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SERF-TTP is the first prospective case-control study to investigate epidemiology, risk factors & outcomes in patients with first episode of idiopathic TTP. METHODS: Each case of TTP is identified upon referral for therapeutic plasma exchange (TPE). Exclusion criteria include organ or allogeneic stem cell transplant, anti-neoplastic therapy or malignancy. 2 age & gender-matched controls are identified for each case. Epidemiologic information, lab data & plasma samples are collected from each case. Case & control data are collected by standardized interview. Relative risk & 95% CI computed by chi-squared tests. ADAMTS13 activity & inhibitor are centrally measured on pre-TPE samples. ADAMTS13 activity is measured by FRETS-vWF73 assay (Peptides Int.). ADAMTS13 inhibitor is assessed by Technozym ADAMTS13 INH ELISA (Technoclone). RESULTS: Data is available for 67 cases & 138 controls. The median age of cases is 40, & 82% are female. Medical history & exposures are shown in Table 1. Clinical & lab characteristics vary by ADAMTS13 activity (Table 2). Low titer ADAMTS13 inhibitors are detectable in some patients with normal ADAMTS13 activity. 30 day survival of cases is 95.7%. Adverse reactions to TPE occur in 59% of patients, most commonly allergic(85%) or citrate-related reactions(65%). 14.7% had a venous access complication, 50% were catheter-related thromboses. 10% of all adverse events required an ICU admission. CONCLUSIONS: Preliminary results from the case-control study suggest that predisposing factors for the development of TTP include recent infection or connective tissue disorder. Cardiovascular disease, prior history of venous thrombosis, clopidogrel use and lower income are more common in TTP cases than controls. Patients with normal ADAMTS13 activity are more likely to present with higher platelet count, abnormal renal function and neurologic symptoms. Case & Control Characteristics Cases (n=67) Controls (n=138) Relative Risk (95% CI) Medical History Connective Tissue Disease 11.9% 2.2% 5.4 (1.5–20.0) Cardiovascular Disease 13.4% 3.6% 3.7 (1.29–10.6) Prior Venous Thrombosis 13.4% 2.9% 4.6 (1.48–14.5) Infection (prior 2 wks) 32.8% 10.1% 3.2 (1.77–5.9) Medications (prior 12 wks) Antibiotics 31.3% 17.4% 1.8 (1.08–2.99) Clopidogrel 4.5% 0.7% 6.4 (0.65–62.9) Income Level < $25,000 42% 18% 2.3 (1.47–3.6) $25,000 – 70,000 37.3% 52.9% 0.7 (0.49–0.99) > $70,000 11.9% 24.6% 0.5 (0.24–0.98) Characteristics by ADAMTS13 activity ADAMTS13 activity N ADAMTS13 inhibitor (>15 u/ml) ADAMTS13 inhibitor titer (mean) Platelets (mean) Creatinine (mean) Neurologic symptoms Survival Comparison of ADAMTS13 ≤20% vs > 20%, p-values: * 0.0028, † 0.003, ‡ 0.73, # 0.48. < 5% 18 (37.5%) 100% 80.9 22,350 1.4 44% 94% 5–20% 4 (8.3%) 100% 76.4 20,000 1.1 75% 100% > 20% 26 (54.2%) 57.7% 22.5 58,810* 4.3† 58%‡ 89.5%#

CD34+ cells that co-express KDR (a VEGF receptor) have been identified in umbilical cord blood (CB) and shown to be rich in primitive stem cell activity. We studied the production of CD34+KDR+ cells in stem cell “expansion” cultures. CD34+ cells were isolated from CB and cultured for 2, 4, and 6 weeks in serum-free medium supplemented with 5% CB plasma in the presence of rhSCF (20 ng/ml), rhTPO, rhFLT-3L and ± rhVEGF (50 ng/ml). By flow cytometry, the fraction of CD34-selected cells that were also KDR+ was 1.6 ± 0.3% prior to culture. After 2 weeks in culture, in the presence of rhSCF, rhTPO, and rhFLT-3L, the percent of CD34+KDR+ cells increased to 5.7 ± 3.2% with a CD34+KDR+ increase of 112-fold and all overall increase of 43-fold in total cell number. After 4 weeks in culture (± VEGF), CD34+KDR+ cells had increased >200-fold. Total cell expansion at week 6 was: 121-fold and 110-fold (with or without VEGF added, respectively). VEGF supplemented cultures had slightly greater numbers of CFU-GM and HPP-CFC. In addition, after 2 weeks in culture (without VEGF), we observed that 7–26% of the KDR+CD34+ were CD38− while cultures with VEGF contained 13–38% CD34+KDR+CD38− cells, possibly indicating the presence of a more primitive stem cell subset in these cultures.

Current platelet crossmatch procedures to select compatible donors for alloimmunized thrombocytopenic patients are hampered by the lack of a convenient platelet storage method. This study examined the feasibility of using washed apheresis donor platelets stored for up to 1 year in a modified Hank's buffer solution at 4 degrees C as crossmatch reagents in an indirect IgG-enzyme immunoassay. Pooled and monospecific HLA and PlA1 antisera were used to determine the antigenic reactivity of donor platelets in relation to duration of storage. There were no significant differences between mean HLA and PlA1 antigen expression in fresh and stored platelets. HLA reactivity was detected on 12 of 13 donor platelet samples stored for 3 to 9 months and on 14 of 17 platelets stored for 12 to 14 months. PlA1 reactivity was maintained at 12 to 14 months for all 12 donor platelet samples tested. In addition, incompatibility remained in 23 of 24 paired fresh and stored platelet crossmatches using individual alloimmunized patient plasmas. These data indicate that both HLA and platelet-specific PlA1 antigen reactivity can be maintained adequately in liquid storage at 4 degrees C for up to 1 year. The availability of a convenient platelet storage method should facilitate the general application of platelet crossmatching procedures for alloimmunized patients.

Six intraoperative blood samples were obtained at intervals from each of 100 individuals undergoing their first liver transplants. The patients fell into the following diagnostic categories: postnecrotic cirrhosis 28, primary biliary cirrhosis 20, sclerosing cholangitis 19, miscellaneous diseases 14, carcinoma/neoplasia 12 and fulminant hepatitis 7. Coagulation factor values in the initial (baseline) blood samples varied by patient diagnosis. In general, all factor levels were reduced except factor VIII:C, which was increased to almost twice normal. The slight intraoperative changes in factors II, VII, IX, X, XI and XII suggested that a steady-state relationship existed between depletion (consumption/bleeding) and repletion (transfusion, transit from extra- to intravascular space), even in the anhepatic state. In contrast, there were rapid and very significant falls in factor VIII and fibrinogen and a less pronounced decrease in factor V, all reaching their nadirs in early to mid-Stage III. The cause of these coagulation changes appears to be activation of the fibrinolytic system.

Platelet-associated IgG was markedly elevated in three patients with myelodysplasia and severe thrombocytopenia that had become refractory to platelet transfusions. The patients were treated with danazol because of its efficacy in treating immune thrombocytopenic purpura where platelet destruction is primarily mediated by IgG autoantibodies. After danazol therapy, the platelet counts of each patient rose and clinical bleeding stopped, and a decline in hemolysis was seen in two patients. Danazol probably impeded the peripheral clearance of cells by macrophages; however, a beneficial effect of danazol on hematopoiesis cannot be excluded.