Hemolysis, Elevated Liver Enzymes, And Low Platelets Syndrome Research Articles

Association between tumor necrosis factor (TNF)-α G-308A gene polymorphism and preeclampsia complicated by severe fetal growth restriction

Background Preeclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome are multifactorial disorders with genetic and environmental components. Given that the tumor necrosis factor (TNF)-α G-308A single nucleotide polymorphism (SNP) affects TNF-α gene transcription and that preeclampsia and HELLP syndrome are characterized by a shift towards a Th1-type maternal immune response with increased TNF-α production, the aim of the current study was to investigate whether this SNP is associated with preeclampsia and HELLP syndrome in a Caucasian population from Hungary. Additionally, we aimed to examine whether TNF-α G-308A polymorphism can influence the risk for fetal growth restriction in preeclamptic patients, which issue none of the earlier studies dealt with. Methods In a case–control study, we analyzed blood samples from 140 preeclamptic patients, 69 patients with HELLP syndrome and 144 normotensive, healthy pregnant women using the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method. We performed also a meta-analysis with our results and those of 8 previously published studies. Results There were no significant differences in the genotype and allele frequencies of the TNF-α G-308A polymorphism between preeclamptic patients and normotensive, healthy pregnant women. However, the mutant (TNF2 or A) allele occurred significantly more frequently in preeclamptic patients with IUGR than in those without IUGR (18.5% versus 7.1%, p = 0.003). In addition, the frequency of the mutant allele carriers was significantly higher among preeclamptic patients with IUGR compared to those without IUGR (30.6% versus 12.8%, p = 0.010). The mutant allele carriers were found to have an increased risk of severe IUGR-complicated preeclampsia, which was independent of maternal age, prepregnancy BMI and primiparity (odds ratio (OR): 2.89, 95% confidence interval (CI): 1.16–7.22, p = 0.023; adjusted OR: 2.78, 95% CI: 1.04–7.45, p = 0.042). Nevertheless, no significant differences were detected in the genotype and allele frequencies of the TNF-α G-308A polymorphism between patients with HELLP syndrome and control subjects. In the meta-analysis, no association was observed between this SNP and preeclampsia (summary OR: 0.956, 95% CI: 0.693–1.319). Conclusions Although the meta-analysis demonstrated a lack of an overall association between TNF-α G-308A polymorphism and preeclampsia, our results suggest a role of this SNP in the risk of severe IUGR-complicated preeclampsia. However, further studies are required with a larger sample size to confirm our findings.

Eclampsia Following Cesarean Section with HELLP Syndrome and Multiple Organ Failure

We present a rare case of postpartum eclampsia with overt acute heart and renal failure, in the absence of any precursive signs of preeclampsia. A 41-year-old parturient underwent elective cesarean section for the delivery of twins under spinal anesthesia. Prior to the procedure, preoperative laboratory examination revealed only traceable proteinuria but she had hypertension perioperatively. Approximately 8 hours after the cesarean section, she developed seizures, followed by evident acute heart and renal failure. The diagnosis of postpartum eclampsia with HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome was established and she was admitted to the surgical intensive care unit for close care. Fortunately, the patient recovered fully and was discharged 26 days later. From this illustrative example, unexplainable and sustained hypertension following cesarean section should serve as a signal to warn the health care staff concerned about the possibility of impending life-threatening postpartum eclampsia.

Membrane cofactor protein mutations in atypical hemolytic uremic syndrome (aHUS), fatal Stx-HUS, C3 glomerulonephritis, and the HELLP syndrome

The hemolytic uremic syndrome (HUS) is a triad of microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment. Genetic studies demonstrate that heterozygous mutations of membrane cofactor protein (MCP;CD46) predispose to atypical HUS (aHUS), which is not associated with exposure to Shiga toxin (Stx). Among the initial 25 MCP mutations in patients with aHUS were 2, R69W and A304V, that were expressed normally and for which no dysfunction was found. The R69W mutation is in complement control protein module 2, while A304V is in the hydrophobic transmembrane domain. In addition to 3 patients with aHUS, the A304V mutation was identified in 1 patient each with fatal Stx-HUS, the HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome, and glomerulonephritis with C3 deposits. A major goal was to assess if these putative mutations lead to defective complement regulation. Permanent cell lines expressing the mutated proteins were complement "challenged," and membrane control of C3 fragment deposition was monitored. Both the R69W and A304V MCP mutations were deficient in their ability to control the alternative pathway of complement activation on a cell surface, illustrating the importance of modeling transmembrane proteins in situ.

Postpartum dexamethasone for women with hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome: a double-blind, placebo-controlled, randomized clinical trial

The purpose of this study was to determine the effectiveness of postpartum dexamethasone in patients with hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. A prospective, randomized, double-blind trial was conducted in which 105 women with HELLP syndrome were enrolled and assigned randomly to treatment or placebo groups following delivery. Duration of hospital stay, maternal morbidity, and laboratory and clinical parameters were evaluated. There was no difference in maternal morbidity or mortality between the 2 groups. There was also no difference in duration of hospitalization and the need for rescue scheme or the use of blood products between groups. Linear model adjustments showed no significant difference between groups with respect to the pattern of platelet count recovery, aspartate aminotransferase, lactate dehydrogenase, hemoglobin, or diuresis. These findings do not support the use of dexamethasone in the puerperium for recovery of patients with HELLP syndrome.

Inflammatory cytokines patterns in the placenta of pregnancies complicated by HELLP (hemolysis, elevated liver enzyme, and low platelet) syndrome

Objective: We investigated the expression pattern and the role of inflammatory cytokines and their receptors in the placentas of pregnancy with HELLP syndrome. Study design: Placentas were collected after cesarean section, 10 from normal pregnancy and 10 from HELLP. The array was performed with GEArray Q Series Human Inflammatory Cytokines & Receptors Gene Array HS-015. The data were confirmed by quantitative real-time PCR. The Student’s t test was used for statistical analysis. Results: Macroarray analysis identified 14 cytokines differentially expressed. PCR confirmed that only IL-10, IL-6-receptor, and TGF-β3 were increased, whilst CCL18, CXCL5, and IL-16 were significantly decreased, in HELLP. Conclusion: The regulation of cytokines involved in angiogenesis and adaptive immune responses may be critical for the placental vascular dysfunction. Our data support the hypothesis that HELLP syndrome could be a placental inflammatory response which leads to a systemic and endothelial dysfunction.

Liver Transplantation for HELLP Syndrome

Of the approximately one in 1000 pregnant women who develop the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP), 2 to 3 per cent develop hepatic complications, including liver failure for which liver transplantation (LT) may be required. Between February 1, 1984, and December 31, 2006, eight women without a history of liver disease underwent LT for complications of HELLP syndrome. All received cadaveric grafts with a mean interval from delivery to LT of 7 days. The mean admission Child-Turcotte-Pugh score was 13.1 (class C), and the mean model for end-stage liver disease score was 40. Manifestations of liver failure included encephalopathy (seven patients), renal failure (four), disseminated intravascular coagulation (three), and respiratory failure (one). There were no intraoperative deaths. Complications of LT included biliary leaks (three patients), reoperation (three), and retransplantation (two). There was one death from sepsis on postoperative day 91 and one death from cholangitis/sepsis more than 5 years postoperatively. After LT, 1-, 5-, and 10-year patient survival rates were 88 per cent, 88 per cent, and 65 per cent; 1-, 5-, and 10-year graft survival rates were 64 per cent, 64 per cent, and 48 per cent. This is the largest single-center report of LT for HELLP. Early recognition and transfer to a transplant center will yield best results with this challenging complication of pregnancy.

Do antiphospholipid antibodies cause preeclampsia and HELLP syndrome?

Antiphospholipid syndrome (APS) is associated with adverse pregnancy outcomes including preeclampsia, recurrent early pregnancy loss, fetal death, and intrauterine growth restriction. Approximately one third of women with APS will develop preeclampsia during pregnancy. The association between antiphospholipid antibodies (aPL) in the absence of the clinical syndrome and preeclampsia is less clear, and a causal relationship has not yet been proven. Testing for aPL should be considered in women with early-onset (< 34 weeks) severe preeclampsia, eclampsia, or HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome, especially when additional clinical features of APS are present. Prospective testing for aPL in women at risk for preeclampsia is not recommended. Current evidence does not justify inclusion of preeclampsia as a major criterion for APS, but preeclampsia could reasonably be included as a secondary or minor criterion in diagnosis when a patient has other clinical features of APS.

Dynamics and incidence patterns of maternal complications in early‐onset hypertension of pregnancy

To describe the variable disease expression and the patterns of development of major maternal morbidity and HELLP (haemolysis, elevated liver enzymes and low platelet count) syndrome in women with different subtypes of hypertensive disorders of pregnancy. Prospective cohort study. Two university hospitals, tertiary care centres. Two hundred and sixteen women participating in a randomised trial of temporising management in early-onset hypertensive disease (PETRA trial). Women were between 24 and 34 completed weeks and had either HELLP syndrome, severe pre-eclampsia, eclampsia or hypertension and fetal growth restriction. Women were delivered in the event of fetal marked heart rate abnormalities, pulmonary oedema, therapy-resistant hypertension or recurrent HELLP syndrome. Trial data were reanalysed to assess the time of onset of major maternal morbidity (e.g. pulmonary oedema, liver haematoma), HELLP syndrome and clinical disease. Associations between clinical parameters and prolongation of pregnancy were explored using logistic regression. Diagnosis from admittance to discharge, major maternal morbidity and prolongation of pregnancy. The median time to delivery or fetal death was 8.2 (range 0.1-44) days. At study entry, 56 women (26%) had more than one diagnosis; this increased to 171 women (79%) by the time of discharge. The incidence of major maternal morbidity (total 26) was 4.2% at 2-4 days after inclusion and a mean of 1.7% (range 0-2%) thereafter per time frame of 3 days. The mean incidence of new or recurrent HELLP syndrome episodes was 5.5% (range 1.9-8.7%) per time frame of 3 days during the first 3 weeks after inclusion. Pre-eclampsia is a dynamic disease, with extensive overlap of subtypes of the syndrome. Prolongation of pregnancy in early-onset hypertensive disorders results in the development of further HELLP syndrome episodes and reversible major maternal morbidity but may improve perinatal healthy survival.

Pregnancy: Kidney Diseases and Hypertension

Pregnancy: Kidney Diseases and Hypertension

The lowest surviving birth weight reported in a systemic lupus erythematosus patient: a review of the literature

The success rates for pregnancies in women with systemic lupus erythematosus (SLE) have improved over the years: however, pregnancy for women with active, serious, organ-threatening lupus continues to be a challenge. Preeclampsia and HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome may complicate pregnancy especially in the setting of advanced maternal age, underlying SLE and chronic renal disease. We report the pregnancy course and outcome for a 35-year old woman with active lupus nephritis at the time of conception who developed severe preeclampsia and HELLP syndrome. The infant was delivered at 26-5/7 weeks gestation, which, associated with intrauterine growth retardation, led to a birth weight of only 470 g. We have reviewed the relevant literature for similar cases of prematurity, very low birth weight, and preeclampsia in the setting of underlying lupus in Medline between 1986 and 2006. This report represents the lowest birth weight pregnancy survival in a lupus patient and the first case of a survival in the second trimester with preeclampsia and HELLP syndrome.

Endothelium -dependent and -independent vasodilatation in preeclampsia and HELLP syndrome

PREECLAMPSIA AND HELLP SYNDROME JUDITH BLAAUW, MARIA G. VAN PAMPUS, GERHARD RAKHORST, JAN G. AARNOUDSE, University Medical Center Groningen, Obstetrics and Gynaecology, Groningen, Netherlands, University Medical Center Groningen, Biomedical Engineering, Groningen, Netherlands OBJECTIVE: Systemic vascular dysfunction is thought to play an important role in preeclampsia (PE) and HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. Vasodilatory reactivity was found to be different in women with PE compared to HELLP syndrome, thereby suggesting different alterations of the vasculature (Fisher et al, AJOG 2000). We studied endothelium-dependent and -independent microvascular reactivity in women with PE, with and without HELLP syndrome. STUDY DESIGN: Skin perfusion, denoted as flux, was measured on the middle finger using laser Doppler perfusion monitoring in 5 pregnant women with PE, in 7 pregnant women with HELLP syndrome, in 12 women with a recent history of PE, and in 13 women with a recent history of HELLP syndrome. Postpartum measurements were performed during a time period of 3-11 months after delivery. Endothelium-dependent and -independent vasodilatation of the skin microcirculation was induced by iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP). Microvascular vasodilatation was calculated as percentage increase from baseline to plateau flux. RESULTS: For both pregnancy and postpartum studies, clinical characteristics such as maternal age, body mass index and blood pressures were similar between the 2 groups. No significant differences in baseline and plateau fluxes, or in ACh-mediated vasodilatation were noticed. Although SNP-mediated vasodilatation in HELLP syndrome during pregnancy was higher, it did not reach statistical significance (table, meanG SEM).

Prediction of HELLP syndrome with assessment of maternal dual hepatic blood supply by using Doppler ultrasound

Early structural and functional changes in the systemic vasculature have been proposed to play a major pathogenetic role in HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Our objective was to assess whether the evaluation of maternal hepatic blood supply is instructive to the prediction of onset of HELLP syndrome. Prospective observation study. Fifty-eight women with severe preeclampsia and 60 healthy pregnant controls at 25-36 weeks gestation. Angle-corrected time-averaged flow velocity and the cross-sectional area of common hepatic artery and portal vein were measured by using Doppler ultrasonography in 58 women with severe preeclampsia and in 60 healthy pregnant controls at 25-36 weeks gestation. Intravascular flow volumes were calculated from the product of the time-averaged velocity and the cross-sectional area. The total liver blood flow was taken as the sum of flow volumes in the hepatic artery and portal vein. The total liver blood flow decreased significantly to about 40% of control in 9 women with severe preeclampsia who developed HELLP syndrome within 4 days after the examination, but not in 49 women with severe preeclampsia without HELLP syndrome. The results indicated that the decrease in dual hepatic blood supply preceded the onset of HELLP syndrome.

Gerard W. Ostheimer “What’s New in Obstetric Anesthesia” Lecture

Gerard W. Ostheimer “What’s New in Obstetric Anesthesia” Lecture

Characteristics and treatment of hepatic rupture caused by HELLP syndrome

The purpose of this study was to review the management of hepatic rupture caused by HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome and to assess maternal and perinatal outcomes of these cases. A retrospective study of HELLP syndrome cases that were complicated by hepatic rupture was conducted. Ten cases of hepatic rupture were identified. The median maternal age was 42.5 +/- 5.9 years (median +/- SD), and the median gestational age at delivery was 35.5 +/- 4.9 weeks. The most frequent signs and symptoms of hepatic rupture were the sudden onset of abdominal pain, acute anemia, and hypotension. Laboratory findings included low platelet count and increased hepatic enzymes. Surgery was performed in 9 cases. One case was treated nonsurgically. The maternal mortality rate was 10%, and the perinatal mortality rate was 80%. A combination of surgical treatment with hepatic artery ligation and omental patching with supportive measures was effective in decreasing the mortality rate in hepatic rupture caused by HELLP syndrome.

Moderate to severe thrombocytopenia during pregnancy

Objective The objective was to investigate obstetric risk factors, complications, and outcomes of pregnancies complicated by moderate to severe thrombocytopenia. Materials and methods A retrospective case-control study comparing 199 pregnant women with moderate to severe thrombocytopenia (platelet count below 100 × 10 9/l) with 201 pregnant women without thrombocytopenia, who delivered between January 2003 to April 2004. Stratified analysis, using the Mantel–Haenszel procedure was performed in order to control for confounders. Results The main causes of thrombocytopenia were gestational thrombocytopenia (GT) (59.3%), immune thrombocytopenic purpura (ITP) (11.05%), preeclampsia (10.05%), and HELLP (Hemolysis, elevated liver enzymes and low platelet count) syndrome (12.06%). Women with thrombocytopenia were significantly older (30.7 ± 5.9 versus 28.7 ± 5.7; p = 0.001) compared with patients without thrombocytopenia, and had higher rates of labor induction (OR = 4.0, 95% CI = 2.2–7.6, p < 0.001) and preterm deliveries (OR = 3.5, 95% CI = 1.9–6.5, p < 0.001). Even after controlling for labor induction, using the Mantel–Haenszel technique, thrombocytopenia was significantly associated with preterm delivery (weighted OR = 3.14, 95% CI = 1.7–6.0, p < 0.001). Higher rates of placental abruption were found in pregnant women with thrombocytopenia (OR = 6.2, 95% CI = 1.7–33.2, p = 0.001). In a comparison of perinatal outcomes, higher rates of Apgar scores <7 at 5 min were noted in infants of mothers with thrombocytopenia (OR = 6.3, 95% CI = 1.8–33.8, p = 0.001), intrauterine growth restriction (IUGR; OR = 4.6, 95% CI = 1.5–19.1, p = 0.003), and stillbirth (65/1000 versus 0 p < 0.001). These adverse perinatal outcomes were found in rare causes of thrombocytopenia such as disseminated intravascular coagulation (DIC), familial thrombotic thrombocytopenic purpura (TTP), anti-phospholipid antibodies (APLA) syndrome, and myeloproliferative disease, and not among patients with GT. Conclusions Moderate to severe maternal thrombocytopenia points to a higher degree of severity of the primary disease, which increases perinatal complications. However, the adverse outcome is specifically attributed to preeclampsia, HELLP syndrome, and rare causes, while the perinatal outcome of GT and ITP is basically favorable. Special attention should be given to patients with thrombocytopenia due to preeclampsia, HELLP syndrome, and rarer causes during pregnancy.

Obstetric admissions to the intensive care unit: a 12-year review

The objective was to ascertain the prevalence, causes and outcome of critically ill obstetric patients admitted to the intensive care unit (ICU). The design was a retrospective collection of data. The setting was a multidisciplinary ICU in a University hospital. All obstetric patients admitted to the ICU over a 12-year period from May 1992 to April 2004 were reviewed. Data collected included demographic characteristics of the patients, pre-existing medical conditions, obstetric complications, invasive procedures required in the ICU and outcome of the patients. The incidence of obstetric admissions to the ICU represented 0.22% of all deliveries during the study period. The majority (84.4%) of patients were admitted to the ICU postpartum. Obstetric haemorrhage (32.8%) and pregnancy-induced hypertension (17.2%) were the two main obstetrical reasons for admission. The remainder included medical disorders (37.5%) and other causes (6.2%). Associated major complications included adult respiratory distress syndrome (ARDS) and HELLP (haemolysis, elevated liver enzymes and low platelets) syndrome. The perinatal mortality rate was 20% and the maternal mortality rate 9.4%. A team approach consisting treatment by obstetricians, intensive care specialists and anaesthesiologists provided optimal care for the patients. Improved management strategies for obstetric haemorrhage and hypertension may significantly reduce maternal morbidity.

A randomised placebo-controlled trial of prolonged prednisolone administration to patients with HELLP syndrome remote from term

Objectives To evaluate the effect of prolonged administration of high-dose prednisolone on early onset HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome during expectant management. Study design A randomized, double-blind trial was performed in 31 pregnant women with HELLP syndrome with an onset before 30 weeks gestation. Patients received either 50 mg prednisolone or placebo intravenously twice a day. Primary outcome measures were the entry-to-delivery interval and the number of recurrent HELLP exacerbations in the antepartum period. Results Serious maternal morbidity was considerable, in particular in the placebo group where even on maternal occurred as a consequence of liver rupture. The mean entry-delivery interval did not differ between the prednisolone group (6.9 days) and the placebo group (8.0 days). However, patients in the prednisolone group had a significant lower risk of a recurrent HELLP exacerbation after the initial crisis had subsided, as compared to patients in the placebo group (HR 0.3, with 95% CI 0.3–0.9). Platelet count recovered faster in the prednisolone group as compared to the placebo group (mean 1.7 days versus 6.2 days, P < 0.01). Conclusions HELLP syndrome remote from term causes high risk for serious maternal morbidity and mortality. When expectant management is pursued in selected patients with a HELLP syndrome remote from term, prolonged administration of prednisolone reduces the risk of recurrent HELLP syndrome exacerbations.

Addition of platelet transfusions to corticosteroids does not increase the recovery of severe HELLP syndrome

Objective The objective was to evaluate the effect of dexamethasone and platelet transfusion treatment on recovery in patients with class 1 hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. Material and methods All women with class 1 HELLP syndrome (true HELLP syndrome) who were seen at the hospital Complejo Hospitalario de la Caja de Seguro Social de Panama, Panama between July 1996 and June 2004 took part in a retrospective, comparative study. They were divided into two groups. One group received dexamethasone and the other group received dexamethasone plus platelet transfusion. True HELLP syndrome was defined as hemolysis, elevated liver enzymes, and maternal platelet nadir ≤50,000 platelets/μl. Main outcome measure The primary endpoint was resolution of the HELLP syndrome as recognized by normalization of the platelet count (≥150,000/μl) and the mean length (measured in days) of the postpartum stay in hospital. Results Forty-six women with true HELLP syndrome were studied. Twenty-six patients received dexamethasone and 20 received dexamethasone plus platelet transfusion. The normalization of the platelet count was significantly more rapid in the dexamethasone group ( p < 0.004) and the postpartum hospital stay was significantly more prolonged in the dexamethasone plus platelet transfusion group ( p < 0.02). There was no maternal death. Conclusions The findings suggest the initiation of high-dose dexamethasone therapy in women with true HELLP syndrome, with the next step being delivery, and probably platelet count ≤50,000/μl alone is not always an indication for platelet transfusion.

Fetal Fatty Acid Oxidation Defects and Maternal Liver Disease in Pregnancy

The objective was to evaluate the relationships between all types of fetal fatty acid oxidation defects and maternal liver disease, including acute fatty liver of pregnancy and hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. This was a case-control study comparing fetal fatty acid oxidation defects to the outcome of maternal liver disease. Fifty case infants with fatty acid oxidation defects were identified, with 25 matched controls collected per case. This generated a total of 50 case infants and 1,250 control infants. Pregnancies were evaluated for the presence of maternal liver disease (comprised of acute fatty liver of pregnancy, HELLP syndrome, and preeclampsia evolving into HELLP syndrome) using a conditional logistic regression model. Subgroup analysis compared long chain to short and medium chain fatty acid defects. Maternal liver disease was noted in 16.00% of all fatty acid oxidation defect pregnancies compared with 0.88% in the general population (odds ratio 20.4, 95% confidence interval 7.82-53.2). These pregnancies demonstrated an 18.1-fold increase in maternal liver disease when compared with our matched population controls with unaffected fetuses. All classifications of fatty acid oxidation defects were at high risk of developing maternal liver disease. Long chain defects were 50 times more likely than controls to develop maternal liver disease and short and medium chain defects were 12 times more likely to develop maternal liver disease. Maternal liver disease is significantly higher across the entire spectrum of fatty acid oxidation defects pregnancies compared with the matched control population. Notably, there is significant risk to the pregnancies with fetuses affected with short and medium chain defects, not just those with fetal long chain fatty acid oxidation defects as previously reported. Future studies should examine the pathophysiology of all infant fatty acid oxidation defects and its implications for maternal liver disease for improved future health outcomes. II-2.

Acute Activation of Endothelium Induces Circulation of Active Von Willebrand Factor in HELLP Sydrome.

Von Willebrand Factor (VWF) is unable to interact spontaneously with platelets under physiological conditions. To induce this interaction, a conversion of the VWF A1-domain into a Glycoprotein Ibα (GpIbα)-binding conformation is required. We recently described a nanobody, designated AU/VWFa-11 that preferentially recognizes the GpIbα-binding conformation (Hulstein et al. 2005 Blood, in press). Using an AU/VWFa-11 based immunosorbant assay, we found that the active form of VWF circulates in VWD type 2B and Thrombotic Thrombocytopenic Purpura. Although these diseases have different phenotypical appearances, both are characterized by thrombocytopenia. Another disease associated with a low platelet count is HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome, a severe form of preeclampsia that compromises pregnancy. In this study, we have compared the levels of activated VWF in the plasma of healthy pregnant women (n=9), patients suffering from preeclampsia (n=6) and patients with HELLP syndrome (n=14) at similar gestational age. In HELLP syndrome, the levels of activated VWF were increased 1.8-fold compared to healthy volunteers (p=0.0001). Moreover, these levels were also increased 1.5-fold compared to the patients suffering from preeclampsia. In order to get insight into the origin of the increased activated VWF levels, a number of other parameters were determined. VWF antigen levels were found to be increased in normal pregnancy (165% ± 32.5), as expected. In preeclampsia and HELLP syndrome these levels were even further increased (178% ± 89.8 and 338% ± 89.3, respectively). In healthy pregnant women and in preeclampsia, VWF propeptide levels were concomitantly increased. In contrast, in HELLP syndrome propeptide levels were increased up to 3-fold compared to propeptide levels in healthy pregnant women (p<0.0001) and 1.8-fold compared to patients with preeclampsia (p<0.04). When we calculated the propeptide /VWF antigen ratio, this ratio was found to be within the normal range in healthy pregnant women (0.11 ± 0.04) and preeclampsia (0.12 ± 0.03). However, this ratio was significantly increased in HELLP syndrome (0.17 ± 0.05, p<0.05). Because these increased ratios may represent secretion of VWF from the Weibel Palade bodies, these data suggests that acute activation of the endothelium occurs in HELLP syndrome and is the source of circulating active VWF. Therefore, we determined the amounts of active VWF secreted by human umbilical vein endothelial cells (HUVEC) in vitro. Medium containing constitutionally secreted VWF and medium from PMA stimulated endothelial cells was collected and the amount of active VWF was measured in the AU/VWFa-11-based immunosorbant assay. A 1.6-fold increase in activated VWF levels was found in medium containing constitutionally secreted VWF compared to normal pool plasma (p<0.05). The amount of activated VWF was increased even up to 2.2-fold in medium of the stimulated endothelial cells (p<0.001) indicating that activation of endothelium in HELLP could indeed result in increased levels of activated VWF. In conclusion, acute activation of the endothelium in HELLP syndrome results in increased amounts of activated VWF. This might well explain the thrombocytopenia associated with HELLP syndrome.