Arab Journal of Gastroenterology 15 (2014) 123–129
Contents lists available at ScienceDirect
Arab Journal of Gastroenterology journal homepage: www.elsevier.com/locate/ajg
Original Article
Procoagulant versus anticoagulant factors in cirrhotic patients Mohamed A. El Bokl a, Amal Shawky a, George S. Riad a, Hisham S. Abdel Fattah b,⇑, Hassan Shalaby b, Ahmed Nady a, Dina Khattab c a
Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt Department of Internal Medicine, Faculty of Medicine, Misr University for Science and Technology, Cairo, Egypt c Department of Clinical Pathology, Faculty of Medicine, Ain Shams University, Cairo, Egypt b
a r t i c l e
i n f o
Article history: Received 9 March 2014 Accepted 3 August 2014
Keywords: Anticoagulants Cirrhosis Procoagulants
a b s t r a c t Background and study aim: Liver cirrhosis leads to decreased production of clotting factors that are generally all produced in the liver except factor VIII and von Willebrand factor. However, cirrhotic patients are not protected from thrombosis. The present study aimed to assess the procoagulant and anticoagulant factors in cirrhotic patients with and without bleeding and/or thrombotic events. Patients and methods: A total of 102 adult subjects were enroled: 51 cirrhotic patients and 51 healthy controls. After full history taking with special attention given to thromboembolic and haemorrhagic events, platelet count, serum albumin, bilirubin, international normalised ratio (INR), PT, partial thromboplastin time (PTT), hepatitis B surface antigen (HBsAg), hepatitis B core (HBc) antibodies, hepatitis C virus (HCV) antibodies, factor VIII, protein C, Protac-induced coagulation inhibition percentage (PICI%) assay and abdominal ultrasound were performed for patients and controls. Upper gastrointestinal endoscopy was conducted for the patients. Results: Compared with control subjects, factor VIII and factor VIII/protein C were significantly higher, while protein C and PICI% were significantly lower among patients. Conclusion: Patients with liver cirrhosis may have a tendency for bleeding or thrombosis according to the balance of coagulant and anticoagulant status. PICI%, the assay that evaluated the functionality of the protein C anticoagulant system, was significantly lower in patients compared to control subjects. Accordingly, low PICI% and high factor VIII/protein C ratio can be taken as an index of hypercoagulability in cirrhotic patients. Ó 2015 Arab Journal of Gastroenterology. Published by Elsevier B.V.
Introduction The balance of coagulation in normal conditions is ensured by the tight control of thrombin generation. This control results from two opposing drivers: The procoagulant and the anticoagulants. Among the procoagulant drivers, factor VIII plays a key role, being responsible together with other factors for boosting thrombin generation [1]. Liver cirrhosis is characterised by clinical bleeding and decreased levels of most procoagulant factors with the notable exceptions of factor VIII and von Willebrand factors (vWF) [2]. However, this is accompanied by a decrease in levels of naturally occurring anticoagulants as anti-thrombin and protein C [3]. The protein C system downregulates haemostasis because it inhibits thrombin as well as the essential cofactors Va and VIIIa. Thrombin initiates this inhibitory pathway by binding a membrane-associated protein, ⇑ Corresponding author. Tel.: +20 01277725777. E-mail address: [email protected] (H.S. Abdel Fattah). http://dx.doi.org/10.1016/j.ajg.2014.08.003 1687-1979/Ó 2015 Arab Journal of Gastroenterology. Published by Elsevier B.V.
thrombomodulin, to activated protein C. Proteins C and S are vitamin K-dependent factors synthesised by hepatocytes. While they are often called anticoagulants, they primarily prevent normal endothelial cells from serving as a site of thrombin generation. Thus, patients with cirrhosis are not naturally auto-anticoagulated as previously believed. This concept is reinforced by clinical evidence indicating that they are not protected and may even be at an increased risk of thrombosis [4]. The basic laboratory tests of coagulation, prothrombin time (PT) and activated partial thromboplastin time (PTT) have been used to assess the risk of bleeding. However, their results are poorly correlated with the onset and duration of bleeding after liver biopsy or other potentially haemorrhagic procedures [5]. This coagulant imbalance associated with liver cirrhosis can be detected by measuring thrombin generation in plasma in the presence and absence of thrombomodulin [6]. An alternative method uses a snake venom extract, Protac. This acts as a surrogate activator of protein C. Results are expressed as a percentage of extract-induced coagulation inhibition measured as the amount
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of thrombin generated in the presence of versus the absence of the venom extract. Protac-induced coagulation inhibition percentage (PICI%) assay is the chromogenic assay, designed to globally evaluate the functionality of the protein C anticoagulant system. It is based on the ability of endogenous activated protein C generated after activation of protein C by snake venom extract (Protac) to reduce the tissue factor-induced thrombin generation [7]. The aim of this study was to assess the imbalance between procoagulant and anticoagulant factors in Egyptian cirrhotic patients with and without bleeding or thrombotic events using the new PICI% assay. Patients and methods A total of 102 adult subjects (51 cirrhotic patients and 51 controls) were included in this case–control study. All were recruited from the Internal Medicine Department, Hepatology inpatient and outpatient clinics of Ain Shams University Hospitals, and Faculty of Medicine, Misr University for Science and Technology (MUST). The study protocol conformed to the ethical guidelines of Ain Shams University and was approved by the local ethics committee of scientific research. Prior to initiation, every subject was informed about the aim of the study and they gave consent. Subjects were divided into two groups: Group ‘‘I’’ Fifty-one patients with cirrhosis with a median age of 55 years (27 males and 24 females) were classified into three groups according to the severity of disease, which was estimated according to the Child–Pugh–Turcotte (CPT) score. Inclusion criteria included patients with cirrhosis diagnosed on the basis of clinical, laboratory and ultrasound results. Group ‘‘II’’ or control group This group included 51 healthy individuals with a median age of 49 years (28 males and 23 females). Exclusion criteria included subjects using any drugs known to interfere with blood coagulation, subjects with ongoing bacterial infections, hepatocellular carcinoma or extra-hepatic malignancy as well as pregnancy and childhood (age 0.05 were considered not significant. Results The present study included 102 subjects divided into two groups. Group I included 51 patients with cirrhosis with a mean age of 55 years, 27 (52.94%) males and 24 (47.06%) females. They were classified into three groups according to the severity of disease, estimated by the CPT score. Group I CPT class A included 17 patients, with a mean age of 53 years, 10 (58.82%) males and seven (41.18%) females. Group I CPT class B included 16 patients, with a mean age of 56 years, eight (50%) males and eight (50%) females. Group I CPT class C included 18 patients with cirrhosis, with a mean age of 53 years, nine (50%) males and nine (50%) females. All patients were hepatic C positive and hepatitis B negative based on negative HBsAg and HBcAb. Group II or (control group) included 51 healthy individuals with a median age of 49 years, 28 (55%) males and 23 (45%) females. The comparison between patients and control subjects regarding age and sex revealed statistically non-significant differences (P = 0.64 and 0.94, respectively). The main demographic characteristics of the study population are summarised in Table 1. The main upper gastrointestinal endoscopic findings of all the patients as well as patients classified according to the CPT score are summarised in Table 2. Tables 3 and 4 demonstrate the comparison between patients and controls as regards the main haemostatic parameters and events and the comparison between patient groups classified according to CPT and controls as regards the main haemostatic parameters, respectively. Table 5 summarises MELD and MELD-XI of all the included patients as well as those of patient groups classified according to CPT. The correlation between PICI% and different procoagulant and anticoagulant factors and the correlation between MELD and MELD-XI and procoagulant and anticoagulant factors are summarised in Tables 6 and 7, respectively. The PICI% showed statistically high significant correlations with all the procoagulant and anticoagulant parameters tested in the study except for PTT which showed no statistically significant difference. The original MELD score showed statistically high significant correlations with the main study parameters except for PICI% and platelet count which
showed no statistically significant correlations. On the other hand, MELD-XI showed no statistically significant correlations with any of the assessed parameters. Of the 51 patients, 35 had a positive history of bleeding; including haematemesis and melaena, seven out of 17 patients with CPT class A, 12 out of 16 patients with CPT class B and 11 out of 18 patients with CPT class C had bleeding. Regarding the distribution of the thromboembolic events (including portal vein thrombosis), 30 of the 51 patients, three out of 17 patients with CPT class A, nine out of 16 patients with CPT class B and all patients with CPT class C were positive for the presence of thromboembolic events. The relation between bleeding events (including haematemesis and melaena) and thromboembolic events (including portal vein thrombosis) and the main study parameters in the study population are summarised in Tables 8 and 9. Bleeding events (including haematemesis and melaena) showed statistically high significant differences with PICI% (P = 0.001), INR (P = 0.001) and platelet count (P = 0.001). Moreover, it showed statistically significant differences with PT (P = 0.050), protein C% (P = 0.018), PTT (P = 0.056) and factor VIII/protein C ratio (P = 0.056). The relation with factor VIII% showed no statistically significant difference (P = 0.574). Regarding thromboembolic events, no statistically significant differences were found in relation to all the assessed parameters. The relation between bleeding events (including haematemesis and melaena) and thromboembolic events (including portal vein thrombosis) revealed statistically non-significant differences (v2 = 0.295, P = 0.578). On comparing the main study parameters in all patients as regards the grades of oesophageal varices, statistically non-significant differences were found with regard to all the study parameters (Table 10). Discussion In the current study, factor VIII, the main powerful procoagulants, was significantly higher in patients with cirrhosis than control subjects. Moreover, the levels of factor VIII significantly correlated with the CPT class. The higher the CPT class the higher the factor VIII level. This difference was significant on comparing controls with patients with CPT class B and on comparing patients
Table 1 Main demographic characteristics of study population. Characteristics
Control subjects (n = 51)
Patients (n = 51)
Patients (CPT score) A (n = 17)
B (n = 16)
C (n = 18)
55 ± 14
53 ± 18.5
56 ± 9.5
53 ± 19.5
28 23
27 24
10 7
8 8
9 9
Aetiology HCV(n) HBV(n)
0 0
51 0
17 0
16 0
18 0
Bleeding events Haematemesis (n) Melaena (n)
0 0
15 20
2 3
5 8
8 9
Thromboembolic events DVT (n) MI (n) CVS or TIA (n) PVT (n)
0 0 0 0
5 6 9 10
0 2 1 0
1 2 3 3
4 2 5 7
Age (years) Mean ± SD
49 ± 16
Gender Males (n) Females (n)
CPT score, Child–Pugh–Turcotte score; CVS, cerebrovascular stroke; HBV, hepatitis B virus; HCV, hepatitis C virus; MI, myocardial infarction; (n), number; PVT, portal vein thrombosis; TIA, transient ischaemic attack.
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Table 2 Main upper gastrointestinal endoscopic findings of study patients. Characteristics
Patients (n = 51)
Oesophageal varices grade
Small Large
Presence of Gastric Varix extension Presence of Portal hypertension gastropathy by upper endoscopy
7 17 7 22
Patients (CPT score) A (n = 17)
B (n = 16)
C (n = 18)
2 2 0 4
1 8 4 8
4 7 3 10
Values are expressed as number of observations among population. CPT score, Child–Pugh–Turcotte score.
Table 3 Comparison between patients and controls as regards the main haemostatic parameters and events. Characteristics Conventional coagulation profile tests
PT (seconds) PTT INR
Platelets 103 Specific coagulation investigations
Factor VIII (%) Protein C (%) PIC I (%) FVIII/PC ratio Bleeding events (n) PVT by U/S (n) Thromboembolic events (n)
Bleeding versus thromboembolic events
Controls (n = 51)
Patients (n = 51)
12 ± 2.5 37 ± 6 1.09 ± 0.1 289 ± 123.5 82 ± 19.2 90 ± 24.5 89 ± 7.37 0.875 ± 0.3 0 0 0
14.2 ± 5.2 40.5 ± 13.25 1.5 ± 0.55 88.5 ± 39.25 94.25 ± 17.83 34.95 ± 14.2 56.67 ± 37.02 2.78 ± 3.39 35 10 30
Z
P 2.51 2.19 4.84 5.28 3.04 5.71 5.77 5.36
0.01 0.028 0.001 0.001 0.001 0.001 0.001 0.001
INR, international normalisation ratio; PICI%, Protac-induced coagulation inhibition percentage; PT, prothrombin time; PTT, partial thromboplastin time. Any percent activity is relative to the reference normal plasma set at 100%.
Table 4 Comparison between patient’s groups classified according to Child–Pugh–Turcotte and controls as regards the main haemostatic parameters. X2
Patients (CPT score) Characteristics Conventional coagulation profile tests
Platelets l03 Specific coagulation investigations
PT (seconds) PTT INR Factor VIII (%) Protein C (%) PICI (%) FVIII/PC ratio
Controls (n = 51)
A (n = 17)
B (n = 16)
C (n = 18)
12 ± 2.5 37 ± 6 1.09 ± 0.1 289 ± 123.5 82 ± 19.2 90 ± 24.5 89 ± 7.375 0.875 ± 0.303
11 ± 2.5 39 ± 8.35 1.48 ± 0.305 90 ± 84 89.8 ± 14.75 45 ± 28.2 79 ± 41.33 1.962 ± 1.38
13 ± 4.15 37.5 ± 12.1 1.26 ± 0.385 81.5 ± 114.25 96.65 ± 12.15 37.6 ± 18.6 56.67 ± 27.32 2.326 ± 1.9
18 ± 6 49 ± 10.6 1.85 ± 0.45 80 ± 70 120 ± 45.3 21.3 ± 12.1 44.4 ± 26.215 5.394 ± 3.618
32. 28. 37. 29. 15. 44. 38. 42.
P value
55 1 50 8 58 0 32 3 33 6 73 0 657 53 9
Contents lists available at ScienceDirect
Arab Journal of Gastroenterology journal homepage: www.elsevier.com/locate/ajg
Original Article
Procoagulant versus anticoagulant factors in cirrhotic patients Mohamed A. El Bokl a, Amal Shawky a, George S. Riad a, Hisham S. Abdel Fattah b,⇑, Hassan Shalaby b, Ahmed Nady a, Dina Khattab c a
Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt Department of Internal Medicine, Faculty of Medicine, Misr University for Science and Technology, Cairo, Egypt c Department of Clinical Pathology, Faculty of Medicine, Ain Shams University, Cairo, Egypt b
a r t i c l e
i n f o
Article history: Received 9 March 2014 Accepted 3 August 2014
Keywords: Anticoagulants Cirrhosis Procoagulants
a b s t r a c t Background and study aim: Liver cirrhosis leads to decreased production of clotting factors that are generally all produced in the liver except factor VIII and von Willebrand factor. However, cirrhotic patients are not protected from thrombosis. The present study aimed to assess the procoagulant and anticoagulant factors in cirrhotic patients with and without bleeding and/or thrombotic events. Patients and methods: A total of 102 adult subjects were enroled: 51 cirrhotic patients and 51 healthy controls. After full history taking with special attention given to thromboembolic and haemorrhagic events, platelet count, serum albumin, bilirubin, international normalised ratio (INR), PT, partial thromboplastin time (PTT), hepatitis B surface antigen (HBsAg), hepatitis B core (HBc) antibodies, hepatitis C virus (HCV) antibodies, factor VIII, protein C, Protac-induced coagulation inhibition percentage (PICI%) assay and abdominal ultrasound were performed for patients and controls. Upper gastrointestinal endoscopy was conducted for the patients. Results: Compared with control subjects, factor VIII and factor VIII/protein C were significantly higher, while protein C and PICI% were significantly lower among patients. Conclusion: Patients with liver cirrhosis may have a tendency for bleeding or thrombosis according to the balance of coagulant and anticoagulant status. PICI%, the assay that evaluated the functionality of the protein C anticoagulant system, was significantly lower in patients compared to control subjects. Accordingly, low PICI% and high factor VIII/protein C ratio can be taken as an index of hypercoagulability in cirrhotic patients. Ó 2015 Arab Journal of Gastroenterology. Published by Elsevier B.V.
Introduction The balance of coagulation in normal conditions is ensured by the tight control of thrombin generation. This control results from two opposing drivers: The procoagulant and the anticoagulants. Among the procoagulant drivers, factor VIII plays a key role, being responsible together with other factors for boosting thrombin generation [1]. Liver cirrhosis is characterised by clinical bleeding and decreased levels of most procoagulant factors with the notable exceptions of factor VIII and von Willebrand factors (vWF) [2]. However, this is accompanied by a decrease in levels of naturally occurring anticoagulants as anti-thrombin and protein C [3]. The protein C system downregulates haemostasis because it inhibits thrombin as well as the essential cofactors Va and VIIIa. Thrombin initiates this inhibitory pathway by binding a membrane-associated protein, ⇑ Corresponding author. Tel.: +20 01277725777. E-mail address: [email protected] (H.S. Abdel Fattah). http://dx.doi.org/10.1016/j.ajg.2014.08.003 1687-1979/Ó 2015 Arab Journal of Gastroenterology. Published by Elsevier B.V.
thrombomodulin, to activated protein C. Proteins C and S are vitamin K-dependent factors synthesised by hepatocytes. While they are often called anticoagulants, they primarily prevent normal endothelial cells from serving as a site of thrombin generation. Thus, patients with cirrhosis are not naturally auto-anticoagulated as previously believed. This concept is reinforced by clinical evidence indicating that they are not protected and may even be at an increased risk of thrombosis [4]. The basic laboratory tests of coagulation, prothrombin time (PT) and activated partial thromboplastin time (PTT) have been used to assess the risk of bleeding. However, their results are poorly correlated with the onset and duration of bleeding after liver biopsy or other potentially haemorrhagic procedures [5]. This coagulant imbalance associated with liver cirrhosis can be detected by measuring thrombin generation in plasma in the presence and absence of thrombomodulin [6]. An alternative method uses a snake venom extract, Protac. This acts as a surrogate activator of protein C. Results are expressed as a percentage of extract-induced coagulation inhibition measured as the amount
124
M.A. El Bokl et al. / Arab Journal of Gastroenterology 15 (2014) 123–129
of thrombin generated in the presence of versus the absence of the venom extract. Protac-induced coagulation inhibition percentage (PICI%) assay is the chromogenic assay, designed to globally evaluate the functionality of the protein C anticoagulant system. It is based on the ability of endogenous activated protein C generated after activation of protein C by snake venom extract (Protac) to reduce the tissue factor-induced thrombin generation [7]. The aim of this study was to assess the imbalance between procoagulant and anticoagulant factors in Egyptian cirrhotic patients with and without bleeding or thrombotic events using the new PICI% assay. Patients and methods A total of 102 adult subjects (51 cirrhotic patients and 51 controls) were included in this case–control study. All were recruited from the Internal Medicine Department, Hepatology inpatient and outpatient clinics of Ain Shams University Hospitals, and Faculty of Medicine, Misr University for Science and Technology (MUST). The study protocol conformed to the ethical guidelines of Ain Shams University and was approved by the local ethics committee of scientific research. Prior to initiation, every subject was informed about the aim of the study and they gave consent. Subjects were divided into two groups: Group ‘‘I’’ Fifty-one patients with cirrhosis with a median age of 55 years (27 males and 24 females) were classified into three groups according to the severity of disease, which was estimated according to the Child–Pugh–Turcotte (CPT) score. Inclusion criteria included patients with cirrhosis diagnosed on the basis of clinical, laboratory and ultrasound results. Group ‘‘II’’ or control group This group included 51 healthy individuals with a median age of 49 years (28 males and 23 females). Exclusion criteria included subjects using any drugs known to interfere with blood coagulation, subjects with ongoing bacterial infections, hepatocellular carcinoma or extra-hepatic malignancy as well as pregnancy and childhood (age 0.05 were considered not significant. Results The present study included 102 subjects divided into two groups. Group I included 51 patients with cirrhosis with a mean age of 55 years, 27 (52.94%) males and 24 (47.06%) females. They were classified into three groups according to the severity of disease, estimated by the CPT score. Group I CPT class A included 17 patients, with a mean age of 53 years, 10 (58.82%) males and seven (41.18%) females. Group I CPT class B included 16 patients, with a mean age of 56 years, eight (50%) males and eight (50%) females. Group I CPT class C included 18 patients with cirrhosis, with a mean age of 53 years, nine (50%) males and nine (50%) females. All patients were hepatic C positive and hepatitis B negative based on negative HBsAg and HBcAb. Group II or (control group) included 51 healthy individuals with a median age of 49 years, 28 (55%) males and 23 (45%) females. The comparison between patients and control subjects regarding age and sex revealed statistically non-significant differences (P = 0.64 and 0.94, respectively). The main demographic characteristics of the study population are summarised in Table 1. The main upper gastrointestinal endoscopic findings of all the patients as well as patients classified according to the CPT score are summarised in Table 2. Tables 3 and 4 demonstrate the comparison between patients and controls as regards the main haemostatic parameters and events and the comparison between patient groups classified according to CPT and controls as regards the main haemostatic parameters, respectively. Table 5 summarises MELD and MELD-XI of all the included patients as well as those of patient groups classified according to CPT. The correlation between PICI% and different procoagulant and anticoagulant factors and the correlation between MELD and MELD-XI and procoagulant and anticoagulant factors are summarised in Tables 6 and 7, respectively. The PICI% showed statistically high significant correlations with all the procoagulant and anticoagulant parameters tested in the study except for PTT which showed no statistically significant difference. The original MELD score showed statistically high significant correlations with the main study parameters except for PICI% and platelet count which
showed no statistically significant correlations. On the other hand, MELD-XI showed no statistically significant correlations with any of the assessed parameters. Of the 51 patients, 35 had a positive history of bleeding; including haematemesis and melaena, seven out of 17 patients with CPT class A, 12 out of 16 patients with CPT class B and 11 out of 18 patients with CPT class C had bleeding. Regarding the distribution of the thromboembolic events (including portal vein thrombosis), 30 of the 51 patients, three out of 17 patients with CPT class A, nine out of 16 patients with CPT class B and all patients with CPT class C were positive for the presence of thromboembolic events. The relation between bleeding events (including haematemesis and melaena) and thromboembolic events (including portal vein thrombosis) and the main study parameters in the study population are summarised in Tables 8 and 9. Bleeding events (including haematemesis and melaena) showed statistically high significant differences with PICI% (P = 0.001), INR (P = 0.001) and platelet count (P = 0.001). Moreover, it showed statistically significant differences with PT (P = 0.050), protein C% (P = 0.018), PTT (P = 0.056) and factor VIII/protein C ratio (P = 0.056). The relation with factor VIII% showed no statistically significant difference (P = 0.574). Regarding thromboembolic events, no statistically significant differences were found in relation to all the assessed parameters. The relation between bleeding events (including haematemesis and melaena) and thromboembolic events (including portal vein thrombosis) revealed statistically non-significant differences (v2 = 0.295, P = 0.578). On comparing the main study parameters in all patients as regards the grades of oesophageal varices, statistically non-significant differences were found with regard to all the study parameters (Table 10). Discussion In the current study, factor VIII, the main powerful procoagulants, was significantly higher in patients with cirrhosis than control subjects. Moreover, the levels of factor VIII significantly correlated with the CPT class. The higher the CPT class the higher the factor VIII level. This difference was significant on comparing controls with patients with CPT class B and on comparing patients
Table 1 Main demographic characteristics of study population. Characteristics
Control subjects (n = 51)
Patients (n = 51)
Patients (CPT score) A (n = 17)
B (n = 16)
C (n = 18)
55 ± 14
53 ± 18.5
56 ± 9.5
53 ± 19.5
28 23
27 24
10 7
8 8
9 9
Aetiology HCV(n) HBV(n)
0 0
51 0
17 0
16 0
18 0
Bleeding events Haematemesis (n) Melaena (n)
0 0
15 20
2 3
5 8
8 9
Thromboembolic events DVT (n) MI (n) CVS or TIA (n) PVT (n)
0 0 0 0
5 6 9 10
0 2 1 0
1 2 3 3
4 2 5 7
Age (years) Mean ± SD
49 ± 16
Gender Males (n) Females (n)
CPT score, Child–Pugh–Turcotte score; CVS, cerebrovascular stroke; HBV, hepatitis B virus; HCV, hepatitis C virus; MI, myocardial infarction; (n), number; PVT, portal vein thrombosis; TIA, transient ischaemic attack.
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Table 2 Main upper gastrointestinal endoscopic findings of study patients. Characteristics
Patients (n = 51)
Oesophageal varices grade
Small Large
Presence of Gastric Varix extension Presence of Portal hypertension gastropathy by upper endoscopy
7 17 7 22
Patients (CPT score) A (n = 17)
B (n = 16)
C (n = 18)
2 2 0 4
1 8 4 8
4 7 3 10
Values are expressed as number of observations among population. CPT score, Child–Pugh–Turcotte score.
Table 3 Comparison between patients and controls as regards the main haemostatic parameters and events. Characteristics Conventional coagulation profile tests
PT (seconds) PTT INR
Platelets 103 Specific coagulation investigations
Factor VIII (%) Protein C (%) PIC I (%) FVIII/PC ratio Bleeding events (n) PVT by U/S (n) Thromboembolic events (n)
Bleeding versus thromboembolic events
Controls (n = 51)
Patients (n = 51)
12 ± 2.5 37 ± 6 1.09 ± 0.1 289 ± 123.5 82 ± 19.2 90 ± 24.5 89 ± 7.37 0.875 ± 0.3 0 0 0
14.2 ± 5.2 40.5 ± 13.25 1.5 ± 0.55 88.5 ± 39.25 94.25 ± 17.83 34.95 ± 14.2 56.67 ± 37.02 2.78 ± 3.39 35 10 30
Z
P 2.51 2.19 4.84 5.28 3.04 5.71 5.77 5.36
0.01 0.028 0.001 0.001 0.001 0.001 0.001 0.001
INR, international normalisation ratio; PICI%, Protac-induced coagulation inhibition percentage; PT, prothrombin time; PTT, partial thromboplastin time. Any percent activity is relative to the reference normal plasma set at 100%.
Table 4 Comparison between patient’s groups classified according to Child–Pugh–Turcotte and controls as regards the main haemostatic parameters. X2
Patients (CPT score) Characteristics Conventional coagulation profile tests
Platelets l03 Specific coagulation investigations
PT (seconds) PTT INR Factor VIII (%) Protein C (%) PICI (%) FVIII/PC ratio
Controls (n = 51)
A (n = 17)
B (n = 16)
C (n = 18)
12 ± 2.5 37 ± 6 1.09 ± 0.1 289 ± 123.5 82 ± 19.2 90 ± 24.5 89 ± 7.375 0.875 ± 0.303
11 ± 2.5 39 ± 8.35 1.48 ± 0.305 90 ± 84 89.8 ± 14.75 45 ± 28.2 79 ± 41.33 1.962 ± 1.38
13 ± 4.15 37.5 ± 12.1 1.26 ± 0.385 81.5 ± 114.25 96.65 ± 12.15 37.6 ± 18.6 56.67 ± 27.32 2.326 ± 1.9
18 ± 6 49 ± 10.6 1.85 ± 0.45 80 ± 70 120 ± 45.3 21.3 ± 12.1 44.4 ± 26.215 5.394 ± 3.618
32. 28. 37. 29. 15. 44. 38. 42.
P value
55 1 50 8 58 0 32 3 33 6 73 0 657 53 9
