Preoperative autologous blood collection before bone marrow harvests in haploidentical related donors: is it justified?

BACKGROUND: With the increasing safety of allogeneic blood supply and declining need for transfusion due to patient blood management, the practice of preoperative autologous donation (PAD) continues to decline. The practice gained popularity during the 1980s and 1990s with the emergence of transfusion-transmitted human immunodeficiency virus and hepatitis C. At the peak of this public concern, the National Marrow Donor Program recommended that marrow donors have 1 to 3 autologous units of blood collected before their marrow harvest to minimize the likelihood of allogeneic transfusion. After three decades, the practice remains prevalent in marrow donors. We aimed to study the efficacy of PAD in healthy marrow donors. STUDY DESIGN AND METHODS: PADs performed before marrow harvest in healthy donors at our center between January 2013 and July 2015 were reviewed. The utilization of autologous units and decrease in hemoglobin levels due to PAD and marrow harvest were studied. Similar practices were assessed in the rest of the United States through a brief survey. RESULTS: Of a total of 262 autologous units collected from 136 donors, 25.2% were wasted. Ninety-nine percent of the marrow donors received at least 1 unit of blood irrespective of the need. PAD contributed to preoperative anemia, exposing three donors to allogeneic blood transfusion. The survey results showed a mixed response with some institutions continuing and others not practicing PAD. CONCLUSION: PADs are not justified in healthy marrow donors as they expose them to a risk of preoperative anemia and hence a greater risk of transfusion.

Cancer type predicts alloimmunization following RhD-incompatible RBC transfusions.

BACKGROUND: Immunosuppressed, RhD-negative oncology patients tend to have lower rates of sensitization to the D antigen when they receive transfusion with RhD-positive blood components. Clinical factors associated with alloimmunization to the D antigen in RhD-negative oncology patients when they receive transfusion with RhD-positive red blood cells (RBCs) have not been well defined. STUDY DESIGN AND METHODS: This was a 4-year, retrospective analysis identifying RhD-negative oncology patients who received RhD-positive RBCs and were not previously alloimmunized to the D antigen. Age, sex, race, ABO group, primary oncology diagnosis, and numbers of RhD-incompatible RBC transfusions were recorded. The association between antibody formation and clinical factors was studied. The incidence of alloanti-D was calculated from a subsequent antibody-detection test performed at least 28 days after receipt of the first transfusion of RhD-positive RBCs. RESULTS: In total, 545 RhD-negative oncology patients received 4295 RhD-positive RBC transfusions. Of these, 76 (14%) became alloimmunized to the D antigen. Diagnosis type was the only factor significantly associated with responder status. The logistic regression model indicated that patients who had myelodysplastic syndrome or solid malignancies were more likely to be responders than those who had acute leukemia. CONCLUSION: We measured a 14% sensitization rate to the D antigen in our RhD-negative oncology population. The rate of alloimmunization was higher in patients who had solid cancers (22.6%) or myelodysplastic syndrome (23%) compared with those who had other hematologic malignancies (7%). Knowledge of diagnoses that predispose to RhD alloimmunization enables better utilization of RhD-negative RBCs during times of shortage.

Platelet aggregometry cannot identify uremic platelet dysfunction in heart failure patients prior to cardiac surgery.

BACKGROUND: Patients with heart failure often have concomitant renal disease which can result in uremic platelet dysfunction. Determining whether uremia has affected platelets by platelet aggregometry can be challenging in these patients since they are often on antiplatelet medications. This study was undertaken to determine if platelet aggregation studies could identify heart failure patients at risk for uremic bleeding prior to cardiac surgery. METHODS: Platelet aggregation studies from three groups were studied and compared: 17 heart failure patients with mild to moderate renal impairment, 17 heart failure patients without renal abnormalities and 17 healthy volunteers. RESULTS: Platelet aggregation was severely impaired in both heart failure groups with and without renal abnormalities compared to healthy controls, and there were no significant differences in platelet aggregation in response to any of the agonists. There was a pan-decrease in platelet aggregation to all agonists in all heart failure patients. CONCLUSION: Platelet aggregometry does not appear to be useful in measuring platelet dysfunction in heart failure patients with mild to moderate renal impairment.

A Rare Case of Acquired Fanconi's Syndrome With Monoclonal Gammopathy in an Infant.

BACKGROUND: Monoclonal gammopathies associated with acquired Fanconi's syndrome (AFS) have been reported in the adult population. AFS is characterized by renal dysfunction resulting in proteinuria, aminoaciduria, hypophosphatemia, glucosuria, and hyperchloremic metabolic acidosis. In this case report, we document the clinical and laboratory findings of a preterm infant with features of both AFS and monoclonal gammopathy in the urine. METHODS: Clinical suspicion of AFS prompted the following laboratory studies to be performed: urine protein electrophoresis (UPEP), urine immunofixation, and urine amino acid analysis with high performance liquid chromatography (HPLC). RESULTS: Urine amino acid analysis revealed aminoaciduria. On UPEP, nonselective glomerular proteinuria was seen with a faint band in the gamma region. Urine immunofixation confirmed the presence of a monoclonal IgG lambda component with free monoclonal lambda light chains. CONCLUSION: To the best of our knowledge, this is the first case of pediatric AFS reported with a monoclonal gammopathy and monoclonal free light chains.

High false-positive rate for monoclonal gammopathy using capillary electrophoresis (CAPILLARYS 2) alone.

BACKGROUND: Capillary zone electrophoresis (CZE) is a newer method of performing serum protein electrophoresis and is considered to be faster and more efficient than agarose gel method. We decided to evaluate CZE as an efficient screening tool for monoclonal gammopathies, and we began recommending immunofixation studies in cases with such minor/subtle distortions to avoid missing monoclonal gammopathies. METHODS: We evaluated 163 serum protein agarose gel electrophoresis (SPAGE) samples between October and November 2011, and 447 serum protein CZE (SPCZE) samples between January 2012 to February 2012 and August 2012 to September 2012. RESULTS: Immunofixation studies were recommended in 51 of 163 cases (31.3%) performed by SPAGE, and in 274 of 447 cases (61.3%) performed by SPCZE. While using SPAGE, of the 51 cases recommended for immunofixation (24 were performed to date), six cases (25.0%) were positive for monoclonal gammopathy. In contrast, while using SPCZE, of the 274 cases recommended for immunofixation (118 were performed to date), 18 cases (15.2%) were positive for monoclonal gammopathy. Using the SPCZE method, of these 18 cases, five (27.8%) had minor/subtle distortions without obvious peaks. Our recommendation rate for immunofixation studies has thus almost doubled (61.3% vs. 31.3%) with the adoption of SPCZE. Yet, using SPCZE has not translated to detecting more cases of true monoclonal gammopathies. CONCLUSION: Therefore, we conclude that there is a high false-positive rate for monoclonal gammopathy using CE alone.

Analysis of prolonged storage on coagulation Factor (F)V, FVII, and FVIII in thawed plasma: is it time to extend the expiration date beyond 5 days?

BACKGROUND: According to AABB standards, fresh-frozen plasma (FFP) should be thawed at 30 to 37°C and expire after 24 hours. An increase in the aggressive management of trauma patients with thawed plasma has heightened the risk of plasma waste. One way to reduce plasma waste is to extend its shelf life, given that the full range of therapeutic efficacy is maintained. We evaluated the effect of prolonged storage at 1 to 6°C on the activity of Factor (F)V, FVII, and FVIII in plasma thawed at 37 or 45°C. STUDY DESIGN AND METHODS: Group O plasma from healthy donors (n=20) was divided into 10 pairs and frozen and stored at not more than -18°C. One sample from each pair was thawed at 37 or 45°C, and all were stored at 1 to 6°C. Samples were analyzed for FV, FVII, and FVIII activity on Days 0, 5, 10, 15, and 20. RESULTS: Plasma thawing time was 17% less at 45°C than at 37°C. No differences were observed between thawing groups in coagulation activity of FV, FVII, and FVIII during the 20-day storage period (p>0.12). In both groups, the activity of FV and FVIII decreased over time but remained within a normal range at 10 days. CONCLUSION: Although levels of plasma clotting factors are reduced in storage, therapeutic levels of FV and FVIII are maintained in thawed plasma stored for up to 10 days at 1 to 6°C. Thawing of FFP at 45°C decreases thawing time but does not affect the activity of FV, FVII, and FVIII.

Technical Note: Use of a Novel Bacterial Culture Sampling Device for Pooled Whole Blood Platelets.

OBJECTIVE: Transfusion associated sepsis is a serious risk after platelet transfusion. Although platelet culture can be performed to avoid such risk, culture results are often available after transfusion due to the 4-hour shelf-life after pooling. To decrease such risk, we implemented a needleless closed system device to culture for contamination before pooling and release for transfusion. METHODS: We customized a needleless device to permit sterile sampling of whole blood platelets without retrograde or cross-contamination. Then aliquots of platelets were injected into culture media for detection of aerobic organisms and cultured for 24 hours but released for transfusion after 12 hours of negative culture. RESULTS: In a period of two years, we used this device in 5,741 whole blood derived pooled platelets and only 24 units tested positive (0.4%) but none of initial positive was later confirmed. There were 11 Staphylococcus and 9 Bacillus species identified. All but one of the positive units were discarded; there was no clinical impact in the patient who received the positive unit. CONCLUSION: This device allows for sampling of whole blood derived platelets before pooling, warranting a transfusion of a culture negative unit after 12 hours of negative culture, consequently reducing transfusion of bacterially contaminated whole blood derived pooled platelets.

Therapeutic plasmapheresis and red blood cell exchange in a sickle cell trait patient with rhabdomyolysis.

We report a case of a 16-year-old African-American male with sickle cell trait and a past medical history significant for asthma that was transferred to our hospital for management of respiratory failure. On the fourth day of hospitalization, the patient was found to have increased creatine kinase (CK) levels and urine myoglobin levels consistent with rhabdomyolysis. No clear etiology was identified. Aggressive standard hydration and urine alkalization were applied without response. On the sixth day of hospitalization, the patient underwent a 1-1.5 plasma volume therapeutic plasma exchange (TPE) resulting in a transient reduction of serum CK and myoglobin by 50%, which became elevated once again within 4 h. Since his clinical presentation resembles exertional rhabdomyolysis documented in patients with sickle cell trait, RBC exchange was performed. The patient tolerated the procedure without complications. In addition to his improved overall condition, the patient's post-exchange CK and serum myoglobin levels dropped dramatically without rebound. To our knowledge, this case represents the first reported case of TPE followed by RBC exchange in a SCT patient with rhabdomyolysis.

Percutaneous occlusion of the left subclavian and celiac arteries before or during endograft repair of thoracic and thoracoabdominal aortic aneurysms with detachable nitinol vascular plugs.

PURPOSE: To review an experience with the Amplatzer vascular plug (AVP) for prevention of type II endoleaks during endovascular aneurysm repair (EVAR) of thoracic and thoracoabdominal aneurysms. MATERIALS AND METHODS: Retrospective review was undertaken of 14 patients undergoing transcatheter occlusion of the left subclavian (n = 12) or celiac artery (n = 2) with the AVP as part of EVAR of thoracic and thoracoabdominal aneurysms at a single institution. Procedural criteria evaluated were success at target vessel occlusion, the number of AVPs used, use of adjunctive embolization devices, and embolization-related ischemic end-organ events. Follow-up imaging criteria included evaluation of persistent target vessel occlusion, evidence of device migration, and the presence and characterization of endoleak secondary to AVP failure. RESULTS: Complete target vessel occlusion was documented for all cases. In six cases, more than one AVP was placed, with an average of 1.5 devices per patient. In two cases, adjunctive coils were placed. Computed tomographic or magnetic resonance angiography follow-up was available for all patients (mean follow-up, 419 days; range 28-930 d). No case showed evidence of device migration or type II endoleak resulting from AVP failure. There was a single instance of left subclavian artery recanalization without type II endoleak. There were no embolization-related ischemic end-organ events. CONCLUSIONS: Transcatheter arterial occlusion of the subclavian and celiac arteries with the AVP is a valuable adjunct to endografting in cases in which side branch embolization is necessary to extend the landing zone.

Proximal-type epithelioid sarcoma of the vulva: relationship to malignant extrarenal rhabdoid tumor.

Proximal epithelioid sarcoma is an extremely uncommon lesion of the vulva, with the potential for aggressive behavior. We report a case of this entity and discuss its relationship to the epithelial-type "malignant rhabdoid tumor" (MRT) of the soft tissue. On the basis of a review of the pertinent information on both these entities, it is concluded that they likely represent biologically different but morphologically and immunohistochemically similar neoplasms. Both proximal epithelioid sarcoma and MRT comprise epithelioid cells with densely eosinophilic cytoplasmic inclusions, and they each lack the INI1 gene product. Nevertheless, the literature suggests that other selected genetic differences between the 2 lesions, and the more rapid and aggressive course of MRT distinguish these tumor types as separate clinicopathologic entities.

Surgical and endovascular repair of aortic coarctation: normal findings and appearance of complications on CT angiography and MR angiography.

OBJECTIVE: A variety of treatment options exist for aortic coarctation, both surgical and catheter-based. Knowledge of the normal radiologic appearance of these, as well as their typical complications, is essential for interpretation of CT and MR angiographic studies in these patients. CONCLUSION: CT and MR angiography are noninvasive techniques that are well suited to follow patients after coarctation repair.

Use of an Intravascular Warming Catheter during Off-Pump Coronary Artery Bypass Surgery in a Patient with Severe Cold Hemagglutinin Disease.

Cold hemagglutinin disease with broad thermal amplitude and high titers presents challenges in treating cardiac-surgery patients. Careful planning is needed to prevent the activation of cold agglutinins and the agglutination of red blood cells as the patient's temperature drops during surgery. We describe our approach to mitigating cold agglutinin formation in a 77-year-old man with severe cold hemagglutinin disease who underwent off-pump coronary artery bypass surgery without the use of preoperative plasmapheresis. This experience shows that the use of an intravascular warming catheter can maintain normothermia and prevent the activation and subsequent formation of cold agglutinins. To our knowledge, this is the first reported use of this technique in a patient with cold hemagglutinin disease. The chief feature in this approach is the use of optimal thermal maintenance-rather than the more usual decrease in cold-agglutinin content by means of therapeutic plasma exchange.

Algorithmic Approach With Clinical Pathology Consultation Improves Access to Specialty Care for Patients With Systemic Lupus Erythematosus.

OBJECTIVES: Harris Health System (HHS) is a safety net system providing health care to the underserved of Harris County, Texas. There was a 6-month waiting period for a rheumatologist consult for patients with suspected systemic lupus erythematosus (SLE). The objective of the intervention was to improve access to specialty care. METHODS: An algorithmic approach to testing for SLE was implemented initially through the HHS referral center. The algorithm was further offered as a "one-click" order for physicians, with automated reflex testing, interpretation, and case triaging by clinical pathology. RESULTS: Data review revealed that prior to the intervention, 80% of patients did not have complete laboratory workups available at the first rheumatology visit. Implementation of algorithmic testing and triaging of referrals by pathologists resulted in decreasing the waiting time for a rheumatologist by 50%. CONCLUSIONS: Clinical pathology intervention and case triaging can improve access to care in a county health care system.

Utility of bone marrow examination for workup of fever of unknown origin in patients with HIV/AIDS.

AIMS: The utility of bone marrow aspiration and biopsy (BMAB) as a diagnostic tool in patients with HIV/AIDS and fever of unknown origin (FUO) is a subject of debate. Because highly active antiretroviral therapy has reduced incidence of opportunistic infections, it is important to reassess the efficacy of BMAB for this diagnostic purpose. To our knowledge, no such studies have been performed in Harris County which has the highest incidence of HIV in the state of Texas. METHODS: We reviewed all BMABs from patients with HIV/AIDS and FUO or persistent cytopenia(s) from 2007 to 2011. RESULTS: Of 57 evaluable patients, BMAB was positive in 24 samples by acid fast bacilli (AFB) or Gomori methenamine silver (GMS) stains (17.5%), presence of granuloma and/or lymphohistiocytic aggregates (31.6%), culture (21.0%) or a combination. Cultures demonstrated Mycobacterium avium/intracellulare (4), M tuberculosis (2), M gordonae (1), Histoplasma capsulatum (3) and Cryptococcus neoformans (2). There were three cases in which a pathogen was grown in culture but that had a negative of 'direct examination' on tissue sections (negative AFB and GMS special stains, no morphological evidence of granuloma/lymphohistiocytic infiltrates). CONCLUSIONS: This study supports the use of diagnostic BMAB as a rapid decision-making tool in patients with HIV and FUO in the proper clinical setting. BMAB demonstrated infection-related evidence prior to positive bone marrow culture in 75% of cases. Special stains and blood cultures had similar diagnostic yield, but BMAB offers faster results. Thus, this procedure assists in clinical decision making and the refinement of treatment in a more timely manner.

Exploring New Ways to Deliver Value to Healthcare Organizations: Algorithmic Testing, Data Integration, and Diagnostic E-consult Service.

As the USA Health Care System undergoes transformation and transitions to value-based models it is critical for laboratory medicine/clinical pathology physicians to explore opportunities and find new ways to deliver value, become an integral part of the healthcare team. This is also essential for ensuring financial health and stability of the profession when the payment paradigm changes from fee-for-service to fee-for-performance. About 5 years ago we started searching for ways to achieve this goal. Among other approaches, the search included addressing the laboratory work-ups for specialists' referrals in the HarrisHealth System, a major safety net health care organization serving mostly indigent and underserved population of Harris County, TX. We present here our experience in improving the efficiency of laboratory testing for the referral process and in building a prototype of a diagnostic e-consult service using rheumatologic diseases as a starting point. The service incorporates algorithmic testing, integration of clinical, laboratory and imaging data, issuing structured comprehensive consultation reports, incorporating all the relevant information, and maintaining personal contacts and an e-line of communications with the primary providers and referral center personnel. Ongoing survey of providers affords testimony of service value in terms of facilitating their work and increasing productivity. Analysis of the cost effectiveness and of other value indicators is currently underway. We also discuss our pioneering experience in building pathology residents and fellows training in integrated diagnostic consulting service.

FTY720 promotes local microvascular network formation and regeneration of cranial bone defects.

The calvarial bone microenvironment contains a unique progenitor niche that should be considered for therapeutic manipulation when designing regeneration strategies. Recently, our group demonstrated that cells isolated from the dura are multipotent and exhibit expansion potential and robust mineralization on biodegradable constructs in vitro. In this study, we evaluate the effectiveness of healing critical-sized cranial bone defects by enhancing microvascular network growth and host dura progenitor trafficking to the defect space pharmacologically by delivering drugs targeted to sphingosine 1-phosphate (S1P) receptors. We demonstrate that delivery of pharmacological agonists to (S1P) receptors S1P(1) and S1P(3) significantly increase bone ingrowth, total microvessel density, and smooth muscle cell investment on nascent microvessels within the defect space. Further, in vitro proliferation and migration studies suggest that selective activation of S1P(3) promotes recruitment and growth of osteoblastic progenitors from the meningeal dura mater.