Background:  The objective of this study was to explore the
relationship, if any, between theserum heat-stable alkaline phosphatase
(HS-ALP) activity and the blood pressure (BP) of patients with
pre-eclampsia and eclampsia.  Method:  The activity of HS-ALP was
measured using the 4 - nitrophenyl phosphate (4 - NPP) method after
incubation at a high temperature of 65\ub0C for exactly 30 minutes in
one hundred normal pregnant women and in another one hundred with
pre-eclampsia/eclampsia. The normal pregnant women were used as
controls. The blood pressure (BP), systolic as well as diastolic was
measured in each of the studied patient using desktop mercury
sphygmomanometer.  Results: In the patients with
pre-eclampsia/eclampsia, it was found that the higher the systolic and
diastolic BP, the higher is the activity of the HS-ALP.  Conclusion: 
It can be concluded that the HS-ALP activity in patients with
pre-eclampsia/eclampsia is positively related to the severity of the
hypertension and therefore this could help in detecting early
complication.Fond :  L'objectif de cette \ue9tude \ue9tait d'explorer le
rapport, s'il y en a, entre l'activit\ue9 thermostable de la
phosphatase alkaline de s\ue9rum (TS-PAL) et la tension
art\ue9rielle (TA) des malades avec la pr\ue9-\ue9clampsie et
l'\ue9clampsie.  M\ue9thode :  L'activit\ue9 de TS-PAL a
\ue9t\ue9 mesur\ue9e en utilisant La m\ue9thode de 4-phosphate
nitroph\ue9nylique (4-PPN) apr\ue8s l'incubation \ue0
temp\ue9rature \ue9lev\ue9e de 65 0C pendant exactement 30
minutes dans cent femmes enceintes normales et dans encore cent avec l'
pre-\ue9clampsie/\ue9clampsie. Les femmes normalement enceintes ont
\ue9t\ue9 employ\ue9es comme commandes. La tension
art\ue9rielle (TA), systolique aussi bien que diastolique a
\ue9t\ue9 mesur\ue9e dans chaque malade \ue9tudi\ue9 en
employant le sphygmomanom\ue8tre mecure de bureau intelligent. 
R\ue9sultats:  Dans les malades avec la pre-\ue9clampsie et
\ue9clampsie, on a constat\ue9 que plus la TA systolique et
diastolique est haute, plus est haute l'activit\ue9 du TS-PAL . 
Conclusion:  On peut conclure que l'activit\ue9 de TS-PAL dans les
patients avec la pre-\ue9clampsie/\ue9clampsie est franchement
li\ue9 \ue0 la s\ue9v\ue9rit\ue9 de l'hypertension et donc
ceci pourrait aider pour d\ue9tecter la toute promi\ue9re
complication

Afonja, O. A.

Aliyu, I. S.

Isah, H. S.

Background: The objective of this study was to explore the relationship, if any, between the serum heat-stable alkaline phosphatase (HS-ALP) activity and the blood pressure (BP) of patients with pre-eclampsia and eclampsia. Method: The activity of HS-ALP was measured using the 4 – nitrophenyl phosphate (4 – NPP) method after incubation at a high temperature of 65 0C for exactly 30 minutes in one hundred normal pregnant women and in another one hundred with pre-eclampsia/eclampsia. The normal pregnant women were used as controls. The blood pressure (BP), systolic as well as diastolic was measured in each of the studied patient using desktop mercury sphygmomanometer. Results: In the patients with pre-eclampsia/eclampsia, it was found that the higher the systolic and diastolic BP, the higher is the activity of the HS-ALP. Conclusion: It can be concluded that the HS-ALP activity in patients with pre-eclampsia/eclampsia is positively related to the severity of the hypertension and therefore this could help in detecting early complication.  Keywords: heat-stable alkaline phosphatase, eclampsia, blood pressure  Annals of African Medicine Vol. 5 (1) 2006: 38–4

Aliyu, IS

Isah, HS

Afonja, OA

AJOL - African Journals Online

Relationship between serum heat-stable alkaline phosphatase activity and blood pressure in patients with pre-eclampsia and eclampsia

Bioline International

Annals of African Medicine Vol. 5, No. 1; 2006: 38 – 41  Relationship between Serum Heat-Stable Alkaline Phosphatase Activity and Blood Pressure in Patients with Pre-Eclampsia and Eclampsia   1I. S. Aliyu, 1H. S.  Isah and 2O. A. Afonja  1Department of Chemical Pathology, Ahmadu Bello University Teaching Hospital, Zaria and 2Department of Clinical Pathology, Lagos University Teaching Hospital, Lagos, Nigeria Reprint requests to: Dr I. S. Aliyu, Department of Chemical Pathology, A. B.U. Teaching Hospital, Zaria, Nigeria. E-mail: iasambo@yahoo.com     Abstract Background: The objective of this study was to explore the relationship, if any, between the serum heat-stable alkaline phosphatase (HS-ALP) activity and the blood pressure (BP) of patients with pre-eclampsia and eclampsia.   Method: The activity of HS-ALP was measured using the 4 – nitrophenyl phosphate (4 – NPP) method after incubation at a high temperature of 65 0C for exactly 30 minutes in one hundred normal pregnant women and in another one hundred with pre-eclampsia/eclampsia. The normal pregnant women were used as controls. The blood pressure (BP), systolic as well as diastolic was measured in each of the studied patient using desktop mercury sphygmomanometer.  Results: In the patients with pre-eclampsia/eclampsia, it was found that the higher the systolic and diastolic BP, the higher is the activity of the HS-ALP.  Conclusion: It can be concluded that the HS-ALP activity in patients with pre-eclampsia/eclampsia is positively related to the severity of the hypertension and therefore this could help in detecting early complication.    Key words: Heat-stable alkaline phosphatase, eclampsia, blood pressure    Résumé Fond : L'objectif de cette étude était d'explorer le rapport, s’il y en a, entre l'activité thermostable de la phosphatase alkaline de sérum (TS-PAL) et la tension artérielle (TA) des malades avec la pré-éclampsie et l'éclampsie. Méthode : L'activité de TS-PAL a été mesurée en utilisant La méthode de 4-phosphate nitrophénylique (4-PPN) après l’incubation à température élevée de 65 0C pendant exactement 30 minutes dans cent femmes enceintes normales et dans encore cent avec l' pre-éclampsie/éclampsie. Les femmes normalement enceintes ont été employées comme commandes. La tension artérielle (TA), systolique aussi bien que diastolique a été mesurée dans chaque malade étudié en employant  le sphygmomanomètre  mecure de bureau intelligent. Résultats: Dans les malades avec la pre-éclampsie et éclampsie, on a constaté que plus la TA  systolique et diastolique est haute, plus est haute l'activité du TS-PAL . Conclusion: On peut conclure que l'activité de TS-PAL dans les patients avec la pre-éclampsie/éclampsie est franchement lié à la sévérité de l'hypertension et donc ceci pourrait aider pour détecter la  toute promiére complication.    Mots clés: Phosphatase alcaline thermostable, éclampsie, tension artérielle   Introduction  Serum alkaline phosphatase measurements are  important in investigating hepatobiliary diseases associated with biliary obstruction1, bone diseases associated with increased osteoblastic activity2 and, to some extent placental insufficiency.3  Several tests have been extensively used to assess foeto-placenta function and development during pregnancy. The placenta is a rich source of enzymes, most of which are of course common to other tissues, but heat-stable alkaline phosphatase, cystyl-aminopeptidase (oxytocinase) and diamine oxidase (histaminase) are relatively specific to this organ.4 39                                     Serum heat-stable alkaline phosphatase and blood pressure in pre-eclampsia and eclampsia. Aliyu I. S. et al. Serum alkaline phosphatase is elevated in pregnancy, especially during the second and third trimesters.  The activity of this enzyme begins to rise at the fourth (4th) month of gestation.  This elevation is a reflection of placental fraction entering the maternal blood, since the human trophoblastic cells are rich in alkaline phosphatase. Therefore, measurement of serum alkaline phosphatase of placental origin is of particular interest in the investigation of placental insufficiency.5The increase in the serum alkaline phosphatase during the second half of pregnancy was recognised and confirmed by many investigators. 6 -12 It was also further confirmed that the alkaline phosphatase that originated in the placenta was heat-stable. 13 - 17The increase, which becomes apparent during the second trimester, continues throughout the third trimester reaching a peak at term, but this disappears within a few weeks after delivery.  Abnormal elevation in the activity of serum heat-stable alkaline phosphatase has been reported in patients with pre-eclampsia few weeks before clinical signs become apparent.18 -22 On the other hand, abnormally low values have been observed in mothers whose pregnancies were at risk owing to hypertension or diabetes.23    Patients and Methods   Patients One hundred pregnant women in the third trimester who presented to the antenatal clinic of Ahmadu Bello University teaching hospital, Zaria with pre-eclampsia/eclampsia or who were admitted into the maternity or labour wards with pre-eclampsia or eclampsia were selected for the study.  The usual diagnostic criteria of oedema, proteinuria and systemic hypertension were used in selecting the pre-eclamptic patients while those with eclampsia had grandmal intrapartum convulsions. The ages of this    group of patients ranged between 16-39 years with a mean of 26.6 years.  Another one hundred (100) women with normal pregnancy at different stages of the third trimester attending the same clinic were used as control. The age of this group of subjects ranged from 17-45 years with a mean of 26.7 years. In all selected subjects, gestational age was determined from the date of last menstrual period (LMP) and clinical measurement of the fundal height and ultrasonographic estimation were also conducted.  The selected patients with pre-eclampsia/eclampsia were further classified into mild pre-eclampsia (were the BP is above 130/90 mmHg but less than 160/100 mmHg with associated oedema and proteinuria), severe pre-eclampsia (when the BP is more than 160/100 mmHg with associated oedema and proteinuria) and eclampsia (when there was a convulsion in addition to the above features).  Approval for the study was obtained from the Ethical Committee of Faculty of Medicine, Ahmadu Bello University, Zaria and informed consent was obtained from all patients.   Methods  Ten millilitres of venous blood specimen was collected by venepuncture from the ante-cubital vein from each patient. The skin over the site of collection was swabbed with methylated spirit and allowed to dry.  A tourniquet was then applied 10 cm above the ante-cubital fossa to make the veins distended with blood.  Sterile 21G size hypodermic disposable needles were used to draw 10 ml of blood from patients and controls. The blood was then transferred into plain specimen bottles containing no anticoagulant.  After 30 – 45 minutes when the sample would have clotted, serum separation was carried out by centrifugation at 4000 rpm for 10 minutes.   The activity of serum heat-stable ALP was then measured.  Sample analysis was carried out for every specimen on the same day of collection. The 4 – nitrophenyl phosphate (4 – NPP) method, which is in use in the Ahmadu Bello University Teaching Hospital (ABUTH) Chemical Pathology laboratory, was used for the analysis of samples in this study. The ALP hydrolyses 4 – nitrophenyl phosphate (4 – NPP) at a pH of 10.3 and temperature of 37 0C to liberate 4 – nitrophenol (yellow complex). The total serum ALP was obtained by reading the absorbance of the 4 – nitrophenol at 510 nm using the spectrophotometer. The serum heat stable alkaline phosphatase activity was determined in the same way except for incubation at 65 0C for exactly 30 minutes to inhibit alkaline phosphatase activity derived from sources other than the placenta, which remain stable at this temperature. The within-run and between-day precision profiles were assessed using pooled sera. The within –run coefficients of variations (CV) for low, medium and high ALP activities were 3.67%, 0.77% and 0.35% respectively, while the corresponding values for the between-run were 6.02%, 1.27% and 0.95%, thus, the method was found to be precise.  Quality control sera provided by BIOTEC Laboratories Ltd, with low, normal and high levels of ALP activity were analysed with each batch of assays to ensure their validity.  Distributions of ALP activities were found to be skewed, hence non-parametric analysis using percentiles were used in measuring the variation.     Results  Table 1 shows the clinical and laboratory characteristics of the controls and the study patients with pre-eclampsia/eclampsia. There was no statistically difference between the maternal and gestational ages among the studied patients and the control group (P > 0.05) while the mean blood pressure in the controls was significantly lower (P < 0.001) than in the patients with pre-eclampsia/eclampsia.   Serum heat-stable alkaline phosphatase and blood pressure in pre-eclampsia and eclampsia. Aliyu I. S. et al.                                     40 There was a higher HS-ALP activity in patients than in controls. This difference in HS-ALP activity between the normal pregnant women and that of the patients with pre-eclampsia/eclampsia is statistically significant (p<0.001). Table 2 showed a normal systolic blood pressure (SBP) in the controls with no significant difference in the HS-ALP activity where as in patients with pre-eclampsia/eclampsia as the SBP increases, the HS-ALP activity increases, hence the higher the SBP, the greater is the HS-ALP activity. This relationship is statistically significant (p < 0.05). Table 3 shows the relationship between DBP and HS-ALP activity for both the controls and patients with pre-eclampsia/eclampsia. There is gradual rise in HS-ALP activity with increase in DBP. The observation is also statistically significant   (p < 0.05).    Table 1: Clinical and Laboratory characteristics of control subjects and patients with pre-eclampsia/eclampsia  Characteristics Mean for controls (range) Mean for study group (range) p value Age (Years) 26.7   (17 – 45) 26.6 (16 – 39) >0.05 Gestational age (weeks) 34.5 (28 – 42) 35 (28 – 42) >0.05 Systolic blood pressure (mmHg) 110.7 (90 – 130) 158.1 (130 – 200) <0.001 Diastolic blood pressure (mmHg) 70.4 (50 – 80) 107.9 (90 – 150) <0.001 Serum HSALP (IU/L) 74.5 (14 – 166) 144.6 (17 – 352) <0.001 HSALP: serum heat-stable alkaline phosphatase   Table 2: Systolic blood pressure and heat-stable alkaline phosphatase activity in controls and in patients with pre-eclampsia/eclampsia  Control group   Study group   Systolic blood pressure (mmHg) n HSALP  (IU/L) Systolic blood pressure (mmHg) n HSALP  (IU/L) 90 – 100  26 72.5  131 – 140  17 119.9  101 – 110  37 74.9  141 – 160  50 139  111 – 130 37 77.4  161 – 200 33 163.9 Total 100  100   HSALP: serum heat-stable alkaline phosphatase; Results of HSALP activities are presented as mean   Table 3: Diastolic blood pressure and heat-stable alkaline phosphatase activity in controls and in patients with pre-eclampsia/eclampsia  Control group   Study group   Diastolic blood pressure (mmHg) n HSALP  (IU/L) Diastolic blood pressure (mmHg) n HSALP  (IU/L) 50 – 65  21 68.7  91 – 105  52 128  66 – 90  79 76.1  106 – 120  42 160.8     121 – 150  6 175.5  Total 100  100   HSALP: serum heat-stable alkaline phosphatase; Results of HSALP activities are presented as mean   Discussion  This study has demonstrated positive relationships between blood pressure, and the activity of serum heat-stable ALP activity in patients with pre-eclampsia/eclampsia. The worse the blood pressure of the studied patient, the higher the serum heat-stable ALP activity. It has also been found in the study that both the systolic and diastolic blood pressures of the patients with pre-eclampsia and eclampsia correlated positively with the serum heat-stable ALP activity (p <0.05). The higher the systolic and diastolic blood pressure, the higher is the serum heat-stable ALP activity. This is similar to findings by Curzen and Morris.11 The widespread disturbance of the maternal vascular endothelium is responsible for the hypertension, altered vascular reactivity, activation of the coagulation cascade and the multisystem damage that accompany pre-eclampsia/eclampsia. 17, 18 The damage on the kidney leads to proteinuria, hyperuricaemia and renal failure. The worsening renal status results in more increase in blood pressure with further decreased in placental perfusion and therefore higher HS-ALP activity.21 - 26   The altered vascular permeability also leads to 41                                     Serum heat-stable alkaline phosphatase and blood pressure in pre-eclampsia and eclampsia. Aliyu I. S. et al. peripheral/pulmonary oedema in addition to the proteinuria and decreased colloid osmotic pressure leading to oedema seen in patient with pre-eclampsia/eclampsia. 26, 27 Because of its reliability, easy accessibility and affordability, it’s hereby recommended that measurement of serum heat-stable ALP activity be used in early diagnosis and management of patients with pre-eclampsia and eclampsia.   References  1. Ellis G, Goldbery AM, Spooner RJ, Wood MA. Serum enzyme tests in diseases of the liver and biliary tree. Am J Clin Path 1951; 70:248-258 2. Ogbodo SO, Okonkwo EJ. Serum alkaline phosphatase isoenzymes pattern in sickle cell anaemia. J Med Lab Sci 1996; 5:104-107 3. Lee ABH, Lewis RL. Alkaline phosphatase activity in normal and toxaemic pregnancy. Am J Obstet Gynecol 1963; 87:1071-1073 4. Wolf PL, Williams D. Practical Clinical enzymology: techniques and interpretation. Wiley – Interscience, 1973; 100-111 5. Posen S, Cornish CJ, Horne M, Saini PK. Placental alkaline phosphatase and pregnancy. Ann NY Acad Sci 1969; 166:733-739 6. Coryn G. Les phosphatase du sang dans le diagnostic des affections osseuses. J Chir 1934; 33:213-218 7. Meranze T, Meranze DR, Rothman MM. Blood phosphatase in pregnancy. Am J Obstet Gynecol 1937; 33:444-450 8. Bodansky B, Campbell K, Ball E. Changes in serum calcium, phosphate and phosphatase activity in pregnant women. Am J Clin Pathol 1939; 19:36-40 9. Beck E, Clark LC. Plasma alkaline phosphatase II: normotive data for pregnancy. Am J Obstet Gynecol 1950; 60:1731-1738 10. Meade BW, Rosalki SB. 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Adeniyi FA, Olatunbosun DA. Origin and significance of the increased plasma alkaline phosphatase during normal pregnancy and pre-edempsia. Br J Obstet Gynaecol 1984; 91:857-862 18. Benster B. Serum heat-stable alkaline phosphatase in pregnancy complicated by hypertension. J Obstet Gynaecol Br Cwlth 1970; 77:990-993 19. Messer RH. Heat-stable alkaline phosphatase as an index of placental function. Am J Obstet Gynecol 1967; 98:459-465 20. Curzen P, Iris Morris RN. Heat-stable alkaline phosphatase in maternal serum. J Obstet Gynaecol Br Cwlth 1968; 75:151-157 21. Hunter RJ. Serum Heat-stable alkaline phosphatase: an index of placental function. J Obstet Gynaecol Br Cwlth 1969; 76:1057-1069 22. Hunter RJ, Pinkerton JHM. Johnston H. Serum placental alkaline phosphatase in normal pregnancy and pre-eclampsia. Obstet Gynecol 1970; 36:536-546 23. Aleem FA. Total and heat-stable Serum alkaline phosphatase in normal and abnormal pregnancies. Obstet Gynecol 1970; 40:163-172 24. Curzen P, Morris I. Serum heat-stable alkaline phosphatase in hypertensive disorders of pregnancy.  J Obstet Gynaecol Br Cwlth 1966; 73:640-547 25. Moss DW, Henderson AR. Enzymes. In: Burtis CA, Ashwood ER (eds).  Tietz fundamentals of clinical chemistry. Saunders, Philadelpia, 1996;312-316,  712-717 26. Robson SC. Hypertension and renal disease in pregnancy. In: Edmonds DK (ed).  Dewhurst’s textbook of obstetrics and gynaecology for postgraduates. Blackwell, Edinburgh, 1999; 166-185 27. Moss DW, Henderson AR. Clinical enzymology. In: Burtis CA, Ashwood ER (eds). Tietz fundamentals of clinical chemistry. Saunders, Philadelpia,1999; 676-684    

Relationship between Serum Heat-Stable Alkaline Phosphatase Activity and Blood Pressure in Patients with Pre-Eclampsia and Eclampsia

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