In vivo ARFI surveillance of subcutaneous hemorrhage (ASSH) for monitoring rcFVIII dose response in hemophilia A dogs

Acoustic Radiation Force Impulse (ARFI) ultrasound is used in ARFI Surveillance of Subcutaneous Hemorrhage (ASSH), a new in vivo hemostasis assay, to assess bleeding response in hemophilia A dogs. ASSH bleeding parameters were calculated from a small dose response study with 7 hemostatically normal dogs and 7 dogs exhibiting severe hemophilia A. Hemophilia A dogs were imaged in the naive state and/or when prophylactically treated with different levels of recombinant canine FVIII before bleeding was induced. A standardized injury of a 1-2mm vein by needle puncture induced subcutaneous bleeding in soft tissue. Bleeding was monitored by ASSH for 60 minutes. There was a significant difference (p<;0.05, Wilcoxon ranksum) in ASSH bleeding rate (BR) and a 34.8% reduction in occurrence of abnormal ASSH time to hemostasis (TTH) between naive hemophilia A and hemophilia A treated to 100% rcFVIII cohorts. These data indicate that ASSH could be relevant in differentiating bleeding responses to different levels of rcFVIII treatment.