| Objective The study was aimed at guiding to prevent and well control localized bleeding reactions induced by subcutaneous injections of LMWHs in patients with unstable angina pectoris.Three principal questions were answered: 1)the optimal pressing duration,2)risk factors of severe subcutaneous hemorrhage,3)possible interaction between the risk factors.Methods 160 newly inpatients with unstable angina pectoris in a tertiary general hospital between December 2015 and October 2016 were selected.All the objects accepted anticoagulant therapy which combined aspirin,clopidogrel and subcutaneous LMWHs injection.The 160 cases were randomizedly divided into 4 groups,each with 40 cases,after the first subcutaneous injection of LMWHs being in hospital,pressing duration namely 0min,3min,5min and 10 min were performed respectively.The maximum diameter of bruising at the injection sites were measured after 6h,24 h,48h and 72 h,and incidence rates of severe localized bleeding reaction at different measuring time were calculated.The Microsoft Excel 2016 was utilized to input data,the SPSS 20.0 and Andersson’s EXCEL software was utilized to statistical analysis.Data about general information and incidence rate of severe subcutaneous hemorrhage were statistically described.The generalized estimation equation was used to explore the changes of subcutaneous hemorrhage over time.The Rank sum test and Chi-square test were utilized to analyze the optimal pressing duration after injection.Variables were screened with univariate analysis and variables which were statistically significant and which were proved to be the influencing factors of bruising induced by subcutaneous LMWHs injection were included in the logistic regression analysis to explore the independent risk factors of severe subcutaneous hemorrhage.In addition,relative excess risk due to interaction(RERI),attributable proportion to the interaction(AP),synergy index(S)and 95% confidence interval of each index were calculated to evaluate the interaction of factors to severe subcutaneous hemorrhage.Results 1.The maximum diameter of bruising were described by medians and interquartile ranges as 1(2)mm,2(6)mm,4(8)mm and 4(6)mm,respectively at 6h,24 h,48h and 72 h after injection,the incidence rates of severe subcutaneous hemorrhage were 2.5%(4/160),16.9%(27/160),25.9%(41/158)and 26.2%(38/145),respectively.2.Generalized estimating equations analysis suggested that differences between subcutaneous hemorrhage existed in patients with different measuring time after subcutaneous injection(P < 0.05).Regarding the outcome of 72 h after the injection as the baseline,the partial regression coefficients of 6h,24 h and 48 h after injection were-2.025(P < 0.05),-0.427(P < 0.05)and-0.044(P > 0.05),the incidence rate of severe subcutaneous hemorrhage between 6h and 72 h after injections was statistically significant,and the same results was found between 24 h and 72 h after injections.No significant difference in the incidence rate of subcutaneous hemorrhage between 48 h and 72 h after injections was found.3.Pressing duration could not significantly affect bruising size(H = 0.426,P = 0.935)after subcutaneous LMWHs injection while statistical significance was found in severe subcutaneous hemorrhage(χ2 = 8.645,P = 0.036),not giving local pressure was superior to pressing in subcutaneous hemorrhage controlling(χ2 = 7.090,P = 0.008).4.Regarding the outcome of 48 hours after injection as the dependent variable,divide the subjects into mild hemorrhage group and severe hemorrhage group.The univariate analysis showed that there were statistically significant differences for four variables between the two groups: sebum thickness(χ2 = 7.934,P = 0.005),body mass index(χ2 = 3.875,P = 0.049),types of LMWHs(χ2 = 4.319,P = 0.038)and localized pressing(χ2 = 7.091,P = 0.008).There was no significant difference in gender,age,history of thrombosis,history of diabetes,history of insulin injection,PLT count,INR value,PT value and APTT value(P > 0.05).5.Unconditional logistic regression analysis: regarding the outcome of 48 hours after injection as the dependent variable,seven independent variables,namely localized pressing,sebum thickness,body mass index,types of LMWHs,gender,age and PLT values were included to fit logistic regression model.No multicollinearity was found among the variables mentioned above.Localized pressing was found to be the independent risk factor(OR = 5.655,95% CI: 1.723~18.557),while the use of enoxaparin sodium(OR = 0.362,95%CI: 0.158~0.829)and sebum thickness ≥30mm(OR = 0.992,95%CI:0.983~1.000)could reduce the incidence rate of severe subcutaneous hemorrhage.Other independent variables were not statistically significant(P > 0.05).6.The results of the interaction between sebum thickness and localized pressing were analyzed with RERI = 4.2915(95% CI:-2.1368~107198),AP = 68.77%(95% CI: 0.2682~1.1072),S = 5.5238(95% CI: 0.1673~18.4224);for localized pressing and types of LMWHs: RERI = 4.4929(95% CI:-1.9393~10.9252),the AP = 79.57%(95% CI: 0.4180~1.1735),S = 30.2979(95% CI: 0.000~17.2326);for sebum thickness and types of LMWHs: RERI = 1.9705(95% CI:-2.6512~6.5922),the AP = 35.89%(95% CI: 0.3008~1.0185),S = 30.2979(95% CI: 0.4315~7.3595),which showed that there were no additive interactions between any two factors mentioned above.Conclusions 1.The incidence rate of severe subcutaneous hemorrhage after subcutaneous injection of LMWHs significantly increases over time,the peak value of incidence rate of bleeding appears at 48 h after injection.2.The optimal pressing duration after subcutaneous LMWHs injection is 0min,that is not pressing.3.Localized bleeding reactions after subcutaneous LMWHs injection are the result of multiple factors.Pressing duration after injection,sebum thickness and types of LMWHs are proved to influence the incidence rate of subcutaneous bleeding,among which the local pressing is the independent risk factors of severe subcutaneous hemorrhage.4.Additive interactions are found between any two factors among sebum thickness,localized pressing and the type of LMWHs.If two factors exist simultaneously,the incidence rate of severe subcutaneous hemorrhage is highter than the sum of independent effects of the two factors. |
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