Project Nr 16 Tissue factor, tissue factor pathway inhibitor, and thrombin-antithrombin complexes in...

Project Nr 16

Tissue factor, tissue factor pathway inhibitor,and thrombin-antithrombin complexes in patients

with abdominal aortic aneurysm undergoing endovascular and open repair.

Kotschy M.1, Witkiewicz W.1,2, Grendziak R.2, Zapotoczny N.2, Dubis J.1, Żuk N.1, Pfanhauser M.2, Kotschy D.3

1 Regional Specialized Hospital in Wrocław, Research & Development Centre Departments: 2 of Vascular Surgery, 3 of Angiology 

The aim of the study was to determinethe concentrations of TF, TFPI, VEGF-A

and TAT complexes in blood plasma of patientswith abdominal aortic aneurysm undergoing

endovascular aortic repair (EVAR)

and open aortic repair (OAR)

• Background

Source: http://www.sirweb.org/patients/abdominal-aortic-aneurysms/

EndoVascular Aortic Repair

Source: http://leedsvascularinstitute.org/AAA_Education_EVAR.php

OpenAorticRepair

Source: http://www.surgeryencyclopedia.com/A-Ce/Aortic-Aneurysm-Repair.html#b

The presence of tissue factor (TF), tissue factor pathway inhibitor (TFPI), vascular endothelial growth factor-A (VAEGF-A) in patients with

damaged aortic wall, with thrombin-antithrombin complexes (TAT) indicating thrombin-generation and appearance of intraluminal thrombin in aortic

aneurysm suggests that haemostatic processes can enhance proteolysis of aortic wall.

Haemostatic factors:

TF, TFPI TAT complex

Haemostasis VEGF

VEGF - A as angiogenic factor

Source: http://www.biooncology.com

Materials and methodsThe studies enrolled 42 patients (38 males and females)in mean age 71 (range 59-86) years in whom presurgery ultrasound and computer tomography revealed presence

of abdominal aortic aneurysm (AAA). Blood was drawn 3 times: before, directly after surgery and 24 hours after EVAR

and OAR. The concentrations of TF, TFPI, VEGF-Aand TAT complexes was measured in plasma using

enzyme immuno-assay with commercial tests.

Kind of repair EVAR n (n = 26 %)

OARn (n=16%)

Gengermale/ female

24/2 92,3/7,7 14/2 87,5 / 12,5

Age (years)mean-range

68 (59-83) 75 (64-86)

Coronary heart diseases

11 34 8 50

Previous Myocardial Infarction

9 29 4 25

Cerebrovascular disease

6 19 2 12,5

Preipheral vascular diseases

2 6 0 0

Hypertension 9 29 6 37,5

Pulmonary diseases 7 22 1 6,25

Renal, prostate diseases

8 25 4 25

Diabetes mellutis 3 9,3 1 6,25

Smoking 20 62,5 12 75

Aneurysm diameter cm range

5,43,5-7,7

8,14,5-10,0

Tab. 1 Some demographic data

of examined patients with AAA

Fig.1

Examined parameters

Controlsn = 50M; SD (range)Me, Q1, Q3

Patients with AAAn = 42M; SD (range)Me, Q1, Q3

p-value

TFpg/ml

133+/- 79(18-290)

230 +/- 139(81-912)

0,03

TFPIng/ml

84+/- 19(52-124)

90+/-23(51-174)

NS

VEGF-Apg/ml

24+/- 14(8-44)

34+/-23(14-144)

NS

TAT complexng/ml

2,2+/-3,5(0,5 – 4,9)Me; Q1, Q31,4; 0,7; 2,2

7,6+/-8,2(1,1 - 33)Me; Q1, Q35,24;2,7;8,8

0,0003

Tab. 2 Haemostatic factors in plasma of patients with AAA and in controls

Examined parameters

EVAR n=26

2Preoperative

M; SD

3End of surgery

M; SD

424 h postoperative

M; SD

p-value

TFpg/ml

229+/- 162(98-912)

131+/-89(60-443)

203+/-112(70-483)

2/3 0,00013/4 0,01

TFPIng/ml

101+/-18(66-134)

114+/-29(65-169)

125+/-30(77-194)

2/30,006

VEGFpg/ml

25+/-9(13-42)

21+/-12(6-43)

33+/-16(14-62

NS

TAT complexesng/ml

9,9+/-9,8

Me, Q1, Q37,8 2,9 12,9

37,9+/-21,6

Me, Q1, Q331,6 25,6 52,0

18,9+/-31,6

Me, Q1, Q39,9 5,9 13,6

2/3 0,00033/4 0,034

Tab. 3 Haemostatic factors during endovascular aortic repair

1 – control 2 – preoperative3 – immediatelly postoperative 4 – postoperative (24 h)

EVAR - endovascular aortic repair

Concentration of TF in Medians during EVAR

Fig. 2

Tab. 4 Haemostatic factors during open aortic repair (OAR)

Examined parameters

OAR n=16

2Preoperative

M; SD

3End of surgery

M; SD

424 h postoperative

M; SD

p-value

TFpg/ml

223+/- 96(75-397)

161+/-88(53-390)

218+/-75(150-389)

2/3, 3/4 <0,02

TFPIng/ml

88+/-24(51-137)

97+/-38(63-174)

87+/-23(62-122)

SN

VEGFpg/ml

38+/-19(13-61)

36+/-30(7-118)

50+/-21(8-84)

SN

TAT complexesng/ml

4,7+/-3,7(0,7 – 14,1)Me, Q1, Q34,3 1,6 14,1

34,5+/-27,2(6,5 – 90,2)Me, Q1, Q324,9 11,2 50,4

51,3+/-42,2(6,4 – 104,8)Me, Q1, Q362 8,2 70,5

2/3 0,00533/4 0,000005

TAT complexes in Medians and Quartiles

1 – control 2 – preoperative3 – immediatelly postoperative 4 – postoperative (24 h)

Fig. 3

TAT complexes during OAR

The relation of its preoperative concentration

1 – control 2 – preoperative3 – immediatelly postoperative 4 – postoperative (24 h)

Fig. 4

Conclusions:

1.Significantly higher [TF] & [TAT] in AAA patients

than in controls.

2.EVAR & OAR activates thrombin-generation in AAA patients

3.The degree of clotting activation after aortic aneurysm repair

depends on preoperative clotting status of patients with AAA.

References:

1.Yamazumi K., Ojro M., Okumura H., Aikon T. ‘An activated state of blood coagulation and fibrynolysis in patients withb abdominal aortic aneurysm.’ Am. J. Surg. 1998; 775:297-301.2.Hobbs S.D., Haggart P., Fegan Ch., Bradburry A.W., Adam D.J. ‘The role of tissue factor in patients undergoing open repair of raptured and nonraptured abdominal aortic aneurysm.’ J. Vasc. Surg. 2007;46:682-686.