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Physiological changes in some hematological and coagulation profile among Sudanese healthy pregnant women.

Introduction

Pregnancy, also known as gravidity or gestation, is the time during which one or more offspring develops inside a woman's womb. [1] In a pregnancy, there can be multiple gestations, as in the case of twins or triplets. Childbirth usually occurs approximately 38 weeks after conception. In case of women who have a menstrual cycle length of 4 weeks, this is approximately 40 weeks from the last normal menstrual period. [2] The World Health Organization defines normal term for delivery as between 37 and 42 weeks. [3] Pregnancy is associated with profound anatomical, physiological, biochemical, and endocrine changes that affect multiple organs and systems. [4] These changes are essential to help the woman adapt to the pregnancy state and to aid fetal growth and survival. The hematologic system must adapt in a number of ways, such as provision of vitamins and minerals for fetal hematopoiesis (iron, vitamin B12, folic acid), which can exacerbate maternal anemia and preparation for bleeding at delivery, which requires enhanced hemostatic function. [5] The most significant hematological changes are physiologic anemia, neutrophilia, mild thrombocytopenia, increased procoagulant factors, and diminished fibrinolysis. [6] Red blood cell (RBC) mass begins to increase at 8-10 weeks of gestation and steadily rises by 20%-30% (250-450 mL) above normal pregnant levels by the end of the pregnancy in women taking iron supplements. [7] Among women not on iron supplements, the RBC mass may only increase by 15%-20%. Plasma levels of factors VII, VIII, IX, and XII, together with fibrinogen and fibrin degradation products, increase during pregnancy. Pregnancy is also associated with enhanced platelet turnover. [8] Coagulation factors remain elevated for up to 8-12 weeks postpartum and assays for them may be falsely negative during this period. Thus, pregnancy is a prothrombotic state. Activated partial thromboplastin time (APTT) is usually shortened in pregnancy, by up to 4 s in the third trimester, largely due to the hormonally influenced increase in factor VIII. However, no marked changes in prothrombin time (PT) or thrombin time occur. [9] Thrombocytopenia (platelets 100 x 109/L) occurs in 0.8%-0.9% of normal pregnant women, while increases in platelet factor and thromboglobulin suggest elevated platelet activation and consumption. [10] The RBC indices change little in pregnancy. However, there is small increase in mean corpuscular volume, of an average of 4 fl. oz in an iron-replete woman, which reaches a maximum at 30-35 weeks gestation and does not suggest any deficiency of vitamins B12 and folate. [11] Also in white blood cells (WBCs) pregnancy is associated with leukocytosis, primarily related to increased circulation of neutrophils. The neutrophil count begins to increase in the second month of pregnancy and plateaus in the second or third trimester, at which time the total white blood cell (TWBC) counts range from 9,000 to 15,000 cells/micro liter. [12]

Materials and Methods

Subjects

This is a cross-sectional descriptive and analytical study conducted at Khartoum teaching hospital, department of gynecology and obstetrics, Sudan. The study population comprised 50 apparently healthy pregnant women aged between 20 and 40 years were recruited into the study while attending for monitoring of their pregnancy. Only women, whose last menstrual date, Human chorionic gonadotropin (HCG), and ultra sound determinations were congruent, were enrolled in this study. No subject had a history of disease, vaginal bleeding during course of the present pregnancy, or received any form of blood transfusion within the past 7 months. Subjects were divided into three pregnancy groups, depending on the duration of pregnancy in to the first, second, and third trimester of pregnancy. We used reference values of the health status of normal pregnant women as controls and comparison. Informed consent was obtained from each subject before recruitment into the study. A meeting interview was used for filling in a questionnaire that designated for matching the study need and all interviews were conducted face-to-face by the researcher in person.

Sample

About 5 mL of venous blood divided in two vacationer tubes, 2.5 mL of whole blood in K2 ethylenediaminetetraacetic acid for complete blood counts and other (2.5 mL) of whole blood with 1:9 ratio of trisodium citrate, were collected and then centrifuged in order to obtain platelets poor plasma for performing PT and APTT. All blood samples were collected between 9 am and 12 noon each day and analyzed within 2 h of collection. Hematological and coagulation analysis were done at room temperature (27.5 [+ or -] 0.5[degrees]C).

Method

Sysmex KX-21 (hematology analyzer) was used for complete blood counts. Hemoglobin (Hb), RBCs, TWBCs, and PLTs were considered to be measured directly, three hydraulic subsystems were used to determine the hemogram; the WBC channel, the RBC channel, the plats channel, and a separate Hb channel. All automated analysis was done after proper bar coding to ease identification. PT and APTT were determined by manual method that based on fibrin clot formation in glass tube. The test measures the plasma clotting time in addition of tissue extract thromboplastin (PT) and activation of contact factors (partial thromboplastin time [PTT]) depend on normal values of PT (12-16 s) and APTT (20-40 s).

Statistical Analysis

Data were entered and analyzed by SPSS program. All demographic data of the study population were presented as mean [+ or -] SD in the text and odds ratio was used for detecting the power of relationship between the determinant and the outcome and 95% confidence interval was calculated.

Result

A total of 50 apparently healthy pregnant women attending Khartoum teaching hospital, department of gynecology and obstetrics were enrolled in this study. According to the age, the study group was divided into four groups first group, the highest percentage (48%) of the pregnant women was between the age of 26 and 30, second group (28%) between 20 and 25, third group (22%) between 31 and 35, and finally the fourth group showed lowest percentage (4%) in the age above 35 years [Table 11. Also, according to the gestation period time that divided into three groups, 30% in their first trimester, 32% in second trimester, and 38% in third trimester [Table 2]. The hematological parameters were represented as follows: the mean value of WBCs was 7.580 cell/mom, RBCs was 4.1 x l012/L, Hb was 11.79 g/dL, platelets was 256 x 109/L, PT mean value of the study group was 13.40 s and PTT was 36.20 s [Table 3].

Discussion

The physiology of a normal pregnancy involves major changes in the hematological parameters and biochemical coagulation system. These changes appear to be related to the development of the uteroplacental circulation and provide a protective mechanism during delivery. In this study, we focus in the primary hematological changes during pregnancy related to Hb, RBCs, TWBCs, PLTs, PT, and PTT among Sudanese healthy pregnant women. In our finding, the RBCs were within normal value and showed no significant differences among the three groups of subjects. This finding supported that during pregnancy, the total blood volume increases by about 1.5 L, mainly to supply the demands of the new vascular bed and to compensate for blood loss occurring at delivery. [9] The result of the blood Hb showed no significant difference between those groups. Also, this may be due to supplementary intake. We found that the TWBCs count showed differences among the three groups and was statistically significant. The highest value was found in the second group followed by the third group and the lowest value found in the first group. This finding was contradictory to the fact that WBC count is increased in pregnancy with the lower limit of the reference range being typically 6,000/cumm. Leukocytosis, occurring during pregnancy is due to the physiologic stress induced by the pregnant state. [12] Also, this finding is contradictory with similar study done by Li et al., [13] among pregnant women and concluded that there was no significant difference of hemogram changes. Platelets count found to be within normal range in vast majority of the women in all three trimesters. This finding agrees with another similar study done by Babiker et al. [14] among Sudanese women were found that there was no significant value among pregnant women in platelets count. Also, this study agrees with the study done by Amah-Tariah et al., [15] among Nigerian women in which platelets showed no significant differences among the three study groups. Also this disagrees with the study done by Boehlen et al., reported that there were decreases in platelets count in normal pregnant women. [16, 17] Also, our finding agrees with another study done by Ichipi-Ifukor et al., concluded that pregnancy in women alters hematological indices such as packed cell volume, Hb, lymphocyte, and platelet counts during normal pregnancy. [16] The result of this study reveals that PT and PTT showed statistically insignificant differences and this indicates that pregnancy is not likely to have any adverse effect on these parameters. This result is consistent with an earlier report by Asaad and Fathelrahman in which the PT and the PTT remains unchanged among pregnant women. [18] Also, this result is consistent with a study reported by Avwioro et al., who recorded no change in the mean PT values among pregnant women. [19] Our result disagrees with different studies found that there were prolonged PT, APTT, and statistical significant among pregnant females. [14, 20, 21]

The limitations of this study were the fact that we did not investigate the fibrinogen concentration, factor VII, and von Willebrand factor among our study participant, due to cost constraints. Although, several authors reported these parameters found to be increase significantly during pregnancy. In the other hand, we focused on available, fast and low cost parameters that can give insight of the health status required for the delivery and healthy offspring.

Conclusion

This study concluded that pregnancy in women did not alter in findings of RBCs, Hb, platelets, PT, and PTT and no significant changes among Sudanese pregnant women. WBCs count showed differences and was statistical significant among the three groups, the highest value was found in the second group followed by the third group and the lowest value found in the first group.

DOI: 10.5455/ijmsph.2016.30092015149

Acknowledgments

We would like to thank all the pregnant women involved in the study, the staff of Khartoum teaching hospital, department of gynecology and obstetrics and medical laboratory staff, and special thanks to Mr. Osama Dai ELnaiem for editing this text.

References

[1.] US Department of Health and Human Services. Pregnancy: Condition Information. National Institutes of Health, 2013. Available at: http://www.nichd.nih.gov/ (last accessed on March 14, 2015).

[2.] Boundless. Introduction to pregnancy and human development. In: Boundless Anatomy and Physiology. Boston, MA: Boundless, 2015.

[3.] World Health Organization. International Statistical Classification of Diseases and Related Health Problems 10th revision. Geneva, Switzerland: WHO, 2006.

[4.] Costantine MM. Physiologic and pharmacokinetic changes in pregnancy. Front pharmacol 2014;5:65.

[5.] Kraemer K, Zimmermann MB (Eds.). Nutritional Anemia. Basel, Switzerland: Sight and Life Press, 2007.

[6.] Paidas MJ, Hossain N, Shamsi TS, Rodger MA, Langhoff-Roos J, Lockwood CJ (Eds.). Hematologic changes in pregnancy. In: Hemostasis and Thrombosis in Obstetrics & Gynecology. Oxford, UK: Wiley-Blackwell, 2011. pp. 1-11.

[7.] Welt, Corrine K., et al. "Female Reproductive Physiology Background Reading".

[8.] Prisco D, Ciuti G, Falciani M. Hemostatic changes in normal pregnancy. Hematol Meet Rep 2009;1(10):1-5.

[9.] Ramsay M. Normal hematological changes during pregnancy and the puerperium. In: The Obstetric Hematology Manual, Pavord S, Hunt B (Eds.). Cambridge, UK: Cambridge University Press, 2010. pp. 1-11.

[10.] Haram K, Svendsen E, Abildgaard U. The HELLP syndrome: clinical issues and management. A review. BMC Pregnancy Childbirth 2009;9:8.

[11.] Crocker IP, Baker PN, Fletcher J. Neutrophil function in pregnancy and rheumatoid arthritis. Ann Rheum Dis 2000;59(7):555-6.

[12.] Chandra S, Tripathi AK, Mishra S, Amzarul M, Vaish AK. Physiological changes in hematological parameters during pregnancy. Indian J Hematol Blood Transfus 2012;28(3):144-6.

[13.] Li H, Chen LF, Wang SY, Wang Y, Shi HM, Wang DQ. Correlation of hemogram changes during pregnancy of healthy women with postpartum blood transfusion. J experimental hematol 2012;20(5):1240-2.

[14.] Babiker HI, Awooda HA, Abdalla SE. Prothrombin time, activated partial thromboplastin time and platelets count in pregnant females and postpartum period with deep venous thrombosis. Int J Hematol Dis 2014;1(1):41-4.

[15.] Amah-Tariah FS, Ojeka SO, Dapper DV. Haematological values in pregnant women in Port Harcourt, Nigeria II: serum iron and transferrin, total and unsaturated iron binding capacity and some red cell and platelet indices. Niger J Physiol Sci 2011;26(2): 173-8.

[16.] Ichipi-Ifukor PC, Jacobs J, Ichipi-Ifukor RN, Ewrhe OL. Changes in haematological indices in normal pregnancy. Physiol J 2013; 2013(5):1-4.

[17.] Boehlen F, Hohlfeld P, Extermann P, Perneger TV, de Moerloose P. Platelet count at term pregnancy: are reappraisal of the threshold. Obstet Gynecol 2000;95(1):29-33.

[18.] Babker AMAAA, Gameel FEMH. Molecular characterization of Prothrombin G20210A gene mutations in pregnant Sudanese women with spontaneous recurrent abortions. RMJ 2015; 40(2):207-9.

[19.] Avwioro OG, Ezeobi JO, Oduola T, Fakunle OO. Prothrombin time and activated partial thromboplastin time in pregnant women in Southern Nigeria. J App Pharm Sci 2013;3(6):179-81.

[20.] Cerneca F, Ricci G, Simeone R, Malisano M, Alberico S, Guaschino S. Coagulation and fibrinolysis changes in normal pregnancy. Increased levels of procoagulants and reduced levels of inhibitors during pregnancy induce a hypercoagulable state, combined with a reactive fibrinolysis. Eur J Obstet Gynecol Reprod Biol 1997;73(1):31-6.

[21.] Erhabor O, Isaac I, Muhammad A, Abdulrahaman Y, Ezimah A, Adias T. Some hemostatic parameters in women with obstetric hemorrhage in Sokoto, Nigeria. Int J Womens Health 2013; 5:285-91.

Alkhansa Osama Mohamed (1), Khalda Mirghani Hamza (1), Asaad Mohammed Ahmed Babker (2)

(1) Department of Hematology and Immunohaematology, College of Medical Laboratory Science, Sudan University of Science and Technology, Khartoum, Sudan.

(2) Department of Medical Laboratory Science, Al-Ghad International College for Applied Medical Science, Al-Madinah Al-Munawarah, Saudi Arabia.

Correspondence to: Alkhansa Osama Mohamed, E-mail: alkhansaosama@gmail.com

Received September 30, 2015. Accepted November 3, 2015
Table 1: Distribution of study group according to age

Age group   Frequency   Percentage

20-25          13          26.0
28-30          24          48.0
31-35          11          22.0
>35            2            4.0
Total          50         100.0

Table 2: Distribution of study group according to trimesters

Trimester   Frequency   Percentage

First          15           30.0
Second         16           32.0
Third          19           38.0
Total          50          100.0

Table 3: Statistical result of cases in three trimesters

Trimester                 First trimester
parameters

                               Mean

WBC x [10.sup.9]/L     6.3467 [+ or -] 1.76022
RBC x [10.sup.12]/L    4.3087 [+ or -] 0.49578
Hb x g/dL             12.2133 [+ or -] .62663
Plate [10.sup.9]/L     255.07 [+ or -] 41.844
PT/s                    13.13 [+ or -] .990
PIT/s                   34.13 [+ or -] 5.817

Trimester                 Second trimester
parameters

                                Mean

WBC x [10.sup.9]/L     8.5188 [+ or -] 1.72326
RBC x [10.sup.12]/L    4.0619 [+ or -] .55242
Hb x g/dL             11.6813 [+ or -] 1.87979
Plate [10.sup.9]/L     257.81 [+ or -] 37.837
PT/s                    13.44 [+ or -] .512
PIT/s                   37.69 [+ or -] 5.351

Timester              Third trimester           Normal range
parameters
                           Mean

WBC x [10.sup.9]/L    7.7632 [+ or -] 2.05189     4.0-11.0
RBC x [10.sup.12]/L   4.0111 [+ or -] 0.48283    3.25-5.76

Hb x g/dL            11.5474 [+ or -] 1.31714    6.20-14.00
Plate [10.sup.9]/L    255.84 [+ or -] 70.507      146-400
PT/s                   13.58 [+ or -] .961         11-15
PIT/s                  36.58 [+ or -] 4.670        25-46

Timester               Normal         Study      Normal
parameters             range          range      mean

WBC x [10.sup.9]/L   4.0-11.0      3.50-12.00    7000
RBC x [10.sup.12]/L  3.25-5.76       3.9-5.6     4.7500
Hb x g/dL            6.20-14.00     11.5-15.5     13.5
Plate [10.sup.9]/L    146-400        150-400     256.24
PT/s                   11-15          11-16       13.5
PIT/s                  25-46          30-40        35

Trimester            Significance
parameters

WBC x [10.sup.9]/L       0.008
RBC x [10.sup.12]/L      0.220
Hb x g/dL                0.359
Plate [10.sup.9]/L       0.989
PT/s                     0.321
PIT/s                    0.168

WBC, white blood cell; RBC, red blood cell; Hb, hemoglobin; PT,
prothrombin time; PTT, partial thromboplastin time.
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Article Details
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Title Annotation:Research Article
Author:Mohamed, Alkhansa Osama; Hamza, Khalda Mirghani; Babker, Asaad Mohammed Ahmed
Publication:International Journal of Medical Science and Public Health
Article Type:Report
Geographic Code:6SUDA
Date:Mar 1, 2016
Words:2737
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