The HELLP Syndrome   A Therapeutic Challenge

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Pre-eclampsia - Is a multisystemic, idiopathic disorder specific to the pregnancy and puerperium of the human species. It is characterized by the clinical triad of:HypertensionProteinuriaEdema. Literature dating from the XIXth century report: Very unusual varieties of severe pre-eclampsia wit

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The HELLP Syndrome A Therapeutic Challenge

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1. The HELLP Syndrome– A Therapeutic Challenge JOHN ESSIEN M.D. JESSICA BARDALES MITAC M.D. J.M RODRÍGUEZ FERNÁNDEZ M.D. EMILIO ORTEGA CALLAVA M.D. HOSPITAL GINECOBSTÉTRICO PROVINCIAL CAMAGÜEY.

7. ERITHROCYTIC MORPHOLOGY PLATELET DISORDERS RENAL COMPROMISE HEPATIC DISORDERS IMMUNOLOGIC DISORDERS GENETIC DISORDERS

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

9. DIAGNOSIS MID-II TRIMESTRE FIRST DAYS POSTPARTUM 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 Elevated Bilirubin >1.2 mg/dl Elevated liver enzymes SGOT >72 UI / L LDH >600 UI / L Low Platelets Platelet Count < 100 × 103 /mm3

11. We can also observe: Excessive body weight increase . Pulse pressure amplification. Systole pressure > 140 mmHg, but diastole pressure < 90 mmHg. Ophthalmic disorders -Minor alterations -Cortical blindness (amaurosis) -Retinal detachment -Vitreous hemorrhage.

12. We can also observe: Elevation of Biomarkers: -HCG -Maternal alfa-fetal protein -LDH -Serum Haptoglobin

13. The presence of these disorders in an hypertensive woman with epigastric and/or right hypochondrial pain, nausea, vomiting; as well as hemolysis, will help in making the right diagnosis.

14. Clasification of the HELLP Syndrome based on the platelet count (MISSISSIPPI)1. Class 1 – Platelet count <50 000/mm3. Class 2 - Platelet count between 50 000 y 100 000/mm3. Class 3 - Platelet count <between 100 000 y 150 000/mm3.

15. Hemolysis + Liver disfunction *LDH = 600 UI/l *ASAT (SGOT) and/or ALAT (SGPT)= 40 UI/l *ALL HAVE TO PRESENT 1Magann E.F., Martín J.N. – Twelve Steps to Optimal Management of HELLP Syndrome. Clinical Obstetrics and Gynecology. Lippincott Williams & Wilkins, Philadelphia, 1999. Vol. 42 No. 3: 532-50.

16. 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 < 100 000/mm3 PARTIAL HELLP– One or two of the above.

17. 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 El diagnóstico diferencial del S. HELLP debe efectuarse con las... Entre los trastornos de consumo de fibrinógeno y CID el hígado graso agudo del embarazo meere especial atención. Veremos más adelante por qué.El diagnóstico diferencial del S. HELLP debe efectuarse con las... Entre los trastornos de consumo de fibrinógeno y CID el hígado graso agudo del embarazo meere especial atención. Veremos más adelante por qué.

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

19. Existen factores de riesgo clínicos y de laboratorio cuya presencia sólos o en combinación nos hacen pensar en la mayor morbilidad materna en el S. HELLP. La elevación de las transaminasas, las enzimas de origen muscular, la creatinina sérica y la plaquetopenia por parte de laboratorio y la presencia de cualquier de los trastornos clínicos mostrados son fuertemente sugerentes de afectación orgánica severa en el HELLP.Existen factores de riesgo clínicos y de laboratorio cuya presencia sólos o en combinación nos hacen pensar en la mayor morbilidad materna en el S. HELLP. La elevación de las transaminasas, las enzimas de origen muscular, la creatinina sérica y la plaquetopenia por parte de laboratorio y la presencia de cualquier de los trastornos clínicos mostrados son fuertemente sugerentes de afectación orgánica severa en el HELLP.

20. MANAGEMENT OF THE HELLP SYNDROME Se plantean 12 pasos para el manejo del S. HELLP de acuerdo al cuadro clínica y la gravedad del mismo.Se plantean 12 pasos para el manejo del S. HELLP de acuerdo al cuadro clínica y la gravedad del mismo.

21. 1. ANTICIPATE THE DIAGNOSIS 2. EVALUATE THE MATERNAL CONDITION 3. EVALUATE THE FETAL CONDITION 4. CONTROL THE HYPERTENSION 5. PROFILAXIS OF CONVULSIONES WITH MgSO4 6. WATER AND ELECTROLITIC BALANCE 7. HEMOTHERAPY 8. MANAGEMENT OF LABOR AND DELIVERY 9. OPTIMIZE PERINATAL CARE 10.INTENSIVE POSTPARTUM TREATMENT OF THE PATIENT 11.BE ALERT FOR MULTIPLE ORGAN FAILURE 12.ADVISE ON FUTURE PREGNANCY El primer paso consiste en...Dado que esta patología se presenta de diversas formas, debemos sospechar la posibilidad de su existencia ante una mujer preeclámptica monitorear los parametros de laboratorio y clínicos adecuados.El primer paso consiste en...Dado que esta patología se presenta de diversas formas, debemos sospechar la posibilidad de su existencia ante una mujer preeclámptica monitorear los parametros de laboratorio y clínicos adecuados.

22. The Maternal Condition can be evaluated by: Complete Hemogram. If platelets<150.000/mm3 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.

23. Bilirubin. Unconjugated bilirubin is increased due to the hemolysis but rarely above 1-2 mg%. Serial evaluation laboratory parameters every 12 to 24 hours or more if necessary. Differential diagnosis with othere pathologies.

24. 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.

25. 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.

26. 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

27. 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.

28. Preventing Convulsions MgSO4: 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. If contraindications of MgSO4 exist, use Phenytoin. Loading dose: 15 mg/kg at 40 mg/min with continous monitorization of the cardiac function and BP every 5 minutes. The therapeutic range is 10-20 µg/ml.

29. Water and Electrolytic Management Objectives: -diuresis of 30-40ml/h. -Limit intake of liquids to 150ml/h. -Balance of electrolytes. REMEMBER NEGATIVE BALANCE=vasoconstriction. EXCESIVE POSITIVE BALANCE= pulmonary damage Monitorization of volume through pulmonary capilar wedge pressure

30. 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/mm3.

31. Hemotherapy To avoid postpartum hemorrhage in a transvaginal delivery the indication for platelet transfusion is a count <40.000/mm3. In the immediate postpartum periodo : Maintain the count >50.000/mm3 abdominal deliveries and >20.000/ mm3 in transvaginal deliveries.

32. 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

33. 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

34. Management of labor and delivery If transabdominal delivery is requiered, perform: Vertical skin incision. Corporeal incision of the uterus (due to scarse development of the inferior segment and abnormal presentationes). Spontaneous delivery of the placenta to avoid hemorrhage

35. 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.

36. Postpartum Intensive Care. Admision in an obstetrical intensive care unit until: Sustained increase in the platelet count and a maintained decrease in LDH. Diuresis >100ml/h for 2 consecutive hours without duiretics. Well controled BP with systolic pressure ? 150 mmHg and diastolic pressure < 100 mmHg. Obvious clinical improvement and absence 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.

37. Postpartum Intensive Care - The use of Dexamethasone ANTEPARTUM: (0,15mg/kg)10mg IV bid - when Platelets <100.000/mm3 - if Platelets 100.000-50.000/mm3 AND Eclampsia, Severe Hypertension, Epigastric Pain POSTPARTUM: 10mg IV bid for 2 dosis, then 5mg bid for 2 additional doses: - when steroids were used in antepartum - suspend when there is clinical and laboratory improvement (platelets >100.000mm3, decreased LDH, diuresis >100 ml/h)

38. Signs of multiple organ failure. Complications: Subcapsular Hematoma Subcapsular hepatica hemorrhage Hepatic Rupture. Therapeutic solutions: Conservative Procedures Surgery. Be on the lookout for:

39. 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

40. 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.

41. THANK YOU!

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