Blood transfusion in the critically ill: does storage age matter?

Morphologic and biochemical changes occur during red cell storage prior to product expiry, and these changes may hinder erythrocyte viability and function following transfusion. Despite a relatively large body of literature detailing the metabolic and structural deterioration that occurs during red cell storage, evidence for a significant detrimental clinical effect related to the transfusion of older blood is relatively less conclusive, limited primarily to observations in retrospective studies. Nonetheless, the implication that the transfusion of old, but not outdated blood may have negative clinical consequences demands attention. In this report, the current understanding of the biochemical and structural changes that occur during storage, known collectively as the storage lesion, is described, and the clinical evidence concerning the detrimental consequences associated with the transfusion of relatively older red cells is critically reviewed. Although the growing body of literature demonstrating the deleterious effects of relatively old blood is compelling, it is notable that all of these reports have been retrospective, and most of these studies have evaluated patients who received a mixture of red cell units of varying storage age. Until prospective studies have been completed and produce confirmative results, it would be premature to recommend any modification of current transfusion practice regarding storage age

Increased permeability-oedema and atelectasis in pulmonary dysfunction after trauma and surgery: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Trauma and surgery may be complicated by pulmonary dysfunction, acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), but the mechanisms are incompletely understood.</p> <p>Methods</p> <p>We evaluated lung capillary protein permeability non-invasively with help of the ⁶⁷Ga-transferrin pulmonary leak index (PLI) technique and extravascular lung water (EVLW) by the transpulmonary thermal-dye dilution technique in consecutive, mechanically ventilated patients in the intensive care unit within 24 h of direct, blunt thoracic trauma (n = 5, 2 with ARDS), and within 12 h of indirect trauma by transhiatal oesophagectomy (n = 8), abdominal surgery for cancer (n = 6) and bone surgery (n = 4). We studied transfusion history, haemodynamics, oxygenation and mechanics of the lungs. The lung injury score (LIS, 0–4) was calculated. Plain radiography was also done to judge densities and atelectasis.</p> <p>Results</p> <p>The PLI and EVLW were elevated above normal in 61 and 30% of patients, respectively, and the PLI directly related to the number of red cell concentrates given (r_s= 0.69, P < 0.001), without group differences. Oxygenation, lung mechanics, radiographic densities and thus the LIS (1.0 [0.25–3.5]) did not relate to PLI and EVLW. However, groups differed in oxygenation and airway pressures and impaired oxygenation related to the number of radiographic quadrants with densities (r_s= 0.55, P = 0.007). Thoracic trauma patients had a worse oxygenation requiring higher airway pressures and thus higher LIS than the other patient groups, unrelated to PLI and EVLW but attributable to a higher cardiac output and thereby venous admixture. Finally, patients with radiographic signs of atelectasis had more impaired oxygenation and more densities than those without.</p> <p>Conclusion</p> <p>The oxygenation defect and radiographic densities in mechanically ventilated patients with pulmonary dysfunction and ALI/ARDS after trauma and surgery are likely caused by atelectasis rather than by increased permeability-oedema related to red cell transfusion.</p

A Novel Screening System for Claudin Binder Using Baculoviral Display

Recent progress in cell biology has provided new insight into the claudin (CL) family of integral membrane proteins, which contains more than 20 members, as a target for pharmaceutical therapy. Few ligands for CL have been identified because it is difficult to prepare CL in an intact form. In the present study, we developed a method to screen for CL binders by using the budded baculovirus (BV) display system. CL4-displaying BV interacted with a CL4 binder, the C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE), but it did not interact with C-CPE that was mutated in its CL4-binding region. C-CPE did not interact with BV and CL1-displaying BV. We used CL4-displaying BV to select CL4-binding phage in a mixture of a scFv-phage and C-CPE-phage. The percentage of C-CPE-phage in the phage mixture increased from 16.7% before selection to 92% after selection, indicating that CL-displaying BV may be useful for the selection of CL binders. We prepared a C-CPE phage library by mutating the functional amino acids. We screened the library for CL4 binders by affinity to CL4-displaying BV, and we found that the novel CL4 binders modulated the tight-junction barrier. These findings indicate that the CL-displaying BV system may be a promising method to produce a novel CL binder and modulator

Complications related to deep venous thrombosis prophylaxis in trauma: a systematic review of the literature

Deep venous thrombosis prophylaxis is essential to the appropriate management of multisystem trauma patients. Without thromboprophylaxis, the rate of venous thrombosis and subsequent pulmonary embolism is substantial. Three prophylactic modalities are common: pharmacologic anticoagulation, mechanical compression devices, and inferior vena cava filtration. A systematic review was completed using PRISMA guidelines to evaluate the potential complications of DVT prophylactic options. Level one evidence currently supports the use of low molecular weight heparins for thromboprophylaxis in the trauma patient. Unfortunately, multiple techniques are not infrequently required for complex multisystem trauma patients. Each modality has potential complications. The risks of heparin include bleeding and heparin induced thrombocytopenia. Mechanical compression devices can result in local soft tissue injury, bleeding and patient non-compliance. Inferior vena cava filters migrate, cause inferior vena cava occlusion, and penetrate the vessel wall. While the use of these techniques can be life saving, they must be appropriately utilized

Fibrinolysis and coagulation in patients with infectious disease and sepsis

Sepsis is often associated with hemostatic dysfunction. This study aimed to relate changes in fibrinolysis and coagulation parameters to sepsis and sepsis outcome. Urokinase-type plasminogen activator (u-PA) antigen, tissue-type plasminogen activator (t-PA) antigen and activity, plasminogen activator inhibitor (PAI) type 1 antigen, PAI activity, antithrombin (AT) III activity, and protein C activity were measured in 24 patients suffering from sepsis or septic shock and the results were compared with those observed in 30 non-sepsis patients with severe infectious disease. The u-PA level was markedly increased in plasma of sepsis patients as compared to non-sepsis patients (11.5 +/- 9.4 versus 1.6 +/- 1.5 ng/ml, p < 0.0001). PAI-1 antigen and t-PA activity showed a significant increase in sepsis patients (320 +/- 390 ng/ml versus 120 +/- 200 ng/ml, and 3.0 +/- 3.6 IU/ml versus 1.0 +/- 0.7 IU/ml, respectively, p < 0.01). AT III was decreased in sepsis patients (58 +/- 28% in sepsis versus 79 +/- 26% in severe infectious disease, p < 0.01) as was protein C (30 +/- 18% versus 58 +/- 27%, p < 0.001). No significant difference was found for t-PA antigen nor for PAI activity. Nonsurvivors of sepsis were distinguished mainly by a high u-PA antigen level and increased t-PA activity. It is concluded that plasma u-PA antigen showed the strongest significant difference, among the parameters evaluated, between sepsis and severe infection. u-PA antigen may be of prognostic value in patients admitted to the medical intensive care unit for severe infectious disease