BioModels Database

A number of therapeutics have been developed or are under development aiming to modulate the coagulation network to treat various diseases. We used a systems model to better understand the effect of modulating various components on blood coagulation. A computational model of the coagulation network was built to match in-house in vitro thrombin generation and activated Partial Thromboplastin Time (aPTT) data with various concentrations of recombinant factor VIIa (FVIIa) or factor Xa added to normal human plasma or factor VIII-deficient plasma. Sensitivity analysis applied to the model revealed that lag time, peak thrombin concentration, area under the curve (AUC) of the thrombin generation profile, and aPTT show different sensitivity to changes in coagulation factors' concentrations and type of plasma used (normal or factor VIII-deficient). We also used the model to explore how variability in concentrations of the proteins in coagulation network can impact the response to FVIIa treatment.

Reactions (62)

[TF] + [VII] ↔ [TF_VII]; {TF} , {VII} , {TF_VII} , {TF} , {VII} , {TF_VII}

Math:

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Notes:

Hockin - Mann, Blood Coagulation Kinetics

[TF] + [VIIa] ↔ [TF_VIIa]; {TF} , {VIIa} , {TF_VIIa} , {TF} , {VIIa} , {TF_VIIa}

Math:

(Details: $View Math$ )

Notes:

Hockin - Mann, Blood Coagulation Kinetics Reaction 2, k4 and k3 value taken as it is

[TF_VIIa] + [VII] → [TF_VIIa] + [VIIa]; {TF_VIIa} , {VII} , {TF_VIIa} , {VII}

Math:

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Notes:

Hockin - Mann, Blood Coagulation Kinetics Reaction 3, k5 value taken as it is

[Xa] + [VII] → [Xa] + [VIIa]; {Xa} , {VII} , {Xa} , {VII}

Math:

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Notes:

Hockin - Mann, Blood Coagulation Kinetics Reaction 4, k6 value taken as it is

[IIa] + [VII] → [IIa] + [VIIa]; {IIa} , {VII} , {IIa} , {VII}

Math:

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Notes:

Hockin - Mann, Blood Coagulation Kinetics Reaction 5, k7 value taken as it is

[TF_VIIa] + [X] ↔ [TF_VIIa_X]; {TF_VIIa} , {X} , {TF_VIIa_X} , {TF_VIIa} , {X} , {TF_VIIa_X}

Math:

(Details: $View Math$ )

Notes:

Hockin - Mann, Blood Coagulation Kinetics Reaction 6, k10 and k9 and k8 value taken as it is

R6b

[TF_VIIa_X] → [TF_VIIa_Xa]; {TF_VIIa_X} , {TF_VIIa_X}

Math:

(Details: $View Math$ )

Notes:

Hockin - Mann, Blood Coagulation Kinetics Reaction 6b, k10 value taken as it is

[TF_VIIa] + [Xa] ↔ [TF_VIIa_Xa]; {TF_VIIa} , {Xa} , {TF_VIIa_Xa} , {TF_VIIa} , {Xa} , {TF_VIIa_Xa}

Math:

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Notes:

Hockin - Mann, Blood Coagulation Kinetics Reaction 7, k12 and k11 - value taken as it is

[TF_VIIa] + [IX] ↔ [TF_VIIa_IX]; {TF_VIIa} , {IX} , {TF_VIIa_IX} , {TF_VIIa} , {IX} , {TF_VIIa_IX}

Math:

(Details: $View Math$ )

Notes:

Hockin - Mann, Blood Coagulation Kinetics Reaction 8, k14 and k13 value taken as it is

R8b

[TF_VIIa_IX] → [TF_VIIa] + [IXa]; {TF_VIIa_IX} , {TF_VIIa_IX}

Math:

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Notes:

Hockin - Mann, Blood Coagulation Kinetics Reaction 8b, k15 value taken as it is

[Xa] + [II] → [Xa] + [IIa] + [F12]; {Xa} , {II} , {Xa} , {II}

Math:

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Notes:

Hockin - Mann, Blood Coagulation Kinetics Reaction 9, k16 value taken as it is

R10

[IIa] + [VIII] → [IIa] + [VIIIa]; {IIa} , {VIII} , {IIa} , {VIII}

Math:

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Notes:

Hockin - Mann, Blood Coagulation Kinetics Reaction 10, k17 value taken as it is

R11

[IXa] + [VIIIa] ↔ [IXa_VIIIa]; {IXa} , {VIIIa} , {IXa_VIIIa} , {IXa} , {VIIIa} , {IXa_VIIIa}

Math:

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Notes:

Hockin - Mann, Blood Coagulation Kinetics Reaction 11, k19 and k18 value taken as it is

R12

[IXa_VIIIa] + [X] ↔ [IXa_VIIIa_X]; {IXa_VIIIa} , {X} , {IXa_VIIIa_X} , {IXa_VIIIa} , {X} , {IXa_VIIIa_X}

Math:

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Notes:

Hockin - Mann, Blood Coagulation Kinetics Reaction 12, k21 and k20 value taken as it is

R12b

[IXa_VIIIa_X] → [IXa_VIIIa] + [Xa]; {IXa_VIIIa_X} , {IXa_VIIIa_X}

Math:

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Notes:

Hockin - Mann, Blood Coagulation Kinetics Reaction 12b, k22 value taken as it is

R13

[VIIIa] ↔ [VIIIa1_L] + [VIIIa2]; {VIIIa} , {VIIIa1_L} , {VIIIa2} , {VIIIa} , {VIIIa1_L} , {VIIIa2}

Math:

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Notes:

Hockin - Mann, Blood Coagulation Kinetics Reaction 13, k24 and k23 value taken as it is

R14

[IXa_VIIIa_X] → [VIIIa1_L] + [VIIIa2] + [X] + [IXa]; {IXa_VIIIa_X} , {IXa_VIIIa_X}

Math:

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Notes:

Hockin - Mann, Blood Coagulation Kinetics Reaction 14, k25 value taken as it is

R15

[IXa_VIIIa] → [VIIIa1_L] + [VIIIa2] + [IXa]; {IXa_VIIIa} , {IXa_VIIIa}

Math:

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Notes:

Hockin - Mann, Blood Coagulation Kinetics Reaction 15, k25_1 is same as k25 - value taken as it is

R16

[IIa] + [V] → [IIa] + [Va]; {IIa} , {V} , {IIa} , {V}

Math:

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Notes:

Hockin - Mann, Blood Coagulation Kinetics Reaction 16, k26 value taken as it is

R17

[Xa] + [Va] ↔ [Xa_Va]; {Xa} , {Va} , {Xa_Va} , {Xa} , {Va} , {Xa_Va}

Math:

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Notes:

Hockin - Mann, Blood Coagulation Kinetics Reaction 17, k28 value taken as it is

R18

[Xa_Va] + [II] ↔ [Xa_Va_II]; {Xa_Va} , {II} , {Xa_Va_II} , {Xa_Va} , {II} , {Xa_Va_II}

Math:

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Notes:

Hockin - Mann, Blood Coagulation Kinetics Reaction 18, k30 value taken as it is

R18b

[Xa_Va_II] → [Xa_Va] + [mIIa] + [F12]; {Xa_Va_II} , {Xa_Va_II}

Math:

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Notes:

Hockin - Mann, Blood Coagulation Kinetics Reaction 18b, k31 value taken as it is

R19

[mIIa] + [Xa_Va] → [IIa] + [Xa_Va]; {mIIa} , {Xa_Va} , {mIIa} , {Xa_Va}

Math:

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Notes:

Hockin - Mann, Blood Coagulation Kinetics Reaction 19, k32 value taken as it is

R20

[Xa] + [TFPI] ↔ [Xa_TFPI]; {Xa} , {TFPI} , {Xa_TFPI} , {Xa} , {TFPI} , {Xa_TFPI}

Math:

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Notes:

Hockin - Mann, Blood Coagulation Kinetics Reaction 20, k34 and k33 value taken as it is

R21

[TF_VIIa_Xa] + [TFPI] ↔ [TF_VIIa_Xa_TFPI]; {TF_VIIa_Xa} , {TFPI} , {TF_VIIa_Xa_TFPI} , {TF_VIIa_Xa} , {TFPI} , {TF_VIIa_Xa_TFPI}

Math:

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Notes:

Hockin - Mann, Blood Coagulation Kinetics Reaction 21, k36 and k35 value taken as it is

R22

[TF_VIIa] + [Xa_TFPI] → [TF_VIIa_Xa_TFPI]; {TF_VIIa} , {Xa_TFPI} , {TF_VIIa} , {Xa_TFPI}

Math:

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Notes:

Hockin - Mann, Blood Coagulation Kinetics Reaction 22, k36 and k35 value taken as it is

R23

[Xa] + [ATIII] → [Xa_ATIII]; {Xa} , {ATIII} , {Xa} , {ATIII}

Math:

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Notes:

Hockin - Mann, Blood Coagulation Kinetics Reaction 23, k38 value taken as it is

R24

[mIIa] + [ATIII] → [mIIa_ATIII]; {mIIa} , {ATIII} , {mIIa} , {ATIII}

Math:

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Notes:

Hockin - Mann, Blood Coagulation Kinetics Reaction 24, k39 value taken as it is

R25

[IXa] + [ATIII] → [IXa_ATIII]; {IXa} , {ATIII} , {IXa} , {ATIII}

Math:

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Notes:

Hockin - Mann, Blood Coagulation Kinetics Reaction 25, k40 value taken as it is

R26

[IIa] + [ATIII] → [IIa_ATIII]; {IIa} , {ATIII} , {IIa} , {ATIII}

Math:

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Notes:

Hockin - Mann, Blood Coagulation Kinetics Reaction 26, k41 value taken as it is

R27

[TF_VIIa] + [ATIII] → [TF_VIIa_ATIII]; {TF_VIIa} , {ATIII} , {TF_VIIa} , {ATIII}

Math:

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Notes:

Hockin - Mann, Blood Coagulation Kinetics Reaction 27, k42 value taken as it is

R28

[CA] + [XII] → [CA] + [XIIa]; {CA} , {XII} , {CA} , {XII}

Math:

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Notes:

Butenas S and Mann KG 2004 paper - CA is contact activator

R31

[XIIa] + [PK] ↔ [XIIa_PK]; {XIIa} , {PK} , {XIIa_PK} , {XIIa} , {PK} , {XIIa_PK}

Math:

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Notes:

Diamond - Systems Biology of Coagulation Initiation Reaction 31, k1 and k-1, value taken as it is

R31b

[XIIa_PK] → [XIIa] + [K]; {XIIa_PK} , {XIIa_PK}

Math:

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Notes:

Diamond - Systems Biology of Coagulation Initiation Reaction 31, kcat value taken as it is

R32

[XII] + [K] ↔ [XII_K]; {XII} , {K} , {XII_K} , {XII} , {K} , {XII_K}

Math:

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Notes:

Diamond - Systems Biology of Coagulation Initiation Reaction 32, k1 and k-1, value taken as it is

R32b

[XII_K] → [XIIa] + [K]; {XII_K} , {XII_K}

Math:

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Notes:

Diamond - Systems Biology of Coagulation Initiation Reaction 32, kcat, value taken as it is

R37

[XIIa] + [ATIII] → [XIIa_ATIII]; {XIIa} , {ATIII} , {XIIa} , {ATIII}

Math:

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Notes:

Diamond - Systems Biology of Coagulation Initiation Reaction 37, k1, value taken as it is

R39

[XIIa] + [XI] ↔ [XIIa_XI]; {XIIa} , {XI} , {XIIa_XI} , {XIIa} , {XI} , {XIIa_XI}

Math:

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Notes:

Diamond - Systems Biology of Coagulation Initiation Reaction 39, k1 and k-1, value taken as it is

R39b

[XIIa_XI] → [XIIa] + [XIa]; {XIIa_XI} , {XIIa_XI}

Math:

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Notes:

Diamond - Systems Biology of Coagulation Initiation Reaction 39, kcat

R41

[XIa] + [ATIII] → [XIa_ATIII]; {XIa} , {ATIII} , {XIa} , {ATIII}

Math:

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Notes:

Diamond - Systems Biology of Coagulation Initiation Reaction 41, k1 value taken as it is

R45

[XIa] + [IX] ↔ [XIa_IX]; {XIa} , {IX} , {XIa_IX} , {XIa} , {IX} , {XIa_IX}

Math:

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Notes:

Diamond - Systems Biology of Coagulation Initiation Reaction 45,k1 and k-1, value taken as it is

R45b

[XIa_IX] → [XIa] + [IXa]; {XIa_IX} , {XIa_IX}

Math:

(Details: $View Math$ )

Notes:

Diamond - Systems Biology of Coagulation Initiation Reaction 45, kcat value taken as it is

R46

[IXa] + [X] ↔ [IXa_X]; {IXa} , {X} , {IXa_X} , {IXa} , {X} , {IXa_X}

Math:

(Details: $View Math$ )

Notes:

Diamond - Systems Biology of Coagulation Initiation Reaction 46,k1 and k-1, value taken as it is

R46b

[IXa_X] → [IXa] + [Xa]; {IXa_X} , {IXa_X}

Math:

(Details: $View Math$ )

Notes:

Diamond - Systems Biology of Coagulation Initiation Reaction 46, kcat value taken as it is

R49

[VIIa] + [X] ↔ [VIIa_X]; {VIIa} , {X} , {VIIa_X} , {VIIa} , {X} , {VIIa_X}

Math:

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Notes:

Diamond - Systems Biology of Coagulation Initiation Reaction 49,k1 and k-1, value taken as it is

R49b

[VIIa_X] → [VIIa] + [Xa]; {VIIa_X} , {VIIa_X}

Math:

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Notes:

Diamond - Systems Biology of Coagulation Initiation Reaction 49, kcat value taken as it is

R50

[IIa] + [Tmod] ↔ [IIa_Tmod]; {IIa} , {Tmod} , {IIa_Tmod} , {IIa} , {Tmod} , {IIa_Tmod}

Math:

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Notes:

Reference http://www.ncbi.nlm.nih.gov/pmc/articles/PMC52171/pdf/pnas01065-0397.pdf Kd of the reaction is 7nM

R51

[IIa_Tmod] + [PC] ↔ [IIa_Tmod_PC]; {IIa_Tmod} , {PC} , {IIa_Tmod_PC} , {IIa_Tmod} , {PC} , {IIa_Tmod_PC}

Math:

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Notes:

Reference http://www.pnas.org/content/103/4/879.full Km = 7.7 microM Kcat = 19.8 (nM.min)^-1 nM^-1

R052

[IIa_Tmod_PC] → [IIa_Tmod] + [APC]; {IIa_Tmod_PC} , {IIa_Tmod_PC}

Math:

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Notes:

Reference http://www.pnas.org/content/103/4/879.full Km = 7.7 microM Kcat = 19.8 (nM.min)^-1 nM^-1

R301

[IIa] + [Fg] → [IIa] + [F]; {IIa} , {Fg} , {IIa} , {Fg}

Math:

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Notes:

Reference http://www.sciencedirect.com/science/article/pii/S0049384800004059 Km = 7.2 uM = 7200 nM Kcat = 5040 min^-1 = 84 s^-1

R053

[APC] + [Va] ↔ [APC_Va]; {APC} , {Va} , {APC_Va} , {APC} , {Va} , {APC_Va}

Math:

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Notes:

Reference http://www.jbc.org/content/256/21/11128.full.pdf+html Kd = 1.4 * 10^-8 M

R055

[APC] + [VIIIa] ↔ [APC_VIIIa]; {APC} , {VIIIa} , {APC_VIIIa} , {APC} , {VIIIa} , {APC_VIIIa}

Math:

(Details: $View Math$ )

Notes:

Assume the same binding charactersitics as Va binding (Reaction 51 in v9)

R054

[APC_Va] → [APC] + [Va_deg]; {APC_Va} , {APC_Va}

Math:

(Details: $View Math$ )

Notes:

Reference http://www.jbc.org/content/263/29/14884.long kcat = 23.7 min^-1 = 0.395 s^-1

R056

[APC_VIIIa] → [APC] + [VIIIa_deg]; {APC_VIIIa} , {APC_VIIIa}

Math:

(Details: $View Math$ )

Notes:

Reference http://bloodjournal.hematologylibrary.org/content/95/5/1714.long kcat = 3 * 1.2 = 3.6 min^-1

R057

[APC] + [IXa_VIIIa] ↔ [APC_IXa_VIIIa]; {APC} , {IXa_VIIIa} , {APC_IXa_VIIIa} , {APC} , {IXa_VIIIa} , {APC_IXa_VIIIa}

Math:

(Details: $View Math$ )

Notes:

Assume same binding characteristics as Reaction no. 52 (VIIIa binding to APC - which has been assume to be same as Reaction 51, Va binding to APC)

R058

[APC_IXa_VIIIa] → [APC] + [IXa] + [VIIIa_deg]; {APC_IXa_VIIIa} , {APC_IXa_VIIIa}

Math:

(Details: $View Math$ )

Notes:

Reference http://bloodjournal.hematologylibrary.org/content/95/5/1714.long kcat = 1.2 min^-1 = 0.02 s^-1

R059

[APC] + [IXa_VIIIa_X] ↔ [APC_IXa_VIIIa_X]; {APC} , {IXa_VIIIa_X} , {APC_IXa_VIIIa_X} , {APC} , {IXa_VIIIa_X} , {APC_IXa_VIIIa_X}

Math:

(Details: $View Math$ )

Notes:

Assume same binding charactersitics as Reaction 55.

R060

[APC_IXa_VIIIa_X] → [APC] + [IXa] + [X] + [VIIIa_deg]; {APC_IXa_VIIIa_X} , {APC_IXa_VIIIa_X}

Math:

(Details: $View Math$ )

Notes:

Assume same reaction kinetics as Reaction 56. kcat = 0.02 s^-1

R47

[Xa] + [VIII] ↔ [Xa_VIII]; {Xa} , {VIII} , {Xa_VIII} , {Xa} , {VIII} , {Xa_VIII}

Math:

(Details: $View Math$ )

Notes:

Diamond - Systems Biology of Coagulation Initiation Reaction 47,k1 and k-1, value taken as it is

R47b

[Xa_VIII] → [Xa] + [VIIIa]; {Xa_VIII} , {Xa_VIII}

Math:

(Details: $View Math$ )

Notes:

Diamond - Systems Biology of Coagulation Initiation Reaction 47, kcat value taken as it is

mw2b7d93e1_fc1b_4fa0_a03b_4d2b2259d14f

[F12] → [F12_deg]; {F12} , {F12}

Math:

(Details: $View Math$ )

Notes:

Assume F1+2 half-life of 2-4 hours based on clinical trials k = log(2)/(2 * 3600) = 9.627E-05 This value should be variable.

[VIIa_X] + [XIa] → [VIIa] + [Xa] + [XIa]; {VIIa_X} , {XIa} , {VIIa_X} , {XIa}

Math:

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Rules (1)

Assignment Rule (name: mw85e2714d_e6e5_47d5_9ffc_d90573faebe1)

IIa_12mIIa = IIa+1.2*mIIa

Math:

(Details: $View Math$ )

BioModels Database

BIOMD0000000611 - Nayak2015 - Blood Coagulation Network - Predicting the Effects of Various Therapies on Biomarkers

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