**2.1.4 Hemolysis, elevated liver enzymes, low platelets –HELLP syndrome**

HELLP syndrome is a variant of severe preeclampsia, first described by Dr. Louis Weinstein in 1982. About 15 to 20 percent of affected patients do not have antecedent hypertension or proteinuria, leading some experts to believe that HELLP is a separate disorder from preeclampsia [Sibai BM1986, Reubinoff BE, 1991]. Both severe preeclampsia and HELLP syndrome may be associated with other hepatic manifestations, including infarction, hemorrhage, and rupture. HELLP develops in approximately 1 to 2 per 1000 pregnancies overall and in 10 to 20 percent of women with severe preeclampsia/ eclampsia. The majority of cases are diagnosed between 28 and 36 weeks of gestation with 70 percent occurring prior to delivery [Sibai BM, Ramadan MK 1993]. Of these patients, approximately 80 percent are diagnosed prior to 37 weeks of gestation and fewer than 3 percent develop the disease between 17 and 20 weeks of gestation. The disease presents postpartum in 30 percent, usually within 48 hours of delivery, but occasionally as long as seven days after birth. Only 20 percent of postpartum patients with HELLP have evidence of preeclampsia antepartum.

#### **Diagnosis and classification of HELLP syndrome**

There is no consensus regarding the degree of laboratory abnormality diagnostic of HELLP syndrome. Some studies use AST (and/or ALT) and LDH values above the upper limit of normal, while others require elevations of at least two standard deviations above the mean. Due to differences in assays used to measure these enzymes, an elevated value in one hospital may be near normal in another.HELLP syndrome and severe preeclampsia are probably part of a disease spectrum. A precise definition of HELLP is necessary for research purposes and for predicting maternal complications. We require the presence of all of the following criteria to diagnose HELLP.

Microangiopathic hemolytic anemia with characteristic schistocytes (also called helmet cells) on blood smear. Other signs suggestive of hemolysis include an elevated LDH or indirect bilirubin and a low serum haptoglobin concentration (≤25 mg/dL).

Platelet count ≤100,000 cells/microL .HELLP syndrome accounts for 21% of maternal thrombocytopenia in pregnancy.

Serum LDH ≥600 IU/L or total bilirubin ≥1.2 mg/dL

Acute Kidney Injury in Pregnancy 161

patients may have an underlying procoagulant state, such as the antiphospholipid syndrome. HELLP may be complicated by hepatic rupture with development of a hematoma beneath Glisson's capsule. Histology of the liver adjacent to the rupture shows periportal hemorrhage and fibrin deposition, along with a neutrophilic infiltrate( hepatic preeclampsia). The hematoma may remain enclosed, or rupture, with hemoperitoneum . A hepatic hematoma rarely occurs in the absence of preeclampsia or HELLP .It is characterized by abdominal pain and many have severe thrombocytopenia, shoulder pain, nausea, and vomiting. If hepatic rupture occurs, swelling of the abdomen from hemoperitoneum and shock is seen. The aminotransferases are elevated, and values of 4000 to 5000 IU/L can occasionally be seen. Imaging using CT or MR is more sensitive than ultrasonography for these lesions. The management of a contained hematoma is to support the patient with volume replacement and blood transfusion, as needed, with consideration of percutaneous embolization of the hepatic arteries. It takes months for the hematoma to resolve completely. Surgical intervention is indicated if there is hemodynamic instability, persistent bleeding, increasing pain, or continued expansion of the hematoma. Operative management includes packing, drainage, hepatic artery ligation, and/or resection of affected areas of the liver. For patients with intractable hemorrhage, administration of recombinant factor VIIa and liver transplantation are recommended.

**Postpartum couse** — Decreasing platelet counts continue until 24 to 48 hours after delivery, while serum LDH concentration usually peaks 24 to 48 hours postpartum. An upward trend in platelet count and a downward trend in LDH concentration should be seen by the fourth postpartum day in the absence of complications. Recovery can be delayed in women with DIC, platelet count less than 20,000 cells/uL, renal dysfunction

**Outcome** is generally good; however, serious complications are relatively common. In a series of 437 women with HELLP syndrome at a tertiary care facility, the following complications were observed DIC — 21 %, Abruptio placentae — 16 %, Acute renal failure — 8 %, Pulmonary edema — 6 %, Subcapsular liver hematoma — 1%, Retinal detachment — 1 %. In addition, 55 % of the patients required blood or blood products, and 2 % required laparotomies for intraabdominal bleeding. 1 % died. Other complications include: adult respiratory distress syndrome, sepsis, and stroke. Wound complications secondary to bleeding and hematomas are common in women with thrombocytopenia. Fetal complications include prematurity (70 %), intrauterine growth restriction and abruptio placenta, and depend largely upon the severity of the disease and the gestational stage. The overall perinatal mortality is 7 to 20 %. However, surviving babies do not have an increased risk of liver disease or thrombocytopenia. Although most liver function tests return to normal postpartum , rarely high total bilirubin may be seen in 20 % even till 3 years post partum. HELLP syndrome with or without renal failure does not affect longterm renal function. The rate of recurrence is 2 - 27 %. Recurrent hepatic rupture in a subsequent pregnancy have been reported, suggesting there may be a genetic predisposition to this condition. Women with a history of HELLP syndrome are at high risk for developing preeclampsia in a subsequent pregnancy. The incidence of preeclampsia varies from 20-50 percent in normotensive women to 75 percent in those with underlying hypertension. There is no evidence that any therapy prevents recurrent

Patients who survive have no hepatic sequelae.

or ascites.

HELLP syndrome.

Serum AST ≥70 IU/L. Some investigators obtain ALT levels instead of, or in addition to, AST levels. An advantage of the AST is that it is a single test that reflects both hepatocellular necrosis and red cell hemolysis.

Women who do not meet all of the above laboratory abnormalities are considered to have partial HELLP syndrome. These patients may progress to complete expression of HELLP syndrome.

Approximately 50% of patients have complete HELLP (all components present), and 50% have incomplete HELLP (at least 1 components present: EL, HEL, ELLP, LP). Some physicians subclassify HELLP based on the severity of thrombocytopenia, as follows: Class 1 - Platelet count < 50,000/μL, Class 2 - Platelet count 50,000-100,000/μL, Class 3 - Platelet count 100,000-150,000/μL
