Thrombotic microangiopathy - the importance of a multidisciplinary approach.

PURPOSE OF REVIEW: The purpose of this review is to highlight the importance of a multidisciplinary thrombotic microangiopathies (TMA) Team. This goal will be accomplished through review of the complement system, discuss various causes of thrombotic microangiopathies (TMA), and aspects of their diagnosis and management. In so doing, readers will gain an appreciation for the complexity of this family of disorders and realize the benefit of a dedicated multidisciplinary TMA Team. RECENT FINDINGS: TMA causes derive from multiple specialty areas, are difficult to timely recognize, pose complex challenges, and require multidisciplinary management. Hematopoietic stem cell transplant-associated TMA (TA-TMA) and TA-TMA related multiorgan dysfunction syndrome (TA-TMA MODS) are areas of burgeoning research; use of complement testing and eculizumab precision-dosing has been found to better suppress complement activity in TA-TMA than standard eculizumab dosing. Newer tests are available to risk-stratify obstetric patients at risk for severe pre-eclampsia, whose features resemble those of TA-TMA MODS. Numerous disorders may produce TMA-like findings, and a systematic approach aids in their identification. TMA Teams elevate institutional awareness of increasingly recognized TMAs, will help expedite diagnostic and therapeutic interventions, and create pathways to future TMA-related research and facilitate access to clinical trials. SUMMARY: Establishment of a TMA-Team is valuable in developing the necessary institutional expertise needed to promptly recognize and appropriately manage patients with TMA.

Peripheral blood stem cell collection: Are midline catheters a viable alternative to central venous catheters?

BACKGROUND: Vascular access is a rate-limiting step for peripheral blood stem cell collection. In the absence of readily accessible superficial veins, placement of tunnelled or non-tunnelled central venous catheters (CVCs) is common. These invasive access routes create medical risks for patients and are associated with logistical challenges, thus prompting a search for alternatives. One such option is the off-label use of midline catheters. STUDY DESIGN AND METHODS: We carried out a literature search for published experience with the use of midline catheters for peripheral blood stem cell collection. Data extracted included whether collections were allogeneic or autologous, donor sex, age and weight, inlet flow rate, total blood volumes (TBV) processed, collection duration, number of collections per donor, and achievement of collection targets. RESULTS: The search produced three reports (one in abstract form) comprising 19 patients and 26 collection events. Donor sex and status were provided for 18 patients; 10 were female, 8 were male, 12 were allogeneic, and 6 autologous. Median (range) for: donor age was 28 (12-59); donor body weight (kg) was 77.5 (45.4-113.4); inlet flow rate (in mL/min) was 66 (28-80); TBV processed (in mL) was 15,880 (6178-21,871); collection duration (in hours) was 5.0 (3.2-7.0); and CD34 × 106/kg collection yield was 5.9 (3.6-23.0). Target CD34 yields were achieved in 14/19 (74%) of donors with 7/19 (37%) requiring two collections days. DISCUSSION: Peripheral blood stem cell collection does appear to be viable via midline-based catheter access, particularly for allogeneic donors and shorter collection courses. Development of institution-specific guidelines and care pathways are recommended.

Therapeutic modalities in thrombotic thrombocytopenic purpura management among Jehovah's Witness patients: A review of reported cases.

INTRODUCTION: Devout members of the Jehovah's Witness faith flatly refuse transfusions of white blood cells, red blood cells, platelets, and plasma. The latter agent is a mainstay in the treatment of thrombotic thrombocytopenic purpura (TTP). Alternative treatment options for Jehovah's Witness patients are needed and reviewed herein. METHODS: Cases of TTP treatment among Jehovah's Witnesses were obtained from the published literature. Key baseline and clinical data were extracted and summarized. RESULTS: A total of 13 reports spanning a 23-year period and 15 TTP episodes were identified. Median (IQR) age was 45.5 (29.0-57.5) and 12/13 (93%) patients were female. Neurologic symptoms were present in 7/15 (47%) episodes at presentation. Disease confirmation with ADAMTS13 testing was present in 11/15 (73%) of episodes. Corticosteroids and rituximab were employed in 13/15 (87%) and 12/15 (80%) of cases, respectively, with apheresis-based therapy employed in 9/15 (60%) episodes. For eligible cases, caplacizumab was used in 4/5 (80%) episodes; average time to platelet response was shortest in these cases. Sources of exogenous ADAMTS13 accepted by patients in this series included cryo-poor plasma, FVIII concentrate, and cryoprecipitate. CONCLUSIONS: Successful management of TTP within the boundaries of the Jehovah's Witness faith is possible.

Effect of erythropoietin on perioperative blood transfusions in primary total hip arthroplasty: A systematic review.

BACKGROUND: Primary total hip arthroplasty (THA) often requires blood transfusion. Transfusions are undesirable due to risks of infectious and noninfectious complications. This systematic review therefore studied the effectiveness of erythropoietin (EPO) in reducing allogeneic transfusion rate during THA. METHODS: Using the MESH terms "Erythropoietin" AND "Total Hip" with restrictions to 'Randomized Controlled Trial', 'Clinical Trial', 'Humans', and 'English', a literature search was performed in PubMed and CINAHL. Articles were scanned by both authors and retained for further review if eligibility was met according to the inclusion criteria defined by the PICOS (population, intervention, comparator, outcomes, study design) configuration. Risk of bias was assessed using the Cochrane risk of bias criteria. Data extracted include patient demographics, intervention versus comparator arm, outcomes, laboratory data, and individual study characteristics. The primary outcome of focus was rate or amount of allogeneic blood transfusions intra- or postoperatively. In 6/8 studies, data permitted calculations of absolute risk reduction (ARR) in transfusion rate (%) and number needed to treat (NNT) to evade transfusions. RESULTS: A total of 8 studies met all eligibility criteria and were retained for data extraction; risk of bias was low-moderate in 7/8 and high in 1/8. Allogeneic transfusion exposure was lowered by the intervention in 7/8 studies with ARR from 9.6% to 33.5% and NNT from 4 to 10. CONCLUSIONS: In the blood conservation systems described, the addition of EPO was effective in reducing allogeneic transfusions. The studies included spanned a nearly 30-year period. Earlier studies incorporated preoperative autologous donation, a now outdated modality.

Caplacizumab as rescue therapy in refractory TTP involving neurologic features.

BACKGROUND: The role of caplacizumab in the routine treatment of immune thrombotic thrombocytopenic purpura (iTTP) remains to be established. CASE SUMMARY: A 56-year-old woman was transferred to our center with iTTP and neurologic features. At the outside hospital, she was initially diagnosed and managed as Immune Thrombocytopenia (ITP). Upon transfer to our center, daily plasma exchange, steroids, and rituximab were initiated. After an initial improvement, refractoriness became evident with a decline in platelet count and continued neurologic abnormalities. Initiation of caplacizumab resulted in rapid hematologic and clinical responses. CONCLUSION: Caplacizumab is a valuable treatment modality in iTTP, particularly in cases associated with refractoriness or neurologic features.

Updates on the mobilization pipeline for hematopoietic stem cell collection.

Hematopoetic Stem Cell Transplantation is a life saving procedure which requires mobilization of stem cells for apheresis procedure. In this review we aimed to examine mobilizing agents that are in use and under investigation. Apheresis practitioners who oversee stem cell collections should be familiar with the recent advances in mobilization agents to utilize most up-to-date information for better patient outcomes.

Acquired methemoglobinemia: A systematic review of reported cases.

INTRODUCTION: Acquired methemoglobinemia may cause cyanosis and tissue ischemia unresponsive to oxygen supplementation. METHODS: We performed a literature search to identify cases of acquired methemoglobinemia published between 1980 and 2020. Clinical, diagnostic, and treatment details were extracted from eligible cases. RESULTS: A total of 76 reports involving 87 cases were analyzed. The median age at presentation was 32.5 with male to female ratio of 1.6. Cyanosis and SpO2 <90 % were reported in 82 % and 60 % of cases, respectively. Dapsone or cocaine-based anesthetics were causative in 52 % of cases; most anesthetic-related cases occurred in the peri-procedural setting. Methylene blue (MB) and red cell transfusion were given in 71 % and 10 % of cases, respectively. Compared to MB untreated patients, MB treated patients were more likely to be cyanotic (91.9 % vs 54.2 %), had higher proportions (%) and levels (g/dL) of methemoglobin (MetHb) - 33.2 % vs 15.3 % and 3.1 g/dL vs 1.2 g/dL, respectively. We found that among cyanotic cases, the median MetHb level was 3.0 g/dL (0.4-12.3 g/dL) with 74 % of values ≥ 1.5 g/dL. An SaO2:SpO2 ratio of >1 was not universally present, but always coincided with an [SaO2-SpO2] delta value greater than zero. CONCLUSIONS: Cyanosis and hypoxemia were not universal findings of acquired methemoglobinemia in our series. In addition, not all patients had cyanosis at MetHb ≥ 1.5 g/dL or an SaO2:SpO2 ratio of >1. All those with an SaO2:SpO2 >1 did, however, have a delta value greater than zero - a finding not previously reported which we feel holds diagnostic value.

"Plasma exchange in a bottle": An overview of efgartigimod for apheresis practitioners.

Efgartigimod represents a first-in-class immunomodulatory agent that is comparable to TPE in reducing immunoglobulin levels. This translates to reductions in Myasthenia Gravis symptom scores with maximal effect following the fourth weekly efgartigimod dose. Efgartigimod received FDA approval in December of 2021 and may be an alternative particularly for patients on long-term TPE regimens of weekly or less frequent. Apheresis practitioners, especially those managing long-term apheresis in seropositive individuals, may therefore see some of their patients transitioned from plasma exchange to efgartigimod. Long-term experience with efgartigimod remains lacking and studies are needed to establish the role of efgartigimod in the acute setting.

Current state of therapeutic apheresis and cellular therapy education for transfusion medicine fellows in the United States.

BACKGROUND: Numerous conditions are responsive to therapeutic apheresis (TA) and cellular therapy (CT) treatments. Both TA and CT are two broad and diverse knowledge fields within transfusion medicine (TM). We therefore sought to survey all the TM fellowship program directors (PDs) in the United States to examine the current fellow state education in TA and CT. METHODS: A 37-question survey was sent to all PDs to collect details of TA and CT training for TM fellows. RESULTS: Responses from 29/51 (56.9%) surveyed programs were received. Most PDs considered TA and CT training for their fellows more than adequate. Two PDs from programs that did not directly oversee TA and CT services at their training sites stated that their program's training in these two areas were only "slightly adequate" or "moderately inadequate." Detailed analysis of training in TA, cell collection, and CT suggests that trainees from programs with direct oversight of these services had longer training and more learning experiences compared to those in which outside rotations were required. CONCLUSIONS: Transfusion medicine fellowship training in TA and CT varies. Most respondents, and particularly those from programs directly overseeing TA services, reported their fellows were adequately prepared in TA. Cellular therapy collections and laboratory operations, however, are less consistent areas of training despite the rapid expansion of these fields. Our survey suggests that a greater emphasis in CT training is needed.

The use of therapeutic plasma exchange as adjunctive therapy in the treatment of coronavirus disease 2019: A critical appraisal of the current evidence.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a major pandemic. While vaccine development moves forward, optimal treatment continues to be explored. Efforts include an ever-expanding number of clinical trials along with newly proposed experimental and off-label investigational therapies; one of which is therapeutic plasma exchange (TPE). There have been a number of publications on TPE use as adjunctive therapy for coronavirus disease 2019 (COVID-19), but no prospective randomized controlled trials (RCTs) have been completed. This article critically appraises the current available evidence on TPE as a treatment modality for SARS-CoV-2 infection.

Transfusion transmitted babesiosis: A systematic review of reported cases.

BACKGROUND: Transfusion transmitted babesiosis (TTB) has a high mortality rate but may go unrecognized, particularly in non-endemic areas. We therefore conducted a systematic review to better characterize clinical aspects of TTB. METHODS: A literature search was conducted in PubMed and CINAHL databases, from which 25 eligible articles describing 60 TTB patients met criteria for data extraction. RESULTS: Symptom evaluation was provided for 25 implicated donors: 18/25 (72%) were asymptomatic while 7/25 (28%) had mild flu-like symptoms but were asymptomatic at time of donation. It was common for a single donor or donation to infect multiple patients. Where reported, species included B. microti - 54/60 (90%), B. duncani - 3/60 (5%), and B. divergens-like/MO-1 - 1/60 (2%). Most TTB patients (44/60, 73%) resided in endemic states, while most TTB deaths 6/9 (67%) occurred in non-endemic states. Severity of hemolysis was proportional to degree of parasitemia. Mortality in our series was 9/60 (15%); most deaths occurred at extremes of the age spectrum: 6/9 non-survivors were aged >55 years, 2/9 were <1 year, only 1/9 was 2-54 years. Number of comorbidities was higher among non-survivors (median = 4) compared to survivors (median = 1). CONCLUSIONS: All implicated donors (for which symptoms data were reported) resulting in TTB infections were asymptomatic at the time of donation, and it was common for a single donor or donation to infect multiple patients. Mortality of TTB appeared highest among those with more comorbidities and in non-endemic states. Heightened awareness of this diagnosis is key in its recognition.

Cobalamin deficiency presenting with thrombotic microangiopathy (TMA) features: A systematic review.

INTRODUCTION: Cobalamin deficiency may result in hematologic characteristics similar to thrombotic microangiopathy (TMA). To facilitate diagnosis, we reviewed reported cases of acquired cobalamin deficiency presenting with TMA features (c.def-TMA). METHODS: A literature search identified reports of c.def-TMA. Deficiency was defined as B12 levels of <118 pmol/L. Corrected reticulocyte counts and reticulocyte production indexes were calculated. Clinical features were presented as proportion abnormal and results summarized as medians and interquartile ranges (IQR). RESULTS: Patient level data was extracted from 41 identified cases. Median age (years) was 43 (30-55) with 21/41 (51%) being female. Cobalamin deficiency was noted in 35/40 (87.5%) but fold increases in MMA and HC were 30 and 6, respectively. The etiology was pernicious anemia in 28/41 (68%) cases. Anemia was both universal and severe, with hemoglobin levels of 55 g/L (4.7-6.6). Hypersegmented neutrophils were noted in 23/37 (62%), schistocytes in 29/38 (76%) and median LDH levels 3981 U/L (2004-5467). The RPI was <3.0% in all patients. Thrombocytopenia occurred in 33/41 (80.5%) with a median platelet count of 91 × 109/L (42-112). Plasma infusion or exchange was initiated in 14/41 (34%) with associated complications in 2 cases. CONCLUSION: Reticulocytopenia (RPI of <3.0%) was a universal finding that aids in differentiating c.def-TMA from other causes of hemolysis. C.def-TMA was associated with severe anemia, generally mild-moderate thrombocytopenia, and significant elevations in LDH.

Long-term plasma exchange as maintenance therapy for cerebellar-type Hashimoto's encephalopathy, a case report.

Hashimoto's encephalopathy (HE) is a presumed autoimmune disorder associated with anti-thyroid autoantibodies and signs and symptoms of encephalopathy. A sub-type of HE is associated with cerebellar dysfunction and ataxia. Immunosuppressive therapy, particularly corticosteroid treatment, is utilized in the majority of cases. Short-term apheresis has been reported with variable patient responses. Here we report the case of a 72 year-old female with an ∼15 year history of cerebellar type HE that had profound improvement in symptoms after long-term apheresis treatment over an ∼2 year period. Following an induction phase, twice-weekly maintenance apheresis of 1 plasma volume reversed long-standing severe gait ataxia that had required a walker, as well as mild cognitive symptoms. This paralleled reductions in anti-thyroid antibody levels. Holidays from apheresis lasting several weeks and/or reductions in maintenance apheresis frequency to once per-week resulted in re-expression of ataxia and cognitive impairments along with a rise in anti-thyroid antibody levels. An apheresis dose-effect was observed whereby parallel rise and fall in both symptomatology and antibody levels would mirror duration between apheresis intervals. To our knowledge, this is the first report of profound therapeutic benefit and a dose-response relationship to long-term apheresis in cerebellar-type HE. This case suggests that maintenance apheresis be considered in responsive patients, particularly in those with contraindications to medical immunosuppression.

Safety analysis of apixaban versus warfarin in patients with advanced kidney disease.

Anticoagulation in patients with advanced kidney disease, defined as those with an eGFR < 25 mL/min, including patients with end-stage renal disease on hemodialysis, remains an area of controversy and debate. Due to safety concerns regarding the increased risk for bleeding in this population, these patients have been excluded from all large-scale, randomized controlled trials to date. Warfarin and apixaban are both FDA-approved for use in this population and although warfarin remains the anticoagulant of choice, apixaban use is steadily increasing. This review combines relevant literature to better understand the risk versus benefit of anticoagulation in patients with severe kidney disease as well as the safety of apixaban versus warfarin in this population. High rates of bleed were found among both anticoagulants in those with severe kidney disease, suggesting that the risk for bleed associated with anticoagulation may not outweigh the benefit of treatment. Apixaban was found to be superior in rates of major bleed in those with ESRD on HD and may be superior to warfarin in those with an eGFR < 25 mL/min. However, large-scale, randomized clinical trials are needed to validate these results. With the continued development of novel agents there may be superior alternatives to apixaban and warfarin in those with severe kidney disease in the future.

Successful Peritoneal Dialysis Catheter Placement in a New End-Stage Renal Disease Patient with Combined Antiphospholipid Syndrome and Factor XI Deficiency.

Coagulopathies and bleeding disorders can affect dialysis outcomes by increasing the thrombosis risk at the arteriovenous access or by causing prolonged bleeding at access or catheter sites. We present the case of a 68-year-old woman with combined antiphospholipid syndrome and factor XI deficiency, with chronic prolongation of activated partial thromboplastin time that was not correctable with fresh-frozen plasma (FFP).The patient had a history of stroke, but was not on antiplatelet therapy because of mucocutaneous bleeding events. She had progressive renal failure attributed to her autoimmune disease, and a decision was made to pursue peritoneal dialysis (PD) when she reached end-stage kidney disease. She was admitted to the hospital the day before her planned PD catheter placement and was transfused with FFP and platelets before placement of a temporary hemodialysis catheter. One session of hemodialysis was performed to minimize uremic platelet dysfunction. The patient was given additional FFP and platelets at the time of PD catheter placement; desmopressin was not used. No thrombotic or bleeding complications occurred, and at 8 months out, the patient has been doing well on PD.In summary, careful perioperative planning led to successful PD initiation in a patient with combined bleeding and clotting disorders.

Perioperative blood ordering optimization process using information from an anesthesia information management system.

BACKGROUND: As part of ongoing perioperative surgical home implantation process, we applied a previously published algorithm for creation of a maximum surgical blood order schedule (MSBOS) to our operating rooms. We hypothesized that using the MSBOS we could show a reduction in unnecessary preoperative blood testing and associated costs. STUDY DESIGN AND METHODS: Data regarding all surgical cases done at UC Irvine Health's operating rooms from January 1, 2011, to January 1, 2014 were extracted from the anesthesia information management systems (AIMS). After the data were organized into surgical specialties and operative sites, blood order recommendations were generated based on five specific case characteristics of the group. Next, we assessed current ordering practices in comparison to actual blood utilization to identify potential areas of wastage and performed a cost analysis comparing the annual hospital costs from preoperative blood orders if the blood order schedule were to be followed to historical practices. RESULTS: Of the 19,138 patients who were categorized by the MSBOS as needing no blood sample, 2694 (14.0%) had a type and screen (T/S) ordered and 1116 (5.8%) had a type and crossmatch ordered. Of the 6073 procedures where MSBOS recommended only a T/S, 2355 (38.8%) had blood crossmatched. The cost analysis demonstrated an annual reduction in actual hospital costs of $57,335 with the MSBOS compared to historical blood ordering practices. CONCLUSION: We showed that the algorithm for development of a multispecialty blood order schedule is transferable and yielded reductions in preoperative blood product screening at our institution.