Justin D. Kreuter

Routine bacterial screening of apheresis platelets on Day 4 using a rapid test: a 4-year single-center experience

The platelet (PLT) Pan Genera Detection test (PGD) is a rapid bacterial detection system used to screen PLTs for bacterial contamination. We report a single center 46‐month experience with secondary screening of apheresis PLTs by PGD testing.

Drug-associated thrombotic microangiopathies.

Thrombotic microangiopathy is a pathological process that results in thrombocytopenia, schistocytes, and organ ischemia. A wide variety of causes of thrombotic microangiopathy have been described, each associated with a different pathological stimulus and predisposition toward certain vascular territories. This review will summarize our understanding of key drugs that have been classically and newly associated with thrombotic microangiopathy as well as mention of treatment options focusing on the role of plasma exchange.

Outcomes of plasma exchange in patients with transplant-associated thrombotic microangiopathy based on time of presentation since transplant.

Transplant‐associated thrombotic microangiopathy (TA‐TMA) is a rare clinical syndrome associated with significant mortality. Although the use of plasma exchange (PE) in TA‐TMA continues to be explored, evidence for its efficacy is debated. We performed a single institution, retrospective study to evaluate the efficacy of PE in treating TA‐TMA patients. Special attention was given to efficacy in relation to the timing of presentation with TA‐TMA since transplant. Thirty‐three patients diagnosed with TA‐TMA and treated with PE between January 1999 and December 2010 were included in the study. Clinical improvement was seen in eight patients (24%); four patients achieved complete resolution while the remaining four achieved partial resolution. All‐cause day‐30 and day‐100 mortality was 33 and 55%, respectively. There was a trend toward a better outcome (complete/partial) for those presenting ≥ 100 days after transplantation (42%) vs. < 100 days after transplantation (14%; P‐value = 0.15). Similarly, those presenting at ≥ 100 days had better, but not significantly, 30‐day and 100‐day all‐cause mortality rates (17 and 33%, respectively) than those presenting at < 100 days (43 and 67%, respectively) (P‐value = 0.25 and 0.08, for 30‐ and 100‐day all‐cause mortality, respectively). This is the first study looking at the efficacy of PE while considering the time of presentation since transplantation and is one of the largest single institution series of TA‐TMA. The overall efficacy of PE is poor; however, patients who present with TA‐TMA ≥100 days after transplant may have better outcome and lower mortality. J. Clin. Apheresis 30:147–153, 2015.

How do I … manage the platelet transfusion–refractory patient?

Platelet transfusion–refractoriness is a challenging and expensive clinical scenario seen most often in patients with hematologic malignancies. Although the majority of platelet transfusion–refractory cases are due to nonimmune causes, a significant minority are caused by alloimmunization against Class I human leukocyte antigens (HLAs) or human platelet antigens (HPAs). Such platelet transfusion–refractory patients can be effectively managed with appropriate antigen‐negative products.

Clinical Outcomes of HLA-DPB1 Mismatches in 10/10 HLA-Matched Unrelated Donor-Recipient Pairs Undergoing Allogeneic Stem Cell Transplant

HLA‐DPB1 matching may impact allogeneic hematopoietic stem cell transplantation (ASCT) outcomes; however, this locus is not in linkage disequilibrium with the remainder of the HLA genes. After classifying HLA‐DPB1 mismatches based on T‐cell epitope, avoiding non‐permissive mismatches may impact survival. We tested this hypothesis at a single academic institution.

BEST TEST with MEDIOCRE RESULTS (at best!): a "call to arms" to correct clinician knowledge deficits in transfusion medicine.

A s we are fully aware in transfusion medicine, blood transfusion is the most common procedure performed in US hospitals. A recent analysis showed that 14.1% of patients admitted to hematology and oncology services received red blood cells and 25.2% of hematology/oncology admissions received platelets. Because it is the most common, it is reasonable to assume that blood transfusion would be one of the medical procedures with which practitioners demonstrate the most familiarity and knowledge. Unfortunately, it appears that this assumption is far from the truth! Published evidence shows that the practitioners ordering transfusions, consenting patients for transfusions, and administering and monitoring such transfusions repeatedly report and/or show a demonstrable lack of knowledge and expertise in this area. As a transfusion medicine specialist, but more importantly as a future patient who might potentially require transfusion therapy, this reality is a frightening prospect! Patients do not want to know that their physicians are ordering and performing procedures on them with limited knowledge and expertise about such procedures. The question is, why is this current state acceptable to our patients or the medical community? The current state should not be acceptable to anyone; therefore, it is “high time” that steps be taken by transfusion medicine specialists in conjunction with their clinical colleagues to close this knowledge gap so the safety and benefits patients from transfusions are maximized. This is a “call to arms” to close the knowledge gap. First let’s look at some of the information describing the current state of knowledge of transfusion medicine among clinical practitioners utilizing a validated transfusion assessment tool. Then we will describe some options that can be utilized to “fill in the gap.” In 2014, Haspel and colleagues published an article that described the development of a validated examination designed to assess the transfusion knowledge of physicians. Members of the Biomedical Excellence for Safer Transfusion (BEST) Collaborative contributed to the project and a 23-question examination was developed. The examination was subjected to Rasch analysis, which showed that the test demonstrated reliability with respect to distinguishing different levels of transfusion medicine knowledge among groups of individuals being assessed. The examination was administered to individuals with basic, intermediate, and expert knowledge in transfusion medicine and yielded mean scores of 42, 62, and 82%, respectively. It was concluded that this validated examination could be used to identify transfusion medicine knowledge deficits and provide guidance for the development of improved transfusion medicine educational curricula. In 2015, Haspel and colleagues subsequently published the results of the first “in-field” use of the validated transfusion medicine assessment tool. The assessment tool was used to evaluate internal medicine residents regarding prior training, attitudes, perceived ability, and actual knowledge in transfusion medicine. It constituted the largest assessment of internal medicine residents’ transfusion medicine knowledge throughout such training and it was the first such assessment to be conducted on an international scale. The examination was completed by 474 internal medicine residents from 23 training programs located in nine countries. The overall mean score was 45.7% with the range at the various sites of 32% to 56%. Although Postgraduate Year (PGY)3 and PGY4 residents did achieve higher mean scores than PGY1 residents, the absolute difference was 6.7% and all fell short of reaching the intermediate level of transfusion medicine knowledge. Internal medicine residents at higher than PGY4 levels had significantly lower examination scores than PGY4 residents, suggesting that transfusion medicine knowledge does not sustain over time. The overall score for knowledge of transfusion reactions was less than 25%, which is particularly disconcerting because 89% of the residents had participated in obtaining “informed consent” for transfusions. Furthermore, these are frequently the physicians providing initial management of transfusion reactions. It was concluded that, on the basis of this international assessment, internal medicine residents have poor transfusion medicine knowledge. The hopeful news is that 65% of the internal medicine residents expressed the view that additional transfusion medicine training would be very or extremely helpful. In this issue of TRANSFUSION, Lin and colleagues report on the use of the BEST Collaborative assessment tool to assess education, attitudes, perception of ability, and knowledge associated with transfusion medicine in an international group of individuals receiving training in the subspecialty of hematology. Before this, there were no studies specifically assessing such knowledge in clinical doi:10.1111/trf.13456

Extracorporeal Photopheresis Improves Survival in Hematopoietic Cell Transplant Patients with Bronchiolitis Obliterans Syndrome Without Significantly Impacting Measured Pulmonary Functions

We carried out the first matched retrospective cohort study aimed at studying the safety and efficacy of extracorporeal photopheresis (ECP) for bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic cell transplantation (HCT). Medical records of 1325 consecutive adult patients who underwent HCT between 2005 and 2015 were reviewed. Seventy-four patients (median age, 51 years) with a diagnosis of BOS were included in the study. After propensity-score matching for BOS severity, 26 patients who underwent ≥3 months of ECP were matched to 26 non-ECP-treated patients, who were assigned an index date corresponding to the ECP start date for their matched pairs. The rate of decline in FEV1 percentage predicted (FEV1PP) decreased after ECP initiation (and after index date in the non-ECP group), with no significant difference between the 2 groups (P = .33). On a multivariable analysis that included baseline transplant and pulmonary function test variables, matched related donor HCT (HR, .1; 95% CI, .03 to .5; P = .002), ECP (HR, .1; 95% CI, .01 to .3; P = .001), and slower rate of decline in FEV1PP before the ECP/index date (HR, .7; 95% CI, .6 to .8; P = .001) were associated with a better overall survival. At last follow-up, non-ECP-treated patients were more likely to be on >5 mg daily dose of prednisone (54% versus 23%; P = .04) and had a greater decline in their Karnofsky performance score (mean difference, -9.5 versus -1.6; P = .06) compared with ECP-treated-patients. In conclusion, compared with other BOS-directed therapies, ECP was found to improve survival in HCT patients with BOS, without significantly impacting measured pulmonary functions. These findings need prospective validation in a larger patient cohort.

Central retinal vein occlusion after plateletpheresis.

A healthy 52-year-old male presented with an acute onset of unilateral vision loss approximately 5 hours after donating platelets (PLTs); the PLT donation was uneventful and the donated product was normal in appearance. Fundoscopy revealed findings consistent with central retinal vein occlusion (CRVO). Fundus photography (see figure, A) documented a dilated, tortuous venous system with diffuse retinal hemorrhages; fluorescein angiography (see figure, B) revealed a delayed arteriovenous transit time, and optical coherence tomography (see figure, C) revealed *cystoid macular edema. There was no history of risk factors for CRVO. Intraocular pressure, complete blood count, erythrocyte sedimentation rate, C-reactive protein, proteins C/S, Factor V Leiden, HbA1c, lipids, serum protein electrophoresis, cryoglobulin, anti-phospholipid antibodies, syphilis, and carotid ultrasonography were unrevealing. Visual acuity improved from 20/200 to 20/20 after two intravitreal bevacizumab injections with resolution of macular edema (see figure, D), retinal hemorrhages (see figure, E), and venous tortuosity. Clinical stability persisted without further treatment over 6 months follow-up. Rare cases of peripheral venous occlusion have been reported after plateletpheresis, but to the authors’ knowledge, this is the first retinal vascular occlusion reported to be temporally associated with plateletpheresis. Speculation has been given to mechanism(s) of thrombosis after plateletpheresis including PLT activation, induction of coagulation activation, and anti-thrombin reduction. Neither the clinical findings nor the background understanding of CRVO pathogenesis offer more specific support for one of these potential mechanisms. It cannot be stated with certainty that PLT donation served as the proximate etiology for this thrombotic event; however, after a complete examination, no other risk factors for CRVO were identified.

High prevalence of monoclonal gammopathy among patients with warm autoimmune hemolytic anemia

levels of multiple immune cell subsets and immunoglobulins suggesting that IgE may be a marker of more robust post-transplant immune reconstitution. Prior history of asthma was associated with elevated IgE, indicating that pre-transplant factors may still influence IgE even years after transplant. Importantly, elevated IgE was not associated with any global or organ-specific measures of cGVHD severity or activity or any acute phase reactants. These results suggest that in patients after allo-HSCT with cGVHD, elevated IgE is not a marker of disease or acute inflammation.