With TTP, intravascular platelet aggregation stimulates a cascade of events leading to end-organ failure. There is endothelial activation and damage, but it is unclear whether this is a consequence or a cause. Elevated levels of unusually large multimers of vWF are identiied with active TTP. Various defects in the ADAMTS13 gene create difering clinical presentations of thrombotic microangiopathy (Camilleri, 2007; Moake, 2002, 2004). In another scheme, antibodies raised against ADAMTS13 neutralize its action to cleave vWF multimers during an acute episode. he end result is micro thrombi of hyaline material consisting of platelets and small amounts of ibrin within arterioles and capillaries. When suicient in number or size, these aggregates produce ischemia or infarctions in various organs.
hrombotic microangiopathies are characterized by thrombocytopenia, fragmentation hemolysis, and variable organ dysfunction. TTP is characterized by the pentad of thrombocytopenia, fever, neurological abnormalities, renal impairment, and hemolytic anemia. HUS typically has more profound renal involvement and fewer neurological aberrations.
hrombocytopenia is usually severe, but fortunately, even with very low platelet counts, spontaneous severe hemorrhage is uncommon. Microangiopathic hemolysis is associated with moderate-to-marked anemia, and erythrocyte transfusions are frequently necessary. he blood smear is characterized by erythrocyte fragmentation with schizocytosis. Reticulocytes and nucleated red blood cells are increased, lactate dehydrogenase (LDH) levels are high, and haptoglobin concentrations are decreased. Consumptive coagulopathy, although common, is usually subtle and clinically insignificant.
The cornerstone of treatment is plasmapheresis with freshfrozen plasma replacement. Plasma exchange removes inhibitors and replaces the ADAMTS13 enzyme (George, 2014; Michael, 2009). Treatment with caplacizumab, the anti-vWF immunoglobulin, inhibits the interaction between ultralarge vWF multimers and platelets (Peyandi, 2016). hese treatments have remarkably improved outcomes in patients with these formerly fatal syndromes. Red cell transfusions are imperative for life-threatening anemia. Treatment is usually continued until the platelet count is > 150,OOO/�L. Unfortunately, relapses are common. Additionally, there may be long-term sequelae such as renal impairment (Dashe, 1998; Vesely, 2015). Treatment for pregnancy-associated HUS, which is complement mediated, uses the anti-C5 humanized monoclonal antibody eculizumab (Ardissino, 2013; Caiigral, 2014; Fakhouri, 2016).
As shown in the Appendix (p. 1256), ADAMTS13 enzyme activity decreases across pregnancy by up to 50 percent (S8nchez-Luceros, 2004). Levels drop even further with the preeclampsia syndrome. his is consonant with prevailing opinions that TTP is more commonly seen during pregnancy. he Parkland Hospital experiences were described by Dashe and coworkers (1998), who identified 11 pregnancies complicated by these syndromes among nearly 275,000 obstetrical patients-a frequency of 1 in 25,000.