Hellp Syndrome: Symptoms, Types, Causes and Treatment

HELLP syndrome is a severe, life-threatening complication that can develop during pregnancy or shortly after delivery. It is best known as a variant of preeclampsia, but its distinct features—hemolysis, elevated liver enzymes, and low platelet count—set it apart as a unique clinical entity. Despite decades of research, HELLP remains a challenging diagnosis, both for clinicians and expectant families. In this article, we explore its symptoms, types, causes, and current approaches to treatment, synthesizing the latest evidence from medical research.

Symptoms of Hellp Syndrome

Recognizing the symptoms of HELLP syndrome is crucial, as early intervention can save lives. Symptoms often develop suddenly, sometimes in women with few or no signs of preeclampsia. The presentation can be subtle or dramatic, making clinical vigilance essential.

Symptom	Frequency	Additional Clues	Sources
Malaise	Very Common	Nonspecific, viral-like	1 4 2 3 5
Epigastric/Right Upper Quadrant Pain	Very Common	May mimic indigestion	1 4 2 3 5
Nausea/Vomiting	Common	Often severe	1 4 2 3 5
Headache	Common	May signal worsening	2 5
Visual Changes	Less Common	Blurred vision, spots	2
Hypertension	Variable	May be absent or mild	1 3 4
Proteinuria	Variable	May be absent	1 3 4

Table 1: Key Symptoms of HELLP Syndrome

Typical Symptom Presentation

Symptoms usually appear before 36 weeks of gestation but can also occur postpartum. Most patients report feeling generally unwell, with prominent right upper abdominal pain—sometimes mistaken for heartburn or gallbladder disease. Nausea and vomiting are common, and about half of patients experience headache or visual changes. Notably, high blood pressure and protein in the urine, classic signs of preeclampsia, may be mild or absent in HELLP 1 2 3 4 5.

Symptom Patterns and Diagnostic Challenges

• Symptom Onset: Symptoms often worsen during the evening and night, with some improvement during the day. This diurnal pattern can delay diagnosis, as lab abnormalities may lag behind clinical symptoms by several hours 5.
• Non-Specificity: The symptoms are not unique to HELLP; they overlap with many other conditions, including viral illnesses and gastrointestinal disorders, making laboratory testing essential for diagnosis 1 4.
• Predictive Value: Clinical symptoms—especially headache, visual changes, epigastric pain, and nausea/vomiting—are more predictive of adverse maternal outcomes than lab values alone 2.

Laboratory and Clinical Correlation

• Laboratory Confirmation: Lab tests are needed to confirm the diagnosis, as up to half of patients do not meet the full lab criteria at symptom onset 5.
• Imaging: Imaging may be required if liver complications or other organ involvement is suspected 4.

Types of Hellp Syndrome

HELLP syndrome is not a one-size-fits-all condition. Its severity and progression can vary, leading to different classification systems that help guide clinical management.

Type/Class	Criteria/Features	Severity	Sources
Complete HELLP	All 3: Hemolysis, ↑Liver enzymes, ↓Platelets	More severe	6 15
Partial/Incomplete HELLP	Only some features present	Milder, better outcome	6 15
Mississippi Class I	Platelets < 50,000/μL	Most severe	15
Mississippi Class II	Platelets 50,000–100,000/μL	Moderate severity	15
Mississippi Class III	Platelets 100,000–150,000/μL	Least severe, atypical	15

Table 2: Types and Classifications of HELLP Syndrome

Classification Systems

• Complete vs. Partial (Incomplete) HELLP:
  • Complete HELLP requires all three diagnostic criteria: hemolysis, elevated liver enzymes, and low platelets.
  • Partial or incomplete HELLP is diagnosed when only one or two of the criteria are met. These cases tend to be milder with a better prognosis 6 15.
• Tennessee and Mississippi Systems:
  • Tennessee Classification: Focuses on lab values—LDH > 600 U/L, AST ≥ 70 U/L, and platelets < 100,000/μL 15.
  • Mississippi Triple-Class System: Further divides HELLP by the nadir platelet count into Class I (<50,000/μL), Class II (50–100,000/μL), and Class III (100–150,000/μL). Lower counts correlate with increased severity and complications 15.

Clinical Implications of Classification

• Severity and Outcomes: Complete HELLP and those in Mississippi Class I are more likely to have severe symptoms, rapid progression, and higher risk of complications such as organ failure or death. Partial or Class III cases tend to have fewer complications and a better outcome 6 15.
• Timing: Most cases emerge between 27–37 weeks of gestation, but up to 30% can occur postpartum 4 15.
• Recurrence: There is a risk of recurrence in future pregnancies, particularly for women with a history of complete or severe HELLP 6.

Causes of Hellp Syndrome

HELLP syndrome’s causes remain an active area of research. While its relationship with preeclampsia is well recognized, the syndrome has unique elements that distinguish its pathogenesis.

Factor	Description	Mechanism/Role	Sources
Genetic Predisposition	Familial tendency, gene variants	Increases risk, multifactorial	7 8
Immune Maladaptation	Abnormal maternal-fetal immunity	Triggers vascular injury	7 10
Endothelial Dysfunction	Damage to vessel lining	Leads to clotting, inflammation	7 10
Complement Activation	Overactive complement system	Microangiopathy, hemolysis	7 8 9 16
Coagulation Activation	Platelet aggregation, DIC	Low platelets, microthrombi	7 10
Antiphospholipid Syndrome	Autoimmune antibodies	Thrombosis, microvascular injury	3
Other Factors	Hypertension, metabolic errors	Modulate risk/severity	10 7

Table 3: Causes and Contributing Factors in HELLP Syndrome

Genetic and Familial Factors

• Genetic Susceptibility: Women with a family history of HELLP or preeclampsia have a greater risk, but no single gene has been pinpointed. Instead, multiple moderate-risk gene variants likely interact with environmental factors 7 8.
• Complement Pathway Mutations: Up to 46% of HELLP patients carry rare mutations in the alternative complement pathway (APC) genes, making the complement system a key contributor. This is similar to atypical hemolytic uremic syndrome (aHUS), a related condition 8 9.

Immune and Inflammatory Mechanisms

• Immunological Maladaptation: An abnormal maternal immune response to the fetus triggers inflammation and vascular injury in the placenta 7 10.
• Endothelial Damage: The inner lining of blood vessels is damaged, leading to platelet activation, clot formation, and reduced blood flow to organs, especially the liver 7 10.

Coagulation and Microangiopathy

• Platelet Consumption: The ongoing vascular injury leads to platelet-fibrin clots in small vessels (microangiopathy), consuming platelets and causing hemolysis (destruction of red blood cells) 7 10.
• Disseminated Intravascular Coagulation (DIC): In about half of HELLP cases, the activation of the clotting system becomes so severe that DIC develops, which can lead to multi-organ failure 7.

Autoimmune and Metabolic Triggers

• Antiphospholipid Syndrome (APS): This autoimmune disorder is associated with an increased risk of HELLP, as antiphospholipid antibodies promote abnormal clotting and microvascular injury 3.
• Metabolic Factors: Rarely, inborn errors of fatty acid metabolism may play a role 10.

Environmental and Pregnancy-Related Factors

• Gestational Age: Most cases occur in the third trimester, but up to 30% develop after delivery 4 15.
• Other Triggers: Hypertension is present in about two-thirds of cases but is not required for diagnosis 1 3 4.

Treatment of Hellp Syndrome

Timely, effective treatment of HELLP syndrome is essential to reduce risks for both mother and baby. Management strategies are tailored according to disease severity, gestational age, and the presence of complications.

Treatment Option	Indication	Benefit/Outcome	Sources
Immediate Delivery	≥34 weeks or severe	Definitive cure, lowest risk	11 15 6
Conservative/Expectant	<34 weeks, stable	Possible pregnancy prolongation	6 15 11 16
Corticosteroids	Variable use	Platelet recovery, fetal lung maturity	12 13 14 15
Antihypertensives	High BP	Prevents stroke/complications	15
Blood Products	Severe anemia/thrombocytopenia	Corrects deficiencies	2 6 11
Complement Inhibitors (e.g., Eculizumab)	Experimental/Severe	Case reports of benefit	8 9 16

Table 4: Major Treatment Approaches for HELLP Syndrome

Principles of Management

• Delivery is Key: The only definitive treatment is delivery of the baby, especially if the mother is at or beyond 34 weeks’ gestation or if her condition is unstable. This leads to gradual resolution of symptoms and laboratory abnormalities 11 15 6.
• Conservative Management: In select patients before 34 weeks, with stable maternal and fetal conditions, close monitoring and supportive care can allow time for fetal lung maturation. However, this approach is controversial and requires intensive monitoring 6 15 11 16.

Supportive and Adjunctive Therapies

• Corticosteroids:
  • For Fetal Benefit: Standard practice is to use corticosteroids (betamethasone or dexamethasone) to accelerate fetal lung maturity if preterm delivery is anticipated 15.
  • For Maternal HELLP: The role of corticosteroids for improving maternal outcomes is debated. Some studies show better platelet recovery, especially with dexamethasone, but not a significant reduction in serious complications or hospital stay. Therefore, routine use for maternal benefit is not universally recommended, except where rapid platelet recovery is crucial 12 13 14 15.
• Blood Pressure Control: Antihypertensive medications are used to keep maternal blood pressure below 155/105 mmHg, reducing the risk of stroke and other complications 15.
• Blood Product Replacement: Transfusions of platelets, red blood cells, or plasma are used if there is severe bleeding, anemia, or low platelet counts 2 6 11.
• Plasma Exchange & Plasmapheresis: In rare, severe, or refractory cases, plasma exchange may be considered 3.

Emerging and Experimental Therapies

• Complement Inhibitors (Eculizumab): Targeted inhibition of the complement system with drugs like eculizumab shows promise in severe or early-onset cases, especially where complement activation is implicated. Case reports describe successful prolongation of pregnancy and maternal recovery, but more research is needed before routine use 8 9 16.
• Immunosuppression: Use of intravenous immunoglobulin or prednisone has been described in association with antiphospholipid syndrome, but not as standard therapy 3.

Mode of Delivery and Postpartum Care

• Vaginal vs. Cesarean Delivery: Vaginal delivery is preferred if the cervix is favorable. Cesarean is chosen if rapid delivery is needed or labor cannot be induced safely 15.
• Postpartum Monitoring: Close observation for at least 48 hours, as symptoms and complications can worsen or emerge after delivery 15.
• Recurrence Risk: Women who have had HELLP syndrome require counseling regarding recurrence risk in future pregnancies and preconception planning 6 15.

Conclusion

HELLP syndrome is a complex and dangerous pregnancy complication that requires rapid recognition and management. Here are the main points:

• Symptoms: HELLP is characterized by malaise, right upper quadrant/epigastric pain, nausea, vomiting, and sometimes headache or visual changes. Blood pressure can be normal or only mildly elevated 1 2 3 4 5.
• Types: The syndrome ranges from complete to partial forms, with classification systems (Tennessee and Mississippi) helping to assess severity and guide care 6 15.
• Causes: Its origins involve genetic predisposition, immune and vascular injury, complement system activation, and sometimes autoimmune triggers like antiphospholipid syndrome 3 7 8 9 10.
• Treatment: Delivery is the mainstay of therapy. Supportive care includes corticosteroids for fetal lung maturity, blood pressure control, and transfusions as needed. Experimental therapies such as complement inhibition are under investigation 11 12 13 14 15 16.
• Prognosis: Prompt diagnosis and expert management are essential for the best maternal and fetal outcomes.

Key Takeaways:

• HELLP syndrome is an obstetric emergency—early detection is lifesaving.
• Symptoms can be subtle and non-specific—lab testing is crucial.
• Delivery is the only definitive cure, but supportive and experimental treatments play important roles.
• Classification systems help guide management and predict outcomes.
• Ongoing research is expanding our understanding and options for care.

By staying vigilant and informed, healthcare professionals can improve the odds for mothers and babies facing this formidable challenge.