What is the differential diagnosis for a pregnant patient at 28 weeks gestation with severe preeclampsia, elevated liver enzymes, epigastric pain, hypertension, and thrombocytopenia?

Differential Diagnosis

This patient has HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low Platelets), which is a severe manifestation of preeclampsia, not a separate disorder. 1 However, given the critical deterioration postpartum with persistent symptoms and worsening thrombocytopenia to 20,000/mm³, you must urgently consider life-threatening complications and alternative diagnoses.

Primary Diagnosis: HELLP Syndrome with Postpartum Progression

• HELLP syndrome is confirmed by the triad of hemolysis, transaminases in the 220s range, and severe thrombocytopenia (now 20,000/mm³) 1, 2
• The persistent epigastric pain, elevated liver enzymes, and progressive thrombocytopenia on postoperative day 5 indicate ongoing disease activity despite delivery 1
• HELLP syndrome can worsen or develop postpartum, with symptoms typically resolving within days to weeks after delivery 2, 3

Critical Complications Requiring Immediate Evaluation

Hepatic Complications (Most Urgent)

• Subcapsular liver hematoma or hepatic rupture: The persistent epigastric pain with severe thrombocytopenia (20,000/mm³) and elevated transaminases is highly concerning for hepatic complications 2
• Perform abdominal ultrasound immediately to evaluate for hepatic hematoma, as this is a life-threatening complication requiring surgical intervention 2
• Hepatic complications are more likely with severe thrombocytopenia and persistent right upper quadrant/epigastric pain 2

Ongoing Severe Preeclampsia/HELLP

• Progressive HELLP syndrome: The worsening platelets (98k → 20k) and persistent symptoms indicate disease progression rather than resolution 1
• This represents failure of delivery to halt the disease process, which occurs in a subset of patients 4, 5

Thrombotic Microangiopathy (TMA)

• Atypical hemolytic uremic syndrome (aHUS) or thrombotic thrombocytopenic purpura (TTP): Consider when HELLP syndrome persists or worsens postpartum beyond 72 hours 6
• Check: LDH (markedly elevated in hemolysis), peripheral smear for schistocytes, ADAMTS13 activity, creatinine for renal involvement 6
• These conditions may mimic or coexist with HELLP syndrome and require different management (plasmapheresis, complement inhibition) 6

Additional Differential Considerations

Hematologic Disorders

• Disseminated intravascular coagulation (DIC): Check PT/PTT, fibrinogen, D-dimer to distinguish from isolated thrombocytopenia 1
• Immune thrombocytopenic purpura (ITP): Less likely given the clinical context and elevated liver enzymes, but consider if isolated thrombocytopenia without other HELLP features 4

Infectious/Inflammatory

• Acute fatty liver of pregnancy (AFLP): Can present similarly but typically with more profound coagulopathy, hypoglycemia, and higher bilirubin 4
• Sepsis with hepatic involvement: Consider if fever, leukocytosis, or other infectious signs present 3

Medication-Related

• Drug-induced liver injury: Less likely but consider if new medications introduced postpartum 4

Immediate Management Priorities

This patient requires immediate escalation of care given the critical thrombocytopenia and persistent symptoms:

• Urgent abdominal imaging (ultrasound or CT) to rule out hepatic hematoma/rupture 2
• Platelet transfusion is indicated for platelet count <50,000/mm³ in the postoperative period and <100,000/mm³ given the risk of bleeding 2
• Escalate antihypertensive therapy: BP in 160s on maximum dose nifedipine (120mg) requires addition of second agent (IV labetalol or hydralazine) 1, 2
• Magnesium sulfate for seizure prophylaxis given severe hypertension and HELLP syndrome 1, 2
• Transfer to ICU/high-dependency unit for continuous monitoring given critical thrombocytopenia and persistent symptoms 2
• Laboratory monitoring: CBC with platelets, comprehensive metabolic panel, LDH, peripheral smear, coagulation studies every 6-12 hours 1, 2

Key Clinical Pitfall

Do not assume HELLP syndrome will automatically resolve after delivery. 4, 5 Approximately 30% of HELLP cases develop postpartum, and some patients experience worsening disease despite delivery. 3 The combination of worsening thrombocytopenia (20,000/mm³) and persistent epigastric pain on POD 5 is particularly concerning for hepatic complications or alternative TMA diagnoses requiring urgent intervention. 2, 6