Precautions during Direct Oral Anticoagulant Introduction in Gynecologic Malignancies: A Single-Center Retrospective Cohort Study
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Design and Participants
2.2. Primary Outcome
2.3. Other Variables
2.4. Statistical Analyses
3. Results
3.1. Characteristics of Study Participants
3.2. Clinical Characteristics of Patients Who Developed VTE Recurrence/exacerbation
3.3. Clinical Characteristics of Patients Who Changed from DOACs to Other Anticoagulants
3.4. Risk Factors for a Primary Outcome
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Variables | Values (N = 63) |
---|---|
Age when DOAC was initiated, years | 65.8 (58.6–72.4) |
Age when DOAC was initiated (≥60 years), N (%) | 45 (71.4%) |
Body mass index (kg/m2) | 23.5 (20.4–25.5) |
Category of body mass index, N (%) | |
Underweight (<18.5 kg/m2) | 6 (9.5%) |
Normal range (18.5–24.9 kg/m2) | 40 (63.5%) |
Obesity (≥25.0 kg/m2) | 17 (27.0%) |
Performance status, N (%) | |
0 | 44 (69.8%) |
1 | 13 (20.6%) |
2 | 6 (9.5%) |
Hypertension, N (%) | 15 (23.8%) |
Diabetes mellitus, N (%) | 5 (7.9%) |
Diagnosis of gynecologic malignancies, N (%) | |
Cervical cancer | 8 (12.7%) |
Endometrial cancer | 21 (33.3%) |
Ovarian cancer | 34 (54.0%) |
FIGO stage, N (%) | |
Cervical cancer (FIGO stage I/II) | 7 (11.1%) |
Cervical cancer (FIGO stage III/IV) | 1 (1.6%) |
Endometrial cancer (FIGO stage I/II) | 12 (19.0%) |
Endometrial cancer (FIGO stage III/IV) | 9 (14.3%) |
Ovarian cancer (FIGO stage I/II) | 8 (12.7%) |
Ovarian cancer (FIGO stage III/IV) | 26 (41.3%) |
Pathological diagnosis, N (%) | |
Cervical cancer (SCC) | 5 (7.9%) |
Cervical cancer (Non-SCC) | 3 (4.8%) |
Endometrial cancer (Type I) | 15 (23.8%) |
Endometrial cancer (Type II) | 6 (9.5%) |
Ovarian cancer (Clear) | 9 (14.3%) |
Ovarian cancer (Non-clear) | 25 (39.7%) |
Location of blood clots when VTE was first diagnosed, N (%) | |
Isolated distal DVT | 27 (42.9%) |
PE or proximal VTE without PE was present | 36 (57.1%) |
Event after initiation of DOAC, N (%) | |
No event | 20 (31.7%) |
Recurrence of VTE | 5 (7.95%) |
Change from DOAC to other anticoagulants | 5 (7.95%) |
Discontinuation of DOAC due to progression of gynecologic malignancies | 3 (4.8%) |
Discontinuation of DOAC due to bleeding | 3 (4.8%) |
Discontinuation of DOAC due to the doctor’s discretion | 16 (25.4%) |
Discontinuation of DOAC due to the subject’s self-judgment | 4 (6.3%) |
Death from gynecologic malignancies | 6 (9.5%) |
Death due to other causes | 1 (1.6%) |
Variables | Values (N = 63) |
---|---|
WBC when VTE was first diagnosed (μ/l) | 6600 (5250–8650) |
Tertiles of WBC, N (%) | |
Tertile 1 (<5600/μL) | 22 (34.9%) |
Tertile 2 (≥5600 and <8100/μL) | 20 (31.7%) |
Tertile 3 (≥8100/μL) | 21 (33.3%) |
Hemoglobin when VTE was first diagnosed (g/dL) | 10.8 (9.8–12.2) |
Tertiles of Hemoglobin, N (%) | |
Tertile 1 (<10.1 g/dL) | 22 (34.9%) |
Tertile 2 (≥10.1 and <12.1 g/dL) | 21 (33.3%) |
Tertile 3 (≥12.1 g/dL) | 20 (31.7%) |
Platelet count when VTE was first diagnosed (∗1000/μL) | 308.0 (210.5–396.0) |
Tertiles of Platelet count, N (%) | |
Tertile 1 (<247 ∗ 1000/μL) | 21 (33.3%) |
Tertile 2 (≥247 and <371 ∗ 1000/μL) | 22 (34.9%) |
Tertile 3 (≥371 ∗ 1000/μL) | 20 (31.7%) |
D-dimer level when VTE was first diagnosed (μg/dL) | 5.1 (2.9–9.0) |
Tertiles of D-dimer, N (%) | |
Tertile 1 (<3.8 μg/dL) | 22 (34.9%) |
Tertile 2 (≥3.8 and <7.6 μg/dL) | 20 (31.7%) |
Tertile 3 (≥7.6 μg/dL) | 21 (33.3%) |
Fibrin monomer level when VTE was first diagnosed (μg/dL) | 6.4 (3.2–43.9) |
Tertiles of Fibrin monomer, N (%) | |
Tertile 1 (<4.7 μg/dL) | 19 (30.2%) |
Tertile 2 (≥4.7 and <15.7 μg/dL) | 17 (27.0%) |
Tertile 3 (≥5.7 μg/dL) | 18 (28.6%) |
Missing | 9 (14.3%) |
Patient | #1 | #2 | #3 | #4 | #5 |
---|---|---|---|---|---|
Age when DOAC was initiated, years | 73 | 62 | 57 | 57 | 49 |
Body mass index (kg/m2) | 19 | 27.5 | 24.4 | 20.5 | 21.4 |
Performance status | 1 | 2 | 0 | 0 | 0 |
Hypertension | No | No | No | No | No |
Diabetes mellitus | No | No | No | No | No |
Diagnosis of gynecologic malignancies | Endometrial cancer | Ovarian cancer | Ovarian cancer | Ovarian cancer | Ovarian cancer |
FIGO stage | IV | III | I | III | III |
Pathological diagnosis | Serous carcinoma | Clear cell carcinoma | Endometrioid carcinoma | Clear cell carcinoma | Clear cell carcinoma |
Situation when VTE was first diagnosed | Before first treatment | Before first treatment | Before first treatment | Before first treatment | Before first treatment |
Location of blood clots when VTE was first diagnosed | PE, proximal~distal DVT | proximal~distal DVT, Stroke | proximal DVT | PE, distal DVT | PE, distal DVT |
D-dimer level when VTE was first diagnosed (μg/dL) | 36.9 | 6.6 | 2.3 | 8.9 | 2.8 |
Fibrin monomer level when VTE was first diagnosed (μg/dL) | 150 | 150 | - | 6 | 3 |
Type of first treatment | Radiation therapy | Primary debulking surgery | Complete surgery | Primary debulking surgery | Primary debulking surgery |
Type and amount of DOAC prescribed | Apixaban, 20 mg/day | Apixaban, 10 mg/day | Edoxaban, 30 mg/day | Edoxaban, 30 mg/day | Edoxaban, 30 mg/day |
Duration of DOAC until recurrence/exacerbation of VTE (days) | 5 | 462 | 18 | 18 | 583 |
Situation when VTE recurrence was diagnosed | After first treatment | After chemotherapy | After first treatment | After first treatment | BSC |
Location of blood clots when VTE recurrence was diagnosed | Stroke | Stroke | proximal~distal DVT | PE | PE |
RECIST when VTE recurrence/exacerbation was diagnosed | - | PD | CR | PD | PD |
Cancer-bearing when VTE recurrence was diagnosed | Yes | Yes | No | Yes | Yes |
Adverse events of DOAC | No | No | No | No | No |
Final prognosis | Cause of illness | Cause of illness | Disease-free survival | Cause of illness | Cause of illness |
Patient | #1 | #2 | #3 | #4 | #5 |
---|---|---|---|---|---|
Age when DOAC was initiated, years | 70 | 65 | 63 | 61 | 39 |
Body mass index (kg/m2) | 24.5 | 23.4 | 24 | 21.3 | 28.4 |
Performance status | 0 | 0 | 1 | 1 | 0 |
Hypertension | No | No | No | No | No |
Diabetes mellitus | No | No | No | No | No |
Diagnosis of gynecologic malignancies | Ovarian cancer | Ovarian cancer | Ovarian cancer | Ovarian cancer | Ovarian cancer |
FIGO stage | III | III | III | III | IV |
Pathological diagnosis | Serous carcinoma | Endometrioid carcinoma | Clear cell carcinoma | Serous carcinoma | Serous carcinoma |
Situation when VTE was first diagnosed | Before first treatment | Before first treatment | Before first treatment | Before first treatment | Before first treatment |
Location of blood clots when VTE was first diagnosed | PE, proximal~distal DVT | PE, distal DVT | PE, proximal~distal DVT | PE, distal DVT | PE, distal DVT |
D-dimer level when VTE was first diagnosed (μg/dL) | 14.8 | 17 | 15.5 | 34 | 14.9 |
Fibrin monomer level when VTE was first diagnosed (μg/dL) | 150 | 88.9 | 5.5 | 7.8 | 11.2 |
Type of first treatment | Primary debulking surgery | NAC | NAC | NAC | NAC |
Type and amount of DOAC prescribed | Rivaroxaban, 30 mg/day | Apixaban, 10 mg/day | Edoxaban, 30 mg/day | Edoxaban, 30 mg/day | Edoxaban, 30 mg/day |
Duration of DOAC until a change from a DOAC to another drug (days) | 3 | 19 | 3 | 60 | 5 |
Situation when a change from a DOAC to another drug | Before first treatment | Before first treatment | After first treatment | After first treatment | After first treatment |
An increase in D-dimer or fibrin monomer levels when a change from a DOAC to another drug (μg/dL) | Fib-monomer 5.6 → 33.9 | D-dimer 6.1 → 21.1 | Fib-monomer 4.2 → 21.8 | Fib-monomer 9.1 → 42.9 | Fib-monomer 14 → 48 |
Days until a change from a DOAC to another drug (days) | 3 | 19 | 3 | 60 | 5 |
Cancer-bearing when a change from a DOAC to another drug | Yes | Yes | Yes | Yes | Yes |
Adverse events of DOAC | No | No | No | No | No |
Final prognosis | Disease-free survival | Cancer-bearing survival | Cause of illness | Disease-free survival | Disease-free survival |
Explanatory Variables | Cases/N (%) | Crude OR (95% CI) | p-Value |
---|---|---|---|
Age when DOAC was initiated | |||
≥60 years | 6/39 (13.3) | 0.54 (0.13–2.19) | 0.4 |
<60 years | 4/14 (22.2) | 1.00 (reference) | NA |
BMI * | |||
Underweight (<18.5 kg/m2) | 0/6 (0.0) | 0.29 (0.002–2.94) | 0.4 |
Normal range (18.5–24.9 kg/m2) | 8/40 (20.0) | 1.00 (reference) | NA |
Obesity (≥25.0 kg/m2) | 2/17 (11.8) | 0.62 (0.11–2.58) | 0.5 |
Performance status | |||
0 | 6/44 (13.6) | 1.00 (reference) | NA |
1 | 3/13 (23.1) | 1.90 (0.40–8.96) | 0.4 |
2 | 1/6 (16.7) | 1.27 (0.13–12.8) | 0.8 |
Diagnosis of gynecologic malignancies * | |||
Cervical cancer | 0/8 (0) | 0.8 (0.005–16.7) | 0.9 |
Endometrial cancer | 1/21 (4.8) | 1.00 (reference) | NA |
Ovarian cancer | 9/34 (26.5) | 5.1 (1.04–50.3) | 0.04 |
FIGO stage, all cancers | |||
FIGO stage I/II | 2/27 (7.4) | 1.00 (reference) | NA |
FIGO stage III/IV | 8/36 (22.2) | 3.57 (0.8–25.2) | 0.13 |
Diagnosis of gynecologic malignancies | |||
Clear cell carcinoma | 4/9 (44.4) | 6.4 (1.34–30.6) | 0.02 |
Ovarian cancer other than clear cell carcinoma or cervical cancer or endometrial cancer | 6/54 (11.1) | 1.00 (reference) | NA |
Location of blood clots when VTE was first diagnosed * | |||
PE or proximal DVT without PE | 10/36 (27.8) | 21.8 (2.57–2854.6) | 0.002 |
Isolated distal DVT | 0/27 (0.0) | 1.00 (reference) | NA |
Blood test when VTE was first diagnosed | |||
WBC | |||
Tertile 1 or 2 (<8100/μL) | 5/42 (11.9) | 1.00 (reference) | NA |
Tertile 3 (≥8100/μL) | 5/21 (23.8) | 2.31 (0.59–9.11) | 0.23 |
Hemoglobin | |||
Tertile 1 (<10.1 g/dL) | 3/22 (13.6) | 1.50 (0.22–10.0) | 0.7 |
Tertile 2 (≥10.1 and <12.1 g/dL) | 2/21 (9.5) | 1.00 (reference) | NA |
Tertile 3 (≥12.1 g/dL) | 5/20 (25.0) | 3.17 (0.54–18.7) | 0.2 |
Platelet count | |||
Tertile 1 or 2 (<37.1 × 104/μL) | 6/43 (14.0) | 1.00 (reference) | NA |
Tertile 3 (≥37.1 × 104/μL) | 4/20 (20.0) | 1.54 (0.38–6.22) | 0.5 |
D-dimer | |||
Tertile 1 or 2 (<7.6 μg/dL) | 3/42 (7.1) | 1.00 (reference) | NA |
Tertile 3 (≥7.6 μg/dL) | 7/21 (33.3) | 6.5 (1.47–28.67) | 0.01 |
Fibrin monomer * | |||
Tertile 1 or 2(<15.7 μg/dL) | 5/36 (13.9) | 1.00 (reference) | NA |
Tertile 3 (≥15.7 μg/dL) | 4/18 (22.2) | 1.78 (0.42–7.25) | 0.42 |
Missing | 1/9 (11.1) | 1.01 (0.09–6.12) | 0.99 |
Explanatory Variables | Adjusted OR (95% CI) | p-Value |
---|---|---|
Diagnosis of gynecologic malignancies | ||
Clear cell carcinoma of the ovary | 18.9 (2.25–350.74) | 0.005 |
Ovarian cancer (other than clear cell carcinoma), cervical cancer, or endometrial cancer | 1.00 (reference) | NA |
Location of blood clots when VTE was first diagnosed | ||
PE or proximal DVT without PE | 55.6 (3.29–11,774.66) | 0.001 |
Isolated distal DVT | 1.00 (reference) | NA |
D-dimer level when VTE was first diagnosed | ||
Tertile 1 or 2 (<7.6 μg/dL) | 1.00 (reference) | NA |
Tertile 3 (≥7.6 μg/dL) | 6.37 (1.17–66.61) | 0.03 |
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Shimizu, T.; Iwama, N.; Tokunaga, H.; Endo, S.; Miyahara, S.; Toki, A.; Watanabe, Z.; Minato, J.; Hashimoto, C.; Ishibashi, M.; et al. Precautions during Direct Oral Anticoagulant Introduction in Gynecologic Malignancies: A Single-Center Retrospective Cohort Study. Cancers 2023, 15, 1132. https://doi.org/10.3390/cancers15041132
Shimizu T, Iwama N, Tokunaga H, Endo S, Miyahara S, Toki A, Watanabe Z, Minato J, Hashimoto C, Ishibashi M, et al. Precautions during Direct Oral Anticoagulant Introduction in Gynecologic Malignancies: A Single-Center Retrospective Cohort Study. Cancers. 2023; 15(4):1132. https://doi.org/10.3390/cancers15041132
Chicago/Turabian StyleShimizu, Takanori, Noriyuki Iwama, Hideki Tokunaga, Shun Endo, Shuko Miyahara, Asami Toki, Zen Watanabe, Junko Minato, Chiaki Hashimoto, Masumi Ishibashi, and et al. 2023. "Precautions during Direct Oral Anticoagulant Introduction in Gynecologic Malignancies: A Single-Center Retrospective Cohort Study" Cancers 15, no. 4: 1132. https://doi.org/10.3390/cancers15041132
APA StyleShimizu, T., Iwama, N., Tokunaga, H., Endo, S., Miyahara, S., Toki, A., Watanabe, Z., Minato, J., Hashimoto, C., Ishibashi, M., Shigeta, S., Shimada, M., & Yaegashi, N. (2023). Precautions during Direct Oral Anticoagulant Introduction in Gynecologic Malignancies: A Single-Center Retrospective Cohort Study. Cancers, 15(4), 1132. https://doi.org/10.3390/cancers15041132