HELLP syndrome SBORNA MD PERINATOLGY DEP VALIEASR HOSPITAL

HELLP syndrome S-BORNA MD , PERINATOLGY DEP, VALI-E-ASR HOSPITAL , TUMS

� The 31 -year-old white primipara with twin pregnancy was admitted to hospital in the 38 th week of gestation with elevated blood pressure (150/100 mm. Hg). After receiving antihypertensive treatment blood pressure was 120/80. All laboratory variables, NORMAL � Few hours after admission to the hospital the contractions started, and the caesarean section was performed � Four hours postpartum she experienced sudden epigastric pain. The blood pressure rose to 190/130. Laboratory findings showed haemolysis, thrombocytopenia, and an increase in serum creatinine and aminotransferases � Intravenous magnesium sulphate was administered. Abdominal ultrasound disclosed an � � � empty uterine cavity without placenta residue. Five hours postpartum, the patient was transferred to the intensive care unit because of poor urine output, drowsiness, and suspicion of DIC. On examination she was sleepy and disoriented. The combination of thrombocytopenia, and elevated liver enzymes suggested a postpartum HELLP syndrome, complicated by DIC. The patient was rehydrated, and treatment was instituted with fresh frozen plasma, red cell transfusion, fresh platelets, and kybernin P (antithrombin III). High serum urea, creatinine, and persistent anuria were compatible with acute renal failure. A high dose of furosemide failed to increase diuresis. Sixteen hours postpartum her blood pressure was 60/40 and oxygen saturation 70%. Few minutes later the patient had acute cardiac arrest, and resuscitation started. Resuscitation was successful, and normal heart action was re-established; blood pressure rose to 150/110, and oxygen saturation was 90%. Laboratory findings were deteriorated, and development of acute renal failure indicated the necessity of urgent dialysis. Following dialysis, the patient was stable, oxygen saturation 98%. Twenty hours postpartum patient developed again cardiopulmonary arrest. Despite resuscitation attempts the outcome was lethal.

Laboratory findings 4 h 10 h 19 h Haemoglobin (g/L) 76 88 104 Platelet count (× 109/L) 69 38 43 Serum urea (mmol/L) 6. 1 7. 1 14 Serum creatinine (µmol/L) 98. 2 170. 9 190. 5 Total bilirubin (µmol/L) 21. 4 39. 3 53. 7 AST (IU/L) 456 772 966 ALT (IU/L) 185 359 651 LDH (IU/L) 1000 734 8478 Fibrinogen (g/L) 7. 1 1. 61 0. 55 D-dimer (µg/L) – 894 985 APTT (s) 47. 8 79. 1 105 PT (s) 30. 1 392 44. 3 INR 1. 8 2. 68 4. 12 �medico-legal autopsy was ordered. An autopsy revealed oedema of the brain and lungs as well as dilatation of right and left ventricles. Hydrothorax (900 m. L), hydroperitoneum (2500 m. L), and hydropericardium (200 m. L) were present.

� Case report A 25 -year-old primigravida female at 28 weeks of gestation was � � � admitted to the emergency department with hemorrhagic shock and history of antepartum fit 4 h before admission. Prenatal care had not been provided since the second trimester and the pregnancy was uneventful until two days before admission where the patient complained of severe headache, epigastric pain and blurred vision with hypertension and proteinuria. Oral antihypertensive drugs were given by family doctor as alleged by relatives, for follow up. On admission, clinical examination revealed a pale and dull patient with disturbed level of consciousness. Multiple tongue bites were evident. The patient’s parameters were as follows HR 140 beat/min, ABP 90/30 mm. Hg. , fundal level nearly 34 weeks, and the cervix was closed with severe vaginal bleeding with clots. Laboratory parameters were as follows: hemoglobin 3 gm/dl, platelets 60, 000/mm 3, peripheral blood film showing hemolytic smear, INR 4, aspartate aminotransferase 500 IU/L, alanine aminotransferase 500 IU/ L, proteinuria of 3þ. Antenatal sonography revealed a living fetus nearly 28 weeks and massive abdominal collection, abdominal tapping with spinal needle revealed bloody nonclotted fluid. Resuscitation was started it was decided to perform an immediate abdominal exploratory laparotomy with delivery by caesarean section.

� abdominal exploratory laparotomy through lower midline incision was done revealing massive hemoperitoneum, cesarean section was done and a living male baby weighing 1. 2 kg was delivered � The uterine incision was closed. But, she developed atonic postpartum hemorrhage from partial couvelaire uterus which was managed by using prostaglandins and B-Lynch brace sutures to minimize uterine bleeding and atony was corrected. � There was massive hemoperitoneum and about 3 L of blood with clots were removed. Also, a continuous accumulation of blood in the pelvis from the upper abdomen so, exploration of the abdomen by manual palpation of the upper abdominal organs revealed enlarged liver with blood clots covering it and active bleeding from surface of the liver and so, a ruptured subcapsular hepatic hematoma was suspected. �. Her laboratory parameters were as follows: hemoglobin 6 gm/dl, platelets 60, 000/mm 3, INR 2, aspartate aminotransferase 2000 IU/L, alanine aminotransferase 1500 IU/L, serum blood urea was 120 mg/dl and serum creatinine 8 mg/dl over the next days with the drains revealed 500 cc/24 h with altered blood clots. � CT brain revealed brain hypoxia and edema. The patient remained haemodynamically unstable requiring further transfusion of fresh frozen plasma, platelets and blood. � She developed acute kidney failure, respiratory insufficiency, liver failure and major coagulopathy. The condition deteriorated and eventually, the patient died after 48 h following cardiac arrest from which she could not be resuscitated. Please cite this article in press as: Elagwany AS, et al. , � A fatal case of complicated HELLP syndrome and antepartum eclamptic fit with ruptured subcapsular liver hematoma

Hellp syndrom � It is a syndrome that is characterized by hepatic endothelial disruption followed by platelet activation, aggregation and consumption, ultimately resulting in ischemia and hepatocyte death. � HELLP Syndrome - 0. 2 to 0. 6% of all pregnancies. � Pre Eclampsia – 5 to 7% of all pregnancies. � Sibai et al reporetd 20% incidence of HELLP in women with pre eclampsia. � 70% cases diagnosed in antenatal period while 30% after delivery. � The findings of this multisystem disease are attributed to- › Abnormal vascular tone › Vasospasm › Coagulation defects� This vasculopathy either limited to hepatic segment or diffusely throughout liver.

HELLP Syndrome �Pre Eclampsia �Parity Multiparous �Nulliparous. Age > 25 yrs < 20 yrs or > 45 yrs. Other relevant • �White race • Family history of PIHhistory • �H/O Poor • �Chronic hypertension pregnancy • �Diabetes mellitus outcome • �Multifetal gestation • Less Antenatal visit

CLINICAL FEATURES � About 7% of cases presents before 27 weeks, 46% cases before 37 weeks and 14% presents at term � With postpartum presentation, the onset is typically within first 48 hrs of delivery. � Right sided upper abdominal pain or pain around stomach 86 -90% � Nausea 45 -85% � Headache 50% � Malaise 80 -90% Signs � Right upper quadrant tenderness 86% � Increased blood pressure 67% � Protenuria 85 -90%. Edema 55 -65% � When to begin testing � So, any pregnant woman presenting in OPD with malaise or viral like illness in 2 nd or 3 rd trimester should be evaluated with CBC and Liver function tests

� Hallmarks of HELLP: Hemolysis, elevated liver enzymes, and low platelets � Hemolysis � Diagnosis requires at least 2 of the following: � ■ Abnormal peripheral smear (schistocytes, burr cells) � ■ Elevated serum bilirubin (≥ 1. 2 mg/d. L) � ■ Low serum haptoglobin � ■ Significant drop in hemoglobin levels, � unrelated to blood loss � Elevated liver enzymes � ■ Aspartate aminotransferase or alanine � aminotransferase at least twice � the upper level of normal � ■ Lactate dehydrogenase at least twice � the upper level of normal. This value � is also elevated in severe hemolysis � Low platelets � ■ <100, 000/mm 3

�the diagnosis of haemolysis is supported by high LDH concentration and the presence of unconjugated bilirubin, but the demonstration of low or undetectable haptoglobin concentration is a more specific indicator. �Platelets (PLTs) < 150· 109/L) in pregnancy may be caused by- › � Gestational thrombocytopenia (GT) (59%), › Immune thrombocytopenic purpura (ITP) (11%), › Preeclampsia (10%), › HELLP syndrome (12%) �PLTs < 100· 109/L are relatively rare in preeclampsia and gestational thrombocytopenia, �frequent in ITP and obligatory in the HELLP syndrome (according to the Sibai definition).

Laboratory criteria for diagnosis — � 1. Low platelets - < 100, 000/µL 2. Elevated liver enzymes – AST > 70 IU/L - LDH > 600 IU/L 3. Hemolysis – Abnormal peripheral smear - Total bilirubin > 1. 2 mg � Leukocytosis � Coagulation factors › If DIC is not present – PT , a. PPT, S. Fibrinogen will be normal › � If fibrinogen < 300 mg/dl along with other lab abnormality – DIC is suspected › � Positive D-dimer test is more sensitive indicator of sub clinical coagulopathy and may be positive before other coagulation studies are abnormal. › � Proteinuria S. uric acid – raised. � Hypogycemia- persistent, profound hypoglycemia inspite of repeated glucose transfusion is peculiar to advanced HELLP syndrome.

Differential diagnosis � 1. Diseases related to pregnancy › � Benign thrombocytopenia of pregnancy › � Acute fatty liver of pregnancy (AFLP) � 2. Infectious and inflammatory diseases, not specifically related to pregnancy: � › Virus hepatitis › � Cholangitis › Cholecystitis › � Upper urinary tract infection › Gastritis › Gastric ulcer › Acute pancreatitis �. Thrombocytopenia › Immunologic thrombocytopenia (ITP) › � Folate deficiency › � Systemic lupus erythematosus (SLE) › � Antiphospholipid syndrome (APS)4. � Rare diseases that may mimic HELLP syndrome › Thrombotic thrombocytopenic purpura (TTP) › � Haemolytic uremic syndrome (HUS)

HELLP % Pregnancies 0. 2%– 0. 6% AFLP 0. 005%– 0. 01% Onset/trimester 3 or postpartum Family history No Occasionally Presence of preeclampsia Yes 50% Typical clinical features Hemolysis (anemia) Thrombocytopenia (50, 000 often) Liver failure with coagulopathy, encephalopathy hypoglycemia, DIC

TENNESSEE CLASSIFICATION Based on laboratory criteria 1. Platelet count < 100, 000/µL 2. AST ≥ 70 IU/L & LDH ≥ 600 IU/L 3. Hemolysis on peripheral smear Partial HELLP Full HELLP Any 2 of 3 criteria All of 3 criteria CLASS I› Platelet ≤ 50, 000/µL(severe thrombocytopenia)› AST ≥ 70 IU/L› LDH ≥ 600 IU/L› Hemolysis on smear � CLASS II› Platelet 50, 000/µL to 100, 000/µL (moderate thrombocytopenia)› AST ≥ 70 IU/L› LDH ≥ 600 IU/L› Hemolysis on smear � CLASS III › Platelet 100, 000/µL to 150, 000/µL (mild thrombocytopenia) › AST ≥ 40 IU/L › LDH ≥ 600 IU/L › Hemolysis on smear � � � � Patients with FULL HELLP syndrome – › Are at higher risk for complication like DIC. › Should be considered delivery within 48 hrs. � Patients with PARTIAL HELLP syndrome – › Candidates for conservative management � Patients with CLASS-I HELLP are at higher risk for maternal morbidity and mortality than CLASS-II & III. � Class III HELLP syndrome is considered as a clinical significant transition stage or a phase of the HELLP syndrome which has the ability of progression

Management in antepartum � • Progressive and sometimes sudden deterioration in maternal and fetal conditions>> patients should be hospitalized and observed in a labor and delivery unit. � • Initially, assume the patient has severe preeclampsia – � intravenous magnesium sulfate to prevent convulsions �– antihypertensive medications as needed to keep BP < 160/105

Management in antepartum �Blood Tests • � Complete blood count with platelet count • Peripheral smear evaluation • Serum AST, lactate dehydrogenase, bilirubin, and coagulation studies. • Creatinine , Help confirm the diagnosis , check for the presence of DIC, massive hemolysis, severe anemia, or renal failure. �, �The first priority is to assess the patient for the presence of cardiovascular complications, signs of liver hematoma or hemorrhage, and abruptio placentae.

Management in antepartum �Fetal assement. �Can delivery wait 48 hours for corticosteroids? • Evaluate fetal status by heart rate monitoring or biophysical profile, and confirm gestational age. � • Then decide whether delivery is indicated or can be delayed for 48 hours so that corticosteroids can be given. � • No room for expectant management. �– Delivery can only be delayed for a maximum of 48 hours—and only when both mother and fetus are stable,

corticosteroids � • Corticosteroid dosing – 2 doses of either betamethasone 12 mg intramuscularly every 12 hours – dexamethasone 12 mg intravenously every 12 hours. � • Initiate delivery within 24 hours after the last steroid dose, with continuous � • monitoring in the labor and delivery unit

Delivery considerations � • HELLP syndrome does not justify immediate cesarean � • Patients with HELLP syndrome in labor or with rupture of membranes can deliver vaginally in the absence of obstetric complications. � • Induction or augmentation of labor is acceptable with either oxytocin infusion or prostaglandins if the fetal gestational age is 32 weeks or more and the cervical Bishop score exceeds

Cesarean Section � • Watch for oozing from surgical sites – it is advisable to insert a subfascial drain and to leave the skin incision open for at least 48 hours to avoid hematoma formation � • Small doses of systemic opioids are best � • For maternal analgesia during labor, give small, intermittent doses of systemic opioids � • Avoid pudendal block because of the potential for bleeding and hematoma formation

Suspected liver hematoma � • rare but potentially lifethreatening • � antepartum, during labor, or in the postpartum period � • severe epigastric or retrosternal pain on inspiration), with or without shoulder/neck pain �. �Suspect when profound hypovolemic shock occurs in a previously hypertensive patient � • Diagnosis can be made by ultrasound or CT of the liver which can intraperitoneal bleeding. � • In most cases, rupture involves the right lobe of the liver and is preceded by a parenchymal liver hematoma.

• Management � • Management depends on maternal hemodynamic status, integrity of the capsule (ruptured or intact), and the fetal condition. � • Choose conservative management – � In hemodynamically stable women with an unruptured hematoma. �– close monitoring of the patient’s hemodynamic and coagulation status and serial assessment of the hematoma with ultrasound or CT scan. � • Avoid exogenous trauma to the liver, such as frequent abdominal palpation, emesis, or convulsions. � • Any sudden increase in intraabdominal pressure can led to rupture of hematoma

• Management liver hematoma: When rupture occurs • Surgical emergency • Maternal resuscitation – transfusion of packed red blood cells to maintain blood pressure and tissue perfusion, – correction of coagulopathy with fresh frozen plasma and platelets • Options at laparotomy include: – packing and drainage (preferred) – ligation of the hepatic lacerations – embolization of the hepatic artery to the affected liver segment, and loosely suturing omentum or surgicalmesh to the liver surface

Postpartum care � • HELLP prior to delivery – � closely monitor postpartum vital signs, intake and output, and symptoms in intensive care or a similar facility for at least 48 hours. � – intravenous magnesium sulfate and antihypertensive medications as needed to keep systolic blood pressure below the standard is 160 mm Hg and diastolic blood pressure below 105 mm Hg � – The rationale for this treatment is to prevent bleeding in the brain if the woman has thrombocytopenia.

Postpartum care � • HELLP appears in the postpartum period �– Since HELLP can appear in the postpartum period, all women with preeclampsia require close monitoring and magnesium sulfate + keep maternal blood pressure below 160 mm Hg systolic and 105 mm Hg diastolic. �Recovery � Mostly completely recover within 72 hours, while others deteriorate further or fail to recover for as long as 1 week after delivery. � • May require intensive monitoring for several days because of the risk of pulmonary edema, renal failure, or adult respiratory distress syndrome.

Watch for sudden hypotension � • Can be an early sign of severe hemolysis �– unrecognized intraperitoneal blood loss � (from surgical sites or ruptured liver hematoma) � Sepsis � relative hypovolemia (excessive vasodilation from antihypertensive drugs such as hydralazine or nifedipine)

Use of steroids �IV steroid- appear to have more rapid onset of action than IM better outcome in improving urine output & laboratory values. �Dose –increases platelet count when given in high doses Duration –Duration of action of this medication is limited. �REBOUND PHENOMENON �Patient may experience a worsening of their laboratory studies 48 -72 hrs after dosing with steroid. – �For most of patient with HELLP syndrome-10 mg IV dexamethasone every 12 hrs until delivery & then 10 mg IV dexamethasone every 12 hrs for additional 3 doses post partum. �For selected high risk cases with profound thrombocytopenia with CNS dysfunction. 20 mg IV dexamethasone every 6 hrs up to 4 doses

Use of steroids � A Cochrane analysis from 2004 concluded that steroid treatment did not affect maternal mortality and outcomes such as placental abruption, pulmonary oedema and liver complications. Steroid is not curative but maycreate a WINDOW OFOPPORTUNITY forintervention before maternalcondition may again deteriorate. � � Platelet transfusion – is required either before or after delivery, � in presence of bleeding from puncture site, wound and intra peritoneal bleeding. � If platelet count <40, 000/µL, 6 – 10 U of platelet is required. � PCV and FFP – required if coagulopathy is present

Recurrence : �Subsequent pregnancies carry a high risk of complications • pre-eclampsia, • recurrence, • prematurity, • IUGR, • abruptio placentae, • perinatal mortality. �