PMID- 21670663
OWN - NLM
STAT- MEDLINE
DCOM- 20111207
LR  - 20131121
IS  - 1473-5733 (Electronic)
IS  - 0957-5235 (Linking)
VI  - 22
IP  - 6
DP  - 2011 Sep
TI  - Activation of coagulation by a thalidomide-based regimen.
PG  - 532-40
LID - 10.1097/MBC.0b013e328348629d [doi]
AB  - Combining thalidomide (Thal) with chemotherapeutic agents or steroid preparations 
      led to improved response rates in the treatment of multiple myeloma. However, 
      deep vein thrombosis (DVT) is one of the most serious side-effects noted with 
      this regimen, and how a Thal-based regimen causes DVT is unclear. We investigated 
      the procoagulant effects of Thal when combined with chemotherapeutic agents in 
      vitro, focusing on tissue factor (TF) and phosphatidylserine. We examined the 
      effects of the chemotherapeutic doxorubicin hydrochloride (Dox) and the steroid 
      dexamethasone (Dex), with or without Thal. Our study used the human vascular 
      endothelial, monocytic, and myeloma cell lines, EAhy926, THP-1, and RPMI8226, 
      respectively. In EAhy926 and THP-1, Dex treatment increased expression of TF, 
      which may induce procoagulant activity (PCA). Upregulation of TF mRNA correlated 
      with activation of the Egr-1 pathway. In Thal and Dex treatments, the increase of 
      PCA induction from phosphatidylserine exposure was modest. In contrast, Dox and 
      Thal-Dox increased phosphatidylserine exposure in both cell types. In THP-1 
      cells, cell surface phosphatidylserine exposure correlated with increased PCA by 
      Dox. Thal alone showed a modest increase in phosphatidylserine exposure in 
      endothelial cells and monocytes. When Thal is given in combination with 
      chemotherapies or Dex, endothelial cell and monocyte PCA may be induced through 
      phosphatidylserine exposure, or TF expression. Induction may be protracted by 
      Thal, which has an antiangiogenic activity. Therefore, prophylactic anticoagulant 
      strategies should be considered in Thal-based combination regimens.
FAU - Hoshi, Asuka
AU  - Hoshi A
AD  - Laboratory Molecular Genetics of Hematology, Graduate School of Healthcare 
      Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 
      Japan.
FAU - Matsumoto, Aya
AU  - Matsumoto A
FAU - Chung, Jihwa
AU  - Chung J
FAU - Isozumi, Yu
AU  - Isozumi Y
FAU - Koyama, Takatoshi
AU  - Koyama T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Blood Coagul Fibrinolysis
JT  - Blood coagulation & fibrinolysis : an international journal in haemostasis and 
      thrombosis
JID - 9102551
RN  - 0 (Annexin A5)
RN  - 0 (Anticoagulants)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Blood Coagulation Factors)
RN  - 0 (Drug Combinations)
RN  - 0 (Phosphatidylserines)
RN  - 0 (leukocyte procoagulant activity)
RN  - 4Z8R6ORS6L (Thalidomide)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - 80168379AG (Doxorubicin)
RN  - 9035-58-9 (Thromboplastin)
SB  - IM
MH  - Annexin A5/analysis
MH  - Anticoagulants/pharmacology
MH  - Antineoplastic Agents/adverse effects/*pharmacology
MH  - Blood Coagulation/*drug effects
MH  - Blood Coagulation Factors/analysis/metabolism
MH  - Cell Line
MH  - Dexamethasone/*adverse effects/pharmacology
MH  - Doxorubicin/*adverse effects/pharmacology
MH  - Drug Combinations
MH  - Drug Interactions
MH  - Endothelial Cells/drug effects/metabolism
MH  - Endothelium, Vascular/cytology/drug effects/metabolism
MH  - Flow Cytometry
MH  - Humans
MH  - Monocytes/drug effects/metabolism
MH  - Multiple Myeloma/complications/drug therapy/pathology
MH  - Phosphatidylserines/*analysis
MH  - Thalidomide/*adverse effects/pharmacology
MH  - Thromboplastin/analysis/*biosynthesis
MH  - Venous Thrombosis/chemically induced/complications
EDAT- 2011/06/15 06:00
MHDA- 2011/12/13 00:00
CRDT- 2011/06/15 06:00
PHST- 2011/06/15 06:00 [entrez]
PHST- 2011/06/15 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
AID - 10.1097/MBC.0b013e328348629d [doi]
PST - ppublish
SO  - Blood Coagul Fibrinolysis. 2011 Sep;22(6):532-40. doi: 
      10.1097/MBC.0b013e328348629d.