Inhibition of platelet activation could decrease thrombotic events in hemodialysis PF4/H antibody-positive patients

Figures & data

Figure 1. Grouping of the study based on PF4/H antibody detection and anti-platelet agent use.

Table 1. Characteristics of platelet factor 4/heparin (PF4/H) antibody-positive and negative patients.

	Antibody-negative (n = 93)	Antibody-positive (n = 64)	p Value
Age, years, mean (SD)	56.43 (17.88)	56.23 (18.66)	0.196
Male/female	46/47	40/24	0.073
Duration of HD, month, mean (SD)	47.68 (17.88)	56.23 (18.66)	0.001
Time of HD per month, hours, median (quartile)	7.5 (1.5)	12.5 (2.5)	0.001
UFH/LMWH	59/34	40/24	0.518
Weight, kg, mean (SD)	61.98 (11.41)	63.03 (14.22)	0.611
SBP, mmHg, mean (SD)	135.7 (19.1)	130.55 (18.3)	0.089
DBP, mmHg, mean (SD)	79.1 (11.4)	79.2 (11.2)	0.987
Haemoglobin, g/L, mean (SD)	108.3 (14.1)	108.1 (17.9)	0.919
Kt/v, mean (SD)	1.42 (0.27)	1.43 (0.37)	0.881
TAC urea, median (quartile)	78.86 (31.92)	53.86 (29.19)	0.001
PCR, median (quartile)	1.02 (0.48)	1.06 (0.81)	0.714
Serum creatinine, μmol/L, mean (SD)	908.8 (280.2)	891.4 (274.7)	0.699
Albumin, g/L, mean (SD)	41.11 (4.85)	40.81 (4.19)	0.793
Calcium, mmol/L, mean (SD)	2.21 (0.23)	2.23 (0.24)	0.667
Phosphorus, mmol/L, mean (SD)	2.13 (0.79)	2.25 (0.71)	0.264
PTH, pg/L, median (quartile)	351.2 (369.1)	285.1 (238.7)	0.176
PLT, 10^9/L, mean (SD)	164.8 (57.4)	167.2 (64.6)	0.810
D-dimer, ng/mL, median (quartile)	0.76 (0.81)	1.11(1.12)	0.030
Pathogen of renal failure, n (%)
Chronic glomerulonephritis	45 (48.4)	30 (46.9)	0.852
Diabetic nephropathy	24 (25.8)	17 (26.6)	0.916
Hypertension	15 (16.1)	12 (18.8)	0.647
Polycystic kidney	4 (4.3)	2 (3.1)	0.706
Others	5 (5.4)	3 (4.6)	0.847
Past thrombosis events, n (%)
Myocardial infarction	3 (3.2)	1 (1.6)	0.516
Cerebral infraction	1 (1.1)	0 (0)	0.405
Others	1 (1.1)	1 (1.6)	0.789

Table 2. Characteristics of patients with and without thrombotic events in follow-up.

	Patients suffering thrombosis (n = 37)	Patients free from thrombosis (n = 120)	p Value
Age, years, mean (SD)	53.81 (19.81)	57.13 (17.61)	0.116
Male/female	20/17	66/54	0.919
Duration of HD, month,  mean (SD)	41.31 (35.24)	45.25 (36.64)	0.760
Time of HD per month,  hours, median (quartile)^a	12.00 (4.50)	9.00 (5.50)	0.122
UFH/LMWH	21/16	78/42	0.364
Kt/v, mean (SD)	1.43 (0.29)	1.43 (0.32)	0.758
TAC urea, median (quartile)^a	56.79 (46.57)	64.13 (31.64)	0.346
PCR, median (quartile)^a	1.07 (0.65)	0.86 (0.70)	0.561

^aAnalyze by Mann–Whitney U test (rank-sum test).

Table 3. Comparison of the incidence of thrombosis between PF4/H antibody-positive and antibody-negative patients (using Fisher exact probability test in 2 × 2 tables).

	Antibody- negative (n = 93)	Antibody- positive (n = 64)	p Value
Myocardial infarction, n (%)	3 (3.2)	6 (9.4)	0.101
Cerebral infarction, n (%)	3 (3.2)	2 (3.1)	0.671
AVF embolism, n (%)	7 (7.5)	10 (15.6)	0.091
Catheter embolism, n (%)	2 (2.2)	4 (6.3)	0.185
Total thrombosis events, n (%)	15 (16.1)	22 (34.4)	0.007

Figure 2. The cumulative frequency of thrombocytopenia was significantly higher in group 3 than in the other five groups. The cumulative frequency of thrombocytopenia in the other five groups was approximated using the Gehan–Breslow–Wilcoxon test.

Table 4. Comparison of platelet counts^a, D-dimer titers^a and platelet factor 4 (PF4)^b at the follow-up.

	Group 1	Group 2A	Group 2B	Group 3	Group 4A	Group 4B	p Value
Mean PLT (10^9/L)	159.8	164.5	262.3	145.8	166.8	194.3	0.001
mean (SD)	(60.8)	(43.9)	(67.6)	(58.6)	(48.9)	(46.7)
Nadir PLT (10^9/L)	129.4	124.8	181.5	95.4	130.3	158.1	0.001
mean (SD)	(57.3)	(38.3)	(48.5)	(34.4)	(38.7)	(48.1)
Mean D-dimer (ng/ml)	0.54	0.51	0.58	1.55	0.98	0.68	0.001
Median (quartile)	(0.48)	(0.67)	(0.31)	(2.53)	(0.80)	(0.60)
Max. D-dimer (ng/ml)	0.69	0.68	0.66	1.97	1.51	0.82	0.001
Median (quartile)	(0.80)	(0.69)	(0.48)	(4.07)	(1.35)	(0.66)
PF4 (IU/mL)	27.1	29.5	21.3	56.9	46.3	41.9	0.001
mean (SD)	(7.4)	(6.8)	(8.5)	(8.9)	(7.8)	(7.4)

^aMeasured every month.

^bMeasured only at the end point.

Figure 3. (A) Of the antibody-positive groups, thrombosis-free survival rates 4A and 4B are significantly higher than 3. (B) Of the antibody-negative groups, patients in groups 1, 2A and 2B manifested a similar incidence of thrombosis. Analyzed by log-rank survival test.

Table 5. Cox proportional hazards regression model for thrombotic events.

	β	SD	p Value	HR	95% CI for HR
Antibody positive^a	1.484	0.533	0.004	4.410	1.608–12.094
Taking clopidogrel^b	−1.350	0.533	0.011	0.259	0.091–0.733
Taking aspirin^c	−0.900	0.414	0.030	0.406	0.180–0.915
Gender^d	−0.041	0.360	0.909	0.960	0.474–1.942
Age^g	−0.004	0.010	0.700	0.996	0.977–1.015
Dialysis hours per week^g	−0.074	0.091	0.417	0.929	0.777–1.110
Duration of dialysis^g	−0.001	0.005	0.806	0.999	0.989–1.009
Applied LWMH for HD^e	−0.518	0.374	0.167	0.596	0.286–1.241
Past thrombotic events^f	−0.160	1.030	0.877	0.853	0.113–6.424

^aPF4/H antibody positive = 1, PF4/H antibody negative = 0.

^bTaking clopidogrel = 1, refusing any anti-platelet agent = 0.

^cTaking aspirin = 1, refused any anti-platelet agent = 0.

^dMale = 1, female = 0.

^eApplied UFH for HD = 1, applied LMWH for HD = 0.

^fPatients who had suffered thrombotic events before the study = 1, patients who did not have any thrombotic events before the study = 0.

^gThe other variables including age, dialysis hours per week and dialytic duration are all continuous.

Table 6. Comparison of parameters^a between PF4/H antibody positive and negative groups surviving from and suffering thrombotic events.

	Survived from thrombosis at follow-up	Suffered thrombosis at follow-up	p Value
Group 1
BT (min)	18.68 (5.37)	16.74 (4.72)	0.344
IPA-Max (%)	67.86 (14.27)	71.06 (15.42)	0.601
PF4 (IU/L)	28.78 (7.19)	29.76 (8.45)	0.643
Group 3
BT (min)	23.12 (6.88)	17.30 (5.64)	0.001
IPA-Max (%)	56.86 (8.37)	73.34 (13.67)	0.001
PF4 (IU/L)	29.38 (7.40)	31.61 (8.08)	0.713

^aMeasured at the start of the study.