Pathophysiology of HELLP Syndrome
HELLP syndrome results from inadequate placental perfusion leading to endothelial dysfunction, which triggers a cascade of platelet aggregation, microangiopathic hemolysis, and hepatic ischemia through fibrin deposition in small vessels. 1
Initial Placental Pathology
The pathophysiologic cascade begins with defective arterial placental perfusion and inadequate placental vessel development, resulting in placental ischemia. 1, 2 This ischemic placenta releases an imbalance of vasoactive substances:
- Increased vasoconstrictors: thromboxane A2, angiotensin, prostaglandin F2, and endothelin-1 are released from the ischemic placenta 2
- Decreased vasodilators: prostacyclin, prostaglandin E2, and nitric oxide production is reduced 2
- The resulting imbalance causes intense systemic vasospasm and multiorgan endothelial damage 2
Endothelial Dysfunction and Systemic Effects
The placenta releases nitric oxide, prostaglandins, and endothelin, which induce platelet aggregation, endothelial dysfunction, and arterial hypertension. 1 Recent evidence suggests the endothelial glycocalyx may be the missing link between angiogenic imbalance and complement activation, with HELLP syndrome falling within the spectrum of secondary microangiopathy due to abnormal complement activation. 3
Multiple genetic, coagulation, and immunologic disorders contribute to the endothelial damage, creating a pro-coagulatory imbalance in the placental microcirculation. 4 Endothelial damage causes:
- Tissue thromboplastin release and coagulation cascade activation due to collagen exposure 4
- Increased thromboplastin in the bloodstream triggering distant coagulation processes 4
- Compensated disseminated intravascular coagulopathy with decreased antithrombin III and protein C activity 4
Microangiopathic Hemolytic Anemia
Fibrin is released from endothelial damage and forms cross-linked networks in small blood vessels. 1 Red blood cells fragment as they pass through this damaged endothelium with fibrin deposition, creating the microangiopathic hemolytic anemia evidenced by schistocytes on peripheral smear and elevated LDH. 5, 6
Fibrin and platelets deposit on endothelial surfaces, directly causing the hemolytic anemia, elevated liver enzymes, and low platelets that define the syndrome. 2
Hepatic Involvement
Hepatic involvement is secondary to fibrin deposition within the hepatic sinusoids, resulting in sinusoidal obstruction and subsequent hepatic ischemia. 1 This mechanism can progress to:
The degree of liver dysfunction correlates directly with the severity of thrombocytopenia and predicts adverse maternal outcomes. 5, 6
Temporal Progression
The intensity of HELLP syndrome peaks 24 hours after delivery, with laboratory abnormalities taking up to 10 days to fully resolve. 5, 2 Approximately 30% of cases occur or worsen within 48-72 hours postpartum, necessitating vigilant monitoring during this critical window. 6
Key Clinical Correlation
LDH serves as a dual marker reflecting both the extent of hemolysis and hepatic dysfunction, making it one of the two best tests (along with platelet count) to monitor disease progression. 5, 6, 2