VEXAS syndrome: A review of bone marrow aspirate and biopsies reporting myeloid and erythroid precursor vacuolation.

Myeloid and erythroid precursor vacuolation is a common dysplastic finding associated with myeloid malignancies, toxins, drug, and nutritional deficiencies. It has been described as a core morphologic feature in VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. We sought to determine the number of cases attributable to VEXAS syndrome in bone marrow biopsies and aspirates (BAMB) reporting myeloid precursor vacuolation. We reviewed 1318 individual BAMB reports from January 2020 to July 2021 where "vacuole(s)," "vacuolation," or "vacuolated" was reported. Bone marrow biopsies with vacuolation confined to blasts or those completed as routine workup prior to stem cell transplant or post induction chemotherapy for AML (acute myeloid leukemia) were excluded. Myeloid and erythroid precursor vacuolation was noted in 219 reports representing 210 patients. The most common etiology was myelodysplastic syndrome (MDS) (38.6%), AML (16.7%), lymphoproliferative disorders and multiple myeloma (7.6%), drug or toxin exposure (5.2%) myeloproliferative neoplasm (MPN) or MPN/MDS overlap syndrome (4.3%). VEXAS syndrome was determined to be the etiology in 2.9% of patients. Two additional cases of VEXAS syndrome with bone marrow biopsies reported in the specified time frame did not explicitly report myeloid or erythroid precursor vacuolation but were identified based on clinical suspicion and repeat BAMB review. Myeloid and erythroid precursor vacuolation is a dysplastic feature attributable to VEXAS syndrome in at least 2.9% of cases. Standardized reporting of vacuolization, triaging of molecular sequencing and optimal treatment of this disorder are critical issues facing those seeing patients with suspected VEXAS syndrome.

Solvent-Detergent Plasma for the Treatment of Thrombotic Microangiopathies: A Canadian Tertiary Care Centre Experience.

Solvent detergent-treated plasma (SDP) is a pathogen-inactivated blood plasma, which in comparison to frozen plasma is associated with lower rates of allergic reaction, transfusion-associated lung injury, and viral transmission. SDP has been available in Canada since 2012. Data on SDP use in Canada remains limited. We present a review of subjects receiving SDP at a large tertiary care centre primarily for thrombotic thrombocytopenic purpura and atypical hemolytic uremic syndrome, demonstrating the tolerability and safety of SDP.

Dysmetabolic hyperferritinemia is associated with normal transferrin saturation, mild hepatic iron overload, and elevated hepcidin.

Hyperferritinemia is common in individuals with the metabolic syndrome (dysmetabolic hyperferritinemia), but its pathophysiology and the degree to which it reflects tissue iron overload remains unclear. We conducted a cross-sectional study evaluating ten cases with dysmetabolic hyperferritinemia for liver iron overload and compared their serum iron indices and urine hepcidin levels to healthy controls. Seven out of ten cases had mild hepatic iron overload by magnetic resonance imaging (MRI) (median, 75 micromol/g dry weight). Cases had higher serum ferritin than controls (median, 672 microg/L vs. 105 microg/L, p < 0.001), but the median transferrin saturation was not significantly different (38% vs. 36%, p = 0.5). Urinary hepcidin was elevated in dysmetabolic hyperferritinemia (median; 1,584 g/mg of creatinine vs. 799 ng/mg of creatinine, p = 0.05). Dysmetabolic hyperferritinemia is characterized by hyperferritinemia with normal transferrin saturation, elevated hepcidin levels, and mild liver iron overload in a subset of patients.

Parvovirus B19 in an immunocompetent adult patient with acute liver failure: an underdiagnosed cause of acute non-A-E viral hepatitis.

There are occasional pediatric reports of parvovirus B19-associated transient acute hepatitis and hepatic failure. A case of a 34-year-old immunocompetent woman who developed severe and prolonged but self-limited acute hepatitis and myelosuppression following acute parvovirus B19 infection is reported. Parvovirus B19 may be the causative agent in some adult cases of acute non-A-E viral hepatitis and acute liver failure.

Cryofibrinogenemia After a Liver Transplant: First Reported Case Posttransplant and a Case-Based Review of the Nontransplant Literature.

Cryofibrinogenemia is a rare disorder in which plasma, not serum, forms a cryoprecipitate. Patients with cryofibrinogenemia may be asymptomatic, or they may have painful ulcers, purpura, livedo reticularis, Raynaud phenomenon, perniosis of the extremities, thrombosis, and arthralgia. Cryofibrinogenemia may be primary or secondary to an underlying disorder such as connective tissue disease, malignancy, infection, drugs, or thromboembolic disease. Here, we present a 41-year-old woman with a pancreatic neuroendocrine tumor who underwent a Whipple procedure in 2003 followed by 2 liver transplants for hepatic metastases. Three years posttransplant, we discovered a biopsy-proven metastatic lesion in her femur. Five years posttransplant, she developed acute, severe pain in both feet, and was found to have cryofibrinogenemia despite immunosuppression post-transplant. Testing for connective tissue diseases and hematologic malignancy were negative. She was treated with high-dose prednisone, which completely resolved her symptoms. We also conducted a review of the literature via a PubMed search to summarize the association of cryofibrinogenemia with malignancy and treating cryofibrinogenemia with corticosteroids. Our study is the first reported case of cryofibrinogenemia that developed secondary to a neuroendocrine tumor posttransplant. Our report suggests that cryofibrinogenemia may occur despite immunosuppression adequate to prevent graft rejection, and that high-dose corticosteroids are an effective treatment for posttransplant cryofibrinogenemia.

Polyclonal hyperviscosity syndrome in IgG4-related disease and associated conditions.

Polyclonal hyperviscosity syndrome (HVS) is rare and has been reported in various disorders of immune dysregulation and lymphoid hyperplasia. IgG4-Related Disease (IgG4-RD) is an emerging disorder often associated with exuberant hypergammaglobulinemia, and this review of seven cases establishes IgG4-RD as an important cause of polyclonal HVS.