Evaluation of the effect of activated carbon on reversing the interference of rivaroxaban on coagulation experiment

doi:10.11958/20220319

Abstract

Abstract:

Objective To study the effect of activated charcoal treatment of rivaroxaban on the results of coagulation tests. Methods The sodium citrate anticoagulant blood samples were collected from the physical examination population after the detection of clinical routine coagulation items. Twenty cases were conveniently taken each time, repeated 24 times, and a total of 480 cases were included. Twenty plasma samples were mixed and configured as normal mixed plasma (NPP), and 1 mL NPP was set as the N1 group. NPP treated with activated carbon was used as the N2 group. NPP added with different mass concentrations of rivaroxaban was used as the N3 group, including 100 μg/L (the N3A group), 200 μg/L (the N3B group), 300 μg/L (the N3C group) and 400 μg/L (the N3D group). Each mass concentration was repeated 6 times. The N3 group was used as the N4 group after treatment with activated carbon. A total of 22 patients in the emergency department who were treated with rivaroxaban for the first time were collected. Blood samples collected 6 h before and 6 h after rivaroxaban were divided into the S1 group and the S2 group, respectively. After treatment with activated carbon, S2 group was used as the S3 group. The mass concentrations of rivaroxaban in the N3 group and the S2 group were determined by liquid chromatography-tandem mass spectrometry. The levels of prothrombin time (PT), activated partial thrombin time (APTT), thrombin time (TT) and fibrinogen (FIB) in the N1 group, the N2 group, the N3 group and the N4 group were detected. The activities of protein C (PC), protein S (PS), antithrombin Ⅲ (AT-Ⅲ) and coagulation factors FⅡ, FⅤ, FⅦ, FⅧ, FⅨ, FⅩ, FⅪ and FⅫ and the activities of anti-Xa factor (Anti-Xa) in the N1 group, the N2 group, the N3 group, the N4 group, the S1 group, the S2 group and the S3 group were also detected in each group. Results Compared with the N1 group, there were no significant differences in PT, APTT, INR, FIB, PC, PS, AT-Ⅲ, Anti-Xa, FⅡ, FⅤ, FⅦ, FⅧ, FⅨ, FⅩ, FⅪ and FⅫ activity in the N2 group. In the N3 group, PT and APTT were prolonged, INR levels were increased, PS, AT-Ⅲ and Anti-Xa activities were increased, and FⅡ, FⅤ, FⅦ, FⅧ, FⅨ, FⅩ, FⅪ and FⅫ activities were decreased (P<0.01). There were no significant differences in PC activity and FIB level. APTT was prolonged in the N4 group, while PS, FⅤ, FⅧ, FⅪ and FⅫ activities decreased (P<0.01). Compared with the N3 group, PT and APTT decreased, INR level, PS, AT-Ⅲ and Anti-Xa activity decreased significantly, FⅡ, FⅤ, FⅦ, FⅧ, FⅨ, FⅩ, FⅪ and FⅫ activities increased in the N4 group (P<0.01). There were no significant differences in FIB level and PC activity between the N3 group and the N4 group. Compared with the S1 group, Anti-Xa activity was increased and APTT was prolonged in the S2 group. APTT was prolonged in the S3 group (P<0.01). Compared with the S2 group, Anti-Xa activity was decreased and APTT was shortened in the S3 group. The levels of PT, INR, APTT and PS, and the activity of Anti-Xa were successively increased in the N3A group, the N3B group, the N3C group and the N3D group, while the activities of FⅤ, FⅦ, FⅧ, FⅨ and FⅪ were successively decreased (P<0.01). There was a positive correlation between rivaroxaban mass concentration and Anti-Xa activity in the N3 group and the S2 group (r_s = 0.989, 0.969, P<0.01). Conclusion Activated carbon can effectively remove rivaroxaban from plasma and reverse the abnormal coagulation index caused by rivaroxaban.

Key words: rivaroxaban, activated charcoal, antithrombin Ⅲ, partial thromboplastin time, blood coagulation factors, coagulation test

CLC Number:

R446.11

Figures/Tables 3

References 21

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组别	PT（s）	APTT（s）		INR			FIB（g/L）	PC（%）	PS（%）
N1组	10.90（10.60，11.00）	30.50（30.05，30.90）		0.93（0.93，0.96）			2.57（2.51，2.78）	112.00（107.00，120.00）	91.60（86.48，98.00）
N2组	10.90（10.63，11.00）	30.90（30.20，31.35）		0.96（0.93，0.97）			2.55（2.39，2.83）	111.00（109.00，119.00）	87.20（82.98，95.80）
N3组	19.20（15.43，26.38）^a	45.25（41.27，50.73）^a		1.67（1.34，2.30）^a			2.49（2.39，2.95）	115.00（113.00，115.75）	165.15（123.55，194.25）^a
N4组	11.05（10.55，11.30）^b	31.15（30.65，32.18）^ab		0.97（0.93，0.99）^b			2.64（2.49，2.84）	111.50（107.25，116.00）	82.60（79.78，88.23）^ab
χ²	47.145^＊＊	53.382^＊＊		46.325^＊＊			1.462	4.481	57.800^＊＊
组别	AT-Ⅲ（%）	Anti-Xa（IU/mL）			FⅡ（%）			FⅤ（%）	FⅦ（%）
N1组	93.00（88.00，99.00）	0.03（0.02，0.04）			98.20（93.40，99.00）			103.10（98.70，112.60）	91.00（88.10，99.80）
N2组	93.00（90.00，98.00）	0.03（0.02，0.03）			96.10（91.15，98.65）			99.90（98.70，123.20）	90.60（98.70，94.90）
N3组	103.00（98.00，105.75）^a	2.56（1.39，3.69）^a			75.05（52.20，82.55）^a			72.85（43.38，88.38）^a	77.45（56.68，91.63）^a
N4组	93.50（90.25，101.25）^b	0.02（0.02，0.04）^b			96.50（92.00，101.43）^b			96.60（90.50，100.80）^ab	93.70（84.55，100.00）^b
χ²	26.207^＊＊	51.406^＊＊	43.996^＊＊			45.288^＊＊		36.814^＊＊
组别	FⅧ（%）	FⅨ（%）			FⅩ（%）			FⅪ（%）	FⅫ（%）
N1组	123.70（120.30，130.80）	99.10（96.20，103.00）			93.80（88.03，102.30）			92.50（88.60，102.60）	72.50（63.60，76.30）
N2组	121.40（117.00，127.20）	99.10（95.20，105.30）			96.50（91.70，114.10）			94.60（82.00，96.60）	70.00（64.30，80.40）
N3组	54.30（47.28，74.75）^a	60.35（47.50，69.30）^a			60.15（43.73，70.18）^a			62.30（47.50，74.88）^a	50.00（44.30，60.40）^a
N4组	115.40（110.98，118.93）^ab	90.08（97.20，101.93）^b			93.80（84.55，107.65）^b			89.35（84.90，92.90）^ab	68.55（60.80，72.93）^ab
χ²	51.000^＊＊	46.185^＊＊			46.254^＊＊			47.750^＊＊	40.772^＊＊

组别	PT（s）	APTT（s）		INR			FIB（g/L）	PC（%）	PS（%）
N1组	10.90（10.60，11.00）	30.50（30.05，30.90）		0.93（0.93，0.96）			2.57（2.51，2.78）	112.00（107.00，120.00）	91.60（86.48，98.00）
N2组	10.90（10.63，11.00）	30.90（30.20，31.35）		0.96（0.93，0.97）			2.55（2.39，2.83）	111.00（109.00，119.00）	87.20（82.98，95.80）
N3组	19.20（15.43，26.38）^a	45.25（41.27，50.73）^a		1.67（1.34，2.30）^a			2.49（2.39，2.95）	115.00（113.00，115.75）	165.15（123.55，194.25）^a
N4组	11.05（10.55，11.30）^b	31.15（30.65，32.18）^ab		0.97（0.93，0.99）^b			2.64（2.49，2.84）	111.50（107.25，116.00）	82.60（79.78，88.23）^ab
χ²	47.145^＊＊	53.382^＊＊		46.325^＊＊			1.462	4.481	57.800^＊＊
组别	AT-Ⅲ（%）	Anti-Xa（IU/mL）			FⅡ（%）			FⅤ（%）	FⅦ（%）
N1组	93.00（88.00，99.00）	0.03（0.02，0.04）			98.20（93.40，99.00）			103.10（98.70，112.60）	91.00（88.10，99.80）
N2组	93.00（90.00，98.00）	0.03（0.02，0.03）			96.10（91.15，98.65）			99.90（98.70，123.20）	90.60（98.70，94.90）
N3组	103.00（98.00，105.75）^a	2.56（1.39，3.69）^a			75.05（52.20，82.55）^a			72.85（43.38，88.38）^a	77.45（56.68，91.63）^a
N4组	93.50（90.25，101.25）^b	0.02（0.02，0.04）^b			96.50（92.00，101.43）^b			96.60（90.50，100.80）^ab	93.70（84.55，100.00）^b
χ²	26.207^＊＊	51.406^＊＊	43.996^＊＊			45.288^＊＊		36.814^＊＊
组别	FⅧ（%）	FⅨ（%）			FⅩ（%）			FⅪ（%）	FⅫ（%）
N1组	123.70（120.30，130.80）	99.10（96.20，103.00）			93.80（88.03，102.30）			92.50（88.60，102.60）	72.50（63.60，76.30）
N2组	121.40（117.00，127.20）	99.10（95.20，105.30）			96.50（91.70，114.10）			94.60（82.00，96.60）	70.00（64.30，80.40）
N3组	54.30（47.28，74.75）^a	60.35（47.50，69.30）^a			60.15（43.73，70.18）^a			62.30（47.50，74.88）^a	50.00（44.30，60.40）^a
N4组	115.40（110.98，118.93）^ab	90.08（97.20，101.93）^b			93.80（84.55，107.65）^b			89.35（84.90，92.90）^ab	68.55（60.80，72.93）^ab
χ²	51.000^＊＊	46.185^＊＊			46.254^＊＊			47.750^＊＊	40.772^＊＊

组别	Anti-Xa（IU/mL）	APTT（s）
S1组	0.02（0.00，0.04）	30.50（29.50，31.50）
S2组	0.66（0.15，1.34）^a	36.95（34.70，39.78）^a
S3组	0.01（0.00，0.04）^b	31.85（30.50，37.65）^ab
χ²	34.211^＊＊	39.721^＊＊

组别	Anti-Xa（IU/mL）	APTT（s）
S1组	0.02（0.00，0.04）	30.50（29.50，31.50）
S2组	0.66（0.15，1.34）^a	36.95（34.70，39.78）^a
S3组	0.01（0.00，0.04）^b	31.85（30.50，37.65）^ab
χ²	34.211^＊＊	39.721^＊＊

组别	PT（s）	APTT（s）	INR		FIB(g/L)	PC（%）	PS（%）	AT-Ⅲ（%）	Anti-Xa（IU/mL）
N3A组	14.73±0.52	40.32±0.43	1.28（1.22，1.32）		2.61±0.29	116.00±2.00	112.13±3.06	94.00±2.00	1.14±0.07
N3B组	16.97±0.50^a	42.90±0.60^a	1.45（1.39，1.50）^a		2.50±0.20	113.83±2.86	152.15±6.14^a	96.50±1.87	2.05±0.14^a
N3C组	21.48±0.66^ab	47.73±0.83^ab	1.86（1.84，1.93）^ab		2.70±0.29	115.17±3.13	174.40±4.04^ab	100.67±2.88^a	3.00±0.11^ab
N3D组	28.67±0.59^abc	52.83±1.14^abc	2.54（2.42，2.56）^abc		2.71±0.32	115.17±1.48	200.78±1.43^abc	108.00±2.83^ab	3.97±0.08^abc
F或χ²	688.457^＊＊	291.364^＊＊	535.618^＊＊		0.715	0.800	516.409^＊＊	37.875^＊＊	853.459^＊＊
组别	FⅡ（%）	FⅤ（%）	FⅦ（%）	FⅩ（%）		FⅧ（%）	FⅨ（%）	FⅪ（%）	FⅫ（%）
N3A组	86.38±2.67	92.40±1.81	94.98±1.30	72.08±2.37		80.28±1.65	71.65±1.63	77.85±1.11	62.17±1.72
N3B组	75.30±5.32^a	83.57±1.99^a	82.48±2.53^a	68.48±1.66		60.65±4.55^a	65.02±1.27^a	67.58±1.08^a	58.21±2.21^a
N3C组	74.00±6.61^a	61.18±2.77^ab	71.91±3.09^ab	52.07±3.42^ab		52.98±1.35^ab	55.28±2.20^ab	56.05±2.77^ab	52.98±1.35^a
N3D组	43.60±2.18^abc	37.70±0.94^abc	50.35±3.10^abc	40.52±0.60^abc		42.53±3.07^abc	44.15±1.73^abc	44.18±1.38^abc	42.53±3.07^abc
F或χ²	96.300^＊＊	910.326^＊＊	314.685^＊＊	359.901^＊＊		176.208^＊＊	285.389^＊＊	423.805^＊＊	107.246^＊＊