Placenta-derived FasL (CD95L), which is toxic to human hepatocytes, leads to hepatocyte apoptosis and necrosis by inducing the expression of TNFα and results in the release of liver enzymes. Hepatic damages are worsened by the disrupted portal and total hepatic blood flow that result as a consequence of the microangiopathies. Collectively, widespread endothelial dysfunction and hepatocellular damage result in global hepatic dysfunction often leading to liver necrosis, haemorrhages, and capsular rupture. Diagnosis
Early and accurate diagnosis, which relies on laboratory tests and imaging exams, is essential for treatment and management and significantly reduces the morbidity rate. However, diagnosis of the syndrome is challenging, especially due to the variability in the signs and symptoms and the lack of consensus amongst healthcare professionals. Similarities to other conditions, as well as normal pregnancy features, commonly lead to misdiagnosed cases or more often, delayed diagnosis.There is a general consensus regarding the main three diagnostic criteria of HELLP syndrome, which include hepatic dysfunction, thrombocytopenia and microangiopathic haemolytic anaemia in patients suspected to have preeclampsia. A blood smear will often exhibit abnormalities, such as schistocytes, bur cells, and helmet cells, which indicate erythrocyte damage. Thrombocytopenia, which is the earliest coagulopathy present in all HELLP syndrome patients, is indicated by low platelet count (below 100 x 109 L-1) or by testing the levels of fibrin metabolites and antithrombin III. Elevated serum levels of certain proteins, in particular, LDH, alanine transaminase (ALT) and aspartate transaminase (AST), are indicative of hepatic dysfunction.
Increasing the understanding of HELLP syndromes pathophysiology will enhance diagnostic accuracy, especially in the early stages. This will lead to advancements in the prevention, management, and treatment of the condition, which will increase the likelihood of both maternal and fetal survival and recovery. Inflammation and coagulation
As a result of endothelial cell injury, a cascade of pathological reactions manifests and become increasingly severe and even fatal as signs and symptoms progress. Following endothelial injury, vasospasms and platelet activation occur alongside the decreased release of the endothelium-derived relaxing factor and increased the release of von Willebrand factor (vWF), leading to general activation of the coagulation cascade and inflammation. Placental components, such as inflammatory cytokines and syncytiotrophoblast particles interact with the maternal immune system and endothelial cells, further promoting coagulation and inflammation. These interactions also elevate leukocyte numbers and interleukin concentrations, as well as increase complement activity. Low platelet count
vWF degradation in HELLP syndrome is inhibited due to decreased levels of degrading proteins, leading to an increased exposure of platelets to vWF. As a result, thrombotic microangiopathies develop and lead to thrombocytopenia. Blood breakdown
As a result of the high number of angiopathies, the erythrocytes fragment as they pass through the blood vessels with damaged endothelium and large fibrin networks, leading to macroangiopathic haemolytic anaemia. As a consequence of hemolysis, lactic acid dehydrogenase (LDH) and hemoglobin are released, with the latter binding to serum bilirubin or haptoglobin. Liver
During the coagulation cascade, fibrin is deposited in the liver and leads to hepatic sinusoidal obstruction and vascular congestion, which increase intrahepatic pressure.