Diagnosis of thrombotic thrombocytopenic purpura with normal ADAMTS13 activity and absence of its inhibitor (anti‐ADAMTS13 antibodies)

Abstract

To the Editor: We read with interest the case report by Martin et al. [1], who described a Jehovah's Witness patient, who was treated for dysuria by trimethoprim-sulfamethoxazole and later found to be febrile, tachycardic, hypotensive, and to have a diffuse urticarial rash. Patient laboratory results revealed anemia, thrombocytopenia with platelets of 76,000 Â 10 9 , elevated lactate dehydrogenase up to 10,041 U/L, and blood smear with >50 schistocytes per 100Â field. The patient's ADAMTS13 activity and its inhibitor (autologous anti-ADAMTS13 antibodies) were normal. The patient was diagnosed with thrombotic thrombocytopenic purpura (TTP) and treated with IVIG, steroids and rituximab. In the light of the recent discovery that inhibition of ADAMTS13 activity (a von Willebrand factor cleaving protease) by its autoantibodies is a hallmark and specific for autoimmune TTP [2,3], normal ADAMTS13 activity and absence of inhibitors in this patient made TTP diagnosis questionable. The moderate thrombocytopenia, increase of LDH and presence of schistocytes could result from HUS, DIC, and other microangiopathic conditions. The authors suggested the hypersensitivity to the drug as a cause of TTP. The hypersensitivity and damage of endothelium or a problem with the complement system points to HUS rather than TTP. In addition, if patient was negative for the autoantibody, what is the rational in using rituximab for the treatment? We understand that there is a lot of confusion in differentiation among different causes of microangiopathic hemolysis and thrombocytopenia (MIHT), because the pathogenesis of microvascular thrombosis is unknown [2]. However, let us agree that an autoimmune nonhereditary TTP diagnosis in patient with MIHT must have low ADAMTS13 activity and the presence of inhibitory anti-ADAMTS13 antibodies. FOUAD N. BOCTOR Response to Boctor and SmithTo the Editor: Drs. Boctor and Smith highlight the difficulty in establishing a correct diagnosis of TTP, a disorder with multiple etiologies ranging from idiopathic (classically associated with ADAMTS13 inhibitor) to secondary causes stemming from pregnancy, drugs, autoimmune reactions, and bone marrow transplantation. Irrespective of the cause, it is critical to distinguish TTP from other microangiopathic processes, such as sepsis, disseminated cancer and malignant hypertension, because the approach to each of these conditions is therapeutically distinct. In our patient, we arrived at the diagnosis of TTP after carefully excluding alternative causes. We excluded sepsisinduced DIC based on the patient's otherwise well observed clinical appearance (despite high fevers), examination (nonhemorrhagic urticarial rash and normal blood pressures), and laboratory tests (normal fibrinogen, urine, and blood cultures). We excluded disseminated cancer and malignant hypertension based on her clinical history, physical examination, and normal blood pressures. Because our patient presented with a normal serum creatinine and maintained normal renal function throughout her hospitaliz...

Nonsteroidal Anti-inflammatory Drug Induced Thrombotic Thrombocytopenic Purpura

“…It is important to recognize that levels of this protein can be variable and even normal in several of the drugs associated with TTP. 8 In one study, the variability in TTP ranged from 13-70%. 9 Therefore, a decrease in ADAMTS13 activity and the presence of its antibody is more complementary to the diagnosis and overall clinical picture.…”

ADAMTS13 activity and inhibitor

“…For now, it should not be used for initial diagnosis or as an indicator of prognosis for short-term outcomes. For additional valuable general references published in the American Journal of Hematology, see [25][26][27][28][29][30][31][32].…”