Contributed by Peter Christakos MD, Ileana Lopez MD, Darell Triulzi, MD FINAL DIAGNOSIS: HEMOLYTIC UREMIC SYNDROME OF PREGNANCY
DISCUSSION:
HUS of pregnancy most commonly occurs in primiparous females after an otherwise uncomplicated gestation and delivery. It is characterized by renal failure, thrombocytopenia and thrombotic MAHA in post partum women without preeclampsia, hemorrhagic shock, DIC or sepsis. The onset of renal failure, thrombocytopenia, MAHA, normal PT, PTT, and relatively mild elevated LFTs support the diagnosis of HUS of pregnancy. Renal failure, the predominant abnormality in this patient, most often occurs in the early postpartum period. HUS is a rare disorder, less common than preeclampsia or HELLP in this patient population. Severe hypertension, congestive heart failure and neurologic symptoms develop secondary to uncontrolled renal failure.
HUS is more common in children than adults, and has been associated with many other disorders, including E. coli 0157:H7 infection (due to a shiga like toxin), HIV, oral contraceptive pills, autoimmune diseases (systemic lupus erythematosus, SLE), bone marrow transplantation, cancer, and cyclosporin and other medications. TTP and HUS are beleived to be different clinical manifestations of the same underlying disease.
The central pathologic feature of both disorders is the formation of platelet thrombi in the microvasculature which may produce tissue ischemia and infarction. Immunohistochemically, the platelet thrombi contain large amounts of von Willebrand factor (VWF). These thrombi cause shearing stress on the red blood cells passing through the capillaries causing fragmentation ( thrombotic MAHA). The etiology of HUS is unknown. Recent studies have suggested that endothelial cells are damaged, thereby releasing large amounts of abnormal ultralarge VWF multimers into the circulation, which in turn, act as potent platelet aggregators. These ultralarge VWF multimers are increased in the serum of patients with acute disease but are not generally present in patients who have recovered from the acute event. If detectable levels are found in the plasma in an asymptomatic patient, it may signify ongoing endothelial injury. Some patients have decreased production of prostacyclin (PGI2), a potent platelet aggregation inhibitor normally produced in the endothelial cell, which may reflect underlying endothelial cell dysfunction. Other evidence exists for immune mediated injury to the vascular endothelium triggering the chain of events. Apoptosis of vascular endothelium has also been hypothesized as a mechanism of endothelial injury. The empiric evidence that patients improve when their plasma is replaced with normal plasma suggests that some unknown beneficial factor is missing from the plasma of patients with HUS.
With plasmapheresis, now the mainstay of treatment, most patients (80-90%) will survive an acute episode of HUS. Plasmapheresis is accomplished by removing the patient's plasma and replacing it with normal plasma. Treatment should begin as early as possible, usually when thrombocytopenia with thrombotic MAHA are noted in the absence of any other conditions to explain these findings. Daily treatments should continue until the patient improves clinically and the thrombocytopenia and the thrombotic MAHA resolves (evidenced by normalization of LDH). In one study, initial response rates to plasmapheresis were 81%. Three quarters of the non-responders died, and 38% of those responding required additional therapy. Most recurrences occur within 1 month of initial treatment, but recurrences may occur up to 5 years later . Plasma infusion can be used alone, but is less effective than plasmapherisis (31% initial response compared to 78%). Steroids and anti-platelet therapy are often used as adjuvant therapy with plasmapheresis. Immunoabsorption, splenectomy, intravenous gamma globulin, and vincristine should be considered as second line therapies, and used when a patient does not respond to pheresis. Other supportive therapies are often needed, including red cell replacement, hemodialysis, antihypertensives, and seizure prophylaxis, especially in children. It is important to avoid platelet transfusions, as they will add to the extent and severity of the microvascular thrombi.
The prognosis for HUS in pregnancy is poor, with a high maternal mortality, ranging from 18-44% and associated fetal loss at 80%. Forty four percent of women had residual neurologic or renal sequelae, most often chronic renal failure. Recurrences occur in over half of patients responding initially, usually within the first 2 months. The risk of recurrence in subsequent pregnancies is low.
REFERENCES
Contributed by Peter Christakos MD, Ileana Lopez MD, Darell Triulzi, MD
