HELLP Syndrome

• Haemolysis (H): Typically microangiopathic in nature, evidenced by schistocytes or burr cells on a peripheral smear, elevated lactate dehydrogenase (LDH) and bilirubin, low serum haptoglobin, and anaemia not attributable to overt blood loss.
• Elevated Liver Enzymes (EL): Marked rise in aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT), usually >70 IU/L or greater than twice the upper limit of normal, with no alternative explanation.
• Low Platelets (LP): Thrombocytopenia, defined as a platelet count below 100 × 10⁹/L (<100,000/microlitre).
  
  

Clinical Timing and Presentation

• Most cases arise between 27 and 37 weeks of gestation, but 15% to 30% initially manifest postpartum, usually within seven days of delivery.
• Symptoms include right upper quadrant (RUQ) or epigastric pain, nausea, vomiting, headache, and generalised malaise. Hypertension and proteinuria are present in 80–85% of cases, though either may be absent at the time of diagnosis.
• Suspicion should be high in any pregnant or postpartum individual presenting with significant new-onset RUQ or epigastric pain in the second half of gestation or early puerperium.
  
  
  

Diagnostic Criteria

• Haemolysis:
  • Schistocytes, burr cells, or polychromasia on peripheral smear.
  • Total bilirubin >1.2 mg/dL (20.5 micromol/L).
  • LDH >600 IU/L or twice the upper limit of normal.
  • Low serum haptoglobin.
• Liver Enzyme Elevation:
  • AST or ALT ≥70 IU/L or >2× upper limit of normal without alternative explanation.
• Thrombocytopenia:
  • Platelet count <100 × 10⁹/L.
    
    

Classification Systems

• Tennessee Classification: Requires presence of haemolysis, elevated liver enzymes, and thrombocytopenia as outlined above.
• Martin/Mississippi Classification:
  • Class 1: Platelets ≤50,000/mm³; LDH ≥600 IU/L; AST/ALT ≥70 IU/L.
  • Class 2: Platelets 50,000–100,000/mm³; same enzyme thresholds.
  • Class 3: Platelets 100,000–150,000/mm³; AST ≥40 IU/L.
    
    

• A leading hypothesis implicates abnormal placental development early in pregnancy. In this model, shallow trophoblastic invasion of the spiral arteries and defective vascular remodelling result in reduced uteroplacental perfusion.
• This inadequate placentation contributes to placental hypoxia, oxidative stress, and endothelial injury, setting the stage for systemic maternal responses that include hypertension and coagulopathy.
  
  

• Immunological intolerance between the maternal immune system and fetal antigens may contribute to a maladaptive systemic inflammatory response.
• HELLP is characterised by enhanced cytokine activity, endothelial dysfunction, and platelet activation.
• Elevated levels of circulating anti-angiogenic factors—such as soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sEng)—have been identified in affected individuals. These antagonise pro-angiogenic signals and promote vascular injury.
• Corticosteroid administration has been shown in some studies to reduce inflammatory markers, further supporting the inflammatory component in the syndrome’s pathogenesis.
  
  

• A genetic predisposition is suspected, particularly among those with a personal or family history of pre-eclampsia or HELLP. Polymorphisms affecting immune regulation, angiogenesis, or complement activity have been proposed but not conclusively validated.
• Epigenetic modifications, including altered DNA methylation, may also contribute to the dysregulation of key genes involved in immune response and vascular integrity during pregnancy.
  
  

• Complement dysregulation, particularly overactivation of the alternative pathway, has been increasingly recognised as a contributor in a subset of HELLP cases.
• This pathway’s involvement suggests overlap with other thrombotic microangiopathies, such as atypical haemolytic uraemic syndrome (aHUS). In rare instances, therapeutic complement blockade (e.g., with eculizumab) has led to transient remission, though this remains investigational.
  
  

• The oxidative stress generated by hypoxic placental conditions contributes to endothelial injury and hepatocellular necrosis.
• Increased proteasome activity and upregulation have been observed in HELLP patients, reflecting heightened cellular turnover and stress responses in hepatocytes and vascular endothelium.
  
  

• Several maternal characteristics have been associated with increased risk of HELLP syndrome:
  • Age over 34 years
  • Multiparity
  • European or white racial background
  • Previous adverse pregnancy outcomes or history of pre-eclampsia
  • Underlying vascular or autoimmune conditions (e.g., systemic lupus erythematosus, chronic hypertension)
    
    

Vascular dysfunction and hepatic injury

• The condition is marked by generalised endothelial dysfunction and vasospasm, leading to microvascular injury, particularly in the liver.
• Hepatic consequences include periportal hepatocyte necrosis, subcapsular haematomas, intra-parenchymal haemorrhage, and, rarely, hepatic infarction.
• Doppler imaging may reveal decreased hepatic perfusion. Histological findings typically include periportal haemorrhage and necrosis, focal parenchymal necrosis, and fibrin or hyaline deposits in hepatic sinusoids.
  
  
  

Immunological and inflammatory mechanisms

• An exaggerated maternal immune response to fetal antigens is hypothesised to cause widespread endothelial dysfunction, platelet activation, and vasoconstriction.
• Elevated levels of pro-inflammatory cytokines and anti-angiogenic markers (such as interleukin-6, soluble fms-like tyrosine kinase 1, and soluble endoglin) have been observed.
• Corticosteroids like dexamethasone appear to downregulate these markers, correlating with clinical improvement.

Placental-mediated endothelial injury

• Inadequate trophoblastic invasion and poor spiral artery remodelling result in placental hypoperfusion and the release of anti-angiogenic factors.
• Soluble VEGF receptor-1 impairs vascular integrity by sequestering VEGF and placental growth factor, reducing their availability to bind endothelial receptors.
• This cascade leads to systemic hypertension, proteinuria, microangiopathic haemolytic anaemia, and platelet consumption.
  
  

Complement system dysregulation

• A proportion of HELLP cases may be linked to excessive activation of the alternative complement pathway, leading to hepatic vascular injury.
• Clinical reports have shown temporary resolution of symptoms with complement inhibition therapy such as eculizumab, though routine use remains investigational.
• Genetic variants affecting complement regulatory proteins may contribute to this mechanism.
  
  

Metabolic hypotheses and fatty acid oxidation

• Rarely, HELLP has been associated with fetal long-chain 3-hydroxyacyl CoA dehydrogenase (LCHAD) deficiency, which leads to the accumulation of toxic fatty acid intermediates.
• Mothers carrying fetuses homozygous for this mutation show a high frequency of HELLP or acute fatty liver of pregnancy.
• Despite the association, routine screening for LCHAD mutations is not recommended in clinical practice.
  
  

Differentiation from pre-eclampsia

• While HELLP and severe pre-eclampsia share a pathophysiological origin, HELLP more often involves hepatic damage and may present without hallmark features such as hypertension or proteinuria.
• Histopathological studies reveal higher incidences of placental vascular supply lesions in HELLP compared to typical pre-eclampsia.
  
  
  
  

Martin/Mississippi Classification of HELLP Syndrome

• Platelet count: 0 to ≤50,000/mm³
• Lactate dehydrogenase (LDH): ≥600 IU/L
• Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT): ≥70 IU/L
• Associated major maternal morbidity: 40% to 60%
  
  

• Platelet count: >50,000 to ≤100,000/mm³
• LDH: ≥600 IU/L
• AST and/or ALT: ≥70 IU/L
• Associated major maternal morbidity: 20% to 40%
  
  

• Platelet count: >100,000 to ≤150,000/mm³
• LDH: ≥600 IU/L
• AST: ≥40 IU/L
• Associated major maternal morbidity: approximately 20%
  
  

Incidence and Prevalence

• HELLP syndrome affects approximately 1 to 8 per 1000 pregnancies.
• Among women with pre-eclampsia, 4% to 20% may develop HELLP syndrome, and in those with eclampsia, the frequency rises to between 10% and 30%.
• Overall, HELLP syndrome is estimated to complicate 0.1% to 0.6% of all pregnancies.
  
  

Timing of Onset

• The majority of cases present between 27 and 37 weeks of gestation.
• In 15% to 30% of cases, onset occurs in the immediate postpartum period, typically within seven days following delivery.
• HELLP may also develop after delivery even when antenatal signs are absent or minimal.
  
  

Ethnic and Demographic Distribution

• The syndrome appears to be more prevalent among white women and those of European descent compared to African-American or Hispanic populations.
• Although advanced maternal age (over 35 years) is a recognised risk factor, most cases occur in women with a mean age of 23 to 25 years.
• This contrasts with typical pre-eclampsia, which tends to affect younger women with a mean age closer to 19 years.

Associated Obstetric Factors

• Approximately 10% of HELLP syndrome cases occur in women with multiple gestations.
• The condition may also co-exist with other hypertensive disorders of pregnancy or follow a previous history of pre-eclampsia.
  
  
  

Symptom Onset and Progression

• HELLP syndrome commonly presents between 28 and 37 weeks of gestation, although symptoms can develop earlier in the late second trimester or even postpartum.
• In postpartum cases (approximately 30%), diagnosis usually occurs within 48 hours of delivery, though some present as late as seven days after birth.
• Symptoms typically develop rapidly and worsen progressively, often over hours to days.
  
  

Common Historical Features

• Right upper quadrant (RUQ) or epigastric pain is the most frequent complaint. This pain may be sharp, constant, or colicky and is related to liver involvement.
• Nausea and vomiting are present in 29% to 84% of patients and may be mistaken for gastrointestinal infection or viral hepatitis.
• Generalised malaise occurs in up to 90% of cases and is frequently non-specific.
• Headache is reported in 33% to 61% of patients.
• Oedema and sudden weight gain may reflect underlying fluid retention.
• Visual disturbances such as blurring or scotomata occur in fewer than 20% of patients and may herald eclamptic complications.
• Jaundice and bleeding tendencies (e.g. haematuria, epistaxis) are uncommon presentations, with bleeding linked to severe thrombocytopenia.
  
  

Severe Historical Presentations

• In some cases, HELLP presents with signs of hepatic rupture or subcapsular haematoma, including:
  • Sudden, severe RUQ or shoulder pain
  • Abdominal distension
  • Nausea, vomiting
  • Dyspnoea or pain on inspiration
  • Hypotension and tachycardia
• These findings may be accompanied by very high aminotransferase levels (up to 6000 IU/L) and are medical emergencies.
  
  

Gestational Age Context

• In a large series, 70% of HELLP cases occurred antenatally:
  • 80% of these were before 37 weeks
  • 20% were before 28 weeks
  • A small minority (<3%) presented as early as 17–20 weeks
    
    

Associated Conditions

• While hypertension and proteinuria are common (present in up to 85% of cases), their absence does not exclude HELLP.
• In some series, thrombocytopenia-related bleeding was a rare initial symptom.
• HELLP may also be complicated by placental abruption, pulmonary oedema, acute kidney injury, retinal detachment, eclampsia, or disseminated intravascular coagulation.
  
  
  

Vital Signs

• Hypertension is common, present in approximately 80% to 85% of patients, though 15% may be normotensive at presentation.
• Tachycardia and tachypnoea may occur, often indicating systemic stress, pain, or haemodynamic compromise.
• Hypotension may be seen in cases of hepatic rupture or severe haemorrhage.
  
  

General Appearance

• Patients may appear acutely unwell with fatigue, pain-related distress, or signs of systemic inflammation.
• Weakness and imbalance can be associated with dehydration or orthostatic hypotension due to vomiting or haemorrhage.
  
  

HEENT (Head, Eyes, Ears, Nose, Throat)

• Sunken eyes and dry mucous membranes are signs of dehydration.
• Periorbital oedema may be noted due to systemic fluid retention.
  
  

Cardiopulmonary Examination

• Pulmonary crackles can be present and are suggestive of noncardiogenic pulmonary oedema.
• Severe cases may exhibit dyspnoea or pain on inspiration, which could be due to hepatic capsular stretch or pleural effusion.
  
  

Abdominal Examination

• Right upper quadrant (RUQ) or epigastric tenderness is observed in 65% to 90% of patients.
• The pain may radiate to the back, chest, or shoulder, particularly if hepatic bleeding or subcapsular haematoma is present.
• Abdominal distension beyond that expected for gestational age may raise suspicion of intraperitoneal bleeding or ascites.
  
  

Extremities

• Nondependent oedema, including swelling of the upper and lower limbs, occurs in over half of patients.
• Brisk tendon reflexes may be evident, reflecting neuromuscular irritability often seen in pre-eclampsia-spectrum disorders.
  
  

Dermatological and Mucosal Findings

• Petechiae, purpura, or epistaxis are uncommon but, when present, suggest thrombocytopenia-related bleeding.
• Jaundice may occur in up to 5% of patients and typically correlates with elevated bilirubin due to haemolysis or hepatic dysfunction.
  
  
  

Severity Indicators

• Patients with subcapsular or intraparenchymal hepatic haematoma may present with:
  • Severe RUQ pain
  • Hypotension and tachycardia
  • Abdominal distension
  • Shoulder or chest pain
  • Haemoperitoneum
• These features indicate a surgical emergency.
  
  

Laboratory Investigations

• Thrombocytopenia is universally present, typically <100 × 10⁹/L.
• Anaemia may occur, but haemoconcentration may mask the degree of haemolysis.
  
  

• Diagnostic findings include schistocytes, burr cells, and polychromasia, indicative of microangiopathic haemolytic anaemia.
  
  

• Typically elevated due to hepatic injury. AST or ALT levels ≥70 IU/L, or >2× the upper limit of normal, are consistent with HELLP syndrome.
  
  

• Elevated levels (>600 IU/L or >2× upper limit of normal) support the diagnosis and reflect both haemolysis and hepatic necrosis.

• Raised total and indirect bilirubin levels suggest haemolysis. A level >1.2 mg/dL is commonly used as a diagnostic threshold.

• Decreased serum haptoglobin levels, though rarely tested, support haemolysis.
  
  

• Normal or mildly prolonged prothrombin time is typical, but 50% may show prolonged aPTT.
• Fibrinogen levels may be reduced (<2.94 micromol/L or <100 mg/dL) in the presence of disseminated intravascular coagulation (DIC).
  
  

• Often elevated due to fibrinolytic activity, particularly in patients with DIC or placental abruption.

• Frequently elevated (>356.9 micromol/L), although not predictive of severity.
  
  

• Creatinine may be increased in cases with renal involvement.
• Electrolyte disturbances may occur with severe illness or renal impairment.

• Hypoglycaemia can reflect hepatic failure.
  
  

• Proteinuria is present in up to 100% of patients. A ratio >0.3 is significant.
  
  

• Helps distinguish HELLP from thrombotic thrombocytopenic purpura (TTP). A ratio <22 suggests HELLP; >22 suggests TTP.
  
  

Imaging Studies

• May reveal hepatic abnormalities such as increased echogenicity, subcapsular haematoma, or ascites.
• Recommended for patients with right upper quadrant tenderness, unexplained anaemia, or suspected liver bleeding.
  
  

• Indicated when hepatic infarction, subcapsular haematoma, or rupture is suspected.
• May demonstrate well-demarcated hypoattenuating regions in hepatic parenchyma, consistent with infarcts or haematomas.

• Should be performed in all cases to assess gestational age, fetal growth, amniotic fluid volume, and umbilical artery Doppler flow.
• Growth restriction may prompt more detailed fetal surveillance.
  
  

• Pathological features include periportal or focal parenchymal necrosis, fibrin deposits in hepatic sinusoids, and hyaline deposition.
• These changes result from hepatic endothelial damage, platelet aggregation, and microvascular thrombosis.
• Involvement of larger hepatic vessels may lead to infarction and subcapsular haematoma.
  
  

Classification Systems in Laboratory Evaluation

• Classifies HELLP syndrome based on platelet count, AST/ALT, and LDH levels:
  • Class 1 (Severe): Platelets ≤50,000/μL; AST/ALT ≥70 IU/L; LDH ≥600 IU/L. Associated with highest morbidity and a 13% risk of bleeding.
  • Class 2 (Moderate): Platelets 50,000–100,000/μL; same biochemical thresholds as Class 1. Bleeding risk ~8%.
  • Class 3 (Mild): Platelets 100,000–150,000/μL; AST/ALT ≥40 IU/L; LDH ≥600 IU/L. No increased bleeding risk.
    
    

• Categorises HELLP as:
  • Complete HELLP: Haemolysis (abnormal smear, LDH >600 IU/L or bilirubin >1.2 mg/dL), platelets <100,000/μL, AST >70 IU/L.
  • Partial HELLP: Includes subtypes with incomplete features:
    • ELLP: Elevated liver enzymes, low platelets, no haemolysis.
    • EL: Elevated liver enzymes only.
    • LP: Low platelets only.
    • HEL: Haemolysis and liver enzyme elevation without thrombocytopenia.
      
      
      
      

Thrombotic Thrombocytopenic Purpura (TTP)

• TTP may be confused with HELLP due to overlapping features such as thrombocytopenia, haemolysis, and neurologic symptoms.
• Unlike HELLP, TTP presents with neurological abnormalities, fever, and renal dysfunction, often without significant liver enzyme elevation.
• Severe thrombocytopenia (<25 × 10⁹/L) is more pronounced than in HELLP.
• The LDH:AST ratio (>22) is suggestive of TTP, whereas HELLP typically has a lower ratio.
• ADAMTS13 activity is significantly reduced (<10%) in TTP, but such testing is not routinely available.
• Delivery does not improve TTP, which instead requires urgent plasma exchange.
  
  

Systemic Lupus Erythematosus (SLE) with/without Catastrophic Antiphospholipid Syndrome (CAPS)

• These autoimmune conditions can mimic HELLP through multi-organ dysfunction, thrombocytopenia, and liver involvement.
• CAPS typically manifests with widespread thrombosis and multiorgan failure.
• A prior history of autoimmune disease, positive antiphospholipid antibodies, and low complement levels support the diagnosis.
• Plasma exchange and immunosuppressive therapies are mainstays of CAPS treatment, in contrast to delivery-focused management in HELLP.
  
  

• AFLP presents with hepatic failure, coagulopathy, and hypoglycaemia, usually in the third trimester or postpartum.
• Distinctive laboratory features include total bilirubin ≥4 mg/dL (predominantly direct), low antithrombin, prolonged PT, and early-onset coagulopathy.
• AFLP is more likely to exhibit hypoglycaemia, hyperammonaemia, metabolic acidosis, and leukocytosis with left shift.
• Liver transaminase levels are typically below 500 IU/L but may rise higher in severe cases.
• In contrast to HELLP, coagulopathy precedes thrombocytopenia in AFLP.
• Diagnosis is clinical, though liver biopsy remains definitive but rarely performed.
  
  
  

Atypical Haemolytic Uraemic Syndrome (aHUS)

• aHUS almost exclusively presents in the postpartum period, often with predominant renal involvement.
• Renal deterioration is typically more severe than in HELLP or TTP, and haemolysis may be more pronounced.
• Coagulation studies remain normal, and liver transaminase elevation is minimal.
• Complement dysregulation is central to pathogenesis, and treatment with eculizumab has shown benefit in select cases.
  
  

Overlap with Preeclampsia with Severe Features

• While HELLP is traditionally considered a variant of preeclampsia, not all cases conform to the classic features of hypertension and proteinuria.
• In preeclampsia, hypertension is more severe and correlates better with disease severity than in HELLP.
• The degree of thrombocytopenia and liver dysfunction is generally milder in preeclampsia.
• Both conditions may occur concurrently, and some experts consider HELLP to represent a more severe end of the preeclampsia spectrum.
  
  

COVID-19 in Pregnancy

• SARS-CoV-2 infection during pregnancy is associated with increased risk of preeclampsia and HELLP.
• Overlap in laboratory abnormalities (e.g., elevated transaminases, thrombocytopenia, coagulopathy) may confound the diagnosis.
• A comprehensive clinical and virological assessment is essential to distinguish COVID-19–associated findings from HELLP.

Additional Differential Diagnoses

• Other conditions to consider include:
  • Eclampsia
  • Viral hepatitis
  • Hyperemesis gravidarum
  • Peptic ulcer disease
  • Nephrolithiasis
  • Thrombocytopenia of other causes (e.g., gestational thrombocytopenia, idiopathic thrombocytopenic purpura)
  • Anaemia and haemolytic syndromes
  • Abruptio placentae
    
    

Immediate Interventions

• Begin seizure prophylaxis with intravenous magnesium sulfate upon suspicion, prior to lab confirmation.
• Initiate blood pressure control immediately for readings ≥160/105 mmHg to prevent maternal stroke or end-organ damage.
• Conduct frequent laboratory monitoring (every 6–12 hours) for full blood count, liver enzymes, coagulation profile, and LDH.
• Implement hourly fluid balance monitoring, especially for urine output, as oliguria may indicate renal compromise.
• Start continuous fetal monitoring, with planning for timely delivery based on maternal-fetal status.
  
  

Corticosteroid Therapy

• Dexamethasone is the main therapeutic agent and should be initiated antepartum or postpartum for:
  • All Class 1 or 2 HELLP cases regardless of gestational age.
  • Class 3 or partial HELLP with eclampsia, severe pain, organ dysfunction, or severe hypertension.
• In pregnancies <34 weeks, delay delivery for 24–48 hours after steroid initiation to benefit fetal lung maturation.
• In pregnancies >34 weeks, delivery is typically recommended 8–12 hours after the first dexamethasone dose.
• Postpartum tapering of dexamethasone occurs over 2 doses if laboratory markers improve.
  
  

Seizure Prophylaxis

• Magnesium sulfate is administered as a continuous infusion and continued for at least 24 hours post-delivery.
• Dose adjustments are required for renal impairment or urine output <25 mL/hour.
• Serum magnesium levels should be monitored to maintain therapeutic range (<9 mg/dL); if exceeded, infusion is paused and resumed at reduced rate when safe.
• In renal failure, a bolus-only strategy may be used.
• Prolonged magnesium therapy (>5–7 days) is avoided due to neonatal risks such as hypotonia and skeletal abnormalities.
• Magnesium also provides neuroprotection for preterm infants when administered antenatally.
  
  

Blood Pressure Management

• Monitor every 15 minutes during hypertensive episodes.
• Aim to reduce systolic BP to <160 mmHg, avoiding drops below 130–140 mmHg to maintain placental perfusion.
• Labetalol is the first-line agent, administered via bolus or continuous infusion.
• Nicardipine is preferred in those with contraindications to beta-blockers (e.g., asthma, cardiac failure).
• Hydralazine is a third-line agent but carries a higher risk of hypotensive overshoot and less favourable maternal outcomes.
  
  

Delivery Planning

• Caesarean section is indicated for obstetric reasons or failure to progress; it may be considered at <30–32 weeks in the absence of labour.
• Platelet count ≤40,000/mm³ at the time of surgery increases bleeding risk, often requiring platelet transfusion.
• Surgical techniques generally follow standard obstetric practice.
• Regional anaesthesia is contraindicated when platelet count is <80 × 10⁹/L due to epidural haematoma risk.
  
  

Bleeding and Coagulation Management

• Platelet transfusion is required when platelet count is <25 × 10⁹/L or <30 × 10⁹/L in the setting of bleeding, massive transfusion, or planned surgery.
• The response to transfusion is transient due to continued consumption.
• Rho(D) immune globulin should be given to Rh-negative patients if type-specific platelets are unavailable.
• Fibrinogen <2.94 micromol/L (<100 mg/dL) necessitates cryoprecipitate or fresh frozen plasma.
  • One unit of cryoprecipitate contains ~1 g of fibrinogen; 6 units are typically needed to restore haemostasis.
• Avoid pudendal or paracervical blocks due to haematoma risk.
• General anaesthesia is used when regional anaesthesia is contraindicated.
  
  

Haematological Support

• Patients with haematocrit ≤25% may require packed red cell transfusion.
• Anaemia is poorly tolerated in HELLP due to increased oxygen demand and coagulopathy.
  
  

Treatment Goals

• Arrest disease progression.
• Prevent transition to Class 1 HELLP and development of major maternal complications.
• Minimise neonatal morbidity and mortality.
• Plan appropriately timed delivery at a facility with intensive care resources.
  
  

Maternal Outcomes

• Maternal mortality ranges from 1–3%. In a review of 2346 cases between 2001 and 2011, the mortality rate was 3.3%, with cerebral haemorrhage being the leading cause of death.
• Severe maternal morbidity is significantly more likely in complete HELLP syndrome than in partial variants (13% vs. 1%).
• In one cohort, 95% of patients were delivered within 48 hours, underlining the need for rapid clinical intervention.
  
  

Common maternal complications

• Disseminated intravascular coagulation (20–21%)
• Placental abruption (16%)
• Acute kidney injury (7–8%)
• Pulmonary oedema (6%)
• Subcapsular liver haematoma or hepatic rupture (1%)
• Intracerebral haemorrhage (<1%)
• Retinal detachment (1%)
• Major bleeding requiring transfusion (55% in some series; 2% required surgical intervention)
  
  

Rare complications

• Cardiac arrest, myocardial ischaemia
• Cerebral oedema, central venous thrombosis, seizures
• Respiratory failure, pulmonary embolism, adult respiratory distress syndrome (ARDS)
• Hepatic infarction and nephrogenic diabetes insipidus
• Sepsis and wound complications, particularly in thrombocytopenic patients
• In early-onset cases (<23 weeks gestation), maternal complications occurred in 45% of pregnancies, predominantly hepatic, CNS-related, and respiratory.
  
  

Neonatal and Perinatal Outcomes

• Preterm birth
• Fetal growth restriction (seen in ~39% of cases)
• Placental abruption
• Intrauterine asphyxia

Other neonatal complications

• Thrombocytopenia (in up to one-third of neonates), with ~4% experiencing intraventricular haemorrhage
• Leukopenia and neutropenia, generally attributed to fetal growth restriction and prematurity
• Neonatal liver function is typically unaffected by maternal HELLP syndrome
  
  

• 63% were terminated
• Of the 21 continued pregnancies, 10 resulted in early fetal death, 6 in stillbirth, 2 in neonatal death, and 3 live births (all at 23 weeks)
  
  

Recurrence and Future Pregnancy Risk

• The recurrence risk of HELLP syndrome in future pregnancies is generally low (2–6%) but can be higher (up to 20%) in certain populations.
• 20–40% of patients with previous HELLP syndrome may develop pre-eclampsia in a subsequent pregnancy.
• The recurrence rate increases to 75% in those with pre-existing hypertensive disorders.
  
  

• 7% had recurrent HELLP
• 18% developed pre-eclampsia
• 18% developed gestational hypertension
  
  

• 24% developed hypertensive disorders (HELLP, pre-eclampsia, or gestational hypertension) in a second pregnancy
• Recurrence was more common after preterm HELLP than after term HELLP (30.3% vs. 16.5%)
• In patients with a history of liver haematoma, 17% experienced recurrence in subsequent pregnancies.
  
  

Long-Term Health Risks

• Women with a history of HELLP syndrome are at increased risk of future cardiovascular disease, including chronic hypertension and coronary artery disease.
• The extent of long-term risk may differ depending on pre-eclampsia subtype, gestational age at onset, and presence of fetal growth restriction.
• There is no consistent evidence of long-term hepatic or renal sequelae in women who recover from HELLP with or without associated complications.
  
  

Haematological and Coagulation Complications

• Occurs in up to 21% of cases.
• Marked by prolonged prothrombin time, elevated fibrin degradation products, and low fibrinogen (<8.82 micromol/L).
• Should be suspected in patients with bleeding and/or abnormal coagulation results.
• Commonly associated with placental abruption.
• Management is supportive, including transfusion of red cells, fresh frozen plasma, platelets, and cryoprecipitate as required.
  
  

• Affects approximately 16% of patients.
• Clinical signs include vaginal bleeding, abdominal pain, and non-reassuring fetal status.
• May occur before or after the onset of DIC.
• Prompt evaluation with full blood count and coagulation studies is essential.
  
  

Renal Complications

• Seen in 2–8% of cases (up to 20% in earlier studies).
• Oliguria followed by elevated serum creatinine and electrolyte imbalances is characteristic.
• May progress to acute tubular necrosis or cortical necrosis requiring dialysis.
• Risk factors include infection, severe systolic hypertension, and anaemia.
• Most patients recover renal function, but up to 20% may have residual damage.
• Renal biopsy may be indicated for prolonged AKI.
• In the presence of AKI, magnesium sulphate dosing must be carefully adjusted to avoid toxicity.
  
  

Respiratory Complications

• Occurs in approximately 6% of cases.
• Presents with dyspnoea, hypoxaemia, tachypnoea, and basal crackles.
• Common in patients with multisystem involvement and fluid mismanagement.
• Requires careful oxygen supplementation and guided diuresis.
• Pulmonary artery catheterisation may be needed in ICU settings for fluid balance monitoring.
• Acute Respiratory Distress Syndrome (ARDS) may further complicate the picture.
  
  
  

Hepatic and Abdominal Complications

• Occurs in about 1% of patients; usually involves the right hepatic lobe.
• Presents with severe RUQ or epigastric pain, nausea, vomiting, and biochemical signs of liver injury.
• Diagnosis is confirmed with ultrasound, CT, or MRI.
• Treatment is generally supportive; however, rupture is a surgical emergency.
  
  

• Indicates hepatic insufficiency and is an ominous sign of terminal hepatic failure.
• Requires prompt correction to prevent coma or death.
  
  

• May develop postpartum in severe cases.
• Differentiation from intra-abdominal haemorrhage is critical.
• Large-volume ascites may predispose to cardiopulmonary compromise.
  
  
  

Cardiovascular and Long-Term Complications

• HELLP syndrome and hypertensive disorders of pregnancy increase the long-term risk of cardiovascular morbidity, including early-onset hypertension and ischemic heart disease.
• These patients should undergo regular cardiovascular risk assessment postpartum for preventive intervention.
  
  
  
  

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