Mortality increases after massive exchange transfusion with older stored blood in canines with experimental pneumonia

Abstract

Key Points• In canine S aureus pneumonia, first randomized blinded trial showing blood transfused at end of storage period increases mortality.• Increased in vivo hemolysis, cell-free hemoglobin, pulmonary hypertension, tissue damage, and gas exchange abnormalities each contributed.Two-year-old purpose-bred beagles (n ‫؍‬ 24) infected with Staphylococcus aureus pneumonia were randomized in a blinded fashion for exchange transfusion with either 7-or 42-day-old canine universal donor blood (80 mL/kg in 4 divided doses). Older blood increased mortality (P ‫؍‬ .0005), the arterial alveolar oxygen gradient (24-48 hours after infection; P < .01), systemic and pulmonary pressures during transfusion (4-16 hours) and pulmonary pressures for ϳ 10 hours afterward (all P < .02). Further, older blood caused more severe lung damage, evidenced by increased necrosis, hemorrhage, and thrombosis (P ‫؍‬ .03) noted at the infection site postmortem. Plasma cell-free hemoglobin and nitric oxide (NO) consumption capability were elevated and haptoglobin levels were decreased with older blood during and for 32 hours after transfusion (all P < .03). The low haptoglobin (r ‫؍‬ 0.61; P ‫؍‬ .003) and high NO consumption levels at 24 hours (r ‫؍‬ ؊0.76; P < .0001) were associated with poor survival. Plasma nontransferrin-bound and labile iron were significantly elevated only during transfusion (both P ‫؍‬ .03) and not associated with survival (P ‫؍‬ NS). These data from canines indicate that older blood after transfusion has a propensity to hemolyze in vivo, releases vasoconstrictive cell-free hemoglobin over days, worsens pulmonary hypertension, gas exchange, and ischemic vascular damage in the infected lung, and thereby increases the risk of death from transfusion. (Blood. 2013;121(9):1663-1672) IntroductionTransfusion of red blood cells (RBCs) is one of the most commonly used, potentially lifesaving medical therapies. Each year, some 80.7 million units of blood are collected in 167 countries worldwide, and approximately 15 million units are collected and transfused in the United States alone. 1,2 RBCs can be stored for up to 42 days to meet inventory needs, and by standard practice the oldest blood is usually used first ("first in, first out"). Food and Drug Administration (FDA) regulations only stipulate that at the end of the storage period 75% of the cells remain in the circulation at 24 hours after transfusion and that hemolysis in the storage bag does not exceed 1%, 3 no other product specification of quality is required. Although 6-week-old stored blood meets current FDA standards, laboratory and clinical studies have raised concerns that "older" blood may not be as safe as blood stored for a shorter duration. [4][5][6][7][8] Refrigerated storage of blood results in a "storage lesion" characterized by rheologic changes, metabolic derangements, changes in oxygen affinity and delivery, oxidative injury to lipids and proteins, RBC shape change, loss of membrane carbohydrates, and reduced RBC lifespan. [8][9][10] The storage lesion resu...

Washing older blood units before transfusion reduces plasma iron and improves outcomes in experimental canine pneumonia

“…1 Briefly, anesthetized animals day 0 were instrumented (external jugular vein catheter, femoral artery catheter, and urinary catheter) followed with placement of a balloon-tipped pulmonary arterial thermodilution catheter and a tracheostomy performed as described. 1,25 Following these procedures, animals were weaned off inhalation anesthesia, and continuous sedation (fentanyl, midazolam, and medetomidine) and mechanical ventilation via a tracheostomy tube were initiated. At time 0 hours (T0), S aureus isolates were prepared and administered via bronchoscope into the right lower lobe of the lung.…”

“…1 Transfusion with older blood is also associated with increased levels of cell-free hemoglobin (CFH), transferrin bound iron (TBI), non-TBI (NTBI) and plasma labile iron (PLI). NTBI represents iron excess bound to proteins that do not normally handle circulating iron, and PLI is the toxic iron moiety in plasma.…”

“…All animals were provided conventional intensive care unit support, including prophylaxis for gastrointestinal ulcer (famotidine 1 mg/kg iv, every 12 hours) and deep venous thrombosis (heparin 3000 IU, sq, every 8 hours) as well as procedures to prevent pressure ulcers (regular position change). Mechanical ventilation, fluid support, and vasopressor therapy were also used and titrated using physiological and laboratory end points using previously described algorithms 1,25 (see the supplemental Methods). Animals alive at 96 hours were considered survivors and were killed while still sedated (Beuthanol; 75 mg/kg IV).…”

The simultaneous occurrence of both hypercoagulability and hypofibrinolysis in blood and serum during systemic inflammation, and the roles of iron and fibrin(ogen)

“…[428][429][430][431][432][433][434][435][436][437][438] As we have shown in the Components and (figure letter in parentheses) Mean fibre diameter (nm) (n = 50) AE SD 10 mL PRP + 5 mL thrombin (8A) 105 AE 3 10 mL PRP + 5 mL thiourea + 5 mL thrombin (8B) 117 AE 4 10 mL PRP + 5 mL phytic acid + 5 mL thrombin (8C) 46 AE 2 10 mL PRP + 5 mL FeCl 3 + 5 mL thrombin (8D) 45 AE 3 10 mL PRP + 5 mL AlCl 3 + 5 mL thiourea (8E) 39 AE 1 10 mL PRP + 5 mL YCl 3 + 5 mL thrombin (8F) 50 AE 2 10 mL PRP + 5 mL FeCl 3 + 5 mL thiourea + 5 mL thrombin (8G) 146 AE 4 10 mL PRP + 5 mL AlCl 3 + 5 mL thiourea + 5 mL thrombin (8H) 66 AE 5 10 mL PRP + 5 mL YCl 3 + 5 mL thiourea + 5 mL thrombin (8I) 69 AE 5 10 mL PRP + 5 mL FeCl 3 + 5 mL phytic acid + 5 mL thrombin (8J) 47 AE 3 10 mL PRP + 5 mL AlCl 3 + 5 mL phytic acid + 5 mL thrombin (8K) 184 AE 8 10 mL PRP + 5 mL YCl 3 + 5 mL phytic acid + 5 mL thrombin (8L) 65 AE 4 previous paragraphs, free iron can have a substantial role in determining the outcome of the clotting process, and this will need to be borne in mind as blood ages. The same is likely true for blood that ages in individuals.…”

Large scale inkjet-printing of carbon nanotubes electrodes for antioxidant assays in blood bags

“…a model AO) and in real samples such as erythrocyte concentrates (ECs), a labile blood product widely used in transfusion medicine, donated by two healthy persons and targeted for blood donation. The latter is of high relevance in blood product research and management since erythrocytes suffer from storage lesions, during storage at 4°C, which alter lipids, proteins, metabolism, and biomechanical properties of the cells [42][43][44][45][46][47][48], resulting in potential adverse effects upon transfusion [47][48][49][50][51][52]. Erythrocytes are enucleated cells not able to synthesize proteins, which requires a solid system (like the repair or destroy box) [53,54] to protect the cells against oxidative stress.…”