Cardiogenic shock complicates successful treatment of refractory thrombotic thrombocytopenia purpura with rituximab.

BACKGROUND: Treatment of thrombotic thrombo-cytopenia purpura (TTP) with daily therapeutic plasma exchange (TPE) may be accompanied by a variety of adjunctive interventions including most recently rituximab. Rituximab, a murine and human monoclonal antibody directed against CD20 antigen on B lymphocytes, is primarily used for treatment of non-Hodgkin's lymphomas. Because of severe and fatal infusion reactions including heart failure, rituximab carries a boxed warning. CASE REPORT: A 20-year-old female presented with TTP. She underwent 17 daily (1 day skipped) TPE. Her platelet (PLT) count reached 150 x 10(9) per L and then gradually declined to 36 x 10(9) per L despite continuing TPE. Because of the refractory behavior of her disease, rituximab was administered. After the rituximab infusion, she developed a nonproductive cough which progressed to a productive cough, acute respiratory failure, chest pain, and hypotension and was moved to intensive care for management of biventricular cardiogenic shock (ejection fraction was 5%-10%). Once stable in the intensive care unit, TPE was resumed. Her PLT count reached 241 x 10(9) per L, and her lactate dehydrogenase decreased to normal after four TPEs. Her heart failure completely resolved and she was discharged. Rituximab was added to her medical record as a drug allergy. CONCLUSION: Refractory TTP has been reported to respond favorably to rituximab when used as an adjunct. Interventions, however, can also carry significant risk as illustrated by the cardiogenic shock in our patient. Use of rituximab for refractory TTP should follow a careful assessment of benefits.

Evaluation of BacT/ALERT plastic culture bottles for use in testing pooled whole blood-derived leukoreduced platelet-rich plasma platelets with a single contaminated unit.

BACKGROUND: In certain countries, whole blood-derived platelet (PLT)-rich plasma PLTs can only be pooled within 4 hours of transfusion. One prerequisite for prestorage pooling is the ability to detect low levels of bacteria from a single unit (approx. 10 colony-forming units [CFUs]/mL) once pooled (10/6 approx. 2 CFUs/mL). This study evaluated the BacT/ALERT (bioMérieux) for detection of bacteria in 1 unit of a 6-unit pool. STUDY DESIGN AND METHODS: Bacillus cereus, Clostridium perfringens, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Staphylococcus epidermidis, Serratia marcescens, Streptococcus viridans, and Propionibacterium acnes were inoculated into single PLT units (target, 10 and 100 CFUs/mL; mean recovered, 5 and 92 CFUs/mL) and then pooled with 5 sterile units. Four milliliters was inoculated into both plastic aerobic and anaerobic bottles, and 0.5 mL was plated (10 sets). RESULTS: All cases were detected when the single unit had at least 6 CFUs per mL. With B. cereus (< or =2 CFUs/mL), all bottles were reactive. With K. pneumoniae and S. viridans (< or =3 CFUs/mL), all samples were detected with a two-bottle set, but not all bottles were reactive. With S. marcescens (< 2 CFUs/mL), only 7 of the 10 sets were reactive. With C. perfringens (0.2 CFUs/mL), only 3 of 10 samples were detected in the anaerobic bottles. CONCLUSIONS: This study evaluates the use of the BacT/ALERT system for detection of bacteria in PLT pools. Overall, the BacT/ALERT detected all contaminated pooled PLTs when the single inoculated unit had a calculated or recovered concentration at least 3 CFUs per mL with 10 different species of bacteria. Low recovered concentrations (< or =2 CFUs/mL) were, in some cases, only detected with a two-bottle set.

Severe hemolytic anemia due to auto anti-N.

Auto anti-N is infrequently encountered and, in most reported cases, does not cause clinical hemolysis. This case reports an auto anti-N associated with severe hemolytic anemia (Hb=2.7 g/dL) in a 6-year-old Caucasian girl with a history of vomiting, fever, and abdominal pain. Upon admission, she was found to have a metabolic acidosis, secondary to her severe anemia, with abnormal liver function tests. As in three other case reports, the autoimmune hemolytic anemia resolved, with disappearance of the auto anti-N, after corticosteroid therapy.

Differentiating thrombotic microangiopathies induced by severe hypertension from anemia and thrombocytopenia seen in thrombotic thrombocytopenia purpura.

Thrombotic microangiopathy (TMA) is a recognized complication of malignant hypertension (HTN). Such patients have blood pressures > or = 200/140 mmHg but the condition is defined by the presence of papilledema and is frequently complicated by acute renal failure. Here we report two patients with severe HTN (systolic > or = 180 mmHg or diastolic > or = 120 mmHg), TMA, thrombocytopenia, renal failure, and, in one case, neurological changes (4 of 5 manifestations of the TTP pentad). A 50-year-old male with HTN presented with blurred vision, dizziness, headache, confusion, renal failure, and a TMA (PLT = 39 x 10(9)/L and LD = 2,781 normal <600 U/L). On presentation, BP was 214/133 mmHg and an ophthalmic exam demonstrated no papilledema. With HTN control over 7 days, his platelet count rebounded (220 x 10(9)/L), LD declined (1,730 U/L), and mental status improved. A 60-year-old female with diabetes, HTN, Lupus erythematosus, mild chronic anemia, and thrombocytopenia presented with abdominal pain, shortness of breath, renal failure, and a TMA (PLT = 83 x 10(9)/L and LD = 2,929 U/L). Blood pressures were 180-210/89-111 mmHg and ophthalmic exam demonstrated no papilledema. With HTN control over 8 days, her platelet count rebounded (147 x 10(9)/L), and LD declined (1,624 U/L). Although in both cases a diagnosis of TTP was considered because of overlap with the classic diagnostic pentad, neither received plasmapheresis. TTP is a diagnosis of exclusion, where there is no other likely diagnosis to explain the TMA. In cases of severe HTN (with or without papilledema), the diagnosis of TTP should be held in abeyance until the effect of HTN control can be assessed.

Validation of BacT/ALERT plastic culture bottles for use in testing of whole-blood-derived leukoreduced platelet-rich-plasma-derived platelets.

BACKGROUND: Bacterial detection of platelet (PLT)-rich-plasma (PRP)-derived PLTs presents unique challenges for countries that do not allow pooling before storage. This study validated the BacT/ALERT for use in testing pooled PRP-derived PLTs with nine contaminating organisms. STUDY DESIGN AND METHODS: Isolates of Bacillus cereus, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Staphylococcus epidermidis, Serratia marcescens, Streptococcus viridans, and Propionibacterium acnes were inoculated into two PRP-derived PLT pools (target, 10 and 100 colony-forming units [CFUs]/mL; actual recovered concentrations, 5 and 90 CFUs/mL). Four milliliters of each postbacterial inoculation sample was inoculated into both plastic aerobic and anaerobic bottles and 0.5 mL was plated onto blood agar. RESULTS: All organisms (excluding P. acnes) were detected in 8.2 to 22.0 and 7.6 to 20.3 hours (10 and 100 CFUs/mL, respectively) and the mean time to detection was 15.0 and 13.1 hours (10 and 100 CFUs/mL, respective). P. acnes was detected with the anaerobic bottles in a mean of 74.9 and 64.3 hours (10 and 100 CFUs/mL, respectively). With E. cloacae, E. coli, K. pneumoniae, S. marcescens, and S. viridans detection with the anaerobic bottles was faster or equivalent to the detection with the aerobic bottles. This was most notable with S. viridans where the anaerobic bottle was reactive on average 21.6 and 10.8 hours (10 and 100 CFUs/mL, respectively) faster than the aerobic bottle. CONCLUSIONS: This study validates the use of the BacT/ALERT system for the detection of bacteria in PRP-derived PLTs in a pooled format. Overall, the use of the BacT/ALERT system allowed the detection of pooled PRP-derived PLTs inoculated with nine bacteria at 10 and 100 CFUs per mL in 7.6 to 22.0 hours (excluding P. acnes).

Quetiapine with lithium or divalproex for the treatment of bipolar mania: a randomized, double-blind, placebo-controlled study.

OBJECTIVE: Evaluate the efficacy and tolerability of quetiapine (QTP) combined with lithium (Li) or divalproex (DVP) in the treatment of acute mania. METHODS: Patients were randomized to 21 days of double-blind treatment with QTP plus Li/DVP, or placebo (PBO) plus Li/DVP. QTP was rapidly dosed up to a maximum of 800 mg/day; Li was dosed to 0.7-1.0 mEq/L; or DVP to 50-100 microg/mL. RESULTS: Fifty-six of 91 (61.5%) individuals in the QTP + Li/DVP group compared with 49 of 100 (49%) taking PBO + Li/DVP completed the study. A significantly greater mean reduction in total Young Mania Rating Scale (YMRS) score was observed at end-point in patients receiving QTP + Li/DVP compared with those in the PBO + Li/DVP group (-13.76 versus -9.93; p = 0.021). The response rate (> or =50% YMRS improvement) was significantly higher in the QTP + Li/DVP group than in PBO + Li/DVP-treated patients (54.3% versus 32.6%; p = 0.005), as was the proportion of patients achieving clinical remission (YMRS < 12) (45.7% versus 25.8%; p = 0.007). Patients receiving QTP + Li/DVP also had a significantly greater improvement in Clinical Global Impressions-Bipolar (CGI-BP) Severity of Illness scores (-1.38 versus -0.78; p = 0.001). The mean last-week dose of QTP was 584 mg/day in patients meeting response criteria. Common adverse events (at least 10% and twice the rate of Li/DVP) in the QTP + Li/DVP group included somnolence, dry mouth, asthenia, and postural hypotension. CONCLUSIONS: Quetiapine combined with either Li or DVP has superior efficacy compared with Li or DVP monotherapy for treating patients with bipolar mania. Combination therapy was well-tolerated and most adverse events were mild, withdrawal because of adverse events being only 5% compared with 6% on Li or DVP monotherapy.

Evaluation of a new generation of plastic culture bottles with an automated microbial detection system for nine common contaminating organisms found in PLT components.

BACKGROUND: A microbial detection system (BacT/ALERT 3D, bioMérieux [formerly Organon Teknika]) has previously been validated with a variety of bacterial contaminants in PLTs. The recovery of nine organisms seeded into PLTs with new plastic culture bottles was studied in comparison to the current glass bottles. The use of plastic instead of glass would be expected to reduce the risk of injury. STUDY DESIGN AND METHODS: Isolates of Bacillus cereus, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Staphylococcus epidermidis, Serratia marcescens, Streptococcus viridans, and Propionibacterium acnes were inoculated into Day 2 (>24 hr <48 hr) apheresis PLT units to 10 and 100 CFUs per mL. Replicate samples (4 mL) were inoculated into both current- and new-generation standard aerobic and anaerobic bottles. RESULTS: All organisms (with the exception of P. acnes) were detected in a mean time of 9.3 to 18.9 hours (10 CFUs/mL) or 8.7 to 18.2 hours (100 CFUs/mL). In aggregate (with the exception of P. acnes), the plastic and glass aerobic bottles had a mean difference in detection of 1.2 hours (p < 0.0001), and the plastic and glass anaerobic bottles had a mean difference of 3.3 hours (p < 0.0001). In all cases, the mean detection time was superior or clinically comparable (within 0.1 hr) with the new plastic bottles. P. acnes (an anaerobic organism) was detected with the new and current anaerobic bottles in a mean of 72.8 and 90.4 hours (10 CFUs/mL) or 64.0 and 80.8 hours (100 CFUs/mL), respectively. The narrower bottle neck and smaller inoculation septum present with the new-generation plastic bottles were inoculated with comparable ease to that of the glass bottles. CONCLUSIONS: These data demonstrate that the new plastic bottles are clinically comparable or superior to the current glass standard aerobic and anaerobic culture bottles.

Monitoring of apheresis platelet bacterial contamination with an automated liquid culture system: a university experience.

BACKGROUND: With 4 million platelet units transfused per year in the United States and with the current estimate of bacteria contamination rate in PLT units, it would be expected that 2000 to 4000 bacterially contaminated units are transfused and associated with 333 to 1000 cases of clinical sepsis. STUDY DESIGN AND METHODS: Apheresis platelets were sampled on Day 2 of storage (collection day=Day 0) and issue (or following outdate, Days 6-8) using a sterile connection device (SCD) to attach a sampling bag. Using aseptic technique and a laminar flow hood, bottles were inoculated and placed onto an automated liquid culture system (BacT/ALERT 3D Microbial Detection System) for 7 days. RESULTS: A total of 2397 apheresis PLT units were sampled. A triple apheresis collection was reactive within 14 hours of the Day 2 sampling (aerobic bottles) and the bags were removed from inventory. Staphylococcus epidermidis was identified in all three contaminated bags. Two double-apheresis collections were found to be contaminated with Proprionibacterium sp. after 6 days of incubation but had been transfused to four patients without discernible clinical sequelae. There was one false-positive aerobic bottle and one false-positive anaerobic result due to inadvertent contamination of a bottle. Thus, the overall true-positive rate was 7 of 2397 apheresis units (0.29%) with a true-positive rate for aerobic organisms of 0.13% and an anaerobic true-positive rate of 0.17%. The false-positive rate was 2 out of 4794 samplings (0.04%) or 2 out of 9588 bottles (0.02%). CONCLUSION: This preliminary data suggests that the use of a SCD, aseptic technique, and a laminar flow hood is associated with a low rate of contamination. In no case did an issue (or outdate) detect contamination that was not detected by the Day 2 culture. Additional surveillance is necessary before we can conclude that a Day 2 sterile culture is truly predictive of an issue (or outdate) sterile culture. Bacterial culture surveillance of PLTs would be expected to save lives and may facilitate an extension in PLT storage.

Evaluation of a new generation of culture bottle using an automated bacterial culture system for detecting nine common contaminating organisms found in platelet components.

BACKGROUND: An automated bacterial culture system (BacT/ALERT 3D, bioMérieux) has been previously validated with a variety of bacteria in platelets. The recovery of bacteria in platelets using a new generation of culture bottles that do not require venting and that use a liquid emulsion sensor was studied. STUDY DESIGN AND METHODS: Bacillus cereus, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Staphylococcus aureus, Staphylococcus epidermidis, Serratia marcescens, Streptococcus viridans, and Propionibacterium acnes isolates were inoculated into Day 2 platelets to concentrations of 10 and 100 CFU per mL. Samples were then studied with current and new aerobic, anaerobic, and pediatric bottles. RESULTS: All organisms, except P. acnes, were detected in a mean time of 9.2 to 20.4 (10 CFU/mL) or 8.7 to 18.6 (100 CFU/mL) hours. P. acnes was detected in a mean time of 69.2 (10 CFU/mL) or 66.0 (100 CFU/mL) hours. The 10-fold increase in inoculum was associated with a mean 9.2 percent difference in detection time. The aerobic, anaerobic, and pediatric bottles had a mean difference in detection time (hours) between the current and new bottles of 0.10 (p=0.61), 0.4 (p=0.38), and 1.0 (p < 0.001), respectively. CONCLUSION: No difference in detection time between the current and new aerobic and anaerobic bottles was demonstrated. The new pediatric bottles had a small but significant delay in detection.

Incidence of allergic reactions with fresh frozen plasma or cryo-supernatant plasma in the treatment of thrombotic thrombocytopenic purpura.

Plasma replacement for thrombotic thrombocytopenic purpura (TTP) is accomplished with various plasma products. This study sought to determine the incidence of allergic reactions with FFP or CPP as replacement in therapeutic plasma exchange (TPE). Forty-one TTP patients were identified retrospectively who received TPE replacement with either FFP (n=21) or CPP (n=20). Anti-histamine was administered prophylactically following the initial occurrence of an allergic reaction (urticaria, respiratory distress, or anaphylaxis with hypotension). Fifty-one allergic reactions occurred in 65.8% of patients. Urticaria comprised 49 of 51 (96%) of reactions and respiratory distress the remaining 4%. No anaphylaxis occurred. Nineteen urticarial reactions occurred in 50% of CPP recipients compared to 71% of FFP recipients (P=0.28). Anti-histamine breakthrough occurred in 36.3% of patients who experienced a previous allergic reaction with CPP and 37.5% with FFP (P=1.0). The overall risk of allergy per unit of plasma was 1.37% (1.23 % CPP, 1.48% FFP), comparable to estimates in non-TTP recipients. The median number of donor exposures preceding the first allergic reaction was 35 and 32, CPP and FFP, respectively (P=0.63). The mean volume of plasma transfused prior to reaction was 9,883 mL for CPP and 9,348 mL for FFP (P=0.85). Neither product was advantageous in preventing allergic complications. Because of the large volume, the number of donor exposures, and prolonged duration of therapy, allergic reactions to plasma are common (65.8%) in the treatment of TTP.

In vivo and in vitro characteristics of double units of RBCs collected by apheresis with a single in-line WBC-reduction filter.

BACKGROUND: A novel apheresis procedure for a blood separator (MCS+, Haemonetics) enables the collection of 2 WBC-reduced RBC units in a single donation by using one disposable set with one in-line WBC-reduction filter (RC2H, Pall Corp.). The objective of this study was to evaluate the filtration performance in connection with different prefiltration RBC storage conditions and with the in vitro and in vivo storage quality of the filtered units. STUDY DESIGN AND METHODS: Sixty-six 2-unit RBC collection and gravity-filtration procedures were completed at three sites, resulting in 132 RBC units. Filtration of the double RBC units was performed at room temperature (RT) within 8 hours of collection (n = 36) and under refrigeration (1-6 degrees C) for up to 24 hours (n = 10) and 72 hours (n = 20) before filtration. RBC quality was compared to that of nonfiltered apheresis RBC units (n = 10). RESULTS: Median filtration time was 6.5 and 14 minutes for units stored at RT and under refrigeration, respectively. All 132 RBC units had residual WBC counts <0.4 x 10(6). The refrigerated units showed a greater mean log reduction in WBCs: 5.06 +/- 0.16 (24 hour) and 4.74 +/- 0.48 (72 hour), respectively, than did RT units: 4.47 +/- 0.28 (p<0.05). RBC loss was less than 12 percent in all cases (mean, 7.8 +/- 1.8%). Minimal differences in volume were observed between the paired RBC units. In vitro RBC storage characteristics of the filtered units were as expected and similar to those of the nonfiltered units. For RBC units held at RT (n = 24), the mean in vivo 24-hour recovery was 81.8 +/- 8.4 percent (double-label). CONCLUSION: Satisfactory filter performance in terms of WBC removal and RBC loss was observed with all 66 procedures, irrespective of storage conditions before filtration.

Transfusion-related bacterial sepsis.

Transfusion-associated bacterial sepsis is a persistent problem in transfusion medicine, posing a greater threat than the combined risks of receiving a blood product contaminated with HIV-1 or 2, hepatitis C virus (HCV), hepatitis B virus (HBV), and human T-cell lymphtrophic virus (HTVL) -I or -II. This article provides a brief overview of the current incidence, clinical presentation, associated blood products and organisms, and the most feasible and effective methods available to reduce the potential risk of transfusion-associated sepsis. Because bacterial contamination of blood products is the most frequent cause of transfusion-transmitted infectious disease, and as no single existing strategy can completely eliminate its risk, it is important that clinical suspicion be high, and any partial solutions additively be implemented.

Number of RBC units and rate of transfusionto anemic HIV-positive patients assigned to receiveWBC-reduced or non-WBC-reduced RBCs: the viral activation transfusion study experience.

BACKGROUND: It is known that the use of filtration to reduce WBCs in RBC units is associated with a 6- to 15-percent loss of RBCs. It is not known if the use of such WBC-reduced RBCs results in an increased need for RBC units or in the transfusion of more units per year to patients with anemia. STUDY DESIGN AND METHODS: In the multicenter Viral Activation Transfusion Study (VATS), anemic HIV-positive patients were randomly assigned to receive either WBC-reduced or non-WBC-reduced RBCs. The number of RBC units transfused per patient and the rate of RBC use were studied. All RBC units given after the enrollment transfusion were counted, until the end of follow-up or the occurrence of bleeding (receiving >5 RBCs within 2 consecutive days). RESULTS: As expected, the WBC-reduced RBC units in VATS were lighter in weight than the non-WBC-reduced units (median weight: WBC-reduced, 300 g; non-WBC-reduced, 330 g; p<0.0001). After the enrollment transfusion, 258 WBC-reduced arm patients received 1279 units of RBCs (average, 5.0 units/patient, median, 2 units) while 262 patients in the non-WBC-reduced arm received 1111 RBCs (4.2 units/patient; median, 2 units). The number of units transfused for anemia was slightly greater in the WBC-reduced arm, but the difference was not significant (p = 0.41). Similarly, the rate of RBC use was somewhat higher in the WBC-reduced arm, but the difference was not significant (p = 0.14). The median was 2.3 units per patient per year of follow-up in the WBC-reduced arm; the median in the non-WBC-reduced arm was 1.2 units. CONCLUSION: This study confirms that WBC-reduced RBC units are significantly lighter in weight than non-WBC-reduced RBCs. However, in the setting of a large, randomized, blinded study of transfusion for anemia, the smaller size of the WBC-reduced RBC units had no significant effect on the number of RBC units transfused or on the rate at which RBC units were used. In this study, the frequency of blood transfusion may have had a greater relationship to the frequency of routine, scheduled appointments or transfusion orders for a specified Hb trigger than to the actual Hb content of the unit.

Evaluation of an automated culture system for detecting bacterial contamination of platelets: an analysis with 15 contaminating organisms.

BACKGROUND: Approximately 1 in 2000 platelet components are bacterially contaminated. The time to detection of 15 seeded organisms in platelets recovered from an automated culture system was studied. STUDY DESIGN AND METHODS: Isolates of Bacillus cereus, Bacillus subtilis, Candida albicans, Clostridium perfringens, Corynebacterium species, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Propionibacterium acnes, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, Serratia marcescens, Streptococcus pyogenes, and Streptococcus viridans were inoculated into Day 2 apheresis platelet components to obtain a final concentration of approximately 10 and 100 CFU per mL (2 units/organism). Each bag was sampled 10 times (20 mL/sample). Four mL of each sample was inoculated into standard aerobic and anaerobic bottles and into aerobic and anaerobic bottles containing charcoal; 2 mL was inoculated into pediatric aerobic bottles (so as to maintain a 1:10 ratio of sample to media) and 1 mL into thioglycollate broth. RESULTS: With the exception of P. acnes, all organisms were detected in a mean of 9.2 to 25.6 hours. A range of 10 serial dilutions in inoculating concentrations was associated with an overall 10.1-percent difference in detection time. A mean of 74.4 and 86.2 hours (100 and 10 CFU/mL inocula, respectively) was required for the detection of P. acnes in anaerobic bottles. CONCLUSION: Bacteria thought to be clinically significant platelet contaminants can be detected in 9.2 to 25.6 hours when the starting concentration is approximately 10 to 100 CFU per mL. P. acnes required considerably longer incubation times for detection (in either aerobic or anaerobic bottles). However, P. acnes is of questionable clinical significance. Such a detection system could be used in either a blood collection center or a transfusion service to screen platelet concentrates for bacterial contamination. Such testing (with sterile sampling performed so as to maintain a closed-bag system) would be expected to save lives and might allow an extension of platelet storage.

Likelihood of D heterozygosity in Mestizo Mexicans and Mexican Americans.

Information on the gene frequencies of the Rh system in the Mexican or Mexican American population is currently not available in the medical literature, thus hindering management of pregnancies at risk for development of hemolytic disease of the newborn. Data from four recent large studies in the broader scientific literature of Mestizo Mexicans and Mexican Americans is reviewed. Gene frequencies are calculated from the pooled data. A table of gene frequencies in the Caucasian and African American population is provided for comparison.

Bacterial contamination of blood products: factors, options, and insights.

Transfusion of bacterially contaminated blood products remains an overlooked problem. However, the risk of receiving a bacterially contaminated unit is greater than the combined risk of HIV-1/2, HCV, HBV, and HTLV I/II [American Association of Blood Banks Bulletin, no. 294, 1996]. Topics covered in this article include: the current incidence, clinical presentation and outcome, effective methods of detection, and ways to reduce bacterial contamination of blood products. There is no one existing strategy that can completely eliminate the risk of bacterial contamination. It is inevitable that partial solutions or combinations of methods will be implemented in the near future.