DOI: http://dx.doi.org/10.18203/2320-1770.ijrcog20213834

Clinical correlates of plasma antithrombin and protein C levels in patients with pre-eclampsia and eclampsia in Sokoto, Northwest Nigeria

Abubakar U. Musa, Aisha I. Mamman, Abubakar A. Panti, Abdul Wahab Alhassan, Anas F. Rabi'u

Abstract


Background: Hypertensive disorders of pregnancy complicate 17% of pregnancies in Sokoto, Nigeria with pre-eclampsia and eclampsia accounting for 6% and 4.29% respectively. Pre-eclampsia and eclampsia stand out as major causes of poor pregnancy outcomes with eclampsia contributing 46% of adolescent maternal mortality in Sokoto. These disorders increase risk of venous thromboembolism, DIC, placental abruption, IUGR, premature delivery and recurrent pregnancy loss. The roles of antithrombin and protein C in disease severity and outcomes of pregnancies in pre-eclampsia/eclampsia are subject of recent researches albeit with conflicting findings. The aim of the study was to determine the plasma antithrombin and protein C levels of pre-eclampsia and eclampsia in Sokoto with a view to assessing any relationship with clinical severity and pregnancy outcomes.

Methods: Prospective comparative study involving 31 each of pregnant women with pre-eclampsia, eclampsia and normotensive pregnancy. Plasma antithrombin and protein C levels were determined via kinetic method using S4 Nortek semi-automated coagulometer. Data analysis was performed using SPSS version 21.0.  

Results: The mean plasma antithrombin and protein C levels for eclampsia, pre-eclampsia and normotensive pregnancy were (61.17±9.13 and 60.00±5.76) vs (71.24±13.15 and 71.06±6.16) vs (85.54±8.77 and 89.64±7.61) respectively; p=0.0001. Severe pre-eclampsia when compared with mild pre-eclampsia had lower antithrombin (70.21±13.58 vs 73.74±12.43; p=0.507) and protein C (70.52±6.27 vs 72.40±6.00; p=0.451) levels respectively, though without statistical significance. Pre-eclampsia with low plasma antithrombin levels had increased risk of preterm delivery when age, gravidity and booking status were factored (OR, 1.2, 95% CI 0.035 to 0.348, p=0.017).

Conclusions: Lower plasma antithrombin and protein C levels were found with eclampsia and severe pre-eclampsia suggesting consumptive depletion of anticoagulants with disease progression. Women with pre-eclampsia and low plasma antithrombin levels were found to have increased odds of having preterm delivery when age, gravidity and booking status were considered.


Keywords


Antithrombin, Protein C, Pre-eclampsia, Eclampsia, Pregnancy, Sokoto

Full Text:

PDF

References


Duley L. The global impact of pre-eclampsia and eclampsia. Semin Perinatol. 2009;33(3):130-7.

Steegers EA, Dadelszen P, Duvekot JJ, Pijnenborg R. Pre-eclampsia. Lancet. 2010;376(9741):631-44.

WHO. WHO Recommendations for Prevention and Treatment of Pre-Eclampsia and Eclampsia. Geneva: WHO; 2011.

Singh S, Ahmed EB, Egondu SC, Ikechukwu NE. Hypertensive disorders in pregnancy among pregnant women in a Nigerian Teaching Hospital. Niger Med J. 2014;55(5):384-8.

Ekele BA, Bello SO, Adamu AN. Clusters of eclampsia in a Nigerian teaching hospital. Int J Gynaecol Obstet. 2007;96(1):62-6.

Airede LR, Ekele BA. Adolescent maternal mortality in Sokoto, Nigeria. J Obstet Gynaecol. 2003;23(2):163-5.

ACOG technical bulletin. Hypertension in pregnancy. Number 219--January 1996 (replaces no. 91, February 1986). Committee on Technical Bulletins of the American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet. 1996;53(2):175-83.

Sibai BM. Diagnosis, prevention, and management of eclampsia. Obstet Gynecol. 2005;105(2):402-10.

Rodie VA. Pre-eclampsia and Eclampsia: Pathophysiology and Treatment Options. Rev Bras Hipertens. 2006;13(2):88-95.

Roberts JM, Cooper DW. Pathogenesis and genetics of pre-eclampsia. Lancet. 2001;357(9249):53-6.

Phipps E, Prasanna D, Brima W, Jim B. Preeclampsia: Updates in Pathogenesis, Definitions, and Guidelines. Clin J Am Soc Nephrol. 2016;11(6):1102-13.

Cunningham FG, Leveno KJ, Bloom SL, Hawth JC, Gilstrap LC, Wenstron KD. Hypertensive Disorders of Pregnancy. IWilliam’s Obstetrics. 22nd ed. New York, NY: McGraw-Hill; 2005: 761-808.

Musa AU, Ndakotsu MA, Ibrahim A, Ahmed Y, Abdul H, Awwalu S. Plasma Levels of Fibrinogen and D-dimer of Eclamptics in Sokoto Northwest Nigeria. EAS J Med Sci. 2019;2(6):290-5.

Mello G, Parretti E, Marozio L, Pizzi C, Lojacono A, Frusca T, et al. Thrombophilia is significantly associated with severe preeclampsia: results of a large-scale, case-controlled study. Hypertension. 2005;46(6):1270-4.

Yalinkaya A, Erdemoglu M, Akdeniz N, Kale A, Kale E. The relationship between thrombophilic mutations and preeclampsia: a prospective case-control study. Ann Saudi Med. 2006;26(2):105-9.

Matsouka CJ. Haemostatic Changes during Pregnancy. Haematology. 2005;8(1):68-71.

Demir C, Dilek I. Natural coagulation inhibitors and active protein c resistance in preeclampsia. Clinics. 2010;65(11):1119-22.

Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007;39(2):175-91.

Araoye MO. Subjects Selection. Research Methodology with Statistics for Health and Social Sciences. 1st ed. Nigeria: Nathadex Publishers; 2004: 115-121.

SIEMENS. Berichrom® Antithrombin III (A) Product Leaflet (OWWRG17E11Rev.04-en). SIEMENS GmbH Germany. 2018;1:1-5.

SIEMENS. Berichrom® Protein C Product Leaflet (OUVVG15E11Rev.04-en). SIEMENS GmbH Germany. 2017;1:1-6.

Duckitt K, Harrington D. Risk factors for pre-eclampsia at antenatal booking: systematic review of controlled studies. BMJ. 2005;330(7491):565.

Saghafi N, Mohammadzadeh VA, Tara F, Pourali L, Dadgar S. Evaluation of selected thrombotic factors among pregnant women with preeclampsia and normal pregnant women. Iran J Reprod Med. 2014;12(12):793-8.

Ekwempu CC. Maternal mortality in eclampsia in the Guinea Savannah region of Nigeria. Clin Exp Hypertens B. 1982;1(4):531-7.

Yakasai IA, Gaya SA. Maternal and fetal outcome in patients with eclampsia at Murtala Muhammad specialist Hospital Kano, Nigeria. Ann Afr Med. 2011;10(4):305-9.

Okogbenin SA, Eigbefoh JO, Omorogbe F, Okogbo F, Okonta PI, Ohihoin AG. Eclampsia in Irrua Specialist Teaching Hospital: a five-year review. Niger J Clin Pract. 2010;13(2):149-53.

Jimoh AAG, Akintade OA, Balogun OR, Aboyeji AP. Eclampsia – A Ten year review in a Nigerian Teaching Hospital. Nigeria Hosp Pract. 2007;1(3):80-3.

Madauci I, Isa Y, Daura B. Hausa Customs. Africa: Northern Nigeria Publishing; 2008: 18-23.

Anorlu RI, Iwuala NC, Odum CU. Risk factors for pre-eclampsia in Lagos, Nigeria. Aust N Z J Obstet Gynaecol. 2005;45(4):278-82.

Tukur J, Umar BA, Rabi'u A. Pattern of eclampsia in a tertiary health facility situated in a semi-rural town in Northern Nigeria. Ann Afr Med. 2007;6(4):164-7.

Harrison KA. The importance of the educated healthy woman in Africa. Lancet. 1997;349(9052):644-7.

Oladokun A, Okewole AI, Adewole IF, Babarinsa IA. Evaluation of cases of eclampsia in the University College Hospital, Ibadan over a 10 year period. West Afr J Med. 2000;19(3):192-4.

Nafaty AU, Melah GS, Massa AA, Audu BM, Nelda M. The analysis of eclamptic morbidity and mortality in the Specialist Hospital Gombe, Nigeria. J Obstet Gynaecol. 2004;24(2):142-7.

Azeez MG, Kashmoola M. Evaluation of Protein C, Protein S and Antithrombin in patients with Preeclampsia. Sch J App Med Sci. 2007;5(5):2028-35.

Mattar F, Sibai BM. Eclampsia. VIII. Risk factors for maternal morbidity. Am J Obstet Gynecol. 2000;182(2):307-12.

Nwobodo EI, Ahmed Y. Maternal Mortality associated with Eclampsia in Sokoto, Nigeria. OJM. 2011;23:1-4.

Awodu OA, Shokunbi WA, Ejele OA. Lupus anticoagulant in Nigerian women with preeclampsia. West Afr J Med. 2003;22(3):240-2.

Soomro S, Kumar R, Lakhan H, Shaukat F. Risk Factors for Pre-eclampsia and Eclampsia Disorders in Tertiary Care Center in Sukkur, Pakistan. Cureus. 2019;11(11):6115.

Holmes VA, Wallace JM. Haemostasis in normal pregnancy: a balancing act? Biochem Soc Trans. 2005;33(2):428-32.

Kaur S, Khan S, Nigam A. Hematological profile and pregnancy: a review. Int J Adv Med. 2014;1(2):68-70.

James AH, Rhee E, Thames B, Philipp CS. Characterization of antithrombin levels in pregnancy. Thromb Res. 2014;134(3):648-51.

Imoru, M, Buseri FI. Protein C and Antithrombin III in Healthy Nigerian Women. Int J Haematol Res. 2015;1(1):20-3.

Okoye HC, Eweputanna LI, Okpani AO, Ejele OA. Associations between pre-eclampsia and protein C and protein S levels among pregnant Nigerian women. Int J Gynaecol Obstet. 2017;137(1):26-30.

Osmanağaoğlu MA, Topçuoğlu K, Ozeren M, Bozkaya H. Coagulation inhibitors in preeclamptic pregnant women. Arch Gynecol Obstet. 2005;271(3):227-30.

Heilmann L, Rath W, Pollow K. Hemostatic abnormalities in patients with severe preeclampsia. Clin Appl Thromb Hemost. 2007;13(3):285-91.

Prabriputaloong S, Insiripong S. The plasma levels of Protein S and Protein C activities among the pregnant women with and without Preeclampsia. Srinagarind Med J. 2013;28:223-6.

Stefano V, Rossi E, Paciaroni K, Leone G. Screening for inherited thrombophilia: indications and therapeutic implications. Haematologica. 2002;87(10):1095-108.

Yenidede I, Silfeter DB, Pekin O, Turgut A, Ulkumen BA, Dayicioglu V. Inherited Thrombophilia and Pre-eclampsia. Int J Bas Clinic Stud. 2016;5(1):26-36.