HELLP Syndrome

Diagnosis
Background
Lab Tests
References
Related Topics

Indications for Testing

Pregnant patient presenting with clinical picture of preeclampsia, thrombocytopenia, or acute liver failure

Criteria for Diagnosis

Diagnostic criteria for HELLP syndrome

Diagnostic Criteria for HELLP Syndorme
	Martin Criteria – 1991	Sibai Criteria – 1993
Hemolysis	LDH >600 U/L	Abnormal peripheral smear (schistocytes) LDH >600 U/L Bilirubin >1.2 mg/dL
Elevated liver enzymes	AST >40 U/L	AST >70 U/L
Low platelets	Platelet count <150x10⁹/L	Platelet count <100x10⁹/L
American Society of Hematology Practice Guide on Thrombocytopenia in Pregnancy, 2013

Patients lacking all 3 of the criteria for HELLP (hemolysis, elevated liver enzymes, and low platelets) can be deemed partial HELLP

Laboratory Testing

CBC – anemia, thrombocytopenia (<100,000/mm³ to meet criteria)
- Peripheral smear with evidence of helmet cells, burr cells, schistocytes (microangiopathic hemolysis)
Liver function tests
- Aspartate aminotransferase (AST) – 2 times the upper reference limit (to meet criteria)
- Lactate dehydrogenase (LD) – markedly elevated (≥600 U/L to meet criteria)
  - LD criteria should be based on the upper limits of normal values in the lab where specimen is processed
Consider other testing if clinically indicated
- Disseminated intravascular coagulation (DIC) evaluation
- Antiphospholipid syndrome
- Hemolysis evaluation

Differential Diagnosis

Thrombocytopenia
- Gestational thrombocytopenia
- Thrombotic microangiopathies
  - Thrombotic thrombocytopenic purpura (TTP)
  - Hemolytic uremic syndrome (HUS)
- Idiopathic thrombocytopenic purpura (primary or secondary)
- Systemic lupus erythematosus
- Antiphospholipid syndrome
- Sepsis/DIC
- Acute fatty liver of pregnancy (AFLP)
Hemolysis
- Thrombotic microangiopathies
  - TTP
  - HUS
- DIC
- Infections
Elevated liver enzymes
- Thrombotic microangiopathies
  - TTP
  - HUS
- DIC
- AFLP
- Acute hepatitis
- Cholangitis/cholecystitis
- Acute pancreatitis

HELLP syndrome refers to the constellation of Hemolysis, Elevated Liver function tests, and Low Platelet count seen in pregnant women and sometimes considered to be a severe form of preeclampsia.

Epidemiology

Incidence – 0.6% of pregnant women (ASH, 2013)
- 5-10% of pregnancies with preeclampsia
- 30-50% of pregnancies with eclampsia
Age – childbearing years
Sex – exclusively in pregnant or postpartum females

Risk Factors

Caucasian race
Multiparity
Age – >34 years
Presence of preeclampsia or eclampsia
Fetus affected with fatty acid oxidation defect – ie, defects such as long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency
Previous pregnancy with HELLP

Pathophysiology

Placenta in preeclampsia is poorly perfused, which releases factors that create endothelial dysfunction
Endothelial dysfunction causes platelet aggregation and altered ratio of thromboxane to prostacyclin
Thrombin-induced activation of the coagulation cascades leads to hemolytic anemia and multiorgan microvascular injury

Selected causes of thrombocytopenia during pregnancy

Selected Causes of Thrombocytopenia During Pregnancy
Disease	Diagnostic features	% of incidence during pregnancy	Laboratory findings	Clinical symptoms	Other
Gestational thrombocytopenia	Onset at late 2^nd or 3^rd trimester Normal PLT outside of pregnancy No neonatal thrombocytopenia	5-9%	PLT >70x10⁹	Typically normal	Diagnosis of exclusion Resolution of thrombocytopenia postpartum No fetal thrombocytopenia
ITP	Onset any trimester Thrombocytopenia outside of pregnancy possible	<1%	PLT <100x10⁹ +/- large PLT on PBS	May have signs of bleeding, bruising, petechiae	Diagnosis of exclusion May be associated with fetal thrombocytopenia
Preeclampsia	Onset in late 2^nd or 3^rd trimester – >20 weeks gestation	5-8%	>0.3 gm urine protein/24 hrs	Systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg	Thrombocytopenia may precede other manifestations of preeclampsia Can present postpartum
HELLP	70% onset in late 2^nd or 3^rd trimester 30% onset postpartum	<1%	MAHA Elevated LFTs and LDH	Any or all signs of preeclampsia may be present 15-20% of cases no HTN or proteinuria present	Variant of preeclampsia
AFLP	Onset 3^rd trimester	<0.01%	PLT >50x10⁹ Elevated LFTs, CR, WBC, uric acid, ammonia Prolonged PT/PTT, decreased fibrinogen Hypoglycemia	RUQ abdominal pain Jaundice Nausea/vomiting Hepatic encephalopathy	MAHA not characteristic Conjugated bilirubin frequently >5 mg/dL Liver dysfunction more significant than in HELLP/preeclampsia
TTP/aHUS	Onset any trimester, but more common during 3^rd or postpartum	<0.01%	MAHA Elevated CR Schistocytes on PBS	Fever Abdominal pain Nausea/vomiting Headache Visual changes Altered mental status	ADAMTS 13 activity <5% in TTP LFT and BP usually normal
Abbreviations: PLT=platelet; PBS=peripheral blood smear; BP=blood pressure; MAHA=microangiopathic hemolytic anemia; CR=creatinine; AFLP=acute fatty liver of pregnancy; PT=prothrombin time; PTT=partial thromboplastin time; LFTs=liver function tests; RUQ=right upper quadrant; LDH=lactate dehydrogenase; WBC=white blood cells; ADAMTS13= a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 From ASH Practice Guide on Thrombocytopenia in Pregnancy, 2013

Clinical Presentation

Usually occurs during pregnancy
- 2/3 of patients are diagnosed antepartum
- Typically does not present prior to 3rd trimester
- Postpartum presentation usually within first week
Symptoms
- Nonspecific – malaise, fatigue
- Gastrointestinal – right upper quadrant pain, nausea, emesis
- Central nervous system – headache, confusion
- Cardiovascular – hypertension
Complications
- Maternal
  - Subcapsular hematomas and liver rupture
  - Abruptio placentae
  - Disseminated intravascular coagulation (DIC)
  - Severe postpartum bleeding
  - Stroke, cerebral hemorrhage
  - Renal failure
  - Increased risk of HELLP in subsequent pregnancies
- Fetal/perinatal
  - Prematurity
  - Placental insufficiency
  - Intrauterine growth restriction
  - Neonatal intraventricular hemorrhage

Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

Recommended Use

Use with hepatic function panel and LD in the diagnosis of HELLP

Hepatic Function Panel 0020416
Method: Quantitative Enzymatic/Quantitative Spectrophotometry

Recommended Use

Use with LD and CBC in the diagnosis of HELLP

Panel includes albumin; alkaline phosphatase; aspartate aminotransferase; alanine aminotransferase; bilirubin, direct; protein; bilirubin, total

Lactate Dehydrogenase, Serum or Plasma 0020006
Method: Quantitative Enzymatic

Recommended Use

Use with hepatic function panel and CBC in diagnosis of HELLP

Hypertension in Pregnancy. American College of Obstetricians and Gynecologists. Washington, DC [Accessed: Jan 2016]

Rajasekhar A, Gernsheimer T, Stasi R, James A. 2013 Clinical Practice Guide on Thrombocytopenia in Pregnancy. American Society of Hematology. Washington, DC [Accessed: Jan 2016]

General References

Bacq Y. Liver diseases unique to pregnancy: a 2010 update. Clin Res Hepatol Gastroenterol. 2011; 35(3): 182-93. PubMed

Haram K, Svendsen E, Abildgaard U. The HELLP syndrome: clinical issues and management. A Review. BMC Pregnancy Childbirth. 2009; 9: 8. PubMed

Hepburn IS, Schade RR. Pregnancy-associated liver disorders. Dig Dis Sci. 2008; 53(9): 2334-58. PubMed

Joshi D, James A, Quaglia A, Westbrook RH, Heneghan MA. Liver disease in pregnancy. Lancet. 2010; 375(9714): 594-605. PubMed

O'Brien JM, Barton JR. Controversies with the diagnosis and management of HELLP syndrome. Clin Obstet Gynecol. 2005; 48(2): 460-77. PubMed

Sibai BM, Ramadan MK, Usta I, Salama M, Mercer BM, Friedman SA. Maternal morbidity and mortality in 442 pregnancies with hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome) Am J Obstet Gynecol. 1993; 169(4): 1000-6. PubMed

Medical Reviewers

Krautscheid, Patti, MS, LCGC, Genetic Counselor, Molecular Genetics and Special Genetics Laboratories at ARUP Laboratories

Lehman, Christopher M., MD, Co-Medical Director, University Hospitals and Clinics Clinical Laboratory; Professor of Clinical Pathology, University of Utah

Disseminated Intravascular Coagulation - DIC

Hemolytic Anemias

Hemolytic Anemias Testing Algorithm

Heparin-Induced Thrombocytopenia - HIT

Thrombotic Microangiopathies - TMA

Last Update: August 2016

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HELLP Syndrome

Indications for Testing

Criteria for Diagnosis

Laboratory Testing

Differential Diagnosis

Epidemiology

Risk Factors

Pathophysiology

Clinical Presentation

General References

Medical Reviewers

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