An 8 yr old boy presents to casualty with history of diarrhea, followed by decreased urine output. Blood examination shows thrombocytes: 90,000/cm3. Diagnosis is

Thrombotic thrombocytopenic microangiopathies are a group of disorders characterized by thrombocytopenia, a microangiopathic hemolytic anemia evident by fragmented RBCs and laboratory evidence of hemolysis, and microvascular thrombosis. They include thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS).TTP and HUS have common features of thrombocytopenia, hemolytic anemia, fever, renal failure, and neurologic disturbances; When patients, paicularly children, have more evidence of renal injury, their condition tends to be called HUS; In adults with the neurologic disease, it is considered to be TTP; In adults, there is often a mixture of both, hence called TTP/HUS.Renal biopsy showing glomerular capillary endotheliosis associated with platelet thrombi, damage to the capillary wall, and formation of fibrin material in and around glomeruli; similar lesions occur in preeclampsia/HELLP (hemolysis, elevated liver enzymes, and low platelet count syndrome), malignant hypeension, and the antiphospholipid syndromeCauses of TTP/HUS:PregnancyDrugs like oral contraceptives, quinine; in renal transplant patients given OKT3 for rejectionCalcineurin inhibitors, cyclosporine, and tacrolimusAntiplatelet agents, ticlopidine, and clopidogrelHIV infectionIn DIC, while thrombocytopenia and microangiopathy are seen, a coagulopathy predominates - with consumption of clotting factors and fibrinogen resulting in an elevated prothrombin time (PT) & activated paial thromboplastin time (aPTT); The PT and aPTT are characteristically normal in TTP or HUS.Hemolytic Uremic Syndrome (HUS): Characterized by acute renal failure, microangiopathic hemolytic anemia, and thrombocytopeniaIt is seen predominantly in children; most of the cases preceded by an episode of hemorrhagic diarrhea; Escherichia coli O157: H7 is the most frequent etiologic serotype, followed by Shigella dysenteriae This Shiga toxin (verotoxin) inhibits the endothelial production of ADAMTS13(normally ADAMTS13 metalloprotease cleaves large multimers of von Willebrand&;s factor)Absent ADAMTS13, these large multimers cause platelet clumping and intravascular hemolysisSome children with complement protein deficiencies express atypical HUS (aHUS), which can be treated with the liver transplantTreatment of adult TTP/HUS is daily plasmapheresis; Patients with childhood HUS from infectious diarrhea are not given antibiotics, as antibiotics are thought to accelerate the release of the toxin and the diarrhea is usually self-limited. No intervention appears superior to suppoive therapy in children with post-diarrheal HUS.Ref: Harrison's 18/e p970