title: Decreased whole blood factor IX activity following hemodilution with hemoglobin A-zero in-vitro.
abstract: Previous studies of hemoglobin-based oxygen carriers and their effects on coagulation have shown conflicting results. This study re-examined the effect of hemoglobin solution on blood coagulation in whole blood using highly purified human hemoglobin Ao (HbAo). Citrated human whole blood samples were diluted 1:1 with HbAo (7gHb/dl) or human serum albumin (HSA; 5g/dl) as a protein control, and both activated partial thromboplastin time (aPTT) and prothrombin time (PT) were measured using a mechanically based whole blood coagulometer. Multiple runs were performed with the same volunteer donor sample. The mean aPTT time of HbAo-diluted samples (105.9 +/- 19.9 sec., n = 41) was significantly longer than the undiluted controls (46.4 +/- 5.6 sec., n = 54) or HSA-diluted blood (77.1 +/- 12.7 sec., n = 41) indicating an abnormal intrinsic coagulation pathway. There was no significant difference between the PT times of the HbAo and HSA-diluted samples. To examine the cause of the prolonged aPTT times with HbAo dilution, we performed activity assays of intrinsic factors XII, XI, IX, and VIII in a citrated human whole blood system diluted 1/5 and 1/10 with normal saline solution (NSS), and then 1:1 with either HbAo, HSA, or NSS. Only the Factor IX activity was significantly depressed by hemodilution (1/5 HbAo 50.20 +/- 8.11; HSA 61.05 +/- 6.72; NSS 74.75 +/- 9.83. 1/10 HbAo 46.50 +/- 5.57; HSA 64.97 +/- 11.01; NSS 67.92 +/- 16.03). These results suggest that in-vitro hemodilution with HbAo causes a hypocoagulatory response through interference with Factor IX function.
authors.affiliation: Miriam Hospital, Providence, RI 02906, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Kim
authors.forename: H W
authors.initials: HW
authors.lastname: Kim
authors.forename: J D
authors.initials: JD
authors.lastname: Sweeney
authors.forename: A G
authors.initials: AG
authors.lastname: Greenburg
mesh_terms: D001777:Blood Coagulation / Q000187:drug effects*; D001779:Blood Coagulation Factors / Q000378:metabolism; D005164:Factor IX / Q000378:metabolism*; D006438:Hemodilution; D006454:Hemoglobins / Q000494:pharmacology*; D006801:Humans; D010314:Partial Thromboplastin Time; D011517:Prothrombin Time
chemical_list: D001779:Blood Coagulation Factors; D006454:Hemoglobins; D005164:Factor IX