Successful management of maternal anti-PP1Pk alloimmunization in pregnancy with therapeutic plasma exchange and intravenous immunoglobulin.

Anti-PP1PK alloimmunization is rare given ubiquitous P1PK expression. Prevention of recurrent miscarriages and hemolytic disease of the fetus and newborn (HDFN) in pregnant individuals with anti-PP1PK antibodies has relied upon individual reports. Here, we demonstrate the successful management of maternal anti-PP1PK alloimmunization in a 23-year-old, G2P0010, with therapeutic plasma exchange (TPE), intravenous immunoglobulin (IVIG), and monitoring of anti-PP1Pk titers. Twice-weekly TPE (1.5 plasma volume [PV], 5% albumin replacement) with weekly titers and IVIG (1 g/kg) was initiated at 9 weeks of gestation (WG). The threshold titer was ≥16. Weekly middle cerebral artery-peak systolic velocities (MCA-PSV) for fetal anemia monitoring was initiated at 16 WG. PVs were adjusted throughout pregnancy based on treatment schedule, titers, and available albumin. Antigen-negative, ABO-compatible RBCs were obtained through the rare donor program and directed donation. An autologous blood autotransfusion system was reserved for delivery. Titers decreased from 128 to 8 by 10 WG. MCA-PSV remained stable. At 24 WG, TPE decreased to once weekly. After titers increased to 32, twice-weekly TPE resumed at 27 WG. Induction of labor was scheduled at 38 WG. Vaginal delivery of a 2950 g neonate (APGAR score: 9, 9) occurred without complication (Cord blood: 1+ IgG DAT; Anti-PP1Pk eluted). Newborn hemoglobin and bilirubin were unremarkable. Discharge occurred postpartum day 2. Anti-PP1Pk alloimmunization is rare but associated with recurrent miscarriages and HDFN. With multidisciplinary care, a successful pregnancy is possible with IVIG and TPE adjusted to PV and titers. We also propose a patient registry and comprehensive management plan.

Drugs and Conditions That May Mimic Hemolysis.

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.

Prepump autologous blood collection is associated with reduced intraoperative transfusions in aortic surgery with circulatory arrest: A propensity score-matched analysis.

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.

Implementation of a Standardized Prenatal Testing Protocol in an Integrated, Multihospital Health System.

OBJECTIVES: When 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. METHODS: For 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. RESULTS: We 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. CONCLUSIONS: Close 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.

Low incidence of D alloimmunization among patients with a serologic weak D phenotype after D+ transfusion.

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.

HLA and MICA allosensitization patterns among patients supported by ventricular assist devices.

BACKGROUND: 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. METHODS: 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. RESULTS: Compared with controls, VAD patients had greater Class I differences between peak and initial PRA (18% vs. 0%, p < 0.0001) and higher peak PRA (24% vs. 6%, p < 0.0001). 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%, p < 0.0001). This risk was still present after adjusting for age, gender, pre-VAD PRA, transfusion and duration of follow-up in a multivariate analysis (p < 0.0001 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. CONCLUSION: Our results suggest that VAD is associated with significant HLA allosensitization independent of common risk factors.

Clinical outcomes using a platelet function-guided approach for secondary prevention in patients with ischemic stroke or transient ischemic attack.

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.

Acute renal failure from xanthine nephropathy during management of acute leukemia.

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.