Leonor P. Fernando

Improved survival with plasma exchange in patients with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome

PURPOSE Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome are uncommon disorders that are generally fatal if left untreated. Plasma exchange therapy is associated with high response rates and improved short-term survival, but most previous studies have been limited by small numbers of patients or short duration of follow-up. METHODS We performed a retrospective cohort analysis in 126 consecutive patients with thrombotic thrombocytopenic purpura/hemolytic uremic syndrome, most of whom were treated principally with plasma exchange at the Sacramento Medical Foundation Blood (Center and the University of California Davis Medical Center between 1978 and 1998. We measured the effect of therapeutic plasma exchange on 30-day mortality, response rate, and overall survival, and determined which factors were associated with 30-day mortality and relapse. RESULTS The overall 30-day mortality was 10% of the 122 patients who received plasma exchange as their principal treatment (a median of 9 exchanges and a mean cumulative infused volume of 43 +/- 77 L fresh frozen plasma); 56% were complete responders and 21% were partial responders. The relapse rate was 13%. The estimated 2-year survival was about 60%; among patients without serious underlying comorbid conditions, the estimated 2-year survival was about 80%. Each unit increase in clinical severity score (on a 0 to 8 scale) was associated with a 2.2-fold (95% confidence interval [CI]: 1.3 to 3.9) increase in the odds of 30-day mortality. Patients who were febrile at presentation were substantially less likely to suffer a relapse (odds ratio = 0.2; 95% CI: 0.03 to 0.9). CONCLUSION Plasma exchange therapy produced high response and survival rates in this large cohort of patients with thrombotic thrombocytopenic purpura/hemolytic uremic syndrome. The Clinical Severity Score may be useful in predicting 30-day mortality, whereas fever at onset was associated with a lesser risk of relapse. Prospective studies should stratify patients according to these prognostic factors.

Significance of antibody to hepatitis B core antigen in blood donors as determined by their serologic response to hepatitis B vaccine

Because large numbers of volunteer blood donors may be disqualified for “false‐positive” results on tests for antibody to hepatitis B core antigen (anti‐HBc), a more specific definition of anti‐HBc enzyme immunoassay (EIA)‐reactive was evaluated, including only those donor samples that were “strongly” reactive (sample‐to‐cutoff absorbance ratio, < 0.45). Results using this definition and other anti‐HBc test methods were compared to the serologic response (antibody to hepatitis B surface antigen [anti‐HBsAg]) to hepatitis B vaccination. Fifty‐eight volunteer blood donors who had previously been deferred as donors, because of reactive anti‐HBc tests (all other blood screening tests were negative, including those for HBsAg and anti‐HBsAg) on two occasions, were vaccinated for hepatitis B. It was assumed that an anamnestic response to vaccine indicated past infection with hepatitis B, while a primary response to vaccine indicated lack of past infection. One (2%) of 43 donors with a historically “weak” anti‐HBc (reactive absorbance ratio, > or = 0.45) had an anamnestic response to vaccine, compared to 8 (53%) of 15 with historically “strong” anti‐HBc (reactive absorbance ratio, < 0.45) (p < 0.005). Anti‐HBc testing using the microparticle EIA method also correlated well with hepatitis B vaccination results. The use of a narrower definition of “reactive” for anti‐HBc EIA testing yielded much more specific, but slightly less sensitive, results.

HIV Transmissions From a Window-Period Platelet Donation

Recently, blood centers began investigational testing for HIV RNA by pooled nucleic acid testing (NAT). A 35-year-old frequent platelet donor tested HIV p24 antigen positive, antibody negative before implementation of NAT. He made 2 platelet donations (day -4 and -11) immediately before testing positive for HIV. The donors HIV seroconversion was monitored, and stored samples were tested retrospectively for HIV RNA. Platelet recipients were tested for HIV infection. The day -4 sample tested positive for HIV RNA by pooled and individual sample NAT. The day -11 sample tested negative for HIV RNA by both NAT tests. The 2 recipients of the day -4 platelets tested HIV RNA and p24 antigen positive. The recipient of the day -11 platelets could not be tested because he had died. HIV NAT would have prevented transmission of HIV had it been available at the time of this donors HIV seroconversion.

Exclusive use of acid citrate dextrose for anticoagulation during extracorporeal photopheresis in patients with contraindications to heparin: An effective protocol†

Extracorporeal photopheresis (ECP) routinely uses heparin for anticoagulation. For patients with contraindications to heparin, alternative anticoagulation using acid citrate dextrose (ACD‐A) has been reported to be safe and effective. However, detailed ECP protocols that exclusively use ACD‐A anticoagulation and minimize citrate toxicity have not yet been published. We report a protocol that completely replaces heparin with ACD‐A for ECP, which was developed at the University of California, Los Angeles (UCLA), and our experience since its implementation. ECP was performed with the UVAR XTS photopheresis system using ACD‐A and control of the rate of citrate infusion. Calcium gluconate solution was administered prophylactically and as needed for symptoms of citrate toxicity. The medical records of patients who underwent ECP using the ACD‐A protocol between January 2003 and July 2006 were reviewed. The incidence and severity of citrate toxicity and the technical data for all procedures were analyzed. During this period, 94 ECP procedures were performed with ACD‐A anticoagulation on five patients. All patients tolerated the procedures well without significant complications. Only minimal symptoms of citrate toxicity (grade 1) were observed in 24.5% of all procedures; symptoms resolved promptly following administration of additional calcium gluconate. In conclusion, an effective protocol for ECP using ACD‐A anticoagulation exclusively in patients with contraindications to heparin employs continuous monitoring of flow rates and prophylactic administration of calcium gluconate to minimize citrate toxicity. J. Clin. Apheresis, 2008. Published 2008 Wiley‐Liss, Inc.

Evidence that use of a second-generation hepatitis C antibody assay prevents additional cases of transfusion-transmitted hepatitis

SUMMARY. The aim of this study was to determine if using hepatitis C antibody (anti‐HCV) enzyme immunoassay version 2.0 (EIA2) in addition to version 1.0 (EIA1) increased the safety of the blood supply. Blood non‐reactive by anti‐HCV EIA1 was transfused in 1990‐92. Stored samples from 40098 units, donated prior to 13 March 1992 were later tested by EIA2. For donor units reactive for anti‐HCV by EIA2. a recombinant immunoblot assay (RIBA2) was also carried out. In 63 cases, recipients of transfusions which were EIAZ negative or EIA2 reactive were tested for anti‐HCV and elevated alanine aminotransferase (ALT) levels 9‐1 2 months after transfusion: pretransfusion anti‐HCV status of recipients was unknown. Among these multitransfused patients receiving units that were negative by both EIA1 and EIA2, 1/26 (4%) had anti‐HCV. Among transfusion recipients of units negative by EIA1, but who received at least one unit reactive by EIA2,4/37 recipients (11%) were anti‐HCV reactive (P = 0.59). For the recipients of EIA2 reactive blood, when the donor unit was RIBA2 non‐reactive. 0/23 recipients were reactive by anti‐HCV. Among the recipients of a RIBA2 indeterminate unit, 1/10 recipients had anti‐HCV, but for patients who received at least one RIBA2 reactive unit, 3/4 recipients had anti‐HCV (P = 0.0 3). Hence. second‐generation anti‐HCV testing detected additional units capable of transmitting hepatitis C that were not detected by first‐generation testing. However, RIBA2 is a more specific method than EM2 for determining units capable of transmitting HCV.

Venous access for hematopoietic progenitor cell collection

Hematopoietic Progenitor Cell (HPC) collection by apheresis is performed in patients and donors to obtain HPCs for transplantation. Although studies have shown these procedures to be safe, successful collection cannot be performed without establishment of venous access. This projects objective was to ascertain the current practices of donor vein assessment and central venous catheter (CVC) usage. Methods: The American Society for Apheresis (ASFA) HPC subcommittee created an electronic survey about precollection vein assessment and line placement, care, and removal in autologous and allogeneic donors. It was distributed to >5,000 possible participants, with one response analyzed per institution. Results: One hundred centers performing autologous and/or allogeneic procedures provided adequate responses for analysis. Donor vein assessment is most often performed by apheresis staff more than 1 week prior to collection. For patients with questionable access, the next step performed most often is secondary assessment for autologous procedures and CVC placement for allogeneic procedures. Most centers use interventional radiology to place CVCs in jugular veins on collection day with placement verification through electronic medical records. Verbal and written postinsertion CVC care instructions are routinely provided. The apheresis team frequently provides postinsertion CVC care for autologous patients. Heparin is used most often for CVC lock. When used, tissue plasminogen activator is usually instilled for up to 60 min. Conclusion: These data summarize the largest single survey of donor vein assessment at institutions performing HPC collections by apheresis. The variations identified in donor venous access practice warrant further investigation and consensus to establish best practices. J. Clin. Apheresis 31:529–534, 2016.