Download Mirjana Kovac , Zeljko Kovac , Zorica Tomasevic , Iva Pruner

HIGH FACTOR VIII AND ADVANCED DISEASE ARE ASSOCIATED WITH
RISK OF RECURRENT THROMBOSIS IN WOMEN WITH BREAST CANCER
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Mirjana Kovac , Zeljko Kovac , Zorica Tomasevic , Iva Pruner , Branko Tomic , Valentina Djordjevic , Dragica Radojkovic
Faculty of Medicine, University of Belgrade, Serbia¹, Blood Transfusion Institute of Serbia, Hemostasis
Department, Belgrade²
3
National Cancer Research Institute, Belgrade, Serbia
4
Institute of Molecular Genetics and Genetic Engineering, University of Belgrade
METHODS
OBJECTIVES
The pathogenesis of recurrent VTE in cancer patients is less well studied.
There is only very limited information on the importance of clinical risk factors, while the role
of biomarkers in this context has never been studied.
A recently proposed predictive model for risk assessment of VTE in cancer patients also
included determination of FVIII activity as a novel biomarker. However, the association
Of FVIII and risk of recurrence of VTE in cancer patients is still missing.
Our study aimed to investigate the association of FVIII level with the risk of recurrent VTE
during breast cancer treatment.
Statistical Analysis
The investigation was conducted as a prospective study between June 2010 and December
2015.
Total of 100 women who developed thrombosis during the breast cancer treatment was
included in the study and followed up for 36 months.
After inclusion in the study, FVIII activity was determined in all subjects.
The final end point that was observed in the study group was recurrent venous thrombosis
thrombosis..
The evaluation of all clinical and laboratory characteristics was done with regard to recurrent
event.
CONCLUSION
Statistical analysis was performed using Statistical Package for Social Sciences 20.0 for Windows (SPSS Inc., Chicago, Illinois, USA).
The normality of continuous variables distribution was evaluated using Kolmogorov-Smirnov and Shapiro-Wilk tests.
Continuous variables data distribution was presented by median and IQR (interquartile range) and compared using Mann Whitney U test.
Categorical values data were compared by Pearson Chi-square test and Fisher´s exact test: risk assessment was presented as odds ratio (OR) and 95% confidence interval (95% CI).
In assessment of prognostic markers for rethrombosis, multivariate binary logistic regression model was used. P value less than 0.05 was considered as statistically significant.
Figure 1 Number of recurrent events during
follow- up
Table 1 Number of recurrent events in relation to the period of anticoagulation
Localisation
4
Frequency
3
2
The first
event
Duration of anticoagulation
The recurrent
(VKA, LMWH)
event
Distal DVT
44
3 months (VKA)
7
Proximal DVT
7
6-12 months (VKA)
1
DVT/ PE
7
long-term (VKA)
1
Isolated PE
10
long-term (VKA)
1
Superficial
24
1 months (LMWH)
7*
Upper limb
8
1-3 months (LMWH or VKA)
0
Table 2 Clinical and laboratory variables
Total
0
0
5
10
15
rethrombosis time (months)
20
25
100
17
Deep venous thrombosis (DVT), pulmonary embolism (PE), vitamin K antagonist (VKA), low molecular
weight heparin (LMWH); after superficial thrombosis one study participant developed PE*
Total of 17% study participants experienced recurrent thrombosis. RVT was observed in the first 12
months in 15, while in two remaining after 16, respectively 23 months. Thus, rethrombosis time expressed
in median (IQR), was 8 (9) months (Figure 1).
From those who developed RVT in the first 12 months, in two of them recurrent event was observed in
the period of anticoagulation. In all cases, RVT developed at he same localisation as the first thrombosis,
except for one woman who experienced PE after 9 months of superficial vein thrombosis (Table 1).
P
OR
Patients of age >50
0.084
0.107
0.008
1.355
Patients with BMI> 25
0.789
0.821
0.193
3.491
Varicose veins/yes
0.030
5.301
1.176
23.895
Previous VTE/yes
0.126
0.208
0.028
1.553
Concomitant diseases/yes
0.827
1.158
0.309
4.347
Advanced disease/yes
0.002
10.437
2.305
47.264
Tamoxifen/Chemotherapy
0.283
2.297
0.503
10.501
FV Leiden mutation
0.632
0.648
0.110
3.829
0.839
0.020
FII G20210A mutation
0.178
8.445
0.379
187.946
0.045
Patients with FVIII >1.5 IU/ml
0.045
6.233
1.042
37.289
With
RVT
(N=17)
P
61.0 (10)
76 (91)
28.3 (7.3)
60 (72)
35 (42)
17 (20.5)
35(42)
63.0 (12)
15 (88)
27.1 (7.5)
11 (65)
11(65)
3 (17.6)
8 (47)
0.631
0.662
0.813
0.530
0.098
0.773
0.711
2 (3)
26 (31)
0
2 (12)
0.964
0.119
II
31 (37)
0.282
III (advanced disease)
24 (29)
4 (23)
11(65)
0.005
13 (15.6)
1 (1.2)
3 (17.6)
2 (11.7)
1.61 (0.71) 1.94 (1.17)
FV Leiden carrier (%)
FII G20210A carrier (%)
FVIII activity, median (IQR),
IU/ml
Patients with FVIII activity>1.5
IU/ml (%)
Rethrombosis time, median
(IQR), months
RESULTS
Investigated variables
Without
RVT
(N=83)
Age, median (IQR), year
Patients of age >50 (%)
BMI, median (IQR)
Patients with BMI> 25 (%)
Varicose veins/yes (%)
Previous VTE/yes (%)
Concomitant diseases/yes (%)
Stage of disease (UICC) (%)
In situ
I
1
Table 3 Prognostic markers for RVT
51(61)
14 (82)
0.100
NA
8.0 (9)
NA
95% CI
Recurrent venous thrombosis (RVT), body mass index (BMI-kg/m2),
venous thromboembolism (VTE)
Recurrent venous thrombosis (RVT), body mass index (BMIkg/m2), interquartile range (IQR), venous thromboembolism
(VTE), not applicable (NA), the stage of disease was classified
using UICC International Union Against Cancer
The patients who developed RVT had significantly higher FVIII; median (IQR), of 1.94 (1.17) than those who stayed free of recurrent during follow-up; 1.61 (0.71); P=0.045.
Between two groups significant difference was observed with regard to the stage of disease, P=0.005 and to the prothrombin G20210A mutation presence, P=0.020 (Table 2).
RVT occurred in 6 of 65 (9%) of women who were considered to be in an early stage of breast cancer and in 11 of 35 (31%) of women who were considered to be in the advanced stage of the disease.
Analysis of clinical and laboratory markers using multivariate binary logistic regression model showed that high FVIII, advanced disease and varicose veins were associated with a risk of recurrent
thrombosis with ant OR of 6.233 (95% CI; 1.042-37.289; P=0.045); OR 10.437 (95% CI; 2.305-47.264; P=0.002), respectively OR 5.301 (95% CI; 1.176-23.895; P=0.030) (Table 3).
CONCLUSION
Factor VIII as a marker of hypercoagulable state represents a contributing factor for the recurrence of VTE
in women with breast cancer. The determination of FVIII could be a valuable tool for RVT risk assessment
during breast cancer treatment.
SSC 2016
Corresponding author:
MD PhD Mirjana Kovac
Blood Transfusion Institute of Serbia, Belgrade ,,Sv.
Sv. Sava 39, 11 000 Belgrade, Serbia
E- mail: [email protected]
22--WOM
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Thrombotic Disorders: Thrombotic disorders in women
Mirjana Kovac
DOI: 10.3252/pso.eu.SSC2016.2016
Poster
presented at: