Thrombomodulin in the management of acute cholangitis-induced disseminated intravascular coagulation

Table 1 Diagnostic criteria for disseminated intravascular coagulation as defined by the Japanese Association for Acute Medicine

	Score
Systemic inflammatory response syndrome criteria1
≥ 3	1
0-2	0
Platelet count (× 103/L)
< 80 or > 50% decrease within 24 h	3
≥ 80 and < 120; or > 30% decrease within 24 h	1
≥ 120	0
Prothrombin time (Value of patient/Normal value)
≥ 1.2	1
< 1.2	0
Fibrin/fibrinogen degradation products (mg/L)
≥ 25	3
≥ 10 and < 25	1
< 10	0
Diagnosis
≥ 4 points	DIC

¹Systemic inflammatory response syndrome criteria: Fever of more than 38 °C or less than 36 °C; Heart rate of more than 90 beats per min; Respiratory rate of more than 20 breaths per minute or a PaCO₂ level of less than 32 mmHg; Abnormal white blood cell count (> 12000/μL or < 4000/μL or > 10% bands). DIC: Disseminated intravascular coagulation.

Table 2 Comparison of patient characteristics between the recombinant human soluble thrombomodulin and control groups

	rTM group(n = 30)	Control group (n = 36)	P value
Age (yr)	77.0 ± 7.7	75.7 ± 9.4	0.554
Sex (Male/Female)	22/8	21/15	0.203
Primary disease (Benign/Malignant)	21/9	21/15	0.327
Severity of cholangitis (Severe/Moderate)	28/2	32/4	0.845
DIC score	5.4 ± 1.4	5.2 ± 1.2	0.523
SIRS score	2.4 ± 1.3	2.6 ± 1.0	0.599
Biliary drainage	25	24	0.123
Anticoagulant drug
AT	26	16	< 0.001
GM	14	30	0.002
NM	4	18	0.004
DS	0	6	0.019
Antibiotics
MEPM	19	14	0.048
IPM/CS	0	7	0.031
DRPM	5	0	0.037
SBT/CPZ	5	14	0.047
TAZ/PIPC	1	1	0.556

DIC: Disseminated intravascular coagulation; SIRS: Systemic inflammatory response syndrome; rTM: Recombinant human soluble thrombomodulin; AT: Antithrombin; GM: Gabexate mesilate; NM: Nafamostat mesilate; DS: Danaparoid sodium; MEPN: Meropenem; IPM/CS: Imipenem/Cilastatin; DRPM: Doripenem; SBT/CPZ: Sulbactam/Cefoperazone; TAZ/PIPC: Tazobactam/Piperacilin.

Table 3 Factors associated with persistent disseminated intravascular coagulation (univariate analysis)

	Persistent DIC (n = 25)	Resolved DIC (n = 41)	P value	OR (95%CI)
Age (> 80 yr)	9	18	0.610	0.72 (0.26-2.0)
Female	7	16	0.431	0. 61 (0.21-1.8)
Primary disease (Malignant)	15	9	0.003	5.3 (1.8-16)
Severity of cholangitis (Severe)	23	37	1.000	1.2 (0.21-7.3)
DIC score (> 6)	12	15	0.442	1.6 (0.58-4.4)
SIRS score (> 3)	11	24	0.313	0.56 (0.20-1.5)
Without biliary drainage	14	3	< 0.001	16 (3.9-66)
Without rTM	19	17	0.010	4.5 (1.5-14)
Without AT	12	13	0.203	2.0 (0.71-5.5)
Without GM	5	17	0.107	0.35 (0.11-1.1)
Without NM	12	32	0.016	0.26 (0.088-0.76)
Without DS	22	37	1.000	0.79 (0.16-3.9)
Plt (< 80 × 103/μL)	12	24	0.452	0.65 (0.24-1.8)
FDP (> 25 μg/mL)	17	20	0.201	2.2 (0.79-6.3)
PT-INR	10	12	0.426	1.6 (0.57-4.6)
Fib (< 200 mg/dL)	7	5	0.186	2.8 (0.78-10)
CRP (> 15 mg/dL)	7	14	0.786	0.75 (0.25-2.2)
T-Bil (> 10 mg/dL)	4	3	0.412	0.49 (0.35-12)

DIC: Disseminated intravascular coagulation; SIRS: Systemic inflammatory response syndrome; rTM: Recombinant human soluble thrombomodulin; AT: Antithrombin; GM: Gabexate mesilate; NM: Nafamostat mesilate; DS: Danaparoid sodium; Plt: Platelet count; FDP: Fibrin/fibrinogen degradation products; PT-INR: Prothrombin time-international normalized ratio; CRP: C-reactive protein; Fib: Fibrinogen; T-Bil: Total bilirubin.

Table 4 Factors associated with persistent disseminated intravascular coagulation (multivariate analysis)

	P value	OR (95%CI)
Primary disease (Malignant)	0.055	3.9 (0.97-16)
Without biliary drainage	0.003	12 (2.3-60)
Without rTM	0.080	4.3 (0.84-22)
Without GM	0.680	1.5 (0.25-8.5)
Without NM	0.188	0.37 (0.083-1.6)
Fib (< 200 mg/dL)	0.403	2.2 (0.35-14)

rTM: Recombinant human soluble thrombomodulin; GM: Gabexate mesilate; NM: Nafamostat mesilate; Fib: Fibrinogen.