, p = 0.002), and fibrin degradation products (1.9 vs. 1.0 mg/L, p = 0.003) were significantly higher than those in control patients. The levels of serum albumin (24.2 vs. 28.6 g/L, p = 0.003) and eGFR (92.1 vs. 103.9 mL/min/1.73 m², p < 0.001) were significantly lower. The scores of these pathological features were positively correlated with the levels of D-dimer (r = 0.21, p = 0.05). During follow-up, 9 (10.7%) patients with pathological features of suspected intra-kidney venous thrombus developed venous thromboembolism, which was significantly more than that of control patients (0%, p = 0.006). Conclusions: Kidney pathological features could indicate intra-kidney venous thromboembolism, and their scores represent the possibility of thrombus. The notice of these features may provide clinical alerts for venous thromboembolism possibility.

A Case of Deep Vein Thrombosis After Recovery From COVID-19 and Its Association With Elevated D-dimers

The coronavirus disease 2019 (COVID-19) continues to be a devastating disease for the elderly population, especially in long-term care facilities, and it presents with varying clinical presentations. We have ample evidence that COVID-19 can predispose to deep vein thrombosis (DVT) and pulmonary embolism (PE) during an active infection. Still, very few cases of DVT have been reported after recovery from COVID-19. The imbalance of the coagulation cascade and the increased release of certain coagulation factors play an essential role in promoting hypercoagulability and vascular endothelial dysfunction. It leads to a rise in the level of fibrin degradation products, D-dimers, which can remain elevated for up to several weeks, even after recovery. It has been suggested that the risk of DVT occurring after recovering from COVID-19 remains high for up to three months. We report a case of a 77-year-old long-term care female resident at a nursing facility, ambulatory at baseline, who was noted to be COVID-19 positive upon routine facility-wide testing per department of health guidelines. She was asymptomatic during her 10-day quarantine period. D-dimer levels during routine labs were high (initial D-dimer level of 1.87 mg/L FEU {normal value: 0.19-0.52 mg/L FEU}), but the patient had no clinical signs and symptoms of DVT. Ultrasound of the bilateral legs was not performed due to low clinical suspicion. The patient received an enoxaparin DVT prophylaxis dose during the quarantine period. Follow-up D-dimer levels were done at frequent intervals after recovery, but D-dimer levels continued to remain elevated up till six weeks after her 10-day quarantine period ended.Based on previous experience with other long-term care residents who suffered from COVID-19, bilateral lower extremity ultrasound was performed, which showed bilateral DVT. Elevated D-dimer levels are a predictor of hypercoagulation complications in COVID-19. Patients with persistently elevated D-dimer levels after recovery from COVID-19 should be screened for thromboembolic complications, even if they are asymptomatic. DVT can occur up to three months post-recovery from COVID-19 infection.

Стан імунної та гемокоагуляційної систем у динаміці вагітності після ДРТ у жінок з інфекціями, що передаються статевим шляхом, в анамнезі

Purpose - to analyze the dynamics of laboratory parameters of functioning of the immune and haemocoagulation systems in pregnant women with a history of sexually transmitted infections (STIs) after pregravid preparation before cycles of assisted reproductive technologies (ART). Materials and methods. The functioning analysis of the immune and hemocoagulation systems of 200 pregnant women with a history of STIs after ART has been conducted. Group I (main) consisted of 100 pregnant women with pregravid preparation before the ART cycle, obstetric and perinatal support and delivery in accordance with the medical and organizational algorithms developed by our team, prognostic methods and treatment and preventive schemes; Group II (main) - 100 pregnant women who were treated using generally accepted prognostic, therapeutic and preventive measures. The control group is 100 practically healthy pregnant women with a favorable reproductive history and an uncomplicated course of pregnancy. The women underwent an in-depth immunological examination. Statistical processing of research results was carried out with the use of programs «Microsoft Excel 5.0» and «Statistica 8.0». Results. It is demonstrated a significant decrease (p&lt;0.05) in lymphocyte levels with properties of natural killers (CD56+) during the gestational period in pregnant women of Group I against Group II; the level of total hemolytic activity of the classical complement activation pathway (CH50) in Group I of pregnant women increased steadily with increasing gestational age; at the end of the II trimester, there was a significant decrease in CH50; in the III trimester of pregnancy, the level of CH50 in Group II was 123±6.7, but in the Group I this figure remained higher. Throughout the II and III trimesters of gestation, there was a probable decrease (p&lt;0.05) of the immunoregulatory coefficient in Group I of pregnant women, due to adequate correction of derivative immunological disorders, compared with pregnant women of Group II. During the residual formation of the placental barrier in Group I pregnant women the active partial thromboplastin time increased significantly during the gestational period and differed significantly from the indicators of Group II; there was a general decrease in the active recalcification time during the II and III trimesters of pregnancy in women of the Group I; a gradual decrease in the level of fibrin and fibrinogen degradation products, unlike the analogous indicator in the Group II, which showed a gradual increase. The level of stable thromboxane metabolite (TxB2) in the II trimester decreased twofold and was lower than in Group II; the level of stable prostacyclin metabolite (6-keto-PGF1α) increased in the III trimester. This led to an increase of PgI2/TxA2 balance in Group I, which corresponded to the physiological requirements of systemic and organ hemodynamics during pregnancy. Conclusions. Development and implementation of effective pregravid preparation before ART cycles in women with a history of STIs and medical correction during pregnancy helps to increase an adaptive compensatory and an adaptive potential in the immune and haemocoagulatory homeostasis of the mother and perinatal protection of the fetus. The study was carried out in accordance with the principles of the Helsinki Declaration. The research protocol was approved by the Local Ethics Committee of the institution specified in the article. The study received informed consent from the women. No conflict of interests was declared by the author.

Abstract 460: Covid-19 And Acute Limb Ischemia: Arterial Thromboemboli Composition And Architecture

Objectives: The incidence of acute limb ischemia (ALI) has increased since the emergence of coronavirus disease 2019 (COVID-19) and has been linked to the serum level of cross-linked fibrin degradation products (D-dimer). The purpose of this study is to understand arterial thromboembolic architecture in patients with ALI and how this is altered by COVID-19 infection. Methods: Arterial thromboembolic specimens were prospectively collected at a single institution, stored in an IRB-approved tissue bank at -80°C for preservation of architecture. Liquid chromatography mass spectrometry (LC-MS/MS) was used to identify in-vivo Factor XIII (FXIII) generated cross-links, critical determinants of clot stability and strength. Protein composition of thromboemboli was compared between COVID and non-COVID patients. Results: Arterial thromboemboli were obtained from four patients. Patient #1 had COVID pneumonia and a D-dimer of 14,690 ng/mL FEU and developed ALI secondary to embolization of an aortic thrombus. Patients #2-4 did not have COVID and developed ALI secondary to synthetic graft thrombosis, septic embolization from endocarditis, and embolization during aortic arch replacement. COVID thromboemboli demonstrated a higher abundance of immune response proteins compared to non-COVID thromboemboli. Eighty-one cross-links were identified across the four specimens (Fig 1). A six-fold greater degree of Fibrinogen Alpha Chain (FibA-FibA) cross-linking was present in the COVID specimen (Mean: 295,100) compared to the mean of the three non-COVID specimens (Mean: 52,973) (Figure 2). Conclusions: A higher degree of cross-linking and increased levels of innate and adaptive immune response proteins appear to be features of arterial thromboemboli in COVID-induced ALI. This supports a virus-associated hypercoagulable state in COVID-19 patients with ALI.