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Objectives Visual inspection of posttransfusion plasma for hemolysis is a key laboratory method in the investigation of possible acute hemolytic transfusion reactions (AHTRs). Many substances and physiologic conditions can mimic hemolysis in vitro. Isolated reports describe specific cases of interference, but a comprehensive listing is lacking. Methods Using an illustrative case, we summarize available literature on substances and conditions that may mimic hemolysis in vitro. We further describe other substances and conditions that may discolor plasma but are unlikely to be mistaken for hemolysis on visual inspection. Results At least 11 substances and conditions have been reported to discolor plasma, in colors ranging from orange to red to brown, including relatively common therapies (eg, eltrombopag, hydroxocobalamin, iron dextran). Other substances are unlikely to be encountered in everyday practice but may mimic hemolysis in particular patient populations. Additional substances may cause plasma discoloration, ranging from blue to green to white, and are associated with a wide variety of therapies and conditions. Conclusions An awareness of the possible preanalytic confounding factors that may mimic hemolysis can aid in the workup of a suspected AHTR. Review of the medical record, use of ancillary testing, and consideration for nonimmune causes of hemolysis can aid in ruling out AHTR.

Preoperative thrombocytopenia is associated with an increased risk of morbidity and mortality following cardiothoracic surgery. We describe a case of a 28-year-old female with a history of myosin heavy chain 9-related disease (MYH9-RD) and a presenting platelet count of 6,000 per microliter undergoing a Bentall procedure for aortic valve insufficiency and a thoracic aortic aneurysm. A multidisciplinary team approach was used in order to optimize the patient for surgery and guide her through the perioperative period. In this report, we discuss the epidemiology and pathophysiology of MYH9-RD and describe the preoperative, intraoperative, and postoperative considerations for such patients presenting for cardiothoracic surgery.

ObjectivesWhen our institution grew into an integrated multihospital health system, we were faced with the need to standardize laboratory processes, including blood bank processes, across all locations. The purpose of this article is to describe our experience of standardizing the protocols for prenatal testing.MethodsFor each hospital in the system, we established service tiers to define tests offered on site or referred to another location. For each prenatal test, we examined the related processes for ways to improve uniformity, efficiency, and reliability. Throughout this process of standardization, we collaborated with the clinical services to gain concurrence on the interpretation and reporting of results.ResultsWe created and implemented a uniform protocol for testing prenatal patients. The protocol standardized the definition of critical titer, instituted criteria to identify passively acquired anti-D, and established a process for the follow-up of women with inconsistent serologic results on Rh(D) typing.ConclusionsClose collaboration with the clinical services ensured that our testing protocol is aligned with the needs of the integrated obstetrics service in the health system. The approach described in this article may provide a plan outline for pathologists facing similar challenges at other integrated health systems.

Objective To evaluate the effect of autologous whole blood (AWB) collection on intraoperative/postoperative allogeneic blood transfusion rate in complex aortic surgery with hypothermic circulatory arrest. Methods This retrospective study included adults who underwent aortic surgery with hypothermic circulatory arrest at a single institution between 2014 and 2019. Out of 509 cases (414 patients), 110 (22%) received the AWB protocol. We performed propensity-score matching, including 35 preoperative and procedural variables, which resulted in 95 well-matched pairs, to compare outcomes in patients who received AWB protocol versus those who did not. Study outcomes were percentage of patients who received transfusion of allogeneic blood products intraoperatively and postoperatively. Results Mean volume of collected autologous blood was 826 ± 263 mL. Intraoperatively, fewer AWB patients received red blood cell concentrate (33% vs 49%; P = .02), plasma (35% vs 62%; P = .0002), platelets (61% vs 81%; P = .003), and cryoprecipitate (43% vs 56%; P = .08) compared with non-AWB patients. During the entire hospital stay, the differences in transfusion rate between the 2 groups were: red blood cells (58% vs 62%; P = .6), plasma (49% vs 66%; P = .01), platelets (72% vs 82%; P = .09), and cryoprecipitate (56% vs 63%; P = .3). Conclusions Pre-pump autologous blood collection may reduce the need for intraoperative transfusion of allogenic non–red-cell blood products in patients undergoing complex aortic surgery with hypothermic circulatory arrest. A larger study is needed to clarify the influence of this association on patient outcomes and resource utilization.

BACKGROUND By consensus definition, the red blood cells (RBCs) of patients that react weak to 2+ in the serologic D test are classified as having the serologic weak D phenotype (weak D). The risk of D alloimmunization in patients with weak D is not well studied. This study retrospectively determined the incidence of D alloimmunization in patients with weak D who received D+ blood products. STUDY DESIGN AND METHODS Patient records at four institutions were reviewed. Eligible patients had at least 1 D typing result with agglutination strength that was weak to 2+ result in gel or tube (Institutions 1-3) or weak to 2+ result in solid phase or a positive tube weak D test using antihuman globulin reagent (Institution 4). All patients received at least 1 D+ allogeneic RBC or platelet transfusion and had a subsequent antibody detection test performed at least 30 days after the first D+ transfusion. RESULTS The incidence of alloanti-D formation was 0.15% (6/4011, at Institutions 1-3) and 5.1% (3/59, at Institution 4; these incidences were significantly different [p = 0.0002]). There were 0.15% (6/4011) patients who had autoanti-D detected; all were at Institutions 1 to 3. CONCLUSIONS Until RHD genotyping is widely available, these data support the fact that patients with serologic weak D may be transfused with D+ RBCs if an urgent transfusion is required. At Institution 4, inclusion of a higher proportion of black patients compared to the other institutions may have affected the incidence of alloimmunization by perhaps including partial D recipients who are at risk of forming D antibodies.

Ventricular assist devices (VADs) are increasingly being used as a bridge to transplantation and have been implicated as a risk factor for allosensitization to human leukocyte antigens (HLA). We investigate the association between VAD and allosensitization to human leukocyte antigens (HLA) and major-histocompatibility-complex (MHC) class I-related Chain A (MICA) antigens.We considered all patients who received a VAD at our institution between 2000 and 2009; 89 of them had pre-VAD and post-VAD (≤6 months after implant) HLA antibody screening. A control group of non-VAD heart transplant candidates was constructed with at least 2 pre-transplant panel-reactive antibody (PRA) tests within 8 months. Two controls were randomly selected/VAD patient matched for year (n = 178). Patients and controls with available sera from these time-points were tested by Luminex/flow PRA single-antigen beads and by MICA antibody Luminex single-antigen beads. Medical records were reviewed for comparison of pre-transplant immunologic risk factors and post-transplant outcomes between the 2 groups.Compared with controls, VAD patients had greater Class I differences between peak and initial PRA (18% vs. 0%, p0.0001) and higher peak PRA (24% vs. 6%, p0.0001). The differences between the 2 groups in Class II were less pronounced than in Class I. Of patients who had single-antigen testing, VAD implantation was significantly associated with development of new HLA antibody specificities (Class I and/or Class II) post-VAD with an increase in calculated PRA (cPRA) post-VAD compared with controls (16% vs. 0%, p0.0001). This risk was still present after adjusting for age, gender, pre-VAD PRA, transfusion and duration of follow-up in a multivariate analysis (p0.0001 and 0.02, respectively). There were no differences in development of MICA antibodies between the 2 groups (14% in both). There was no significant difference in the incidence of pre-transplant positive T-cell crossmatch, pre-transplant donor-specific HLA antibodies, rejection episodes or graft survival between the 2 groups.Our results suggest that VAD is associated with significant HLA allosensitization independent of common risk factors.

By consensus definition, the red blood cells (RBCs) of patients that react weak to 2+ in the serologic D test are classified as having the serologic weak D phenotype (weak D). The risk of D alloimmunization in patients with weak D is not well studied. This study retrospectively determined the incidence of D alloimmunization in patients with weak D who received D+ blood products.Patient records at four institutions were reviewed. Eligible patients had at least 1 D typing result with agglutination strength that was weak to 2+ result in gel or tube (Institutions 1-3) or weak to 2+ result in solid phase or a positive tube weak D test using antihuman globulin reagent (Institution 4). All patients received at least 1 D+ allogeneic RBC or platelet transfusion and had a subsequent antibody detection test performed at least 30 days after the first D+ transfusion.The incidence of alloanti-D formation was 0.15% (6/4011, at Institutions 1-3) and 5.1% (3/59, at Institution 4; these incidences were significantly different [p = 0.0002]). There were 0.15% (6/4011) patients who had autoanti-D detected; all were at Institutions 1 to 3.Until RHD genotyping is widely available, these data support the fact that patients with serologic weak D may be transfused with D+ RBCs if an urgent transfusion is required. At Institution 4, inclusion of a higher proportion of black patients compared to the other institutions may have affected the incidence of alloimmunization by perhaps including partial D recipients who are at risk of forming D antibodies.

Dysregulation of one or more elements in hemostatic system can cause an increased risk of bleeding or hypercoagulability (thrombosis). Highly complex platelets play an important role in hemostasis and thrombosis through adhesion to subendothelium, release of coagulation factors in granules, and aggregation. A hereditary or acquired deficiency in one or more procoagulant factors can lead to excessive bleeding. Hereditary or acquired deficiency or dysfunction of regulatory proteins such as antithrombin, protein C, and protein S can lead to a hypercoagulability. Polymorphisms such as factor V Leiden or prothrombin gene G20210A or rare mutations can cause hypercoagulability. Antiphospholipid syndrome or lupus anticoagulant is a common cause of acquired thrombophilia with increased risk of arterial and venous thrombosis. Many current diagnostic laboratory tests can be often affected by concurrent clinical conditions or anticoagulant therapy. To identify the patients in a risk of bleeding or hypercoagulability, a battery of diagnostic laboratory tests should be performed in a stepwise manner by diagnostic algorithm beginning with high-yield screening tests followed by appropriate specific confirmatory tests. Consultation and comprehensive narrative interpretation by coagulation specialists are of great importance for correct interpretation of the results related to clinical conditions.

Background and Purpose— Antiplatelet therapy nonresponse is associated with worse clinical outcomes. We studied the clinical outcomes associated with platelet function-guided modifications in antiplatelet therapy in patients with ischemic stroke or transient ischemic attack. Methods— From January 2005 to August 2007, 324 patients with ischemic stroke underwent platelet function testing using platelet aggregometry. Aspirin nonresponse was defined as a mean platelet aggregation ≥20% with 0.5 mg/mL arachidonic acid and/or ≥70% with 5 μmol/L adenosine diphosphate. Clopidogrel nonresponse was defined as a mean platelet aggregation ≥40% with 5 μmol/L adenosine diphosphate. A modification was any increase in antiplatelet therapy occurring after testing. Clinical outcomes were compared between patients with and without platelet function-guided antiplatelet therapy modifications using univariate and propensity score-adjusted analyses. Results— In patients with ischemic stroke or transient ischemic attack, 43% (n=128) and 35% (n=54) were nonresponders to aspirin and clopidogrel, respectively. After platelet function testing, antiplatelet therapy was increased in 23% of patients (n=73). After propensity score matching (n=61 in each group), antiplatelet therapy modification was associated with significantly increased rates of death, ischemic events, or bleeding (hazard ratio, 2.24; 95% CI, 1.12–4.47; P =0.02) compared with no modification in antiplatelet therapy and a trend toward increased bleeding (hazard ratio, 3.56; 95% CI, 0.98–12.95; P =0.05). No differences in ischemic events were observed. Conclusions— Platelet function-guided modification in antiplatelet therapy after an ischemic stroke or transient ischemic attack was associated with significantly higher rates of adverse clinical outcomes.

Blood transfusions can be life-saving in the appropriate setting. The vast majority of transfusions are completed without incident, but every transfusion recipient is at risk of a variety of adverse events (termed transfusion reactions) that can occur during, shortly after or long after the

Background: Induction chemotherapy (IC) in Acute Myeloid Leukemia (AML) leads to significant bone marrow suppression. The standard clinical practice to prevent or manage cytopenia related complications, namely anemia or bleeding, has been red blood cell (RBC) and platelet (PLT) transfusion. Accumulating evidence suggests no advantage to patients (pts) managed with liberal transfusion strategies compared to a restrictive approach. However, prior studies excluded patients with bone marrow failure conditions such as AML; hence it remains unclear whether a similar approach can be extrapolated for AML pts. We undertook this study to evaluate the effects of transfusions on treatment outcomes and complications in AML. Methods: Adult pts diagnosed with AML (excluding acute promyelocytic leukemia) at the Cleveland Clinic from 01/2008 - 12/2012 who underwent IC with 7+3 (full dose of cytarabine and anthracycline) and had complete adverse event data were included. Variables including demographics, preexisting comorbidities, AML disease characteristics, organ dysfunction (neurologic, cardiac, pulmonary, renal, hepatic, bleeding and thromboembolic events), infections (bloodstream infection, pneumonia and clostridium difficile associated diarrhea) and treatment response [complete remission (CR), incomplete remission (CRi), persistent disease (PD) and 30-day mortality] were assessed. The outcome of interest was any correlation between the total number of PLT and/or RBC transfusions and (i) organ impairment, (ii) infections, and (iii) treatment outcomes during the induction period. Culture confirmed bloodstream infections included vancomycin resistant enterococcus (VRE), gram-positive bacteria (except VRE), gram-negative bacilli and fungemia. Univariable and multivariable logistic regression models adjusted for potential confounders were performed for each outcome category. Odds ratio (OR) with 95% confidence intervals (CI) are reported. Results: Of 192 pts, 48% (n=93) were female, 85% (n=163) were Caucasian, 54% (n=103) were In univariable analysis a higher number of RBC and PLT transfusions was associated with an increased risk of bloodstream infections (OR=1.03; CI,1.01-1.05; p=0.001). In multivariable analysis increased number of transfused RBCs and PLTs was associated with lower CR rates (OR=0.94; CI,0.91-0.97; p Conclusion: In multivariable analysis the number of RBC and PLT transfusions during AML IC is associated with a slightly increased risk for cardiac, pulmonary and some infectious complications. Higher numbers of transfusions also appear to be associated with lower CR rates. These data can inform future prospective studies designed to determine the benefits and risks of a restrictive transfusion policy in the AML population. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Sekeres: TetraLogic: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees.

Tumor lysis syndrome is a potentially life-threatening complication of induction chemotherapy for treatment of lymphoproliferative malignancies. Serious complications of tumor lysis syndrome are rare with the preemptive use of allopurinol, rasburicase, and urine alkalinization. We report a case of oliguric acute renal failure due to bilateral xanthine nephropathy in an 11-year-old girl as a complication of tumor lysis syndrome during the treatment of T-cell acute lymphoblastic leukemia. Xanthine nephrolithiasis results from the inhibition of uric acid synthesis via allopurinol which increases plasma and urinary xanthine and hypoxanthine levels. Reports of xanthine nephrolithiasis as a cause of tumor lysis syndrome are rare in the absence of defects in the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) enzyme. Xanthine nephropathy should be considered in patients who develop acute renal failure following aggressive chemotherapy with appropriate tumor lysis syndrome prophylaxis. Urine measurements for xanthine could aid in the diagnosis of patients with nephrolithiasis complicating tumor lysis syndrome. Allopurinal dosage should be reduced or discontinued if xanthine nephropathy is suspected.

Purpose Ventricular assist device (VAD) is implicated in HLA-sensitization. We investigate the association between VAD and HLA & MICA sensitization. Methods and Materials Of VAD patients in our institute (00-09); 89 had pre-VAD antibody testing and another in 6 months post-VAD. The comparison group was no-VAD heart transplant candidates; 2 randomly selected/VAD patient matched for year of initial PRA. Results Follow-up was longer in the non-VADs to increase capturing non-VAD increases in PRA (53 vs. 28 days, p=0.001). The number of transfusions was higher in VADs (15 vs. 2), p Table 1 ). In patients with single antigen testing, VAD was associated with new HLA antibody specificities and increased cPRA (16 (0-41)% vs. 0%, p Figure 1 ). Conclusions VAD is associated with HLA sensitization independent of other risk factors. It was not significantly associated with differences in rejection or allograft survival, but may represent a barrier to transplant by limiting donors and lengthening of wait time. Table 1 VAD nonVAD p Class I Pk % 24 (7-72) 6 (2-26) Class I Diff 18 (3-52) 0 (0-1) Class II Pk % 4 (1-16) 2 (1-5) .04 Class II Diff 2 (0-13) 0 .0001

Aim VADs are increasingly used as a bridge to transplantation and are implicated as a risk factor for allosensitization. We investigated in a matched case-control study the association between VAD and PRA changes (peak & significant increase ⩾20%). Methods We analyzed records of VAD recipients at our institute from 00-09 (n = 384) and included patients with pre-VAD PRA testing and another PRA test within 6 months post-VAD (n = 100). PRA testing was performed by screening flowPRA beads (One Lambda, CA). A control group was constructed from heart transplant candidates evaluated in the same time frame with no VAD (n = 830) for whom we had ⩾3 PRA tests within 8 months pre-transplant (n = 445). Two controls were randomly matched for each VAD case based on yr of initial PRA test. Results Follow-up was longer in the controls (median:103 vs 33; p Table 1 ). Multivariable models adjusted for gender, race, pre-VAD PRA, duration of VAD and blood transfusion yet the associations remained unchanges. Of VAD patients, that had a significant increase in C1 PRA and single antigen testing performed 81% (35/43) showed development of new HLA antibody specificities post-VAD. Conclusions Our results suggest that VAD is associated with CI allosensitization independent of other risk factors. These findings have important clinical implications and warrant prospective studies to better understand VAD associated allosensitization.

Higher Incidence of Class II Human Leukocyte Antigen (HLA)Allosensitization in Patients Supported with Pulsatile Ventricular Assist Devices (VAD) M. Askar, A. Zhang, L. Klingman, M. Mastroianni, A. Nowacki, P. Reville, J. Gatto, S. Bakdash, N. Smedira, R. Starling, G. Gonzalez-Stawinski. Allogen Laboratoires, Cleveland Clinic; Doisey College of Health Sciences, St. Louis University; Department of Quantitative Health Sciences, Cleveland Clinic; College of Arts and Sciences, The Ohio State University; Clinical Pathology, Cleveland Clinic; Cardiothoracic Surgery, Cleveland Clinic; Cardiovascular Medicine, Cleveland Clinic.