Download

Shaik Kareemulla et al. J Sci Res Pharm, 2018;7(3):35-41

World Inventia Publishers

J

ournal of

S

cientific

R

esearch in

P

harmacy

http://www.jsrponline.com/

Vol. 7, Issue 3, 2018 ISSN: 2277-9469

Case Report

APPRAISAL OF CLINICAL PHARMACIST IN EVANGELIZING PHARMACEUTICAL CARE PLAN FOR A GRAVE

CONTINGENCY PRE- ECLAMPSIA PRECIPITATING HELLP SYNDROME: A CASE STUDY

Shaik Kareemulla 1 _{*, Nasera Salwa} 2_{, Rimsha Naseer} 2_{, Tahoura Fiyaz} 2_{, Hajera saja} 2_{, Naila Noohi Maryam} 2

* 1 _{PhD Research scholar, Jaipur National University (JNU), Jaipur, Rajasthan, INDIA.}

2 _{Pharm D, Shadan College of pharmacy, Jawaharlal Nehru Technological University (JNTU), Hyderabad, Telangana, INDIA.}

Received on: 01-03-2018; Revised and Accepted on: 22-03-2018

ABSTRACT

H

KEYWORDS: Pre-eclampsia, Thrombophilia, NICE guidelines, Maternal hypotension, Hemolysis, Oligohydramnios, Alpha fetoprotein.

INTRODUCTION

H

(HBP), is a long term medical condition in which blood pressure in the arteries is persistently elevated. High blood pressures usually do not cause symptoms. Long term High Blood Pressure is a major risk factor for Coronary Artery Disease, Stroke, Heart Failure, Peripheral Vascular Disease, Vision Loss, Chronic Kidney Disease and Dementia. Hypertension is classified as Primary (Essential) Hypertension and

Secondary Hypertension. About 90–95% of cases are Primary

Hypertension occurs due to Lifestyle Modifications and Genetic factors. Life style factors contributing the risk of Primary Hypertension include Excess salt in the diet, Excess body weight, Smoking and Alcohol

use. About 5–10% of cases are Secondary Hypertension occurs due to

*Corresponding author:

Shaik Kareemulla PhD Research scholar,

Jaipur National University (JNU), Jaipur, Rajasthan, INDIA. * E-Mail: [email protected]

DOI:

identifiable causes like Chronic Kidney Disease, Narrowing of Kidney Arteries, Endocrine Disorder and Use of Birth Control Pills. Blood pressure is expressed by two measurements i.e., Systolic pressure and Diastolic pressure, which are the maximum and minimum pressures respectively. For adults, Normal blood pressure at rest will be within the

range of 100–130 mmHg Systolic and 60–80 mmHg Diastolic. A person

suffer with Hypertension if the resting blood pressure is >150/90 mmHg. Ambulatory blood pressure monitoring over a 24 hour period is more accurate when compared to Office based blood pressure measurement. Hypertension is rarely accompanied by symptoms, and its identification is confirmed by different screening methods.

Hypertensive patients have cardinal symptom of headaches [1]_{. These}

patients also suffer from Light headedness, Vertigo, Tinnitus (buzzing or hissing in the ears), Altered vision and fainting episodes. On physical examination, hypertension may be associated with the presence of changes in the optic fundus and is investigated by ophthalmologist. Severity of the retinopathy is roughly correlated with the duration or the severity of the hypertension.

Secondary Hypertension:

artery stenosis (RAS) is associated with localized abdominal bruit to the left or right of the midline (unilateral RAS), or in both locations (bilateral RAS). Contraction of aorta causes a decreased blood pressure in the lower extremities there by delaying femoral arterial pulses. Pheochromocytoma may cause abrupt ("paroxysmal") episodes of hypertension accompanied by Headache, Palpitations, Pale Appearance and Excessive Sweating.

Blood Pressure classified in four different categories:

Normal blood pressure: Blood pressure is said to be normal if value is 120/80 mm Hg. (mean difference > 1o).

Prehypertension: In Prehypertension, Systolic Blood Pressure ranges from 120 to 139 mm Hg and Diastolic Blood Pressure ranges from 80 to 89 mm Hg. Prehypertension tends to get worse as the time progresses.

Stage 1 Hypertension: In Stage 1 Hypertension, Systolic Blood Pressure ranges from 140 to 159 mm Hg and Diastolic Blood Pressure ranges from 90 to 99 mm Hg.

Stage 2 Hypertension: It is a severe stage of Hypertension having Systolic Blood Pressure > 160 mm Hg and Diastolic Blood Pressure > 100 mm Hg.

NOTE: Gestational Hypertension or Pregnancy Induced Hypertension (PIH) is increase of blood pressure in pregnant women after 20 weeks gestation without the presence of proteinuria or other signs of Preeclampsia [2]_.

Commonly used Drugs in the Treatment of Pre-Eclampsia:

Methyldopa: It is a choice of drug to treat hypertension in pregnant women. It can be given either by mouth or through intravenous administration. Onset of effects is around 5 hours and lasts for 24 hours. Severe side effects include breakdown of red blood cells, liver abnormalities and allergic reactions. Methyldopa belongs to alpha-2 adrenergic receptor agonist family, acts by stimulating brain to decrease the activity of the sympathetic nervous system.

Nifedipine: Nifedipine is a popular and widely used drug for the treatment of hypertension in pregnancy. It is safe at any gestation [3]_. The use of sublingual nifedipine should be avoided to minimise the risk of sudden maternal hypotension and foetal distress occurs due to placental hypoperfusion. Abrupt hypotension is potentiated on concomitant administration of magnesium sulphate (Used as prophylactic agent against eclamptic seizures).

Calcuim Channel Blockers: These drugs act by inhibiting Ca2+ _influx into vascular myocytes causing vasoconstriction and reducing vascular resistance. It has minimal effects on cardiac conduction and heart rate. There is minimal excretion into breast milk. Nifedipine, a slow release drug is the most commonly prescribed calcium channel blocker prescribed at a dose of 10 to 20 mg twice daily during initial stages [4]_. Once control is established, slow release drug converts to a sustained release preparation of 30 to 60 mg daily. A second line alternative of calcium channel blockers is amlodipine given at a dose of 5 to 10 mg once daily. Amlodipine is also to treat Eclampsia patients but safety data is lacking.

Diuretics:Besides the mobilization of liquid from the intravascular to extravascular space that correspond six to eight litres of the total body water, a return of 950 mEq of total body sodium is accumulated during pregnancy. It is observed that urinary sodium excretion increase occurs between three to five days after birth and is due to increase of atrial natriuretic peptide in the first week after delivery resulting in inhibition of aldosterone, angiotensin II and vasopressin. Several approaches have been proposed to accelerate the postpartum maternal recovery, but the effectiveness in treating hypertension in the postpartum period, remain to be unsuccessful. Patients with preeclampsia and eclampsia may experience persistent hypertension after delivery because of excess of total body water and inadequate secretion of sodium and is due to reduced glomerular filtration. Loop diuretic act in patients with fluid

overload, resulting in decrease of blood volume and blood pressure. It also play an important role in maintain a low central venous pressure, pulmonary capillary wedge pressures, raising colloid osmotic pressure, preventing the development of pulmonary oedema and congestive heart failure[5]_.

Iron Supplementation: Iron deficiency anemia is prevalent among pregnant women living in industrialized countries. Iron supplements (30 mg/day) are routinely prescribed to prevent the disease. Recently studies reported that dietary iron should be increased from 18 mg/day & 23 mg/day during the second & third trimesters respectively to 27 mg/day throughout the pregnancy for all age groups. Based on the literature review, a daily dose of iron (30 mg elemental iron) during

pregnancy improves women’s iron status and protects infants from iron

deficiency anemia [6]_{. Studies also reported daily dose of iron to non} anemic pregnant women improve birth weight. However, higher dosages are not recommended because of the potential negative effects

like mineral absorption, oxidative pathways and adverse

gastrointestinal symptoms.

Proton Pump Inhibitors: Proton pump inhibitors (PPIs) are a group of drugs acts by decreasing stomach acid production for longer durations.

These drugs are most potent acid secretion inhibitors. H2-receptor

antagonists also have similar effects as that of Proton pump inhibitors (PPIs), but different mechanism of action is different. The gastric H+/K+ ATPase are the primary target to treat acid related diseases. Proton pump inhibitors (PPIs) are weak bases composed of two moieties, a substituted pyridine with pKa value of 4.02 and benzimidazole with pKa value of 1.03. PPIs are acid activated prodrugs converts excess acid to sulfenic acids or sulfenamides and reacts covalently with one or more cysteines. Due to covalent binding, inhibitory effect of PPIs lasts much longer than plasma Half-life. However, the short half-life of the drugs in blood decreases the efficacy of acid suppression, particularly at night. All PPIs heal peptic ulcers and have favourable results in treating reflux esophagitis. PPIs combined with antibiotics to eradicate Helicobacter pylori infections.

Haemolysis: Hemolysis is the rupturing (lysis) of red blood cells (erythrocytes) and the release of their contents (cytoplasm) into surrounding fluid (e.g. blood plasma). It occurs both invivo and invitro (inside or outside the body). Hemolysins damages host cytoplasmic membrane, causing cell lysis and death. The activity of toxin is easily observed with assays involving the lysis of red blood cells. Hemolysins

attack the phospholipid of the host cytoplasmic membrane [7]_{. As}

phospholipid lecithin (phosphateidyl choline) is often used as substrate, these enzymes are called lecithinases or phospholipases. Haemolysins also affect the sterols of the host cytoplasmic membrane. Hemolysis inside the body occurs due to medical conditions, including many

Gram-positive bacteria (e.g., Streptococcus, Enterococcus, and

Staphylococcus), parasites (e.g., Plasmodium), autoimmune disorders (e.g., drug-induced hemolytic anemia), and genetic disorders (e.g., Sickle-cell disease or G6PD deficiency). Hemolysis leads to hemoglobinemia due to release of haemoglobin into the blood plasma. In vitro hemolysis is caused by improper technique during collection of blood specimens, either by mechanical processing of blood, or by bacterial action in cultured blood specimens.

Hellp Syndrome: It is a clinical syndrome characterized by thrombocytopenia, hemolytic anemia, and liver dysfunction occurs due to microvascular endothelial activation and cell injury. The pathophysiology of HELLP syndrome is ill-defined. HELLP is a variant disorder of preeclampsia. In preeclampsia, defective placental vascular remodelling occurs during 16 to 22 weeks of pregnancy with the second

wave of trophoblastic invasion [8]_{. Hypoxic placenta releases many}

HELLP. Acute maternal immune rejection occurs due to contact of immune competent maternal cells with genetically distinct foetus, altering the maternal-foetal immune balance and causing endothelial dysfunction, platelet activation, aggregation and arterial hypertension. Inborn errors of fatty acid oxidative metabolisms, long chain fatty acid mutations and medium chain fatty acid mutations cause liver damage, inhibiting mitochondrial oxidation of fatty acids required for

ketogenesis. Placental instigated acute inflammatory condition also targets the liver to make it abnormal. Dysfunction in the complement system via excessive activation or defective regulation has been proposed to cause damage to hepatic vessels in HELLP. Many attempts are done to understand the pathogenesis of HELLP syndrome, but the true pathology still remains as a mystery.

Liver Function Test: LFTs play a significant role in the evaluation and treatment of patients with hepatic dysfunction. Liver performs the metabolism of carbohydrate, protein and fats. Certain enzymes and end products of the metabolic pathway which are very sensitive for abnormality occurrence considered as biochemical marker of liver dysfunction. Examples for biochemical markers are serum bilirubin, alanine amino transferase, aspartate amino transferase, ratio of aminotransferases, alkaline phosphatase, gamma glutamyl transferase, ′ nucleotidase, ceruloplasmin and -fetoprotein. Isolated or conjugated alterations of biochemical markers of liver damage challenge the clinicians during the liver disorder diagnosis. The term liver chemistry tests is frequently used but less defined phrase and to assess hepatic function and hepatic injury.

Serum Bilirubin: Bilirubin is a catabolic product of haemoglobin

produced within the reticuloendothelial system, released in

unconjugated form, enters into the liver and is converted to conjugated forms bilirubin and diglucuronides by UDP-glucuronyltransferase enzyme. Total Normal serum bilirubin varies from to μmol/L, indirect unconjugated bilirubin level is less than μmol/L and direct conjugated bilirubin less than μmol/L. The serum bilirubin levels more than μmol/L suggest liver diseases and levels above μmol/L indicate abnormal laboratory liver tests. Jaundice occurs when bilirubin becomes visible in the sclera, skin, and mucous membranes. The occurrence of unconjugated hyperbilirubinemia due to over production of bilirubin, seen in genetic defect of UDP-glucuronyltransferase causing Gilbert's syndrome, Crigler-Najjar syndrome, reabsorption of large

hematomas and ineffective erythropoiesis [9]_{. In viral hepatitis,}

hepatocellular damage, toxic liver injury, ischemic liver injury and

higher levels of serum conjugated bilirubin are observed.

Hyperbilirubinemia in acute viral hepatitis is proportional to the degree of histological injury of hepatocytes and longer course of the disease. Parenchymal liver diseases or incomplete extrahepatic obstruction due to biliary canaliculi have lower serum bilirubin values when compared to malignant obstruction of common bile duct and infiltrative diseases

like tumours and granuloma. Raised Serum bilirubin from . μmol/L

to . μmol/L in acute inflammation of appendix has been observed. In normal asymptomatic pregnant women total and free bilirubin concentrations are significantly lower during all three trimesters and a decreased conjugated bilirubin is observed in second and third trimesters.

Alanine Amino Transferase (ALT): ALT is found in kidney, heart, muscle and liver (greater concentration) compared with other tissues of

the body. ALT is purely cytoplasmic catalysing the transamination

reaction. Normal serum ALT is 7–56 U/ L. Elevated values up to 300 U/L

are considered nonspecific. Marked elevations of ALT levels greater than 500 U/L observed in persons with diseases that affect hepatocytes such as viral hepatitis, ischemic liver injury (shock liver) and toxin-induced liver damage. Viral hepatitis A, B, C, D, E are responsible for a marked increase in aminotransferase levels. The increase in ALT associated with hepatitis C infection tends to be more when compared to hepatitis A or B. Moreover in patients with acute hepatitis C, serum ALT is measured periodically for about 1 to 2 years. Persistence of elevated ALT for more than six months after the occurrence of acute hepatitis helps in diagnosing chronic hepatitis. ALT levels are elevated in persons with non-alcoholic steato hepatitis than in patients with uncomplicated hepatic steatosis. Hepatic fat accumulation in childhood obesity and non-alcoholic fatty liver disease also causes serum ALT elevation [10]_. Increased ALT level get associated with reduced insulin sensitivity, adiponectin and glucose tolerance and increase in amounts of free fatty acids and triglycerides. ALT level is normally elevated during 2nd trimester in asymptomatic normal pregnancy. serum ALT levels in symptomatic pregnant patients like hyper-emesis gravidarum ALT level is found to be 103.5U/L, in pre-eclampsia patients ALT level is found to be 115U/L and in haemolysis with low platelet count patients ALT level is found to be 149U/L. coffee and caffeine consumption also reduces the risk of elevated serum ALT activity in excessive alcohol consumption, viral hepatitis, iron overload, overweight, and impaired glucose metabolism.

Aspartate Amino Transferase (AST): AST catalyse transamination reaction. AST exist in two different isoenzyme forms i.e., mitochondrial and cytoplasmic form but are genetically distinct. Higher concentration of AST is found in heart compared with other tissues of the body like liver, skeletal muscle and kidney. Normal serum AST is 0 to 35U/L. Elevated mitochondrial AST seen in extensive tissue necrosis during myocardial infarction and chronic liver diseases. About 80% of AST activity of the liver is contributed by the mitochondrial isoenzyme, whereas most of the circulating AST activity in normal people is derived

from the cytosolic isoenzyme [11]_{. However the ratio of mitochondrial}

AST/ALT Ratio: The ratio of AST to ALT has more clinical importance than examining individual elevated LFT levels. A coenzyme

pyridoxal-5\'-phosphate deficiency depresses serum ALT activity and

consequently increases the AST/ALT ratio. The ratio increases in progressive liver functional impairment and found 81.3% sensitivity and 55.3% specificity in identifying cirrhotic patients. Whereas mean ratio of 1.45 and 1.3 was found in alcoholic liver disease and post

necrotic cirrhosis respectively [12]_{. The ratio greater than 1.17 was found}

in one year in cirrhotic patients. An elevated ratio greater than 1 shows advanced liver fibrosis and chronic hepatitis C infection. However, an AST/ALT ratio greater than 2 is present in alcoholic hepatitis. A recent study differentiated non-alcoholic steato-hepatitis (NASH) from alcoholic liver disease showing AST/ALT ratio of 0.9 in NASH and 2.6 in patients with alcoholic liver disease (ALD). In both Wilson's disease and Hyperthyroidism, ALT/AST ratio exceeds by 4.5 levels.

Alkaline Phosphatase (ALP): ALP is present in mucosal epithelia of small intestine, proximal convoluted tubule of kidney, bone, liver and placenta. It performs lipid transportation in intestine and calcification in bone. Normal serum ALP is 41 to 133U/L. In acute viral hepatitis, ALP usually remains normal or moderately increased. Elevation of ALP with prolonged itching is seen in Hepatitis A patients with cholestasis. Tumours secrete ALP into plasma resulting to form tumour specific isoenzymes like Regan, Nagao and Kasahara. Hepatic and bony metastases also cause elevated levels of ALP. Other diseases like infiltrative liver diseases, abscesses, granulomatous and amyloidosis also increase ALP levels. A mild elevated level of ALP is seen in cirrhosis, hepatitis and congestive cardiac failure. Low levels of ALP occur in hypothyroidism, pernicious anaemia, zinc deficiency and congenital hypophosphatasia. ALP activity is significantly higher in third trimester of asymptomatic normal pregnancy showing extra production from

placental tissue [11]_{. ALP levels in hyperemesis gravidarum is 21.5U/L, in}

pre-eclampsia is 14U/L, and 15U/L in haemolysis with low platelet

count is seen during symptomatic pregnancy. Transient

hyperphosphataemia in infants is a benign condition characterized by elevated ALP levels of several folds without evidence of liver or bone disease and it returns to normal level by 4 months [13]_{. ALP has been} found elevated in peripheral arterial disease which is independent of traditional cardiovascular risk factors. Clinicians often get confused in differentiating liver diseases and bony disorders due to elevated ALP levels in both disorders. Measurement of gamma glutamyl transferase helps in differentiating as it is raised in cholestatic disorders and not in bone diseases.

Gamma Glutamyl Transferase (GGT): GGT is a microsomal enzyme present in hepatocytes, biliary epithelial cells, renal tubules, pancreas and intestine. It is also present in cell membrane transporting the peptides into the cell across the cell membrane and involved in glutathione metabolism. The normal level of GGT ranges from 9 to 85 U/L. In acute viral hepatitis, levels of GGT reach the peak levels in second or third week of illness and remain elevated for 6 weeks. Other conditions like uncomplicated diabetes mellitus, acute pancreatitis, myocardial infarction, anorexia nervosa, Gullian barre syndrome, hyperthyroidism, obesity and dystrophica myotonica causes elevated levels of GGT [14]_{. Elevated serum GGT levels of more than 10 times is} observed in alcoholism which is partly related to structural liver damage, hepatic microsomal enzyme induction and alcoholic pancreatic damage. GGT is also an early marker of oxidative stress because serum

antioxidant carotenoids namely lycopene, -carotene, -carotene, and

-cryptoxanthin are inversely associated with alcohol-induced increase of serum GGT found in moderate and heavy drinkers. There is a significant positive correlation between serum GGT and triglyceride levels in diabetes and level decreases with insulin treatment. Serum GGT does not correlate with hepatomegaly in diabetes mellitus. Serum GGT activity is significantly less in the second and third trimesters of normal asymptomatic pregnancy. The levels of GGT in hyperemesis gravidarum is 45U/L, in pre-eclampsia is 17U/L, and 35U/L in hemolysis with low platelet count and elevated liver enzymes is found during symptomatic pregnancy. The primary usefulness of GGT is limited in diagnosing bone diseases as GGT is not found in bone.

5′ Nucleotidase NTP : NTP is a glycoprotein spreads throughout the tissues of body localised in cytoplasmic membrane catalysing release of inorganic phosphate from nucleoside-5-phosphates. The normal range

is 0 to 15U/L. Raised levels of NTP activity is found in patients with obstructive jaundice, parenchymal liver disease, hepatic metastases and bone disease. NTP is precise marker of hepatic primary or secondary tumours. ALP levels also increased in conjugation with NTP levels suffering with hepatic obstruction due to malignancy. Elevation of NTP is found in acute infective hepatitis and also in chronic hepatitis. In acute hepatitis, elevation of NTP activity is more when compared with chronic hepatitis and is attributed to shedding of plasma membrane with Ecto NTP activity due to cell damage and leakage of bile. Serum NTP activity

is significantly higher in second and third trimesters of pregnancy [15]_.

Ceruloplasmin: Ceruloplasmin synthesis occurs in the liver and is acute phase protein. It binds with the copper and serves as a major copper carrier in the blood. Normal plasma level of ceruloplasmin is 200 to 600mg/L. Elevated levels are seen in infections, rheumatoid arthritis, pregnancy, Non-Wilson liver disease and obstructive jaundice. Declined

levels are seen in neonates, Menke’s disease, kwashiorkor, marasmus,

copper deficiency and Aceruloplasminemia. In Wilson's disease ceruloplasmin level is depressed. Decreased rate of ceruloplasmin synthesis result in copper accumulation in liver due to copper transport defect in Golgi apparatus, since ATP7B is affected. Serum ceruloplasmin levels are elevated in chronic active liver disease (CALD) and decreased

in Wilson’s disease (WD). Hence it is the most reliable routine chemical

screening test to differentiate CALD and WD.

Α Alpha-Fetoprotein (AFP): AFP gene is highly activated in foetal liver but is significantly suppressed after birth. The mechanisms that trigger AFP transcriptional suppression in postpartum liver are not clearly described. AFP is the major serum protein in developing mammalian foetus produced in high levels by foetal liver and visceral endoderm of the yolk sac and produced in low levels by foetal gut and kidney. AFP is required for female fertility during embryonic development to protect developing female brain from prenatal exposure to estrogen. The normal level of AFP is to μg/L. An AFP value above 400 – μg/L has been considered to be a confirmed diagnosis for hepatocellular carcinoma (HCC) in patients with cirrhosis. High AFP concentration i.e., ≥ μg/L in HCC patients get associated with greater tumour size, bilobar involvement, portal vein invasion and a lower median survival rate. There are three different AFP variants, differing in their sugar chains (AFP-L1, AFP-L2, and AFP-L3). AFP-L1, the non- Lens culinaris agglutinin (LCA) -bound fraction, is the main glycoform of AFP in the serum of patients with non-malignant chronic liver disease. In contrast, Lens culinaris-reactive AFP, also known as AFP-L3, is the main glycoform of AFP in the serum of HCC patients and it can be detected in 1/3rd of patients with small HCC (< 3 cm), when cut-off values of 10% to 15% are used. AFP-L3 acts as a marker for clearance of HCC after treatment [16]_{. It is reported that an AFP-L3 level of 15% or more is} correlated with HCC- associated portal vein invasion. Estimating the AFP-L3 / AFP ratio is helpful in diagnosis and prognosis of HCC. There is a direct association between second-trimester maternal serum alpha-fetoprotein levels and the risk of sudden infant death syndrome (SIDS), which is mediated by impaired foetal growth and preterm birth.

Note: Laboratory liver tests helps to elucidate the alteration of markers that reflect the liver disease. Assessment of enzyme abnormalities such as predominant pattern of enzyme alteration, magnitude of enzyme alteration, isolated elevation, rate of change and nature of the course of alteration helps in the diagnosis of the disease. A single laboratory liver test in screening liver disease is not helpful because many liver diseases may be associated with normal levels. The pattern of enzyme abnormality, interpreted in the context of the patient’s symptoms also helps in directing the subsequent diagnosis.

CASE REPORT

Lft in Pre-Eclampsia: Preeclampsia is multisystem disorder cause damage to cardiovascular system, kidneys, brain and liver. Pregnancy-induced hypertension (PIH) is responsible for significant maternal and perinatal morbidity. This study is performed to compare the liver function tests in preeclampsia with normal pregnancy.

Hyderabad. The subjects were divided into two groups. Group A consists of 50 cases of preeclampsia having blood pressure > 140/90 mmHg, proteinuria in 24 hours > 300 mg and oedema; Group B consists of 50

normal pregnant women having 20 weeks of gestation. Patient’s

demographic profile, BMI, parity, period of gestation, blood pressure and presenting complaints of all subjects are recorded. Serum bilirubin and plasma levels of liver enzymes ALT, AST and ALK are also measured.

Results: Mean BMI of the cases is found to be 29.04 + 3.97 and that of controls was 26.54 + 3.11. Mean value of serum bilirubin is found to be

10.78 + 3.74 micromol/L and in control group, it is found to be 7.92 + 2.42 micromol/L (p < 0.001). Mean values of enzyme ALT is found to be 55.81 + 31.93 U/L while in the control group, it is found to be 15.22 + 3.30 U/L (p < 0.001). Mean serum AST is found to be 41.34 + 10.76 U/L and in the control group, it is found to be 24 + 2.54 U/L (p < 0.001). Mean ALK level before delivery is found to be 454.16 + 243.69 U/L, and in control group, it is found to be 181.34 + 66.76 U/L (p < 0.001). Conclusion: Increase in levels of serum bilirubin and liver enzymes ALT, AST and ALK are found in preeclampsia patients.

Pharmaceutical Care Plan: SOGC and NICE guidelines cite fair evidence that women with onset of gestational hypertension prior to 34 weeks gestation are more likely to develop preeclampsia than women with later onset hypertension, and that these women have an increased risk of complications such as IUGR. This evidence is consistent with the distinction between early and late presenting disease that has been recently considered. There are several investigational laboratory markers for risk of preeclampsia, such as leptin, placental growth factor and plasminogen activator inhibitor, which have not been shown individually to have sufficient predictive value to be clinically useful. All women diagnosed with hypertension in pregnancy should be assessed for the presence or absence of preeclampsia. Many women with HDP will develop preeclampsia, and the JNC report notes that up to 25% of women with chronic (pre-existing) hypertension will develop preeclampsia. Women with severe hypertension should be carefully monitored for the development of preeclampsia. Women with high risk for preeclampsia should have more definitive evaluation of proteinuria than women at low risk, and high-risk women should also be evaluated for preeclampsia through other clinical and laboratory evaluations. Significant proteinuria for the identification of preeclampsia is defined across guidelines as greater than or equal to 300 mg of protein in a 24 hour urine collection [17]_{. The ACOG practice bulletin regarding chronic} hypertension notes that although protein: creatinine ratios of 0.15 to 0.3 have been used to identify women who should be evaluated with 24 hour urine for proteinuria. In addition to specific testing for proteinuria, SOGC and SOMANZ guidelines recommend that women with risk factors should receive a stratified clinical and lab evaluation work-up beyond routine baseline antenatal lab tests; this recommendation is based on fair evidence. Such testing for women at risk would include complete blood count and differential, blood film, platelet count, coagulation studies, serum creatinine, glucose, liver enzymes, and serum albumin. SOGC guidelines include uric acid in testing for women at risk due to a reported association of elevated uric acid and perinatal complications.

The ACOG practice bulletin Chronic Hypertension in Pregnancy notes that serum uric acid may be helpful in diagnosing superimposed preeclampsia. The JNC report advocates reinstituting antihypertensive therapy for any woman with chronic (pre-existing) hypertension when blood pressure reaches systolic readings of 150-160 mmHg or diastolic of 100-110 mmHg. The recommendation for instituting treatment at this threshold is geared toward preventing severe hypertension during pregnancy, since there are reports of high rates of foetal loss and maternal mortality among women with severe chronic (pre-existing) hypertension in the first trimester [18]_{. This threshold for treatment is} also cited by NICE guidelines for both chronic (pre-existing) and gestational hypertension. ACOG stresses that women with severe chronic (pre-existing) hypertension (systolic blood pressure 160 mmHg or greater or diastolic blood pressure 110 mmHg or greater) should have antihypertensive therapy initiated or continued to reduce the risk of maternal stroke.

control goal of 140-160/90-100 mmHg to avoid prolonged exposure to severe systolic hypertension and loss of maternal cerebral vascular auto

regulation [19]_{. The target for severe hypertension cited by NICE}

guidelines, < 150/100 mmHg but not lower than 80 mmHg diastolic, does not differ from the NICE target for non-severe hypertension. RAAS active drugs, including ACE inhibitors, ARB and renin inhibitors, have been associated with foetal abnormalities, although the evidence is of poor quality. All guidelines recommend discontinuing these agents and not initiating them during pregnancy. In women with confirmed HDP, testing should be conducted for end-organ dysfunction. Other than proteinuria testing, there is insufficient evidence to define which lab assessments are most useful in monitoring women with hypertensive disorders of pregnancy, and the validity of tests alone or in combination has not been reported. There is poor quality evidence regarding the predictive value of specific positive tests, although negative tests can be useful.33 In addition to routine antenatal lab testing, most guidelines recommend that women with suspected preeclampsia should be evaluated with a complete blood count (haemoglobin, white blood cell count and differential, platelet count, blood film), electrolytes and renal function (serum creatinine), and liver function tests (transaminases, bilirubin). SOGC guidelines also recommend coagulation studies (INR and aPTT, fibrinogen) and serum uric acid, glucose and urinalysis, with additional baseline labs as indicated. ACOG notes that elevated serum uric acid may be particularly useful in distinguishing preeclampsia in women with chronic (pre-existing) hypertension who first present late in pregnancy. NST is the most common antepartum screening test; it is easily performed on an outpatient basis and requires minimal staff. BPP has a lower false positive rate than NST alone, and is supplanting contraction stress test as follow up to a nonreactive NST. BPP includes the individual components of NST, foetal breathing movements, foetal movement, foetal tone, and quantification of amniotic fluid volume. ACOG recommends NST or BPP frequently if IUGR is suspected or for women with preeclampsia. Modified BPP that includes NST and assessment of amniotic fluid depth for oligohydramnios appears to be as predictive as other approaches.

Diet and Nutrition: There is no clear evidence that advising pregnant women to increase their energy intake, providing energy or protein supplements, or prescribing a low energy diet to overweight women protects against pre-eclampsia. Also unclear is whether advice to reduce dietary salt intake during pregnancy has any impact. Several nutritional agents have been suggested to have a role in preventing pre-eclampsia. Dietary supplementation with at least 1 g of calcium a day reduces the relative risk of pre-eclampsia, but with no clear effect on the risk of stillbirth or the baby dying before discharge from hospital (9 trials, 6763 babies; relative risk 1.04, 95% confidence interval 0.65 to

1.66). The effects seemed strongest for high risk women and those with

low dietary calcium. Data from the recent World Health Organization trial of women with low calcium intake support a modest reduction in the risk of pre-eclampsia associated with calcium supplementation

rather than placebo (171/4151 v 186/4161; relative risk 0.91, 0.69 to

1.19).There were also reductions in the risk of severe gestational

hypertension (relative risk 0.71, 0.61 to 0.82), eclampsia (0.68, 0.48 to 0.97), and delivery before 32 weeks (0.82, 0.71 to 0.93). Antioxidants, primarily vitamins C and E, also seem to reduce the risk of pre-eclampsia [20]_{. This seems to be associated with an increase in preterm} birth (3 trials, 585 women; relative risk 1.38, 1.04 to 1.82), but there is insufficient evidence for conclusions about the impact on perinatal mortality.

Drugs: Antiplatelet drugs, primarily low dose aspirin, reduce the relative risk of pre-eclampsia by 19% (95% confidence interval 12% to 25%) and of stillbirth or neonatal death by 16% (4% to 26%; 38 trials, 34 010 women). This means that 69 women (51 to 109) would need to be treated with low dose aspirin to prevent one case of pre-eclampsia; for high risk women 18 (13 to 30), for moderate-low risk 188 (74 to 303). To prevent one baby death 227 women (128 to 909) need to be treated. Follow up of children at 2 years of age is reassuring that low dose aspirin is safe during pregnancy [21]_{. This is the only intervention} shown to reduce the risk both of pre-eclampsia and its complications. Women at high risk should be offered low dose aspirin. From a public health perspective, it may also be worth considering for more widespread use.

Timing of Birth: Manage pregnancy in women with pre-eclampsia conservatively (that is, do not plan same-day delivery of the baby) until 34 weeks. Consultant obstetric staff should document in the woman's notes the maternal (biochemical, hematological and clinical) and fetal thresholds for elective birth before 34 weeks in women with pre-eclampsia. Consultant obstetric staff should write a plan for antenatal fetal monitoring during birth. Offer birth to women with pre-eclampsia before 34 weeks, after discussion with neonatal and anesthetic teams and a course of corticosteroids has been given if:





consultant plan.

Recommend birth for women who have pre-eclampsia with severe hypertension after 34 weeks when their blood pressure has been controlled and a course of corticosteroids has been completed. Offer birth to women who have pre-eclampsia with mild or moderate

hypertension at 34+0 _{to 36}+6 _{weeks depending on maternal and fetal}

condition, risk factors and availability of neonatal intensive care.

Recommend birth within 24–48 hours for women who have

pre-eclampsia with mild or moderate hypertension after 37+0 _weeks.

Professional Relationship among Health Care Professionals: Clear communication among care team members is essential for optimal, safe and consistent management of women with HDP. SOGC, NICE and SOMANZ guidelines all recommend that facilities develop protocols that can be accessed by all staff to ensure consistent, quality care. Guidelines recommend that facilities have protocols in place that include general management protocols for preeclampsia, protocols for severe hypertension management, and indications for seizure prophylaxis in preeclampsia. SOMANZ guidelines recommend that OB units post protocols for the administration of LMWH when epidural anaesthesia or analgesia is administered. ACOG-AAP guidelines recommend informing the obstetrician, midwife or nurse practitioner of any woman presenting to labor and delivery who is found to have hypertension on initial evaluation. Other communications among team members recommended in guidelines include informing anaesthesia when women with preeclampsia are admitted and discussion among the patient and neonatal, obstetric and anaesthesia team members if birth before 34 weeks is considered. Written care plans with parameters for maternal and foetal surveillance and maternal follow-up are advocated in NICE guidelines. Antenatal steroids should be considered for women at risk for preterm delivery who present between 24 and 34 weeks gestation. There is strong evidence to recommend steroids for all women presenting with preeclampsia before 34 weeks gestation. The evidence is less clear regarding antenatal steroids for women presenting with gestational hypertension without evidence of preeclampsia at less than 34 weeks gestation; although one third of these women will develop preeclampsia, it is unlikely that they will deliver within 7 days of presentation. SOGC guidelines recommend consideration of antenatal steroids for women with gestational hypertension without signs or symptoms of preeclampsia who present at less than 34 weeks gestation if delivery is contemplated within the next 7 days based on expert consensus, and some guidelines recommend discussion with the

neonatal team [22]_{. Long term treatment of women with HDP should be}

reviewed at 2 weeks postpartum for those who remain on anti-hypertensive drugs. NICE recommends a medical review for women with HDP who remain on anti-hypertensive drugs two weeks after discharge, since many women with gestational hypertension may actually have a pre-existing hypertensive disorder. SOGC guidelines recommend that women with severe preeclampsia, especially those who presented or delivered before 34 weeks, should be screened for pre-existing hypertension, underlying renal disease and thrombophilia.

REFERENCES:

1. National High Blood Pressure Education Program. The Fifth

Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Bethesda, National Institutes of Health; page no: 525-537.

2. Hansson L, Zanchetti I, et al. Effects of intensive blood-pressure

3. Brown MJ, Palmer CR, Castaigne A. et al. Morbidity and mortality in patients randomised to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the International Nifedipine GITS study, page no: 366-372.

4. Hansson L, Lindholm LH, Niskanen L. et al. Effect of

angiotensin-converting-enzyme inhibition compared with

conventional therapy on cardiovascular morbidity and mortality in hypertension, page no: 611-616.

5. Dahlof B, Devereux RB, Kjeldsen SE. et al. Cardiovascular

morbidity and mortality in the Losartan Intervention For Endpoint Reduction in Hypertension study (LIFE): a randomised trial against atenolol, page no: 995-1003.

6. Karlberg BE, Andrup M, Oden A. for the Swedish TARKA trialists.

Efficacy and safety of a new long-acting drug combination, trandolapril/verapamil as compared to monotherapy in primary hypertension, page no: 140-145.

7. Pahor M, Psaty BM, Alderman MH. et al. Health outcomes

associated with calcium antagonists compared with other first-line antihypertensive therapies, page no: 1949-1954.

8. Wei SQ, Audibert F, Hidiroglou N, Sarafin K, Julien P, Wu Y, Luo

ZC, Fraser WD. Longitudinal vitamin D status in pregnancy and

the risk of pre-eclampsia, page no: 832–839.

9. Kasawara KT, do Nascimento SL, Costa ML, Surita FG, e Silva JL.

Exercise and physical activity in the prevention of

pre-eclampsia: systematic review, page no: 1147–1157.

10. Zhang J, Klebanoff MA, Roberts JM. Prediction of adverse

outcomes by common definitions of hypertension in pregnancy,

page no: 261–267.

11. Von Dadelszen P, Magee LA, Roberts JM. Subclassification of

preeclampsia. Hypertension in pregnancy official journal of the International Society for the Study of Hypertension in Pregnancy

, page no: 143–148.

12. Buchbinder A, Sibai BM, Caritis S, Macpherson C, Hauth J,

Lindheimer MD, Klebanoff M, Vandorsten P, Landon M, Paul R, Miodovnik M, Meis P, Thurnau G. Adverse perinatal outcomes are significantly higher in severe gestational hypertension than

in mild preeclampsia, page no: 66–71.

13. Kasawara KT, do Nascimento SL, Costa ML, Surita FG, e Silva JL.

Exercise and physical activity in the prevention of

pre-eclampsia: systematic review, page no: 1147–1157.

14. National High Blood Pressure Education Program Working

Group on High Blood Pressure in Pregnancy. Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy, page no: 183-195.

15. Meis PJ, Goldenberg RL, Mercer BM. et al. for the Maternal-Fetal

Medicine Units Network of the National Institute of Child Health and Human Development. The preterm prediction study: risk factors for indicated preterm births, page no: 562-567.

16. Caritis S, Sibai B, Hauth J. et al. for the National Institute of Child

Health and Human Development Network of Maternal-Fetal Medicine Units. Predictors of pre-eclampsia in women at high risk, page no: 946-951.

17. Kramer MS, Demissie K, Yang H, Platt RW, Sauve R,

Liston R.Fetal and Infant Health Study Group of the Canadian Perinatal Surveillance System. The contribution of mild and moderate preterm birth to infant mortality, page no: 843-849.

18. Ananth CV, Joseph KS, Oyelese Y, Demissie K, Vintzileos AM.

Trends in preterm birth and perinatal mortality among singletons, page no: 1084-1091.

19. Tsatsaris V, Goffin F, Munaut C. et al. Overexpression of the

soluble vascular endothelial growth factor receptor in preeclamptic patients: pathophysiological consequences, page no: 5555-5563.

20. Koga K, Osuga Y, Yoshino O. et al. Elevated serum soluble

vascular endothelial growth factor receptor 1 (sVEGFR-1) levels in women with preeclampsia, page no: 2348-2351.

21. Torry DS, Wang HS, Wang TH, Caudle MR, Torry RJ.

Preeclampsia is associated with reduced serum levels of placenta growth factor, page no: 1539-1544.

22. Zhang J, Bowes WA Jr. Birth-weight-for-gestational-age patterns

by race, sex, and parity in the United States population, page no: 200-208.

How to cite this article:

Shaik Kareemulla et al. APPRAISAL OF CLINICAL PHARMACIST IN EVANGELIZING PHARMACEUTICAL CARE PLAN FOR A GRAVE CONTINGENCY PRE- ECLAMPSIA PRECIPITATING HELLP SYNDROME: A CASE STUDY. J Sci Res Pharm 2018;7(3):35-41.