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1.  Effect of haemodilution, acidosis, and hypothermia on the activity of recombinant factor VIIa (NovoSeven®) 
BJA: British Journal of Anaesthesia  2008;101(3):324-331.
A range of plasma volume expanders is used clinically, often in settings where haemostasis may already be impaired. The haemostatic agent, recombinant activated factor VII (rFVIIa, NovoSeven®), may be used to improve haemostasis but potential interactions with different volume expanders are poorly understood.
Clot formation was measured by thromboelastography (TEG) using blood from healthy volunteers. In vitro effects of rFVIIa with haemodilution, acidosis, and hypothermia were examined. Conditions were induced by dilution with NaCl (0.9%), lactated Ringer's solution, albumin 5%, or hydroxyethyl starch (HES) solutions [MW (molecular weight) 130–670 kDa]; by adjusting pH to 6.8 with 1 M HEPES (N-2-hydroxyethylpiperazine-N′-2-ethanesulphonic acid) buffer; or by reducing temperature to 32°C. We also studied the effect of low vs high MW HES (MW 200 vs 600 kDa) and rFVIIa on in vivo bleeding time (BT) in rabbits.
Haemodilution progressively altered TEG parameters. rFVIIa improved TEG parameters in the presence of acidosis, hypothermia or 20% haemodilution (P<0.05). At 40% haemodilution, the rFVIIa effect was diminished particularly with high MW HES. In vivo, rFVIIa shortened the BT (P<0.05) with low but not high MW HES.
Efficacy of rFVIIa was affected by the degree of haemodilution and type of volume expander, but not by acidosis or hypothermia.
PMCID: PMC2517151  PMID: 18565966
blood, haemodilution; complications, acidosis; hypothermia; measurement techniques, thromboelastography; rFVIIa; surgery, haemostatic response
2.  Early activation of the coagulation system during lower body negative pressure 
We considered that a moderate reduction of the central blood volume (CBV) may activate the coagulation system. Lower body negative pressure (LBNP) is a non-invasive means of reducing CBV and, thereby, simulates haemorrhage. We tested the hypothesis that coagulation markers would increase following moderate hypovolemia by exposing 10 healthy male volunteers to 10 min of 30 mmHg LBNP. Thoracic electrical impedance increased during LBNP (by 2·6 ± 0·7 Ω, mean ± SD; P < 0·001), signifying a reduced CBV. Heart rate was unchanged during LBNP, while mean arterial pressure decreased (84 ± 5 to 80 ± 6 mmHg; P < 0·001) along with stroke volume (114 ± 22 to 96 ± 19 ml min−1; P < 0·001) and cardiac output (6·4 ± 2·0 to 5·5 ± 1·7 l min−1; P < 0·01). Plasma thrombin–antithrombin III complexes increased (TAT, 5 ± 6 to 19 ± 20 μg l−1; P < 0·05), indicating that LBNP activated the thrombin generating part of the coagulation system, while plasma D-dimer was unchanged, signifying that the increased thrombin generation did not cause further intravascular clot formation. The plasma pancreatic polypeptide level decreased (13 ± 11 to 6 ± 8 pmol l−1; P < 0·05), reflecting reduced vagal activity. In conclusion, thrombin generation was activated by a modest decrease in CBV by LBNP in healthy humans independent of the vagal activity.
PMCID: PMC2839247  PMID: 19656165
haemorrhage; hypovolemia; pancreatic polypeptide; thrombin generation; vagal activity
3.  Effect of Haemostatic Control Resuscitation on mortality in massively bleeding patients: a before and after study 
Vox Sanguinis  2008;96(2):111-118.
Background and Objectives
Evidence supporting the use of platelets and plasma in resuscitation of massive bleedings is questionable. Current consensus guidelines recommend restrictive use. Our aim was to determine the effect of changing the transfusion practice on 30-day survival in massively bleeding patients.
Materials and Methods
Consecutive adult patients receiving more than 10 units of red blood cells (RBC) within 24 h 2 years prior to (2002–2003) and 2 years after (2005–2006) a change in transfusion practice were included. In 2004, we implemented Haemostatic Control Resuscitation (HCR) with preemptive use of platelets and plasma, administered in transfusion packages, comprising 5 units of RBCs, 5 units of fresh-frozen plasma and 2 units of platelet concentrates (PC), when massive bleeding occurred or upon arrival at the emergency room and thereafter directed by thrombelastography throughout the peri- and postoperative period.
In 2005–2006, the 442 patients received more PCs within 24 h from admission [mean 5·0 (SD 4·2) vs. 1·7 (2·0); P < 0·0001] and had a smaller decrease in platelet count during the bleeding episode [91·5 (81·2) vs. 119·7 (100·8) × 109/l; P = 0·0025] than the 390 patients treated in 2002–2003. Thirty-day mortality was reduced in 2005–2006 (20·4% vs. 31·5%; P = 0·0002) and at 90-day (22·4% vs. 34·6%; P < 0·0001) as compared to 2002–2003.
In patients who experience massive bleeding, HCR with platelets and plasma, as guided by thrombelastography, is associated with improved survival. While confirmation from a randomized controlled trial is urgently needed, HCR may be considered in these patients.
PMCID: PMC2667686  PMID: 19152603
massive bleeding; plasma; platelets; transfusion; thrombelastography

Results 1-3 (3)