Daily therapeutic PEX has to be started as soon as possible (at least 1 but preferably 1.5 plasma volume exchanges daily),
with plasma infusion to be considered only if PEX is not available.
congintal TTP , plasma infusion is sufficient to correct ADAMTS13 severe deficiency
the typical initial schedule requires 10 to 15 mL/kg daily until clinical remission and platelet and LDH normalization and then regular maintenance infusions throughout pregnancy and puerperium (usually twice a month)
For autoimmune TTP, immunosup-pressive therapy is also required; corticosteroids are used as first-line therapy (we usually prescribe oral prednisolone, 1 mg/kg daily), with association of azathioprine as steroid-sparing drug, if appropriate.
Although anti-CD20 therapy has been reported as a salvage therapy in life-threatening gravidic TTP,21 rituximab should be avoided based on the lack of safety evidence in pregnancy and should only be considered postpartum.
If remission is achieved (clinical stability, platelet normalization, and absence of hemolysis), then pregnancy is carried on as long as maternal and fetal conditions allow it.
Along with maternal clinical and biochemical monitoring (including serial ADAMTS13 evaluations),
fetal conditions need to be regularly assessed through fetal ultrasound examination and uterine artery Doppler scan.
The type and frequency of maintenance treatment will be customized but will be needed in almost all women throughout the postpartum period;
in the more benign cases, steroids will be sufficient to suppress autoantibody production, while in the more severe cases, PEX will be continued throughout pregnancy.
In our clinical practice, we monitor ADAMTS13 activity level at least monthly after remission with the aim of maintaining preferably 20% to 25%. The latter alarm threshold for ADAMTS13 activity has been chosen for 2 reasons:
(1) the physiological decline of ADAMTS13 reaches a minimum activity of 25% to 30% during regular pregnancies in healthy women .
(2) reduced levels of ADAMTS13 activity (,25%) in the first trimester may be associated with an increased risk of gravidic complications (both gravidic TTP and miscarriage). Once the platelet count is 50 000/mL, low-dose aspirin and/or thromboprophylaxis with low-molecular-weight heparin can be considered to reduce the risk of additional placental vascular damage, based on fetal and placental scan and overall venous thrombotic risk.
In our clinical practice, we do not routinely prescribe aspirin to all TTP women during pregnancy, unless there is a specific gynecologic indication, since the pathogenesis of clots in acute TTP does not depend on cyclooxygenase-mediated platelet–platelet aggregation but on inappropriate ULVWF-mediated platelet clumping. Last, but not least, we have to consider also the risk of concurrent TMAs during the same pregnancy
and the risk of different gravidic TMAs in subsequent pregnancies. In particular, the risk of PE seems to be higher in women with a history of aTTP (31% vs 3% )The association may be at least partially explained by common risk factors (ie, black race and obesity, both associated with PE and TTP), but also by the possible overlap of pathogenetic mechanisms (for example, through complement activation). Obviously, the coexistence of different TMAs requires a complex multidisciplinary evaluation and appropriate treatment choices.
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