Impact of experimental haemodilution on platelet function, thrombin generation and clot firmness: effects of different coagulation factor concentrates.
BACKGROUND
Haemodilution during resuscitation after massive haemorrhage may worsen the coagulopathy and perpetuate bleeding.


METHODS
Blood samples from healthy donors were diluted (30 and-60%) using crystalloids (saline, Ringer's lactate, Plasmalyte(TM)) or colloids (6% hydroxyethylstarch [HES130/0.4], 5% human albumin, and gelatin). The effects of haemodilution on platelet adhesion (Impact R), thrombin generation (TG), and thromboelastometry (TEM) parameters were analysed as were the effects of fibrinogen, prothrombin complex concentrates (PCC), activated recombinant factor VII (FVIIa), and cryoprecipates on haemodilution.


RESULTS
Platelet interactions was already significantly reduced at 30% haemodilution. Platelet reactivity was not improved by addition of any of the concentrates tested. A decrease in TG and marked alterations of TEM parameters were noted at 60% haemodilution. HES130/0.4 was the expander with the most deleterious action. TG was significantly enhanced by PCC whereas rFVIIa only caused a mild acceleration of TG initiation. Fibrinogen restored the alterations of TEM parameters caused by haemodilution including those caused by HES 130/0.4. Cryoprecipitates significantly improved the alterations caused by haemodilution on TG and TEM parameters; the effects on TG disappeared after ultracentrifugation of the cryoprecipitates.


CONCLUSIONS
The haemostatic alterations caused by haemodilution are multifactorial and affect both blood cells and coagulation. In our in vitro approach, HES 130/0.4 had the most deleterious effect on haemostasis parameters. Coagulation factor concentrates did not improve platelet interactions in the Impact R, but did have favourable effects on coagulation parameters measured by TG and TEM. Fibrinogen notably improved TEM parameters without increasing thrombin generation, suggesting that this concentrate may help to preserve blood clotting abilities during haemodilution without enhancing the prothrombotic risk.
Haemotherapy-Haemostasis Department, Hospital Clinic, IDIBAPS, Barcelona, Spain.
Carolina
C
Caballo
Gines
G
Escolar
Maribel
M
Diaz-Ricart
Irene
I
Lopez-Vílchez
Miguel
M
Lozano
Joan
J
Cid
Marcos
M
Pino
Joan
J
Beltrán
Misericordia
M
Basora
Arturo
A
Pereira
Ana M
AM
Galan
D001777:Blood Coagulation / Q000187:drug effects; D001779:Blood Coagulation Factors / Q000494:pharmacology*; D001792:Blood Platelets / Q000378:metabolism*; D003102:Colloids / Q000494:pharmacology; D000077324:Crystalloid Solutions; D005260:Female; D006438:Hemodilution / Q000009:adverse effects*; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000494:pharmacology*; D007552:Isotonic Solutions / Q000494:pharmacology*; D008297:Male; D010973:Platelet Adhesiveness / Q000187:drug effects*; D013916:Thrombelastography; D013917:Thrombin / Q000378:metabolism*
D001779:Blood Coagulation Factors; D003102:Colloids; D000077324:Crystalloid Solutions; D006895:Hydroxyethyl Starch Derivatives; D007552:Isotonic Solutions; D013917:Thrombin