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.