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Grading of Peripheral Cytopenias due to Splenomegaly and Hepatitis B Cirrhotic Portal Hypertension | OMICS International
ISSN: 2167-1095
Journal of Hypertension: Open Access
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Grading of Peripheral Cytopenias due to Splenomegaly and Hepatitis B Cirrhotic Portal Hypertension

Yunfu Lv1*, Wan Yee Lau1,2, Xiaoyu Han1, Xiaoguang Gong1, Qingyong Ma3, Shunwu Chang1, Hongfei Wu1, Yejuan Li1 and Jie Deng1

1Department of General Surgery, Hainan Provincial People’s Hospital, Haikou 570311, P R China

2Faculty of Medicine, The Chinese University of Hong Kong, P R China

3Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi’an Jiaotong, University, Xi’an 710061, P R China

*Corresponding Author:
Yunfu Lv
Department of General Surgery
Hainan Provincial People’s Hospital
Haikou 570311, P R China
Tel: 086-136-87598368
E-mail: [email protected]

Received Date: September 12, 2014; Accepted Date: September 19, 2014; Published Date: September 24, 2014

Citation: Lv Y, Lau WY, Han X, Gong X, Ma Q, et al. (2014) Grading of Peripheral Cytopenias due to Splenomegaly and Hepatitis B Cirrhotic Portal Hypertension. J Hypertens 3:182. doi:10.4172/2167-1095.1000182

Copyright: © 2014 Lv Y, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Visit for more related articles at Journal of Hypertension: Open Access

Abstract

Background: Splenomegaly due to hepatitis B cirrhotic portal hypertension is common in clinical practice, and it is often complicated by monolineage or multilineage cytopenias. We attempted to answer the following questions based on our 20 years of observation and research: can peripheral cytopenias be graded and what are the effects of peripheral cytopenia grades on clinical outcomes?

Objectives: This study aimed to investigate the grading of peripheral cytopenia in patients with splenomegaly due to hepatitis B cirrhotic portal hypertension and its effect on clinical outcomes.

Methods: Data from 330 patients with splenomegaly due to hepatitis B cirrhotic portal hypertension were collected from January 1991 to December 2011. All data were analysed with SPSS 13.0. Univariate and multivariate analyses were performed. The various forms of cytopenia were scored and graded according to the F value of the multiple linear regression equation. Depending mainly on the severity, cytopenia was graded as mild, moderate, or severe, and was given a total score of 3 points, respectively. Their relationships with clinical outcomes on follow up (cured, improved, no change or dead) were then compared.

Results: All patients in this study were treated with splenectomy +/- devascularization or total porto-systemic shunting operation. Of 330 patients, 99 (30%) patients had monolineage cytopenia, 118 (35.8%) bilineage cytopenia, and 113 (34.2%) trilineage cytopenia. On univariate analysis, severity of erythropenia was related to a significant difference in surgical outcome on intra-group comparison (P<0.05). On multivariate analysis, thrombocytopenia was related to a significant difference in surgical outcome when compared with leukopenia and erythropenia (P<0.05). A significant difference in surgical outcome existed among the three grades (mild, moderate, and severe) of cytopenia (P<0.05).

Conclusion: Peripheral cytopenias had significant impact on clinical outcomes. The more severe the cytopenias, the worse the surgical outcomes. Thrombocytopenia was a major factor affecting surgical outcomes. The thrombocytopeniabased three-level grading of cytopenia provided a basis for analyzing individual patients, planning treatment, and assessing prognosis in clinical practice.

Keywords

Cirrhotic portal hypertension; Cytopenia; Grading; Clinical significance

Introduction

Peripheral cytopenia is a reduction in number of blood cells in peripheral blood, including a leukocyte (WBC) count of <4.0×109/L, an erythrocyte (RBC) count of <4.0×1012/L, and/or a platelet (PLT) count of <100×109/L. Peripheral cytopenia is common in patients with splenomegaly as a consequence of hepatitis B cirrhotic portal hypertension. Peripheral cytopenia plays a significant role among many factors which affect surgical outcomes in these patients [1]. In this study, peripheral cytopenias were graded, and the relationship of the grade with surgical outcomes and its clinical significance were investigated.

Clinical Data

General information

This is a retrospective study. Of 330 patients with splenomegaly due to hepatitis B cirrhotic portal hypertension complicated by peripheral cytopenias operated between January 1991 to December 2011, there were 225 males and 105 females, making a male to female ratio of 2.2:1. The patients’ ages ranged from 15 to 79 (mean 45) years. Hepatitis B cirrhosis was confirmed by histopathology on hepatic biopsy specimens taken during operations (Figure 1). The average spleen size was 224 mm×159 mm×95 mm, as measured by ultrasound or computed tomogram (CT) scan. Upper gastrointestinal imaging and endoscopy revealed medium-to-severe varices in distal esophagus and gastric fundus. Sixty-seven patients (20.3%) were admitted into hospital for gastrointestinal hemorrhage, and 224 (67.9%) had a previous history of haemorrhage. Splenectomy was carried out after blood transfusion to supplement the deficient white blood cells (WBC), red blood cells (RBC) or platelet (PLT). In addition, 306 patients received extensive devascularization around the cardia (plus a splenorenal vein shunt in 54 patients), five received a mesocaval shunt, and five received a portacaval shunt. Thus, 14 patients received splenectomy only.

hypertension-pathology

Figure 1: Pathology of cirrhosis 40x.

Statistical analysis

All data were analysed using SPSS 13.0. Statistical significance was assessed using the chi-square test for univariate analyses or multiple linear regression for multivariate analyses; a P value <0.05 was considered significant.

Results

The surgical outcomes were classified as cured, improved, no change or dead. Those classified as cured met the following criteria: disappearance of ascites, abdominal distension, and hemorrhage, with increase in blood cell counts to normal, improvement in liver function, and no severe postoperative complications. Those who were classified as dead either died during hospitalization or on follow up. Those who showed no change in their clinical course, blood cell counts and liver function were classified as no change. All others were considered as improved. Scoring was as follows: a PLT count of >50 <100×109/L was scored as 1, 30-50×109/L as 2, and <30×109/L as 3; a RBC count of 3-4×1012/L was scored as 0, and <3×1012/L as 1; a WBC count of 2-4×109/L was scored as 0, and <2×109/L as 1. Therefore, peripheral cytopenias were graded as mild (<2), moderate (2-3) or severe (>3) (Table 1). The effects of the different total scores on surgical outcomes are shown in Table 2. Comparison of outcomes between the three grades revealed significant differences (P<0.005).

Item Mild Moderate Severe
PLT >50 30-50 <30
(Score) 1 2 3
RBC >3 02-Mar <2
(Score) 0 1 1
WBC >3 02-Mar <2
(Score) 0 0 1
Total score <2 02-Mar >3

Table 1: Grading of peripheral cytopenias

Total score Case number Surgical outcome χ2, P value
Cured (%) Improved (%) No change/Death (%)
0-1 205 118 (57.6%) 73 (35.6%) 14 (6.8%) χ2 = 104.775 P = 0.005
02-Mar 95 40 (42.1%) 43 (45.3%) 12 (12.6%)
04-May 30 10 (33.3%) 14 (46.7%) 6 (20.0%)

Table 2: Comparison of the influence of different scores on the therapeutic effect

Comparisons of surgical outcomes for each patient with monolineage cytopenia are shown in Table 3. Patients with monolineage cytopenia had significantly better surgical outcomes than those with multilineage cytopenia (Tables 4 and 5).

Group Scoring Patient number Surgical outcomes χ2, P value
Cured (%) Improved (%) No change/Dead (%)
Leukopenia (×109/L, n = 14) <2 1 1 (100) 0 0 χ2 = 1.478, P = 0.478
02-Mar 10 6(60) 4 (40) 0
03-Apr 3 1 (33.3) 2 (66.7) 0
Erythropenia (×1012/L, n = 58) <2 4 3 (75) 0 1 (25) χ2 = 10.908, P = 0.028
02-Mar 20 16 (80) 2 (10) 2 (10)
03-Apr 34 16 (47.1) 16(47.1) 2 (5.8)
Thrombocytopenia (×109/L, n = 27) 3 3 1 (33.3) 2 (66.7) 0 χ2 = 2.220, P = 0.695
2 1 1 (100) 0 0
1 23 15 (65.2) 7 (30.4) 1 (4.4)

Table 3: Comparisons of surgical outcomes for each monolineage peripheral cytopenia

Item Patient number Surgical outcome χ2, P value
Cured (%) Improved (%) No change/Dead (%)
Monolineage cytopenias 99 60 (60.6%) 33 (33.3%) 6 (6.1%) χ2 = 7.446,
Bilineage cytopenias 118 51 (43.2%) 51 (43.2%) 16 (13.6%) P = 0.024

Table 4: Comparison of surgical outcomes between monolineage cytopenias and bilineage cytopenias

Item Patient number Surgical outcome χ2, P value
Cured (%) Improved (%) No change/Dead (%)
Monolineage cytopenias 99 60 (60.6) 33 (33.3) 6 (6.1) χ2 = 7.819
Multilineage cytopeniasa 231 103 (44.6) 102 (44.2) 26(11.2) P = 0.02

Table 5: Comparison of surgical outcomes between monolineage cytopenias and multilineage cytopenias

Comparison among thrombocytopenia, leucopenia, and erythropenia revealed a significant difference, indicating that thrombocytopenia was the major influential factor of surgical outcomes (Table 6).

Item T value P value
Thrombocytopenia 2.827 0.005
Erythropenia -0.439 0.661
Leukopenia 1.516 0.13
Constant 1.395 0

Table 6: Multiple linear regression analysis of cytopenias in 330 patients

Discussion

Over 90% of patients with splenomegaly due to hepatitis B cirrhotic portal hypertension are complicated with cytopenias [2], of which, 70% develop multilineage cytopenia and 30% develop monolineage cytopenia. The effect of mild peripheral cytopenia on a patient is usually not a matter of concern. However, severe leukopenia causes immune dysfunction and reduces the patient’s resistance to infection. Severe erythropenia can result in ischemia, hypoxia, and even necrosis of tissues. Severe thrombocytopenia can result in reduced hemostasis and increased risk of bleeding, which can be life-threatening. In this paper, the causes of death of the patients included surgical wound bleeding, postoperative wound exudation, abdominal cavity infection and hepatic encephalopathy, but decreased peripheral blood cells is the basic and underlying factor. The greater the number of different types of decreased blood cells and the more severe the reduction, the greater is the risk to the patient.

In our study on monolineage cytopenia, only the severity of erythropenia was related to a significant difference in surgical outcomes on intra-group comparison (P<0.05). Although thrombocytopenia was not shown to be significant on univariate analysis, it was the only significant influential factor of surgical outcomes on multiple linear regression analysis (P<0.005).

The grading of cytopenias was based on: (i) the multiple linear regression equation Y = 1.395+0.151PLT which was obtained from the multiple linear regression analysis with a constant P=0.001. This indicated that the multiple linear regression analysis was feasible in this study. The analysis demonstrated thrombocytopenia to be the main factor affecting surgical outcomes (P<0.005). Therefore, the grading was based on thrombocytopenia and a score of 1-3 was assigned to the different levels of thrombocytopenia. (ii) The significant difference on intra-group comparison of erythropenia in monolineage cytopenias with a P<0.05. A RBC count of ≤ 3×1012/L was given a score of 1. (iii) Although leukopenia was shown to have no significant difference on both univariate and multivariate analyses, in clinical practice patients with extremely low WBC are susceptible to serious infections resulting in adverse effects. Therefore, a WBC count of ≤ 2×109/L was given a score of 1. A total score of <2 indicated mild cytopenia, 2-3 indicated moderate cytopenia, and >3 indicated severe cytopenias. A comparison of surgical outcomes between the three grades revealed a significant difference (P<0.005), demonstrating that severe cytopenia have a significantly worse prognosis than mild cytopenia. Thus, it is scientific and feasible to grade cytopenia by this scoring method. If cytopenia is caused by hypersplenism, this grading can also be applied to grade hypersplenism or at least it can be used as a reference. Non-surgical treatment is preferred for mild cytopenia, while surgical treatment (splenectomy) is generally preferred for severe cytopenia. After removal of an enlarged spleen, blood count increased significantly [3]. In principle, non-surgical treatment is also preferred for moderate cytopenia, and surgical treatment should only be considered after failed non-surgical treatment for these patients.

Thrombocytopenia is a significant and common complication of hepatitis B cirrhotic portal hypertension [4,5]. It is related not only to retention of blood cells in the spleen, blood cell aggregation, and enhanced phagocytosis by macrophages [6], but also to viral hepatitis infection and compensation and regulation of marrow [7]. Djordevic et al. [8,9] suggested that extreme thrombocytopenia can be a risk factor for decreased survival. A PLT count of <30×109/L can cause variceal hemorrhage in distal esophagus and gastric fundus, and intraoperative and postoperative massive hemorhage [10], which can be lifethreatening. Therefore, PLT transfusion should be performed before or during operation to increase the PLT count to 50×109/L, to ensure safety of the patients. Transfusion should also be performed when bleeding occurs. Cui et al. [11] reported that combined transfusion of PLT and fibrinogen (FB) could achieve even better effect. Splenectomy should be carried out when the PLT count does not increase significantly after transfusion of 12-24 units of PLT or decreases to the original lowest count 1-2 days after the transfusion [12]. Mastuura et al. [13] suggested that a high postoperative PLT count was also a risk factor of decreased survival, and therefore the patient should be closely monitored for a high PLT count postoperatively [14,15] and appropriate treatment should be administrated immediately when necessary.

The main limitations of this study are that it is a retrospective study, the data came from a single center and all patients in this study had hepatitis B cirrhosis. Whether the results of this study can be applied to other patients require further studies.

All patients who were enrolled in this study underwent splenectomy, though it might be performed for a variety of reasons such as gastrointestinal bleeding, splenomegaly or hypersplenism. Cytopenia grading is of clinical significance in disease severity assessment, academic communication, communication with patients and their relatives, choosing treatment, and deciding on perioperative management in the future.

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