ORIGINAL ARTICLE
Correlation of Thrombocytopenia with Grading of Esophageal
Varices in Chronic Liver Disease Patients
Amanullah Abbasi, Nazish Butt, Abdul Rabb Bhutto and S.M. Munir
ABSTRACT
Objective: To determine the severity of thrombocytopenia in different grades of esophageal varices.
Study Design: Cross-sectional analytical study.
Place and Duration of Study: Jinnah Postgraduate Medical Centre, Karachi, Medical Unit-III, Ward-7 from January to
December 2008.
Methodology: Subjects were eligible if they had a diagnosis of cirrhosis. Patient with advanced cirrhosis (Child-Pugh
class C), human immunodeficiency virus (HIV) infection, hepatocellular carcinoma, portal vein thrombosis, parenteral drug
addiction, current alcohol abuse and previous or current treatment with β-blockers, diuretics and other vasoactive drugs
were excluded from the study. All patients under went upper gastrointestinal endoscopy after consent. On the basis of
platelet count patients were divided into four groups; Group I with platelets ≤ 20000/mm3, Group II with values of 2100050000/mm3, Group III with count of 51000-99000/mm3 and Group IV with count of 100000-150000/mm3. Correlation of
severity of thrombocytopenia with the grading of esophageal varices was assessed using Spearman’s correlation with
r-values of 0.01 considered significant.
Results: One hundred and two patients with thrombocytopenia and esophageal varices were included in the study. There
were 62 (60.8%) males and 40 (39.2%) females. The mean age of onset of the disease in these patients was 49.49±14.3
years with range of 11-85 years. Major causes of cirrhosis were hepatitis C (n=79, 77.5%), hepatitis B (n=12, 11.8%),
mixed hepatitis B and C infection (n=8, 7.8%) and Wilson’s disease (n=3,2.9%). Seven patients had esophageal grade I,
24 had grade II, 35 had grade III, and 36 had grade IV. Gastric varices were detected in 2 patients. Portal hypertensive
gastropathy were detected in 87 patients. There was an inverse correlation of platelet count with grading of esophageal
varices (r=-0.321, p < 0.001).
Conclusion: The severity of thrombocytopenia increased as the grading of esophageal varices increased. Thrombocyte
count was significantly and inversely correlated with the grade of esophageal varices.
Key words:
Thrombocytopenia. Grading. Esophageal varices. Correlation. Chronic liver disease. Hepatitis C.
INTRODUCTION
Esophageal and para-esophageal varices are abnormally
dilated collateral veins within the wall of the esophagus
that project directly into the lumen and are prone to
haemorrhage. These are a result of portal hypertension
secondary to cirrhosis.1,2 Bleeding from gastro-esophageal
varices is the most serious and life threatening
complication of cirrhosis, accounts for 10% of all cases
of bleeding from the upper gastrointestinal tract.
Approximately two-third of patients with decompensated
cirrhosis and one third of those with compensated
cirrhosis have varices at the time of diagnosis.3 About
30% of these patients will experience an episode of
variceal haemorrhage within one year of the diagnosis of
varices.4-5 Patients with advanced cirrhosis have a complex
haemostatic disturbance, and thrombo cytopenia
(platelet count < 150,000/µl) is a common complication
Ward-7, Jinnah Postgraduate Medical Centre, Karachi.
Correspondence: Dr. Amanullah Abbasi, Ward-7, Jinnah
Postgraduate Medical Centre, Karachi.
E-mail: draman_ullah2000@yahoo.com
Received January 31, 2009; accepted April 16, 2010.
in patients of chronic liver disease (CLD).6-8 Thrombocytopenia is reported in as many as 76% of cirrhotic
patients.9 In CLD patients, the pathogenesis of thrombocytopenia is multifactorial. Possible causes include splenic
sequestration of platelets, suppression of platelet
production in bone marrow, and decreased activity of
the hematopoietic growth factor thrombo-poietin.10
The objective of the study was to determine the
correlation of the thrombocytopenia with esophageal
variceal grading, that may predict the large esophageal
varices and help select patients for upper gastrointestinal endoscopy.
METHODOLOGY
This cross-sectional analytical study was conducted at
Hepatology Unit of Ward-7, Jinnah Postgraduate Medical
Centre, Karachi, from January to December 2008.
Subjects were eligible if they had a diagnosis of cirrhosis
based on history, physical examination, biochemical
parameters and liver biopsy in some cases. All patients
of cirrhosis with esophageal varices and concomitant
thrombocytopenia were included in the study. Patient
with advanced cirrhosis (Child-Pugh class C), antibodies
Journal of the College of Physicians and Surgeons Pakistan 2010, Vol. 20 (6): 369-372
369
Amanullah Abbasi, Nazish Butt, Abdul Rabb Bhutto and S.M. Munir
against human immunodeficiency virus (HIV), hepatocellular carcinoma and portal vein thrombosis evident on
ultrasonography, parenteral drug addiction, current
alcohol abuse, previous or current treatment with
β-blockers, diuretics and other vasoactive drugs were
excluded from the study. Demographic data such as
age, gender and residence were recorded. At entry, a
full medical history was taken. All patients underwent a
complete physical examination.
Haematological and biochemical workup included
complete blood picture, liver function tests, prothrombin
time, albumin and total protein estimation. All patients
were asked about alcohol intake and tested for hepatitis
BsAg, anti-HCV antibody using ELISA method to
determine the cause of liver cirrhosis. Tests for other
causes of cirrhosis (serum ceruloplasmin and slit lamp
examination for Wilson’s disease, tests for autoantibodies for autoimmune liver disease, iron studies for
hemochromatosis) were carried out only if there was a
suggestive clue.
A verbal and written consent for extended examination
was taken from patients and/or their attendants after
explaining the intention of procedure. All patients
underwent upper gastrointestinal endoscopy after
consent. All patients were kept fasting overnight prior to
the procedure at our institution. All the endoscopies
were performed by the first author. Endoscopic variceal
band ligation was our first line management for patients
with active variceal bleeding. They were evaluated for
the presence and grade of esophageal varices (EV), the
presence of gastric varices and portal hypertensive
gastropathy. In the presence of esophageal varices size
was graded as I-IV using the Paquet grading system.11
On the basis of severity of thrombocytopenia patients
was divided into three groups; group I with platelet count
of ≤ 20000/µL, group II with count of 21000-50000/µL,
group III with count of 51000-99000/µL and group IV
with count of 100000-150000/µL. Correlation of severity
of thrombocytopenia with the grading of esophageal
varices was assessed. Upper gastrointestinal endoscopy
was done on Olympus EVIS 180 Series endoscopes.
Correlation of thrombocytopenia with grading of esophageal
varices was analyzed by applying Spearman’s rank
correlation test. A p-value of < 0.01 was considered as
significant correlation. Descriptive statistics were
obtained for the variables where applicable, using SPSS
version 15.
RESULTS
A total of 130 patients were reviewed, out of whom 102
patients with thrombocytopenia and esophageal varices
were included in the study. There were 62 (60.8%)
males and 40 (39.2%) females. The mean age of onset
of the disease in those patients was 49.49±14.3 years
with range of 11-85 years. Anti-HCV antibody was positive
370
in 79 (77.5%), hepatitis BsAg in 12 (11.8%), mixed
hepatitis B and C infection in 8 (7.8%) and Wilson’s
disease in 3 (2.9%) patients. The presenting symptoms
were haemetemesis in 47 (45.07%), ascites in 17
(16.6%), malena in 6 (5.88%), and hepatic
encephalopathy in 21 (20.6%). Seven patients had
esophageal variceal grade I, 24 had grade II, 35 had
grades III and 36 had grade IV. Gastric varices were
detected in 2 patients. Portal hypertensive gastropathy
were detected in 87 patients. Thrombocytopenia was
found to have correlation with grading of esophageal
varices presented in Table I. Spearman’s rank
correlation test revealed an inverse relation between
platelet count and grading of esophageal varices
(r=-0.321). It was a significant correlation with p-value of
< 0.001, suggested that, as platelet count decreased the
grading of esophageal varices increased as shown in
Table II.
Table I: Correlation of thrombocytopenia with grading of EV (n=102).
Platelet count
≤ 20000
EV grade
Number of
Grade I
Grade II
Grade III
Grade IV
00
00
1
2
(33.33%) (66.66%)
21000-50000
00
04
11
(13.33%) (36.66%)
50000-99,000
05
(8.92%)
100,000-150,000
15
patients
3
(2.94%)
15
30
(50%)
(32.35%)
17
56
19
(26.78%) (33.92%) (30.35%) (54.90%)
02
05
04
02
13
(15.38%) (38.46%) (30.77%) (15.38%) (12.74%)
Table II: Correlation of esophageal varices and other variables in
patients of liver cirrhosis.
Variables
Mean±SD
Platelets
66715.69± 30481.41
-.321*
r
p-value
Haemoglobin
8.955±2.374
-.195
0.051
Biluirbin
3.319±5.463
-.086
0.456
Albumin
2.747±0.604
-.036
0.791
0.001
*Correlation is significant at the 0.01 level (2-tailed).
DISCUSSION
The main aim of the present study was to evaluate the
correlation of thrombocytopenia with the grade of the
esophageal varices. Variceal gastrointestinal bleeding is
a life threatening complication of portal hypertension in
patients with chronic liver disease, leading to significant
morbidity and mortality as well as higher hospital care
costs.12-13 Variceal haemorrhage occurs in 25-35% of
patients with cirrhosis and accounts for 80-90% of
bleeding episodes in these patients.13
The study showed that male gender had a greater
frequency of chronic liver disease and its complications.
The mean age of developing CLD in developing
countries including Pakistan is much lower as compared
to developed countries. In this study, hepatitis caused by
C and B viruses was the leading cause of cirrhosis, but
none of the patients had alcoholic liver disease as an
underlying pathology. In Pakistan, it is estimated that at
Journal of the College of Physicians and Surgeons Pakistan 2010, Vol. 20 (6): 369-372
Correlation of thrombocytopenia with grading of esophageal varices in chronic liver disease patients
least 9 million people harbor Hepatitis B virus, and over
14 million are chronically infected with Hepatitis C.14-17
Esophageal varices being an inclusion criterion were
present in all patients in this study, but only 46.07% of
the patients presented with haemetemesis. Guidelines
of the American Association for the Study of Liver
Diseases (AASLD) suggest that patients with Child's
stage A liver cirrhosis and signs of portal hypertension,
specifically a platelet count of less than 140,000/mm ,
and/or enlarged portal vein diameter of greater that
13 mm or those classified as Child's B or C at diagnosis
should have screening endoscopy.18 AASLD guidelines
recommend endoscopic screening of patients with
cirrhosis for varices and treatment of patients with
medium/large varices to prevent bleeding. Recommended
endoscopic screening intervals are 1-3 years, depending
on presence/absence of varices and whether patient
has compensated/decompensated liver disease.19-20
However, this recommendation imposes a major burden
on endoscopy units and incurred high costs on patients.
Thrombocytopenia was previously suggested as
important and reliable predictor of varices in CLD
patients studied in different studies.21-25 In this study, the
severity of thrombocytopenia was evaluated as the nonendoscopic factor to predict the size and grade of
esophageal varices. This study found significant
correlation between severity of thrombocytopenia and
EV in CLD patients. Severity of thrombocytopenia was
found to be inversely related to the grading of EV. This
study model helps the general practitioners and
physicians working in the villages and peripheries of the
country where the facilities of ultrasonography and
endoscopy are not available to practice a prophylactic
approach for esophageal varices without waiting for the
above mentioned investigations. It also makes it easier
to filter appropriate patients to refer to the tertiary care
centres for endoscopy. Selecting patients for an upper
GI endoscopy becomes cost effective and on the other
hand, defines patients who need a critical management.
The treatment can be planned on the basis of severity of
thrombocytopenia and therefore, patient can be referred
early, to tertiary care unit bandligation and primary
prophylaxis of haemetemesis.
CONCLUSION
The severity of thrombocytopenia increased with the
increasing grade of esophageal varices. The platelet
count was significantly and inversely correlated with
grading of esophageal varices so that, as the grading of
esophageal varices increased the count of platelets
decreased.
REFERENCES
1.
Cotran RS, Kumar V, Collins T, Robins SL, editors. Robbins
pathologic basis of disease. 6th ed. Philadelphia: WB Saunders; 1999.
2.
Sherlock S, Dooley J. Diseases of the liver and biliary system.
10th ed. Oxford (UK): Wiley Blackwell Science; 1997.
3.
Jenny L, Eulenia R, Nolasco ML, Venancio IG, Ernesto OD,
Virgilio PB. Clinical predictors of bleeding from esophageal
varices: a retrospective study. Phillipine J Gastroenterol 2006; 2:
103-11.
4.
Paunescu V, Grigorean V, Popesco C. [Risk factors for
immediate outcome of gastrointestinal bleeding in patients with
cirrhosis]. Chirurgia (Bucur) 2004; 99:311-22. Romanian.
5.
Murachima N, Ikeda K, Kobayashi M, Saitoh S, Chayama K,
Tsabuta A, et al. Incidence of the appearance of the red colour
sign on esophageal varices and its predictive factors: long-term
observation of 359 patients with cirrhosis. J Gastroenterol 2001;
36:368-74.Comment in: p. 433-5.
6.
Zwicker JI, Drews RE. Hematologic disorders and the liver. In:
Schiff ER, Sorrell MF, Maddrey WC, editors. Schiff's diseases of
the liver. Philadelphia: Lippincott Williams & Wilkins; 2007. p. 349-63.
7.
Hedner U, Erhardtsen E. Hemostatic disorders in liver diseases.
In: Schiff ER, Sorrell MF, Maddrey WC, editors. Schiff's diseases
of the liver. Philadelphia: Lippincott Williams & Wilkins; 2003. p.
625-36.
8.
Fiore LD, Brophy MT, Deykin D. Hemostasis. In: Zakim D, Boyer
TD, editors. Hepatology: a text book of liver disease.
Philadelphia: WB Saunders; 2003. p. 549-80.
9.
Giannini EG. Review article: thrombocytopenia in chronic liver
disease and pharmacologic treatment options. Aliment Pharmacol
Ther 2006; 23:1055-65.
10. Nascimbene A, Iannacone M, Brando B, De Gasperi A. Acute
thrombocytopenia after liver transplant: role of platelet
activation, thrombopoietin deficiency and response to high dose
intravenous IgG treatment. J Hepatol 2007; 47:651-57. Epub 2007
Jul 23. Comment in: p. 625-9.
11. Paquet KJ. Prophylactic endoscopic sclerosing treatment of the
esophageal wall in varices: a prospective controlled trial.
Endoscopy 1982; 14:4-5.
12. Arguedas MR, Heudebert GR, Eloubedi MA, Abrams G, Fallon
MB. Cost- effectiveness of screening, surveillance, and primary
prophylaxis strategies for esophageal varices. Am J Gastroenterol
2002; 97:2441-52.
13. Sharara AI, Rockey DC. Gastroesophageal variceal haemorrhage.
N Engl J Med 2001; 345:669-81.
14. Janjua NZ, Nizami MA. Knowledge and practice of barbers
about hepatitis B and C transmission in Rawalpindi and
Islamabad. J Pak Med Assoc 2004; 54:116-9.
15. Qureshi H. Viral hepatitis- are we ready to control? The medical
spectrum. J Pak Med Assoc 2003; 24:1-2.
16. Akhter J. Surgeon and hepatitis B and C. J Coll Physicians Surg Pak
2004; 14:327-8.
17. Ambreen G, Iqbal F. Prevalence of hepatitis C in patients on
maintenance hemodialysis. J Coll Physicians Surg Pak 2003; 13:15-7.
18. Qureshi W, Adler DG, Davila R, Egan J, Hirota W, Leighton J,
et al. ASGE guideline: the role of endoscopy in the management
of variceal haemorrhage, updated July 2005. Gastrointest Endosc
2005; 62:651-5. Comment in: Gastrointest Endosc 2006; 63:735.
19. Damico G, Garcia Tsao G, Cales P, Escorsell A, Nevens F,
Cestari R, et al. Diagnosis of portal hypertension: how and when.
Journal of the College of Physicians and Surgeons Pakistan 2010, Vol. 20 (6): 369-372
371
Amanullah Abbasi, Nazish Butt, Abdul Rabb Bhutto and S.M. Munir
esophageal varices in alcoholic cirrhotic patients. Gastroenterology
1999; 116:A1211.
In: de Franchis R. Portal hypertension III. Proceedings of the
third Baveno international consensus workshop on definitions:
methodology and therapeutic strategies. Oxford (UK): Blackwell
Science; 2001.p. 36-64.
23. Zaman A, Hapke R, Flora K, Rosen HR, Bennet K. Factors
predicting the presence of esophageal or gastric varices in
patients with advanced liver disease. Am J Gastroenterol 1999; 94:
3292-6.
20. de Franchis R. Updating consensus in portal hypertension:
report of the Baveno III consensus workshop on definitions,
methodology and therapeutic strategies in portal hypertension.
J Hepatol 2000; 33:846-52.
24. Madhotra R, Mulcahy HE, Wilner I, Reuben A. Prediction of
esophageal varices in patients with cirrhosis. J Clin Gastroenterol
2002; 34:81-5. Comment in: p. 4-5.
21. Chalasani N, Imperiale TF, Ismail A, Sood G, Carey M, Wilcox CM,
et al. Predictors of large esophageal varices in patients with cirrhosis.
Am J Gastroenterol 1999; 94:3285-91. Comment in: p. 3103-5.
25. Hong WD, Zhu QH, Huang ZM, Chen XR, Jiang ZC, Xu SH,
et al. Predictors of esophageal varices in patients with HBV-related
cirrhosis: a retrospective study. BMC Gastroenterol 2009; 9:11.
22. Freeman JG, Darlow S, Cole AT. Platelet count as a predictor of
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