HELLP Syndrome · What Is It, Causes, Diagnosis, Treatment, and More

HELLP syndrome is a life-threatening pregnancy complication characterized by the triad of Hemolysis, Elevated Liver enzymes, and Low Platelet count. HELLP syndrome may occur in up to 1% of all pregnancies, with most cases occurring throughout pregnancy during the third trimester, between 27-37 weeks, however cases have been reported even before 23 weeks. Less commonly, HELLP syndrome may develop within 48 hours of birth in the postpartum period.  

Early diagnosis is critical, as severe illness or death can occur in up to 25% of individuals afflicted. Individuals who develop HELLP syndrome require immediate, intensive treatment to ensure the best possible outcomes for both the pregnant individual and the fetus. 

Preeclampsia is a new onset of hypertension with proteinuria or other severe features occurring after 20 weeks of gestation or during the postpartum period. On the other hand, HELLP syndrome refers to a thrombotic microangiopathy characterized by the presence of hemolysis, elevated liver enzymes, and low platelet count. In HELLP syndrome, hypertension and proteinuria may not be present. Both conditions may coexist in 70-80% of cases. 

For preeclampsia, hypertension is defined as systolic blood pressure greater than or equal to 140 mmHg or diastolic blood pressure greater than or equal to 90 mmHg. Additionally, proteinuria or symptoms of significant end-organ dysfunction (e.g., renal insufficiency, impaired liver function, pulmonary edema, or persistent cerebral or visual symptoms) must also be present. Although it has long been believed that HELLP is a complication of severe preeclampsia, recent research supports that HELLP may be a different condition since 15-20% of those who develop HELLP do not have either hypertension or proteinuria. 

The exact cause of HELLP syndrome is still unknown; however, the pathogenesis has been associated with an inflammatory response in the placenta–liver axis. HELLP syndrome often occurs as a complication of preeclampsia or eclampsia.  

The hemolysis that occurs in HELLP syndrome happens when red blood cells become damaged as they circulate through the systematically impaired endothelial cells. High blood pressure can additionally damage the vascular endothelium and thereby excessively activate the coagulation cascade leading to the consumption of platelets, formation of blood clots, and ultimately low platelet counts. Some of these clots may deposit in the hepatic blood vessels, causing congestion, thereby leading to increased intrahepatic pressure and, consequently, liver damage and elevated liver enzymes.  

Risk factors for HELLP include a history of preeclampsia or HELLP in previous pregnancies; a family history of HELLP or preeclampsia, history of autoimmune diseases; multiparity, which comprises over 50% of HELLP cases; age over 30 years; and SARS-CoV-2 infection during pregnancy. The antiphospholipid syndrome (APLS) has also been associated with early onset of HELLP. 

The hallmark symptoms of HELLP syndrome include right upper quadrant abdominal pain or epigastric pain resulting from liver distension. Individuals may experience general symptoms like nausea, vomiting, generalized edema, malaise, headache, visual changes, or jaundice. As the individual’s condition worsens, the damaged liver may swell and, in some cases, the liver capsule may rupture, leading to subcapsular hematoma. Subcapsular hematomas may present with severely increased right upper quadrant or epigastric pain, dyspnea, pallor, nausea, and vomiting. 

If HELLP is not treated, it can result in life-threatening complications, including placental abruption, preterm delivery, acute kidney injury, pulmonary edema, acute respiratory distress syndrome, stroke, and retinal detachment. Additionally, placental abruption or liver hematoma rupture may lead to disseminated intravascular coagulation (DIC), a widespread clotting disorder that can cause damage to multiple organs. 

Diagnosis of HELLP is based on the triad of laboratory findings that make up the syndrome’s name: hemolysis, elevated liver enzymes, and low platelets (i.e., thrombocytopenia).   

There are variations in diagnostic criteria from experts; however, the American College of Obstetrics and Gynecology (ACOG) states the presence of two of three of the following are needed for diagnosis: lactate dehydrogenase (LDH) greater than or equal to 600 IU/L; liver enzymes AST and ALT greater than twice the upper limit of normal; and platelet count less than 100,000 cells/microL. Hemolysis may also be confirmed by the presence of fragmented red blood cells (i.e., schistocytes) on a peripheral blood smear and by identifying elevated bilirubin levels or low haptoglobin levels on a blood test.   

HELLP can be further classified based on the severity of the low platelet count. According to the Mississippi classification HELLP syndrome is classified into three categories. Class I HELLP syndrome (i.e., platelet count below 50,000/microL, AST/ALT ≥ 70 IU/L, LDH ≥ 600 IU/L) is the most severe, with a higher rate of morbidity and mortality than Class II (i.e., platelet count between 50,000 to 100,000/microL) and Class III (i.e., platelet count between 100,000 to 150,000/microL, AST/ALT ≥ 40 IU/L) HELLP syndromes. 

Treatment of HELLP syndrome is typically conducted in tertiary care centers with both adult and neonatal intensive care units.  

The ultimate treatment of HELLP syndrome is the delivery of the fetus and the placenta, after which the signs and symptoms of HELLP typically resolve. Immediate delivery is recommended for individuals who have reached 34 weeks of pregnancy, those who have not reached a viable gestational age, in cases of fetal demise, or if placental abruption is present.  The typical course of treatment for pregnancies between 24 weeks and 34 weeks gestation is the administration of corticosteroids (e.g., betamethasone) to aid in fetal lung maturation, followed by delivery. Vaginal delivery is preferred to reduce the risk of bleeding and clotting complications associated with cesarean delivery. Some individuals may benefit from a blood transfusion, specifically a red blood cell transfusion in cases of severe anemia or a platelet transfusion to prevent excessive bleeding during birth. 

Additional measures are aimed at managing complications, such as administering antihypertensive medications (e.g., hydralazine, labetalol, methyldopa, or nifedipine) to stabilize blood pressure and IV magnesium sulfate to prevent seizures. Close monitoring of the maternal platelets count and liver enzymes should be conducted every 12 hours, even after delivery.