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Research Article: Observational Study

Changes in hemostatic factors after kidney transplantation

A retrospective cohort study

Jun, Kang Woong MDa; Cho, Jinbeom MD, PhDa; Kim, Mi Hyeong MD, PhDb; Hwang, Jeong Kye MD, PhDb; Park, Sun Cheol MD, PhDc; Moon, In Sung MD, PhDd; Kim, Ji Il MD, PhDe,∗

Editor(s): Chen., Robert

Author Information
doi: 10.1097/MD.0000000000027179
  • Open

Abstract

1 Introduction

Chronic kidney disease (CKD) affects hemostasis through various complex mechanisms, and in end-stage renal disease (ESRD), patients can experience both thrombotic complications and bleeding diathesis.[1] Hemorrhagic diathesis is attributed to the accumulation of protein degradation products, leading to reduced platelet production, platelet dysfunction, vessel wall damage, and deficiency of clotting factors II, V, IX, and X. ESRD-associated anemia also contributes to platelet dysfunction.[2] Hypercoagulability is attributed to changes in the coagulation cascade, with increased fibrinogen, plasma tissue factor, clotting factors XIIa and VIIa, activated protein C (PC), thrombin-antithrombin complexes, d-dimers, and prothrombin fragments, as well as reduced antithrombin III (AT III) activity.[3]

The effects of kidney transplantation (KT) on coagulation profiles and postoperative thrombotic complications are controversial. KT is a major operation, which can increase thromboembolic complications in CKD patients.[4] Deira et al[5] reported significantly decreased AT III and PC activity on the first postoperative day (POD), suggesting an increased thrombosis risk. Other studies reported correction of hypercoagulability after KT.[6,7]

This study was performed to characterize prothrombotic factor activity in patients with CKD before and after KT, and to analyze changes in these factors after KT.

2 Materials and methods

This retrospective single-center study was approved by the institutional review board of Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Korea (KC20RISI0792). From December 2009 to December 2014, 676 individuals with CKD underwent KT at our institute. We excluded 309 patients meeting these criteria: plasmapheresis before or after KT; early allograft failure (≤1 month); or anticoagulant or antiplatelet agents ≤1 month before or after (eg, newly diagnosed coronary arterial disease (CAD), symptomatic venous thromboembolism (VTE), and so on after KT (Fig. 1). Thus, 367 recipients were included in the study.

Figure 1
Figure 1:
Flow sheet of patients’ selection.

2.1 Data collection

We collected the following information from electronic medical records: demographics, CKD etiology, type of renal replacement therapy (RRT), number of mismatched human leukocyte antigens, type of immunosuppressive agents, episodes of acute rejection, or delayed graft function (DGF); defined as an acute kidney injury, which necessitates a dialysis intervention in the first week of kidney transplantation; within a month post–KT, and bleeding/thrombotic events. Blood samples for coagulation factors were collected the day before transplantation and on POD7, 14, and 28. The following hemostatic parameters were prospectively analyzed (reference ranges in parentheses): hemoglobin (12–16 g/dL); platelet count (140–400 × 109/L); prothrombin time (70%–125.7%); activated partial thromboplastin time (APTT; 21.9–36.7 seconds); international normalized ratio (0.89–1.2); d-dimer (≤0.6 mg/dL); fibrinogen (160–350 mg/dL); protein S (PS) activity (60%–120%); PC activity (70%–130%); AT III activity (80%–120%); homocysteine (3–15 μmol/L); lupus anticoagulant (LA; ≤1:3 on screening test/confirmation test); anticardiolipin (aCL) IgG (<10 U/mL); aCL IgM and IgA (absent on qualitative test); clotting factor VIII (60%–150%); and clotting factor IX (60%–150%). Data regarding inherited disorders, such as factor V Leiden mutation and prothrombin G20210A mutations, and platelet adhesion-aggregation tests were too scarce to analyze in this study. Prothrombotic factors were defined as follows: decreased PS activity; decreased PC activity; decreased AT III activity; increased homocysteine; presence of LA; presence of aCL (IgG, IgA, or IgM); increased factor VIII level; or increased factor IX level.

2.2 Postoperative imaging

Patients at our institute routinely undergo color duplex ultrasound on POD1, 7, 14, and 28 and magnetic resonance angiography on POD7 or 14 to evaluate the condition of the graft kidney (perfusion and renal artery resistive index) and the presence of peri-graft fluid (hematoma or lymphocele) or hydronephrosis. Magnetic resonance angiography is performed on POD7 in cases with multiple donor renal arteries or suboptimal environments of the donor renal artery or recipient iliac artery, such as heavy calcifications or atheroma of the artery. To detect lower extremity deep DVT, we perform bilateral, whole-leg color duplex ultrasound on POD7, 14, and 28, or at any time when clinically indicated.[8] When bleeding is suspected (eg, suddenly decreased blood pressure and hemoglobin or bloody discharge in the Jackson-Pratt drains [Cardinal Health, Waukegan, IL]), we perform nonenhanced abdominal computed tomography to assess hematoma around the allograft kidney.

2.3 Immunosuppressive regimen

The typical immunosuppressive regimen at our institute was described previously.[9] All kidney recipients receive basiliximab (Simulect, Novartis Pharmaceuticals Co., Basel, Switzerland) 20 mg on POD0 and 4 or antithymocyte globulin (ATG) (Thymoglobulin, Sanofi Genzyme, Cambridge, MA) 1.25 mg/kg from POD0 to 4 as induction immunosuppressants (in case of highly sensitized patients or expanded criteria deceased donor). Maintenance immunosuppression consists of tacrolimus (Tacrobell, Chong Kun Dang Pharmaceuticals Co., Seoul, Korea; Prograf, Astellas Pharma Inc., Toyama, Japan), corticosteroid, and either mycophenolate mofetil (Cellcept, Hoffmann-La Roche Inc., Nutley, NJ) or mycophenolate sodium (Myfortic, Novartis Pharmaceuticals Co.).

2.4 Surgery

Recipient surgery was performed through an extraperitoneal “hockey stick” incision with creation of standard vascular anastomoses and extravesical ureteroneocystostomy. JP drains remained in the extraperitoneal space until drainage was <50 mL/day for 2 consecutive days.

2.5 Statistical analysis

Summary statistics are presented as frequency (percentage) for categorical variables and median (range) for continuous variables. χ2 and Fisher exact test were used to compare categorical variables. Kruskal-Wallis test was used to compare continuous variables because the normality assumption was not satisfied with the Kolmogorov-Smirnov test. Repeated measures data were analyzed using a generalized linear mixed model to compensate for missing data, and distribution conditions for each variable are expressed as mean ± standard error. Bonferroni correction was used because of multiple comparisons. Two-sided P values <.05 were considered statistically significant. All analyses were performed using SAS 9.4 software (SAS Institute, Inc., Cary, NC).

3 Results

Table 1 summarizes demographics and short-term (≤1 month) outcomes post-KT of the 367 patients in this study. Deceased-donor KT accounted for 36.8% (135/367) of transplants, acute rejection occurred in 4.1% (15/367) of patients, and DGF occurred in 3.3% (12/367) of patients. All patients with DGF received kidneys from deceased donors.

Table 1 - Demographic characteristics and surgical outcomes according to pre-operative renal replacement therapy.
Total (n = 367) HD (n = 209) PD (n = 90) None (n = 68) P
Age, y 44.0 (32.3–55.8) 43.8 (31.9–55.7) 45.9 (35.2–55.7) 42.5 (39.0–46.0) .13
Sex (male/female) 220/147 127/82 56/34 37/31 .57
History of smoking (n) 35 (9.5) 20 (9.6) 9 (10) 6 (8.8) .97
BMI, kg/m2 23.0 (19.5–26.5) 22.4 (19.2–28.6) 22.8 (21.7–26.7) 22.7 (19.0–26.4) <.05
Cause of ESRD (n) <.05
CGN 137 (37.3) 74 (35.4) 33 (36.7) 30 (44.1)
 DM 42 (11.4) 26 (12.4) 12 (13.3) 4 (5.9)
 Hypertension 74 (20.2) 45 (21.4) 26 (28.9) 3 (4.4)
 Others 114 (31.1) 64 (30.6) 19 (21.1) 31 (45.6)
Type of donor (n) < .05
 Living 232 (63.2) 128 (61.2) 37 (41.1) 67 (98.5)
 Deceased 135 (36.8) 81 (38.8) 53 (58.9) 1 (1.5)
No. of KT (n) <.05
 1st 330 (89.92) 185 (88.52) 87 (96.67) 58 (85.29)
 2nd < 37 (10.08) 24 (11.48) 3 (3.33) 10 (14.71)
Mismatch no. of HLA (n) .41
0 34 (9.3) 20 (9.6) 6 (6.7) 8 (11.8)
 1 12 (3.3) 7 (3.4) 0 5 (7.4)
 2 65 (17.7) 37 (17.7) 16 (17.8) 12 (17.7)
 3 95 (26) 51 (24.4) 25 (27.8) 19 (27.9)
 4 67 (18.3) 43 (20.6) 17 (18.9) 7 (10.3)
 5 65 (17.7) 35 (16.8) 19 (21.1) 11 (16.2)
 6 29 (7.9%) 16 (7.7) 7 (7.8%) 6 (8.8%)
Acute rejection within a month (n) 15 (4.1%) 13 (6.2%) 1 (1.1%) 1 (1.5%) .07
Delayed graft function (n) 12 (3.3%) 7 (3.3%) 5 (5.6%) 0 (0) .15
Values are presented as number (%) for categorical variables, and median (interquartile range) for continuous variables.P values are calculated by Kruskal–Wallis test for continuous variables and χ2 or fisher test for categorical variables.BMI = body mass index, CGN = chronic glomerular nephritis, DM = diabetes mellitus, HD = hemodialysis, HLA = human leukocyte antigen, KT = kidney transplantation, PD = peritoneal dialysis.

Table 2 shows prothrombotic factors pre- and post-KT in each RRT subgroup (hemodialysis [HD], peritoneal dialysis [PD], and preemptive). Pre-transplantation, hemoglobin was below normal and d-dimer and homocysteine levels were above normal in all subgroups. Fibrinogen was within normal range, except in PD which was above normal. Platelet counts, prothrombin time, APTT, fibrinogen, PS activity, and PC activity were normal. The following factors significantly differed according to dialysis modality pre-transplantation: hemoglobin, and D-dimer were higher in HD patients than PD patients; and fibrinogen, PS activity, PC activity, AT III, and homocysteine were higher in PD patients than HD patients (P < .05). After KT, most prothrombotic factors differed significantly from pre-KT values (Table 2). Hemoglobin decreased from 10.5 ± 1.7 g/dL pre-KT to 9.5 ± 1.3 mg/dL and 9.6 ± 1.2 g/dL on POD7 and 14, but rose to almost normal on POD28 (11.4 ± 1.3 g/dL) (P < 0.05). d-dimer was increased pre-KT (1.3 ± 1.4 mg/dL) and remained above normal on POD7, 14, and 28 (2.7 ± 2.1, 2.0 ± 1.9, and 1.7 ± 1.5 mg/dL, respectively), with no significant differences from pre-KT. Homocysteine decreased from 21.9 ± 14.5 μmol/L pre-KT to normal on POD7, 14, and 28 (12.4 ± 7.8, 12.4 ± 6.8, and 14.5 ± 6.0 μmol/L, respectively) (P < .05). For the entire group, fibrinogen remained in the normal range pre- and post-KT. However, in the PD subgroup, fibrinogen was increased pre-KT (386.5 ± 78.7 mg/dL) and decreased on POD7, 14, and 28 (242.7 ± 72.7, 286.3 ± 93.9, and 283.1 ± 80.5 mg/dL, respectively) (P < .05). PC activity was higher post-KT than pre-KT but remained in the normal range throughout the study in all subgroups (P < .05). LA and aCL rates were lower at POD28 than pre-KT (7.1% vs 0.8% and 13.6% vs 4.0%, respectively) (P < .05). Elevated factor VIII rates did not differ throughout the study. Prevalence of increased factor IX was significantly higher on POD7, 14, and 28 than pre-KT (P < .05).

Table 2 - Comparison of the prothrombotic factors before and after kidney transplantation in each patient group.
Pre-transplantation 7th POD 14th POD 28th POD P
Hemoglobin, g/dL Total 10.5 ± 1.7 9.5 ± 1.3 9.6 ± 1.2 11.4 ± 1.3 <.05
HD 10.9 ± 1.8 9.6 ± 1.3 9.5 ± 1.3 11.3 ± 1.3 <.05
PD 10.3 ± 1.7 9.3 ± 1.2 9.7 ± 1.3 11.4 ± 1.3 <.05
None 9.8 ± 1.3 9.3 ± 1.1 9.4 ± 1.1 11.4 ± 1.3 <.05
P < .05 P = .29 P = .55 P = .74
Platelet (×109/L) Total 185.6 ± 59 161.6 ± 57 183.2 ± 60.9 214.5 ± 72.6 <.05
HD 179.7 ± 56.4 162.9 ± 61.4 183.5 ± 64.5 211.8 ± 75.4 <.05
PD 195.6 ± 65.3 155.7 ± 56.6 182.7 ± 62.3 214.3 ± 74.3 <.05
None 190.5 ± 56.3 165.1 ± 41.5 182.9 ± 47.1 223.4 ± 61.2 <.05
P = .10 P = .24 P = .95 P = .23
PT (%) Total 91.6 ± 13.2 84.6 ± 15.4 96.7 ± 13.6 110.4 ± 17.1 < .05
HD 92.4 ± 12.6 84.3 ± 15.6 96.9 ± 13.4 111.7 ± 16.7 <.05
PD 93.2 ± 14.9 85 ± 15.8 95.3 ± 15.3 106 ± 20.3 <.05
None 87.2 ± 11.5 85 ± 14.3 97.8 ± 11.7 112.2 ± 11.8 <.05
P < .05 P = .70 P = .77 P = .09
APTT, s Total 26.9 ± 5.9 25.8 ± 5.8 23.9 ± 5 22.5 ± 6.1 <.05
HD 27.3 ± 6.8 26.4 ± 6.3 23.9 ± 4.2 22.4 ± 4 <.05
PD 26 ± 4.3 25.1 ± 5.3 24.4 ± 7.2 23.5 ± 10.2 <.05
None 27 ± 4.4 25.1 ± 4.8 23.2 ± 3.9 21.5 ± 2.8 <.05
P = .07 P < .05 P = .51 P = .38
d-dimer, mg/dL Total 1.3 ± 1.4 2.7 ± 2.1 2 ± 1.9 1.7 ± 1.5 .24
HD 1.1 ± 0.8 2.7 ± 2 2.1 ± 2.2 1.6 ± 1.6 .24
PD 1.0 ± 0.9 2.4 ± 2.4 1.8 ± 1.4 1.7 ± 1.3 .06
None 1.3 ± 1 3.1 ± 1.8 2 ± 1.2 1.6 ± 1.1 .31
P < .05 P < .05 P = .25 P = .30
Fibrinogen, mg/dL Total 322.4 ± 89.3 215.3 ± 70.3 241.3 ± 92.2 264 ± 84.2 < .05
HD 295.9 ± 80.6 207.4 ± 65.9 230.9 ± 86.3 266.2 ± 85.4 <.05
PD 386.5 ± 78.7 242.7 ± 72.7 286.3 ± 93.9 283.1 ± 80.5 <.05
None 325.3 ± 88.1 205.4 ± 72 218.5 ± 90.4 234.9 ± 80.3 <.05
P < .05 P < .05 P < .05 P = .05
PS activity (%) Total 90.9 ± 32.1 66.2 ± 22.4 76.5 ± 26.2 93.8 ± 37 .89
HD 86.9 ± 30.7 65.2 ± 22 76.2 ± 25.2 93.4 ± 46.3 .37
PD 98.3 ± 33.1 65.6 ± 23.8 76.7 ± 27.7 95.5 ± 22.9 .28
None 93.4 ± 33.5 69.4 ± 22.1 76.8 ± 27.4 92.8 ± 21.1 .76
P < .05 P = .57 P = .98 P = .67
PC activity (%) Total 100.6 ± 22.7 102.4 ± 24.8 119.6 ± 26 127.6 ± 23.1 <.05
HD 99.2 ± 21.4 101 ± 24.3 119.1 ± 26.9 124.3 ± 25.5 <.05
PD 108.2 ± 24.5 102.7 ± 27.9 119 ± 23.6 129.3 ± 20.9 <.05
None 94.7 ± 21.6 105.8 ± 22.6 121.7 ± 26.6 134.2 ± 17.5 <.05
P < .05 P = .45 P = .57 P = .21
ATIII activity Total 87 ± 13.9 88.1 ± 14 101.4 ± 14.8 109.9 ± 13.5 <.05
(%) HD 84.2 ± 13.7 88.5 ± 13 101.8 ± 14.6 110.5 ± 10.1 <.05
PD 91.9 ± 13.3 88.1 ± 15.1 99 ± 16.6 105.5 ± 20.7 <.05
None 89.2 ± 13.1 87 ± 15.5 103 ± 13.2 113.8 ± 7.8 <.05
P = .49 P = .80 P = .41 P = .33
Homocystein, μmol/L Total 21.9 ± 14.5 12.4 ± 7.8 12.4 ± 6.8 14.5 ± 6 <.05
HD 19.6 ± 13 12.3 ± 8.7 12.6 ± 7.8 14.1 ± 4.8 <.05
PD 23.3 ± 12 12.7 ± 6.4 11.3 ± 5.5 14.4 ± 7.9 <.05
None 27.2 ± 19.7 12.4 ± 6.7 13.1 ± 5.4 15.7 ± 6.2 <.05
P < .05 P = .27 P = .11 P = .45
LA (%) Total 7.1 2.1 0.4 0.8 <.05
HD 7.3 1.2 0 0 <.05
PD 9 4.4 1.5 3.3 .18
None 4.4 1.7 0 0 .07
P = .54 P = .28 P = .45 P = .45
aCL (%) Total 13.6 10.0 8.0 4.0 <.05
HD 15.5 12.4 10.8 2.9 <.05
PD 11.9 5.8 5.7 6.7 .24
None 10.3 8.5 3.3 3.9 .12
P = .49 P = .29 P = .14 P = .83
Factor VIII Total 34.4 50 61.8 33.3 .06
HD 25 33.3 66.7 50 .13
PD 50 80 66.7 0 .42
None 30 40 50 0 .54
P = .53 P = .07 P = .74 P = .99
Factor IX Total 6.3 9.4 35.3 33.3 < .05
HD 0 0 33.3 50 <.05
PD 10 10% 25 0 .37
None 10 20% 50 0 .07
P = .51 P = .27 P = .55 P = .99
Values are presented as mean ± standard error for continuous variables, and percentages for categorical variables.
Prevalence of cases of positive result.
Prevalence of cases of increased result.P values are calculated by longitudinal data analysis for the comparison of each operative stage, and calculated by Kruskal–Wallis test for continuous variables and χ2 or Fisher test for categorical variables in the comparison of each patient group.aCL = anticardiolipin, APTT = activated partial thromboplastin time, ATIII = antithrombin III, HD = hemodialysis, LA = lupus anticoagulant, PC = protein C, PD = peritoneal dialysis, POD = postoperative day, PS = protein S, PT = prothrombin time.

Table 3 presents the comparison between basiliximab and ATG induction group. Hemoglobin decreased from 10.5 ± 1.7 g/dL versus 10.8 ± 1.6 g/dL pre-KT to 9.5 ± 1.3 g/dL versus 8.9 ± 1.4 g/dL POD7 (P < .05), 9.6 ± 1.2 g/dL versus 9.1 ± 1.6 g/dL on POD14 (P < .05) and return to normal after POD28 (P < 0.05). Platelet counts decreased from 186.3 ± 59.5 (x109/L) versus 180.3 ± 54.8 (×109/L) pre-KT (P < .05) to 166.4 ± 55.8 (×109/L) versus 126.3 ± 53.9 (×109/L) on POD7 (P < .05) and return to normal after POD14, respectively (P < .05). These decrements in hemoglobin and platelet counts were more pronounced in ATG groups comparing with basiliximab ones, and platelet counts were lower in ATG groups throughout the study period compared to basiliximab ones after KT (126.3 ± 53.9 (×109/L) versus 166.4 ± 55.8 (×109/L) POD7; 157.8 ± 53.2 (109/L) versus 186.7 ± 61.2 (×109/L) POD14; 187.7 ± 80.0 (×109/L) versus 218.2 ± 70.9 (×109/L) POD28, respectively) (P < .05). d-dimer was increased in both basiliximab and ATG groups after KT; however, there was no significant difference (3.0 ± 3.0 mg/dL vs 2.6 ± 1.9 mg/dL POD7 [P > .05], 2.5 ± 2.7 mg/dL vs 2.0 ± 1.7 mg/dL POD14 [P > .05], 1.7 ± 1.5 mg/dL vs 1.4 ± 1.3 mg/dL POD28 [P > .05]).

Table 3 - Comparison of the prothrombotic factors before and after kidney transplantation between basiliximab and ATG induction group.
Basiliximab (N = 323) ATG (N = 44)
n Mean ± SD or n (%) P for within group (a) n Mean ± SD or n (%) P for within group (a) P for between group
Hemoglobin, g/dL 0.07 (c)
 Pre 322 10.5 ± 1.7 44 10.8 ± 1.6 0.31 (d)
 7th POD 323 9.5 ± 1.3 <.05 44 8.9 ± 1.4 <.05 <0.05 (d)
 14th POD 323 9.6 ± 1.2 <.05 44 9.1 ± 1.6 <.05 <0.05 (d)
 28th POD 323 11.4 ± 1.3 <.05 44 11.0 ± 1.5 0.42 0.06 (d)
P for time within group (b) <.05 <.05
Platelet (×109/L) <.05 (c)
 Pre 323 186.3 ± 59.5 44 180.3 ± 54.8 0.53 (d)
 7th POD 323 166.4 ± 55.8 <.05 44 126.3 ± 53.9 <.05 <.05 (d)
 14th POD 323 186.7 ± 61.2 0.91 44 157.8 ± 53.2 <.05 <.05 (d)
 28th POD 323 218.2 ± 70.9 <.05 44 187.7 ± 80.0 0.45 <.05 (d)
P for time within group <.05 <.05
PT (%) 0.06 (c)
 Pre 323 91.2 ± 13.2 44 94.8 ± 12.9 0.53 (d)
 7th POD 318 84.9 ± 15.0 <.05 44 82.7 ± 18.2 <.05 <.05 (d)
 14th POD 299 96.9 ± 13.3 <.05 44 95.0 ± 15.3 0.96 <.05 (d)
 28th POD 268 110.7 ± 16.5 <.05 44 108.6 ± 20.3 <.05 <.05 (d)
P for time within group <.05 <.05
APTT, s <.05 (c)
 Pre 323 26.9 ± 6.0 44 26.9 ± 5.3 0.99 (d)
 7th POD 318 25.7 ± 6.0 <.05 44 26.7 ± 4.8 0.80 0.33 (d)
 14th POD 298 23.7 ± 4.1 <.05 44 25.3 ± 9.1 0.13 <.05 (d)
 28th POD 268 22.1 ± 3.8 <.05 44 25.2 ± 12.9 0.15 <.05 (d)
P for time within group <.001 0.318
d-dimer, mg/dL <.05 (c)
 Pre 319 1.4 ± 1.4 44 0.9 ± 0.8 <.05 (d)
 7th POD 319 2.6 ± 1.9 <.05 44 3.0 ± 3.0 <.05 0.28 (d)
 14th POD 316 2.0 ± 1.7 <.05 44 2.5 ± 2.7 <.05 0.10 (d)
 28th POD 302 1.7 ± 1.5 <.05 41 1.4 ± 1.3 <.05 0.37 (d)
P for time within group <.05 <.05
Fibrinogen, mg/dL 0.47 (c)
 Pre 220 321.9 ± 91.1 43 324.9 ± 80.5 0.98 (d)
 7th POD 249 218.3 ± 72.5 <.05 44 198.4 ± 53.1 <.05 0.09 (d)
 14th POD 251 242.6 ± 94.7 <.05 44 234.2 ± 76.8 <.05 0.56 (d)
 28th POD 93 266.6 ± 86.4 <.05 37 257.6 ± 79.1 <.05 0.70 (d)
P for time within group <.05 <.05
PS activity (%) 0.90 (c)
 Pre 320 91.3 ± 32.9 43 87.9 ± 25.5 0.48 (d)
 7th POD 247 67.2 ± 22.7 <.05 44 60.5 ± 20.2 <.05 0.09 (d)
 14th POD 251 77.4 ± 26.1 <.05 44 71.1 ± 26.1 <.05 0.16 (d)
 28th POD 92 93.8 ± 26.1 0.43 35 93.7 ± 57.1 0.49 0.80 (d)
P for time within group <.05 <.05
PC activity (%) 0.70 (c)
 Pre 317 101.1 ± 23.0 43 96.7 ± 19.9 0.23 (d)
 7th POD 247 103.0 ± 24.6 0.07 43 98.9 ± 26.3 0.56 0.211 (d)
 14th POD 251 120.9 ± 25.9 <.05 44 112.2 ± 25.8 <.05 0.029 (d)
 28th POD 92 129.2 ± 23.8 <.05 35 123.4 ± 21.0 <.05 0.040 (d)
P for time within group <.05 <.05
ATIII activity (%) <0.05 (c)
 Pre 320 87.2 ± 14.1 43 85.6 ± 12.2 0.472 (d)
 7th POD 248 87.8 ± 14.1 0.832 44 89.4 ± 13.5 0.117 0.411 (d)
 14th POD 252 101.9 ± 14.6 <.05 44 98.4 ± 16.0 <.05 0.218 (d)
 28th POD 94 110.6 ± 12.8 <.05 37 108.0 ± 15.2 <.05 0.117 (d)
P for time within group <.05 <.05
Homocystein, μmol/L 0.607 (c)
 Pre 320 22.2 ± 14.9 44 20.3 ± 11.7 0.42 (d)
 7th POD 246 12.3 ± 7.9 <.05 44 13.1 ± 6.9 <.05 0.51 (d)
 14th POD 247 12.3 ± 6.9 <.05 43 13.0 ± 6.5 <.05 0.57 (d)
 28th POD 88 14.2 ± 5.1 <.05 35 15.2 ± 7.8 <.05 0.58 (d)
P for time within group <.05 <.05
LA (%)
 Pre 321 21 (6.5) 43 5 (11.6) 0.21 (f)
 7th POD 245 6 (2.5) <.05 44 0 (0)
 14th  POD 246 1 (0.4) <.05 43 0 (0)
28th POD 86 1 (1.2) 0.08 36 0 (0)
P for time within group <.05
aCL (%) 0.11 (c)
 Pre 308 37 (12.0) 44 11 (25.0) <.05 (d)
 7th POD 246 25 (10.2) 0.203 44 4 (9.1) <.05 0.97 (d)
 14th POD 245 21 (8.6) <.05 43 2 (4.7) <.05 0.53 (d)
 28th POD 89 3 (3.4) <.05 36 2 (5.6) <.05 0.33 (d)
P for time within group <.05 <.05
Factor VIII (%) 0.68 (c)
 Pre 25 8 (32.0) 7 3 (42.9) 0.59 (d)
 7th POD 25 13 (52.0) 0.077 7 3 (42.9) 0.957 0.69 (d)
 14th POD 26 16 (61.5) <.05 8 5 (62.5) 0.161 0.98 (d)
 28th POD 3 1 (33.3) 0.996 0 0 (0)
P for time within group 0.08 0.38
Factor IX (%) 0.49 (c)
 Pre 25 1 (4.0) 7 1 (14.3) 0.37 (d)
 7th POD 25 2 (8.0) 0.379 7 1 (14.3) 0.973 0.64 (d)
 14th POD 26 10 (38.5) <.05 8 2 (25.0) 0.632 0.50 (d)
 28th POD 3 1 (33.3) 0.273 0 0 (0)
P for time within group <.05 0.62
P value by mixed model for repeated measurement (MMRM) for continuous variables and generalized estimating equation (GEE) method for binary outcomes.(a) P for comparison between pre-transplantation and each POD value within group.(b) P for time within group.(c) P for interaction between group and time.(d) P for comparison between groups within each time point.Values are presented as mean ± standard error for continuous variables, and percentages for categorical variables.
Prevalence of cases of positive result.
Prevalence of cases of increased result.P values are calculated by longitudinal data analysis for the comparison of each operative stage, and calculated by Kruskal–Wallis test for continuous variables and χ2 or fisher test for categorical variables in the comparison of each patient group.aCL = anticardiolipin, APTT = activated partial thromboplastin time, ATG = antithyomocyte globulin, ATIII = antithrombin III, HD = hemodialysis, LA = lupus anticoagulant, PC = protein C, PD = peritoneal dialysis, POD = postoperative day, PS = protein S, PT = prothrombin time.

Table 4 presents the comparison between LDKT and DDKT groups. Hemoglobin and platelet counts were lower in DDKT group throughout the study period compared to LDKT group. Hemoglobin decreased from 10.1 ± 1.6 g/dL versus 11.3 ± 1.8 g/dL pre-KT to 9.7 ± 1.3 g/dL versus 9.1 ± 1.2 g/dL POD7, 9.7 ± 1.2 g/dL versus 9.3 ± 1.2 g/dL on POD14 and recovered normal range in both groups after POD28 (P < .05). Platelet counts decreased from 185.0 ± 61.8 (×109/L) vs 185.0 ± 61.8 (×109/L) pre-KT to 173.3 ± 56.4 (×109/L) and 141.4 ± 52.5 (109/L) on POD7 (P < .05) and were restored after POD14, respectively. These decrements in hemoglobin and platelet were steeper in DDKT group (P < .05). d-dimer was increased in both LDKT and DDKT groups after KT, and except for POD7 when the LDKT groups showed higher level of d-dimer (2.9 ± 2.1 mg/dL vs 2.2 ± 1.9 mg/dL, P < .05), there was no significant difference between 2 groups during the study period.

Table 4 - Comparison of the prothrombotic factors before and after kidney transplantation between LDKT and DDKT group.
LDKT (N = 232) DDKT (N = 135)
n Mean ± SD or n (%) P for within group (a) n Mean ± SD or n (%) P for within group (a) P for between group
Hemoglobin, g/dL <.05 (c)
 Pre 232 10.1 ± 1.6 134 11.3 ± 1.8 <.05 (d)
 7th POD 232 9.7 ± 1.3 <.05 135 9.1 ± 1.2 <.05 <.05 (d)
 14th POD 232 9.7 ± 1.2 <.05 135 9.3 ± 1.2 <.05 <.05 (d)
 28th POD 232 11.5 ± 1.3 <.05 135 11.2 ± 1.4 0.68 0.06 (d)
P for time within group (b) <.05 <.05
Platelet (×109/L) <.05 (c)
 Pre 232 185.0 ± 61.8 135 186.6 ± 54.0 0.80 (d)
 7th POD 232 173.3 ± 56.4 <.05 135 141.4 ± 52.5 <.05 <.05 (d)
 14th POD 232 185.9 ± 61.5 0.81 135 178.5 ± 59.9 0.09 0.26 (d)
 28th POD 232 224.3 ± 71.0 <.05 135 197.8 ± 72.5 <.05 <.05 (d)
P for time within group <.05 <.05
PT (%) <.05 (c)
 Pre 232 90.8 ± 13.0 135 93.1 ± 13.4 0.11 (d)
 7th POD 227 86.9 ± 13.1 <.05 135 80.8 ± 18.1 <.05 <.05 (d)
 14th POD 215 98.3 ± 13.8 <.05 128 94.0 ± 12.8 0.41 <.05 (d)
 28th POD 191 113.8 ± 14.7 <.05 121 105.0 ± 19.1 <.05 <.05 (d)
P for time within group <.05 <.05
APTT, s <.05 (c)
 Pre 232 27.4 ± 6.8 135 26.1 ± 3.9 <.05 (d)
 7th POD 227 25.6 ± 4.6 <.05 135 26.2 ± 7.4 0.82 0.34 (d)
 14th POD 215 23.5 ± 4.1 <.05 127 24.6 ± 6.2 <.05 0.06 (d)
 28th POD 191 21.7 ± 3.7 <.05 121 23.8 ± 8.4 <.05 <.001 (d)
P for time within group <.05 <.05
d-dimer, mg/dL <.05 (c)
 Pre 230 1.4 ± 1.4 133 1.2 ± 1.2 0.19 (d)
 7th POD 228 2.9 ± 2.1 <.05 135 2.2 ± 1.9 <.05 <.05 (d)
 14th POD 227 2.0 ± 1.8 <.05 133 2.0 ± 2.0 <.05 0.92 (d)
 28th POD 217 1.7 ± 1.6 <.05 126 1.6 ± 1.3 <.05 0.99 (d)
P for time within group <.05 <.05
Fibrinogen, mg/dL <.05 (c)
 Pre 171 323.2 ± 87.4 92 320.9 ± 93.1 0.90 (d)
 7th POD 184 214.9 ± 72.5 <.05 109 216.0 ± 66.7 <.05 0.97 (d)
 14th POD 185 230.1 ± 93.1 <.05 110 260.3 ± 87.8 <.05 <.05 (d)
 28th POD 75 255.2 ± 84.2 <.05 55 276.1 ± 83.4 <.05 0.20 (d)
P for time within group <.05 <.05
PS activity (%) 0.25 (c)
 Pre 230 89.3 ± 31.9 133 93.6 ± 32.2 0.20 (d)
 7th POD 184 66.5 ± 21.9 <.05 107 65.6 ± 23.5 <.05 0.78 (d)
 14th POD 185 77.0 ± 24.1 <.05 110 75.5 ± 29.4 <.05 0.63 (d)
 28th POD 76 96.1 ± 41 0.071 51 90.3 ± 30.3 0.525 0.28 (d)
P for time within group <.05 <.05
PC activity (%) 0.11 (c)
 Pre 230 99.9 ± 21.5 130 101.7 ± 24.7 0.46 (d)
 7th POD 183 104.7 ± 23.8 <.05 107 98.4 ± 26.1 0.42 0.05 (d)
 14th POD 185 121.0 ± 26.2 <.05 110 117.2 ± 25.7 <.05 0.27 (d)
 28th POD 76 129.0 ± 24.4 <.05 51 125.6 ± 21.2 <.05 0.27 (d)
P for time within group <.05 <.05
ATIII activity (%) 0.26 (c)
 Pre 230 88.2 ± 13.7 133 85.1 ± 13.9 <.05 (d)
 7th POD 183 89.7 ± 14.1 0.27 109 85.3 ± 13.5 0.94 <.05 (d)
 14th POD 186 103.5 ± 14.4 <.05 110 97.9 ± 14.9 <.05 <.05 (d)
 28th POD 76 112.9 ± 8.5 <.05 55 105.7 ± 17.6 <.05 <.05 (d)
P for time within group <.05 <.05
Homocystein, μmol/L 0.05 (c)
 Pre 230 21.9 ± 15.8 134 22.0 ± 12.1 0.973 (d)
 7th POD 182 10.9 ± 7.5 <.05 108 15.0 ± 7.6 <.05 <.05 (d)
 14t POD 183 11.2 ± 4.6 <.05 107 14.3 ± 9.3 <.05 <.05 (d)
 28th POD 71 13.9 ± 5.3 <.05 52 15.3 ± 6.8 <.05 <.05 (d)
P for time within group <.05 <.05
LA (%)
 Pre 231 12 (5.2) 133 14 (10.5) 0.06 (g)
 7th POD 182 3 (1.7) 0.07 107 3 (2.8) 0.67 (f)
 14th POD 183 1 (0.6) <.05 106 0 (0)
 28th POD 71 1 (1.4) 0.20 51 0 (0)
P for time within group <.05
aCL (%) 0.110 (c)
 Pre 225 30 (13.3) 127 18 (14.2) <.05 (d)
 7th POD 182 23 (12.6) 0.20 108 6 (5.6) 0.019 0.97 (d)
 14th POD 182 18 (9.9) 0.10 106 5 (4.7) 0.004 0.53 (d)
 28th POD 73 3 (4.1) <.05 52 2 (3.9) 0.018 0.33 (d)
 p for time within group <.05 <.05
Factor VIII (%) 0.117 (c)
 Pre 21 7 (33.3) 11 4 (36.4) 0.83 (d)
 7th POD 21 10 (47.6) 0.492 11 4 (54.6) 0.019 0.08 (d)
 14th POD 20 10 (50.0) 0.17 14 11 (78.6) 0.012 0.17 (d)
 28th POD 1 0 (0) <.05 2 1 (50.0) 0.042 0.70 (d)
P for time within group 0.08 <.05
Factor IX (%)
 Pre 21 1 (4.8) 11 1 (9.1) >.99 (f)
 7th POD 21 2 (9.5) 11 1 (9.1) >.99 >.99 (f)
 14th POD 20 7 (35.0) 14 5 (35.7) 0.19 >.99 (f)
 28th POD 1 0 (0) 2 1 (50.0) 0.19
P for time within group 0.39
P value by mixed model for repeated measurement (MMRM) for continuous variables and generalized estimating equation (GEE) method for binary outcomes.(a) P for comparison between pre-transplantation and each POD value within group.(b) P for time within group.(c) P for interaction between group and time.(d) P for comparison between groups within each time point.Values are presented as mean ± standard error for continuous variables, and percentages for categorical variables.
Prevalence of cases of positive result.
Prevalence of cases of increased result.P values are calculated by longitudinal data analysis for the comparison of each operative stage and calculated by Kruskal–Wallis test for continuous variables and χ2 or Fisher test for categorical variables in the comparison of each patient group.aCL = anticardiolipin, APTT = activated partial thromboplastin time, ATIII = antithrombin III, DDKT = deceased donor kidney transplantation, HD = hemodialysis, LA = lupus anticoagulant, LDKT = living donor kidney transplantation, PC = protein C, PD = peritoneal dialysis, POD = postoperative day, PS = protein S, PT = prothrombin time.

Table 5 shows patients with ≥1 positive prothrombotic factor pre- and post-KT in each RRT subgroup. Pre-transplant, the prevalence of ≥1 positive prothrombotic factor was 82.0%. The prevalence decreased on POD7, 14, and 28 to 55.3%, 29.7%, and 14.2%, respectively (P < .05). The same trend occurred in all RRT subgroups, although the differences were not statistically significant. The number of positive (abnormal) prothrombotic factors per patient was 1.4 ± 0.9 pre-KT and decreased significantly post-KT to 0.9 ± 0.1 on POD7, 0.4 ± 0.6 on POD14, and 0.2 ± 0.6 on POD28 (P < .05). Similar changes were noted in each RRT subgroup, which was statistically significant on multiple comparison analysis (P < .05) (Table 6).

Table 5 - Patients with ≥1 positive prothrombotic factors before and after kidney transplantation in each patients group.
Pre-transplantation 7th POD 14th POD 28th POD P
Total (n = 367) 301 (82) 203 (55.3) 109 (29.7) 52 (14.2) <.05
HD (n = 209) 163 (78) 114 (54.6) 63 (30.1) 24 (11.5) <.05
PD (n = 90) 78 (86.7) 48 (53.3) 23 (25.6) 15 (16.7) <.05
None (n = 68) 60 (88.2) 41 (60.3) 23 (33.8) 13 (19.1) <.05
P .067 .646 .518 .215
Values are presented as numbers (%).
P values are calculated by longitudinal data analysis.
P values are calculated by χ2.HD = hemodialysis, PD = peritoneal dialysis, POD = postoperative day.

Table 6 - Number of positive prothrombophilic factors per each patient before and after kidney transplantation in each patients group.
Pre-transplantation 7th POD 14th POD 28th POD P
Total (n = 367) 1.4 ± 0.9 0.9 ± 1 0.4 ± 0.6 0.2 ± 0.4 <.05
HD (n = 209) 1.4 ± 1 0.8 ± 0.9 0.4 ± 0.6 0.1 ± 0.4 <.05
PD (n = 90) 1.4 ± 0.8 1 ± 1.1 0.3 ± 0.6 0.2 ± 0.5 <.05
None (n = 68) 1.3 ± 0.8 1 ± 1.1 0.4 ± 0.7 0.2 ± 0.4 <.05
P .89 .58 .58 .21
Values are presented as mean ± standard deviation and median (IQR).
P values are calculated by longitudinal data analysis.
P values are calculated by kruskal wallis test.HD = hemodialysis, PD = peritoneal dialysis, POD = postoperative day.

4 Discussion

Patients with CKD have an increased risk of both thrombosis and bleeding. The main reported hemostatic abnormalities in CKD are increased tissue factor, von Willebrand factor, factor XIIa, factor VIIa, activated PC, fibrinogen, and plasminogen activator inhibitor-1, and reduced tissue plasminogen activator.[10] As CKD advances, platelet dysfunction and hemorrhagic complications appear, with mucocutaneous bleeding, gastrointestinal bleeding, and, less frequently, hemothorax, hemoperitoneum, and intracranial or retroperitoneal bleeding.[11] It is unclear why bleeding problems predominate in one patient, whereas thrombotic complications occur in others.[3]

Previous reports of hypercoagulability in patients with CKD have reported varying mechanisms. We examined eight hemostatic factors previously reported as possible contributors to thrombosis after KT. At least one of these prothrombotic factors was present in 82.0% of our study population pre-KT, with 1.4 ± 0.9 factors per patient.[12]

Patients with CKD exhibit abnormalities of various proteins and amino acids, including homocysteine.[13] Plasma homocysteine levels are inversely related to glomerular filtration rate, with hyperhomocysteinemia observed in up to 85% to 100% of people with ESRD.[13] Elevated homocysteine levels are associated with increased risk of venous and arterial thrombosis.[14] In our study, d-dimer and homocysteine were increased above normal pre-transplant, suggesting a hypercoagulable state. Antiphospholipid antibodies (APLAs), including aCL, anti-β2GP-1 antibody, and LA, also promote thrombosis. LA is more strongly associated with increased thrombotic risk than aCL or anti-B2GP-1 antibody, and a “triple positive” profile (all 3 APLAs) confers the highest risk.[15] In one study, the prevalence of LA, IgG aCL, IgM aCL, and polyvalent aCL in a healthy population was 3.6%, 4.6%, 4.6%, and 5.5%, respectively.[16] In a general population study, positive LA, aCL, and anti-β2GP-1 antibody rates were 7%, 15%, and 11%, respectively, at initial testing and 5%, 9%, and 13% at 12-week retesting.[17] Our pre-KT rates were 7.1% for LA and 10.5% for aCL, which were higher than in the healthy population. Although false-positive LA may occur with oral anticoagulants, we excluded patients receiving this therapy.[18] Our pre-KT prevalence of elevated factor VIII was 34.4%, which was likewise higher than the 11% rate reported in a normal population.[19]

Uremia is strongly associated with platelet dysfunction, increasing the risk of hemorrhagic events. The pathogenesis of platelet dysfunction in uremia is multifactorial: platelet-platelet (aggregation) and platelet-vessel wall (adhesion) interactions appear crucial.[20] In this study, platelet counts decreased from 185.6 ± 59 (×109/L) pre-transplant to nadir (161.6 ± 57 [×109/L]) at POD7, then recovered to normal at POD28 as uremia and anemia improved. Anemia plays a role in platelet dysfunction, as platelets are more dispersed, impairing their adherence to endothelium. Furthermore, red blood cells enhance platelet function by releasing adenosine diphosphate, inactivating prostacyclin, and scavenging nitric oxide; thus, their reduced number in anemia contributes to platelet dysfunction.[21] Erythropoietin to correct anemia in CKD reduces the risk of uremic bleeding.[10] In this study, pre-KT hemoglobin was decreased below normal in all RRT subgroups suggesting an increased hemorrhagic risk in ESRD patients. Several reports have suggested that RRT might promote hypercoagulability in patients with CKD. As compared to HD, PD is known to increase the thrombotic tendency via increased levels of platelets, fibrinogen, clotting factor VII, and plasminogen activator inhibitor-1.[22–26] Inversely, HD appears to activate the coagulation cascade by reducing coagulation inhibitors, such as PC, PS, and AT III.[6,27] In the present study, the HD group had elevated d-dimer and decreased PS, PC, and AT III activity levels compared to the PD group, which might indicate a decline in the circulating levels of coagulation inhibitors. By contrast, the PD group had higher levels of homocysteine and fibrinogen than the HD group. The increased levels of fibrinogen observed in PD patients compared to those in HD patients or nondialyzed patients. These results might be explained by the chronic peritoneal irritation that can occur during dialysis, as fibrinogen can act as an acute-phase protein.[13]

The percentage of patients with ≥1 positive prothrombotic factor decreased from 82.0% pre-KT to 14.2% by POD28. In patients with ≥1 positive prothrombotic factor before transplantation, 9.0% developed bleeding complications and 3.3% had thrombotic complications post-transplantation. However, these rates were not significantly different from those in patients without these factors. However, we analyzed the number of positive prothrombotic factors at each clinical course. The number of prothrombotic decreased from 1.4 ± 0.9 pre KT to 0.2 ± 0.4 by POD28 which was significant. These results also support improvement in hemostatic status after KT.

Plasma homocysteine levels, which were above normal pre-KT, normalized by POD7 and remained within the normal range through POD28. These changes were expected because homocysteine levels are highly dependent on glomerular filtration rate. As increased plasma homocysteine levels are an independent risk factor for cardiovascular disease and thromboembolic events,[28] our results suggest that the risk of these events would decrease after KT.

Over the first month postoperatively, the prevalence of APLAs decreased to rates found in the general population.[16,17] Conversely, d-dimer was elevated throughout this period. d-dimer, the smallest fibrinolysis-specific degradation product in the circulation,[29] is detected within 2 hours of intravascular thrombus formation and circulates with a half-life of approximately 6 hours.[30,31] After general surgery, d-dimer levels peak at approximately 1 week and then decrease 5% to 10% per day, remaining above normal for up to 1 month.[32] In the present study, d-dimer levels similarly peaked on POD7 and remained elevated on POD28, suggesting that they reflected nonspecific findings of any major operation.

ATG, along with basiliximab, is one of the most widely used induction immunosuppressant agents in KT. ATG, targets a broad range of T-cell surface antigens, including CD2, 3, 5, 8, 28, 45, the T-cell receptor, CD154 which are activate in primary antigenic signaling. And ATG also contains antibodies against natural killer cell marker and antibodies against CD20; a B-cell surface marker.[33,34] As a result, ATG interacts with large range of antigens on immune and nonimmune cell type, inducing apoptosis of B-cells, peripheral T-cells and NK cells, and plasma cells (CD138+).[33–36]

There are many comparative studies between ATG and basiliximab, and it is well known that ATG presents more hematologic side effect, such as anemia, lymphocytopenia, and thrombocytopenia. [33,37,38] de Nattes et al[38] reported that thrombocytopenia and hemolytic anemia occurring after ATG inductions probably might be heteroimmune origin via an interaction with a common Fc-receptor epitope in the different cell lines. In this study, 44 patients (12%) received ATG induction and others received basiliximab (323 patients, 88%) for induction therapy. Anemia was observed in both ATG group and basiliximab group at POD7 and 14; however, hemoglobin was significantly lower in ATG group (P < 0.5). Moreover, thrombocytopenia was observed at POD7 and recovered to normal range after POD14 in ATG group. In previously reported studies, anemia after KT occurred about 40% of patients, which was usually caused by or aggravated by blood losses during the surgery or hemodilution due massive fluid therapy in perioperative periods.[38,39] Anemia in both groups might be multifactorial, however, thrombocytopenia presented in ATG group, especially at POD7, might the side effect of ATG.

Comparative analyses were also performed between LDKT and DDKT groups. Hemoglobin and platelet count were lower in DDKT groups throughout the study period compared to LDKT groups after KT. Decrements in hemoglobin and platelet counts were steeper in DDKT group (P < 0.05). In DDKT groups, APTT was prolonged and fibrinogen was increased within normal limit range DDKT group (P < 0.05); D-dimer was slightly increased in LDKT after transplantation (P < 0.05). These results might be related to the special condition DDKT, i) emergent surgery, ii) longer total ischemic time is longer which results in longer surgery time, increased bleeding risk, and a more required massive fluid resuscitation, iii) relatively high rate of DGF and rejection, and iv) ATG induction for those with expanded criteria donor.

A main strength of this study was the exclusion of patients receiving pre- or postoperative antiplatelet agents or anticoagulants; thus, the study cohort was more hematologically “pure” than that of our previous study.[12] We also evaluated the number of prothrombotic factors per patient and demonstrated that this number decreased post-KT. The study has some drawbacks. We did not analyze various confounders that may affect hemostatic factors, such as type of immunosuppressive agent,[40] presence of cytomegalovirus infection,[41] donor factors, or ischemic time.[14] The follow-up duration was only 28 days, limiting our results to short-term outcomes.

However, this study focused on overall characteristics of hemostatic factors before and after KT and produced results that validated previous findings and hypotheses and provide a basis for future studies.

5 Conclusions

Before KT, most recipients exhibited prothrombotic tendencies, in terms of decreased hemoglobin, increased d-dimer and homocysteine, and increased prevalence of LA and aCL. By POD28, most of these abnormalities had improved or resolved. This improvement in thrombotic factors after KT may decrease the risk of cardiovascular disease, thromboembolic events, and mortality in recipients. These results are considered to be the major pathophysiologic effects on the hemostatic factors following KT. Based on this study, we suggest that improvement of renal function after KT might play an important role in recovery of hemostatic parameters in CKD patients, who simultaneously suffered from thrombosis and bleeding tendency. Finally, in order to identify the mechanism of hemostatic problems not only in CKD patients but also long-term effects of KT, further investigations, and longer follow up durations are warranted.

Author contributions

Conceptualization: Ji Il Kim, Jinbeom Cho.

Data curation: Jinbeom Cho, Kang Woong Jun, Mihyeong Kim, Jeong Kye Hwang

Formal analysis: Jinbeom Cho, Kang Woong Jun, Sun Cheol Park

Funding acquisition: Ji Il Kim

Investigation: Jinbeom Cho, Kang Woong Jun, Mihyeong Kim

Methodology: In Sung Moon, Kang Woong Jun

Project administration: Jinbeom Cho, Ji Il Kim

Resources: Kang Woong Jun, Ji Il Kim, Sun Cheol Park.

Software: Kang Woong Jun, Mihyeong Kim, Jeong Kye Hwang

Supervision: Kang Woong Jun, Mihyeong Kim, Jeong Kye Hwang

Validation: Jinbeom Cho, Kang Woong Jun, Mihyeong Kim

Visualization: Jinbeom Cho, Kang Woong Jun, Mihyeong Kim

Writing – original draft: Kang Woong Jun, Jinbeom Cho.

Writing – review & editing: Kang Woong Jun, Ji Il Kim, Jinbeom Cho.

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Keywords:

chronic kidney disease; end stage renal disease; hemostatic factors; kidney transplantation

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