Jessica L. Poisson

Vironome of Kaposi Sarcoma associated Herpesvirus-Inflammatory Cytokine Syndrome in an AIDS patient reveals co-infection of Human Herpesvirus 8 and Human Herpesvirus 6A

KSHV inflammatory cytokine syndrome (KICS) is a newly described condition characterized by systemic illness as a result of systemic, lytic KSHV infection. We used Illumina sequencing to establish the DNA vironome of blood from such a patient. It identified concurrent high-level viremia of human herpesvirus (HHV) 8 and 6a. The HHV8 plasma viral load was 5,300,000 copies/ml, which is the highest reported to date; this despite less than five skin lesions and no HHV8 associated lymphoma. This is the first report of systemic HHV6a/KSHV co-infection in a patient. It is the first whole genome KSHV sequence to be determined directly from patient plasma rather than cultured or biopsied tumor material. This case supports KICS as a new clinical entity associated with KSHV.

Is it quinine TTP/HUS or quinine TMA? ADAMTS13 levels and implications for therapy†

Thrombocytopenia with or without microangiopathy following quinine is often referred to as quinine “hypersensitivity.” When schistocytes are present it is frequently termed “quinine‐associated TTP/HUS.” A severe deficiency of the vWF‐cleaving protease, ADAMTS13, is associated with idiopathic TTP. A previous study of patients with “quinine‐associated TTP/HUS” found that ADAMTS13 activities were not abnormal in 12/12 patients. A retrospective review of TTP patients with quinine‐associated thrombotic microangiopathy (TMA) for whom ADAMTS13 was measured before plasma exchange was performed. Six patients were identified. All were females (age range: 43 to 73, mean = 61.7 years) and had taken quinine for leg cramps. Four of the six experienced renal failure requiring dialysis. Five of the patients had D‐Dimers levels measured, all were elevated. In four patients the levels were ≥18 times the upper limit of normal. ADAMTS13 was normal in four patients and mildly decreased in two patients. We conclude that while thrombocytopenia and schistocytosis can be seen in quinine‐associated TTP/HUS, the pathophysiology seems to be distinct from that seen in most cases of idiopathic TTP (i.e., severely decreased ADAMTS13 with an inhibitor). We recommend that a TMA in association with quinine be consistently referred to as quinine‐associated thrombotic microangiopathy (quinine‐TMA) to better distinguish this entity from idiopathic TTP. The use of plasma exchange in quinine‐TMA is called into question. J. Clin. Apheresis, 2009.

Proximal-Type Epithelioid Sarcoma

Proximal-type epithelioid sarcoma (PES) is a rare variant of epithelioid sarcoma (ES) presenting in either a proximal extremity or axial location. Compared to the classic type of ES, the proximal variant demonstrates more aggressive behavior. The classic and proximal epithelioid variants of ES are characterized by co-expression of cytokeratin and vimentin. Loss of integrase interactor-1 (INI1) staining is a recently characterized feature that narrows the differential diagnosis. * PES : proximal-type epithelioid sarcoma ES : epithelioid sarcoma WHO : World Health Organization IHC : immunohistochemical EMA : epithelial membrane antigen INI1 : integrase interactor-1 MRT : malignant rhabdoid tumors MPNST : malignant peripheral nerve sheath tumors WT-1 : Wilms’ tumor-1

The treatment of nephrogenic systemic fibrosis with therapeutic plasma exchange.

Background: Nephrogenic systemic fibrosis (NSF), also known as nephrogenic sclerosing dermopathy (NSD), is a rare progressive fibrosing disease associated with gadolinium based dyes in patients with renal disease. The exact pathophysiology is not well understood. Accepted treatments include corticosteroids, immune modulators, PUVA, rituximab and extracorporeal photopheresis (ECP). Apheresis is utilized when symptoms continue to progress. However, the paucity of centers offering ECP can be inhibitory to care. Small case reports have been published illustrating moderate treatment success with therapeutic plasma exchange (TPE). Methods: Chart review found two patients; both were African‐American women with systemic lupus erythematosus (SLE), status post renal transplant, who had biopsy documented NSF. The patients were still symptomatic, despite maximal medical management, so they underwent TPE series for symptom management. Medical therapy with immune modulators was continued in conjunction to TPE. Response to treatment was evaluated using subjective reporting to the primary care team. Results: The patients reported significant improvements in subjective pain levels after TPE. Patient 1 reported decreased skin and contracture pain after the 3rd treatment, with similar results for a second series 6 months later. Patient 2 reported drastic improvement in pain symptoms and rarely required pain medication during hospital course. No adverse reactions occurred during treatment. Conclusions: TPE is a therapy option for patients with NSF without access to ECP. TPE was well‐tolerated, easily assessable, and effective; however the etiology of the improvement following TPE is unknown. Larger studies will help further determine the efficacy of TPE for NSF. J. Clin. Apheresis 28:317–320, 2013.

Rapid increases in parasitemia following red cell exchange for malaria

Exchange transfusion is frequently used as an adjunctive treatment of severe malaria, although the efficacy of exchange transfusion as therapy for severe malaria remains controversial. The major perceived benefit of exchange transfusion is the rapid reduction of parasite load. However, no previous report has shown the dynamic change in parasitemia shortly following an acute load reduction. We report a 20‐year‐female who developed cerebral malaria and 30% parasitemia after traveling to Africa. In addition to antimalarial treatment, red cell exchange (RCX) was begun emergently with an automated blood‐cell separator. Parasitemia dropped from 30 to 15% immediately after the procedure but rapidly increased to 25% after 50 min. The second procedure was performed 12 h after the first procedure. Her neurologic status returned to baseline on Day 2, and she was discharged on Day 6. Rapid increases in parasitemia can be observed after mechanical load reduction following RCX. J. Clin. Apheresis, 2011.

Seasonal association of thrombotic thrombocytopenic purpura

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP), a thrombotic microangiopathy, is a clinical diagnosis, characterized by microangiopathic hemolytic anemia and thrombocytopenia without another likely explanation. Some initiators of the disease are well represented in the literature, such as certain drugs, malignancies, and viral illness; however, there are less objective factors still being investigated, with references to hormonal, stress, and seasonal variations considered anecdotally. A better insight of these factors would aid in understanding the pathophysiology of the disease.

Performance evaluation of the Helena V8 capillary electrophoresis system.

OBJECTIVES To compare the performance characteristics of the Helena V8® and Sebia CAPILLARYS2® automated capillary electrophoresis systems to agarose gel serum protein electrophoresis (SPE) and immunofixation electrophoresis (IFE) using the Helena SPIFE3000®. DESIGN AND METHODS Serum protein electrophoresis and immunosubtraction was performed on 100 consecutive patient samples comparing two capillary-electrophoresis platforms with agarose-gel SPE and IFE; IFE was used as the gold standard. Chart review was performed on patients where results were discordant between methods. Analytical precision was determined using Sebias normal and abnormal controls. RESULTS The sensitivities of the CAPILLARYS2, V8, and SPIFE3000 agarose gel for identification of monoclonal gammopathies were respectively 97.4 (95%CI 91.1-100), 92.3 (95%CI 82.2-100), and 89.9 (95%CI 79.1-97.6). The specificities of the CAPILLARYS2, V8, and SPIFE3000 agarose gel were respectively 57.6 (95%CI 45.0-70.2), 72.2 (95%CI 61.0-83.3), and 75.4 (95%CI 60-82.8). These analytical performance characteristics were statistically equivalent between systems (P>0.05). The analytical precision of the capillary-based methods was also statistically equivalent. Chart review of available data from discordant samples revealed that 7/10 patients had a history of multiple myeloma or known monoclonal gammopathy and were being treated or monitored. All discordant samples had low concentration monoclonal proteins (<0.3g/dL). Both capillary-based methods performed poorly (collectively <50% accuracy) at detecting low concentration non-IgG antibodies (IgA, IgM, and light chain monoclonal gammopathies) compared to IFE. CONCLUSIONS The Helena V8 and Sebia CAPILLARYS2 were analytically equivalent to the SIFE3000 for identification of IgG monoclonal gammopathies >0.3g/dL. Interpreters using the automated immunotyping/immunosubstraction systems performed poorly at detecting low concentration and non-IgG monoclonal gammopathies.

Acquired peanut hypersensitivity after transfusion

to within-type patients. While the cutoff level for this practice varies among blood banks, proposed cutpoints range from 128 to 250. The blood bank at our institution performs a single 1:200 saline dilution of plasma, followed by an immediatespin tube test using A1 and B red blood cells (Immucor, Norcross, GA), to assess the isohemagglutinin levels in group O units. If either cell has a positive reaction, these units are only released to group O patients. To determine whether PAS C PLTs contain lower levels of isohemagglutinins when compared to plasma PLTs, a retrospective review of anti-A and/or -B titer results was undertaken for all group O PLT units received from December 12, 2011, to April 24, 2013. A total of 5471 group O PLT units were received during the study period. There were 3516 conventional plasma units and 1955 PAS C units (see Table 1). For conventional PLT units, 43 of 3516 (1.22%) had titers of more than 200 versus two of 1955 (0.10%) for PAS C units (p < 0.0001; Fisher’s exact test). The two PAS C units with titers of more than 200 were Parts 1 and 2 from the same donor. The findings we report are based on a cutoff value of 200 that is more than double what other centers have chosen. As a result, this less sensitive measure may give us fewer positive reactions than would be seen in other centers. However, we have not seen an increase in associated transfusion reactions, and it remains our policy to test at this cutoff. This single-center, retrospective review found that group O plasma PLT units had an anti-A and/or -B titer greater than 200 twelve times more often than PAS C units. This difference was found to be highly significant. These findings strongly suggest that a reduction in plasma leads to a concomitant reduction in isohemagglutinin levels. This decrease in titer may result in reduced hemolysis when incompatible PLT units are issued.

Anti‐Jka that are detected by solid‐phase red blood cell adherence but missed by gel testing can cause hemolytic transfusion reactions

Kidd blood group antibodies are notorious for transient detection and hemolytic transfusion reactions. This report compares the rate of detection of anti‐Jka when using gel column agglutination versus solid‐phase red blood cell adherence (SPRCA) testing and documents the occurrence of hemolytic transfusion reactions in 17 recently transfused patients who developed anti‐Jka that were detectable by SPRCA but were undetectable by gel.

Non-specific red cell reactivity in an obstetric population.

Abstract Objective: To examine non-specific red cell reactivity (NSR) on antibody (Ab) screening of obstetric inpatients. Methods: Observational study of 5438 obstetric inpatients (2009–2013). Ab-positive patients were identified and their records reviewed for NSR, other antibodies, transfusion reactions or hemolytic disease of the fetus/newborn (HDFN). Evaluation of NSR frequency by test era assessed the impact of an institutional change to solid-phase screening in 2011. Results: Of obstetric inpatients, 5.3% had at least one positive Ab screen; 1.6% had NSR. Of NSR-positive patients, 16.7% had identifiable Abs that pre-dated NSR; 25% had concurrent Abs and 8.5% had subsequent Ab identification. In 49.1%, NSR resolved during follow-up. The frequency of NSR was higher after the change to solid-phase Ab screening, but specific Ab frequency was similar in both testing periods. No transfusion reactions or cases of HDFN were noted in this cohort. Conclusions: NSR is found in 1–2% of obstetrical inpatients at our institution, and has more than doubled since the initiation of solid-phase screening. Although likely clinically insignificant by itself, NSR is commonly found in relation to other red cell Abs and may precede their development.