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).

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.

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.