Status of hospital-based blood transfusion services in low-income and middle-income countries: a cross-sectional international survey.

OBJECTIVES: Blood transfusion is life-saving for patients experiencing acute blood loss and severe anaemia. In low-income and middle-income countries (LMICs), low blood donation rates and unavailability of whole blood and blood components (blood products) impairs timely blood transfusion. To fulfil patient-specific blood orders, a hospital blood transfusion service (HBTS) receives orders from a prescriber for blood transfusion, tests and prepares blood products for the patient. This study sought to describe the current state of LMIC HBTS. DESIGN: A cross-sectional survey explored LMIC HBTS access to blood products, testing methods, policies and structure. Surveys were administered in English, Spanish, French and Russian, followed by a mixed-methods analysis. SETTING: HBTS within LMICs. PARTICIPANTS: From among 124 public and private facilities invited to participate, we received 71 (57%) responses. Of these responses, 50 HBTS from 27 LMICs performed on-site blood transfusions. RESULTS: Most LMIC HBTS perform blood collection to generate blood products for their patients (36/47, 77%); few relied exclusively on an external supply of blood products (11/47, 23%). The primary reason for blood transfusion was adult anaemia for non-malignant conditions (17/112, 15%). Testing methods varied by gross national income per capita. Blood transfusion delays to patients were common (17/30, 57%) attributed to inadequate blood inventories (13/29, 45%). Other barriers included lack of regular clinician education about transfusion (8/29, 28%) and sustainable financial models for the HBTS (4/29, 14%). CONCLUSION: This survey describes the status of HBTS in diverse LMICs, illustrating that the availability of blood products remains a principal problem, requiring HBTS to generate its own facility's blood supply. Currently, blood shortages are not reported as a patient-specific adverse event making systematic tracking of delays in transfusion difficult. These findings highlight areas for further exploration related to the lack of available blood inventories for transfusions at HBTS in LMICs.

Global survey of transfusion medicine curricula in medical schools: Challenges and opportunities.

BACKGROUND: Physician's knowledge in transfusion medicine (TM) is critical for patient safety. Therefore, ensuring that medical schools provide adequate education in TM is important. The aim of this study was to assess the status of TM education at a global level. STUDY DESIGN AND METHODS: A comprehensive anonymous survey to assess TM education in existing medical school curricula was developed. The survey was distributed to deans and educational leads of medical schools in a range of low-, medium-, high-, and very high-human development index (HDI) countries. It included 20 questions designed to assess specific domains including structure of TM curriculum and teaching faculty. RESULTS: The response rate was 53%. The majority of responding schools from very-high-HDI countries offered a 6-year curriculum after high school or a 4-year curriculum after college education, whereas most schools from medium-HDI countries offered a 5-year medical curriculum. A formal teaching program was available in only 42% of these schools in contrast to 94% of medical schools from very high-HDI. Overall, 25% of all medical schools did not offer structured TM teaching. When offered, most TM teaching was mandatory (95%) and integrated within the third and fourth year of medical school. Formal assessment of TM knowledge was done in 72% of all responding medical schools. More than half of the deans considered the TM education in their medical schools as inadequate. CONCLUSION: Despite its limitations, the current survey highlights significant gaps and opportunities of TM education at a global scale.

How do I manage O- red blood cell inventory.

Currently there are no widely accepted guidelines regarding the appropriate use of O- red blood cells (RBCs). Although there has been a decline in overall RBC utilization since 2010, the use of O- RBCs has continued to proportionally increase over this time period resulting in frequent shortages. When faced with these shortages, we implemented some simple strategies that resulted in a significant decrease in annual O- RBC utilization from 10% to 7.5% despite an increase in total RBC utilization. These strategies included collaboration with the clinical staff, improving practices within the blood bank, and having our health system partner with our blood supplier. Herein, we detail our strategies for hospital transfusion services to improve O- RBC utilization. Most of these can be easily implemented and do not require additional resources.

Closed-Loop- and Decision-Assist-Guided Fluid Therapy of Human Hemorrhage.

OBJECTIVES: We sought to evaluate the efficacy, efficiency, and physiologic consequences of automated, endpoint-directed resuscitation systems and compare them to formula-based bolus resuscitation. DESIGN: Experimental human hemorrhage and resuscitation. SETTING: Clinical research laboratory. SUBJECTS: Healthy volunteers. INTERVENTIONS: Subjects (n = 7) were subjected to hemorrhage and underwent a randomized fluid resuscitation scheme on separate visits 1) formula-based bolus resuscitation; 2) semiautonomous (decision assist) fluid administration; and 3) fully autonomous (closed loop) resuscitation. Hemodynamic variables, volume shifts, fluid balance, and cardiac function were monitored during hemorrhage and resuscitation. Treatment modalities were compared based on resuscitation efficacy and efficiency. MEASUREMENTS AND MAIN RESULTS: All approaches achieved target blood pressure by 60 minutes. Following hemorrhage, the total amount of infused fluid (bolus resuscitation: 30 mL/kg, decision assist: 5.6 ± 3 mL/kg, closed loop: 4.2 ± 2 mL/kg; p < 0.001), plasma volume, extravascular volume (bolus resuscitation: 17 ± 4 mL/kg, decision assist: 3 ± 1 mL/kg, closed loop: -0.3 ± 0.3 mL/kg; p < 0.001), body weight, and urinary output remained stable under decision assist and closed loop and were significantly increased under bolus resuscitation. Mean arterial pressure initially decreased further under bolus resuscitation (-10 mm Hg; p < 0.001) and was lower under bolus resuscitation than closed loop at 20 minutes (bolus resuscitation: 57 ± 2 mm Hg, closed loop: 69 ± 4 mm Hg; p = 0.036). Colloid osmotic pressure (bolus resuscitation: 19.3 ± 2 mm Hg, decision assist, closed loop: 24 ± 0.4 mm Hg; p < 0.05) and hemoglobin concentration were significantly decreased after bolus fluid administration. CONCLUSIONS: We define efficacy of decision-assist and closed-loop resuscitation in human hemorrhage. In comparison with formula-based bolus resuscitation, both semiautonomous and autonomous approaches were more efficient in goal-directed resuscitation of hemorrhage. They provide favorable conditions for the avoidance of over-resuscitation and its adverse clinical sequelae. Decision-assist and closed-loop resuscitation algorithms are promising technological solutions for constrained environments and areas of limited resources.

Effect of freezing plasma at -20°C for 2 weeks on prothrombin time, activated partial thromboplastin time, dilute Russell viper venom time, activated protein C resistance, and D-dimer levels.

To assess the impact of preanalytical variables of time and temperature on prothrombin time (PT), activated partial thromboplastin time (aPTT), dilute Russell viper venom time (DRVVT), activated protein C resistance (APCR), and d-dimer, samples from 23 healthy individuals and 18 patients having coagulopathy with known abnormal PT and aPTT were collected. Plasma from each individual was separately pooled and aliquoted; the first 2 aliquots were stored at room temperature then analyzed at 2 hours (baseline) and 4 hours postcollection. The remaining aliquots were stored at -20°C and thawed for analysis at 48 hours, 1, and 2 weeks. In both healthy participants and participants with coagulopathy, PT, aPTT, APCR, DRVVT, and D-dimer had no significant changes at 4 and 48 hours, and 1 and 2 weeks postcollection compared to baseline, or the changes were less than 10%. The results indicate PT, aPTT, DRVVT, APCR, and d-dimer can be stored for 2 weeks at -20°C without compromising clinical interpretation in both healthy individuals and individuals with coagulopathy. Increasing storage time will facilitate sample processing from off-site clinics.

Transplantation of high panel-reactive antibody left ventricular assist device patients without crossmatch using on-bypass pheresis and alemtuzumab.

BACKGROUND: Highly sensitized (HS) left ventricular assist device (LVAD) patients with high panel-reactive antibody (PRA) levels present a challenge. Alemtuzumab, a potent depleting agent for T and B lymphocytes (months to years), and plasmapheresis, offer an opportunity for heart transplantation to these patients who might die of VAD complications on the transplant waiting list. This study compared rates of acute rejection and survival of a HS LVAD cohort with a contemporaneous control group after heart transplant. METHODS: Clinical courses of 31 consecutive patients who underwent transplantation between January 2006 and January 2011 were reviewed. Eight patients with a T or B PRA of 70 or more (HS+) received non-crossmatched, ABO-compatible hearts using intraoperative plasmapheresis and alemtuzumab induction. Controls (HS-) received basiliximab induction. Acute rejection was defined as International Society for Heart and Lung Transplantation grades 2R or higher, or antibody-mediated rejection. RESULTS: The difference in survival between HS+ and HS- groups at 1 year (100% vs 94%) or at a mean follow-up of 2.3 and 2.4 years (75% vs 70%) was not significant. Retrospective lymphocytotoxic crossmatches were positive in 7 of 8 HS+ patients (6 T+ and B+, 1 B+) vs none in the HS- group (p < 0.001). There was a trend toward increased risk of cellular rejection per 100 patient-days beyond 1 year in the HS+ group (p = 0.07). Risk of humoral rejection was significantly increased in the HS+ group (38% vs 4%; p = 0.04). CONCLUSIONS: Heart transplantation with plasmapheresis and alemtuzumab in HS LVAD patients, most with a positive crossmatch, does not compromise midterm survival. The expected higher rates of rejection, especially beyond the first postoperative year, demand adjustments in surveillance strategies and immunosuppressive management.

Human IgA-inducing protein from dendritic cells induces IgA production by naive IgD+ B cells.

Over the last several years, there has been a great deal of progress in characterizing the role of dendritic cells (DCs) in the activation and modulation of B cells. DC-secreted chemokines can induce B cell trafficking to the lymph nodes. DC-produced survival factors such as B cell-activating factor of the TNF family and a proliferation-inducing ligand have been shown to be essential for B cell maturation, but have also been implicated in class-switch recombination and B cell lymphoma survival. Recently added to this list of DC-derived factors effecting B cells is IgA-inducing protein (IGIP). In this study, we characterize production of IGIP by human DCs, and examine its capacity to induce IgA class switching and differentiation of naive B cells in vitro. Monocyte-derived DCs were cultured in vitro with TLR agonists (TLR3, 4, 5, and 9) and other factors, including CD40 ligand, GM-CSF, and IL-4 as well as the neuropeptide vasoactive intestinal peptide. Under in vitro stimulation with vasoactive intestinal peptide and CD40L, IGIP mRNA expression could be up-regulated as much as 35-fold above nonstimulated samples within 12-48 h. Naive B cells cultured with exogenous recombinant human IGIP produced IgA in greater quantities than nonstimulated controls. Finally, we demonstrate that IGIP stimulation drives the production of mu-alpha switch circles from IgM(+)IgD(+) naive human B cells, indicating its role as an IgA switch factor.

A prospective audit program to determine blood component transfusion appropriateness at a large university hospital: a 5-year experience.

Predetermined transfusion guidelines, pretransfusion approval, and transfusion audits are useful tools in the education of those ordering blood components, potentially resulting in the reduction of inappropriate use of blood components. Our institution requires mandatory prospective audits for a proportion (10%) of packed red blood cell unit orders and all orders for fresh frozen plasma, platelets, and cryoprecipitate. Cases where the blood bank physician recommends against a transfusion and the ordering physician concurs, or when blood components are released against blood bank's recommendation, are referred to the transfusion committee. Transfusion committee members review the medical records to determine the circumstances surrounding the transfusion request as well as patient outcomes relating to their receiving or not receiving the transfusion. We analyzed 220 transfusion episodes brought before the transfusion committee from 2001 to 2005. The most requested blood component denied or changed was fresh frozen plasma. With only a few exceptions, the denial or change of blood components had no adverse effect on the patient. Nonetheless, these interventions were deemed appropriate by the transfusion committee. In most cases, blood components released based on the demand of the ordering physician, despite the advice of the blood bank physician, were deemed as inappropriate transfusions. This study therefore suggests that prospective audits of blood component orders can help reduce inappropriate transfusions and can be a valuable educational tool for the ordering physicians as well as for residents in training.

Plasmapheresis for diffuse alveolar hemorrhage in a patient with Wegener's granulomatosis: case report and review of the literature.

We present a case of a 20-year-old male with Wegener's Granulomatosis involving the upper respiratory tract, lungs, and kidneys. In his fourth hospital admission, the patient presented with diffuse alveolar hemorrhage and poor pulmonary function: FiO2 of 100% and PEEP of 17cm H2O on intubation. Due to a fast clinical deterioration while receiving drug therapy (cyclophosphamide and methylprednisolone), we performed nine daily 1-volume therapeutic plasma exchanges (TPE) using 5% albumin as replacement fluid. TPE resulted in a decrease in cytoplasmic anti-neutrophil cytoplasm antibodies (c-ANCA) titer from 1:1,024 to 1:16. On the ninth day of plasmapheresis, his pulmonary status was markedly improved with FiO2 of 60% and PEEP of 8 cm H2O. The patient was later extubated and discharged home in stable condition. Wegener's Granulomatosis with pulmonary hemorrhage is not included in the current guidelines for therapeutic apheresis; therefore, we report this case and, if warranted, propose this condition to be included in the guidelines.

Sequestration of anti-Cra in the placenta: serologic demonstration by placental elution.

BACKGROUND: Few cases of antibodies to the Cromer (a) antigen have been described during pregnancy. Interestingly, the anti-Cr(a) titers decreased during pregnancy, and although the newborns were Cr(a)+, the direct antiglobulin tests (DATs) were negative and hemolytic disease of the newborn (HDN) was not observed. Cromer antigens reside on the decay-accelerating factor (DAF), which is expressed on the fetal derived syncytiotrophoblast layer of the placenta. It has been postulated that Cromer antibodies are not transported to the fetus, but are bound to placental DAF, thereby protecting the fetus from HDN and causing the disappearance of Cromer antibody in maternal plasma. This report is the first to demonstrate Cromer antibody sequestration by the placenta. CASE REPORT: A G4P1 woman with an anti-Cr(a) presented for prenatal care during her fourth pregnancy. The anti-Cr(a) titer decreased from 64 at 7 weeks gestation to undetectable after 25 weeks. At delivery, the infant had no evidence of HDN. The infant's DAT was negative, and the maternal plasma, cord plasma, and the cord blood eluate were negative with screening cells, the infant's cord cells, and the mother's cells. Placental eluates revealed anti-Cr(a). CONCLUSIONS: This is the fourth case report of a Cromer (a-) woman producing anti-Cr(a) during pregnancy, and the first demonstrating anti-Cr(a) sequestration in the placenta. The presence of anti-Cr(a) in the placental eluate, but not in the cord plasma, maternal plasma, or cord blood eluate, strongly supports the hypothesis that DAF at the fetomaternal interface absorbs anti-Cr(a) from the maternal circulation blocking its passage to the fetus.

Blood bank on-call physician's experiences at a large university medical center.

BACKGROUND: The responsibilities of the blood bank on-call physician (blood bank physician from here on) encompass many aspects of transfusion medicine and physician education. This physician is available 24 hours a day to address any issues concerning the collection and transfusion of blood and blood components. The purpose of this study was to identify and categorize the issues that may confront a blood bank physician. STUDY DESIGN AND METHODS: Each call received over a 4-month period was logged and the resolution documented. The calls were grouped into five categories: donor issues, therapeutic procedure issues, patient issues, physician education issues, and requests for blood components not meeting previously defined transfusion guidelines. RESULTS: The blood bank physician received 224 calls during the study period. To resolve each issue, an additional 1 to 14 telephone calls were needed to gather further information. Number of calls by category were donor issues, 20 (8.9%); therapeutic procedure issues, 9 (4.0%); patient issues, 4 (1.8%); physician education issues, 33 (14.7%); and requests for blood components not meeting previously defined transfusion guidelines, 158 (70.6%). Requests for blood components were denied in 39.8 percent of the cases not meeting guidelines. Other forms of therapy were warranted in 20.9 percent of the cases. CONCLUSION: This study revealed that 85.3 percent of the calls referred to the blood bank physician related to physician education and the appropriateness of blood component orders. These results emphasize the need for ongoing education of medical staff in transfusion medicine issues.

Detection of antibodies to human immunodeficiency virus (HIV) that recognize conformational epitopes of glycoproteins 160 and 41 often allows for early diagnosis of HIV infection.

On the basis of human immunodeficiency virus (HIV) needlestick studies, the time to seroconversion for anti-HIV antibodies is 1-9 months (mean, approximately 2-3 months). However, an earlier marker of an immune response to HIV often occurs-serum anti-HIV antibodies reactive with live HIV-infected cells, termed "early HIV antibodies." The specificities of these antibodies are characterized by the recognition of type-specific conformational epitopes of the HIV envelope glycoprotein (gp) 160 and gp41. By use of a third-generation native HIV(IIIB) gp160 enzyme immunoassay (EIA), detection of HIV antibodies occurred, on average, 33 days earlier than did detection by commercial EIA and 25 days earlier than did detection by the reference antigen and reverse-transcription polymerase chain reaction (RT-PCR) assays in 3 of 5 HIV seroconversion panels. A fourth panel possessed early HIV antibodies that reacted with HIV(213) but not with HIV(IIIB), allowing for detection of HIV antibodies approximately 3 weeks earlier than by RT-PCR or other current tests.