Consensus recommendations on flow cytometry for the assessment of inherited and acquired disorders of platelet number and function: Communication from the ISTH SSC Subcommittee on Platelet Physiology.

Flow cytometry is increasingly used in the study of platelets in inherited and acquired disorders of platelet number and function. However, wide variation exists in specific reagents, methods, and equipment used, making interpretation and comparison of results difficult. The goal of the present study was to provide expert consensus guidance on the use of flow cytometry for the evaluation of platelet disorders. A modified RAND/UCLA survey method was used to obtain a consensus among 11 experts from 10 countries across four continents, on the appropriateness of statements relating to clinical utility, pre-analytical variables, instrument and reagent standardization, methods, reporting, and quality control for platelet flow cytometry. Feedback from the initial survey revealed that uncertainty was sometimes due to lack of expertise with a particular test condition rather than unavailable or ambiguous data. To address this, the RAND method was modified to allow experts to self-identify statements for which they could not provide expert input. There was uniform agreement among experts in the areas of instrument and reagent standardization, methods, reporting, and quality control and this agreement is used to suggest best practices in these areas. However, 25.9% and 50% of statements related to pre-analytical variables and clinical utility, respectively, were rated as uncertain. Thus, while citrate is the preferred anticoagulant for many flow cytometric platelet tests, expert opinions differed on the acceptability of other anticoagulants, particularly heparin. Lack of expert consensus on the clinical utility of many flow cytometric platelet tests indicates the need for rigorous multicenter clinical outcome studies.

Ex Vivo Assessment of Different Oral Anticoagulant Regimens on Pump Thrombosis in a HeartWare Ventricular Assist Device.

BACKGROUND: In light of decreased intracranial hemorrhage with direct oral anticoagulants and concerns about their safety in continuous flow left ventricular assist devices, we conducted an ex vivo study of thrombus formation using multiple anticoagulation agents. METHODS: A continuous flow left ventricular assist device (HeartWare ventricular assist device) hemocompatibility loop was run using human blood under 7 conditions: control (no anticoagulation or antiplatelet); in vitro addition of aspirin; in vitro addition of apixaban at low dose (equivalent 2.5 mg twice daily); addition of apixaban at high dose (equivalent 5 mg twice daily); patients on warfarin; patients on apixaban (5 mg twice daily); and patients on dabigatran (150 mg twice daily). The primary outcome was time to formation of intrapump thrombosis. Secondary outcomes were reduction in clotting times over 1 hour, hemolysis, reduced platelet aggregation, and von Willebrand activity. RESULTS: Twenty-one runs were completed. Times to thrombosis in median (interquartile range) were control, 131 (127-134.5); in vitro aspirin, 124 (114.5-137); and patients on dabigatran, 131 (130.5-135.5) minutes, respectively. Times in patients on warfarin were, 137 (136.5-143.5); in vitro low-dose apixaban, 141 (138.5-142); and patients on apixaban, 140 (138-142.5) minutes, respectively. No thrombus formed in the in vitro high-dose apixaban group. There were no significant differences between the individual groups. When all apixaban groups were compared with nonapixaban groups, the time to thrombosis formation was significantly longer, 143 (137-150) versus 133.5 (128.5-140) minutes, P=0.02. There were similar changes in lactate dehydrogenase levels and other secondary end points. CONCLUSIONS: In an in vitro study of anticoagulation using human blood in a mock loop with a HeartWare HVAD, we demonstrated similar thrombosis times for apixaban and warfarin. Time to clotting was longer in the combined apixaban groups compared with combined other groups, but thrombosis times between individual groups were not significantly different.

A comparison of lumboperitoneal and ventriculoperitoneal shunting for idiopathic intracranial hypertension: an analysis of economic impact and complications using the Nationwide Inpatient Sample.

OBJECT: Complications following lumboperitoneal (LP) shunting have been reported in 18% to 85% of cases. The need for multiple revision surgeries, development of iatrogenic Chiari malformation, and frequent wound complications have prompted many to abandon this procedure altogether for the treatment of idiopathic benign intracranial hypertension (pseudotumor cerebri), in favor of ventriculoperitoneal (VP) shunting. A direct comparison of the complication rates and health care charges between first-choice LP versus VP shunting is presented. METHODS: The Nationwide Inpatient Sample database was queried for all patients with the diagnosis of benign intracranial hypertension (International Classification of Diseases, Ninth Revision, code 348.2) from 2005 to 2009. These data were stratified by operative intervention, with demographic and hospitalization charge data generated for each. RESULTS: A weighted sample of 4480 patients was identified as having the diagnosis of idiopathic intracranial hypertension (IIH), with 2505 undergoing first-time VP shunt placement and 1754 undergoing initial LP shunt placement. Revision surgery occurred in 3.9% of admissions (n = 98) for VP shunts and in 7.0% of admissions (n = 123) for LP shunts (p < 0.0001). Ventriculoperitoneal shunts were placed at teaching institutions in 83.8% of cases, compared with only 77.3% of first-time LP shunts (p < 0.0001). Mean hospital length of stay (LOS) significantly differed between primary VP (3 days) and primary LP shunt procedures (4 days, p < 0.0001). The summed charges for the revisions of 92 VP shunts ($3,453,956) and those of the 6 VP shunt removals ($272,484) totaled $3,726,352 over 5 years for the study population. The summed charges for revision of 70 LP shunts ($2,229,430) and those of the 53 LP shunt removals ($3,125,569) totaled $5,408,679 over 5 years for the study population. CONCLUSIONS: The presented results appear to call into question the selection of LP shunt placement as primary treatment for IIH, as this procedure is associated with a significantly greater likelihood of need for shunt revision, increased LOS, and greater overall charges to the health care system.

Dr. Otto "Tiger" Freer: inventor and innovator.

Every neurosurgeon develops his or her own standard approach to common intracranial pathologies in terms of the order in which different stages are performed and which instruments are used to perform individual tasks. The majority of the basic steps in performing a craniotomy are learned through repetition and practice during residency training. Significant amounts of energy are devoted to mastering technical skills and developing an operative rhythm. What often receives little attention is the historical origin of the instruments that make the work possible. The Freer elevator represents a particularly interesting example. To people unfamiliar with the accomplishments of turn-of-the-century laryngologist Otto "Tiger" Freer, it can be assumed that the name of the instrument in one's hand is simply named for what it can do, that is, to "free" the nasal mucosa from the bony and cartilaginous septum during the transsphenoidal approach. The technique this master surgeon spent his life and career perfecting is now repeated almost daily by skull base neurosurgeons approaching pathologies from the inferior frontal lobe to the foramen magnum. In reviewing his life and work, the authors of this paper discovered an interesting creative process that led to the design of the eponymous instrument. Additionally, they discovered important advances toward the development of the transnasal approach and in our understanding of the anterior skull base. They present a historical perspective on the life and accomplishments of Dr. Freer and the ubiquitous surgical instrument that he invented and popularized.