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Background Therapeutic plasma exchange (TPE) is often used to decrease serum triglyceride levels in hypertriglyceridemic pancreatitis (HTGP), although there is a lack of high-quality data directly attributing improved clinical outcomes to TPE. There are currently no large studies evaluating the treatment of HTGP without TPE. Study design and methods This study retrospectively analyzes clinical and laboratory outcomes of 115 encounters at Massachusetts General Hospital (MGH) wherein a HTGP patient was treated without TPE and compares these outcomes to those of HTGP patients in the literature treated with TPE. Results After management without TPE, the median reduction in serum triglycerides was 48% (IQR 29%-63%) on day one and 74% (IQR 60%-84%) on day two in 115 episodes of acute HTGP. The reductions were comparable to those reported in several large published case series after a course of TPE (65.8% to 81% reduction). In 25 episodes among 24 patients, treatment included admission to an intensive care unit. There was no significant difference in mortality or rates of local complication, mechanical ventilation, or use of vasoactive medication or renal replacement therapy between this ICU subset and published cohorts (all P > .05). Conclusions HTGP patients who do not receive TPE do not experience inferior outcomes compared to patients in the literature treated with TPE. The added value of TPE in HTGP, if any exists, needs to be demonstrated in controlled trials.

Background In a recent study, we determined that 30% of frequent plateletpheresis donors collected using the Trima Accel Automated Blood Collection System (Terumo BCT) had a CD4+ T-cell count below 200 cells/μL. Whether CD4+ T-cell lymphopenia is associated with donation using other plateletpheresis instruments is unknown. Study design and methods We obtained blood samples from 30 current frequent Fenwal Amicus plateletpheresis donors. All participants had made 20 to 24 plateletpheresis donations in the most recent 365-day period, and all had previously donated over 50 times on the Fenwal Amicus instrument. Blood samples were analyzed to determine blood counts, including CD4+ and CD8+ counts. Results Of 30 study participants, none had a CD4+ count below 200 cells/μL. There was one participant with a CD4+ count between 200 and 300 cells/μL. This individual was over the age of 55 and had a history of more than 300 lifetime plateletpheresis sessions. One participant had a CD8+ count below the lower limit of normal (125 cells/μL) and a normal CD4+ count. Conclusion We did not detect severe CD4+ lymphopenia in frequent platelet donors undergoing plateletpheresis with the Fenwal Amicus. Since the Fenwal Amicus does not incorporate a leukoreduction system chamber, this finding supports the hypothesis that such chambers-found in the Trima Accel instrument-contribute to CD4+ lymphopenia in frequent platelet donors.

Patients with immune-mediated thrombotic thrombocytopenic purpura (iTTP) often experience life-threatening relapses of the disease, and rituximab (RTX) can be used to mitigate relapse risk. However, the predictors of relapse in iTTP and the magnitude and duration of effect of RTX remain key unanswered questions. Using a multi-institutional cohort of consecutive adult patients with iTTP, we used survival analysis to compare relapse rates between patients who received RTX during the index presentation with acute iTTP and those who did not. Of 124 patients, 60 (48%) received RTX and 34 (27%) experienced relapse. Median time to relapse was 3.71 (interquartile range, 1.75-4.9) and 1.33 (interquartile range, 0.43-2.35) years for RTX-treated and untreated patients, respectively. RTX conferred protection from relapse at 1 year of follow-up (P = .01) but not at 5 years of follow-up. Extended Cox regression was then used to identify predictors of relapse and to estimate the protective effect of RTX. The following parameters were independently associated with increased risk for subsequent relapse: presenting in iTTP relapse (hazard ratio [HR], 2.97; 95% confidence interval [CI], 1.4-6.4), age younger than 25 years (HR, 2.94; 95% CI, 1.2-7.2), and non-O blood group (HR, 2.15; 95% CI, 1.06-4.39). RTX initially provided protection from relapse (HR, 0.16; 95% CI, 0.04-0.70), but this effect gradually diminished, returning to the baseline risk for untreated patients at approximately 2.6 years. Patients who are young, have non-O blood group, or present with relapsed iTTP are at increased risk for subsequent relapse. RTX appears to confer short-term protection from relapse.

ObjectivesNo validated screening methods identify patients at risk for human leukocyte antigen (HLA) alloimmune-mediated platelet refractoriness (alloPR). We determined if bead-based HLA antibody tests could predict risk of developing HLA alloPR.MethodsHematopoietic progenitor cell transplant patients screened for HLA antibodies without prior refractoriness were identified. Phenotype bead screening results were compared between patients who later did and did not develop alloPR.ResultsSeven of 27 patients identified subsequently developed alloPR. The panel reactive antibody (PRA) and mean fluorescence intensity (MFI) of the 10 most reactive beads in the initial screen were significantly higher among patients who later developed alloPR (P < .001). Specifically, PRA of more than 30% and mean MFI of 1,500 or more in the most reactive beads identified at-risk patients. Administration of HLA-compatible platelets yielded significant posttransfusion count increments compared with routine platelets.ConclusionsHLA antibody screening by phenotype bead assay may prospectively identify at-risk patients for the development of alloPR. However, clinical trials are needed to validate these findings.

BACKGROUND Alloantibodies recognizing human leukocyte antigens (HLA) can cause immune-mediated refractoriness to platelet transfusion. An association between HLA alloimmunization and red blood cell (RBC) alloimmunization has been suggested but remains uncertain. STUDY DESIGN AND METHODS We tested for HLA alloantibodies in 660 patients with and without RBC alloantibodies. Calculated panel reactive antibody (cPRA) values were determined for HLA alloimmunized patients. Current and historical diagnoses and blood product exposure were catalogued. Variables associated with high-level HLA alloimmunization (cPRA ≥ 90%) were evaluated. RESULTS The cohort included 366 women and 294 men with median age of 66 years (interquartile range [IQR], 53-76). The number of patients with and without RBC alloantibodies was 447 and 213, respectively. Among patients with and without RBC alloantibodies, 20.6% and 8.5% had a cPRA ≥ 90%, respectively (p

The PLASMIC score is a recently described clinical scoring algorithm that rapidly assesses the probability of severe ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) deficiency among patients presenting with microangiopathic haemolytic anaemia. Using a large multi-institutional cohort, we explored whether an approach utilizing the PLASMIC score to risk-stratify patients with suspected immune thrombotic thrombocytopenic purpura (iTTP) could lead to significant cost savings. Our consortium consists of institutions with an unrestricted approach to ADAMTS13 testing (Group A) and those that require pre-approval by the transfusion medicine service (Group B). Institutions in Group A tested more patients than those in Group B (P < 0·001) but did not identify more cases of iTTP (P = 0·29) or have lower iTTP-related mortality (P = 0·84). Decision tree cost analysis showed that applying a PLASMIC score-based strategy to screen patients for ADAMTS13 testing in Group A would have reduced costs by approximately 27% over the 12-year period of our study compared to the current approach. Savings were primarily driven by a reduction in unnecessary therapeutic plasma exchanges, but lower utilization of ADAMTS13 testing and subspecialty consultations also contributed. Our data indicate that using the PLASMIC score to guide ADAMTS13 testing and the management of patients with suspected iTTP could be associated with significant cost savings.

The Harvard TMA Research Collaborative is a multi-institutional registry-based effort to study thrombotic microangiopathies (TMA). Laboratory and clinical parameters were recorded for 254 cases of suspected autoimmune thrombotic thrombocytopenic purpura (TTP). Patients with severe ADAMTS13 deficiency (activity ≤10%, N = 68) were more likely to be young, female and without a history of cancer treatment or transplantation. While all patients with severe deficiency were diagnosed with autoimmune TTP, those without severe deficiency frequently had disseminated intravascular coagulation, drug-associated TMA and transplant-related TMA. Patients with severe ADAMTS13 deficiency had superior overall survival at 360 d compared to those without severe deficiency (93·0% vs. 47·5%, P 0·0001). Almost all patients with severe deficiency received therapeutic plasma exchange (TPE), but the use of TPE in patients with ADAMTS13 activity10% varied significantly across the institutions in our consortium (13·2-63·8%, P 0·0001). Nevertheless, 90-d mortality was not different in patients with ADAMTS13 activity10% between the three hospitals (P = 0·98). Our data show that patients with severe ADAMTS13 deficiency represent a clinically distinct cohort that responds well to TPE. In contrast, TMA without severe ADAMTS13 deficiency is associated with increased mortality that may not be influenced by TPE.

The a disintegrin and metalloprotease with thrombospondin type 1 motifs, member 13 (ADAMTS13) activity assay has become important in distinguishing autoimmune thrombotic thrombocytopenic purpura from other forms of thrombotic microangiopathy (TMA). Although the significance of severe deficiency in ADAMTS13 (activity levels 10% or less) has been well defined, little data are available on the clinical importance of mild to moderate deficiency (activity levels 11%-70%) among patients with TMA.We conducted a retrospective study using the Harvard TMA Research Collaborative Registry. Among 254 patients who met the inclusion criteria for TMA, 186 patients with ADAMTS13 activity levels greater than 10% were divided into moderate-deficiency (11%-40%), mild-deficiency (41%-70%), and no-deficiency (greater than 70%).Compared with mild or no deficiency, moderate ADAMTS13 deficiency correlated with older age; higher bilirubin and international normalized ratio; and increased frequency of sepsis, shock, or multiorgan failure. Platelet counts, lactate dehydrogenase levels, and the presence of renal or neurologic dysfunction did not vary across the three patient cohorts. While moderate ADAMTS13 deficiency was associated with increased 90-day mortality in univariate analysis, this association was no longer significant in multivariate analysis. Variables that independetly predicted 90-day mortality in this cohort of patients included Charlson comorbidity index, alanine aminotransferase level, platelet count, creatinine, and the presence of sepsis, shock, or multiorgan failure.Moderately deficient ADAMTS13 activity identifies a cohort of patients with TMA who are at increased risk for 90-day mortality. The ADAMTS13 activity level in this group is not an independent predictor of poor outcomes but instead appears to be a marker of disease acuity.

Among the syndromes characterised by thrombotic microangiopathy, thrombotic thrombocytopenic purpura is distinguished by a severe deficiency in the ADAMTS13 enzyme. Patients with this disorder need urgent treatment with plasma exchange. Because ADAMTS13 activity testing typically requires prolonged turnaround times and might be unavailable in resource-poor settings, a method to rapidly assess the likelihood of severe ADAMTS13 deficiency is needed.All consecutive adult patients presenting to three large academic medical centres in Boston, MA, USA, with thrombotic microangiopathy and a possible diagnosis of thrombotic thrombocytopenic purpura between Jan 8, 2004, and Dec 6, 2015, were included in an ongoing multi-institutional registry (the Harvard TMA Research Collaborative). Univariate analysis was used to identify covariates for a logistic regression model predictive of severe ADAMTS13 deficiency (≤10% activity). A clinical point score was generated, and its diagnostic performance was assessed using internal and external validation cohorts and compared to clinical assessment alone.214 patients with thrombotic microangiopathy were included in the derivation cohort. A seven-component clinical prediction tool, termed the PLASMIC score, was developed and found to reliably assess the pretest probability of severe ADAMTS13 deficiency (C statistic 0·96, 95% CI 0·92-0·98). Our diagnostic model was reproducibly accurate in both the internal (0·95, 0·91-0·98) and external (0·91, 0·85-0·95) validation cohorts. The scoring system also more consistently diagnosed thrombotic microangiopathy due to severe ADAMTS13 deficiency than did standard clinical assessment, as measured by C statistic (0·96, 95% CI 0·92-0·98 for PLASMIC vs 0·83, 0·77-0·88 for clinical assessment; p0·0001) and mean Brier score (0·065 for PLASMIC vs 0·111 for clinical assessment; mean paired difference 0·05, 95% CI 0·01-0·08; p0·0001). When utilised in addition to clinical assessment, the PLASMIC score contributed significant discriminatory power (integrated discrimination improvement 0·24, 95% CI 0·11-0·37).We have developed and validated a clinical prediction tool-the PLASMIC score-to stratify patients with thrombotic microangiopathy according to their risk of having severe ADAMTS13 deficiency. We have shown that this scoring system is superior to standard clinical assessment in addressing the diagnostic challenge presented by thrombotic microangiopathy. Its use, together with clinical judgment, may facilitate treatment decisions in patients for whom timely results of ADAMTS13 activity testing are unavailable.The Luick Family Fund of Massachusetts General Hospital.

Therapeutic plasma exchange (TPE) is a proven treatment for thrombotic thrombocytopenic purpura (TTP) characterized by severe ADAMTS13 deficiency, but the efficacy of TPE in suspected TTP with an ADAMTS13 activity level of more than 10% remains controversial.We conducted a propensity score (PS)-matched study of 186 adult patients included in the Harvard Thrombotic Microangiopathy (TMA) Research Collaborative registry who presented with TMA suggestive of TTP but an ADAMTS13 activity level of more than 10%.Before matching, patients treated with TPE (n = 71) differed from untreated patients (n = 115) by several clinical measures. PS matching was performed to address clinical disparities between the two groups and resulted in a well-balanced cohort of 59 TPE-treated patients paired with 59 untreated controls, all of whom had TMA. After matching, we observed no significant difference in the primary outcome of 90-day survival between the treated and untreated groups (hazard ratio, 0.88; 95% confidence interval [CI], 0.44-1.77; p = 0.72). In-hospital mortality (odds ratio [OR], 0.77; 95% CI, 0.34-1.75; p = 0.53) and the percentage of patients with platelet count recovery (OR, 1.58; 95% CI, 0.77-3.26; p = 0.21) also did not differ significantly between the two matched groups.Our data suggest that routine use of TPE in the diverse group of TMA patients without severe ADAMTS13 deficiency may not significantly improve outcomes.

Background Endovascular aneurysm repair (EVAR) reduces the morbidity and mortality associated with abdominal aortic aneurysm repair, but in some patients endoleak or aneurysm expansion may necessitate secondary open conversion (SOC). We reviewed the outcomes after delayed SOC following EVAR in consecutive patients at a single center. Methods We retrospectively reviewed all patients undergoing EVAR to identify a cohort undergoing delayed SOC in a single center between 1998 and 2008. We analyzed delayed SOC patients for operative indications, technique, and early outcomes. We made specific comment on the surgical techniques used, with respect to partial or total endograft explantation. Results Delayed SOC was carried out in 10/285 (3.5%) consecutive patients implanted with the Zenith endograft; during this period, two further patients had SOC after initial EVAR in another center. Graft types were Zenith ( n = 10), Talent ( n = 1), and AneuRx ( n = 1). Indications for open conversion were infected graft ( n = 3), sac expansion ( n = 3), type 1 endoleak ( n = 2), type 2 endoleak ( n = 2), juxtarenal aneurysm ( n = 1), and rupture ( n = 1). Explantation techniques were partial explantation with in situ replacement ( n = 7), full explantation with axillobifemoral bypass ( n = 3), in situ replacement ( n = 1), and suturing ( n = 1)Complete stent explantation was required in 4 patients with axillo-bifemoral bypass in three of them. 7 patients had partial stent explantation and one patient stent was left insitu. Postoperative morbidities included myocardial infarction ( n = 1), renal dialysis ( n = 1), and chest infection ( n = 3). No 30-day mortality was noted, and all patients were discharged from hospital and remain well with median follow-up of 5 months (interquartile range 1.7-26.7). Conclusion SOC after EVAR is feasible in selected patients with low morbidity and mortality. Partial explantation with in situ replacement, in the absence of sepsis, may be the preferred revascularization option but may require long-term follow-up.

BACKGROUND: Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related fatality reported to the Food and Drug Administration. Donor screening may reduce TRALI risk. This study sought to compare the efficacy and safety of different TRALI risk-reduction strategies at a hospital-based donor center. STUDY DESIGN AND METHODS: Samples from 1053 donors who answered questions regarding pregnancy and transfusion history were tested for HLA Class I and II antibodies using a flow cytometry–based screening assay. Donor history was compared with the presence of HLA alloantibodies. These data were used to model several TRALI risk-reduction strategies. The medical records of patients transfused fresh-frozen plasma (FFP) from highly alloimmunized donors were retrospectively reviewed for TRALI. RESULTS: HLA alloimmunization was observed among 25.4 percent (256/1009) of all female donors and among 12.0 percent (3/25) of those male donors who gave a history of prior transfusion. Prior pregnancy, reported by 52.6 percent (531/1009) of females, correlated significantly with HLA alloimmunization (p

Transfusion-related acute lung injury (TRALI) is a leading cause of transfusion-associated morbidity and mortality. The National Heart, Lung, and Blood Institute (NHLBI) and Canadian Consensus Conference definitions of TRALI exclude cases of mild TRALI. As a result, many cases of mild TRALI are likely to be missed. Three cases are reported in which patients experienced the acute onset of breathlessness in association with transfusion of blood components containing human leukocyte antigen (HLA) antibodies reactive with recipient HLA antigens. Despite the sudden onset of a pulmonary syndrome in association with transfusion, clinicians caring for these patients did not consider TRALI, and no case would meet recent consensus definitions. Nevertheless, supporting clinical and serologic evidence for TRALI was found in each case. Benefits in recognizing mild cases of TRALI include quantifying the true incidence of TRALI, understanding the physiology of mild versus severe TRALI, and preventing subsequent cases of TRALI due to donors found to have HLA antibodies.

Immunoglobulin A (IgA) deficiency may result in the development of anti-IgA antibodies. Such antibodies may result in anaphylaxis when patients receive standard blood products. Hemophilia A is a deficiency of clotting factor VIII that results in a significant coagulopathy and bleeding in the perioperative period unless precautions are taken. We present a case of successful management of combined hemophilia A and IgA deficiency in a patient undergoing repeated sternotomy for aortic valve replacement.

Collection of hematopoietic progenitor cells by apheresis (HPC-A) requires separation of cells by density. Previous studies highlighted the challenges of HPC-A collection from patients with abnormal red blood cells (RBCs). TEMPI syndrome is a recently described condition defined by teleangiectasias, elevated erythropoietin and erythrocytosis, monoclonal gammopathy, perinephric fluid collections, and intrapulmonary shunting. Patients with TEMPI syndrome have responded to therapies used to treat plasma cell dyscrasias and may benefit from autologous HPC transplantation. We report HPC-A collection from a patient with TEMPI syndrome that was complicated by severe iron deficiency.The patient received granulocyte-colony-stimulating factor (G-CSF) and plerixafor for HPC mobilization and underwent 3 days of HPC-A collection.The patient presented for collection with a microcytic erythrocytosis. Over 3 days, approximately 50 L of whole blood was processed, and 2 × 10(8) CD34+ cells were collected (2.8 × 10(6) CD34+ cells/kg). The mean collection efficiency (CE), percentage of mononuclear cells, hematocrit (Hct), and RBC count were 18%, 90%, 14%, and 9 × 10(11) , respectively. Altering collection variables to avoid RBC contamination reduced CE. Ficoll preparations of the products after freeze-thaw showed RBC contamination and hemolysis. Postthaw viability exceeded 95%. The products were not RBC reduced or washed. There were no adverse reactions during or after infusion.HPC-A collection from a patient with TEMPI syndrome was complicated by microcytic erythrocytosis, leading to RBC contamination and hemolysis in the product. Adequate HPCs were collected and the patient tolerated infusion without RBC depletion or washing. Our report highlights difficulties of HPC-A collection from iron-deficient patients.

Acquired cold urticaria is a condition characterized by the onset of pruritic hives, swelling, and occasional severe systemic reactions, during the rewarming phase, after cold exposure. Pulmonary thromboendarterectomy (PTE) is a cardiac surgical procedure where organized thrombus is excised from the pulmonary vasculature in order to improve pulmonary blood flow and relieve pressure on the right ventricle. A PTE requires institution of deep hypothermic circulatory arrest (DHCA) in order to reduce blood flow from collateral vessels during thrombus excision. We describe a case of PTE performed under DHCA in a patient with ACU.

LVP is used to manage diuretic-resistant ascites in cirrhotic patients. Albumin administration prevents complications including acute kidney injury and paracentesis-induced circulatory dysfunction, but the optimal dose is unclear. We sought to assess adherence to guidelines enacted in July 2011 at our center for reducing the albumin dose administered at large-volume paracentesis (LVP) and evaluate the cost and rate of complications of LVPs before and after guideline enactment. All LVPs performed on cirrhotic patients in our center’s Department of Radiology between July 2009 and January 2014 were studied. Outcomes included adherence to guidelines, LVP complications, and administered albumin cost. Groups were compared using Student’s t tests for continuous data and Chi-square or Fisher’s exact tests for categorical data. A repeated measurements model accounted for patients with multiple LVPs. Of the 935 LVPs, 288 occurred before guideline implementation (group 1) and 647 occurred after (group 2). The mean dose of albumin administered was 13.7 g/L of ascites removed in group 1 versus 10.3 g/L in group 2 (p

Alloimmune platelet refractoriness (alloPR) among actively bleeding surgical patients with thrombocytopenia represents a life-threatening problem. Here we present three cases in which surgical bleeding was complicated by life-threatening thrombocytopenia and alloPR. We demonstrate that the human leukocyte antigens (HLA) antibodies associated with alloPR are broadly reactive and in high concentration, are not removed by hemodilution, and are not absorbed by transfusion of multiple doses of platelet concentrates. HLA alloPR may be under-recognized among surgical patients. Research is needed to develop pre-operative screening methods that will identify patients in need of specialized platelet support using HLA compatible donor products.

Thrombopoietin (TPO) is the major regulator of megakaryopoiesis. Measurement of serum TPO levels may help distinguish between various causes of thrombocytopenia and predict treatment response to TPO receptor agonists. Serum TPO levels from 118 healthy volunteers and 88 patients with abnormal platelet counts were measured using a quantitative ELISA assay. The mean (range) TPO level in healthy volunteers was 39 (7-99) pg/mL. TPO values were correlated with the patient's diagnosis, platelet count, and response to TPO receptor agonists. 88 patients with history of consumptive thrombocytopenia (39) or hypoproliferative thrombocytopenia (49) were analyzed. Median (interquartile range) TPO level for consumptive thrombocytopenia patients was 63 (48-98) pg/mL with a corresponding median (interquartile range) platelet count of 73 (28-146) × 10(9) /L. In contrast, hypoproliferative thrombocytopenia patients had platelet counts [59 (30-117) × 10(9) /L] comparable with consumptive thrombocytopenia patients, but significantly higher serum TPO levels [706 (358-1546) pg/mL, P0.0001]. Analysis of 21 ITP patients treated with TPO receptor agonists demonstrated that a TPO level95 pg/mL was associated with lack of clinical response (P0.002). TPO levels may have diagnostic utility in discriminating between patients with hypoproliferative and consumptive thrombocytopenia. Elevated TPO levels in ITP patients may predict a poor clinical response to treatment with TPO receptor agonists.

Transfusion-related acute lung injury (TRALI) is a major cause of transfusion-related morbidity and mortality. Although the pathogenesis of TRALI is incompletely understood, substantial data from hemovigilance systems, large case series, clinical trials, and animal models have identified antileukocyte antibodies as a major precipitant and have contributed to the development of concrete interventions to reduce the risk of TRALI. This review presents the clinical data supporting specific donor management strategies to reduce TRALI risk and their observed clinical efficacy. Novel strategies that use the donor health questionnaire combined with testing are discussed, and important challenges that remain going forward are explored.

Infertility is a significant medical problem that affects many couples. Evaluation is the starting point for treatment of infertility as it may suggest specific causes and appropriate treatment modalities. Although the history and physical examination provide important information, specific diagnostic tests are required to evaluate infertility. Because the causes of infertility can be multifactorial, a systematic approach typically is used and involves testing for male factor, ovulatory factor, uterotubal factor, and peritoneal factor. Many of these diagnostic tests are laboratory based, including semen analysis, serum progesterone level, serum basal follicle-stimulating hormone level, and clomiphene citrate challenge, and can be done by the primary care physician. Moreover, by understanding the infertility evaluation, the primary care physician can serve as an important resource for advice about infertility. This article briefly reviews the diagnostic approach to infertility, with particular emphasis on important laboratory tests used for evaluation.