Discussion:

Hemolysis in idiopathic TTP is mechanical and nonimmune mediated, thus Coombs testing is usually negative. Nowadays, autoimmune diseases caused acquired TTP have been explored broadly, which caused vascular endothelial cell damage, release of a large number of vWF, lack of vWF-cp or inhibition of vWF-cp activity, leading to microaggregation of platelets and vWF-fibrinogen, vessel occlusion, and rapid reduction of platelets, and finally resulting in occurrence of TTP6. Coombs testing could be positive in that case, and usually ended with fatality in adult literature 7. A variety of autoimmune disorders may develop several years after the recovery of TTP and such observations highlight the necessity of clinical surveillance 6, however, the guidelines are still missing.
The diagnosis of TTP requires clinical judgment in addition to measurement of ADAMTS13 activity 8. Since rapid ADAMTS13 activity assessment is not available in routinely, leading to diagnostic wanderings with potentially severe consequences on prognosis by delaying therapeutic plasma exchange (TPE) in cases of diagnosis uncertainty. Our current practice continues to treat patients with PEX if they have clinical features of TTP with no alternative diagnosis, even if the ADAMTS13 activity is not available. However, we must balance the risks and benefits for PEX procedure at the first place. Common risks are as follows: hemorrhage or pneumothorax complicating the insertion of central venous catheter, thrombosis or sepsis attributed to central venous catheter, anaphylactic reaction to plasma and cardiac tamponade related to catheter insertion 9. As in this case, the patient responded well with treatment of timely PEX and corticosteroids, however, femoral catheterization associated DVT occurred. It is most probably caused by endothelial damage secondary to intravenous catheters. Then, loss of physiological thromboresistance, leukocyte adhesion to damaged endothelium, complement consumption, abnormal vWF release and fragmentation, and increased vascular shear stress may then sustain and amplify the microangiopathic process. We hypothesis that tries to explain the complications of PEX considers that PEX removed autoantibodies and corrected PLT deficiency, resulting in thrombosis. Low-molecular-weight heparin thromboprophylaxis plus antiplatelet when the platelet count > 50 × 109/l were suggested in clinical work 10. Previous studies have shown that the frequency of mechanical complications is greater with femoral catheterization than with subclavian and internal jugular catheterization 11. However, no specific guidelines regarding catheterization pathway was made yet.
Although the PEX-based method is the recommended acquired TTP treatment worldwide 12, other options could be considered for treating recurring or refractory TTP cases, or when severe adverse effects related to PEX such as bleeding or thrombosis appear13. Since 2002, therapeutic interventions aiming to B-cell depletion and reduction of autoantibodies, with rituximab, appear very effective both as induction therapy for the initiation of remission, as well as maintenance therapy, some even advocate the use of rituximab as routine initial treatment together with PEX and corticosteroids 14; however, the frequencies of severe neurologic abnormalities, exacerbations, and death have not changed, while the frequency of relapse has decreased 15. Recently, treatment of acute episodes of TTP with increasing use of rituximab and the addition of new agents, such as caplacizumab16 and recombinant ADAMTS13 showed to be more effective.
We anticipate that more effective treatment will improve the quality and duration of life for patients in remission from TTP. With more effective treatments, the need for PEX and the risks for complications from PEX may decrease.