PMID- 20050927
OWN - NLM
STAT- MEDLINE
DCOM- 20100916
LR  - 20100611
IS  - 1365-2516 (Electronic)
IS  - 1351-8216 (Linking)
VI  - 16
IP  - 3
DP  - 2010 May
TI  - Thrombin generation and fibrinolysis in anti-factor IX treated blood and plasma 
      spiked with factor VIII inhibitor bypassing activity or recombinant factor VIIa.
PG  - 510-7
LID - 10.1111/j.1365-2516.2009.02164.x [doi]
AB  - Activated prothrombin complex concentrates (aPCC) and recombinant activated 
      factor VIIa (rFVIIa) are two important therapies in haemophilia patients with 
      inhibitors and improve clot stability. We hypothesized that potential differences 
      in procoagulant and fibrinolytic actions of aPCC and rFVIIa may lie in the clot 
      stability against fibrinolytic activation. We used thrombin generation, 
      fluorescence detection and thromboelastometry in anti-factor IXa (FIXa) 
      aptamer-treated whole blood (WB) and plasma to evaluate: (i) generation of 
      thrombin and activated factor X (FXa) and (ii) viscoelastic properties of blood 
      clots in the presence of tissue plasminogen activator (tPA) after addition of 
      aPCC (0.4 U mL(-1)) or rFVIIa (60 nm). Peak thrombin generation increased from 85 
      +/- 19 nm in aptamer-treated plasma to 276 +/- 83 nm and 119 +/- 22 nm after 
      addition of aPCC and rFVIIa respectively (P < 0.001). FXa activity increased 
      within 20 min by 87 +/- 6% and by 660 +/- 97% after addition of aPCC and rFVIIa 
      respectively (P < 0.001). TPA-induced lysis time increased from 458 +/- 378 s in 
      aptamer-treated WB to 1597 +/- 366 s (P = 0.001) and 1132 +/- 214 s (P = 0.075), 
      after addition of aPCC and rFVIIa respectively. In this haemophilia model using 
      the anti-FIXa aptamer, the larger amount of thrombin was generated with aPCC 
      compared with rFVIIa, while FXa generation was more rapidly increased in the 
      presence of rFVIIa. Furthermore, clot formation in anti-FIXa aptamer-treated WB 
      was less susceptible to tPA-induced fibrinolysis after adding aPCC compared with 
      rFVIIa.
FAU - Bolliger, D
AU  - Bolliger D
AD  - Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA, 
      USA.
FAU - Szlam, F
AU  - Szlam F
FAU - Molinaro, R J
AU  - Molinaro RJ
FAU - Escobar, M A
AU  - Escobar MA
FAU - Levy, J H
AU  - Levy JH
FAU - Tanaka, K A
AU  - Tanaka KA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091229
PL  - England
TA  - Haemophilia
JT  - Haemophilia : the official journal of the World Federation of Hemophilia
JID - 9442916
RN  - 0 (Antifibrinolytic Agents)
RN  - 0 (Blood Coagulation Factor Inhibitors)
RN  - 0 (Blood Coagulation Factors)
RN  - 0 (Recombinant Proteins)
RN  - 37224-63-8 (prothrombin complex concentrates)
RN  - 9001-27-8 (Factor VIII)
RN  - EC 3.4.21.21 (Factor VIIa)
RN  - EC 3.4.21.22 (Factor IXa)
RN  - EC 3.4.21.5 (Thrombin)
RN  - EC 3.4.21.6 (Factor Xa)
SB  - IM
EIN - Haemophilia. 2010 May;16(3):567
MH  - Antifibrinolytic Agents/pharmacology
MH  - Blood Coagulation/*drug effects
MH  - Blood Coagulation Factor Inhibitors/pharmacology
MH  - Blood Coagulation Factors/*therapeutic use
MH  - Factor IXa/*antagonists & inhibitors
MH  - Factor VIII/antagonists & inhibitors
MH  - Factor VIIa/*therapeutic use
MH  - Factor Xa/metabolism
MH  - Fibrinolysis/drug effects
MH  - Hemophilia A/*drug therapy
MH  - Humans
MH  - Recombinant Proteins/therapeutic use
MH  - Thrombin/*metabolism
EDAT- 2010/01/07 06:00
MHDA- 2010/09/18 06:00
CRDT- 2010/01/07 06:00
PHST- 2010/01/07 06:00 [entrez]
PHST- 2010/01/07 06:00 [pubmed]
PHST- 2010/09/18 06:00 [medline]
AID - HAE2164 [pii]
AID - 10.1111/j.1365-2516.2009.02164.x [doi]
PST - ppublish
SO  - Haemophilia. 2010 May;16(3):510-7. doi: 10.1111/j.1365-2516.2009.02164.x. Epub 
      2009 Dec 29.