Volume 198, Issue 5 , Pages e6-e8, May 2008
HELLP syndrome: an atypical presentation
Article Outline
HELLP syndrome without proteinuria or hypertension is rare. We present the case of a 33-year-old primigravid who initially was diagnosed with pulmonary embolism. The patient was readmitted with a diagnosis of subcapsular hematoma and eventually diagnosed with HELLP syndrome with a sequela of hepatic rupture.
Key words: atypical presentation, HELLP syndrome, hepatic rupture
HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome accounts for 0.2-0.6% of all pregnancies. This condition comprises 10% of the cases of severe preeclampsia and approximately 50% of eclampsia cases. Preeclampsia, eclampsia, and HELLP syndrome afflict many women and result in a large percentage of maternal and perinatal morbidities. It is important that clinicians make an accurate diagnosis of these conditions, to prevent any adverse outcome. In general, most women will have a classical presentation of preeclampsia (hypertension and proteinuria) at > 20 weeks gestation. However, recent studies suggested that some women will develop preeclampsia without the manifestations of classical symptoms. Atypical cases are those that may develop prior to 20 weeks, or present with signs and symptoms of preeclampsia without hypertension or proteinuria, or those cases with subtle abnormalities in laboratory findings.
Case Report
We present the case of a 33-year-old primigravida at 31 weeks gestation with a chief complaint of sudden shortness of breath. The patient also complained of an intense, sharp, stabbing midsternal chest pain (intensity 9/10) radiating to the back. The patient indicated that the pain intensified with deep breathing or when lying flat on her back/stomach. The patient also has a history of smoking, which continued during pregnancy.
In the emergency room, the patient presented with a blood pressure of 122/82 mmHg, a pulse of 84, and a respiratory rate of 20. Physical examination was pertinent with reproducible midsternal chest wall tenderness. Other findings included hemoglobin of 13.7 g/dL, hematocrit of 41%, platelet count of 179,000 mm3, creatinine of 0.8 mg/dL, aspartate aminotransferase (AST) of 94 IU/L, alanine transaminase (ALT) of 153 IU/L, and total bilirubin of 0.5 mg/dL. Subsequently, urinalysis was ordered and noted to be negative for protein. A helical chest CT scan showed decreased attenuation in the distal branches of both right and left lower lobe pulmonary arteries, suspicious of bilateral pulmonary emboli. Venous Doppler studies of the lower extremities, however, were negative. Fetal ultrasound revealed an estimated fetal weight of < 10th percentile and a biophysical profile of 8/8. The perinatologist consulted recommended corticosteroids for fetal lung maturity and twice weekly follow-up. The diagnosis at this time was pulmonary embolism. The patient was initially anticoagulated with intravenous heparin (therapeutic dose) and was subsequently maintained on low molecular weight heparin at 10,000 units every 12 hours. The following day, the patient's platelet count subsequently dropped to 100,000 mm3. This was attributed to heparin use. Platelet count subsequently increased to 139,000 mm3 (Table). The patient was discharged home 2 days later on low molecular weight heparin at 10,000 units every 12 hours.
TABLE. Trends in the laboratory values
| Day protein | Platelets (mm3) | AST (IU/L) | ALT (IU/L) | Total bilirubin (mg/dL) | Creatinine (mg/dL) | Urine (mg/dL) |
|---|---|---|---|---|---|---|
| First admission | ||||||
 1 | 179,000 | 194 | 153 | 0.5 | 0.8 | (−) |
| 2 | 100,000 | 83 | 112 | 0.4 | 0.6 | (−) |
| 3a | 139,000 | (−) | (−) | (−) | (−) | 0 |
| Second admission | ||||||
| 1 | 142,000 | 192 | 183 | 0.4 | 0.6 | 30 |
| 1, 8 hours | 41,000 | 1280 | 740 | 1.4 | (−) | (−) |
| 2 | 66,000 | 1069 | 79 | 1.6 | 0.6 | (−) |
| 11 | 287,000 | 86 | 198 | 1.8 | 0.5 | 30 |
aAfter steroid administration. |
The patient returned to the emergency room 5 days later with a chief complaint of acute epigastric pain radiating to the back. The patient indicated that the pain began 6 hours prior and with moderate to severe intensity, duration of 6 hours and intensity of 8/10. The patient had a blood pressure of 136/71 mmHg, pulse of 68, and a respiratory rate of 24, with direct tenderness at the right upper quadrant without rebound or guarding. A right upper quadrant sonogram revealed a suspicious subcapsular hematoma (Figure 1) confirmed by an abdominal CT scan (Figure 2). The patient's laboratory findings were as follows: hematocrit 35%, platelet count 142,000 mm3, AST 192 IU/L, and ALT 183 IU/L. Low molecular weight heparin was discontinued. After 8 hours, the patient's platelet count dropped to 41,000 mm3 and hematocrit was 27%. Due to worsening maternal status, an emergent placement of an inferior vena cava filter and a cesarean section were performed. A viable male infant was delivered with Apgars of 5 and 7 at 1 and 5 minutes and a birthweight of 1250 g. Intraoperative findings revealed massive hemoperitoneum and a diffusely congested liver with 2 capsular hematomas covering areas of spontaneous rupture. Hemostasis was achieved by coagulating the denuded liver surfaces using argon beam. The postoperative diagnosis was HELLP syndrome. Magnesium sulfate was given for seizure prophylaxis. The patient was transfused with multiple packed red blood cells and other blood products. The patient was referred to our institution's transplant team for possible liver transplantation. Follow-up abdominal CT scan (Figure 3) showed a subcapsular hematoma without a noticeable increase in size. The patient was discharged after 11 days in stable condition. On follow-up visits with her obstetrician, the patient was reported to exhibit normal physical findings.
FIGURE 1.
Right upper sonogram showing a complex right hepatic subcapsular fluid collection
Image published with permission of Kyuran Ann Choe, MD.
FIGURE 2.
Abdominal CT scan showing a low-attenuation fluid collection of the liver consistent with subcapsular hematoma
Image published with permission of Kyuran Ann Choe, MD.
FIGURE 3.
Abdominal CT scan showing a subcapsular hepatic hematoma with further development of areas with increased attenuation within the hematoma consistent with organizing blood
Image published with permission of Kyuran Ann Choe, MD.
Comment
To date, there is considerable variation in the definition and terminology of HELLP syndrome.1 The diagnostic criteria used is not only variable but inconsistent.2 Hemolysis, defined as the presence of microangiopathic hemolytic anemia is the hallmark of HELLP syndrome.3 The expected laboratory findings include microangiopathic hemolysis, abnormal peripheral smear (schistocytes, burr cells, echinocytes), elevated serum bilirubin (indirect form), low serum haptoglobin levels, elevated lactate dehydrogenase (LDH) levels, and a significant drop in hemoglobin levels.2 The second component of the HELLP syndrome triad is elevated liver enzymes. This is likewise defined imprecisely depending on the literature reviewed. Weinstein3 defined elevated liver enzymes as abnormal serum levels of AST, ALT, and bilirubin values. However, the clear-cut cut-off levels were not specifically defined. In subsequent clinical studies, abnormal AST and ALT levels were reported to be 17 to 72 IU/L, while abnormal platelet count ranged from 75,000 to 150,000 mm3.4, 5, 6 Of note, hypertension and/or proteinuria may be absent in 10-15% of preeclamptic patients.2
Our case report attempts to illustrate the diagnostic dilemma that a clinician faces in diagnosing an atypical presentation of HELLP syndrome. As illustrated by this case, HELLP syndrome can occur in the setting of a normotensive patient without proteinuria, but with other symptoms present (right upper quadrant pain, epigastric pain, shortness of breath, and retrosternal chest pain). HELLP syndrome is not always evident in cases wherein the expected hemolysis, thrombocytopenia, or liver enzyme elevation occurs singularly. It is likewise exceedingly difficult to diagnose hepatic rupture in its early stages because of its varied presentation.7 The key to diagnosis is, therefore, a high index of suspicion.
A crucial point to making the diagnosis of HELLP syndrome is the consideration of hepatic rupture secondary to anticoagulant therapy. Numerous case reports allude to hepatosplenic rupture secondary to antithrombolytic agents, warfarin, and intravenous heparin and newer unfractionated heparin preparations such as tinzaparin.8, 9, 10, 11 In a case report of a splenic rupture secondary to intravenous heparin use, anticoagulation therapy spanned 5 days.12 In contrast, intravenous heparin treatment in our patient lasted only for a day. It is indeed a truly rare event when an organ spontaneously ruptures without any detectable lesion. Arguably, this supports a theoretical prior pathology in this patient's liver (periportal necrosis in HELLP syndrome) that eventually led to hepatic rupture secondary to HELLP syndrome. Additionally, the subcutaneous heparin dose that our patient received is not reported anywhere in literature as a dose that could potentially cause the rupture of an intraabdominal viscera.13 It would be ideal to validate the diagnosis of HELLP syndrome through placental pathology, which unfortunately was not performed in this case.
There were several pitfalls of diagnosis of HELLP syndrome in this case. The primary pitfall was the fact that shortness of breath and retrosternal pain was attributed to pulmonary embolism (PE). This finding was based on an imaging study that indicated a suspicion of bilateral PE despite normal pulse oximetry and venous Doppler studies. Second, slight elevations in blood pressure, mild thrombocytopenia, and mild elevations in liver enzymes are possible manifestations of early HELLP syndrome. In this particular case, the patient subtly presented with shortness of breath, chest pain, and elevated liver enzymes unaccompanied by thrombocytopenia or hemolysis. When the succeeding laboratory results manifested HELLP syndrome, the initial diagnosis of pulmonary embolism was still maintained. Third, the rebound increase in platelets was attributed to steroid administration only.4 Hence, the diagnosis of HELLP syndrome was eliminated by default from the differential diagnosis. Last, on readmission, the fact that the patient exhibited a severe right upper quadrant pain secondary to subcapsular hematoma should have clued the clinician to a finding of HELLP syndrome. Fortunately, the patient survived such a devastating and potentially fatal sequela of liver rupture.
In summary, we describe a case of HELLP syndrome with an atypical presentation initially diagnosed and treated as pulmonary embolism. We therefore recommend a rational stepwise approach toward the diagnosis of HELLP syndrome and its atypical presentation to prevent the costly consequence of a missed diagnosis and its accompanying maternal and perinatal morbidity and mortality. In a patient presenting with any unexplainable laboratory abnormality of either hemolysis or elevated liver enzymes or low platelets, the index of suspicion for HELLP syndrome should remain high in the presence of symptoms, in this case, shortness of breath and retrosternal pain.14 Once a patient returns with worsening symptoms, we recommend using ancillary tests such as uterine Doppler studies or abdominal sonogram, which could lead to the correct diagnosis of HELLP syndrome.
References
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- . HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome: the benefit of corticosteroids. Am J Obstet Gynecol. 1999;181:300–309
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- . Spontaneous splenic rupture complicating anticoagulant or thrombolytic therapy. Am J Med. 1993;94:433–437
- . Spontaneous rupture of the liver (A complication of oral anticoagulant therapy). Arch Surg. 1979;114:734–735
- . Spontaneous rupture of liver and spleen with severe intra-abdominal bleeding during streptokinase treatment of deep venous thrombosis. Vasa. 1977;6:369–371
- . Splenic spontaneous rupture (SSR) and hemoperitoneum associated with low molecular weight heparin: a case report. Support Care Cancer. 2003;11:336–338
- . Hémorragie gravissime par rupture d'hématome souscapsulaire rate saine au cours d'héparinisation pour désoblitération artérielle. Lyon Chirurgical. 1968;64:961–964
- . Spontaneous splenic rupture due to subcutaneous heparin therapy. J Emerg Med. 2000;18:421–426
- . Preeclampsia: diagnosis and management of the atypical presentation. J Matern Fetal Neonatal Med. 2006;19:381–386
Reprints not available from the authors.
PII: S0002-9378(07)02346-0
doi:10.1016/j.ajog.2007.12.034
© 2008 Mosby, Inc. All rights reserved.
Volume 198, Issue 5 , Pages e6-e8, May 2008
