Objective To investigate the blood clotting dysfunction of invasive pulmonary aspergillosis(IPA)and the therapeutic effect of low molecular hepafin in a mouse model.Methods The neutropenic IPA mouse model was constructed by being given cyclophosphamide to depress immunologic function,and then intranasally challenged with Aspergillus fumigatus conidia.(1)Blood clotting function were assessed by bleeding time,clotting time,platelet count and antithrombase-III(AT-III)activity.Seventy-two mice were randomly assigned into 4 groups.Group A received only normal saline.group B received normal saline to substitute the cycloph0sphamide,and the rest equal to group D.Group C received normal saline to substitute the AspergiUus fumigatus conidia suspension,and the rest equal to group D.Group D(model group)received cyclophosphamide(intraperitoneally,150 mg/kg,d4,d1)and Aspergillus fumigatus conidia suspension(intranasally,40 μL/mouse,1.5×10∧5/mL,d0).Six mice were randomly sacrificed in each group for analysis of blood clotting function per 24 h after inoculation for 3 times.(2)Therapeutic effect of low molecular heparin was determined by survival time of IPA mice.One hundred and eighteen mice were randomly assigned into 4 groups after challenged with 6×10 conidia/mouse and received one of the following regimens daily from dl to d7 after challenge,vehicle(group E,n=29),low molecular heparin(group F,n=30,subcutaneous injection,1000 IU/kg,qd×7 d),amphotericin B(group G,n=29,intraperitoneal,1 m kg,qd×7 d),low molecular heparin plus amphotericin B(group H,n=30).Mice survivals were recorded once daily to d21 after innoculation.Results (1)AT-III activity of group D decreased significantly 24 h after innoculation.Bleeding time and clotting time decreased significantly and AT—III activity decreased sequentially 48 h after innoculation.The platelet decreased significantly 72 h after innoculation,and bleeding time shoaened further.Clotting time was longer than that 0f 48 h.but still shorter than norm al and AT-III activity decreased sequentially.There were significant differences when comparing group D with group A,B and C(all Plt;0.01).And there was no significant difference between group A,B and C(all Pgt;0.05).(2)Survival analysis indicated that the therapeutic effect of low molecular hepafin plus amphotericin B was better than that of amphotericin B or low molecular heparin alone.No therapeutic effect was found in group F(group E vs group F,Pgt;0.05,both group E and group F compared with group H,P lt;0.01.Group H vs group G,P lt;0.05.Both group E and group F compared with group G,P lt;0.05).Conclusions The results suggest that there is blood clotting dysfunction in IPA mice and AT—III activity may be an early index to monitor the disfunction.Compared with the therapeutic effect of amphoterinein B alone,low molecular hepafin plus amphoterincin B can prolong survival of neutropenic IPA mice