HELLP Syndrome: 7 Years' Experience from one Referral Center in South-Eastern Turkey
Authors
G Bayhan, M Yayla, AC Erden
Institution
Address of Correspondence:Gohan Bayhan, M.D. ,
Dept. of Gynecology and Obstetrics, Dicle University Medical School, Diyarbakor, TURKEY
Tel: +90 412 2488051
Fax: +90 412 2488430
E-mail: bayhan@tr-net.net.tr
Source
Nagoya Medical Journal 43:205-214(2000)
INTRODUCTION
HELLP syndrome (Hemolysis, Elevated Liver enzymes, and Low Platelet count) is associated with poor maternal and fetal outcomes (1). Maternal mortality has been estimated to be as high as 24% (2). Patients with HELLP syndrome are also at great risk of pulmonary edema, adult respiratory distress syndrome, abruptio placenta, disseminated intravascular coagulation, ruptured liver hematomas and acute renal failure. Perinatal mortality is equally high, ranging from 79 to 367 per 1000 live births and neonatal complications correlate with the severity of maternal disease (3). Many clinicians view HELLP syndrome as an entity of preeclampsia and because of varied symptomatology, the initial diagnosis may be obscured. Before delivery, aggressive obstetric management is directed toward stabilization of the affected organ systems, if possible, timely interruption of the pregnancy in the early phase of the accelerated disease progression when the fetal lung maturity is obtained (4). Definitive therapy is delivery. Parturient with HELLP syndrome are often critically ill, their infants are frequently premature and their conditions are compromised. Management criteria should include a multidisciplinary approach in a tertiary care center. Mothers with HELLP syndrome should be identified promptly and delivered in level II or III centers with appropriate facilities, for management of the newborn infants at risk (5).
The aim of this study is to evaluate the epidemiology, clinic features and maternal-perinatal outcomes in HELLP syndrome during 7 years' period in a referral center.
MATERIALS AND METHODS
The Obstetrics Clinics at the Dicle University Hospital serves as referral center for an area that includes of 5 cities and 24 villages in South Eastern Turkey. This hospital has approximately 1000-1200 deliveries annually. During the 7-year period, January 1, 1991, through November 31, 1997, 104 of the pregnancies managed at this center were complicated by HELLP syndrome. These patients were reviewed in a retrospective study according to the representing symptoms, demographic and laboratory findings, characteristics of delivery and perinatal-maternal prognosis.
Routine laboratory evaluation included serial measurements of complete blood cell count, liver function tests, coagulation profile, and renal function tests. HELLP syndrome was defined by the presence of all three of the following criteria : hemolysis (characteristic peripheral blood smear and serum lactate dehydrogenase (LDH) levels > 600 U/L or total bilirubin > 1.2 mg/dl), serum aspartate aminotransferase (AST) >70 U/L, and platelet counts < 100 000/mm3.
Acute renal failure was diagnosed in the presence of oliguria-anuria in association with severe reduction in renal function (creatinine clearance of < 20 ml/min). The diagnosis of pulmonary edema was defined on the clinical signs and symptoms and chest X-ray findings. Ascites and pulmonary effusion were diagnosed on clinical signs and ultrasonographic examinations. Disseminated intravascular coagulation was defined as the presence of low platelets (<100 000/mm3), low fibrinogen (<300 mg/dl), high fibrin degradation products (>16ug/ml) and prolonged prothrombin (>14 seconds) and partial thromboplastin times (>40 seconds). Cerebral pathologies were defined also after clinical signs and tomographic evaluation. Abruptio placenta was diagnosed respecting clinical and sonographic findings.
To prevent and control seizures, women with severe preeclampsia and eclampsia routinely received magnesium sulfate as a 3 g intravenous and 9 g intramuscular loading dose followed by intramuscular 4.5 g 4-6 hourly or 1-1.5g/hour intravenously and stopped in the postpartum 24th hour. Blood pressure, patellar reflex, urine output and respiratory function were observed during therapy. Nifedipine 10mg, when diastolic blood pressures exceed 110mm Hg and alpha-methyldopa (tid 250-500mg) routinely were administered to control severe hypertension. Blood and blood products were used to correct coagulation disorders and anemia as needed. Corticosteroids were used when platelet count persisted under 30000/mm3. Women received betamethason 12mg in two doses 12 hours apart before the 34th weeks of gestation. Laparotomy was performed when necessary to control major intraabdominal bleeding. Statistical analysis was performed by Chi-square test, a p value of <0.05 was considered as statistically significant.
RESULTS
During the study period, there were 730 pregnancies complicated by hypertensive disorders in our center. Half of these patients were complicated by preeclampsia, one third by eclampsia and the remaining by chronic hypertension. One hundred four patients with HELLP syndrome (14.2%) were initially presented by preeclampsia (n:47, 45.2%) or eclampsia (n:48, 46.2%). The incidence of HELLP syndrome among women with preeclampsia in our population was 12.8% and the incidence among women with eclampsia was 19.8%.
Low socio-economic status, uneducated women, irregular prenatal control, inadequate first therapeutic intervention, bad transport conditions and late admission to our center were the main characteristics of the HELLP cases. HELLP syndrome in adolescent period was seen in 25% of the cases. Primigravid patients were 31.7% of the group. The mean maternal age was 27.04Ž±7.19 years (range: 17-45 years). Characteristics of patients with HELLP syndrome are summarized at Table I.
Prodromal signs and symptoms of women with HELLP syndrome.were edema, headache, visual disturbances and epigastric pain in decreasing order respectively. Table II describes the time of onset of patients with HELLP syndrome regarding gestational age and delivery. HELLP syndrome was seen at the prepartum period in 61.5% and at the postpartum period in 38.5% of the cases. In the postpartum group the onset of clinical manifestations developed within 48 hours after delivery. More than one third of the cases was admitted before 33rd gestational weeks, and approximately one third after 37th gestational weeks. Most of the cases were developed in the antepartal period.
Analysis of the mode of delivery with gestational age is shown in Figure ŽÝ. The mean gestational age was 34.38Ž±4.20 weeks ranging between 24-40 gestational weeks. In HELLP pregnancies at <28 weeks, none were delivered by cesarean section, whereas in gestations >28 weeks the cesarean section rate was 50%. Four patients (3.8%) had died before delivery. Cesarean section was performed in 26 patients (26%) and cesarean hysterectomy in 2 (%2). In the majority of cases with HELLP syndrome deteriorating maternal and fetal condition and failure to progress were the main indications of abdominal delivery. Seventy-six patients (75%) were referred from local hospitals, 17 of them were referred after delivery because of different complications .
Table III lists serious maternal complications. Abruptio placenta was the most frequent complication (15.4%). Cerebral findings (10.6%), acute renal failure (9.6%), ascites or pleural effusion (9.6%) were the causes of other frequent maternal morbidity. Overall, 45.2% of the patients required blood or blood products to correct hypovolemia, anemia or coagulopathy. Maternal mortality was seen in 9.61% of the cases (n:10). The majority of cases were died from hepatic, renal, cerebral and pulmonary causes. Table IV shows the causes of maternal mortality in patients with HELLP syndrome.
Overall perinatal mortality was seen in 62 cases (59.6 %). Forty-three of them had delivered in our center with 51.8% perinatal mortality, 15 in village hospital or in home with 88.2% perinatal mortality (p<0.05) (Figure ŽÝŽÝ). Four fetuses died in utero during maternal resuscitation. Most of the perinatal deaths were related to intrauterine asphyxia (low Apgar scores in 86%) and extreme prematurity (46.5%).
DISCUSSION
Since the term "HELLP syndrome" was introduced in 1982 by Weinstein (6), controversies persist about its diagnosis, management, and prognosis. The pathophysiologic mechanisms are not known exactly.
The incidence of HELLP syndrome among patients with preeclampsia-eclampsia in this study was 14.2%. This extremely high incidence is due to the high rate of complicated cases referred to our institution and not being recognized initially in first medical centers moreover promptly at the ours one. The incidence of HELLP syndrome in women with eclampsia was 19.8%. This high incidence supports the reports of Miles et al (7) that there is a strong association between HELLP syndrome and eclampsia and its presence may be a predisposing factor in the development of eclampsia.
Mean gestational age at delivery in the HELLP cases was reported as 32Ž±4 weeks (8). Our HELLP cases were delivered at a mean gestation of 34Ž±4 weeks, after a very short antepartum observation period. We thought that the majority of our cases had diagnosed lately.
It was reported that the 39% of the HELLP cases received regular prenatal control (9) Our cases received prenatal control in only a rate of 29%.
Maternal mortality rate is reported between 0-240 per thousand (9). In the report of Argueta et al (10), HELLP syndrome was seen commonly in patients with preterm pregnancies, with a maternal mortality rate of 55.5 per thousand. Our maternal mortality rate (96 per thousand) was higher than reported one because of the characteristics shown at the Table I.
The incidence of cesarean delivery in patients with HELLP was reported as 76.2% (11). Our incidence was 50%. This lower incidence is due to the policy of not being done cesarean section before 30-32nd gestational weeks.
Perinatal mortality was reported 7.7-60.0% in HELLP cases (9,10,12). We found it 59.6% in HELLP cases and we related it to the late admission to hospital, delayed diagnose also to the unsatisfactory neonatal intensive care unit conditions.
HELLP syndrome is also reported to be a major cause of renal failure in developing countries (13). Sibai et al (5) reported 7.7% of acute renal failure in these cases. We found renal compromise in 9.6% of the cases.
Disseminated intravascular coagulopathy can be seen in 21% and abruptio placenta in 16% of the HELLP cases (5). Our findings were 3.8% and 15.4% respectively.
Sibai et al (5) reported an incidence of emergency laparotomy of 2% in HELLP cases because of intraabdominal bleeding. Our results are similar (2%).
Patients with progressive deterioration in laboratory findings presented delayed resolution of their disease. Consequently our management in HELLP syndrome is prompt delivery in 24-48 hours in an attempt to reduce the incidence of complications, although conservative management was frequently used in better health care facilities (14,15). Complete reversal of HELLP can be obtained in 43% of patients and perinatal mortality can be found as 14% in HELLP patients with temporising treatment (15).
The prophylactic administration of platelets does not appear to have a decreasing effect in the incidence of postpartum hemorrhagic complications (16). We used platelet infusions only in severe thrombocytopenic patients (<30000/mm3).
Magann et al (11) postulated that the use of corticosteroids in properly selected patients could result in lessened overall maternal morbidity and mortality, shorter patient stays in recovery and intensive-care areas and shorter overall hospitalization with reduced medical care costs. We preferred this regimen only in cases with extremely lower platelet counts.
Martin et al (17) recommended that a trial of plasma exchange with fresh-frozen plasma be considered in HELLP syndrome. Our treatment policy is close observation of fluid intake and output, transfusions as needed, corticosteroids in persistent cases and supportive care.
Raval et al (2) showed that infants born to preeclamptic mothers who developed HELLP syndrome need for resuscitation at delivery and a higher incidence of postnatal cardiopulmonary instability. Our perinatal mortality is high as well because of extreme prematurity.
This study supports that HELLP syndrome is associated with increased maternal and perinatal morbidity and mortality in underdeveloped areas. This high incidence of complications reflects the high risk and negligence of primary obstetric care. HELLP syndrome is a life threatening condition in hypertensive pregnancies especially in uneducated population with bad pregnancy control, unsatisfactory and late medical approach. We considered that, with progressing infrastructure in the region, educational level will be better and by improved health services and routine antenatal care will mostly prevent this serious obstetric complication.
REFERENCES
Pampus MG, Wolf H, Westenberg SM, van der Post JA, Bonsel GJ, Treffers PE. Maternal and perinatal outcome after expectant management of the HELLP syndrome compared with pre-eclampsia without HELLP syndrome. Eur J Obstet Gynecol Reprod Biol 1998, 76:31-6
Raval DS, Co S, Reid MA, Pildes R. Maternal and neonatal outcome of pregnancies complicated with maternal HELLP syndrome. J Perinatol 1997, 17:266-9
DÓÕsch J, Hohmann M, KÝÉl PG. Neonatal morbidity and mortality associated with maternal haemolysis elevated liver enzymes and low platelets syndrome. Eur J Pediatr 1997, 156:389-91
Dreyfus M, Tissier I, Baldauf JJ, Ritter J. HELLP syndrome. Review and update. J Gynecol Obstet Biol Reprod 1997, 26:9-15
Sibai BM, Ramadan MK, Usta I, Salama M, Mercer BM, Friedman SA. Maternal morbidity and mortality in 442 pregnancies with hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome). Am J Obstet Gynecol 1993, 169:1000-6
Weinstein L. Syndrome of hemolysis, elevated liver enzymes, and low platelet count: a severe consequence of hypertension in pregnancy. Am J Obstet Gynecol 1982, 142:159-67
Miles JF Jr, Martin JN Jr, Blake PG, Perry KG Jr, Martin RW, Meeks GR. Postpartum eclampsia: a recurring perinatal dilemna. Obstet Gynecol 1990, 76:328-31
Audibert F, Friedman SA, Frangieh AY, Sibai BM. Clinical utility of strict diagnostic criteria for the HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. Am J Obstet Gynecol 1996, 175:460-4
Sibai BM. The HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets): Much ado about nothing? Am J Obstet Gynecol 1990 , 162: 311-6
Argueta Z×öiga M, Neri M»Ïdez C, Lira Plascencia J, IbargÝÆngoitia F, VÛquez JuÓez ME. HELLP syndrome. 7-year experience at the National Institute of Perinatology. Gynecol Obstet Mex 1995, 63:217-21
Magann EF, Roberts WE, Perry KG Jr, Chauhan SP, Blake PG, Martin JN Jr. Factors relevant to mode of preterm delivery with syndrome of HELLP (hemolysis, elevated liver enzymes, and low platelets). Am J Obstet Gynecol 1994, 170:1828-32
Van Bogaert LJ. Perinatal mortality and preeclampsia/eclampsia: influence of HELLP syndrome on the primigravida. J Gynecol Obstet Biol Reprod 1995, 24:323-6
Randeree IG, Czarnocki A, Moodley J, Seedat YK, Naiker IP. Acute renal failure in pregnancy in South Africa. Ren Fail 1995, 17:147-53
Schiff E, Friedman SA, Sibai BM. Conservative management of severe preeclampsia remote from term. Obstet Gynecol 1994, 84:626-30
Visser W, Wallenburg HC.Temporising management of severe pre-eclampsia with and without the HELLP syndrome. Br J Obstet Gynaecol 1995, 102:111-7
Roberts WE, Perry KG Jr, Woods JB, Files JC, Blake PG, Martin JN Jr: The intrapartum platelet count in patients with HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome: is it predictive of later hemorrhagic complications? Am J Obstet Gynecol 1994, 171:799-804
Martin JN Jr, Files JC, Blake PG, Norman PH, Martin RW, Hess LW, Morrison JC, Wiser WL. Plasma exchange for preeclampsia. I. Postpartum use for persistently severe preeclampsia-eclampsia with HELLP syndrome. Am J Obstet Gynecol 1990, 162:128-37
Tables
Table I Characteristics of patients with HELLP syndrome
Characteristics n %
Low socioeconomic status 88 84.6
Uneducated (no primary education) 75 72.1
No prenatal control 73 70.2
Any therapy before admission 41 39.4
Age <21 26 25.0
Age 21-34 57 54.8
Age >35 21 20.2
Parity 0 33 31.7
Parity 1-4 38 36.6
Parity >5 33 31.7
Table. II Time of onset of HELLP syndrome (n:87)
Time of onset n %
<28 (Gestational weeks) 5 5.7
28-32 27 31.0
33-37 31 35.6
>37 24 27.6
Antepartum onset 64 61.5
Postpartum onset 40 38.5
Delivery before admission 17 16.3
Table III Maternal complications in patients with HELLP syndrome