**Clinical manifestations**

Clinical manifestations are nonspecific (nausea, vomiting, headache in 50%, epigastric or right upper quadrant pain in 50%).Early HELLP syndrome is often misdiagnosed as heartburn, hence a high index of suspicion for HELLP syndrome is important. All patients with HELLP syndrome do not meet the strict criteria for preeclampsia. Hypertension (blood pressure ≥140/90) and proteinuria are present in approximately 85 %, 15% have diastolic blood pressure (BP) >90 mm Hg but either or both may be absent in women with severe HELLP syndrome (Sibai, 2004). Some patients are asymptomatic, major complications can occur despite normal blood pressure and proteinuria. These include DIC, abruptio placentae, acute renal failure, pulmonary edema, subcapsular liver hematoma, retinal detachment or stroke. Jaundice and ascites may also be present. Bleeding may occur due to thrombocytopenia. Thrombocytopenia is usually moderate, with counts rarely <20,000/μL. Major hemorrhage is uncommon. Maternal thrombocytopenia reaches a nadir at 24-48 hours postpartum. The maternal mortality rate with HELLP is 1%. The perinatal mortality rate is 11%. Fetal growth restriction is common. Neonates may be at increased risk for thrombocytopenia.

#### **Treatment**

Management is like preecclapsia .Delivery is the ultimate cure and should be planned immediately if >34 weeks or can be delayed for 24-48 hours if <34 weeks' gestation to administer corticosteroids if the patient is asymptomatic and the fetal testing is normal. Magnesium sulfate (MgSO4) should be administered intrapartum and postpartum, regardless of blood pressure levels, to prevent seizures (eclampsia). Approximately 6-10 units of platelets is administered at the time of skin incision, and an additional 6 units are administered if oozing is noted during the surgery. Also platelet transfusion is indicated if the platelet count is less than 20,000 cells/uL. If cesarean delivery is planned platelet transfusion, is recommended to achieve platelet count greater than 50,000 cells/uL. Thrombocytopenia and elevated liver function tests worsen postpartum but should start normalizing by the third postpartum day. The use of steroids for HELLP is controversial.

**Management of hepatic complications** — Marked elevations in serum aminotransferases are not typical of uncomplicated HELLP; when they occur, the possibility of hepatic infarction, subcapsular hematoma, or viral hepatitis should be considered. Marked elevation in serum aminotransferases (usually 1000 to 2000 IU/L or higher) associated with right upper quadrant pain and fever is characteristic of hepatic infarction; this diagnosis can be confirmed by hepatic imaging. These infarcts resolve post partum. These

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

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

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 -

Clinical manifestations are nonspecific (nausea, vomiting, headache in 50%, epigastric or right upper quadrant pain in 50%).Early HELLP syndrome is often misdiagnosed as heartburn, hence a high index of suspicion for HELLP syndrome is important. All patients with HELLP syndrome do not meet the strict criteria for preeclampsia. Hypertension (blood pressure ≥140/90) and proteinuria are present in approximately 85 %, 15% have diastolic blood pressure (BP) >90 mm Hg but either or both may be absent in women with severe HELLP syndrome (Sibai, 2004). Some patients are asymptomatic, major complications can occur despite normal blood pressure and proteinuria. These include DIC, abruptio placentae, acute renal failure, pulmonary edema, subcapsular liver hematoma, retinal detachment or stroke. Jaundice and ascites may also be present. Bleeding may occur due to thrombocytopenia. Thrombocytopenia is usually moderate, with counts rarely <20,000/μL. Major hemorrhage is uncommon. Maternal thrombocytopenia reaches a nadir at 24-48 hours postpartum. The maternal mortality rate with HELLP is 1%. The perinatal mortality rate is 11%. Fetal growth restriction is common. Neonates may be at increased risk

Management is like preecclapsia .Delivery is the ultimate cure and should be planned immediately if >34 weeks or can be delayed for 24-48 hours if <34 weeks' gestation to administer corticosteroids if the patient is asymptomatic and the fetal testing is normal. Magnesium sulfate (MgSO4) should be administered intrapartum and postpartum, regardless of blood pressure levels, to prevent seizures (eclampsia). Approximately 6-10 units of platelets is administered at the time of skin incision, and an additional 6 units are administered if oozing is noted during the surgery. Also platelet transfusion is indicated if the platelet count is less than 20,000 cells/uL. If cesarean delivery is planned platelet transfusion, is recommended to achieve platelet count greater than 50,000 cells/uL. Thrombocytopenia and elevated liver function tests worsen postpartum but should start normalizing by the third postpartum day. The use of steroids for HELLP is controversial. **Management of hepatic complications** — Marked elevations in serum aminotransferases are not typical of uncomplicated HELLP; when they occur, the possibility of hepatic infarction, subcapsular hematoma, or viral hepatitis should be considered. Marked elevation in serum aminotransferases (usually 1000 to 2000 IU/L or higher) associated with right upper quadrant pain and fever is characteristic of hepatic infarction; this diagnosis can be confirmed by hepatic imaging. These infarcts resolve post partum. These

necrosis and red cell hemolysis.

Platelet count 100,000-150,000/μL

**Clinical manifestations** 

for thrombocytopenia.

**Treatment** 

syndrome.

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. Patients who survive have no hepatic sequelae.

**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 or ascites.

**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 HELLP syndrome.

Acute Kidney Injury in Pregnancy 163

patients with HUS. P-aHUS may be related to alternative C3 convertase dysregulation. A lack of control of the alternative C3 convertase leads to complement-induced lesions of the endothelial cells. Acquired (anti-FH antibodies) or constitutional (inactivating mutations in FH, FI, or MCP coding genes or activating mutations in factor B and C3 coding genes) with dysregulation of the alternative C3 convertase has been established as a risk factor for the occurrence of aHUS. It is assumed that excessive activation of the alternative C3 convertase leads to complement activation. Pregnancy may trigger the onset or subsequent relapses. Mutations in the SCR19-20 domains of factor H are less frequent in P-aHUS

It occurs in primipara and is characterized by renal failure, anemia and hypertension. The risk for P-aHUS is highest during a second pregnancy. Onset is within hours to days post partum. Symptoms can begin before delivery, but the onset in most cases is delayed for 48 hours or more after delivery (mean four weeks). HUS may follow a normal pregnancy or be preceded by findings indistinguishable from preeclampsia. HUS with severe renal failure more frequently presents in the postpartum period. Presenting symptoms are often nonspecific , although majority (60%) present with bleeding. Hypertension is seen in 75% of cases. Hemolysis and anemia may be absent at presentation in 50% of cases. DIC is rare. **Labs** - Obligate findings include hemolytic anemia (hematocrit < 30% with schistocytes on peripheral smear) and thrombocytopenia under 100,000/μ L (50% of patients will have counts < 20,000/μ L). LDHis usually >600 U/liter. Hemolytic anemia is coomb's negative. There may be hypocomplementemia, deficiency in prostaglandins or antithrombin levels. HUS is a clinical diagnosis. Tissue biopsy is not required. In problematic cases when renal

**Outcomes**- The outcomes are poor. 80-90% survive acute episode. There is a high maternal mortality of 18-44% and fetal loss is seen in 80%. 62% reached ESRD by 1 month. Outcomes do not differ between patients with pregnancy-related and non-pregnancy–related aHUS. Pregnancies in female patients with complement abnormalities are complicated by fetal loss and preeclampsia in 4.8% and 7.7%,respectively. (Fadi Fakhouri,2010) Almost half have residual neurologic or chronic renal failure. Recurrences occur in 50%. Long-term sequelae, such as hypertension and chronic renal failure, are observed in 44% of patients with HUS.

**Treatment** includes Plasmapheresis. Plasma infusion alone is less effective. Steroids, antiplatelet therapy, Immunoabsorption, splenectomy, IV gamma globulin therapy have been used in different studies. Renal failure is managed by hemodialysis. Antihypertensives are used for control of blood pressure. Platelet transfusions should be avoided. Heparin and fibrinolytic agents and anti thrombin III concentrates may be used. Dilatation and curettage

TTP is characterized by the pentad of microangiopathic hemolytic anemia, thrombocytopenia, renal insufficiency, fever, and neurologic abnormalities. TTP usually occurs antepartum , about 12 % in the first trimester, 56 % in the second trimester, and 33 % in the third trimester/postpartum(Egerman RS, 1996), There may be mild renal failure and severe neurological involvement (headache, altered consciousness, seizures, hemiparesis), and fever. Severe thrombocytopenia and hemolytic anemia may be seen. Examination

patients compared with non-pregnancy–related aHUS.

**2.1.5.1 Hemolytic uremic syndrome(HUS)/Idiopathic post partum failure** 

biopsy is done it shows mesangiolysis and glomerular simplification.

should be considered when the disease occurs very close to delivery.

The perinatal mortality rate is as high as 30%.

**2.1.5.2 Thrombotic thrombocytopenic purpura** 
