OBJECTIVE: To investigate the value of pre-treatment albumin/fibrinogen ratio (AFR) on the prognosis of patients with diffuse large B-cell lymphoma (DLBCL). METHODS: The data of DLBCL patients in the Affiliated Hospital of North Sichuan Medical College from April 2014 to March 2021 were retrieved, and 111 newly diagnosed patients who completed at least 4 cycles of R-CHOP or R-CHOP-like chemotherapy with complete data were included in the study. The clinical, laboratory examination and follow-up data of the patients were collected, and the receiver operating characteristic curve (ROC) was drawn according to patients' AFR before treatment and the survival status at the end of the follow-up, which could be used to preliminarily evaluate the predictive value of AFR for disease progression and patients' survival outcome. Furthermore, the correlation of AFR with the clinical and laboratory characteristics, progression-free survival (PFS) and overall survival (OS) was analyzed, and finally, univariate and multivariate Cox proportional hazard regression models were used to analyze factors affecting PFS and OS of DLBCL patients. RESULTS: The ROC curve indicated that AFR level had a moderate predictive value for PFS and OS in DLBCL patients, with the area under the curve (AUC) of 0.616 (P =0.039) and 0.666 (P =0.004), respectively, and the optimal cut-off values were both 9.06 for PFS and OS. Compared with high-AFR (≥9.06) group, the low-AFR (<9.06) group had a higher proportion of patients with Lugano III-IV stage ( P <0.001), elevated lactate dehydrogenase (P =0.007) and B symptoms (P =0.038). The interim analysis of response showed that the overall response rate (ORR) in the high-AFR group was 89.7%, which was significantly higher than 62.8% in the low-AFR group (P =0.001). With a median follow-up of 18.5 (3-77) months, the median PFS of the high-AFR group was not reached, which was significantly superior to 17 months of the low-AFR group (P =0.009). Similarly, the median OS of high-AFR group was not reached, either, which was significantly superior to 48 months of the low-AFR group (P < 0.001). In multivariate Cox regression analysis, AFR <9.06 was an independent risk factor both for PFS and OS (HR _PFS=2.047, P =0.039; HR _OS=4.854, P =0.001). CONCLUSION Pre-treatment AFR has a significant value for the prognosis evaluation in newly diagnosed DLBCL patients.
Humans ; Prognosis ; Fibrinogen ; Disease-Free Survival ; Albumins/therapeutic use* ; Hemostatics/therapeutic use* ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

OBJECTIVETo explore the therapeutic effect of qi benefiting blood activating method (QB-BAM) on acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients with blood stasis syndrome (BSS) by observing its effect on plasma fibrinogen (Fg) and D-dimer (D-D) levels.

METHODSSixty AECOPD patients with BSS were randomly assigned to the treated group and the control group, 30 in each group. All patients received conventional therapy for AECOPD. Those in the treated group were additionally injected with Shengmai Injection and Tanshinone IIA Injection. Clinical efficacy and indices including levels of Fg, D-D, PaO2, and PaCO2 were measured and compared before and after treatment.

RESULTSThe effective rate was 93.3% (28/30 cases) in the treated group, higher than that of the control group [73.3% (22/30 cases) , P < 0.05]. There was no significant difference in all indices between the treated group and the control group before treatment (P >0.05). After treatment all indices were significantly improved in the two groups (P < 0.01). But in the treated group levels of Fg and D-D decreased more and levels of PaO2 increased more (P < 0.01). Plasma levels of Fg and D-D levels were negatively correlated with PaO2 (r = -0.493, r = -0.438, P < 0.01) before treatment, and also negatively correlated with PaO2 (r = -0.452, r = -0.325, P < 0.01, P < 0.05) after treatment, but they were not significantly correlated with PaCO2 before and after treatment (P >0.05).

CONCLUSIONSQBBAM could play a therapeutic role in improving prethrombotic states of AECOPD patients with BSS. Plasma levels of Fg and D-D were related to the severity of AECOPD.

Acute Disease ; Drugs, Chinese Herbal ; therapeutic use ; Fibrin Fibrinogen Degradation Products ; Fibrinogen ; Hemostatics ; Humans ; Plasma ; Pulmonary Disease, Chronic Obstructive ; drug therapy ; Qi

Drug Combinations ; Fibrinogen ; therapeutic use ; Fistula ; etiology ; therapy ; Groin ; Humans ; Lymphatic Diseases ; etiology ; therapy ; Postoperative Complications ; therapy ; Thrombin ; therapeutic use ; Treatment Outcome

BACKGROUNDFibrinogen-depleting agents are promising in the treatment of cerebral ischemic disease. They were studied by many trials, and the outcomes were different because of different regimens and different doses. In this study, we assessed the efficacy and safety of defibrase on acute cerebral infarction in China.

METHODSA search using Chinese hospital knowledge database (CHKD) and MEDLINE database for randomized controlled trials was carried out. A CHKD (1994 June 2005) search was performed with the keyword "defibrase", then a second search for the keyword "acute cerebral infarction"; a MEDLINE search (1950 June 2005) was performed with the following keywords: [(cerebral ischemia), OR (acute cerebral infarction), OR (stroke)], AND [defibrase]. Meta-analysis was performed with RevMan software 4.2.

RESULTSIncluded were 14 studies comparing the efficiency and safety of defibrase with other drugs in the treatment of acute cerebral infarction. Patients' records were pooled (total 646 patients; defibrase, n = 328, no defibrase n = 318). Neurological deficit score (NDS) before treatment showed weighted mean differences (WMD) = 0.95, 95% confidence interval (CI) = (-0.60, 2.50), P = 0.23; NDS after treatment showed WMD = -2.20, 95% CI = (-4.21, -0.18), P = 0.03; Barthel index at 3 months showed WMD = 4.45, 95% CI = (-0.13, 9.03), P = 0.06; the plasma fibrinogen level before treatment showed WMD = 0.02, 95% CI = (-0.16, 0.19), P = 0.86; plasma fibrinogen level after treatment showed WMD = -1.51, 95% CI = (-1.88, -1.15), P < 0.00 001.

CONCLUSIONSWith the given dose and regimen of defibrase in China, defibrase may play a role of anticoagulation. It might inhibit the progression of stroke and prevent the recurrence of stroke.

Acute Disease ; Adult ; Aged ; Batroxobin ; therapeutic use ; Cerebral Infarction ; blood ; drug therapy ; Fibrinogen ; analysis ; Fibrinolytic Agents ; therapeutic use ; Humans ; Middle Aged

OBJECTIVETo evaluate the therapeutic effect of individualized defibrase therapy according to the level of plasma fibrinogen (FIB) in patients with acute cerebral infarction (ACI).

METHODSSixty patients with ACI (within 72 h after onset) were randomly divided into defibrase group (n=30) and control group (n=30). The patients in defibrase group received intravenous defibrase infusion at different first doses (15, 10, and 5 U) according to plasma FIB level (>4 g/L, 2-4 g/L, and 1.3-2 g/L) before treatment. Plasma FIB was measured every 12 h after the first dose of defibrase, and when plasma FIB was over 1.3 g/L, intravenous infusion of 5 U defibrase was given to maintain plasma FIB within the range of 0.70-1.13 g/L over a period of 7 days. The plasma prothrombin time (PT), activated partial thromboplastin time (APTT) and FIB before and after the 7-day treatment were measured, and the scores of Chinese stroke scale (CSS) after 14 days of treatment and Activity of Daily Living (ADL) after 3 months were recorded.

RESULTSAfter 7 days of treatment, plasma PT and APTT were significantly prolonged lengthened and plasma FIB was lowered in defibrase group. The scores of CSS improved in defibrase group after 14 days of treatment, showing significant difference from those of the control group. The clinical effective rate was 80% in defibrase group, significantly higher than that in the control group (50%). The scores of ADL after 3 months were similar between the 2 groups, but the percentage of independent living and mild dependency was significantly higher in defibrase group (93.3% vs 70.0%). No intracerebral and extracerebral hemorrhage occurred in defibrase group the during treatment, no did death occur after 3 months of treatment.

CONCLUSIONDefibrase therapy based on plasma FIB level can rapidly and effectively lower plasma FIB, reduce neurological impairment and improve the quality of life in patients with ACI.

Acute Disease ; Adult ; Aged ; Aged, 80 and over ; Batroxobin ; therapeutic use ; Cerebral Infarction ; drug therapy ; Female ; Fibrinogen ; metabolism ; Fibrinolytic Agents ; therapeutic use ; Humans ; Male ; Middle Aged

OBJECTIVE: To observe the changes of plasminogen activator inhibitor-1 and D-dimer during continuous blood purification (CBP) and related factors. METHODS: Sixteen patients who were diagnosed with multiple organ dysfunction syndrome (MODS) were randomly divided into 2 groups: 8 patients received standard continuous blood purification with heparin anticoagulation, and the other 8 received CBP without anticoagulation. Ten normal blood samples were collected from healthy volunteers as controls. All patients underwent CBP for 8 h. Blood was taken from those patients at 0, 15, 60, 120 and 480 min during the CBP. Plasma plasminogen activator inhibitor-1, D-dimer and serum TNF-α and IL-1β were measured by ELISA. RESULTS: Plasma levels of PAI-1 and D-dimer were increased significantly compared with those in the control group (P<0.05). Plasma level of PAI-1 was reduced (P<0.05) and D-dimer was increased (P<0.05) after the CBP. The level of plasma PAI-1 in the heparin group was significant reduced compared with the group of CBP without anticoagulation (P<0.05). There was negative correlation between the level of PAI-1 and the dosage of heparin used during a CBP session in the heparin group (r=-0.746, P<0.001). CONCLUSION The level of PAI-1 and D-dimer is higher in patients with MODS than that in the normal controls. After the CBP treatment, there is significant decrease in PAI-1 and increase in D-dimer in both groups. Heparin used during CBP can reduce PAI-1 which intensifies its function of anticoagulation.
Anticoagulants ; therapeutic use ; Fibrin Fibrinogen Degradation Products ; analysis ; Heparin ; therapeutic use ; Humans ; Interleukin-1beta ; blood ; Plasminogen Activator Inhibitor 1 ; blood ; Renal Dialysis ; Tumor Necrosis Factor-alpha ; blood

To investigate the clinical and immunological features of dermatomyositis (DM) complicated with macrophage activation syndrome (MAS). The demographic and clinical characteristics of five patients diagnosed with DM complicated with MAS hospitalized in the Department of Rheumatology and Immunology, Peking University People ' s Hospital from 2011 to 2021 were collected. The results of clinical manifestations, laboratory tests, immunological features, treatments and prognosis were analyzed and summarized. In this study, five female patients in Peking University People's Hospital with an average age of 63.8 (44.0-83.0) years and an average disease duration of 16.1 (1.5-48.0) months. All the patients had typical DM rash (such as heliotrope sign, V/shawl sign or Gottron's sign/papules). They all had muscle involvement (including myalgia or muscle weakness). Two patients had positive myositis-specific antibodies (MSAs), in which case 1 had anti-TIF1-γ antibody and case 5 had anti-NXP-2 antibody. Four patients had interstitial lung disease except case 3. All of the cases developed MAS in the active stage of DM. Common manifestations of MAS in these five patients included high-grade fever, cytopenia, decreased fibrinogen, elevated ferritin and increased soluble CD25. Case 1 presented with neutropenia (0.6×10⁹ /L), thrombocytopenia (26.0×10⁹ /L), hypofibrinogenemia (0.9 g/L), markedly elevated ferritin (26 331.0 μg/L), decreased NK cell activity. Case 2 had anaemia (hemoglobin 81.0 g/L), thrombocytopenia (55.0×10⁹ /L), hypertriglyceridemia (4.7 mmol/L), hypofibrinogenemia (1.2 g/L), elevated ferritin (>100 000.0 μg/L), hemophagocytosis in bone marrow. Case 3 had anaemia (hemoglobin 88 g/L), decreased fibrinogen (1.9 g/L), increased ferritin (>27 759.0 μg/L), splenomegaly, hemophagocytosis in bone marrow. Case 4 suffered from neutropenia(0.3×10⁹ /L), anaemia(hemoglobin 78 g/L), hypertriglyceridemia (4.2 mmol/L), hypofibrinogenemia (0.9 g/L), increased ferritin (>100 000.0 μg/L), and decreased NK cell activity. Case 5 presented anaemia (hemoglobin 60.0 g/L), thrombocytopenia (67.0×10⁹ /L), hypertriglyceridemia (12.7 mmol/L), decreased fibrinogen (1.1 g/L), and elevated ferritin (>923.0 μg/L). All the patients were treated with methylprednisone pulse therapy (200-500 mg) combined with cyclosporine while case 5 received rituximab after methylprednisone pulses. In addition, case 3 also received the combination of mycophenolate mofetil. Case 1 was given etoposide while case 4 was treated with cyclophosphamide and repeated plasmapheresis at the same time. Moreover, intravenous immunoglobulin was added meantime apart from case 3. The condition of four patients improved significantly, nevertheless case 4 experienced recurred pulmonary symptoms and died of respiratory failure. As for complications about infection, case 2 had bacterial infection with high level procalcitonin (PCT) before MAS treatment and condition was improved after empiric antibacterial therapy. Case 3 had cytomegalovirus DNAemia before diagnosis of MAS and viral titer turned negative after ganciclovir therapy. After treatment of MAS, four patients developed cytomegalovirus DNAemia except case 3, in which case 5 was co-infected with bacteria. To sum, DM complicated with MAS is relatively rare, and its patients are of ten in life-threatening condition. Early detection, treatment and prevention of infection during treatment are critical to improve the prognosis.
Humans ; Female ; Middle Aged ; Dermatomyositis/complications* ; Macrophage Activation Syndrome/complications* ; Afibrinogenemia/complications* ; Autoantibodies ; Neutropenia ; Thrombocytopenia/complications* ; Ferritins/therapeutic use* ; Hypertriglyceridemia/complications* ; Fibrinogen/therapeutic use*

OBJECTIVE: To observe the effects of histones on lung injury and von Willebrand factor (vWF) and fibrinogen (FIB) levels in mice, and to explore the protective effect of heparin. METHODS: Twenty-four male C57BL/6 mice aged 6-10 weeks were divided into control group, histone group and histone+heparin group according to random number table method with 8 mice in each group. The mice in the histone group were injected with histone (50 mg/kg) via the tail vein, and the mice in the histone+heparin group were injected with unfractionated heparin (400 U/kg) via the tail vein at 1 hour after administration of histone, and those in the control group were given the same amount of normal saline. Four hours after histone injection, the lungs of the mice were harvested and the lung wet/dry weight ratio (W/D) and the pulmonary water contents were measured. The pathological changes in lung tissue were observed by hematoxylin and eosin (HE) staining under microscope, and the extent of lung injury was evaluated. The positive expression of vWF which was the marker of endothelial cell injury was observed by immunohistochemistry. The real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the expression level of FIB mRNA in lung tissue. RESULTS: The lung W/D ratio and pulmonary water contents in the histone group were significantly higher than those in the control group [lung W/D ratio: 6.19±0.53 vs. 4.54±0.25, pulmonary water contents: (82.59±2.03)% vs. (78.52±1.51)%, both P < 0.01]. The lung W/D ratio and pulmonary water contents in the histone+heparin group were significantly lower than those in the histone group [lung W/D ratio: 4.84±0.35 vs. 6.19±0.53, pulmonary water contents: (79.21±1.48)% vs. (82.59±2.03)%, both P < 0.01], indicating that the heparin could reduce histone-induced pulmonary edema. Histological examination showed that the alveolar structure of the control group was intact, and the alveolar cavity was clean without exudation. In the histone group, the lungs were significantly damaged. The alveolar wall was thickened, infiltrated by inflammatory cells and focally alveolar hemorrhage, edema, associated with alveolar fibrin deposition and micro-thrombus formation. The lung histopathological score in the histone group was significantly higher than that in the control group (5.15±0.87 vs. 0.18±0.17, P < 0.01). All of the pathological changes were significantly alleviated in the histone+heparin group, and the histopathological score of the lung was significantly lower than that in the histone group (2.28±0.72 vs. 5.15±0.87, P < 0.01), indicating that the histone-induced lung injury was improved by heparin. Immunohistochemistry showed that high vWF expressions of lung tissue were observed in the histone group while there was almost no positive expression in the control group, and the vWF expression in the histone+heparin group was significantly reduced, indicating that heparin protected mice against histone-induced endothelial cell injury. The FIB mRNA expression of lung tissue in the histone group was about 49.82 times of the control group (2^-ΔΔCT: 55.30±18.84 vs. 1.11±0.45, P < 0.01), and the expression of FIB mRNA in the histone+heparin group was decreased, which was 23.87 times of the control group (2^-ΔΔCT: 26.50±9.97 vs. 1.11±0.45, P < 0.01), but it was significantly lower than that in the histone group (2^-ΔΔCT: 26.50±9.97 vs. 55.30±18.84, P < 0.01), indicating that heparin could inhibit histone-induced hypercoagulable environment in lung. CONCLUSIONS Histone causes pulmonary edema, endothelial cell injury and coagulation activation. Heparin could effectively attenuate histone-induced lung injury and coagulation activation.
Animals ; Fibrinogen/metabolism* ; Fibrinolytic Agents/therapeutic use* ; Heparin/therapeutic use* ; Histones ; Lung/metabolism* ; Male ; Mice ; Mice, Inbred C57BL ; von Willebrand Factor/metabolism*

Hemophagocytic syndrome (HPS) is a severe disease characterized by excessive release of inflammatory cytokines caused by abnormal activation of lymphocytes and macrophages, which can cause multiple organ damage and even death. Panniculitis is a disease characterized by inflammation of subcutaneous adipose tissue. We effectively treated 2 patients with panniculitis-associated HPS with ruxolitinib. Case 1: A 70-year-old male started with intermittent plantar swelling and pain, and then developed leukocytosis, mild anemia, multiple red maculopapules with painless subcutaneous nodules on the forehead, neck and bilateral lower legs. The patient was treated with prednisone and leflunomide for improvement. After that, repeated fever and rash occurred again. After admission to our hospital, we found his leukocyte and hemoglobin decreased, ferritin raised, fibrinogen and natural killer (NK) cell activity decreased, and hemophagocytic cells were found in bone marrow aspiration. The skin pathology was consistent with non-suppurative nodular panniculitis. He was diagnosed with nodular panniculitis associa-ted HPS. He was treated with glucocorticoid, cyclosporine, etoposide and gamma globule, but the disease was not completely controlled. After adjusting etoposide to ruxolitinib, his symptoms and abnormal laboratory findings returned to normal. After 2 months he stopped using ruxolitinib due to repeated infections. During the follow-up, though the prednisone dose was tapered, his condition was stable. Case 2: A 46-year-old female patient developed from intermittent fever, erythematous nodular rash with tenderness, leukopenia, and abnormal liver function. antibiotic therapy was ineffective. She improved after glucocorticoid treatment, and relapsed after glucocorticoid reduction. There were fever, limb nodules, erythema with ulcerative necrosis, intermittent abdominal pain when she came to our hospital. Blood examination showed that her white blood cells, red blood cells and platelets were decreased, fibrinogen was decreased, triglyceride was increased, ferritin and soluble interleukin-2 receptor(SIL-2R/sCD25) were significantly raised, and hemophagocytic cells were found in bone marrow aspiration. It was found that Epstein-Barr virus DNA was transiently positive, skin Staphylococcus aureus infection, and pulmonary Aspergillus flavus infection, but C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were normal, and no evidence of tumor and other infection was found. Skin pathology was considered panniculitis. The diagnosis was panniculitis, HPS and complicated infection. Antibiotic therapy and symptomatic blood transfusion were given first, but the disease was not controlled. Later, dexamethasone was given, and the condition improved, but the disease recurred after reducing the dose of dexamethasone. Due to the combination of multiple infections, the application of etoposide had a high risk of infection spread. Ruxolitinib, dexamethasone, and anti-infective therapy were given, and her condition remained stable after dexamethasone withdrawal. After 2 months of medication, she stopped using ruxolitinib. One week after stopping using ruxolitinib, she developed fever and died after 2 weeks of antibiotic therapy treatment in a local hospital. In conclusion, panniculitis and HPS are related in etiology, pathogenic mechanism and clinical manifestations. Abnormal activation of Janus-kinase and signal transduction activator of transcription pathway and abnormal release of inflammatory factors play an important role in the pathogenesis of the two diseases. The report suggests that ruxolitinib is effective and has broad prospects in the treatment of panniculitis associated HPS.
Humans ; Male ; Female ; Middle Aged ; Aged ; Lymphohistiocytosis, Hemophagocytic/drug therapy* ; Glucocorticoids/therapeutic use* ; Epstein-Barr Virus Infections/complications* ; Etoposide/therapeutic use* ; Prednisone/therapeutic use* ; Herpesvirus 4, Human ; Panniculitis/complications* ; Dexamethasone/therapeutic use* ; Exanthema/complications* ; Ferritins/therapeutic use* ; Anti-Bacterial Agents/therapeutic use* ; Fibrinogen/therapeutic use*

OBJECTIVETo examine the procoagulant effects of thrombolytic agent on hemostasis and study the role of hemostatic markers as predictors of clinical outcomes.

METHODSIn the present study, eighteen patients with acute myocardial infarction (AMI) received 1.5 or 2.0 million U nonspecific urokinase (UK), or 70 approximately 80 mg fibrin-specific recombinant tissue plasminogen activator (rt-PA) and did not use heparin until 8 hours after intravenous injection of the above agents. Eight patients with AMI and without thrombolytic therapy were enrolled as controls. Coagulant and thrombolytic activity markers included thrombin-antithrombin III complex (TAT), D-dimer, fibrinogen (Fg), FMPV/Amax. All markers were determined before, immediately, 1, 2, 4 and 8 hours after the administration of thrombolytic agents respectively.

RESULTSMolecular marker of thrombin generation--TAT showed an activated coagulant state immediately after thrombolytic therapy. Level of TAT showed no significant changes between every two observed phases in controls. However, level of TAT increased significantly from 4.95 +/- 1.75 microg/L ( 4.63 +/- 1.37 microg/L) to 14.71 +/- 3.31 microg/L (14.25 +/- 2.53 microg/L) before and immediately after administration of thrombolytic agents UK (or rt-PA). There was significant difference between level of serum TAT of patients with and without thrombolytic therapy (P < 0.05). Patients achieving clinical reperfusion had lower TAT level than those failing in thrombolytic therapy, and higher FMPV/Amax level than controls. D-dimer, a surrogate of thrombolytic activity increased markedly and Fg significantly declined after thrombolytic therapy (P < 0.05).

CONCLUSIONSThrombin generation occurred in plasma in response to excess fibrinolysis induced by thrombolytic therapy. Both urokinase and rt-PA had procoagulant action. This transient activation of the coagulant system might contribute to early reocclusion. These data provided the theoretical support for simultaneous administration of anticoagulant therapy with thrombolytic agents. These results also suggested that TAT might be useful in predicting clinical outcomes of patients treated with thrombolytic therapy for AMI.

Aged ; Antithrombin III ; Biomarkers ; blood ; Female ; Fibrin Fibrinogen Degradation Products ; metabolism ; Fibrinogen ; metabolism ; Fibrinolytic Agents ; therapeutic use ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; blood ; drug therapy ; Peptide Hydrolases ; blood ; Recombinant Proteins ; therapeutic use ; Thrombolytic Therapy ; Tissue Plasminogen Activator ; therapeutic use ; Urokinase-Type Plasminogen Activator ; therapeutic use