Bernard J. Silver

Rapid resolution of GVHD after orthotopic liver transplantation in a patient treated with alefacept

To the editor: Graft-versus-host disease (GVHD) after transfusion of nonirradiated blood products or solid tumor transplantation is a rare but lethal complication associated with mortality of 80% to 90%[1][1][][2]–[3][3] and occurs when immunocompetent donor T cells from the graft recognize

Drug-induced immune-mediated thrombocytopenia in the intensive care unit.

A 62-year-old woman with prosthetic mitral valve was admitted for explant of an infected prosthetic knee. Perioperatively, she was bridged with heparin and started on empiric vancomycin and piperacillin-tazobactam. Platelet counts dropped precipitously within 2 days reaching a nadir of 6000/μL, without any bleeding. Decline persisted despite substituting heparin with bivalirudin. Antiplatelet factor 4 and anti-PLA1 antigen were negative. Schistocytes were absent. Antibiotics were substituted with daptomycin for suspected drug-induced thrombocytopenia. Pulse dose of intravenous immunoglobulin was initiated with rapid normalization of platelet count. She tested positive for IgG antiplatelet antibodies to vancomycin and piperacillin-tazobactam thereby confirming the diagnosis. Drug-induced immune-mediated thrombocytopenia is an underrecognized cause of thrombocytopenia in the intensive care units. Clinicians should be cognizant of this entity, and a definitive diagnosis should be sought if feasible.

Postsplenectomy thromboembolic disease in congenital sideroblastic anaemia.

This case report describes a case of congenital sideroblastic anaemia, one of the prototype disorders of erythroid haem biosynthesis. In this instance it was not recognised until after the patient had undergone splenectomy and developed refractory thromboembolic disease.

Screening for SF3B1 mutations is a useful tool to differentiate between acquired clonal and non-clonal sideroblastic anemia

Sideroblastic anemia (SA) is one of the major types of anemia encountered in clinical practice. Th ere are three primary types, namely congenital SA, acquired clonal SA and acquired reversible SA. All patients with SA have anemia and ring sideroblasts (RS) in the bone marrow (BM) [1,2]. However, there are many clinical and pathologic overlap features that can complicate the diagnosis. While congenital and acquired reversible SA are nonmalignant conditions, acquired clonal SAs are usually associated with either myelodysplastic syndromes (MDS) or myelodysplastic/myeloproliferative neoplasms (MDS/ MPN), blood cancers associated with severe cytopenias and increased risk for transformation to acute myeloid leukemia. Th erefore, it is imperative that we successfully distinguish between acquired clonal SA from non-clonal causes of SA. Th e current clinicopathologic criteria used to diagnose acquired clonal SA is based on the 2008 World Health Organization (WHO) classifi cation. Although it is very helpful in diagnosing patients who have overt dysplasia and cytogenetic changes characteristic of MDS or MDS/ MPN, it is clear that some patients do not meet morphologic or cytogenetic criteria but clearly have symptomatic diseases leading to delayed diagnosis and treatment. Furthermore, some patients with congenital SA, exemplifi ed by X-linked SA (XLSA) in females, can have clinicopathologic features that overlap with acquired clonal SA. Biomarkers that can be tested in either BM or blood samples and that have a rapid turn-around time can lead to a faster diagnosis of acquired clonal SA and exclusion of non-malignant causes of SA. Recurrent genetic alterations are helpful in prognosis, diagnosis, risk stratifi cation and predicting treatment response in MDS. For example, TP53 , EZH2 , ETV6 , RUNX1 and ASXL1 mutations are predictors of poor overall survival [3,4]. TP53 mutations can predict progression in lower-risk MDS [5], and the presence of TET2 , DNMT3A and SF3B1 mutations can predict a good therapeutic response to hypomethylating agents in MDS [6,7]. Splicing factor 3b, subunit 1 ( SF3B1 ) mutations are frequently found in MDS with RS, and have been associated with RS formation and perturbation of mitochondrial iron traffi cking [8 – 10]. In the present study, we hypothesized that SF3B1 mutations may be useful as a diagnostic biomarker for patients with acquired clonal SA who present with cytopenias and/or minimal morphologic changes suggestive of MDS but not suffi cient to make a defi nitive diagnosis of the disease. To prove our hypothesis, we performed Sanger sequencing of all coding exons of SF3B1 in six patients with persistent anemia and RS without BM evidence of dysplasia suggestive of MDS and a normal karyotype by metaphase cytogenetics (MC) at clinical manifestation. All patients were seen at the Cleveland Clinic and consented to an approved Institutional Review Board (IRB) protocol. Samples were collected in accordance with the Declaration of Helsinki. Th e median age of the group was 38 years (range, 6 – 75) (Table I). Patient 1 was a 24-year-old male who was hospitalized for recurrent left lower extremity deep vein thrombosis. Two years prior, the patient underwent splenectomy for a splenic rupture secondary to infectious mononucleosis. A complete blood count (CBC) showed normocytic anemia, thrombocytosis and Pappenheimer bodies. A BM biopsy showed a slightly hypercellular BM for his age (80%), with erythroid hyperplasia, megaloblastoid changes, no dysplasia in megakaryocytes and granulocytes and numerous RS. MC was unremarkable. Copper levels were within normal limits. At the molecular level the patient was wild type (WT) for JAK2 , BCR / ABL , HFE and SF3B1. Clinical suspicion for XLSA was raised and was confi rmed by the presence of an ALAS2 mutation. Indeed, the patient also developed recurrent venous thromboembolism (VTE), a known complication post-splenectomy in patients with XLSA [11]. L eu k L ym ph om a D ow nl oa de d fr om in fo rm ah ea lth ca re .c om b y U ni ve rs ity o f N ew ca st le o n 01 /0 1/ 15

Hemophagocytic lymphohistiocytosis secondary to localized large B-cell lymphoma in a patient with history of knee arthroplasty

Hemophagocytic lymphohistiocytosis secondary to localized large B-cell lymphoma in a patient with history of knee arthroplasty Vahid Entezari, Eberechi Agwa, Sory J. Ruiz, Steven A. Lietman, Bernard J. Silver & Armin G. Jegalian a Department of Orthopedic Surgery, Cleveland Clinic, Cleveland, OH, USA b Department of Hematologic Oncology and Blood Disorders, Cleveland Clinic, Cleveland, OH, USA c Department of Clinical Pathology, Cleveland Clinic, Cleveland, OH, USA Published online: 29 May 2015.

Prolongation of Both PT and aPTT

The global coagulation tests, prothrombin time (PT) and activated partial thromboplastin time (aPTT), are commonly used to screen for coagulation deficiencies and are usually done in preparation for surgery. Simultaneous prolongation of both times can be found in severe hepatic disease, vitamin K deficiency, and disseminated intravascular coagulation. In the absence of these disorders, one must consider inherited deficiencies or acquired inhibitors of those factors in the distal or the common portion of the coagulation pathway. While these constitute a group of rare bleeding disorders, they are important to recognize as they can result in severe bleeding, either spontaneously or with surgical procedures. This chapter reviews the pathobiology of those acquired and inherited conditions that cause concurrent prolongation of the PT and aPTT as well as specific management considerations.

Spontaneous perinephric hematoma due to acquired factor X deficiency in AL amyloidosis

Spontaneous perinephric hematoma (SPH) is a rare entity whose diagnosis is challenging because of its varied clinical presentation and lack of any specific etiology. We report a 34-year-old African-American male who presented with left flank pain and was found to have a large left perinephric hematoma, in the setting of undiagnosed AL amylodosis. The case illustrates that while a SPH due to the vascular angiopathy of amyloid is rare, when amyloidosis is associated with abnormal coagulation studies or bleeding at multiple sites, it should be considered because of its protean systemic manifestations and potential response to chemotherapy.