Objective:To develop a nomogram based on the monocyte-to-lymphocyte ratio (MLR) for predicting the risk of aortic-related adverse events within 30 days in patients with acute uncomplicated type B aortic intramural hematoma.Methods:This single-center retrospective cohort study screened consecutive patients with acute uncomplicated type B aortic intramural hematoma treated at the Emergency and Cardiovascular Medicine Departments of the General Hospital of the Northern Theater Command from April 2018 to April 2024. Patients were divided into two groups based on the optimal MLR cut-off value for predicting aortic-related adverse events: low MLR and high MLR group. MLR was defined as the ratio of monocytes to lymphocytes. Aortic-related adverse events were defined as a composite of aortic-related death or aortic intramural hematoma progression (including aortic dissection and penetrating aortic ulcers) within 30 days. The receiver operating characteristic (ROC) curve identified the optimal MLR cut-off value. Multivariate logistic regression was used to identify independent predictors of aortic-related adverse events within 30 days, based on which nomogram models were constructed: the clinical characteristics model and the clinical characteristics-MLR model. The DeLong test was used to evaluate the diagnostic performance of different risk models. The additional predictive value of MLR was assessed using the net reclassification index (NRI) and integrated discrimination improvement (IDI).Results:A total of 332 patients were included, of whom 217 were male (65.4%), with an average age of (64.3±9.4) years. A total of 107 aortic-related adverse events occurred during the 30-day follow-up period. The optimal cut-off value for MLR was 0.529. There were 189 cases in the low MLR group (MLR<0.529) and 143 cases in the high MLR group (MLR≥0.529). The rate of aortic-related adverse events was higher in the high MLR group compared to the low MLR group (44.1% (63/143) vs. 23.3% (44/189), P<0.001), mainly due to a higher rate of progression to aortic dissection (9.8% (14/143) vs. 1.1% (2/189), P<0.001) and penetrating aortic ulcers (31.5% (45/143) vs. 20.6% (39/189), P=0.025). Multivariate analysis identified diabetes ( OR=0.25, 95% CI 0.08-0.78, P=0.017), anemia ( OR=3.45, 95% CI 1.28-9.27, P=0.014), maximum descending aorta diameter ( OR=1.08, 95% CI 1.02-1.15, P=0.007), ulcer-like projections ( OR=4.04, 95% CI 2.26-7.24, P<0.001), and MLR ( OR=6.61, 95% CI 2.50-17.46, P<0.001) as independent predictors of aortic-related adverse events during the 30-day follow-up period. The clinical characteristics model includes diabetes, anemia, ulcer-like projections and maximum diameter of the descending aorta, and the clinical characteristics-MLR model includes the above clinical characteristics and MLR. The results of the DeLong test showed that the clinical characteristic-MLR model demonstrated a higher area under the ROC curve compared to the clinical characteristic model alone (0.784 (95% CI 0.736-0.841) vs. 0.742 (95% CI 0.691-0.788), P=0.031). The continuous NRI was 0.461 (95% CI 0.237-0.685, P<0.001) and the IDI was 0.077 (95% CI 0.043-0.112, P<0.001), indicating that the inclusion of the MLR in the model significantly improved the predictive accuracy. Conclusion:The integration of MLR with other clinical characteristics improves the early identification of high-risk patients with acute uncomplicated type B aortic intramural hematoma, optimizing clinical decisions and improving patient outcomes.

Aim To investigate the clinical characteristics and related factors of post-implantation syndrome(PIS)following the prophylactic application of non-steroidal anti-inflammatory drugs(NSAID)after thoracic endovascular aortic repair(TEVAR).Methods A total of 510 adult patients who had received prophylactic NSAID after TEVAR at General Hospital of Northern Theater Command from September 2013 to April 2024 were consecutively included in the study.The patients were divided into two groups based on the occurrence of PIS postoperatively:the PIS group(34 pa-tients,6.67％)and the non-PIS group(476 patients,93.33％).General information,past medical history and surgical features were compared between the two groups.Univariate and multivariate Logistic regression analysis were used to i-dentify predictors of PIS.The ROC curve was used to assess the overall diagnostic performance of the risk factors.Results The baseline data and clinical characteristics of PIS group and non-PIS group were compared.The rate of gen-der as male,chest and back pain on adimission,limb ischaemia on admission,systolic blood pressure on admission,use of angiotensin converting enzyme inhibitor(ACEI)/angiotensin receptor blocker(ARB)drugs during hospitalization,preop-erative white blood cell(WBC)count and surgical approach involving an incision in PIS group were higher than those in non-PIS group,and the age,preoperative estimated glomerular filtration rate(eGFR)level and use of statin drugs during hospitalization were lower than those in non-PIS group,all differences were statistically significant.Postoperative C-reac-tive protein level,incidence of clinical adverse events during postoperative hospitalization,and time of postoperative hospi-talization were increased in PIS group compared with those in non-PIS group.There was no significant difference in the incidence of aortic adverse events between the two groups(P＜0.05).Univariate and multivariate Logistic regression a-nalysis identified patients' age＜60 years(OR=4.671,95％CI:1.348～16.188,P=0.015),increased preoperative WBC count(OR=3.582,95％CI:1.469～8.735,P=0.005),and surgical approach involving an incision(OR=8.339,95％CI:1.849～37.610,P=0.006)as independent predictors for PIS.The results of the ROC curve analysis showed that the area under the curve of patients' age＜60 years,increased preoperative WBC count,femoral arteriotomy ac-cess,and the three combined diagnoses in predicting the occurrence of PIS after TEVAR were 0.653(95％CI:0.573～0.733),0.686(95％CI:0.600～0.771),0.699(95％CI:0.627～0.770),0.826(95％CI:0.765～0.887).Conclusion Despite the prophylactic use of NSAID,some patients develop PIS after TEVAR.Patients' age＜60 years,elevated preoperative WBC count,and femoral artery incision approach are independent risk factors for PIS after preventive medication.Additionally,the incidence of PIS increased with the number of independent risk factors present.

Aim To investigate the clinical characteristics and related factors of post-implantation syndrome(PIS)following the prophylactic application of non-steroidal anti-inflammatory drugs(NSAID)after thoracic endovascular aortic repair(TEVAR).Methods A total of 510 adult patients who had received prophylactic NSAID after TEVAR at General Hospital of Northern Theater Command from September 2013 to April 2024 were consecutively included in the study.The patients were divided into two groups based on the occurrence of PIS postoperatively:the PIS group(34 pa-tients,6.67％)and the non-PIS group(476 patients,93.33％).General information,past medical history and surgical features were compared between the two groups.Univariate and multivariate Logistic regression analysis were used to i-dentify predictors of PIS.The ROC curve was used to assess the overall diagnostic performance of the risk factors.Results The baseline data and clinical characteristics of PIS group and non-PIS group were compared.The rate of gen-der as male,chest and back pain on adimission,limb ischaemia on admission,systolic blood pressure on admission,use of angiotensin converting enzyme inhibitor(ACEI)/angiotensin receptor blocker(ARB)drugs during hospitalization,preop-erative white blood cell(WBC)count and surgical approach involving an incision in PIS group were higher than those in non-PIS group,and the age,preoperative estimated glomerular filtration rate(eGFR)level and use of statin drugs during hospitalization were lower than those in non-PIS group,all differences were statistically significant.Postoperative C-reac-tive protein level,incidence of clinical adverse events during postoperative hospitalization,and time of postoperative hospi-talization were increased in PIS group compared with those in non-PIS group.There was no significant difference in the incidence of aortic adverse events between the two groups(P＜0.05).Univariate and multivariate Logistic regression a-nalysis identified patients' age＜60 years(OR=4.671,95％CI:1.348～16.188,P=0.015),increased preoperative WBC count(OR=3.582,95％CI:1.469～8.735,P=0.005),and surgical approach involving an incision(OR=8.339,95％CI:1.849～37.610,P=0.006)as independent predictors for PIS.The results of the ROC curve analysis showed that the area under the curve of patients' age＜60 years,increased preoperative WBC count,femoral arteriotomy ac-cess,and the three combined diagnoses in predicting the occurrence of PIS after TEVAR were 0.653(95％CI:0.573～0.733),0.686(95％CI:0.600～0.771),0.699(95％CI:0.627～0.770),0.826(95％CI:0.765～0.887).Conclusion Despite the prophylactic use of NSAID,some patients develop PIS after TEVAR.Patients' age＜60 years,elevated preoperative WBC count,and femoral artery incision approach are independent risk factors for PIS after preventive medication.Additionally,the incidence of PIS increased with the number of independent risk factors present.

Objective:To develop a nomogram based on the monocyte-to-lymphocyte ratio (MLR) for predicting the risk of aortic-related adverse events within 30 days in patients with acute uncomplicated type B aortic intramural hematoma.Methods:This single-center retrospective cohort study screened consecutive patients with acute uncomplicated type B aortic intramural hematoma treated at the Emergency and Cardiovascular Medicine Departments of the General Hospital of the Northern Theater Command from April 2018 to April 2024. Patients were divided into two groups based on the optimal MLR cut-off value for predicting aortic-related adverse events: low MLR and high MLR group. MLR was defined as the ratio of monocytes to lymphocytes. Aortic-related adverse events were defined as a composite of aortic-related death or aortic intramural hematoma progression (including aortic dissection and penetrating aortic ulcers) within 30 days. The receiver operating characteristic (ROC) curve identified the optimal MLR cut-off value. Multivariate logistic regression was used to identify independent predictors of aortic-related adverse events within 30 days, based on which nomogram models were constructed: the clinical characteristics model and the clinical characteristics-MLR model. The DeLong test was used to evaluate the diagnostic performance of different risk models. The additional predictive value of MLR was assessed using the net reclassification index (NRI) and integrated discrimination improvement (IDI).Results:A total of 332 patients were included, of whom 217 were male (65.4%), with an average age of (64.3±9.4) years. A total of 107 aortic-related adverse events occurred during the 30-day follow-up period. The optimal cut-off value for MLR was 0.529. There were 189 cases in the low MLR group (MLR<0.529) and 143 cases in the high MLR group (MLR≥0.529). The rate of aortic-related adverse events was higher in the high MLR group compared to the low MLR group (44.1% (63/143) vs. 23.3% (44/189), P<0.001), mainly due to a higher rate of progression to aortic dissection (9.8% (14/143) vs. 1.1% (2/189), P<0.001) and penetrating aortic ulcers (31.5% (45/143) vs. 20.6% (39/189), P=0.025). Multivariate analysis identified diabetes ( OR=0.25, 95% CI 0.08-0.78, P=0.017), anemia ( OR=3.45, 95% CI 1.28-9.27, P=0.014), maximum descending aorta diameter ( OR=1.08, 95% CI 1.02-1.15, P=0.007), ulcer-like projections ( OR=4.04, 95% CI 2.26-7.24, P<0.001), and MLR ( OR=6.61, 95% CI 2.50-17.46, P<0.001) as independent predictors of aortic-related adverse events during the 30-day follow-up period. The clinical characteristics model includes diabetes, anemia, ulcer-like projections and maximum diameter of the descending aorta, and the clinical characteristics-MLR model includes the above clinical characteristics and MLR. The results of the DeLong test showed that the clinical characteristic-MLR model demonstrated a higher area under the ROC curve compared to the clinical characteristic model alone (0.784 (95% CI 0.736-0.841) vs. 0.742 (95% CI 0.691-0.788), P=0.031). The continuous NRI was 0.461 (95% CI 0.237-0.685, P<0.001) and the IDI was 0.077 (95% CI 0.043-0.112, P<0.001), indicating that the inclusion of the MLR in the model significantly improved the predictive accuracy. Conclusion:The integration of MLR with other clinical characteristics improves the early identification of high-risk patients with acute uncomplicated type B aortic intramural hematoma, optimizing clinical decisions and improving patient outcomes.

Objective:Evaluate the safety of the bioresorbable scaffold (BRS) series implanted.Methods:This is a cohort study, which included 377 patients with acute coronary syndrome (ACS) who underwent elective percutaneous coronary intervention (PCI) with Neovas-BRS implantation from July 2019 to April 2022 at the Northern Command General Hospital. The patients were divided into the series BRS group ( n=63) and single BRS group ( n=314). We compared PCI related data between two groups, as well as all-cause death, cardiac death, non-fatal myocardial infarction, target vessel revascularization, stroke, and bleeding of type 2 to 5 defined by the Bleeding Academic Research Consortium of America (BARC) during follow-up. We also compared the major adverse cardiovascular and cerebrovascular events (MACCE), which includes all-cause death, non-fatal myocardial infarction, target vessel revascularization and stroke, as well as the net adverse clinical events (NACE), which includes MACCE and bleeding of BARC type 2 to 5. Procedural immediate success was defined as a residual stenosis of<20% with successful stent implantation and post-PCI target vessel flow grade up to TIMI 3. The images of 11 patients in the series BRS group who underwent optical coherence tomography (OCT) were analyzed. Results:A total of 377 patients were finally enrolled, aged (52.5±10.7) years, including 80.4% (303/377) males . The immediate success rate of PCI was 100% in both groups. The number of ≥50% stenotic lesions, number of target vessels, SYNTAX score, number of post-application expansion balloons, number of guidewires, total stent length, contrast volume and operation time were higher in the series BRS group than in the single BRS group (all P<0.05). There was no significant difference in the proportion of intravascular ultrasound and OCT application between the two groups. One patient in the single BRS group had an ischemic stroke during postoperative hospitalization, but there were no death, non-fatal myocardial infarction, target vessel revascularization, or BARC 2 to 5 bleeding events occurred during hospitalization in both groups. Follow up time was 352.0 (193.0, 421.0) days. There was no statistically significant difference between the two groups in the incidence of all-cause death (0 vs. 0.6% (2/314), P=1.000), cardiogenic death (0 vs. 0.3% (1/314), P=1.000), nonfatal myocardial infarction (0 vs. 1.0% (3/314), P=1.000), target lesion revascularization (3.2% (2/63) vs. 1.6% (5/314), P=0.736), BARC type 2 to 5 bleeding (3.2% (2/63) vs. 5.7% (18/314), P=0.604), MACCE (3.2% (2/63) vs. 2.9% (9/314), P=0.894), and NACE (6.3% (4/63) vs. 8.6% (27/314), P=0.553) during the follow-up period. OCT results of the 11 (17.5%) patients in the series BRS group indicated that 3 patients (27.3%) achieved non-overlapping connection, and the immediate stent expansion rate was (95.47±0.04) %. In 8 patients with BRS overlapping connections, immediate stent expansion rate was (90.32±0.44) %. Conclusion:In patients with low to intermediate-risk ACS, serial implantation of RBS in long coronary lesions is safe and feasible, and achieves the similar short-term outcomes as single BRS implantation.

Objective:To analyze the efficacy of second-line regimens and prognostic factors in patients with first-relapsed multiple myeloma (MM) treated with bortezomib, cyclophosphamide, and dexamethasone (BCD).Methods:A retrospective cohort study. Clinical data were collected in first-relapsed MM patients after BCD treatment from three tertiary hospitals in north China from July 2009 to October 2022. Patients were classified according to the second-line regimen into the immunotherapy group, single novel agent group [either proteasome inhibitor (PI) or immunomodulatory drug (IMiD)], combination treatment group (both PI+IMiD), and traditional treatment group. Responses to second-line regimens and survival data were analyzed. The Kaplan-Meier method was used for survival analysis and the Cox proportional risk model was used for univariate and multivariate analyses.Results:A total of 217 patients were enrolled including 8.8% (19/217) in the immunotherapy group, 48.4% (105/217) in the PI/IMiD group, 29.9% (65/217) in the PI+IMiD group, and 12.9% (28/217) in the traditional treatment group. The median age was 62 years (range 31-83 years) and 56.2% (122/217) were males. The overall response rates (ORRs) in the four groups were 94.7% (18/19) vs. 56.2% (59/105) vs. 73.8% (48/65) vs. 32.1% (9/28) ( χ2=24.55; P<0.001), respectively. The progression-free survival (PFS) of the second-line regimens (2ndPFS) was 17.7 vs. 9.0 vs. 9.2 vs. 4.6 months ( χ2=22.74; P<0.001), respectively, among which patients in the PI/IMiD and PI+IMiD groups had comparable 2ndPFS ( χ2=1.76; P=0.923). Patients with high-risk cytogenetic abnormalities (HRCAs) achieved the longest 2ndPFS of 22.0 months in the immunotherapy group ( χ2=15.03; P=0.002). Multivariate analysis suggested that immunotherapy ( HR=0.11, 95% CI 0.05-0.27), achievement of efficacy of partial response or better ( HR=0.47, 95% CI 0.34-0.66), and non-aggressive relapse ( HR=0.25, 95% CI 0.17-0.37) were independent prognostic factors of 2ndPFS. Conclusion:In this real-world study, immunotherapy was associated with a more favorable efficacy and PFS for first-relapsed MM patients after BCD treatment, with similar outcomes in patients with HRCAs.

Objective:To investigate the different types of renal artery involvement in Stanford type B aortic dissection (TBAD) and the comparison of clinical effecacy after thoracic endovascular aortic repair (TEVAR).Methods:This is a retrospective cohort study included 330 patients with TBAD and renal artery involvement treated with TEVAR from June 2002 to September 2021 in General Hospital of Northern Theater Command of the PLA. According to aortic CTA image, unilateral renal artery involvement conditions were divided into 5 types: the true lumen type (renal artery opening completely from the true lumen), false lumen type (renal artery opening completely from the false lumen), double lumen type (renal artery opening from the true and false double lumen), compression type (renal artery opening connected with the true lumen, but the renal artery opening was extremely squeezed by the inner membrane), open type (renal artery opening with intimal tear). There were seven types of bilateral renal artery involvement: true-true type (true lumen-true lumen type), true and false type (true lumen-false lumen type), true-double type (true lumen-double lumen type), true-opening type (true lumen-opening type), false-false type (false lumen-false lumen type), false-compression type (false lumen-compression type), double-double type (double lumen-double lumen type). The primary observation index of this study was the comparison of postoperative renal function and the incidence of clinical adverse events of different types of renal artery involvement. One-way ANOVA test, Kruskal-Wallis H test and paired sample rank sum test were used to compare postoperative renal function between different types of bilateral renal artery involvement. The Chi-square test or Fisher′s exact probability test were used to compare the near and long term adverse events between different types of bilateral renal artery involvement. Kaplan-Meier method was used to compare the all-cause mortality of patients with severe renal functional injury and non-severe renal functional injury before surgery. Results:The average age of the patients included in this study was (53±11) years, including 276 males (83.6%) and 54 females (16.4%). There were statistical difference in the level of serum creatinine (preoperative: H=18.686, P=0.005, postoperative: H=18.101, P=0.006) and cystatin C (preoperative: H=17.566, P=0.007, postoperative: H=10.433, P=0.016), pre-and post-operative, between the seven groups of TBAD patients with different renal artery involvement types ( P<0.05), and the false-false type group shown the worst kidney function. However, no statistically significant differences were shown when comparing their pre- and post-operative change values ( P>0.05). The 30-day follow-up result showed that there were statistically significant differences in the incidence of postoperative acute kidney injury ( χ2=15.623, P=0.007), aorta-related adverse events ( χ2=15.523, P=0.010), and intraoperative endoleak ( χ2=17.935, P=0.004) among the seven groups, and the false-false group was the highest (2/9, 5/9 and 5/9, respectively). In terms of long-term follow-up results, there were statistically significant differences in all-cause death ( χ2=14.772, P=0.011) and non-aortic death ( χ2=15.589, P=0.008) among the seven groups. Kaplan-Meier survival analysis showed that patients with worse pre-operative renal function showed higher long-term all cause death (17.7% vs. 4.8%, P=0.009). Conclusions:For TBAD patients with renal artery involvement, there were differences in renal function among different types, and TEVAR showed no significant effect on renal function in TBAD patients. The long-term all cause death was higher in patients with worse renal function pre-operative.

Objective:To investigate the risk factors of acute Stanford type B aortic dissection (TBAD) complicated with pleural effusion (PE) and the short-term and long-term outcomes of thoracic endovascular aortic repair (TEVAR).Methods:A case-control study. The clinical and imaging data of 1 083 patients with acute TBAD admitted to the General Hospital of Northern Theater Command from April 2002 to December 2020 were retrospectively analyzed, including 211 cases with pleural effusion and 872 cases without pleural effusion. The baseline analysis of the two groups of patients was performed. The risk factors associated with pleural effusion were analyzed by binary logistic regression, and the results were expressed as odds ratio ( OR) and 95% confidence interval ( CI). According to the quantity of pleural effusion, they were simultaneously divided into small pleural effusion group and medium large pleural effusion group, to compare the short-term and long-term effects of TEVAR patients with different amounts of pleural effusion. Results:The incidence of pericardial effusion (17.5% vs. 3.8%, P<0.001), anemia (21.3% vs. 12.5%, P=0.001), aortic spiral tear (49.8% vs. 37.8%, P=0.002), dissection tear over diaphragm (57.8% vs. 48.1%, P=0.011), serum creatinine [85 (69, 111) vs. 81 (67, 100) μmol/L, P=0.011] and white blood cell levels[(11.3±4.2)×10 9/L vs. (10.3±4.2)×10 9/L, P=0.002] in acute TBAD pleural effusion group were significantly higher than those in non-pleural effusion group, and the hemoglobin level was significantly lower than that in non-pleural effusion group [(128±20) vs. (133±17) g/L, P<0.05]. Logistic stepwise regression analysis showed that pericardial effusion ( OR=5.038,95% CI 2.962-8.568, P<0.001), anemia ( OR=2.047,95% CI 1.361-3.079, P=0.001), spiral tear ( OR=1.551,95% CI 1.030-2.336 , P=0.002) and elevated white blood cell ( OR=1.059,95% CI 1.011-1.102, P=0.005) were independent risk factors for TBAD complicated with pleural effusion. The incidences of all-cause death (4/19 vs. 1.5% vs. 0.9%, P<0.001), aortogenic death (4/19 vs. 0.7% vs. 0.7%, P<0.001) and aortic related adverse events (4/19 vs. 1.5% vs. 1.1%, P<0.001) in patients with large pleural effusion during TEVAR operation were significantly higher than those in patients with small pleural effusion and those without pleural effusion, and the differences were statistically significant. At 1 month follow-up after TEVAR, the incidence of all-cause death (4/16 vs. 3.3% vs. 1.6%, P<0.001), aortogenic death (4/16 vs. 0.8% vs.0.7%, P<0.001), aorta related adverse events (4/16 vs. 4.1% vs. 4.7%, P=0.013) and overall clinical adverse events (4/16 vs.9.8% vs. 6.7%, P=0.014) in the medium and large thoracic group were significantly higher than those in the small pleural effusion group and no pleural effusion group, and the differences were statistically significant. At 1 year follow-up after TEVAR, the incidence of all-cause death (4/15 vs. 4.9% vs. 3.9%, P=0.004), aortogenic death (4/15 vs.2.5% vs. 2.1%, P<0.001), aorta related adverse events (5/15 vs. 11.5% vs. 9.4%, P=0.012) and overall clinical adverse events (5/15 vs. 18.9% vs. 13.1%, P=0.029) in the medium and large thoracic group were significantly higher than those in the small pleural effusion group and no pleural effusion group, and the differences were statistically significant. Conclusions:Single center data showed that pericardial effusion, anemia, spiral tear and elevated white blood cell were independent risk factors for acute TBAD complicated with pleural effusion; the early (1 month) and long-term (1 year) rates of all-cause death, aortic mortality, aortic adverse events and overall clinical adverse events were significantly higher in TBAD patients with moderate pleural effusion after TEVAR, and moderate and large pleural effusion was an independent risk factor for near and long-term aortic related adverse events after TEVAR surgery.

A 43-year-old female patient was admitted with recurrent thrombosis for more than 2 years and thrombocytopenia for more than 1 year. Both arterial and venous thromboses developed especially at rare sites even during anticoagulation therapy such as cerebral venous sinus thrombosis. Antinuclear antibody, anti-ENA antibody and antiphospholipid antibody were all negative. Platelet count elevated to normal after high dose glucocorticoid and intravenous immunoglobulin (IVIG). Immune thrombocytopenia was suspected. When 4 grade thrombocytopenia recurred, intravenous heparin, rituximab 600 mg, IVIG and eltrombopag were administrated. After 3 weeks, thrombocytopenia did not improve, and new thrombosis developed instead. Screening of thrombophilia related genes revealed PROS1 gene heterozygous mutation and MTHFR TT genotype. Low amount of serum IgG κ monoclonal protein was detected. Heparin-induced thrombocytopenia was differentiated and excluded. Finally, serum negative antiphospholipid syndrome was considered the most likely diagnosis. Dexamethasone 20 mg/day × 4 days combined with sirolimus 2 mg/day was prescribed. The patient was discharged with low molecular weight heparin. At one month, her headache was greatly relieved. The platelet count raised to 20-30×10 9/L, and no new thrombosis or bleeding was reported.