Levels Of Fibrin Degradation Products Research Articles

Evaluation of coagulation status using clot waveform analysis in general ward patients with COVID-19.

Coronavirus disease (COVID-19)-related systemic cytokine response induces the production of procoagulant factors, which predisposes patients to a prothrombotic state. Viscoelastic testing can identify the degree of hypercoagulability, which is related to outcomes. We aimed to study the changes in clot waveform analysis (CWA) parameters in COVID-19 patients on hospital admission compared to those in a group of healthy individuals. We conducted a retrospective study of COVID-19 patients admitted to general wards and evaluated demographic and clinical parameters as well as laboratory parameters, including coagulation parameters. CWA data from patients (n = 62) with COVID-19 prior to the initiation of anticoagulation therapy were compared with those from healthy controls (n = 67). The measured CWA parameters were min1, min2, max2, and delta change. CWA, fibrinogen, and D-dimer values were higher in COVID-19 patients than in healthy controls (p < 0.001). CWA profiles were consistent with hypercoagulability and characterized by an increase in density, velocity, and acceleration of clot formation. Activated partial thromboplastin time, fibrinogen, D-dimer, and C-reactive protein (CRP) values were higher in patients in whom all CWA parameters were raised than in patients with just a few elevated CWA parameters, while Sequential Organ Failure Assessment scores, prothrombin time, fibrin degradation product levels and platelet counts did not differ between the two groups. CWA variables showed hypercoagulopathy on admission in COVID-19 patients who were hospitalized in the general ward, and this pattern was more pronounced in critically ill patients with elevated fibrinogen, D-dimer, and CRP levels. Our results may help identify patients at high risk of thromboembolism.

Anti-Inflammatory Activity of Biofield Energy Treated Proprietary Test Formulation on Cecal Slurry, LPS and E. coli Induced Systemic Inflammatory Response Syndrome (SIRS) Model in Sprague Dawley Rats

The aim of this experiment was to evaluate the anti-inflammatory potential of the Biofield Energy Treated Proprietary Test Formulation and Biofield Energy Treatment per se to the animals on Cecal Slurry, LPS, and E. coli-induced systemic inflammatory response syndrome (SIRS) model in Sprague Dawley rats. The parameters studies in this experiment includes tumour necrosis factor alpha (TNF-α), interleukin-6 (IL-6), macrophage inflammatory protein-2 (MIP-2), matrix metallopeptidase 9 (MMP9), fibrin degradation products (FDP), Substance P, inducible nitric oxide synthase (iNOS) were analysed using ELISA assay. A test formulation was formulated including minerals (magnesium, zinc, calcium, selenium, and iron), vitamins (ascorbic acid, pyridoxine HCl, vitamin E, cyanocobalamin, and cholecalciferol), Panax ginseng extract, β-carotene, and cannabidiol isolate. The constituents of the test formulation were divided into two parts; one section was defined as the untreated test formulation, while the other portion of the test formulation and three group of animals received Biofield Energy Healing Treatment (prayer) remotely for about 3 minutes by a renowned Biofield Energy Healer, Mr. Mahendra Kumar Trivedi. The level of TNF-α was significantly (p≤0.001) decreased by 46.94% and 55.91% in the G6 (Cecal Slurry, LPS and E. coli along with Biofield Energy Treatment per se to animals from day -15) group as compared to the disease control group (G2) and the untreated test formulation (G4), respectively. The level of IL-6 was significantly (p≤0.001) reduced by 51.44% and 42.92% in the G6 group as compared to the disease control (G2) group and untreated test formulation group, respectively. The level of MIP-2 was significantly reduced by 21.52% and 31.54% (p≤0.001) in the G6 group as compared to the G2 and G4 groups, respectively. The level of MMP-9 was significantly decreased by 40.13% (p≤0.001) and 20.92% in the G6 and G8 groups, respectively as compared to the G2 group. Moreover, the level of FDP was significantly (p≤0.001) decreased by 38.22% and 50.53% in the G6 group as compared to the G2 and G4 groups, respectively. The level of substance P was significantly (p≤0.001) decreased by 36.96% and 38.20% in the G6 group as compared to the G2 and G4, groups, respectively. The level of iNOS was significantly (p≤0.001) decreased by 35.41% in the G6 group as compared to the G4 group. Overall, the data suggested the anti-inflammatory potentials of the Biofield Energy Treated test formulation and Biofield Energy Treatment per se along with preventive measure on the animal with respect to various inflammatory conditions that might be beneficial various types of systemic inflammatory disorders specially sepsis, trauma, septic shock or any types of injuries. Therefore, the results showed the significant slowdown the inflammation-related disease progression and its complications/symptoms in the preventive Biofield Energy Treatment group per se group (G6) comparatively with the disease control group.

Fibrinogen, fibrin degradation products and risk of sarcopenia

Increasing data suggests that chronic low-grade inflammation plays an important role on development of sarcopenia. The present study was designed to identify the association between fibrinogen, fibrin degradation products (FDP) and sarcopenia risk in hospitalized old patients.A total of 437 patients were enrolled in this cross-sectional study (148 with sarcopenia and 289 without sarcopenia). Sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia (AWGS) 2019 criteria. Body composition, grip strength and gait speed were performed to participants. Fibrinogen, FDP levels were measured. Logistic regression analyses were carried out to assess the association between fibrinogen and sarcopenia, between FDP and sarcopenia, respectively.Compared to non-sarcopenic patients, fibrinogen and FDP levels were found to be higher in the sarcopenic group (3.07 g/L vs 2.79 g/L, 1.75 μg/mL vs 1.00 μg/mL, respectively, p < 0.05). Multiple linear regression analysis showed a significant negative association between fibrinogen and gait speed (β: -0.164, p = 0.008), and muscle strength (β: -0.231, p < 0.001). Multivariable logistic regression analysis showed that fibrinogen and FDP were independently associated with sarcopenia (odds ratio 1.32 [95% confidence interval 1.03, 1.70], p = 0.009; odds ratio 1.07 [95% confidence interval 1.01, 1.19], p = 0.049, respectively). ROC curve revealed that the cutoff values of fibrinogen and FDP to predict sarcopenia risk were 2.54 g/L and 1.15 μg/mL, respectively.In hospitalized old patients, serum fibrinogen and FDP levels are elevated in sarcopenia patients than those without sarcopenia. Fibrinogen and FDP are associated with sarcopenia in a concentration-dependent manner.

An evaluation of the Japanese Society on Thrombosis and Hemostasis criteria for disseminated intravascular coagulation as a predictor of prognosis in patients with infection.

A criterion for disseminated intravascular coagulation (DIC) that reflects the status of controlled coagulopathy would be useful for determining when to stop treatment. Use of the DIC criteria of the Japanese Society on Thrombosis and Hemostasis (JSTH) for predicting the outcome during recombinant soluble thrombomodulin (thrombomodulin alfa, TM-α) treatment was evaluated. A retrospective, multicenter survey was conducted in 798 medical facilities in Japan. Of the 4342 patients who underwent TM-α treatment, 193 with infection-associated DIC were investigated. The 28-day mortality rate increased with the increase in JSTH DIC scores at the end of TM-α treatment, with a Cramer's coefficient of association of 0.431. A reduced platelet count (odds ratio [OR]: 0.847, P<.001), prolonged prothrombin time ratio (OR: 5.681, P<.001), decreased fibrinogen level (OR: 0.995, P<.001), higher level of fibrinogen and fibrin degradation products (OR: 1.009, P=.026), and lower antithrombin activity (OR: 0.973, P<.001) were correlated with 28-day mortality. On multivariate analysis, the JSTH DIC score at the completion of TM-α therapy was a predictor of mortality (OR: 1.591, 95% CI: 1.219-2.077). The JSTH DIC score at the end of anticoagulation therapy may be a reliable tool for predicting the outcome in patients with infection-associated DIC.

Prevention of peritoneal pelvic adhesion formation in women of reproductive age

The objective: a prevention of the peritoneal pelvic adhesions formation in women of reproductive age in the postoperative periodMaterials and methods. 132 women with tubal infertility were examined: І group – main one (n=68) and ІІ group – comparison group (n=64). In the postoperative period, the patients of the main group received treatment and prevention measures according to the developed approach (intraoperative administration of anti-adhesion gel 50 ml and 1 suppository of the tiotriazolin a day rectally from the 1st day after surgery for 14 days), and the comparison group – according to the traditional approach. 30 healthy women were examined as a control group.The level of fibrinogen, fibrinogen /fibrin degradation products (FDP), protein-bound hydroxyproline and free hydroxyproline were studied in blood. Pain syndrome was assessed on a 10-point scale.Results. An increase in fibrinogen and FDP levels in the plasma of all examined women were found. But in the main group the concentration of FDP from 4 hours after intervention was significantly higher (5.31±0.24 mg/l) compared to the comparison group (4.53±0.17 mg/l). The level of protein-bound hydroxyproline in the blood serum of the examined women demonstrated its significant increase in the comparison group 12 hours after surgery, with a maximum after 24 hours and maintaining the concentration in 1.9 times higher after 3 days (p&lt;0.05). The level of free hydroxyproline in the main group was significantly (in 1.4–1.6 times) higher than in the comparison group.The increase of the fibrinolytic capacity (p&lt;0.05) in the peritoneal fluid was found during postoperative period. The period of hyperemia in II group lasted 2 times longer than in I group. Also, II group predominates in the number of patients with hyperthermia for more than 3 days – 10 (15.6 %), compared with I group – 4 patients (5.8 %). The duration of stay in the hospital dominated in II group with a standard treatment regimen in the postoperative period – 3.1 %, compared with I group – 1.9 %.The patients after operation in I group evaluated postoperative pain on average by 1.8 points (p=0.00), in II group – at 3.6 points (p=0.06). Synthetic opioid analgesics and nonsteroidal anti-inflammatory drugs were administered intramuscularly for analgesia. The patients in II group required more injections per patient.Conclusions. The proposed approach is effective, pathogenetically reasonable and can be used as a pathogenetic prevention of adhesions formation in women of reproductive age.

Globulin, the albumin-to-globulin ratio, and fibrinogen perform well in the diagnosis of Periprosthetic joint infection

BackgroundAlthough periprosthetic joint infection (PJI) is a severe complication of total joint arthroplasty (TJA), the diagnosis of PJI remains challenging. Albumin (ALB), globulin (GLB), the albumin-to-globulin ratio (AGR), and fibrinogen could be indicators of the body’s inflammatory state. This study aimed to compare the diagnostic accuracy of these biomarkers with that of other inflammatory biomarkers in PJI patients.MethodsWe conducted a retrospective cohort study that included a consecutive series of patients undergoing debridement antibiotic irrigation and implant retention (DAIR), one-stage or the first stage of a two-stage revision total knee arthroplasty (TKA) or total hip arthroplasty (THA) for acute (n = 31) or chronic (n = 51) PJI, or revision TKA or THA for aseptic failures (n = 139) between January 2017 and December 2019 in our hospital. The 2013 criteria of the Musculoskeletal Infection Society (2013 MSIS) were used as the reference standard for the diagnosis of PJI. The preoperative ALB, GLB, AGR, fibrinogen, D-dimer, platelet count, fibrin degradation product (FDP), platelet-to-lymphocyte (PLR), platelet count to mean platelet volume ratio (PVR), neutrophil-to-lymphocyte ratio (NLR), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were assessed. The receiver operating characteristic curve (ROC), sensitivity, and specificity were utilized to compare different biomarkers.ResultsCompared with the aseptic patients, the GLB, D-dimer, fibrinogen, FDP, platelet count, PVR, PLR, NLR, ESR, and CRP levels of PJI patients were significantly higher (P < 0.01); however, the ALB and AGR levels were significantly lower (P < 0.01). The area under the curve (AUC), sensitivity and specificity were 0.774, 67.50, 77.54% for ALB; 0.820, 57.50, 89.86% for GLB; 0.845, 66.25, 93.48% for AGR; 0.832, 78.48, 78.95% for fibrinogen; 0.877, 81.48, 85.07% for ESR; 0.909, 83.95, 88.89% for CRP; 0.683, 55.22, 75.83% for D-dimer; 0.664, 38.81, 88.33% for FDP; 0.678, 52.44, 79.86% for platelet count; 0.707, 48.78, 86.33% for PVR; 0.700, 51.22, 80.58% for PLR; and 0.678, 52.44, 81.30% for NLR, respectively. In the clinic, GLB, AGR and fibrinogen could be used for diagnosis of patients suspected of having PJI.ConclusionOur study demonstrated that GLB, AGR, and fibrinogen were promising biomarkers in the diagnosis of PJI.

Pulmonary coagulation and fibrinolysis abnormalities that favor fibrin deposition in the lungs of mouse antibody-mediated transfusion-related acute lung injury.

Transfusion-related acute lung injury (TRALI) is a life-threatening disease caused by blood transfusion. However, its pathogenesis is poorly understood and specific therapies are not available. Experimental and clinical studies have indicated that alveolar fibrin deposition serves a pathological role in acute lung injuries. The present study investigated whether pulmonary fibrin deposition occurs in a TRALI mouse model and the possible mechanisms underlying this deposition. The TRALI model was established by priming male Balb/c mice with lipopolysaccharide (LPS) 18 h prior to injection of an anti-major histocompatibility complex class I (MHC-I) antibody. Untreated mice and mice administered LPS plus isotype antibody served as controls. At 2 h after TRALI induction, blood and lung tissue were collected. Disease characteristics were assessed based on lung tissue histology, inflammatory responses and alterations in the alveolar-capillary barrier. Immunofluorescence staining was used to detect pulmonary fibrin deposition, platelets and fibrin-platelet interactions. Levels of plasminogen activator inhibitor-1 (PAI-1), thrombin-antithrombin complex (TATc), tissue factor pathway inhibitor (TFPI), coagulation factor activity and fibrin degradation product (FDP) in lung tissue homogenates were measured. Severe lung injury, increased inflammatory responses and a damaged alveolar-capillary barrier in the LPS-primed, anti-MHC-I antibody-administered mice indicated that the TRALI model was successfully established. Fibrin deposition, fibrin-platelet interactions and platelets accumulation in the lungs of mouse models were clearly promoted. Additionally, levels of TATc, coagulation factor V (FV), TFPI and PAI-1 were elevated, whereas FDP level was decreased in TRALI mice. In conclusion, both impaired fibrinolysis and enhanced coagulation, which might be induced by boosted FV activity, increased pulmonary platelets accumulation and enhanced fibrin-platelet interactions and contributed to pulmonary fibrin deposition in TRALI mice. The results provided a therapeutic rationale to target abnormalities in either coagulation or fibrinolysis pathways for antibody-mediated TRALI.

Abnormal Coagulation Function of Patients With COVID-19 Is Significantly Related to Hypocalcemia and Severe Inflammation.

This study aimed to detect, analyze, and correlate the clinical characteristics, blood coagulation functions, blood calcium levels, and inflammatory factors in patients with mild and severe COVID-19 infections. The enrolled COVID-19 infected patients were from Wuhan Jin Yin-tan Hospital (17 cases, Wuhan, China), Suzhou Infectious Disease Hospital (87 cases, Suzhou, China), and Xuzhou Infectious Disease Hospital (14 cases, Xuzhou, China). After admission, basic information was collected; X-ray and chest CT images were obtained; and data from routine blood tests, liver and kidney function, myocardial enzymes, electrolytes, blood coagulation function, (erythrocyte sedimentation rate) ESR, C-reactive protein (CRP), IL-6, procalcitonin (PCT), calcitonin, and other laboratory tests were obtained. The patients were grouped according to the clinical classification method based on the pneumonia diagnosis and treatment plan for new coronavirus infection (trial version 7) in China. The measurements from mild (56 cases) and severe cases (51 cases) were compared and analyzed. Most COVID-19 patients presented with fever. Chest X-ray and CT images showed multiple patchy and ground glass opacities in the lungs of COVID 19 infected patients, especially in patients with severe cases. Compared with patients with mild infection, patients with severe infection were older (p = 0.023) and had a significant increase in AST and BUN. The levels of CK, LDH, CK-MB, proBNP, and Myo in patients with severe COVID-19 infection were also increased significantly compared to those in patients with mild cases. Patients with severe COVID-19 infections presented coagulation dysfunction and increased D-dimer and fibrin degradation product (FDP) levels. Severe COVID-19 patients had low serum calcium ion (Ca2+) concentrations and high calcitonin and PCT levels and exhibited serious systemic inflammation. Ca2+ in COVID-19 patients was significantly negatively correlated with PCT, calcitonin, D-dimer, PFDP, ESR, CRP and IL-6. D-dimer in COVID-19 patients was a significantly positively correlated with CRP and IL-6. In conclusion, patients with severe COVID-19 infection presented significant metabolic dysfunction and abnormal blood coagulation, a sharp increase in inflammatory factors and calcitonin and procalcitonin levels, and a significant decrease in Ca2+. Decreased Ca2+ and coagulation dysfunction in COVID-19 patients were significantly correlated with each other and with inflammatory factors.

Levels of Fibrin Degradation Products at Admission With Acute Ischemic Stroke Correlate With the NIH Stroke Scale Score 1 h After Intravenous Thrombolysis.

Background: Fibrin degradation products (FDPs) are fragments released by the plasmin-mediated degradation of fibrinogen or fibrin. Whether plasma levels of these fragments can predict the thrombolytic effect of recombinant tissue plasminogen activator (r-tPA) remains unknown.Methods: We performed a hospital-based study of patients with acute ischemic stroke (AIS) to explore the relationship between FDP levels at admission and the NIH Stroke Scale (NIHSS) score 1 h after thrombolysis treatment. In this retrospective, single-center study, the data of all patients with AIS who received r-tPA treatment at Beijing Tiantan Hospital from January 2019 to October 2020 were collected and analyzed. Demographic and clinical data, including laboratory examinations, were also analyzed.Results: A total of 339 patients with AIS were included in this study. Of these, 151 showed favorable effects of r-tPA, and 188 showed unsatisfactory effects at 1 h after thrombolysis. Overall, we found an inverse relationship between the FDPs levels at admission and the NIHSS score. A significant difference was observed when using the interquartile range of the FDPs levels (1.31 μg/mL) as a cutoff value (P = 0.003, odds ratio [OR] = 1.95, 95% confidence interval [CI]: 1.26–3.01), even after adjusting for confounding factors (P = 0.003, OR = 2.23, 95% CI: 1.31–3.77). In addition, significant associations were observed in the tertile (T3) and quartile (Q3, Q4) FDP levels when compared with T1 or Q1. A nomogram was also employed to create a model to predict an unsatisfactory effect of r-tPA. We found that FDP levels, white blood cell count, age, D-dimer level, and body mass index could influence the thrombolytic effect of r-tPA.Conclusion: In conclusion, the present study demonstrated that the levels of FDPs at admission can be used as a prognostic factor to predict the curative effect of r-tPA.

The impact of neutrophil extracellular traps on deep venous thrombosis in patients with traumatic fractures

BackgroundDeep venous thrombosis (DVT) is the most common complication in patients with traumatic fractures. The neutrophil extracellular traps (NETs) can promote thrombus formation. In this prospective study, we investigated the role of NETs in thrombosis in patients with traumatic fractures to evaluate whether the biomarkers of NETs can be used to help predict the risk of thrombosis. MethodsTraumatic fracture patients were enrolled in this prospective observational cohort study. Healthy controls (Control); patients with lower extremity fractures who neither present with nor develop DVT (Trauma non-DVT); patients with lower extremity fractures who do not present with DVT but do develop DVT (Trauma DVT); and patients with lower extremity fractures who present with DVT (DVT) were included. NETs biomarker levels of Citrullinated Histone H3 (H3Cit), cell-free DNA (cfDNA) and nucleosomes in the plasma were determined. The D-dimer and fibrin(-ogen) degradation products (FDP) level in plasma was measured. Statistical analysis of the test results was performed to assess changes in NETs biomarker levels during thrombosis in patients with traumatic fractures. ResultsThe H3Cit levels in the DVT group were significantly greater than in the Trauma non-DVT group and Trauma DVT group (1.88(1.11, 3.35) ng/ml Vs 0.38(0.10, 1.17) ng/ml, P ≤ 0.05). The level of cfDNA was significantly greater in patients with traumatic fractures and was higher after thrombosis than before. The levels of D-dimer in the DVT, Trauma DVT, and Trauma non-DVT groups were significantly greater than in the Control group (5.11(3.97, 8.11) mg/l; 6.12(2.59, 18.49) mg/l; 2.99(0.99, 9.02) mg/l Vs 0.18(0.08,0.24) mg/l, P < 0.05). The distribution of FDP levels in each group was similar to that of D-dimer. Data are presented as medians (25th percentile, 75th percentile). ConclusionsNETs released by neutrophils are involved in the formation of DVTs in patients with traumatic fractures. H3Cit and cfDNA can assist the diagnosis of DVT in patients with traumatic fractures.

Хронические субдуральные гематомы головного мозга: проблемы и решения. Часть 2. Новая концепция лечения хронических субдуральных гематом и результаты

The observed dramatic 6–60-fold increase in fibrin degradation product levels in the cSDH cavity compared to peripheral blood was the rationale that underpinned the development of new concept for treatment of chronic subdural hematoma. The minimally invasive surgery results are reported, demonstrating decrease in fatality rate from 12–18% to 1.2% compared to craniotomy, as well as disappearance of severe post-operative complications, such as cerebral collapse. According to 1–10-year follow-up data, 91.7% of patients have shown good recovery.

Clinical Significance of Pro-inflammatory Cytokines and Their Correlation with Disease Severity and Blood Coagulation in Septic Patients with Bacterial Co-infection.

To evaluate the clinical significance of pro-inflammatory cytokines for disease severity and coagulation in septic patients with bacterial co-infection. A total of 92 patients with sepsis admitted to intensive care unit (ICU) from January 2017 to August 2020 were enrolled and their clinical data were retrospectively analyzed. Forty-seven patients (51.1%) had a single infection by Klebsiella pneumoniae or Acinetobacter baumannii (single-infection group), and 45 patients (48.9%) were infected by both species (co-infection group). We compared the clinical characteristics and disease severity among the 92 patients. Disease severity was defined as ICU stay time and 30-day mortality. Plasma concentrations of pro-inflammatory cytokines and their correlation with disease severity and blood coagulation were analyzed. The 30-day mortality in the co-infection group (35.5%) was significantly higher than in the single-infection group (19.1%). The levels of IL-6 and TNF-α in the co-infection group were higher than in the single-infection group. Moreover, high levels of IL-6, IL-8, and TNF-α were positively correlated with disease severity (Spearman P value < 0.05). High levels of IL-6 and TNF-α were negatively correlated with the platelet count (Spearman P value < 0.05) and positively correlated with prothrombin time, and plasma levels of fibrin degradation product and D-dimer levels (Spearman P value < 0.05 for all). Septic patients with bacterial co-infection had increased plasma levels of pro-inflammatory cytokines. Furthermore, a positive correlation between high levels of pro-inflammatory cytokines and increased disease severity and depressed blood coagulation function for septic patients with co-infection was identified.

Clinical profiles of hyperglycemic crises: A single-center retrospective study from Japan.

Aims/IntroductionThe aim of the present study was to clarify the pathophysiologies of hyperglycemic crises in Japanese patients.Materials and MethodsThis was a retrospective study of patients with hyperglycemic crises admitted to Kumamoto Medical Center, Kumamoto, Japan, between 2012 and 2019. Patients were classified as having diabetic ketoacidosis (DKA), hyperglycemic hyperosmotic syndrome (HHS) or a mixed state of the two conditions (MIX), and laboratory data and levels of consciousness at hospital admission, as well as the rates of mortality and coagulation disorders, were compared.ResultsThe diagnostic criteria for hyperglycemic crisis were met in 144 cases, comprising 87 (60.4%), 38 (26.4%) and 19 (13.2%) cases of DKA, HHS and MIX, respectively. Type 1 diabetes was noted in 46.0 and 26.3% of patients in the DKA and MIX groups, respectively. Fibrin degradation product and D‐dimer levels were significantly higher in the HHS group than in the DKA group (DKA and HHS groups: fibrin degradation product 7.94 ± 8.43 and 35.54 ± 51.80 μg/mL, respectively, P < 0.01; D‐dimer 2.830 ± 2.745 and 14.846 ± 21.430 μg/mL, respectively, P < 0.01). Mortality rates were 5.7, 13.2 and 5.3% in the DKA, HHS and MIX groups, respectively. Seven patients (4.9%), four of whom were in the MIX group, had acute arterial occlusive diseases.ConclusionsThe low frequency of type 1 diabetes in DKA and MIX might be responsible for reduced insulin secretion in Japanese populations. Patients with hyperglycemic crises have increased coagulability, and acute arterial occlusion needs to be considered, particularly in MIX.

Evaluation of markers of thrombosis and fibrinolysis in malaria patients in tertiary care hospital in Central India

Background: Cases of malaria are known to be associated with variable degrees of coagulopathy asevident from abnormalities of screening coagulation assays in a large number of patients during theillness. However, attempts to use laboratory parameters as indicators of the severity of theunderlying coagulopathy and for monitoring disease progression have met with only partial success.Methods: This prospective study was conducted in the department of Pathology in RuxmanibenDeepchand Gardi Medical College, Ujjain. Blood samples of all the patients diagnosed positive withmalaria were collected in vials containing ethylene tetra-acetic acid tri potassium salt forhematological parameters and in trisodium citrate tubes for coagulation assays. Result: Out of thetotal positive cases, PT was prolonged in 65% of total cases, Percentage positivity for prolonged PTfor falciparum and vivax is 60% and 68.5% respectively. APTT has raised 47% of malaria positivecases with percentage positivity for falciparum and vivax 48% and 45.7% respectively. 55% of totalcases showed raised levels of fibrin degradation products, which included 48% of falciparum casesand 60% of vivax cases. Out of 120 positive cases of malaria, D- Dimer was raised 41.7% cases.Conclusion: As blood is the chief component affected by malaria, not only proper examination ofperipheral smears is required for detection and species identification, but a careful evaluation ofother laboratory parameters should be done irrespective of the malarial species for the earlydiagnosis of compensatory and non-compensatory consumptive coagulopathy.

Direct hemoperfusion using a polymyxin B-immobilized polystyrene column for COVID-19.

ObjectiveTo evaluate the efficacy and safety of direct hemoperfusion using a polymyxin B‐immobilized polystyrene column (PMX‐DHP) in severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐positive pneumonia patients.MethodsThis study was a case series conducted at a designated infectious diseases hospital. Twelve SARS‐CoV‐2‐positive patients with partial pressure of arterial oxygen/percentage of inspired oxygen (P/F) ratio < 300 were treated with PMX‐DHP on two consecutive days each during hospitalization. We defined day 1 as the first day when PMX‐DHP was performed. PMX‐DHP efficacy was assessed on days 7 and 14 after the first treatment based on eight categories. Subsequently, improvement in P/F ratio and urinary biomarkers on days 4 and 8, malfunctions, and ventilator and extracorporeal membrane oxygenation avoidance rates were also evaluated.ResultsOn day 14 after the first treatment, disease severity decreased in 58.3% of the patients. P/F ratio increased while urine β2‐microglobulin decreased on days 4 and 8. Cytokine measurement pre‐ and post‐PMX‐DHP revealed decreased levels of interleukin‐6 and the factors involved in vascular endothelial injury, including vascular endothelial growth factor. Twenty‐two PMX‐DHPs were performed, of which seven and five PMX‐DHPs led to increased inlet pressure and membrane coagulation, respectively. When the membranes coagulated, the circuitry needed to be reconfigured. Circuit problems were usually observed when D‐dimer and fibrin degradation product levels were high before PMX‐DHP.ConclusionsFuture studies are expected to determine the therapeutic effect of PMX‐DHP on COVID‐19. Because of the relatively high risk of circuit coagulation, coagulation capacity should be assessed beforehand.

Коагулопатия при инфекции COVID-19.

Введение. Известно о коагулопатиях при инфекциях коронавирусами SARS и MERS. Цель исследования: изучить накопленную информацию о коагулопатии при инфекции COVID-19. Материалы и методы. В библиотеке PubMed провели поиск по ключевым словам «COVID-19», «coagulopathy». Обнаружили 15 публикаций, содержащих результаты оригинальных исследований. Результаты. При тяжелом течении заболевания наблюдают цитокиновый шторм, более высокие уровни Д-димера и продуктов деградации фибрина (ПДФ), более длительное протромбиновое время и активированное частичное тромбопластиновое время. Данные о частоте развития синдрома диссеминированного внутрисосудистого свертывания противоречивы. Заключение. У пациентов с COVID-19 с острой дыхательной недостаточностью наблюдается выраженная гиперкоагуляция. Всем госпитализированным пациентам с COVID-19 рекомендована фармакологическая тромбопрофилактика низкомолекулярными гепаринами или фондапаринуксом. Донорскую плазму для пассивной иммунотерапии нужно переливать только в рамках клинических исследований. Background. Coagulopathies are known for infections with SARS and MERS coronaviruses. Objectives: the reviewing the early accumulated information on coagulopathy in COVID-19. Patients / Methods. In PubMed Library with the keywords «COVID-19», «coagulopathy» we selected 15 publications containing the results of original studies. Results. In severe cases of the disease, a cytokine storm is observed, higher levels of D-dimer and fibrin degradation products (FDP), longer prothrombin time and activated partial thromboplastin time. Data about incidence of disseminated intravascular coagulation are contradictory. Conclusions. Patients with COVID-19 with acute respiratory failure exhibit severe hypercoagulation. Pharmacological thromboprophylaxis with low molecular weight heparins or fondaparinux is recommended for all hospitalized patients with COVID-19. Donor plasma for passive immunotherapy should be transfused only as part of clinical trials.

Clinical Investigation and Biological Mechanism of Tigecycline on Coagulation Disorders in Cancer Patients

Tigecycline, a first representative of the new class of glycylcycline antibacterial drugs, has been approved by FDA for using in the treatment of complicated skin and skin structure infections and community-acquired pneumonia in adults in 2005. It has been widely used in hospitals due to its broad-spectrum activity against pathogens. Pre-clinical studies showed that tigecycline has a significant anti-bacterial effect with low and mild adverse drug reactions (ADRs), including nausea, vomit or some other ADRs. Accompany with the huge increase of tigecycline usage in China, more and more side effects began to arouse people's attention. Here, we found that tigecycline can cause coagulation abnormalities in cancer patients, especially with hematological malignance, through clinical observation and retrospective analysis. To analyze the effect and risk factors of tigecycline on coagulation index in severely infected patients with hematologic cancer, we screened the cases admitted to department of hematology from three hospitals treated with tigecycline from Nov, 2015 to Oct, 2019. Then we compared the differences among the prothrombin time (PT), prothrombin time activity (PT %), the international standardization ratio (INR), part of the activation of prothrombin time (APTT), fibrinogen (FBG), thrombin time (TT), D-Dimer, fibrin degradation products (FDP), platelet (PLT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (CRE), and c-reactive protein (CRP) before and after the tigecycline treatment. Meanwhile, we tend to establish the relationship between coagulation function and the time of tigecycline usage. In addition, for exploring the potential cause of abnormal coagulation induced by tigecycline, we evaluated the underlying biological mechanisms via Chinese hamster ovary (CHO) cells treated by tigecycline in vitro and subsequent RNA-sequencing analysis. A total of 129 qualified cases were included for analysis, including 71 males (55%) and 58 females (45%), with average age of 49.5±15.9 years old. After the treatment with tigecycline, PT, APTT and TT were significantly prolonged (P &amp;lt; 0.05). The INR, D-Dimer and FDP levels also increased (P &amp;lt; 0.05), but the FBG concentration was significantly reduced (P &amp;lt; 0.05) which indicated the possibility of hypofibrinogenaemia. Moreover, the coagulation parameters were tremendously changed in the early stage after intravenous infusion of tigecycline for anti-infection. There was no significant change in PLT count, but the levels of ALT, AST, CRE and CRP in the patients were statistically significant declined (P &amp;lt; 0.05). Most of all, the liver and kidney function of the patients was recovered after the infection was controlled by tigecycline treatment. In addition, the adhesion and stretching function of CHO cells were significantly suppressed after tigecycline treatmentin vitro. Lastly, bulk RNA-sequencing assay showed significant abnormalities in gene sets associated with platelet-activation and coagulation, such as PKFP, PLA2g7, PDGFRA, PDGFRB, PAFAH1b3, PDGFA, PECAM1, PDGFC and MPIG6b. Furthermore, adhesion regulating molecules RPN13, CHL1, ICAM5, TLCN were also downregulated by tigecycline treatment. What's more, these key genes which showed above need to be further validated in blood samples of AML patients when treated with tigecycline. Taken together, tigecycline can cause coagulation disorders in blood cancer patients. As we known, blood cancer could disturb the normal hematopoietic reconstitution in bone marrow, which resulted in abnormal numbers and functions of the peripheral blood lineages. Hence, these ADRs can accelerate the disease progression, cause severe bleeding and increase the risk of mortality in these patients. The biological mechanism study of this abnormality showed that tigecycline could inhibit platelet activation and the expression of adhesion regulators, which may increase the risk of bleeding and threaten the safety of patients. Therefore, the monitoring of coagulation index during tigecycline treatment should be adopted. Disclosures No relevant conflicts of interest to declare.

Successful Use of Argatroban to Treat a Critically Ill Patient with Coagulopathy and Nephropathy Secondary to COVID-19.

Data from early case series of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) indicated that disordered thrombosis and hemostasis were frequent features of coronavirus disease 2019 (COVID-19) portending a worse outcome.[1] [2] [3] [4] For example, in a case series of 191 patients from two Wuhan hospitals, an elevated admission D-dimer level was associated with almost a 20-fold increased risk of death.[5] A further single center study of 183 patients from another Wuhan hospital found that elevated fibrin degradation product levels, as well as a prolonged prothrombin time and activated partial thromboplastin time (APTT), were associated with a significantly higher mortality.[6]

Hematologic Parameters of COVID - 19: A Review on Alteration of Hematologic Laboratory Findings

Corona virus 2019 (COVID –19) is a public health emergency and according to the recent statistic of World Health Organization (WHO), this novel virus has infected all continents. During this outbreak, there is an urgent need for documentation of laboratory predictors to discriminate between mild and severe forms of this virus. In this pandemic, prompt identification of clinical and laboratory prognostic factors of progression towards critical and lethal forms of this disease is mandatory. During this new infection, lymphopenia, thrombocytopenia, sometimes neutrophilia, elevation of D-dimer, prolongation of prothrombin time (PT), and Partial Thromboplastin Time (PTT), and also increased level of fibrin degradation products (FDP) could occur. Moreover, elevation of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), procalcitonin, ferritin, Lactate dehydrogenase (LDH), and interleukin -6 (IL- 6) are other laboratory features. These parameters will enable risk stratification and favorable allocation of limited and technical resources particularly in under developed countries. In this review article, alteration of hematologic laboratory findings has been discussed.

Cultivating a Better Understanding of COVID-19 Amidst a Shifting Landscape.

As COVID-19 swept across the globe, emergency physicians stood on the front lines of a pandemic unlike any seen in our lifetimes. In areas where cases surged, we rapidly assessed and stabilized large numbers of critically ill patients using the limited data available to us, for that is, fundamentally, what we do. In the beginning, we relied on first principles. Vital signs are vital. Isolate the infected. Intubate ARDS early.