Application Of Recombinant Human Thrombopoietin In Critically Ill Patients With Sepsis-Associated Thrombocytopenia

Background and PurposeSepsis is a life-threatening organ dysfunction caused by the dysregulation of the body’s response to infection,with high morbidity and fatality rate.Thrombocytopenia is a common complication of sepsis,and progressive thrombocytopenia is a marker of poor prognosis in patients with sepsis.Thus the idea that an elevated platelet count might improve patient outcomes has been proposed.At present,platelet transfusion is the main method to increase platelet count,but it is limited due to blood strain,transfusion adverse reaction,transfusion ineffective and other reasons.Recombinant human thrombopoietin(rhTPO)is a synthetic TPO which has the same structure and action as endogenous thrombopoietin(TPO).It is widely used in solid tumor chemotherapy,but rarely used in patients with sepsis related thrombocytopenia.Most of the previous studies were retrospective studies,and the inclusion criteria of some studies were sepsis 1.0,which had certain limitations.Therefore,this study explored the effect of rhTPO on patients with sepsis associated thrombocytopenia(SAT)under the definition of Sepsis 3.0,so as to find an effective way to increase platelets and improve the prognosis of patients with SAT.MethodsA prospective randomized controlled study was conducted.100 patients with sepsis and thrombocytopenia admitted to the intensive care unit(ICU)of the First Affiliated Hospital of Zhengzhou University from August 2019 to October 2020 were enrolled.The enrolled patients were divided into recombinant human thrombocytopenia group(rhTPO group)and routine group(control group)by random number table method,with 50 cases in each group.Both groups were strictly followed the guideline of sepsis 3.0.On the basis,rhTPO group received rhTPO 15000U once for 7days.(1)General information of the patients was recorded,such as gender,age,source of infection,acute physiology and chronic health score(APACHEⅡ score)were recorded.(2)The level of platelet count(PC),blood coagulation function[prothrombin time(PT)and prothrombin activity(PTA)],myocardial enzyme[troponin(TnI)],liver and kidney function[aspartate aminotransferase(AST),total bilirubin(TBil)and creatinine(Cr)]and inflammatory biomarkers[procalcitonin(PCT)and C-reactive protein(CRP)]were recorded before(D0)and 1(D1),3(D3),5(D5)and 7(D7)days after the application of rhTPO;(3)The infusion volume of blood components were recorded;(4)The length of stay in ICU,total length of stay and total cost of stay and 28 day mortality were recorded.(5)According to whether PC was less than 50×109/L,100 patients were regrouped:PC≥50×109/L(group A)and PC<50×l09/L(group B),and the effect of rhTPO application under different PC conditions was compared.Results1.A total of 100 subjects were included in this study,including 56 males(56%)and 44 females(44%),aged 20-75 years.In the RHTPO group,there were 30 males(60%)and 20 females(40%),aged 23-75 years,with an average age of(56.48±13.58)years.In the control group,there were 26 males(52%)and 24 females(48%),aged 20-75 years,with an average age of(57.92±12.69)years.The origin of infection was 40(40%)in lung,25(25%)in abdomen,13(13%)in bloodstream,10(10%)in urinary tract,and 12(12%)in other cases.2.There were no significant differences in gender,age,source of infection,APACHE Ⅱ score,PC before application of rhTPO,blood coagulation function,liver and kidney function,and infection indexes between the two groups(all P>0.05).3.On the 5th and 7th days after the application of RHTPO,PC in the rhTPO group was significantly higher than that in the control group,and the difference between the two groups was statistically significant[PC(×109/L):63.94±44.01 vs 49.85±29.26 on day 5 and 125.85±112.31 vs 76.81 ±50.87 on day 7,all P<0.05)].4.There were no significant differences in coagulation function[prothromb in time(PT),prothrombin activity(PTA)],liver and kidney function[aspartateaminotransferase(AST),total bilirubin(TBil),blood creatinine(Cr)],myocardial enzymes[troponin(TnI)],procalcitonin(PCT)and C-reactive protein(CRP)]between the two groups before and on the 1,3,5,7 days after the application of rhTPO(all P>0.05).5.The amount of platelet transfusion in the rhTPO group was lower than that in the control group[platelets(treatment amount);0(0,0.00)vs 0(0,2.00)],the difference was significant in statistics(P=0.001).There were no statically significant differences in red blood cell,plasma and cryoprecipitate infusion between the two groups(all P>0.05).6.There were no statistically significant differences in mechanical ventilation time,ICU stay time,total stay time,hospitalization cost,and mortality(all P>0.05).7.The mechanical ventilation time,ICU stay time and total hospitalization time of A group(PC≥50×109/L)were longer than B group(PC<50×109/L),but the difference was not statistically significant(P>0.05).The absolute value of PC increase in TPO A group was higher than that of TPO B group,but the difference was not statistically significant(P>0.05).Conclusion1.Recombinant human thrombocytopenia can significantly increase the PC of patients with sepsis-associated thrombocytopenia,thereby reduce the amount of platelet transfusion.2.Recombinant human thrombocytopenia is safe and has no obvious effect on liver and kidney function.3.Recombinant human thrombocytopenia cannot shorten the length of patient’s ICU stay time and total hospital stay time,it cannot reduce 28-day mortality.