Clinical TTP relapse: tpenia or MAHA with reduction in ADAMTS13 level
ADAMTS 13 relapse: no thrombocytopenia or anemia, only ADAMTS 13 <20%[ although by definition initial diagnosis of TTP needs enz levels < 10%]
In a patient with suspected TTP, calculate PLASMIC score.
Send ADAMTS 13 level and level of ADAMTS 13 inhibitor.
LDH, peripheral smear review
Look for reversible causes ( tend to have fewer relapses if reversible or transient risk factors)
Current RX:
1. Plasma exchange with FFP
2. Immunosuppression -steroids
3. Rituxan to eliminate the B lymphocytes making the acquired Ig G antibody against ADAMTS 13
4. Caplacizumab: a synthetic antibody which inhibits the interaction between platelets and the von Willebrand factor A1 domain ( thus inducing a type 2M VWD acquired, so stopping the plt from being trapped by the large VWD multimers):
"Data do not support the routine use of caplacizumab in unselected patients with iTTP (grade IB). Major outcomes of clinical concern such as mortality and cardiovascular and neurological events are not significantly reduced by caplacizumab. The possible up-front reduction in TPE requirement and hospital stay associated with caplacizumab must be balanced against the significant safety signals seen for relapse and hemorrhage" [ ASH education book 2022]
It reduces TTP recurrence to 13% compared to 38% in the standard arm.
The use of rituxan upfront does not reduce late recurrence of TTP although it reduces recurrence in the short term ( 5 yr ).
Clinical factors in early relapse:
Afro Caribbean population at risk, same HLA genotypes as in SLE
6% of TTP relapse around the 12 month mark and every 1-2 yr
Other immune suppressants such as mycophenolate and bortezomib should be considered in CD 20 resistant cases
Rituxan rx is effective in preventing clinical relapses
ADAMTS 13 relapses may be asymptomatic in 60% but in 40% CNS symptoms such as headache, lethargy even stroke and GI symptoms have been reported rarely.
