Nine years of cascade filtration for thrombotic thrombocytopenic purpura.
Thrombotic thrombocytopenic purpura (TTP) continues to attract physicians' attention because of its unpredictable course and underlying pathogenetic mechanisms. It is also attractive because of its optimal response to therapeutic plasma exchange (PE) even in the most severe cases. The usual approach to its treatment is conventional PE with plasma substitution and only recently fresh frozen plasma (FFP) has been substituted by cryodepleted or virally inactivated plasma with clinical results that are, if not better, at least comparable with the ones attained when FFP is employed. Nonetheless, no consensus exists regarding the optimal PE fluid and this is not of marginal interest as even after PE treatment mortality is still from 15 to 20%. On the contrary, some consensus exists on the pathogenetic relevance of the exceedingly large Von Willebrand (vWF) multimers whose presence parallels the clinical course and appears to be determined by the abnormalities in the production or function and survival of vWF-cleaving proteases which is auto-antibody mediated. In both cases plasmapheresis without plasma infusion is relatively ineffective, perhaps because it does not increase protease activity. Paradoxically, cascade filtration (CF) can produce the same favorable results without replacing any protease activity. As with CF, the replacement is the autologous plasma with approximately 20% levels of vWF, fibrinogen, fibronectin, IgM and circulating immune complexes and 75% of albumin, IgGs, AT III and proteins whose molecular weight exceeds 250-300000 Da. Our experience with CF for TTP began in 1994. Since then, 16 patients have undergone CF combined with decreasing amounts of FFP supplementation and since 1998 without any allogeneic FFP supplementation in 9 cases. Twenty-four patients (96%) treated with no or minimal amounts of FFP survived but four (16%) experienced from one to four recurrences associated with cutaneous, paradental, cholecystic and vaginal infections. Only one patient died (5%) after the second CF procedure. There were no untoward effects related to the procedure itself and up to 18 procedures in one patient were carried out over 16 months, 10 with the patient in her sixth month of pregnancy and four in the post partum period in preparation for a splenectomy. Remission was achieved after an average number of treatments (10.7 +/- 6.8); a result that compares favorably with those of our historical control group of 47 cases (14 +/- 13). The patient's exposure to allogenic plasma which was 10.8 +/- 4.6 plasma U/session was reduced to 0 in 10 patients, to 1.4 +/- 1.2 and 4.4 +/- 2.3 plasma U/session, respectively, for seven and nine patients receiving PE + CF and CF with same plasma supplementation as described in our previous article. Based on our experience, we believe CF is presently the optimal treatment for patients with classic, sporadic TTP.
Valbonesi
M
M
Department of Immunohematology, San Martino University Hospital, Genova, Italy. mauro.valbonesi@hsanmartino.liguria.it
Giannini
G
G
D005260:Female; D006440:Hemofiltration / Q000379:methods; D006801:Humans; D010951:Plasma Exchange / Q000379:methods*; D010956:Plasmapheresis / Q000379:methods*; D011247:Pregnancy; D011697:Purpura, Thrombotic Thrombocytopenic / Q000628:therapy*