IN THE NAME OF GOD

Tehran university of medical science

Baharlou hospital

GRAND ROUND

MD,M.pouradinehN.azarakhshi

Patient’s introduction:

Ms . Leila Asgari /32 years old/ married

She has 3 babiesJOB: home keeperSource of information : patient (reliable)Time of admission in the ward :

93/07/10

CHIEF COMPLAIN:

spotting Abdominal painvertigo and headacheFatigueurine incontinency and fecal incontinency

Drug history:

MethyldopaFolic acidvitamins

The most important points in history:

3 NVD delivery which last one was 4 days beforeBrain tumor surgery (lipoid cyst) 10 years ago HTN ovarian cyst surgery 8 years ago

:Positive point of ROS

:ecchymosis in hands

Peripheral vascular sys :From 1 month ago she experienced edema which got worth when she

came to hospital. as you see it seems 3 +

Vital sign:

mmHg130/80BP:RR:18Temprature:36Height:163 cmweight:80 KgPR: 62

Most important points in physical exam:

ecchymosis in handsskin :icteric Sclera :ictericGeneralized edema (+4)

Lab data:DATE WBC RBC Hb HCT

7/10 16.2 5.07 15.5 48.3

7/11 18.3 3.83 12.3 38.7

7/12 18.6 3.02 9.5 31.2

7/13 21.4 3.33 10.2 32.8

7/14 16 3.13 9.8 31.6

DATE MCV MCH MCHC PLATELET

7/10 98.4 32.5 33.1 117

7/11 101 32.1 32.1 102

7/12 103.3 30.8 29.8 76

7/13 98.5 30.6 31.3 88

7/14 101 31.3 31 75

DATE NEUTROPHIL LYMPHOCYTE MONOCYTE EUSINOPHIL

7/10 80 15 3 2

7/11 85 12 2 1

7/12 87 10 2 1

7/13 85 12 2 1

7/14 81 14 2 1

*PT control time : 12 s

DATE PT PATIENT INR PTT PATIENT TIME

7/10 ---------------- --------- ----------------------

7/11 15.7 1.7 40

7/12 19.1 2.4 37

7/13 18 2.3 38 7/14 16 1.8 38

DATE FBS UREA Creatinine

Uric acid

7/10 ---------- -------------------

---------------- ------------------

7/11 -------------- 45 1.6 8.4

7/12 100 62 1.8 8.3

7/13 119 68 1.5 8.5

7/14 108 56 1.1 5.3

DATE SGOT SGPT ALP NA K 7/10 ---------------- --------------- ------------- -------------- --------------

7/11 135 267 988 -------- 2.9

7/12 83 143 673 141 ----------

7/13 57 51 778 138 4.4

7/14 47 50 607 138 4.4

DATE Total bilirubin Direct bilirubin LDH 7/10 --------------------- -------------------------------- ---------

7/11 9.1 5.8 7807/12 9.6 5.8 7887/13 7.1 3.2 8207/14 ------------------------ --------------------------------- ------------

The acronym HELLP was coined by Weinstein in 1982 to describe a syndrome consisting of Hemolysis, Elevated liver enzymes and Low platelet count.

HELLP Syndrome - 0.2 to 0.6% of all pregnancies.

PATHOGENESIS The findings of this multisystem disease are attributed to-

Abnormal vascular toneVasospasm Coagulation defectsThis vasculopathy either limited to hepatic segment or diffusely throughout liver.More commonly involves smaller terminal arterioles yielding a characteristic histological features

RISK FACTORSHELLP

SyndromePre Eclampsia

Parity Multiparous Nulliparous

Age >25yrs <20yrs or > 45 yrs

Other relevant history

•White race•H/O Poor

pregnancy outcome

•Family history of PIH•Chronic

hypertension•Diabetes mellitus•Multifetal

gestation•Less Antenatal

visit

Typical patient Young, White woman ≥25yrs Multiparous Heavy with severe generalized edema 2nd or 3rd trimester c/o Rt. Upper quadrant pain since few days for

which she might be taking antacids. c/o malaise since few days, which may be out

of proportion to the discomfort expected by the stage of pregnency

Blood pressure is only slightly raised. Edema & proteinuria may or may not be

present

So, any pregnant woman presenting in OPD with malaise or viral like illness in 2nd or 3rd trimester should be evaluated with CBC and Liver function tests

Laboratory findings Thrombocytopenia occurs first followed

by raised liver enzymes and last is hemolysis.

Laboratory criteria for diagnosis —1. Low platelets - < 100,000/µL2. Elevated liver enzymes – AST > 70 IU/L

- LDH > 600 IU/L3. Hemolysis – Abnormal peripheral smear - Total bilirubin > 1.2mg%

Leukocytosis Coagulation factors

If DIC is not present – PT , aPPT, 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 Diagnosis1. 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

3. 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)

Complications Maternal complications Eclampsia Abruptio placentae DIC Acute renal failure Severe ascites Cerebral oedema Pulmonary oedema Wound hematoma/infection

Maternal complications

Subcapsular liver hematoma Liver rupture Hepatic infarction Recurrent thrombosis Retinal detachment Cerebral infarction Cerebral Haemorrhage Maternal death

Fetal/neonatal complications

Perinatal death IUGR Preterm delivery Neonatal thrombocytopenia RDS

Spontaneous rupture of a Subcapsular liver haematoma in pregnancy is a rare, but life threatening complication.

Occurs 1 in 40,000 to 1 in 250,000 deliveries and about 1% to < 2% of the cases with the HELLP syndrome. Rupture most often occurs in the right liver lobe. The symptoms are sudden-onset severe pain in the epigastric and right upper abdominal quadrant radiating to the back, right shoulder pain, anaemia and

hypotension. The condition may be diagnosed by ultrasound,

CT or magnetic resonance imaging (MRI) examination.

Hepatic rupture may also occur in the post-partum period.

MANAGEMENT PLAN

Identification - clinical features - lab findings - D/D from other condition

Admission to hospital Stabilization•IV line ,Cross match•Catheterization•Respi assessment

Fetal assessment(NST,BPP,Color doppler )

Transport to tertiary care centre or latency for 24-48 hrs

Termination of pregnancy

Conservative approach for 48-72 hrs (<32wks POG, Partial HELLP,Tertiary health cenre)

Rebound / Resolution

●Monitor by lab Ix ●Stop MgSO4 24 hrs of delivery ●Continue antihypertensive & steroid

MANAGEMENT

In general, there are three major options for the management of women with severe preeclampsia and HELLP syndrome

These include: 1) Immediate delivery which is the primary choice at 34

weeks' gestation or later.2) Delivery within 48 hours after evaluation, stabilization

of the maternal clinical condition and Steroid treatment. At 27 to 34 weeks of gestation, this option appears appropriate and rational for the majority of cases.

3) Expectant (conservative) management for more than 48–72 hours may be considered in pregnant women before 27 weeks' gestation. In this situation, Steroid treatment is often used, but the regimens vary considerably.

Decision making in management

<32 wks 32-34wks >34wks

↓ ↓ ↓

Admit & conservative Mx Steroids Deliver

↓ ↓ No

Manage Pt based on Is pt eligible for conservative Mx ?

Clinical response during ↓ Yes

Period of observation Counsel pt abt benefit of continuing of

pregnency for ≥2 wks for lung maturity

↓

Worsens Stable Transfer pt to tertiary care centre

↓ ↓

Deliver Monitor pt in tertiary care centre

Role of steroids Whereas delivery is the mainstay of

treatment for the HELLP syndrome, Steroid treatment is a possible addendum. Present alternatives for Steroid treatment are:

1) Standard steroid treatment on maternal HELLP.

2) High-dose dexamethasone treatment of the mother.

3) Treatment with repeated doses to reduce maternal morbidity and hastening recovery.

Benefit of steroid treatment for the HELLP syndrome was first reported in 1984.

Mech. Of Action- Unknown Proposed mech - diminish oedema, inhibit

endothelial activation and reduce endothelial dysfunction

↓ Prevention of thrombotic microangiopathic anaemia, Inhibition of cytokine production

↓ induce anti-inflammatory effects in the HELLP syndrome

Effect of steroid depends on- Dose, Route & Duration of treatment

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.

Patient may experience a worsening of their laboratory studies 48-72 hrs after dosing with steroid .– REBOUND PHENOMENON

Dosing schedule For most of patient with HELLP syndrome-10mg 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.20mg IV dexamethasone every 6hrs up to 4

doses

Recent evidence about the value of steroid treatment on maternal HELLP

In first largest randomized double blind, placebo controlled (dexamethasone versus placebo) study of 132 women by Fonseca et al. reported shorter mean hospitalization but no significant differences were found in recovery of platelet counts or liver enzymes.

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 may create a WINDOW OF OPPORTUNITY for intervention before maternal condition may again deteriorate.

Role of trasfusion Platelet transfusion – is required eithr

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.

Antithrombin III transfusion- correct hypercoagulability, stimulate prostacyclin production, regulate thrombin-induced vasoconstriction, improve foetal status.

In contrast to the use of heparin, antithrombin has not been shown to increase the risk of bleeding.

The potential benefit from antithrombin treatment of women with HELLP syndrome might be a reasonable objective to be tested in future well designed multicenter studies.

Management of post-partum HELLP syndrome

In most women with a HELLP syndrome, the maternal PLT counts continue to decrease immediately post-partum with an increasing trend on the third day.

About 30% of the HELLP syndromes develop after birth.

The time of onset ranged from few hrs to 7 days; the majority within the first 48 hoursafter delivery.

In post-partum HELLP syndrome, risk of renal failure and pulmonary oedema is significantly increased.

Since early post-partum administration of high-dose CS might accelerate recovery , its routine administration is highly advocated (10 mg of dexamethasone every 12 hours)

However, a randomized study showed that adjunctive use of intravenous dexamethasone for postpartum patients with severe preeclampsia did not reduce disease severity or duration.

There was no difference in maternal morbidity, duration of hospital stay, need for rescue scheme or the use of blood products between the groups.

These findings did not support the use of dexamethasone in the puerperium for recovery of women with HELLP .

Risk of recurrence and pre-conceptional counselling

Sibai has shown that oral contraceptives are safe in women with a prior HELLP syndrome.

Women with a history of the HELLP syndrome carry an increased risk of at least 20% (range 5–52%) that some form of gestational hypertension will recur in a subsequent gestation

Women with a history of HELLP syndrome at or before 28 weeks' gestation during the index pregnancy are at increased risk for several obstetric complications (preterm birth, pregnancy-induced hypertension and increased neonatal mortality) in a subsequent pregnancy.

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