INDEX RISK FACTORS FOR THE HIGH PREVALENCE OF HELLP SYNDROME AND THE OUTCOME
H. Guler Sahin, MD, Department of Obstetrics and Gynecology
Huseyin Avni Sahin, MD, Department of Family Medicine
Idris Sahin, MD, Department of Internal Medicine
Kevser Onbasi, MD, Department of Internal Medicine
University of Yuzuncu Yil, Medical Faculty, Van, Turkey
Correspondence: Assistant Professor Guler Sahin, Assistant Professor
Yuzuncu Yil Universitesi Tip Fakultesi
Kadin Hastaliklari ve Do um Anbilim Dali
Van / TURKEY
Objective: To identify the risk factors associated with HELLP syndrome Material and Methods: 36 patients with HELLP syndrome and severe preeclampsia or eclampsia consisted group one and 130 patients with severe preeclampsia or eclampsia without HELLP syndrome consisted the control group. The groups were compared for maternal age, education, number of pregnancies gestational age antenatal care history of hypertension presence of underlying disease, blood pressure, edema proteinuria nausea epigastric pain, headache, blurred vision, maternal and perinatal outcomes, route of delivery, rate of stillbirth, maternal mortality, complications and days of hospital stay. Statistical analyses were performed with the SPSS statistics program using the Mann Whitney-U, Chi-Square and Student T tests to examine differences between the two groups. A value of P £ 0.05 was considered significant. Results: The rate of HELLP syndrome was 21.08 % and the rate in severe preeclampsia and eclampsia were 15.17 % and 33.33 % respectively. Maternal age, lack of antenatal care, delay in seeking medical attention were significantly associated with HELLP syndrome. 65.7 % of HELLP syndrome had upper gastrointestinal syndrome symptoms on presentation. The rate of stillbirth, maternal mortality rate, rate of complications, the mean days of hospital stay were significantly higher, the mean Apgar scores at five minutes, the mean gestational age, the rate of adolescent pregnancies were lower in the HELLP syndrome group. Conclusion: Age, gestational age, antenatal care, delay seeking medical attention, upper quadrant pain, nausea and vomiting are important risk factors in the diagnosis and the prognosis of HELLP syndrome.
Severe preeclampsia may manifest as a multisystem disease and covers a spectrum of presentations that not all of them are likely to be equally dangerous. HELLP Syndrome a typical form of preeclampsia or eclampsia characterized by hepatic dysfunction, microangiopathic hemolytic anemia and trombocytopenia is reported to occur 2 to 12 % of patients with severe preeclampsia and 30 to 50% of eclamptic gravidas (1)
Since 1982 it is reported to be associated with maternal deaths in a range between 1% and 24 %. (2) In the developed world in spite of the development of tertiary care facilities advanced field of maternal fetal medicine blood banking techniques and sophisticated intensive care capabilities for both the mother and the baby, maternal and perinatal deaths continue to occur in association with HELLP syndrome (3)
The purpose of this study was to identify risk factors associated with the development of HELLP syndrome. The information obtained may help to distinguish and profile the risk factors and if possible prevent HELLP syndrome in order to reduce the factors responsible for maternal and perinatal deaths in severe preeclampsia and eclampsia.
Material and Methods:
From September 1997 to June 1 2000, 112 cases of severe preeclampsia and 54 cases of Eclampsia were managed at the University of Yuzuncu Yil Medical Faculty Hospital, Department of Obstetrics and Gynecology in Van, Turkey. The institution is a referral center that serves the urban, as well as rural, mostly economically disadvantaged population. During the study period all of the patient hospitalized with the diagnosis of eclampsia and severe preeclampsia soon after admission underwent blood screening which included complete blood cell count including platelets, urine analyses and liver renal chemistry panel. Presenting symptoms were recorded coagulation studies and other supplemental laboratory tests were performed. HELLP Syndrome was diagnosed if the following were present.
1). Trombocytopenia: platelet counts £ 50000 /ml was defined as HELLP Syndrome Class 1. Platelet count between > 50000 and £ 100000/ml was defined as Class 2 and platelet count > 100000 but £ 150000 cells /ml was defined as Class 3.
2). Hemolysis, increased lacticdehidrogenase serum concentration (LDH) >400 u/l decreased hemoglobin and hemotocrit, increased Total Billuribin ³ 1,2 mg/dl and abnormal peripheral smear.
3). Elevated liver enzymes: increased serum concentration of aspartate aminotransferase (AST) ³ 70 u/l, alanine aminotransferase (ALT) ³50 u/l lactic dehydrogenase ³ 400 u/l
During the study period 130 patients with signs and symptoms of preeclampsia (94) 72,3 % or eclampsia (36) 27.5% without HELLP Syndrome and 36 patients with signs and symptoms of preeclampsia (18) 50 % or eclampsia (18) 50 % with HELLP syndrome were compared.
Eclampsia was defined as the occurrence of convulsions together with hypertension (Blood pressure of at least 140/90 mmHg or an increase of at least 30 mmHg in systolic and 15 mmHG in diastolic blood pressure) proteinuria (at least (+) protein in a random urine sample or greater than 0,3 g/l in a 24 hour collection) and pretibial edema. Severe preeclampsia was defined as blood pressure greater than 160/110 mm Hg, Proteinuria ³ 3+ on dipstick and pretibial edema.
The variables evaluated included age, education, parity, prenatal care, gestational age, history of hypertension, presence of underlying disease (renal disease, DM, Chronic Hypertension) Blood pressure (systolic and diastolic) nausea, epigastric pain, headache, blurred vision. The duration of symptoms of preeclampsia or eclampsia, proteinuria, maternal and perinatal outcomes, route of delivery, rate of stillbirth, 5 minute Apgar scores, maternal mortality, days of hospital stay and complications.
Statistical analyses were performed with the SPSS statistics program using the Mann Whitney-U, Chi-Square and Student T tests to examine differences between the two groups. A value of P £ 0.05 was considered significant.
There were 166 patients with severe preeclampsia and eclampsia. 36 of these patients also had HELLP syndrome. The rate of HELLP syndrome was 21.69 %. The rate of severe preeclampsia and eclampsia were 67.47 % and 32.53 % and the rate of HELLP syndrome in severe preeclampsia and eclampsia were 16.07 % and 33.33 % respectively.
The 36 severe preeclamptic or eclamptic patients with HELLP syndrome consisted group one and the 130 severe preeclamptic or eclamptic patients without HELLP syndrome consisted group two.
The mean platelet count, AST, ALT, LDH, Total bilirubin and haemotocryt values were 82.196 cells/ml, 316 iu, 251 iu, 883 iu, 1.94 mg/dL and 35.11 % in the HELLP group respectively on admission. These values were significantly different in the HELLP syndrome group compared to the control group as shown in Table I. 16.7 % of HELLP syndrome was in class one, 44.4 % in class two and 36.1 % in class three on admission.
The demographic obstetric and clinical characteristics of the 2 groups are summarized in table 1. Most of the patient in both groups were uneducated, the mean age was higher among patients with HELLP syndrome (32.61) compared to control group (29.53), the difference was statistically significant. (P=0.045) The percentage of adolescent pregnancy was higher in the control group, 6.1 % and lower in HELLP group 2.85 %but the results were not statistically significant. (P=0.43) The difference between the mean numbers of pregnancies was not significant (P=0.789) and no antenatal care was significantly higher among cases of HELLP syndrome. (P=0.019) The commonest underlying disease with HELLP was chronic Hypertension (16.7 %).
The mean gestational age in the HELLP Syndrome and the control group were 31.17 weeks and 33.46 respectively (P= 0.025). There were significant differences in gestational age. The difference between the blood pressures and edema were not significant as shown in Table I. 65,7 % had epigastric pain, nausea and vomiting, 37,1 % had blurred vision, 54,2 % had headache in the HELLP syndrome group, versus 51,9 %, 32,1 % and 60 % in the control group.
Perinatal outcomes were significantly worse in the HELLP syndrome group. The mean Apgar scores at 5 minutes were 3.33 versus 5.53 in the HELLP syndrome and the control group respectively. (P=0.003) Still birth rate was 36.1 % versus 18.5 % in the HELLP syndrome and the control group respectively. (P=0.025)The maternal mortality rate was 13.9 % in the HELLP syndrome group and 0.8 % was in the control group. (P=0.0001). The differences were significant. The mean days of hospital stay was 7.14 day and significantly longer in the HELLP group compared to control group (5.65). (P=0.01) 41.7 % of the HELLP syndrome group delivered with caesarian section and 58.3 % by the vaginal route. These rates in the control group were 26.9 and 73.1 respectively and the differences were not significant
These results are summarized in Table II.
The rate of abruptio placenta was 5.55 % and 1.54 % in the HELLP Syndrome group and the control group. The indication for caesarian delivery were abruptio placenta 14.28 %, insensitivity to induction 7.14 %, acute fetal distress 42.85 %, abnormal lie 14.28 %, rapidly changes in maternal signs 21.42 % in the HELLP syndrome group and abruptio placenta 6.06 %, fetal distress 51.51 %, insensitivity to induction 18.18 %, abnormal lie 6.06 %, rapidly changes in maternal signs 3.03 %, dystocia 15,15 % in the control group
The maternal complications were acute renal failure 13.88 % and all needed dialysis, 2.78 % patients developed intracerebral hemorrhage, 2.78 % had DIC, 2.78 % had pulmonary edema in the HELLP syndrome group whereas 2.3 % had renal failure, 2.3 % developed intracerebral hemorrhage 0.76 % had pulmonary edema, 0.76 % had cardiopulmonary arrest, 0.76 % had retinal detachment in the control group. These results are shown in Table III. Discussion:
HELLP syndrome is an expression of severe preeclampsia and eclampsia with a reported incidence raging between 2 and 18.9 %(4). It has been reported that HELLP syndrome occurs in 2 to 12 % of patients with severe preeclampsia and 30-to 50 of eclamptic gravidas (1) Mortality rate has been reported to rage between 1% and 24 % and Christy M. Isler has reported that most deaths had occurred among women with class I HELLP syndrome, delay in diagnosis was associated with mortal consequences and hemorrhage in the hepatic or central nervous system or vascular insult to the cardiopulmonary or renal system were associated with increased mortality risk(2) We undertook this investigation to examine the risk factors for the development of HELLP Syndrome and to reduce the impact by making it possible for special care to be given to the patient who have the risk factors for the development of HELLP syndrome.
Our results are near the upper limits of this published data. The rate of HELLP syndrome in the study was 21.69 %. The rate of severe preeclampsia and eclampsia were 67.47 % and 32.53 % and the rate of HELLP syndrome in severe preeclampsia and eclampsia were 16.07 % and 33.33 % respectively.
No antenatal care, maternal age and delay in seeking medical attention were the main risk factors in the development of HELLP syndrome. The increased incidences in the older multiparous women are probably related to an underlying problem, which most commonly was chronic hypertension. However other conditions that lead to chronic vascular diseases probably carry a significant risk for the development of HELLP syndrome. Fisher et al. Performed kidney biopsies on both nulliparous and multiparous patients with preeclampsia and found prevalences of chronic renal lesions of 16.3 % and 51% respectively (5) These findings could be the explanation of higher rate of HELLP syndrome in multiparous aged women. In our study because of lack of antenatal care most of the study population had not been tested for previous underlying disease and delay seeking medical attention were significantly associated with the development of HELLP syndrome. And these patients were usually seen at a stage where complication of preeclampsia had occurred.65.7 % had epigastric pain, 54.2 % had headache .31.64 % had blurred vision on admission. Sibia et al reported 65%, Weinstein et al. have reported 84% nausea and vomiting and 86% epigastric pain in their series of women with HELLP syndrome. (4,6) Which are similar to our results. These findings highlight the importance of the upper quadrant or epigastric pain with or without nausea and vomiting in the third trimester, which should be investigated for HELLP syndrome.
Delay in diagnosis leads to delay in appropriate treatment and this results in an increase in the mortality and the morbidity rate, which was significantly high for the mother and the baby in our series of HELLP syndrome group. It has been reported that the neonatal morbidity and mortality are related to gestational age rather than the presence or absence of HELLP syndrome. (7) Our results support these views as gestational ages were significantly lower and neonatal outcomes were significantly worse in the HELLP syndrome group in our study. The rate of intra uterine exitus on admission was significantly higher in the HELLP syndrome group, which we concluded were due to delay in seeking appropriate medical attention. Although there are contrary points treatment with high dose steroids have been reported to have beneficial effects on these rates (8,9,10,11). The results point out the importance of antenatal care early diagnosis and treatment especially for the advanced aged pregnancies that present with upper quadrant pain, nausea, vomiting and preeclampsia or eclammpsia or superimposed preeclampsia.
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2. Isler CM et al. Maternal mortality associated with HEELP syndrome. Am J Obstet Gynecol. 1999;181-4: 924-8
3. Kirshon B, Hinkley C, Cotton D,Miller J. Maternal mortality in a maternal fetal medicine intensive care unit. J Reprod Med. 1990;35:25-8.
4. Sibai MB, Ramadan MK, Usta I et al. Maternal morbidity and mortality in 442 pregnancies with hemolysis, elevated liver enzymes and low platelets (HELLP syndrome) Am J Obstet Gynecol. 1993;169: 1000-1006
5. Agudelo AC. Kafury-Goeta AC. Case Control Study of risk factors for complicated eclampsia. Obstetrics & Gynecology. 1997;90-2:172-5
6. Weinstein L. Preeclampsia/Eclampsia with hemolysis elevetade liver enzymes and thrombocytopenia. Obstet Gynecol. 1985;66:657-60
7. Abramovici D et al. Neonatal outcome in severe preeclampsia at 24 to 36 weeksÕ gestation: Does the HELLP syndrome matter? Am J Obstet Gynecol. 1999;180-1:221-5
8. Gracia PVD. Caceres EG. Dexamethasone in the post-partum treatment of HELLP syndrome. International Journal of Gynecology & Obstetrics. 1997;59:217-21
9. Martin JN et al. Better maternal outcomes are achieved with dexamethasone therapy for postpartum HELLP syndrome. Am J Obstet Gynecol. 1997;177-5:1011-17
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11. Magann EF et al. Corticosteroids for the enhancement of Fetal Lung Maturity: Impact on the gravida with preeclampsia and the HELLP syndrome. Aust NZ J Obstet Gynaecol. 1993;33-2:127-31
Table I : Demographic, obstetric and clinical characteristics
Group I N=36
HELLP Syndrome Group II N=130
Mean age (years) 32.61 29.53 0.045
Adolescent pregnancy ratio 0.0285 0.061 0.43
Mean number of pregnancies 5.06 5.26 0.789
Antenatal care rate 19.4 40.8 0.019
Mean Gestational age (weeks) 31.71 33.46 0.025
Mean Systolic blood pressure (mmHg) 16.83 17.61 0.555
Mean Diastolic blood pressure (mmHg) 10.42 11.12 0.150
Edema (1+É.3+) 1.03 1.33 0.187
Proteinuria (1+É..4+) 3.137 3.198 0.515
Mean Haemotocyrt (%) 35.11 36.98 0.042
Mean Thrombocyt Count (cells/ml) 82.196 219.78 0.001
Mean AST (iu/l) 316 37.63 0,001
Mean ALT (iu/l) 251 32.48 0,001
Mean LDH (iu/l) 883 314.13 0,002
Mean Total Bilirubin mg/dL 1.94 0.606 0,001
Epigastric pain, Nausea, Vomiting (%) 0.67 0.47 0.036
Blurred Vision (%) 0.39 0.32 0.408
Headache (%) 0.61 0.54 0.439 Table II: Perinatal and maternal outcomes
Group I N=36
HELLP Syndrome Group II N= 130
Mean Apgar score at 5 minutes 3.33 5.53 0.003
Still birth rate 36.1 18.5 0.025
Mean days of hospital stay 7.14 5.65 0.010
Maternal mortality rate 13.9 0.8 0.0001
Route of delivery Vaginal 58.3 73.1 0.089
Caesarian 41.7 26.9 0.089
Table III: Complications
Group I N=36
HELLP Syndrome Group II N=130
Acute renal failure 13.88 % 2.30 %
Intracerebral hemorrhage 5.55 % 2.30 %
DIC 2.78 % 0 %
Pulmonary edema 2.78 % 0.76 %
Cardiopulmoner arrest 2.78 % 0.76 %
Retinal detachment 0 % 0.76 %