Analysis Of Clinical Features And Prognostic Factors In Patients With Acquired Coagulation Factor Deficiency

A.ObjectivePatients with acquired coagulation factor deficiency often have a good prognosis after the use of glucocorticoids and replacement therapy.However,due to the rarity of this type of disease and insufficient clinical understanding,it is easy to cause delays in the disease.The purpose of this study is to evaluate the clinical characteristics of patients with different types of acquired coagulation factor deficiency,analyze the changes of coagulation indicators before and after treatment,and analyze the factors which affecting treatment outcome and survival of patients.B.MethodsThe clinical data of 67 patients with acquired coagulation factor deficiency who were treated in Qilu Hospital of Shandong University from January 1,2010 to December 31,2022 were analyzed retrospectively,including the baseline characteristics,laboratory tests,treatment plans,treatment outcomes,and adverse reactions during treatment.The study population includes 38 patients with acquired hemophilia A,4 patients of acquired factor V deficiency and 25 patients of acquired vitamin K-dependent coagulation factor deficiency.The baseline characteristics,laboratory examination and changes of coagulation indexes before and after treatment were analyzed,and the factors affecting the prognosis were discussed.C.Resultsclinical featuresSixty-seven patients were enrolled,including 38(56.7%)patients with AHA,4(6.0%)patients with AFVD,and 25(37.3%)patients with AVKCFD.Among patients with AHA,it was more common in women under 60 years of age and in men over 60 years of age(P=0.006).The same was true in AVKCFD patients,but the difference was not statistically significant(P=0.121).The number of AVFD patients under 60 years of age and over 60 years of age was equal in both sexes.Potential causes of AHA in this study included rheumatic disease,solid tumors,hematologic tumors,cystoid,and history of antibiotic use.The underlying cause of AFVD is Sjogren’s syndrome.Potential causes in patients with AVKCFD include a history of rodenticide misuse,warfarin overdose,and chemical exposure.In AHA,AFVD and AVKCFD patients,the proportion of severe bleeding was 57.9%,25.0%and 48.0%,respectively.In AHA patients,skin ecchymosis was the most common clinical manifestation in 24 cases(63.5%)followed by 13 cases(34.2%)of musculosoft tissue hematoma,11 cases(29.0%)of gross hematuria,etc.AFVD patients presented with hematuria,lower extremity skin hemorrhagic sites,and gastrointestinal bleeding.In AVKCFD patients,hematuria was the most common clinical manifestation in 15 cases(60.0%),followed by skin ecchymosis in 11 cases(44.0%)and oral mucosal bleeding in 10 cases(40.0%).Laboratory characteristicsIn AHA patients,the activated partial thromboplastin time(APTT)was longer(P<0.001),FⅧ:C level was lower in those with factor Ⅷ(FⅧ)inhibitor titers>30Bu(P=0.002);FⅧ inhibitor titer had no effect on the severity of bleeding in patients(P=1.000).The APTT was longer(P=0.016)and fibrinogen(FIB)levels were lower(P=0.024)in those with FⅧ:C<1%.Prognosis analysis1.Univariate analysis showed that AHA patients who were complicated with malignant tumors(P=0.031),prolonged interval between disease onset and treatment(P=0.015),longer APTT(P=0.044)and FⅧ:C<1%(P=0.048)was a risk factor for lower complete remission(CR)rate of AHA patients.Multivariate analysis showed that patients with AHA who were complicated with malignant tumor(P=0.224),prolonged APTT(P=0.410),long duration from disease onset to treatment(P=0.122)and FⅧ:C<1%(P=0.205)were not independent risk factors affecting the complete response rate of patients with AHA.2.Analysis of related factors affecting the time for AHA patients to reach CR showed that FⅧ inhibitor titer level>20Bu(P=0.008),FⅧ:C<1%(P=0.0448),onset to treatment time>10 days(P=0.0448)are adverse prognostic factors leading to prolonged CR time in AHA patients.3.Survival analysis of patients with AHA showed that age≥60 years old(P=0.007),male(P=0.001),combined with malignant tumor(P<0.001)and not achieving CR(P=0.031)were risk factors for low survival of patients with AHA.4.After receiving vitamin K treatment,APTT of AVKCFD patients was significantly shortened compared with that before treatment(P<0.001),prothrombin time(PT)was significantly shorter than before treatment(P<0.001),and international normalized ratio(INR)was also lower than before treatment(P=0.004).Safety analysisAmong the AHA patients,3 patients in the group treated with glucocorticoid combined with immunosuppressant developed infection;In the group treated with glucocorticoid alone,2 patients developed infection and 1 patient showed elevated blood glucose.No adverse events were observed in other treatment groups,and there was no statistically significant difference between different treatment groups(P=0.594).No adverse events were observed in 4 patients with AFVD during treatment.Only 1 of 25 patients with AVKCFD developed a rash during hemostasis.D.Conclusions1.AHA and AFVD are rare in acquired coagulation factor deficiency except for AVKCFD patients,and AFVD is especially rare.There is a large difference in the individual clinical onset of the patients,so timely diagnosis and treatment is very important in clinical practice.In addition,the patient’s primary disease should be identified and the cause of the disease should be targeted.2.Univariate analysis shows that patients with AHA complicated with malignant tumor,prolonged duration from disease onset to treatment,long APTT and FⅧ:C<1%are risk factors for low CR rate in patients with AHA,but multivariate analysis suggests that these factors are not independent risk factors affecting patients achieve to CR.3.The titer level of FⅧ inhibitor>20Bu,FⅧ:C<1%,onset to treatment time>10 days are adverse prognostic factors leading to prolonged CR time in AHA patients.4.Age≥60 years old,male,combined with malignant tumor and not achieving CR are risk factors for lower survival rate of AHA patients.5.Patients with acquired coagulation factor deficiency may still relapse after achieving CR,and regular review is required.Patients with sustained remission can gradually extend the review time.