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1.  Complications following an unnecessary peri-operative plasma transfusion and literature review 
Plasma is used to correct coagulopathies, but not all coagulation abnormalities are clinically significant enough to require correction before an invasive procedure. We report an 82-year-old female who, in response to a mildly prolonged INR of unknown etiology, was unnecessarily transfused with plasma in advance of elective surgery. The patient suffered a moderately severe transfusion reaction, including hives and voice hoarseness, which caused a 4-week delay in her surgery. This delay and adverse reaction could have been avoided had the principles of evidence based plasma therapy, which we herein review, been followed and if the etiology of the mildly elevated INR been investigated before the day of her surgery.
PMCID: PMC4140061  PMID: 25161359
Allergic reaction; guidelines; plasma; transfusion
2.  Stored Platelet Functionality is Not Decreased After Warming with a Fluid Warmer 
Anesthesia and analgesia  2013;117(3):575-578.
Warming of IV administered fluids and blood products is routinely performed in the operating room to help maintain normothermia. Current guidelines recommend against the warming of platelets (PLTs), although there is no evidence for this prohibition in the literature. Our goal in this pilot study was to determine if the warming of stored PLTs had any effect on their function.
Ten units of three-day-old PLT rich plasma-derived whole blood PLTs were acquired from the transfusion service. A 5 mL aliquot was taken from each unit before warming (control samples). The remainder of the unit was then passed into a blood warming device and held there for two minutes. Post-warming (warmed) PLT samples were then collected from the effluent end of the warming device. PLT aggregometry assays with adenosine diphosphate, collagen, and arachidonic acid as agonists were performed on the control and warmed samples. Thromboelastrography (TEG®) tests were also performed on the control and warmed samples from six of the 10 PLT units.
The mean temperature of the control and warmed samples was 22.4 ± 0.5°C and 37.8 ± 2.3°C, respectively. There was no significant difference (all P ≥ 0.13) in any of the PLT aggregometry assays or in the maximum amplitude of the TEG® test between the control and the warmed samples. The observed mean of only one parameter decreased (PLT aggregometry with 5 µM adenosine diphosphate), by 5% (95% CI: −115% to 105%). The maximum change observed was PLT aggregometry with arachidonic acid as agonist, which increased by 116% (95% CI: −91% to 323%).
Although small in size, the results of this study do not support the prohibition against mechanical PLT warming. Studies of PLT activation after warming are also warranted.
PMCID: PMC3784352  PMID: 23921655
3.  The Effect of salvaged blood on Coagulation Function as measured by Thromboelastography 
Transfusion  2012;53(6):1235-1239.
There is concern that salvaged blood has the potential to activate the coagulation system, which might place patients at risk of thrombotic complications. The aim of this study was to determine whether transfusion of salvaged blood after total knee arthroplasty (TKA) would lead to procoagulopathic changes as measured by thromboelastography (TEG), and furthermore if washing would reduce this risk.
Twenty two patients undergoing TKA were enrolled. Control samples were venous blood samples taken before surgery. Test samples were created by mixing the control samples with postoperatively salvaged blood, either washed or unwashed. TEG profiles were measured, noting the time to initiate clotting (R), the time of clot formation (K), the angle of clot formation (α-angle), and the maximum strength of clot (MA).
The changes in the coagulation profile from control samples to test samples were consistent for both the washed and unwashed groups: R time decreased, MA decreased, and K and alpha-angle remained the same. However, the changes were more pronounced in the unwashed group than the washed group, with a 61% decrease in R time as compared with 14%, and a 26% drop in MA as compared with 6%.
The addition of salvaged blood to the patient’s preoperative blood resulted in decreased clot strength as well as decreased time to initial clot formation. This suggests that the reinfusion of postoperatively salvaged washed or unwashed blood after TKA favors a change towards a more hypocoagulable state, and washing appears to reduce this effect.
PMCID: PMC3521840  PMID: 22934712
Autotransfusion; Blood transfusion; Coagulation; Salvaged blood; Thromboelastography; Total knee arthroplasty
4.  Quantification of Changes in Oxygen Release from Red Blood Cells as a Function of Age Based on Magnetic Susceptibility Measurements 
The Analyst  2011;136(14):2996-3003.
This study extends the in vitro understanding of the RBC storage lesion by serially analyzing the RBC’s magneophoretic mobility, a property dependent on the content and oxygenation or oxidation state of hemoglobin (Hb) iron, during storage. Four prestorage leukoreduced, AS-5 preserved RBC units were stored between 1–6°C for 42 days. Weekly starting on storage day 7, each unit was sampled, the aliquot divided into 3 portions and subjected to different reactions: one portion was exposed to room air to produce oxyhemoglobin (oxyHb), another portion was mixed with sodium nitrite to produce methemoglobin (metHb), while the third portion was desaturated of oxygen (deoxyhemoglobin, deoxyHb) using nitrogen gas. These portions were placed into a cell tracking velocimetry (CTV) apparatus which measured both the settling velocity (us) of the RBCs as well as their magnetically induced velocity (um). The um/us ratio depends on the oxygenation or oxidation state and quantity of iron within the RBC. RBC density was measured by percoll centrifugation. There was a significant reduction in the um/us ratio for the deoxyHb RBC portion as storage time elapsed, with a smaller but still significant reduction in the um/us ratio for the metHb portion. The average RBC density decreased very slightly during storage, as determined by percoll centrifugation technique, although the average settling velocity (another measure of cell density) seemed to fluctuate during storage. The decrease in magnetophoretic mobility of the deoxyHb portion, presented as the ratio of um/us, is explicable either by Hb’s increased affinity for oxygen during storage, or a loss of iron from the cells.
PMCID: PMC3981609  PMID: 21647486
6.  Significant association between ABO blood group and pancreatic cancer 
AIM: To evaluate whether the ABO blood group is related to pancreatic cancer risk in the general population of the United States.
METHODS: Using the University of Pittsburgh’s clinical pancreatic cancer registry, the blood donor database from our local blood bank (Central Blood Bank), and the blood product recipient database from the regional transfusion service (Centralized Transfusion Service) in Pittsburgh, Pennsylvania, we identified 274 pancreatic cancer patients with previously determined serological ABO blood group information. The ABO blood group frequency was compared between these patients and 708 842 individual, community-based blood donors who had made donations to Pittsburgh’s Central Blood Bank between 1979 and 2009.
RESULTS: The frequency of blood group A was statistically significantly higher amongst pancreatic cancer patients compared to its frequency amongst the regional blood donors [47.63% vs 39.10%, odds ratio (OR) = 1.43, P = 0.004]. Conversely, the frequency of blood group O was significantly lower amongst pancreatic cancer patients relative to the community blood donors (32.12% vs 43.99%, OR = 0.60, P = 0.00007). There were limited blood group B (n = 38) and AB (n = 17) pancreatic cancer patients; the overall P trend value comparing patient to donor blood groups was 0.001.
CONCLUSION: The ABO blood group is associated with pancreatic cancer risk. Future studies should examine the mechanism linking pancreatic cancer risk to ABO blood group.
PMCID: PMC2992676  PMID: 21105191
ABO blood group; Pancreatic adenocarcinoma; Surveillance; Risk reduction; Epidemiology
7.  Complications following an unnecessary peri-operative plasma transfusion and literature review 
The Korean Journal of Hematology  2012;47(4):298-301.
Plasma is used to correct coagulopathies, but not all coagulation abnormalities are clinically significant enough to require correction before an invasive procedure. We report an 82 year old female who, in response to a mildly prolonged INR of unknown etiology, was unnecessarily transfused with plasma in advance of elective surgery. The patient suffered a moderately severe transfusion reaction, including hives and voice hoarseness, which caused a 4-week delay in her surgery. This delay and adverse reaction could have been avoided had the principles of evidence based plasma therapy, which we herein review, been followed and if the etiology of the mildly elevated INR been investigated before the day of her surgery.
PMCID: PMC3538803  PMID: 23320010
Plasma; FFP; Transfusion; Allergic; Reaction; Complication
8.  Blood Utilization After Primary Total Joint Arthroplasty in a Large Hospital Network 
HSS Journal  2013;9(2):123-128.
Since a study in orthopedic hip fracture patients demonstrated that a liberal hemoglobin (Hb) threshold does not improve patient morbidity and mortality relative to a restrictive Hb threshold, the standard of care in total joint arthroplasty (TJA) should be examined to understand the variability of red blood cell (RBC) transfusion following TJA.
The study aimed to answer the following questions: (1) What is the blood utilization rate after primary TJA for individual surgeons within a large hospital network? (2) What is the comparison of hospital charges, length of stay (LOS), and discharge locations among TJA patients who were and were not transfused?
A retrospective study was conducted on 3,750 primary total knee arthroplasties (TKAs) and 2,070 primary total hip arthroplasties (THAs), and data was retrospectively collected over a 15-month period on the number of RBCs transfused per patient, along with demographic and cost details. The number of patients who received at least 1 RBC unit and the number of RBCs transfused per patient was calculated and stratified by surgeon.
In the postoperative period, 19.3% TKA patients and 38.5% THA patients received a RBC transfusion. Transfusion rates following TJA varied widely between surgeons (TKA 4.8–63.8%, THA 4.3–86.8%). Transfused TKA patients received an average of 1.65 ± 0.03 RBCs, and THA patients received an average of 1.97 ± 0.14 RBCs. LOS and hospital charges for blood transfusion patients were higher than nontransfused patients.
Blood utilization after primary TJA varies greatly among surgeons, suggesting that resources may be misallocated. These findings highlight the need to standardize RBC transfusion practice following TJA.
Electronic supplementary material
The online version of this article (doi:10.1007/s11420-013-9327-y) contains supplementary material, which is available to authorized users.
PMCID: PMC3757482  PMID: 24009534
total joint arthroplasty; blood utilization; transfusion rate; blood management; red blood cell (RBC) transfusion; intervention
9.  Platelet Transfusion – the Art and Science of Compromise 
Many modern therapies depend on platelet (PLT) transfusion support. PLTs have a 4- to 7-day shelf life and are frequently in short supply. In order to optimize the inventory PLTs are often transfused to adults without regard for ABO compatibility. Hemolytic reactions are infrequent despite the presence of ‘high titer’ anti-A and anti-B antibodies in some of the units. Despite the low risk for hemolysis, some centers provide only ABO identical PLTs to their recipients; this practice might have other beneficial outcomes that remain to be proven. Strategies to mitigate the risk of hemolysis and the clinical and laboratory outcomes following ABO-matched and mismatched transfusions will be discussed. Although the PLTs themselves do not carry the D antigen, a small number of RBCs are also transfused with every PLT dose. The quantity of RBCs varies by the type of PLT preparation, and even a small quantity of D+ RBCs can alloimmunize a susceptible D− host. Thus PLT units are labeled as D+/–, and most transfusion services try to prevent the transfusion of D+ PLTs to D– females of childbearing age. A similar policy for patients with hematological diseases is controversial, and the elements and mechanisms of anti-D alloimmunization will be discussed.
PMCID: PMC3725020  PMID: 23922541
Platelets; ABO; Rh; Mismatch; Hemolysis; Alloimmunization; Antibody
10.  The impact of suctioning RBCs from a simulated operative site on mechanical fragility and hemolysis 
Intraoperative cell salvage exerts shear stress upon RBCs, particularly as they are suctioned from the surgical field. Shear stress can result in overt hemolysis or it can cause sublethal injury to the suctioned RBCs. The mechanical fragility (MF) test uses shear stress to measure the extent of RBC sublethal injury. RBCs that have sustained sublethal injury are more susceptible to shear stress induced hemolysis. In this study we suctioned whole blood samples from an artificial surgical field to determine if pre-menopausal female RBCs would demonstrate greater resistance to hemolysis and less sublethal injury compared to that of males and post-menopausal females.
Ten CPD-preserved whole blood units from these 3 donor groups were obtained and samples suctioned at -150 mmHg from a simulated surgical field. The MF test was then performed and the % hemolysis calculated. In addition the MF test was serially performed on these whole blood units during the 21 days of storage.
There were no differences in the extent of hemolysis or RBC shear stress resistance after suctioning between the 3 donor groups. During storage the pre-menopausal female RBCs demonstrated higher shear stress tolerance compared to the males or post-menopausal females at all of the time points.
Although during static storage pre-menopausal female RBCs in CPD-preserved whole blood demonstrated higher shear stress tolerance, this enhanced resistance was not observed after suctioning from a simulated surgical field.
PMCID: PMC3065624  PMID: 21461301
Red blood cell; Mechanical fragility; Suctioning; Cell salvage; Hemolysis; Storage lesion; Peri-operative
11.  The how's and why's of evidence based plasma therapy 
The Korean Journal of Hematology  2010;45(3):152-157.
Although traditionally fresh frozen plasma (FFP) has been the product of choice for reversing a significant coagulopathy, the modern blood bank will have several different plasma preparations which should all be equally efficacious in reversing a significant coagulopathy or arresting coagulopathic bleeding. Emerging evidence suggests that for a stable patient, transfusing plasma for an INR≤1.5 does not confer a hemostatic benefit while unnecessarily exposing the patient to the risks associated with plasma transfusion. This review will discuss the various plasma products that are available and present some of the current literature on the clinical uses of plasma.
PMCID: PMC2983046  PMID: 21120202
Fresh frozen plasma; FFP; FP24; Plasma; Evidence; Transfusion; INR; PTT
12.  Changes in hematologic indices in caucasian and non-caucasian pregnant women in the United States 
The Korean Journal of Hematology  2012;47(2):136-141.
The objective of this study was to determine if there are differences in common red blood cell (RBC) indices and platelet concentrations during pregnancy and to establish if any observed differences in these parameters were based on the patient's ethnicity.
From an electronic perinatal database which stores laboratory and clinical information on a large number of births at a regional hospital specializing in obstetrical care, RBC index and platelet concentration data were retrospectively analyzed at various time points throughout pregnancy. RBC index data was collected from 8,277 pregnant women (5,802 Caucasian pregnant women and 2,475 non-Caucasian pregnant women). Platelet concentration data was available from 8252 pregnant women (5,784 Caucasian pregnant women and 2,468 non-Caucasian pregnant women).
Hemoglobin (HGB) levels were significantly higher amongst Caucasian women compared to non-Caucasian women (P at least <0.01) starting at 27 weeks gestation and proceeding until term. There was no significant difference in the mean PLT counts between Caucasian and non-Caucasian pregnant women at any point during gestation.
There are ethnic differences in HGB levels, but not the platelet concentrations, during pregnancy. Based on this finding it would be reasonable to conduct formal prospective studies to determine the clinical significance of this difference and to establish the threshold for diagnosing gestational anemia, especially in pregnant non-Caucasian women.
PMCID: PMC3389063  PMID: 22783361
Anemia; Complete blood count; Hemoglobin; Pregnancy; Reference Ranges
Transplantation  2010;90(5):483-493.
If ‘bridging’ to allotransplantation is to be achieved by a pig liver xenograft, adequate hepatic function needs to be assured.
We have studied hepatic function in baboons after transplantation of livers from α1,3-galactosyltransferase gene-knockout (GTKO,n=1) or GTKO pigs transgenic for CD46 (GTKO/CD46,n=5). Monitoring was by liver function tests and coagulation parameters. Pig-specific proteins in the baboon serum/plasma were identified by Western blot. In 4 baboons, coagulation factors were measured. The results were compared with values from healthy humans, baboons, and pigs.
Recipient baboons died or were euthanized after 4-7 days following internal bleeding associated with profound thrombocytopenia. However, parameters of liver function, including coagulation, remained in the near-normal range, except for some cholestasis. Western blot demonstrated that pig proteins (albumin, fibrinogen, haptoglobin, plasminogen) were produced by the liver from day 1. Production of several pig coagulation factors was confirmed.
After the transplantation of genetically-engineered pig livers into baboons (1) many parameters of hepatic function, including coagulation, were normal or near-normal; (2) there was evidence for production of pig proteins, including coagulation factors, and (3) these appeared to function adequately in baboons, though inter-species compatibility of such proteins remains to be confirmed.
PMCID: PMC2933286  PMID: 20606605
α1; 3-galactosylransferase gene-knockout; acute liver failure; baboon; coagulation; coagulation factors; liver; pig; genetically-modified; xenotransplantation
15.  What every physician should know about transfusion reactions 
PMCID: PMC1913131  PMID: 17638948

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