hellpsyndrome

1. HELLP
SYNDROME

2. INDRODUCTION
• The spectrum of disease
resulting from pathophysiology of
pre-eclampsia continues to
challenge diagnostic accuracy of
clinicians.
• Out of pre- eclampsia’s various
manifestations, a specific entity is
HELLP syndrome.

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

4. DEFINITION
• 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.

5. INCIDENCE
•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.

6. PATHOGENESIS
• 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.
• More commonly involves smaller terminal
arterioles yielding a characteristic histological
features

7. 1)Classical histological lesion in LIVER
• Periportal or focal parenchymal necrosis in which
hyaline deposits of fibrin like material
↓
Obstruction of hepatic blood flow
↓
Periportal necrosis
Intra hepatic hemorrhage
Subcapsular hematoma
Eventual rupture of Glisson’s capsule

8. 2) HEMOLYSIS
• Hemolysis is due to a microangiopathic
haemolytic anaemia (MAHA).
The term is now commonly described as
thrombotic thrombocytopenic purpura.
More recently the term thrombotic
microangiopathy is used to describe the
syndrome charecterized by
 Hemolytic anemia
 RBC fragmentation
 Thrombocytopenia
 Thrombotic lesions in small blood vessels

9. • Red cell fragmentation caused by high-velocity
passage through damaged endothelium appears
to represent the extent of small vessel
involvement with intima damage, endothelial
dysfunction and fibrin deposition.
• Presence of fragmented (schizocytes) or
contracted red cells with spicula (Burr cells) in
the peripheral blood smear reflects the
haemolytic process and strongly suggests the
development of MAHA.

10. • Peripheral smear shows-
 Spherocytosis
 Schizocytes
 Reticulocytosis
 Anisocytosis
 Triangular cells
 Helmet cells
 Burr cells
 Polychromasia

11. • Destruction of red blood cells by haemolysis causes
increased serum lactate dehydrogenase (LDH) levels and
decreased haemoglobin concentrations.
• Haemoglobinaemia or haemoglobinuria is macroscopically
recognizable in about 10% of the women.
• Liberated haemoglobin is converted to unconjugated
bilirubin in the spleen or may be bound in the plasma by
haptoglobin.
• The haemoglobin-haptoglobin complex is cleared quickly by
the liver, leading to low or undetectable haptoglobin levels in
the blood, even with moderate haemolysis.

12. • Low haptoglobin concentration can be used
to diagnose haemolysis and is the preferred
marker of haemolysis.
• Thus, 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.

13. 3) THROMBOCYTOPENIA
•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%)

14. • 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).
• Decreased Platelet count in the HELLP
syndrome is due to their increased
consumption.
• Platelets are activated, and adhere to
damaged vascular endothelial cells, resulting
in increased platelet turnover with shorter
lifespan.

15. •DIC is the primary process in HELLP
syndrome as suggested by some
investigators but most patients show
no abnormality on coagulation
studies.
•Patient who develop DIC generally
are having well developed HELLP
syndrome.

16. Immune system disorder theory
• The diffuse systemic nature & aetiopathology of
HELLP syndrome explained by possibility that Pre
eclampsia intrinsically is an immunologically mediated
systemic disorder.
• Abnormal T & B lymphocyte function observed in
patient with HELLP Syndrome .
• There is an increased neutrophil- endothelial
adhesiveness in pre- eclamptic patients
↓
Explains diffuse vascular implication of disease
process

17. RISK FACTORS
HELLP
Syndrome
Pre 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

18. CLASSIFICATION
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

19. MISSISSIPI CLASIFICATION (2006)
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 to100,000/µL (moderate thrombocytopenia)
 AST ≥ 70 IU/L
 LDH ≥ 600 IU/L
 Hemolysis on smear

20. CLASS III
 Platelet 100,000/µL to150,000/µL (mild thrombocytopenia)
 AST ≥ 40 IU/L
 LDH ≥ 600 IU/L
 Hemolysis on smear

21. • 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.

22. DIAGNOSIS
CLINICAL FEATURES
• The clinical presentation in most cases is
vague & may be missed completely if higher
degree of suspicion is not maintained.
• 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.

23. Symptoms
• 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%

24. 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

25. •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

26. Laboratory findings
• Thrombocytopenia occurs first followed by raised liver enzymes and last is
hemolysis.
• 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 > 1.2mg%

27. • 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.

28. 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

29. 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)

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

31. Maternal complications
•Subcapsular liver hematoma
•Liver rupture
•Hepatic infarction
•Recurrent thrombosis
•Retinal detachment
•Cerebral infarction
•Cerebral Haemorrhage
•Maternal death

32. Fetal/neonatal complications
•Perinatal death
•IUGR
•Preterm delivery
•Neonatal thrombocytopenia
•RDS

33. • 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.

34. 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

35. 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.

36. 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

38. 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.

39. • 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

40. In fetus
• Benefit from steroid treatment of the HELLP
syndrome was reported in a publication from
1993 where less frequent grade III and IV IVH,
necrotizing enterocolitis (NEC), retrolental
fibroplasia and fewer neonatal deaths were
observed.
• In addition to accelerate foetal lung maturity,
antenatal steroid has been used to reduce the
risk of IVH and NEC in selected cases of the
HELLP syndrome.

41. 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

42. 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

43. 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.

44. Steroid is not curative but
may create a WINDOW
OF OPPORTUNITY for
intervention before
maternal condition may
again deteriorate.

45. 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.

46. • 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.

47. 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.

48. • 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 .

49. • Women with a HELLP syndrome who
demonstrate progressive elevation of bilirubin
or creatinine for more than 72 hours after
delivery may benefit from plasma exchange
with fresh frozen plasma.
• In the case of continuing haemolysis,
persistent thrombocytopenia and
hypoproteinaemia, post-partum erythrocyte
and thrombocyte substitution, as well as
albumin supplementation, are standard
treatment regimens

50. 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

51. •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.

52. 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.

53. THANK YOU