Patient characteristics
2491 patients were screened for eligibility, of which 907 patients were enrolled in the present study. The inclusion flowchart is presented in Figure A. Table 1. displays the baseline characteristics of the study population. The median age of the population was 84 years (IQR 78–88), 615 were female (68%), and 56% had an ASA score ≥ 3. Subgroup analysis was performed for patients using vitamin K antagonists and antiplatelet therapy. Both groups were compared to each other and to patients who did not use anticoagulants (Table 2). As seen in Table 2, there are differences between the three groups in all baseline characteristics excluding the variables; preoperatively hemoglobin level, BMI and type of anesthesia. Three subgroups were compared (AP vs. VKA), (AP vs. no anticoagulation) and (VKA vs. no anticoagulation) to determine differences between anticoagulation types.
Table 1
Baseline characteristics of the 907 included patients
Factor
|
Overall (907)
|
No anticoagulation (492)
|
Anticoagulation (415)
|
P-value*
|
Age (median (IQR)
|
84 (78–88)
|
83 (76–88)
|
84 (79–88)
|
0.046₸
|
Female Gender (obs (%))
|
615/907 (67.8)
|
355/492 (72.2)
|
260/415 (62.7)
|
0.002*
|
NHFS (median (IQR))
|
5 (4–6)
|
5 (4-5.5)
|
5 (4–5)
|
0.003¥
|
ASA score
|
|
|
|
0.000*
|
1–2 (obs, %)
|
393/898 (43.8)
|
263/487 (54.0)
|
130/411 (31.6)
|
|
3–4 (obs, %)
|
505/898 (56.2)
|
224/487 (46.0)
|
281411 (68.4)
|
|
Preoperatively Hb level (mean (± SD))
|
7.98 (0.03)
|
8.01 (0.04)
|
7.93 (0.05)
|
0.179₸
|
Preoperatively GFR (mean (± SD))
|
66.0 (21.6)
|
69.0 (20.0)
|
62.4 (22.9)
|
0.000¥
|
BMI
|
|
|
|
0.186*
|
< 18.5 (obs (%))
|
38/583 (6.5)
|
20/287 (7.0)
|
18/296 (6.1)
|
|
18.5–30 (obs (%))
|
487/583 (83.5)
|
245/287 (85.4)
|
242/296 (81.8)
|
|
> 30 (obs (%))
|
58/583 (10.0)
|
22/287 (7.6)
|
36/296 (12.1)
|
|
Time to surgery (median (IQR))
|
20.4 (14.5–26.6)
|
19.6 (13.4–24.6)
|
21.5 (15.3–30.6)
|
0.721¥
|
Anesthesia
|
|
|
|
0.004*
|
Spinal (obs (%))
|
777/902 (86.1)
|
437/490 (89.2)
|
340/412 (82.5)
|
|
General (obs (%))
|
125/902 (13.9)
|
53/490 (10.8)
|
72/412 (17.5)
|
|
Notes: *Pearson’s Chi-squared test, ₸ Student’s t-test, ¥ Wilcoxon rank-sum test
Abbreviations: NHFS. Nottingham Hip Fracture Score; Hb. Hemoglobin in mmol/L; GFR. glomerular filtration rate in ml/min/1.73m^2; ASA. American Society of Anesthesiology; BMI. Body Mass Index
Anticoagulation therapy is vitamin K antagonists and antiplatelet therapy combined.
|
Table 2
Baseline characteristics of subgroups
Factor
|
No anticoagulation (492)
|
Vitamin k antagonists (141)
|
Antiplatelet therapy (213)
|
P-value*
|
Age (median (IQR)
|
83 (76–88)
|
84 (80–88)
|
84 (79–88)
|
0.034^
|
Female Gender (obs (%))
|
355/492 (72.2)
|
92/142 (64.8)
|
132/213 (61.8)
|
0.017*
|
NHFS (median (IQR))
|
5 (4-5.5)
|
5 (4–6)
|
5 (4–6)
|
0.015”
|
ASA score
|
|
|
|
< 0.001*
|
1–2 (obs, %)
|
263/487 (54.0)
|
35/141 (24.8)
|
83/211 (39.3)
|
|
3–4 (obs, %)
|
224/487 (46.0)
|
106/141 (75.2)
|
128/211 (60.7)
|
|
Preoperative Hb level (mean (± SD))
|
8.01 (0.92)
|
7.96 (1.02)
|
7.92 (0.91)
|
0.421^
|
Preoperative GFR (mean (± SD))
|
69.0 (20.0)
|
59.0 (21.4)
|
64.4 (23.3)
|
< 0.001”
|
BMI
|
|
|
|
0.434*
|
< 18.5 (obs (%))
|
20/287 (7.0)
|
7/100 (7.0)
|
10/154 (6.5)
|
|
18.5–30 (obs (%))
|
245/287 (85.4)
|
79/100 (79.0)
|
127/154 (84.5)
|
|
> 30 (obs (%))
|
22/287 (7.6)
|
14/100 (14.0)
|
17/154 (11.0)
|
|
Time to surgery (median (IQR))
|
19.6 (13.4–24.6)
|
24.4 (18.5–37.0)
|
18.8 (13.1–24.8)
|
< 0.001”
|
Anesthesia
|
|
|
|
0.350*
|
Spinal (obs (%))
|
437/490 (89.2)
|
125/142 (88.0)
|
180/211 (85.3)
|
|
General (obs (%))
|
53/490 (10.8)
|
17/142 (12.0)
|
31/211 (14.7)
|
|
Notes: *Pearson’s Chi-squared test, ₸ Student’s t-test, ¥ Wilcoxon rank-sum test, “Kurskal-Wallis, ^linear regression
Abbreviations: NHFS. Nottingham Hip Fracture Score; Hb. Hemoglobin in mmol/L; GFR. glomerular filtration rate in ml/min/1.73m^2; ASA. American Society of Anesthesiology; BMI. Body Mass Index
|
Patients using antiplatelet therapy compared to no anticoagulation
Patients using AP were significantly older than patients who did not use anticoagulantion (84 years versus 82 years, P = 0.03). Also, less female patients were found in the AP group compared to no anticoagulation use (132 (62%) versus 355 (72%), P = 0.007). Higher NHFS score was found in the AP group (5 (4–6) versus 5 (4–6), P = 0.009), and high ASA score (ASA score ≥ 3) was found in the AP group (128 patients (61%) versus 224 patients (46%), P = < 0.001).
Patients using vitamin K antagonists compared to no anticoagulation
When VKA use was compared to no anticoagulation, higher ASA score (ASA score ≥ 3) was found (106 patients (75%) versus 224 patients (46%), P = < 0.001). Also, prolonged time to surgery was found when VKA was compared to no anticoagulation use, 24.4 hours (18.5–37.0) versus 19.6 hours (13.4–24.6), P = < 0.001.
Patients using vitamin K antagonists compared to antiplatelet therapy
Prolonged time to surgery was found when vitamin K was compared to AP (24.4 hours (18.5–37.0) versus 18.8 (13.1–24.8), P = < 0.001, respectively).
International normalized ratio
At admission, mean INR for patients using vitamin K antagonists was 3.19 (± 1.71). The mean preoperative INR after correction was 1.48 (± 0.25). Correction was performed using vitamin K in 55% of the patients and in 9% of the patients additional prothrombin complex concentrate was necessary besides vitamin K. In 8% of the patients receiving correction of the INR, only a prothrombin complex concentrate was used. 22% of the patients using vitamin K antagonists received no correction. Of these patients, 12 had an INR ≤ 1.5 (1.2 (± 0.2)) and eight-teen patients had an INR > 1.5 (2.1 (± 0.4)). No complications occurred in the last group. Two patients with an INR > 1.5 without correction received general anesthesia.
Outcome measures
Univariable analysis was performed on perioperative variables as displayed in Table 3. No difference was found in the 30-day mortality (9% without anticoagulation versus 10% with anticoagulation, P = 0.620) nor the 1-year mortality between the groups who did and who did not use anticoagulation drugs (26% versus 29% respectively, P = 0.287).
Table 3
Univariable analysis no anticoagulation use versus anticoagulation use
Factor
|
Overall (907)
|
No anticoagulation (492)
|
Anticoagulation (415)
|
P-value
|
Surgery time (min)
|
|
|
|
0.664*
|
< 45 min(obs (%))
|
132/903 (14.6)
|
75/490 (15.3)
|
57/413 (13.8)
|
|
≥ 45 min, < 90 min (reference) (obs (%))
|
665 /903 (73.7)
|
361/490 (73.7)
|
304/413 (73.6)
|
|
≥ 90 min (obs (%))
|
106/903 (11.7)
|
54/490 (11.0)
|
52/413 (12.6)
|
|
Minimally invasive surgical approach (obs (%))
|
223/906 (24.6)
|
120/491 (24.4)
|
103/415 (24.8)
|
0.895*
|
Hb loss (mmol/L) (mean ± SD)
|
1.59 (0.87)
|
1.53 (0.80)
|
1.64 (0.93)
|
0.053¥
|
Estimated blood loss (mL) (mean ± SD)
|
238.2 (143.8)
|
237.9 (136.6)
|
237.1 (144.9)
|
0.738¥
|
Packed cell supplementation (units) (mean ± SD)
|
0.23 (0.75)
|
0.15 (0.61)
|
0.33 (0.88)
|
< 0.001¥
|
Pain day 1 (VAS) (mean ± SD)
|
2.40 (2.16)
|
2.24 (2.01)
|
2.60 (2.27)
|
0.030¥
|
Postoperative drain (obs (%))
|
544/900 (60.4)
|
300/488 (61.5)
|
244/412 (59.2)
|
0.491*
|
Haematoma (obs (%))
|
122/803 (15.2)
|
49/429 (11.4)
|
73/374 (19.5)
|
0.001*
|
Reoperation for haematoma (obs (%))
|
11/888 (1.2)
|
6/484 (1.2)
|
5/404 (1.2)
|
0.998*
|
Reoperation for luxation (obs (%))
|
18/888 (2.0)
|
9/484 (1.9)
|
9/404 (2.2)
|
0.698*
|
Deep SSI (obs (%))
|
44/883 (5.0)
|
26/481 (5.4)
|
18/402 (4.5)
|
0.528*
|
Ready for discharge (days) (median (IQR))
|
5 (3–7)
|
4 (3–7)
|
5 (3–8)
|
0.006¥
|
Re-admission (obs (%))
|
83/879 (9.4)
|
46/479 (9.6)
|
37/400 (9.3)
|
0.858*
|
Mortality
|
|
|
|
|
30-day mortality
|
87/907 (9.6)
|
45/492 (9.2)
|
42/415 (10.1)
|
0.620*
|
One-year mortality
|
251/907 (27.7)
|
129/492 (26.2)
|
122/415 (29.4)
|
0.287*
|
Notes: *Pearson’s Chi-squared test, ¥ Wilcoxon rank-sum test,
Abbrevations: Hb. Haemoglobin in mmol/L; VAS. Visual Analogue Scale; SSI. Surgical Site Infection.
Anticoagulation therapy is vitamin K antagonists and antiplatelet therapy combined.
|
More packed cells were supplemented in patients using anticoagulation compared to patients without anticoagulation, 0.33 (± 0.88) units versus 0.15 (± 0.61) units, respectively. Hematoma’s were reported more frequently in patients with anticoagulation use compared to patients without anticoagulation, 20% vs. 11%, P = 0.001, respectively. Also more pain was reported in patients with anticoagulation with a reported VAS of 2.60 (± 2.27) versus 2.24 (± 2.01) P = 0.030, one day post-surgery. There was no statistically significant difference in the frequency of post-surgery placed wound drains.
Subgroup analysis are displayed in Table 4. Both vitamin K antagonists and antiplatelet therapy were associated with more packed cell supplementation compared to no anticoagulation use (0.44 units versus 0.15 units, P = < 0.001, and 0.26 units versus 0.15 units, P = 0.026 respectively). Also, the use of vitamin K antagonists was associated with a higher incidence of hematomas compared to no anticoagulation (23% versus 11%, P = 0.001). No association for the occurrence of hematoma was found between the other subgroups. At last, patients who used vitamin K antagonists needed more days to be ready for discharge compared to no anticoagulation, 5.5 days (4–9) versus 4 days (3–7), P = < 0.001.
Table 4
Univariable subgroup analysis
Factor
|
No anticoagulation (492)
|
Vitamin K antagonist (141)
|
Antiplatelet therapy (213)
|
P-value*
|
Surgery time (min)
|
|
|
|
0.711*
|
< 45 min(obs (%))
|
75/490 (15.3)
|
22/141 (15.6)
|
26/212 (15.6)
|
|
≥ 45 min, < 90 min (reference) (obs (%))
|
361/490 (73.7)
|
100/141 (70.9)
|
163/212 (76.9)
|
|
≥ 90 min (obs (%))
|
54/490 (11.0)
|
19/141 (13.5)
|
23/212 (10.9)
|
|
Minimally invasive surgical approach (obs (%))
|
120/491 (24.4)
|
43/142 (30.3)
|
47/213 (22.1)
|
0.205*
|
Hb loss (mmol/l) (mean ± SD)
|
1.53 (0.80)
|
1.59 (1.05)
|
1.62 (0.9)
|
0.323”
|
Estimated blood loss (mL) (mean ± SD)
|
237.9 (136.6)
|
242.8 (149.4)
|
235.3 (136.8)
|
0.946”
|
Packed cell supplementation (units) (mean ± SD)
|
0.15 (0.6)
|
0.44 (1.1)
|
0.26 (0.8)
|
< 0.001”
|
Pain day 1 (VAS) (mean ± SD)
|
2.24 (2.0)
|
2.62 (2.4)
|
2.56 (2.2)
|
0.158”
|
Postoperative drain (obs (%))
|
300/488 (61.5)
|
83/142 (58.5)
|
129/210 (61.4)
|
0.799*
|
Haematoma (obs (%))
|
49/429 (11.4)
|
30/130 (23.1)
|
30/188 (16.0)
|
0.004*
|
Reoperation for haematoma (obs (%))
|
6/484 (1.2)
|
3/136 (2.2)
|
1/208 (0.5)
|
0.357*
|
Reoperation for luxation (obs (%))
|
9/484 (1.9)
|
2/136 (1.5)
|
7/208 (3.4)
|
0.381*
|
Deep SSI (obs (%))
|
26/481 (5.4)
|
7/135 (5.2)
|
8/207 (3.9)
|
0.691*
|
Ready for discharge (days) (median (IQR))
|
4 (3–7)
|
5.5 (4–9)
|
4 (3–7)
|
< 0.001”
|
Re-admission (obs (%))
|
46/479 (9.6)
|
18/136 (13.2)
|
15/204
|
0.198*
|
Mortality
|
|
|
|
|
30-day mortality
|
45/492 (9.2)
|
18/142 (12.7)
|
20/213 (9.4)
|
0.448*
|
One-year mortality
|
129/492 (26.2)
|
47/142 (33.1)
|
59/213 (27.7)
|
0.272*
|
Notes: *Pearson’s Chi-squared test, ₸ Student’s t-test, ¥ Wilcoxon rank-sum test, “Kurskal-Wallis, ^linear regression
Abbreviations: Abbrevations: Hb. Haemoglobin in mmol/L; VAS. Visual Analogue Scale; SSI. Surgical Site Infection.
|
Clopidogrel (Plavix)
Twenty-three patients used clopidogrel (Plavix). The median age of these patients was 85 years (78–90), and 74% was female. A median NHFS of 5 (4–6) was found, and 78% of the patients had an ASA score ≥ 3. A mean preoperative hemoglobin level of 7.9 (7.4–8.4) was found, and a mean preoperative GFR of 72 (56–85). For BMI, 83% of the patients had a BMI between 18.5 and 30. Time to surgery showed a median of 22.8 hours (17.8–26.9) and most patients (70%) received spinal anesthesia. For clopidogrel the mean Hb loss was 1.5 mmol/L (1-2.2). The estimated blood loss was 238 mL (± 143) and the number of units of packed cells supplemented was 0.23 (± 0.75).