1. HELLP Syndrome– A Therapeutic Challenge Layali Jodeh Razan Malhees 5 th year mdical students

2. Pre-eclampsia multisystemic, idiopathic disorder specific to the pregnancy and puerperium of the human species. It is characterized by the presence of ;  Hypertension  Proteinuria

3. 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.

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

5. The reported incidence 0.2-0.6% Approximately 4 to 12 percent of patients with preeclampsia develop superimposed HELLP syndrome. Elevated perinatal morbidity and mortality. Maternal Mortality 35%.

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

7. 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

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

9. DIAGNOSIS Third TRIMESTRE FIRST DAYS POSTPARTUM 31% 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.

10. 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 >72 UI / L LDH >600 UI / L  Low Platelets Platelet Count < 100 × 10 3 /mm 3

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

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

13. Clinical Presentation  Approximately 90 percent of patients present with generalized malaise  65 percent with epigastric pain  30 percent with nausea and vomiting  31 percent with headache.

15. 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 50 000 y 100 000/mm 3.  Class 3 - Platelet count <between 100 000 y 150 000/mm 3.

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

17.  Complete HELLP – *Microangiopathic hemolytic anemia in women with severe pre-eclampsia *LDH ≥ 600 UI / L *SGOT ≥ 70 UI/l * Thrombocytopenia < 100 000/mm 3  PARTIAL HELLP– One or two of the above.

18. MANAGEMENT OF THE HELLP SYNDROME

19. 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

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

21. The Maternal Condition can be evaluated by:  Complete hemogram. If platelets <150.000/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.

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

23. 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.

24. 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 80-90 mmHg.

25.  Hydralazine: Bolus of 5-10 mg IV every 20- 40 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

26.  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.

27. 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.

28. 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.

29. 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

30. 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

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

32. 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.

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

34. (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 72-96 hours postpartum indicates severe compromise of compensatory mechanisms and possibel MULTIPLE ORGAN FAILURE.

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

36. 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.

38. Advising on future pregnancies.  The risk of recurrence of preeclampsia - eclampsia is 42-43% and for the HELLP syndrome: 19-27%.  The risk of recurrence of preterm delivery is high, about 61%. 1

39. 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.

40. THANK YOU!