HELLP syndrome

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Overview
HELLP syndrome is a life-threatening obstetric complication considered by many to be a variant of pre-eclampsia. Both conditions occur during the later stages of pregnancy, or sometimes after childbirth.

HELLP is an abbreviation of the main findings:
 * Hemolytic anemia
 * Elevated Liver enzymes and
 * Low Platelet count

Signs and symptoms
Often, a patient who develops HELLP syndrome has already been followed up for pregnancy-induced hypertension (gestational hypertension), or is suspected to develop pre-eclampsia (high blood pressure and proteinuria). Up to 8% of all cases present after delivery.

There is gradual but marked onset of headaches (30%), blurred vision, malaise (90%), nausea/vomiting (30%), "band pain" around the upper abdomen (65%) and tingling in the extremities. Edema may occur but its absence does not exclude HELLP syndrome. Arterial hypertension is a diagnostic requirement, but may be mild. Rupture of the liver capsule and a resultant hematoma may occur. If the patient gets a seizure or coma, the condition has progressed into full-blown eclampsia.

Patients who present symptoms of HELLP can be misdiagnosed in the early stages, increasing the risk of liver failure and morbidity. Rarely, post caesarean patient may present in shock condition mimicking either pulmonary embolism or reactionary haemorrhage.

Diagnosis
In a patient with possible HELLP syndrome, a batch of blood tests is performed: a full blood count, liver enzymes, renal function and electrolytes and coagulation studies. Often, fibrin degradation products (FDPs) are determined, which can be elevated. Lactate dehydrogenase is a marker of hemolysis and is elevated (>600 U/liter). Proteinuria is present but can be mild.

A positive D-dimer test in the presence of preeclampsia has recently been reported to be predictive of patients who will develop HELLP syndrome. D-dimer is a more sensitive indicator of subclinical coagulpathy and may be a positive before coagulation studies are abnormal.

Classification
The platelet count has been found to be moderately predictive of severity: under 50 million/L is class I (severe), between 50 and 100 is class II (moderately severe) and >100 is class III (mild). This system is termed the Mississippi classification.

Pathophysiology
The exact cause of HELLP is unknown, but general activation of the coagulation cascade is considered the main underlying problem. Fibrin forms crosslinked networks in the small blood vessels. This leads to a microangiopathic hemolytic anemia: the mesh causes destruction of red blood cells as if they were being forced through a strainer. Additionally, platelets are consumed. As the liver appears to be the main site of this process, downstream liver cells suffer ischemia, leading to periportal necrosis. Other organs can be similarly affected. HELLP syndrome leads to a variant form of disseminated intravascular coagulation (DIC), leading to paradoxical bleeding, which can make emergency surgery a serious challenge.

Treatment
The only effective treatment is delivery of the baby. Several medications have been investigated for the treatment of HELLP syndrome, but evidence is conflicting as to whether magnesium sulfate decreases the risk of seizures and progress to eclampsia. The DIC is treated with fresh frozen plasma to replenish the coagulation proteins, and the anemia may require blood transfusion. In mild cases, corticosteroids and antihypertensives (labetalol, hydralazine, nifedipine) may be sufficient. Intravenous fluids are generally required.

Epidemiology
Its incidence is reported as 0.2-0.6% of all pregnancies. Of women with (pre)eclampsia, 4-12% also develop signs of a "superimposed" HELLP syndrome. Mortality is 7-35% and perinatal mortality of the child may be up to 40%. HELLP usually begins during the third trimester, and usually in Caucasian women over the age of 25. (Padden, 1999.) Rarely, cases have been reported as early as 23 weeks gestation.

History
HELLP syndrome was identified as a distinct clinical entity (as opposed to severe preeclampsia) by Dr Louis Weinstein in 1982.