Fresh Whole Blood Research Articles

Fresh whole blood use by forward surgical teams in Afghanistan is associated with improved survival compared to component therapy without platelets

In Afghanistan, a substantial portion of resuscitative combat surgery is performed by US Army forward surgical teams (FSTs). Red blood cells (RBCs) and fresh frozen plasma (FFP) are available at these facilities, but platelets are not. FST personnel frequently encounter high-acuity patient scenarios without the ability to transfuse platelets. An analysis of the use of fresh whole blood (FWB) at FSTs therefore allows for an evaluation of outcomes associated with this practice. A retrospective analysis was performed in prospectively collected data from all transfused patients at six FSTs from December 2005 to December 2010. Univariate analysis was performed, followed by two separate propensity score analyses. In-hospital mortality was predicted with the use of a conditional logistic regression model that incorporated these propensity scores. Subset analysis included evaluation of patients who received uncrossmatched Type O FWB compared with those who received type-specific FWB. A total of 488 patients received a blood transfusion. There were no significant differences in age, sex, or Glasgow Coma Scale in those who received or did not receive FWB. Injury Severity Scores were higher in patients transfused FWB. In our adjusted analyses, patients who received RBCs and FFP with FWB had improved survival compared with those who received RBCs and FFP without FWB. Of 94 FWB recipients, 46 FWB recipients (49%) were given uncrossmatched Type O FWB, while 48 recipients (51%) received type-specific FWB. There was no significant difference in mortality between patients that received uncrossmatched Type O and type-specific FWB. The use of FWB in austere combat environments appears to be safe and is independently associated with improved survival to discharge when compared with resuscitation with RBCs and FFP alone. Mortality was similar for patients transfused uncrossmatched Type O compared with ABO type-specific FWB in an austere setting.

Evaluation of the quality of blood components obtained after automated separation of whole blood by a new multiunit processor

The Reveos system (Terumo BCT) is a fully automated device able to process four whole blood (WB) units simultaneously into a plasma unit, a red blood cell (RBC) unit, and an interim platelet (PLT) unit (IPU). Multiple IPUs can be pooled to form a transfusable PLT product. The aim of our study was to evaluate the quality of components made with the Reveos system from either fresh (2-8 hr) or overnight-held WB. A prototype of the Reveos system was used to process WB. RBCs were resuspended in SAGM, leukoreduced, and assayed for in vitro quality variables during a 42-day storage period at 2 to 6 °C. Twenty-four-hour in vivo recovery was determined on Day 42. Plasma was assayed for cellular contamination and activation variables. IPUs were pooled with SSP+ additive solution for in vitro quality assessments during a 7-day storage period at room temperature. Reveos-produced RBCs and plasma units met the predefined requirements. RBC recovery was superior to control units. On Day 42, hemolysis was below 0.8% and in vivo recovery was above 75% for all RBCs. Cellular contamination was lower for Reveos-produced plasma. PLT yield was higher with overnight-stored WB. PLT quality was well maintained during storage with no significant differences between the two groups. Blood components prepared with the Reveos from fresh or overnight-held WB meet quality criteria without any relevant difference between the two groups. The Reveos system has the potential to increase efficacy and standardization of blood component preparation.

Transfusion de sang frais total en temps de guerre : expérience du groupement médicochirurgical Warehouse durant la période 2006–2009

ObjectiveThe specificities of military medicine have led to the maintenance of fresh whole blood (FWB) transfusion. Study designThe aim of our study was to evaluate this practice at the French military hospital in Kabul between 2006–2009. Patients and methodsDuring our study period, 19 FWB transfusions were performed and the data from 15 FWB transfusions could be analyzed. We studied the number of units by recipient, the characteristics of recipients, the results of blood tests performed after transfusion, the incidents in donors and recipients, the period for obtaining a unit of FWB and mortality of recipients. ResultsA total of 66 units of FWB were transfused in 15 patients. The median number of FWB units transfused was three per patient. Thirteen out of 15 (87%) were combat-related casualties. All units were tested before transfusion for HIV with rapid diagnostic tests. Every blood samples of donors were negative for pathogens screened at the French Blood Service. No incident in donors and in recipients was reported. The average time between collection and transfusion was 140±197minutes (median 43min). Mortality in recipients was 27% (n=4). ConclusionIn our study, the FWB transfusion was not associated with incidents. Nonetheless, this practice should be used only for exceptional situations like military conflicts where risks of FWB are lower than the absence of transfusion.

The US Military Experience With Fresh Whole Blood During the Conflicts in Iraq and Afghanistan

Since its introduction in the early part of the last century, fresh whole blood (FWB) has been used by the US military as a battlefield expedient resuscitation method, even after the development of component therapy in the 1960s. In the recent conflicts in Iraq and Afghanistan, FWB was used once more, often collected in the setting of a walking blood bank (WBB). Considerable research and opinion from military circles has cited these experiences and sparked renewed interest in FWB as an effective resuscitation tool in the setting of trauma. Despite efforts by the US military to improve the effectiveness and safety of FWB through a series of widely published guidelines, transfusion transmitted infections (TTI) remain a vexing challenge. These experiences in Iraq and Afghanistan will help inform a larger discussion regarding the reintroduction of FWB in civilian trauma resuscitation.

The immunomodulatory effects of hypertonic saline on sepsis patients

To approach the immunomodulatory effects of hypertonic saline (HTS) on sepsis patients. Twenty-four septic patients admitted to surgical intensive care unit (SICU) received 5% HTS for fluid resuscitation were prospectively enrolled from January 2009 to September 2010. Blood samples were collected at 15 minutes before, and at 15 minutes and 6, 12, and 24 hours after HTS infusion, the ability of respiratory burst of polymorphonuclear neutrophils (PMN) and the surface expression of CD11b and L-selectin in fresh whole blood was evaluated with flow cytometer. The plasma was collected to determine the solubility intercellular adhesion molecule-1 (sICAM-1), solubility L-selectin (sL-selectin), tumor necrosis factor-α(TNF-α) and interleukins (IL-6, IL-1β). The baseline before HTS infusion was set as 100. Six hours after HTS infusion, the ability of respiratory burst of PMN was significantly increased [(160.0±19.6)%] compared with the baseline (P<0.05), and then gradually recovered to normal level. The expression of CD11b and L-selectin in the surface of PMN was reduced rapidly at 15 minutes after HTS infusion, and to nadir at 12 hours [(70.4±5.7)%, (70.6±8.1)%], and L-selectin recovered to the normal level at 24 hours. Within short-term of HTS infusion, plasma inflammatory factor TNF-α was significantly decreased, and sustained a low level until 12 hours, and then gradually increased. There was no change in IL-1β. IL-6 and sICAM-1 was gradually increased, and peaked at 24 hours and 12 hours respectively, and remained at a high level. sL-selectin increased shortly at 15 minutes after HTS infusion compared with baseline, and remained the level to 12 hours, and recovered to baseline at 24 hours. Delayed administration of HTS may have an immunomodulatory effect on sepsis patients, which could inhibit the activation of PMN.

Fresh Whole Blood Use for Hemorrhagic Shock

Transfusion support of patients with hemorrhagic shock has changed over time with the development of storage and processing methods. Transfusion medicine developed during World War I with the use of whole blood, and now in the developed world, component therapy predominates. In contrast, there is still clinical use of fresh whole blood (FWB) in the developing world, in a minority of children's hospitals, and in combat settings. Although there is a rationale for the use of FWB in massively bleeding patients compared with the use of individual components, it has rarely been analyzed in prospective randomized clinical trials. Recent retrospective studies in adult trauma and mixed critically ill patients have revived this decades-old controversial question of the value of FWB for patients with severe shock and coagulopathy or those at risk. The risks of FWB use have also been highlighted recently, which has caused some to focus on reducing these risks with alternative processing and storage methods. It is important to recognize that current processing and storage methods for components have also not been adequately explored to determine whether they affect clinical outcomes. In this article, we review potential benefits and risks of FWB use for patients with hemorrhagic shock from any cause, and how current and future processing and storage methods may affect efficacy and safety of FWB in this population. We intend this review to stimulate hypothesis generation and clinical investigation in determining when FWB may be indicated and how to optimally process and store FWB to maximize its risk-benefit ratio.

Betwixt Scylla and Charybdis

Betwixt Scylla and Charybdis

Symposium on fresh whole blood for severe hemorrhagic shock: From in-hospital to far forward resuscitations

This report is prepared for The Hemostasis and Oxygenation Research (THOR) Network and based on presentations of invited THOR investigators. In order to make it available to a larger group of interested readers it has been agreed to publish the report in TRASCI, as a “what is happening?” in view of its importance and novelty. On June 14th 2011 the first symposium on fresh whole blood (FWB) was held in Bergen, Norway. THOR network leadership, which includes Tor Hervig, PhD, MD, Geir Strandenes, MD, Erling Bekkestad Rein, MD, and Philip C. Spinella, MD, organized the event. It was sponsored by the Royal Norwegian Navy Medical Service, Norwegian Armed Forces Medical Services and Caridian BCT. The objective of this meeting was to bring together investigators from around the world who are interested in analyzing the efficacy and safety of FWB for patients with severe traumatic hemorrhagic shock and to determine the initial steps in developing a research program in this area. The THOR network is specifically interested in determining if FWB can improve morbidity and mortality in combat casualties with life threatening hemorrhagic shock. A three-year research proposal has been developed by the THOR network to determine (1) if FWB donation adversely affects donor performance of combat related skills, (2) the optimal storage solution, temperature, and acceptable storage duration for FWB, (3) the logistics of providing FWB in a combat environment safely to include optimal transport and administration methods. The symposium speakers were tasked with reviewing current data on; coagulopathy associated with massive traumatic bleeding, immunology of transfusion, outcomes associated with FWB use, logistic and medical issues of the use of FWB in far forward situations, training required for medics on FWB collection and administration, the risks of FWB and stored blood components and methods to mitigate these risks. The meeting concluded with a discussion of the THOR network’s three-year research program.

Gemcitabine Degradation in Whole Blood from Humans, Dogs, Cats, and Horses

The purpose of this in vitro study was to compare the degradation of gemcitabine (2’, 2’-difluorodeoxycytidine, dFdC), in Fresh Whole Blood (FWB) from humans, dogs, cats, and horses. A better understanding of the comparative degradation of gemcitabine may aid in the optimal design of therapeutic regimens in veterinary species. Fresh whole blood from humans, dogs, cats, and horses was spiked with dFdC and plasma was analyzed for dFdC and 2’, 2’-difluorodeoxyuridine (dFdU) by high performance liquid chromatography. In these species, there was an initial rapid degradation of dFdC with a concomitant proportional increase in dFdU. Degradation of gemcitabine appeared similar in humans, dogs, and horses (p>0.05) whereas metabolism was slower in the cat than human (p=0.014), dog (p=0.010), or horse (p=0.0015). Based on these in vitro findings, dosing schemes for humans, dogs, and horses may be similar. In contrast, gemcitabine degradation occurred more slowly in the cat; this difference may dictate a different dosing scheme for optimal response in this species.

A Panoramic View of Blood and Blood Product: Use in the Past Half Century

ABSTRACTBackgroundMany changes regarding the use of blood and blood products for resuscitation of severely injured patients have occurred in the past 50 years. This study presents these changes.Study designA review of resuscitation regimens over 50 years is presented.ResultsDuring the 1960s, hemorrhage shock (HS) was treated with whole blood (WB) and balanced electrolyte solution (BES); fresh WB restored the labile factors (FV and FVIII) during massive transfusion (MT). When component therapy with red cells (RBC) was started, plasma (FFP) had to be added; patients with MT received a 2/5 RBC/FFP ratio. Platelets were reserved for oozing or counts below 50,000. During the Vietnam conflict, many recommended supplemental albumin therapy. A large prospective randomized study showed that albumin therapy caused many adverse effects including coagulopathy. During the 1980s, the National Institute of Health (NIH) responded to a shortage of FFP by initiating a consensus development conference (CDC) which concluded that FFP was not indicated without an established coagulopathic bleeding; animal HS models showed FFP was beneficial. During the 1990s, military surgeons recommended a 1/1 FFP/RBC ratio. Studies, herein, demonstrated that a 0.3/1 FFP/RBC ratio effectively restored procoagulants; whereas, ratios above 0.45/1 FFP/RBC caused increased BES needs and longer stays.ConclusionInitial therapy for HS should be BES followed by RBC to maintain hemoglobin, perfusion and urine output. FFP should be supplemented after 5 units RBC using a 0.5 FFP/ RBC until hemostasis is obtained. Platelets should be added for ‘medical’ oozing and thrombocytopenia.How to cite this articleLucas CE. A Panoramic View of Blood and Blood Product: Use in the Past Half Century. Panam J Trauma Critical Care Emerg Surg 2012;1(3):139-145.

Characterization of blood components separated from donated whole blood after an overnight holding at room temperature with the buffy coat method

With buffy coat (BC) processing of whole blood (WB) donations, increase in WB storage time to facilitate overnight holding before the separation of blood components would be a logistically attractive development. This study undertakes a comparative in vitro characterization of blood components prepared from WB samples that were either processed within 8 hours or stored overnight at room temperature before processing by the BC method. The WB units (400 mL) collected were either processed within 8 hours (fresh blood) or stored overnight (overnight blood) at room temperature. WB units were separated into individual-component red blood cells (RBCs), BC, and plasma. The in vitro quality of these blood components (RBCs, pooled platelet concentrates [PCs], and plasma) was analyzed during storage. Levels of 2,3-diphosphoglycerate (2,3-DPG) were found to be significantly lower immediately after processing, compared with the fresh WB samples, in RBCs that had been separated from an overnight-hold sample. However, this difference was not apparent after 14 days of storage. In pooled PCs, measurements for glucose, lactate, PO(2), PCO(2), extent of shape change, and hypotonic shock response were similar. The platelet yield in PCs prepared from an overnight-hold WB sample was significantly higher, while CD62P expression and annexin V binding were lower (p < 0.05). For frozen plasma (FP), no significant differences were observed for the coagulation factors (F)II, FVII, FV, F IX, FX, and FXI; fibrinogen; and von Willebrand factor content between the 8- and 24-hour FP. The FVIII was the component that was most sensitive to the prolongation of production time and it only had 80% of the activity of the 8-hour FP. These data suggest that blood components (RBCs, pooled PCs, and FP) separated from WB that has been stored overnight at room temperature by the BC method are of acceptable quality.

Hemostatic and Pharmacologic Resuscitation: Results of a Long-Term Survival Study in a Swine PolyTrauma Model

We have previously demonstrated that valproic acid (VPA), a histone deacetylase inhibitor, and spray-dried plasma (SDP) improve early survival after lethal hemorrhage and polytrauma, but their effect on long-term survival and organ function remains untested. Yorkshire swine (n=27; 6-8/group) underwent a protocol simulating different phases of trauma care: (1) prehospital-rib fracture, soft-tissue injury, hemorrhage (50% blood volume), 30 minutes of shock, and infusion of 0.9% saline (3× shed blood); (2) early hospital/treatment-grade IV liver (partial amputation of the median lobe) and grade V splenic (transection of spleen into three pieces) injuries to simulate rupture of contained hematomas, followed by 30 minutes of uncontrolled hemorrhage. Animals were treated with (a) Hextend (6% hetastarch), (b) fresh whole blood (FWB), (c) SDP, and (d) VPA (300 mg/kg) plus Hextend. VPA was given during the prehospital phase, and the volumes of Hextend, FWB and SDP (reconstituted in water) matched shed blood; (3) repair/resuscitation-liver injury was controlled by suture control of the transected edge, and splenic injury was treated by partial splenectomy; 1 hour after repair of injuries, surviving animals were fully resuscitated with packed red blood cells; and (4) monitoring-survival was monitored for 7 days (primary endpoint), and blood samples were drawn serially to measure organ function. Only 25% of the Hextend-treated animals survived. Addition of VPA improved survival to only 50% (p=0.28), whereas treatment with SDP and FWB increased survival significantly to 83% and 100%, respectively (p<0.05). Surviving animals showed no long-term organ dysfunction, postoperative hemorrhage, and delayed complications. In a clinically relevant lethal polytrauma model, administration of SDP significantly improves survival without any long-term organ dysfunction or complications.

Fresh Whole Blood Transfusions In The Austere Environment

The use of Fresh Whole Blood (FWB) transfusions can be a powerful tool for the Special Operations Forces (SOF) medic to treat uncontrolled hemorrhage. In fact, it may be the only tool currently available for hemostatic resuscitation, which along with hypotensive resuscitation, forms the basis for Damage Control Resuscitation (DCR). Until now, no comprehensive protocol has existed for conducting FWB transfusions in austere environments. The United States Special Operations Command (USSOCOM) sponsored Curriculum Evaluation Board (CEB), which is responsible for authoring the Tactical Emergency Medical Protocols (TMEPs) has produced a protocol. This article serves as its introduction.

Evaluation of the overnight hold of whole blood at room temperature, before component processing: platelets (PLTs) from PLT‐rich plasma

Whole blood (WB) must be refrigerated within 8 hours to optimize Factor VIII: C yield, but chilled platelets (PLTs) are rapidly removed from circulation and cannot be used clinically. It is logistically preferable to hold WB overnight at room temperature for next-day processing. We compared in vitro quality of PLT-rich plasma (PRP)-derived PLT concentrates (PCs) from fresh versus overnight-held WB. Four units of WB were pooled and split to prevent donor-dependent differences. One unit was processed immediately; three others were held at room temperature and processed after 24 to 26 hours. After soft-spin centrifugation, PRP was separated from the red blood cells. PRP was hard-spun to make PLT-poor plasma, and the PLTs were resuspended in approximately 60 mL of plasma and stored for 7 days (n = 8 paired experiments by two blood centers). After overnight hold, the PLT concentration was 1.37 × 10(9) ± 0.19 × 10(9) /mL versus 1.03 × 10(9) ± 0.32 × 10(9) /mL for freshly prepared PCs (p < 0.05). pH and glucose were significantly lower and lactate higher for overnight-held units on Day 1, but by Day 5, the differences had disappeared. Hypotonic shock response was initially better, 73 ± 14% for overnight-held versus 53 ± 12% for freshly processed (p < 0.001), but this difference also disappeared during storage. Activation marker CD62P was not different. In vitro storage conditions produce immediate differences after preparation, which disappear throughout storage. PCs from overnight-held WB have similar in vitro variables as from freshly processed WB. These findings warrant confirmation in clinical trials, but underscore the possibility of use of these PCs as being equivalent to those obtained from freshly processed WB.

Storage of interim platelet units for 18 to 24 hours before pooling: in vitro study

The Atreus 3C system (CaridianBCT) automatically produces three components from whole blood (WB), a red blood cell (RBC) unit, a plasma unit, and an interim platelet (PLT) unit (IPU) that can be pooled with other IPUs to form a PLT dose for transfusion. The Atreus 3C system also includes a PLT yield indicator (PYI), which is an advanced algorithm that provides an index that is shown to correlate well with the amount of PLTs that finally end up in the IPU bag. The aim of our in vitro study was to compare the effects of holding WB overnight versus processing WB fresh (2-8 hr), both with 18- to 24-hour storage of the IPUs before pooling into a transfusable PLT dose. WB was processed either fresh (within 8 hr after collection, Atreus F) or after overnight storage (14-24 hr, Atreus S) without agitation at 22 ± 2 °C. After a subsequent resting time of 18 to 24 hours on a flat-bed shaker, five IPUs were selected for pooling with 200 mL of PAS II for in vitro quality assessments during a 7-day storage period (n = 10 in each arm). IPUs were selected for pooling using the PYI of the Atreus 3C system. During storage, the glucose concentration was lower (p < 0.05) and the lactate concentration was higher (p < 0.05) in Atreus S pools, but no differences in the glucose consumption rate were noted. Adenosine triphosphate levels and hypotonic shock response reactivity were higher in Atreus S (p < 0.05). No significant differences in PLT counts, contents, mean PLT volume, lactate dehydrogenase, pO(2) , pCO(2) , extent of shape change, and CD62P between groups were detected. pH was maintained higher than 6.8 (Day 7). With exception of 2 units in the Atreus S arm, swirling remained at greater than 2 in all units at all times. Our results suggest that PLTs prepared from fresh or overnight-stored WB and pooled after 18 to 24 hours meet necessary in vitro criteria without any relevant differences between both groups. Using the PYI, comparable yields can be obtained between WB processed within 2 to 8 hours and WB stored overnight.

Comparison of platelet transfusion as fresh whole blood versus apheresis platelets for massively transfused combat trauma patients (CME)

At major combat hospitals, the military is able to provide blood products to include apheresis platelets (aPLT), but also has extensive experience using fresh whole blood (FWB). In massively transfused trauma patients, we compared outcomes of patients receiving FWB to those receiving aPLT. This study was a retrospective review of casualties at the military hospital in Baghdad, Iraq, between January 2004 and December 2006. Patients requiring massive transfusion (≥10 units in 24 hr) were divided into two groups: those receiving FWB (n = 85) or aPLT (n = 284) during their resuscitation. Admission characteristics, resuscitation, and survival were compared between groups. Multivariate regression analyses were performed comparing survival of patients at 24 hours and at 30 days. Secondary outcomes including adverse events and causes of death were analyzed. Unadjusted survival between groups receiving aPLT and FWB was similar at 24 hours (84% vs. 81%, respectively; p = 0.52) and at 30 days (60% versus 57%, respectively; p = 0.72). Multivariate regression failed to identify differences in survival between patients receiving PLT transfusions either as FWB or as aPLT at 24 hours or at 30 days. Survival for massively transfused trauma patients receiving FWB appears to be similar to patients resuscitated with aPLT. Prospective trials will be necessary before consideration of FWB in the routine management of civilian trauma. However, in austere environments where standard blood products are unavailable, FWB is a feasible alternative.

Resuscitation with Fresh Whole Blood Ameliorates the Inflammatory Response After Hemorrhagic Shock

Citing recent retrospective data showing that resuscitation with fresh whole blood (FWB) rather than crystalloid and blood components resulted in decreased mortality among injured soldiers, the authors of this article hypothesized that the transfusion of FWB results in less systemic inflammation and organ injury compared to crystalloid resuscitation after hemorrhagic shock. They employed a mouse model of hemorrhagic shock, cannulating the femoral arteries of mice and then assigning them to one of four arms: a sham group (no hemorrhage or resuscitation), hemorrhage without resuscitation, resuscitation with lactated ringer's solution (LR), and resuscitation with FWB.

Inhibition of amikacin on platelet aggregation and blood coagulation

Objective To observe the inhibition of amikacin in vitro on platelet aggregation and blood coagulation tests, and to study its effects on hemostasis and the related mechanisms.Methods Plateletrich plasma and platelet-poor plasma from donors were mixed with different concentration of amikacin, which was divided into four groups:0 mg/L, 30 mg/L, 91 mg/L and 910 mg/L group.The maximial ratio of platelet aggregation induced by ADP were measured with Platelet Aggregation Analyzer.The expression levels of P-selectin, GP Ⅱ b/Ⅲ a and Fg-R were determined with Flow Cytometer.The PT, APTT, TT and Fg of platelet-poor plasma were detected with Blood Coagulation Analyzer. The four concentration of amikacin mentioned above and two anticoagulants (62.5 U/ml of sodium heparin and 109 mmol/L of sodium citrate)were interacted with fresh whole blood, in which the blood CT and plasma Ca2+ were detected. Blood samples were collected from 10 patients with acute lower respiratory tract infection before and 30 minutes after routine amikcin treatment respectively.The maximial ratio of platelet aggregation, the expression levels of P-selectin, GPⅡ b/Ⅲa and Fg-R induced by ADP were measured; while PT, APTT, CT and plasma Ca2+ were determined.Results At 30 mg/L of amikacin group, the maximal ratios of platelet aggregation (65.8±3.9)%, the expression levels of P-selectin (9.2 ± 1.0)% and Fg-R (12.6 ± 1.7)% were statistically lower than those [(88.0 ±4.6%, (16.1 ± 1.3)% and (31.0 ±2.5)%]at 0 mg/L of amikacin group ( t = 9.442,8.432,9.993,P ＜ 0.01 ).At 30 mg/L of amikacin group, the APTT (80.5 ±6.8) s and CT ( 857 ± 66) s were significantly higher than those [(33.0 ± 3.6) s and (447 ± 35 ) s] at 0 mg/L of amikacin group ( t = 11.312, 13.211, P ＜ 0.01 ). There was a negative correlation between amikacin concentration and maximial ratio of platelet aggregation ( r = - 0.832, P ＜ 0.05 ), but a positive correlation between amikacin concentration and inhibitory rates of platelet aggregation ( r = 0.939, P ＜0.05) was observed, as well as APTT (r ＞0.870, P＜0.05).At 30 mg/L, 91 mg/L, and 910 mg/L of amikacin groups, the P-selectin and Fg-R expression were remarkably inhibited with a dose-dependent manner, the CT was notably enhanced [Fwithin subjects =21.44, 26.24, ( ＞29.81 ), P ＜0.01].At 0 mg/L,30 mg/L, 91 mg/L and 910 mg/L of amikacin groups, the PT values were ( 14.7 ± 1.9) s, ( 15.2 ± 1.7) s,(15.6±1.5) s and (22.1 ±2.1) s, respectively (F=8.21,P＜0.05), but there was no markeddifference for the levels of GP Ⅱ b/Ⅲ a, TT, Fg and plasma Ca2+ among the four groups ( P ＞ 0.05 ).After 30 minutes of amikacin treatment, the maximial ratio of platelet aggregation (51.6 ± 10.1)%, the expression levels of P-selectin (6.8 ± 1.8) % and Fg-R ( 20.1 ± 5.8 ) % were significantly lower than those [(66.8 ± 11.4)%, ( 10.9 ±3.1 )% and (28.5 ±7.4)%] before amikacin treatment, but APTT (49.8 ±5.9) s and CT (660 ±59) s were remarkably higher than those [(26.9 ±3.8) s and (410 ±45) s] before amikacin treatment, respectively ( t = 5.456,8.875,7.423,10.012,11.322, P ＜ 0.01 ), while the GP Ⅱ b/Ⅲ a expression, PT and Ca2+ concentration had no significant changes ( P ＞ 0.05).Conclusions There are inhibitory effects of amikacin on platelet aggregation mainly through the inhibition of both fibrinogen receptor activation and secretion reaction of activated platelet. Amikacin may also inhibit pathway of coagulation system factor to prevent blood coagulation.Therefore, risk of hemorrhage may be investigated in the patients with amikacin for anti-infection treatment. Key words: Amikacin; Platelet aggregation; Blood coagulation; Receptors,fibrinogen

Interferon production in peripheral blood cells of patients with pulmonary mycobacterial disease

Production of interferon (IFN)-alpha and IFN-gamma were examined in 31 patients with acute tuberculosis, 12 patients with atypical mycobacterial disease. IFN production was examined in cultures of unseparated fresh whole blood. Production of IFN-alpha was induced by hemagglutinating virus of Japan and production of IFN-gamma was induced by PHA. Patients with mycobacterial disease produced significantly less IFN-alpha than healthy subjects. In patients with acute tuberculosis, effective chemotherapy for 2 months restored IFN-alpha production. Patients produced less IFN-gamma than healthy subjects, but the difference was not significant. Patients with high serum CRP levels tended to produce little IFN-alpha. These results suggest that measurement of IFN production is useful for immunological evaluation of patients with mycobacterial disease.

Resuscitation With Fresh Whole Blood Ameliorates the Inflammatory Response After Hemorrhagic Shock

Hemorrhagic shock is the leading cause of potentially preventable death after traumatic injury. Hemorrhage and subsequent resuscitation may result in a dysfunctional systemic inflammatory response and multisystem organ failure, leading to delayed mortality. Clinical evidence supports improved survival and reduced morbidity when fresh blood products are used as resuscitation strategies. We hypothesized that the transfusion of fresh whole blood (FWB) attenuates systemic inflammation and reduces organ injury when compared with conventional crystalloid resuscitation after hemorrhagic shock. Male mice underwent femoral artery cannulation and hemorrhage to a systolic blood pressure of 25 mm Hg +/- 5 mm Hg. After 60 minutes, the mice were resuscitated with either FWB or lactated Ringer's solution (LR). Mice were decannulated and killed at intervals for tissue histology, serum cytokine analysis, and vascular permeability studies. Separate groups of mice were followed for survival studies. When compared with FWB, mice resuscitated with LR required increased resuscitation fluid volume to reach goal systolic blood pressure. When compared with sham or FWB-resuscitated mice, LR resuscitation resulted in increased serum cytokine levels of macrophage inflammatory protein-1alpha, interleukin-6, interleukin-10, macrophage-derived chemokine, KC, and granulocyte macrophage colony stimulating factor as well as increased lung injury and pulmonary capillary permeability. No survival differences were seen between animals resuscitated with LR or FWB. Resuscitation with LR results in increased systemic inflammation, vascular permeability, and lung injury after hemorrhagic shock. Resuscitation with FWB attenuates the inflammation and lung injury seen with crystalloid resuscitation. These findings suggest that resuscitation strategies using fresh blood products potentially reduce systemic inflammation and organ injury after hemorrhagic shock.