Abstract
Abstract INTRODUCTION: Therapeutic plasma exchange with infusion of FFP (TPE/FFP) is a standard therapy for TTP. However TPE requires insertion of central lines and is associated with increased morbidity such as line-related infections and sepsis. Danazol has two relevant properties: immune modulation and enzyme induction. The former was exploited in autoimmune diseases such as ITP and the latter in disorders of enzyme deficiencies such as hereditary angioneurotic edema. TTP is an autoimmune disorder with deficiency of the enzyme, ADAMTS13. We investigated danazol therapy in patients with TTP and measured ADAMTS13 activities prior to and post danazol. METHODS: We studied 7 patients (pts) with diagnosis of TTP, and 10 non-TTP pts (4 ITP, 2 thrombocytopenias of other cause, 2 autoimmune hemolytic anemia, 2 lympho- or myeloproliferative disorders). Both TTP and non-TTP patients were treated with danazol. All 7 TTP patients were female with mean age of 42. Four of the TTP patients (Group A) failed or had complications with TPE/FFP, requiring over 2 wks of hospitalization prior to starting danazol. The new regimen includes (1) administration of danazol at 200 mg 2–4 times daily, (2) removal of central lines and discontinuation of TPE when platelet counts stabilized, (3) infusion of FFP through peripheral vein. While monitoring platelet counts and LDH, FFP infusion was gradually tapered and stopped and danazol was continued for an additional 8–20 wks. In the remaining pts with TTP (Group B), danazol was started on admission along with TPE in two pts and FFP alone in one. ADAMTS13 was assayed by the FRETS-vWF73 method [Brit J Haem2005; 129:93] before and after 2–5 wks of danazol. Parameters evaluated were clinical and laboratory improvement, complications, requirement for TPE and FFP, and levels of ADAMTS13 activity. RESULTS: All 4 pts in Group A, who failed or had complications with TPE/FFP, responded well to the regimen, requiring fewer TPE and FFP infusions. The mean number of TPE was reduced by 88% post-danazol and mean number of FFP reduced by 79%. Their hospital stays were shorter. The 3 pts (Group B) who received danazol on admission also responded well. Patient B#1, with 20 yr history of TTP and numerous recurrences, required 1–2 weeks of hospitalizations with the new regimen, compared to 3–8 wks in her previous admissions. Patient B#3 who had FFP infusion alone had an excellent response but danazol had to be stopped because of abnormal liver function; she then relapsed necessitating TPE/FFP. ADAMTS13 activities were measured in 5 TTP pts: mean activity rose from 25.2% pre-danazol to 80.2% post (p=0.007). In the 10 non-TTP pts, the mean activity increased from 61.1% to 75.0% (p=0.03) pre-/post-danazol. CONCLUSION. Danazol with FFP infusion was effective in all TTP pts. Danazol significantly reduced requirement of TPE and infusion of FFP and increased ADAMTS13 activity in both TTP and non-TTP patients. Use of danazol with FFP infusion through peripheral veins avoided complications of central lines required for TPE and reduced hospital stays. We suggest that early addition of danazol and early switching from TPE/FFP to the new regimen would benefit patients with TTP. However, a larger-scale randomized prospective study is needed to rigorously evaluate the efficacy and indications for this regimen.