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​Cihat Şen, ​Nicola Volpe

Cecilia Villain, Daniel Rolnik, M. Mar Gil

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Murat Yayla, Oluş Api

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Resul Arısoy

Evaluation of platelet count and platelet function in intrahepatic cholestasis of pregnancy

Mehmet Sıddık Evsen, Hatice Ender Soydinç, Ali Özler, Serdar Başaranoğlu, Talip Karaçor, Ahmet Yalınkaya, Derya Uçmak, Muhsin Kaya

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Evaluation of platelet count and platelet function in intrahepatic cholestasis of pregnancy . Perinatal Journal 2012;20(2):45-48 DOI: 10.2399/prn.12.0202003

Author(s) Information

Mehmet Sıddık Evsen1,
Hatice Ender Soydinç1,
Ali Özler1,
Serdar Başaranoğlu1,
Talip Karaçor1,
Ahmet Yalınkaya1,
Derya Uçmak2,
Muhsin Kaya3

  1. Dicle Üniversitesi Tıp Fakültesi Kadın Hastalıkları ve Doğum Anabilim Dalı- Diyarbakır TR
  2. Dicle Üniversitesi Tıp Fakültesi Dermatoloji Anabilim Dalı- Diyarbakır TR
  3. Dicle Üniversitesi Tıp Fakültesi Gastroenteroloji Anabilim Dalı- Diyarbakır TR
Publication History

Manuscript Received: April 10, 2012

Earlyview Date: June 19, 2015

Conflicts of Interest

No conflicts declared.

Platelet count (PC) and function have been reported to be increased in inflammatory incident. The aim of the study is to evaluate PC and mean platelet volume (MPV) in patients with intrahepatic cholestasis of pregnancy (ICP) and to compare them to normal pregnancies.  
The patients with ICP and newborns files were retrospectively reviewed at Obstetrics and Gynecology Department, Dicle University between January 2009-December 2011. During the study period 6,743 birth was found in our clinic. Twenty-two patients with ICP identified and 32 subject enrolled as a control group which have no systemic disease or risk factors that may complicate pregnancy. Groups were compared in terms of demographic, biochemical parameters, PC, MPV, and Apgar scores.
The incidence of patients with ICP was found to be 3.2/1000 in this study. The average time to diagnose is 34.2±2.2 gestational weeks. Pruritus (72.7%) were found to be the most common presenting symptom in patients and the 13.6% of patients present jaundice. There was no difference in the average birth weight of newborns and 1-5 Apgar scores between the two groups. Four (18.2%) patients of the ICP developed fetal distress and three of these patients had meconium stained amniotic fluid. There was no fetal distress or meconium stained amniotic fluid in the control group. The average PC in patient and control group were 268.9 x 109 K/uL and 226.5 x 109 K/uL respectively (p=0.037) and MPV were 10.6 fL and 8.9 fL (p=0.004) respectively. Platelet count and MPV were significantly higher in patients with ICP when compared to control group.
Increased platelet count and function in patients with intrahepatic cholestasis of pregnancy may be indicative of inflammation.

Pregnancy, intrahepatic cholestasis, platelet count, platelet function test.

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disease with unclear etiology which may start at any week after 30th gestational week, usually may recover by delivery. The symptoms mostly complained by the patients are the itching especially on extremities and excoriated skin caused by itching.[1] Many causes have been accused in the etiology of cholestasis of pregnancy; however, the primary reason cannot be explained clearly. Increased bile acid levels in the cases of intrahepatic cholestasis of pregnancy cause itching on skin and jaundice. It has been reported that risks such as preterm labor, amniotic fluid with meconium, fetal distress and intrauterine fetal loss are increased in terms of fetus.[2,3] Platelet count (PC) and its function have increased in systemic inflammatory disease.[4] In this study, we aimed to evaluate PC and its functions in ICP cases and to compare them with the control group.
In this study, 22 patients who applied to Obstetrics and Gynecology Department of Dicle University in between January 2009 and December 2011 and diagnosed as ICP were evaluated. Data during applications were collected from hospital archives and patient files. Patients were evaluated in terms of age, gravida, parity, number of living children, gestational week, newborn Apgar scores, liver function tests, full blood count, urinalysis, and biochemical parameters. Platelet count (PC) and mean platelet volume (MPV) were compared between patient group and control group. Patients were examined by abdominal USG in order to exclude liver and bile duct pathologies and cases without any pathology were included into the study. Patients who were found to have allergic diseases, dermatitides, chronic liver diseases, disease that may cause biliary obstructions (cholelithiasis – choledocholithiasis), hypothyroidism, hyperthyroidism, hypertensive diseases that may affect liver functions (preeclampsia, eclampsia, HELLP), pregnancy-induced acute hepatic lipidosis by differential diagnosis and patients who did not give birth in our clinic were excluded from the study.
Steroid treatment was applied to 12 (54.5%) patients at 28th-34th gestational week in order to provide fetal lung maturation. Thirty-two pregnants who had no systemic disease or risk factor that may complicate the pregnancy were included into the control group.
Data were evaluated on SPSS (Statistical Package for Social Sciences) for Windows 15.0 (SPSS, Inc., Chicago, IL, USA), Epi info and Excel for statistical analysis. Numerical data were controlled by Kolmogrov-Smirnov test if they were distributed regularly or not, and Mann-Whitney U test was applied since there was no regular distribution. Results were found statistically significant at 95% confidence interval and when p <0.05. Approval of Ethics Committee of Dicle University was obtained.
Twenty-two patients with ICP diagnosis and 32 patients (as control group) who had no pathology complicating pregnancy were included into this study. It was found that there were 6,743 deliveries in our clinic within the specified period. Demographic and obstetric data of cases are presented in Table 1.
It was observed that application symptoms of the patients were itching (72.7%) and jaundice (13.6%). Mean PC and MPV values in patients with ICP were found as significantly increased compared to the control group. Liver function tests and mean PC and MPV values are listed in Table 2. Mean diagnosis period of patients during application to clinic after symptoms appeared was 34.2±2.2 gestational week and all patients were at or below 37th gestational week.
In the patient group, it was confirmed that four (18.2%) cases had fetal distress and it was found that amniotic fluid was stained by meconium in three of these patients. In the control group, no fetal distress and amniotic fluid with meconium was observed. Newborn birth weights and Apgar scores of patients are shown in Table 3. There was no neonatal mortality in any newborn.
ICP incidence was found as 0.32% in this study. Kurt et al.[5] found that incidence of Central Anatolia is 1.4%. Incidence of the disease varies regionally; while it was reported as 0.32% in the USA and as 0.2-1.5% in Europe, it was reported high as 6.5-27.6%.[1,6-9]
The etiology of the disease is complex and it is considered that factors such as hormones, diets etc. High level of liver function test (ALT, AST) is the most significant indication accompanying the diagnosis. ICP is diagnosed by the presence of liver function test abnormality and excluding other etiological reasons causing jaundice and itching. Itching was a symptom in 72.7% of patients during application. Jaundice generally becomes evident 1-4 weeks after itching.[1] HELLP syndrome should be considered particularly during differential diagnosis, because preterm labor is required in the treatment of HELLP syndrome while the management of ICP cases can be followed up to term by appropriate treatment and follow up. In both cases where hepatic enzyme is found high, HELLP syndrome diagnosis is ruled out due to non-existence of hypertension, proteinuria and thrombocytopenia.[1]
The disease should be followed-up closely after diagnosis and medical treatment should be applied. Although chenodeoxycholic acid may be given, ursodeoxycholic acid should be preferred since it is safer for both mother and baby and its advantage of decreasing preterm labor risk by perinatal morbidity.[10] Placental ischemia has been reported in the cases of intrahepatic cholestasis of pregnancy; placental ischemia and oxygenation disorder may cause fetal complications such as fetal distress, preterm labor, fetal cardiac dysrhythmia and baby with meconium. Nevertheless, pathophysiology of fetal adverse effects have not been understood clearly yet. It has been considered that abnormal contractions occurring in chorionic vessels have major roles on placental pathologies.[11,12]
Platelets are the smallest shaped elements of the blood and they have a role in thrombosis. However, they also include mediators in the granules secreted which have vasoconstrictor effect. Activated platelets include granules which include pro-inflammatory mediators (thromboxane A2, serotonin, leukotriene) and free oxygen radicals; they cause thrombotic activity to increase and micro-vascular circulation to get disorder. Effects of platelets which are in the circulation of pro-thrombotic activity are bigger. MPV is a cheap, easy and effective method for the evaluation of platelet functions; its high level is a parameter showing the increase of platelet synthesis and function.[4,13,14] MPV was found significantly high in diseases such as rheumatoid arthritis associated with inflammation, ankylosing spondylitis, acute ischemic stroke, familial Mediterranean fever and acute pancreatitis.[4,15-17]
In the literature, the only study comparing PC and MPV in ICP cases was conducted by Kebapcilar et al.[18] In their study, 40 cases with ICP were compared with 40 control pregnants. Consequently, they reported that patient group had lower 1st and 5th minute Apgar scores and higher MPV values compared to the control group. In our study, there was statistically significant difference between the MPV values of patients with ICP and the control group; however, Apgar scores were found similar.
Consequently, PC and increase in the functions of patients with ICP compared to the control group may be an indication of inflammation.
1. Williamson C, Mackillop L. Diseases of the liver, biliary system, and pancreas. In: Creasy RK, Resnik R, editors. Creasy&Resnik’s Maternal-Fetal Medicine. 6th ed. Philadelphia: Saunders Elsevier; 2009. p. 1059-77.
2. Lammert F, Marschall HU, Glantz A, Maternl S. Intrahepatic cholestasis of pregnancy: molecular pathogenesis, diagnosis and management. J Hepatol 2000;33:1012-21.
3. Beuers U, Pusl T. Intrahepatic cholestasis of pregnancy: a heterogeneous group of pregnancy related disorders? Hepatology 2006;43:647-49.
4. Yazici S, Yazici M, Erer B, Erer B, Calik Y, Bulur S, et al. The platelet functions in patients with ankylosing spondylitis: anti-TNF-alpha therapy decreases the mean platelet volume and platelet mass. Platelets 2010;21:126-31.
5. Kurt A, Ecevit A, Kısa B, İnce DA, Tarcan A, Yanık FB. İntrahepatik kolestazlı gebelerin neonatal sonuçları. Perinatoloji Dergisi 2011;19:10-14.
6. Reyes H, Taboada G, Ribalta J. Prevalence of intrahepatic cholestasis of pregnancy in La Paz, Bolivia. J Chronic Dis 1979; 32:499-504.
7. Glantz A, Marschall HU, Mattsson LA. Intrahepatic cholestasis of pregnancy: relationships between bile acid levels and fetal complication rates. Hepatology 2004;40:467-74.
8. Rioseco AJ, Ivankovic MB, Manzur A, Hamed F, Kato SR, Parer JT et al. Intrahepatic cholestasis of pregnancy: a retrospective case-control study of perinatal outcome. Am J Obstet Gynecol 1994;170:890-5.
9. Laifer SA, Stiller RJ, Siddiqui DS, Dunston-Boone G, Whetham JC. Ursodeoxycholic acid for the treatment of intrahepatic cholestasis of pregnancy. J Matern Fetal Med 2001;10:131-5.
10. Arrese M, Reyes H. Intrahepatic cholestasis of pregnancy: a past and present riddle. Ann Hepatol 2006;5: 202–5.
11. Sepulveda WH, Gonzalez C, Cruz MA, Rudolph MI. Vasoconstrictive effect of bile acids on isolated human placental chorionic veins. Eur J Obstet Gynecol Reprod Biol 1991;42:211-5.
12. Lammert F, Marschall HU, Glantz A, Matern S. Intrahepatic cholestasis of pregnancy: molecular pathogenesis, diagnosis and management. J Hepatol 2002; 33:1012-21.
13. Martin JF, Trowbridge EA, Salmon G, Plumb J. The biological significance of platelet volume: its relationship to bleeding time, platelet thromboxane B2 production and megakaryocyte nuclear DNA concentration. Thromb Res 1983; 32:443-60.
14. Chaouate A, Weitzenblum E, Higenbottam T. The role of thrombosis in severe pulmonary hypertension. Eur Respir J 1996;9:356-63.
15. Makay B, Türkyılmaz Z, Ünsal E. Mean platelet volume in children with familial Mediterranean fever. Clin Rheumatol 2009;28:975-8.
16. Yazici S, Yazici M, Erer B, Erer B, Calik Y, Ozhan H, Ataoglu S. The platelet indices in patients with rheumatoid arthritis: mean platelet volume reflects disease activity. Platelets 2010; 21:122-5.
17. Yılmaz N, Özkan OV, Büyükbaş S, Can Y, Öztürk HO, Aydoğan A, Yönden Z. Akut pankreatit hastalarında ortalama trombosit hacmi. Klinik ve Deneysel Araştırmalar Dergisi 2011;2:362-5 .
18. Kebapcilar AG, Taner CE, Kebapcilar L, Bozkaya G. High mean platelet volume, low-grade systemic coagulation, and fibrinolytic activation are associated with pre-term delivery and low Apgar score in intrahepatic cholestasis of pregnancy. J Matern Fetal Neonatal Med 2010;23:1205-10.
Table 1.
Comparison of demographic and obstetric data of the groups.
Table 2.
Comparison of hematologic and biochemical parameters of the groups.
Table 3.
Comparison of newborn results of the groups.