HELLP Syndrome A Therapeutic Challenge Dr.Z.Naderi Iran University of Medical Siences

Literature dating from the XIXth century report: Very unusual varieties of severe pre- eclampsia with complicated progress. These unusual descriptions of pre- eclampsia are recognised today as the HELLP Syndrome. Today: HELLP Syndrome is considered to be an association of characteristic hepatic and hematologic disorders.

WEINSTEIN WEINSTEIN(1982) H H HEMOLYSIS EL EL ELEVATED LIVER ENZYMES LP LP LOW PLATELETS HELLP

The reported incidence % Approximately 10 to 20 percent of patients with preeclampsia develop superimposed HELLP syndrome. Elevated perinatal morbidity and mortality. Maternal Mortality 35%.

Risk Factors  Previous history of preeclampsia or HELLP  Variety of genetic variants Nulliparity is not a risk factor for HELLP Syndrom.

 ERITHROCYTIC MORPHOLOGY  PLATELET DISORDERS  RENAL COMPROMISE  HEPATIC DISORDERS  IMMUNOLOGIC DISORDERS  GENETIC DISORDERS Factors to consider Factors to consider :

HELLP SYNDROME : POSIBLE PATHOPHYSIOLOGY CAUSAL AGENTES : Increase in volume., Fetal presence / decidual cell?, Vasospasm?, Deficiente vascular repair?, Idiopathic? Vasculo-endothelial Disorder Platelet Agregation/Consumption Fibrin Activation/Consumption Selective organic Isquemia/nsuficiency Variable Manifestations

The Causal Factors induce:  Thrombocytopenia  Microangiopathic Hemolytic Anemia  Periportal necrosis and distension of the liver´s Glisson´s capsule.

Third TRIMESTRE (28-36 W ) FIRST DAYS (48 h)POSTPARTUM 30% Antepartum diagnosis is made in 70% between 27 and 37 weeks of gestation.Antepartum diagnosis is made in 70% between 27 and 37 weeks of gestation. HELLP Syndrom

 Only 20 % of postpartum patients with HELLP had evidence of preeclampsia antepartum.

Criteria for establishing the diagnosis of the HELLP Syndrome  Hemolysis Abnormal peripherical blood smear ( reveal spherocytes, schistocytes, triangular cells and burr cells ) Elevated Bilirubin >1.2 mg/dl  Elevated liver enzymes SGOT >70 UI / L LDH >600 UI / L  Low Platelets Platelet Count < 100 × 10 3 /mm 3

We can also observe  Excessive body weight increase.  Ophthalmic disorders -Minor filterations -Cortical blindness (amaurosis) -Retinal detachment -Vitreous hemorrhage.

We can also observe Alternation in biomarkers Increase in ; - Maternal alfa-fetal protein -LDH Decrease in ; -Serum Haptoglobin -Hematocrit

Clinical Presentation  Approximately 90 percent of patients present with generalized malaise  40-90% percent with epigastric pain  30-85% percent with nausea and vomiting  30-60% percent with headache,visual changes,jaundice 5%,ascites.

Clinical presentation BP>140/90 mmhg and proteinuria are present in approximateiy 85 % of cases.

Clasification of the HELLP Syndrome based on the platelet count (MISSISSIPPI )1.  Class 1 – Platelet count <50 000/mm 3.  Class 2 - Platelet count between y /mm 3.  Class 3 - Platelet count <between y /mm 3.

Another classification based on the partial or complete expression of the HELLP Syndrome(MEMPHIS)1.

 Complete HELLP *Microangiopathic hemolytic anemia in women with severe pre- eclampsia *LDH ≥ 600 UI / L *SGOT ≥ 70 UI/l * Thrombocytopenia < /mm 3  PARTIAL HELLP– One or two of the above.

Differential Diagnosis of the HELLP Syndrome

THROMBOTIC MICROANGIOPATHIES -Thrombotic thrombocytopenic purpura - Microangiopathic hemolytic anemia induced by sepsis or drugs - Hemolytic Uremic Syndrome FIBRINOGEN CONSUMPTION DISORDERS– CID -Acute fatty liver -Sepsis - Severa Hypovolemia / Hemorrhage (Abruptio/Amniotic fluid embolism) CONNECTIVO TISSUE DISORDERS -Systemic Lupus Erithematosus Differential Diagnosis of the HELLP Syndrome

* PRIMARY RENAL DISEASE Glomerulonefritis *OTHERS Hepatic encephalopathies Viral hepatitis Hyperemesis Gravidarum Idiopathic Thrombocytopenia Renal calculi Peptic ulcer Pielonephritis Apendicitis Diabetes Mellitus

MANAGEMENT OF THE HELLP SYNDROME

The Maternal Condition can be evaluated by:  Complete hemogram. If platelets < /mm 3 requieres more study.  Liver Enzymes. The elevation of the transaminases and LDH is a sign of hepatic disfunction.  Renal function. Deficencies in renal function are observed in late stages of the illness. Creatinine and Uric acid levels are variable.

Evaluating the Fetal Condition  Determine the gestational age.  Evaluate fetal well-being: Non-stress test, Tolerance to contracction test and/or biophysical profile.  Use corticosteroids between 24 and 34 weeks to improve fetal pulmonary maturity/neonatal pulmonary function as well as maternal and perinatal results.

 Bilirubin. Unconjugated bilirubin is increased due to the hemolysis but rarely above 1-2 mg%.  Differential diagnosis with othere pathologies.

Controlling the hypertension  80-85% of patients with HELLP need control of their BP to avoid significant maternal and perinatal morbidity and mortality.  Treat systolic BP when>150mmHg and avoid placental hypoperfusion maintaining the diastolic BP not less than mmHg.

 Hydralazine: Bolus of 5-10 mg IV every min. If uneffective or unavailable, use labetalol, nifedipine o sodium nitroprussiate.  Labetalol: Initial bolus of 20 mg IV, with increases in dosage until a satisfactory BP is obtained or up to maximum dose of 300 mg.  Nifedipina oral(not sublingual) at usual dosage. Choice of hypotensive medication

 Sodium Nitroprussiate is a fast acting hypotensive agent(venous and arterial) which can be used in an hypertinsive crisis when all other hypotensive drugs have failed Loading dose: 0,25 μg/kg/min, increasing upto 10 μg/kg/min. Above this dose there is a greater risk of cyanide intoxication of the fetus. When using, remember it’s photosensitivty and sever rebound effect.

Hemotherapy The base of hemotherapy in patients with HELLP is the transfusion of platelets.  The usual dose is one unit per every 10 kg of corporal weight.  Spontaneous bleeding occurs in most cases with a platelet count of <50.000/mm 3.

Hemotherapy  The aggresive use of Dexamethasone in patients with HELLP and severe thrombocytopenia has eliminated virtually all need for platelet transfusion.  Other therapeutic alternatives: -Plasmaphersis -Immunoglobulins

Preventing Convulsions  MgSO 4  MgSO 4 : Initial bolus of 4-6g IV, followed by a continous infusion at 1,5- 4g/h, individualized according to the patient. Continue 48 horas o more postpartum until clinical and laboratory signs of improvement are obtained. Phenytoin  If contraindications of MgSO 4 exist, use Phenytoin.

Management of labor and delivery When considering termination of gestation in a patient with HELLP, determine:  Gestational age.  Maternal and fetal conditions.  Fetal presentation.  Cervical maturity

Management of labor and delivery  timing of delivery – if > 34 weeks gestation, deliver – if < 34 weeks gestation, administer corticosteroids, then deliver in 48 hours

GA w with unfavorable cervix cesarean Delivery

Optimizing perinatal care.  The main risk for the fetus in pregnancies with HELLP is it´s prematurity.  The use of corticosteroids decreases the morbidity associated with pulmonary immaturity in preterm babies.  Delivery should be in a center with capability of treating these children with a major risk of cardiopulmonary instability.

Postpartum Intensive Care.  Admision in an obstetrical intensive care unit until: (1)Sustained increase in the platelet count and a maintained decrease in LDH. (1)Diuresis >100ml/h for 2 consecutive hours without duiretics.

(3 ) Well controled BP with systolic pressure 150 mmHg and diastolic pressure < 100 mmHg. (4) Obvious clinical improvement and bsence of complications. The absence of improvement of the thrombocytopenia within hours postpartum indicates severe compromise of compensatory mechanisms and possibel MULTIPLE ORGAN FAILURE.

Postpartume course  Decreasing PLT continue until h  Serum LDH usually peaked h

Maternal outcome  Abruptio placentae 16%  Acute renal failure 8%  Pulmonary edema 6%  Subcapsular hematoma 1%  Retinal detachment 1%

 Signs of multiple organ failure.  Complications: -Subcapsular Hematoma -Subcapsular hepatica hemorrhage -Hepatic Rupture. Be on the lookout for:

Hepatic Rupture  The incidence of hepatic rupture varies from one in 40,000 to one in 250,000 pregnancies.  Hepatic infarction is even more rare and commonly involves the right lobe.  It is believed to be a continuum of preeclampsia, in which areas of coalescing hemorrhage result in thinning of the capsule and intraperitoneal hemorrhage.

Hepatic Rupture  Epigastric pain, shoulder pain,nausea,vometing  Swelling of abdomen,hemoperitoneum,shock  Aminotransferases = IU/L CT and MRI is more dependable than ultrasonography

Hepatic Rupture  Management : volume replacement and blood transfusion stability in the size of hematoma and normal lab tests out patient follow up

Hepatic Rupture Percutaneous embolization of the hepatic arteries is reasonable first-line therapy in woman who are hemodinamically stable.

Advising on future pregnancies.  The risk of recurrence of preeclampsia - eclampsia is 20% and for the HELLP syndrome: 2-6%  The risk of recurrence of preterm delivery is high, about 70%. 1

Advising on future pregnancies  Maternal lab parameters don’t predict fetal mortality.  Maternal HELLP doesn’t affect fetal/neonatal liver function.

Conclusions  HELLP Syndrome and its management still poses a problem in modern obstetrics  Precise diagnosis and early treatment with non-mineral corticosteroides such as Dexamethasone may help achieve favorable maternal and perinatal results.

THANK YOU!