A Novel Case of Compound Heterozygous Type 3 Von Willebrand Disease.

Von Willebrand disease (VWD) is the most common inherited bleeding disorder worldwide. Genetic mutations in the von Willebrand gene may result in either quantitative (Types 1 or 3) or qualitative defects (Type 2) of von Willebrand Factor (vWF). Type 3 is the rarest and most severe form of VWD, resulting in a virtual absence of vWF.

Pan-PIM kinase inhibitors enhance Lenalidomide's anti-myeloma activity via cereblon-IKZF1/3 cascade.

Multiple myeloma remains an incurable disease, and continued efforts are required to develop novel agents and novel drug combinations with more effective anti-myeloma activity. Here, we show that the pan-PIM kinase inhibitors SGI1776 and CX6258 exhibit significant anti-myeloma activity and that combining a pan-PIM kinase inhibitor with the immunomodulatory agent lenalidomide in an in vivo myeloma xenograft mouse model resulted in synergistic myeloma cell killing without additional hematologic or hepatic toxicities. Further investigations indicated that treatment with a pan-PIM kinase inhibitor promoted increased ubiquitination and subsequent degradation of IKZF1 and IKZF3, two transcription factors crucial for survival of myeloma cells.

Validation of the STA-Liatest DDi assay for exclusion of proximal deep vein thrombosis according to the latest Clinical and Laboratory Standards Institute/Food and Drug Administration guideline: results of a multicenter management study.

: Recommended strategy for venous thromboembolism (VTE) diagnosis includes the use of sensitive D-dimer (DDi) assays along with pretest probability (PTP) assessment. The Clinical and Laboratory Standards Institute (CLSI) recently issued a guideline (US FDA endorsed) on DDi in VTE exclusion. Such guideline specifies the ideal D-dimer assay characteristics and target population.

Trends in Bone Marrow Sampling and Core Biopsy Specimen Adequacy in the United States and Canada: A Multicenter Study.

Objectives: To assess bone marrow (BM) sampling in academic medical centers.

Methods: Data from 6,374 BM samples obtained in 32 centers in 2001 and 2011, including core length (CL), were analyzed.

Results: BM included a biopsy (BMB; 93%) specimen, aspirate (BMA; 92%) specimen, or both (83%).

IgM Myeloma with Plasma Cell Leukemia: Case Report and Literature Review.

IgM multiple myeloma (MM) is a rare entity representing approximately 0.5% of all MM. It should be distinguished from malignant neoplasms of B cells with plasmacytic differentiation such as Waldenstrom macroglobulinemia (WM) and marginal zone lymphoma with plasmacytic differentiation.

Cases of transfusion-transmitted babesiosis occurring in nonendemic areas: a diagnostic dilemma.

Background: Transfusion-transmitted babesiosis (TTB) has been rapidly increasing in incidence since the beginning of the 21st century. Asymptomatic individuals with Babesia infection are able to donate blood in the United States because of the lack of specific blood donation testing. Blood products collected in Babesia-endemic areas are distributed nationally; thus, clinicians in nonendemic states may fail to include babesiosis in the differential diagnosis of a patient who had a recent transfusion history and a fever of unknown origin.

Characterization of Mast Cell Activation Syndrome.

Background: Mast cell activation syndrome (MCAS), a recently recognized nonneoplastic mast cell disease driving chronic multisystem inflammation and allergy, appears prevalent and thus important. We report the first systematic characterization of a large MCAS population.

Method: Demographics, comorbidities, symptoms, family histories, physical examination and laboratory findings were reviewed in 298 retrospective and 115 prospective patients with MCAS.

Assessment of Bleeding and Thrombosis Based on Aspirin Responsiveness after Continuous-Flow Left Ventricular Assist Device Placement.

Pump thrombosis (PT) is a severe complication of left ventricular assist device (LVAD) support. This study evaluated PT and bleeding after LVAD placement in patients responsive to a standard aspirin dose of 81 mg using platelet inhibition monitoring compared with initial nonresponders who were then titrated upward to achieve therapeutic response. Patients ≥ 18 years of age with initial placement of HeartMate II LVAD at our institution and at least one VerifyNow Aspirin test performed during initial hospitalization were included.

D-Dimer Use and Pulmonary Embolism Diagnosis in Emergency Units: Why Is There Such a Difference in Pulmonary Embolism Prevalence between the United States of America and Countries Outside USA?

Objective: Although diagnostic guidelines are similar, there is a huge difference in pulmonary embolism (PE) prevalence between the United States of America (US) and countries outside the USA (OUS) in the emergency care setting. In this study, we prospectively analyze patients' characteristics and differences in clinical care that may influence PE prevalence in different countries.

Methods: An international multicenter prospective diagnostic study was conducted in a standard-of-care setting.

Validation of STA-Liatest D-Di assay for exclusion of pulmonary embolism according to the latest Clinical and Laboratory Standard Institute/Food and Drug Administration guideline. Results of a multicenter management study.

: Combined clinical pretest probability (PTP) and D-dimer testing have great diagnostic value for pulmonary embolism exclusion. To harmonize performance levels of D-dimer assays available on the market, the Clinical and Laboratory Standard Institute (CLSI) has published a guideline, endorsed by the US Food and Drug Administration (FDA). Such guideline specifies the ideal D-dimer assay characteristic and target population.

Diagnosing Spindle Cell Variant of Primary Cutaneous B-Cell Lymphoma: Potential Pitfalls and Solutions.

Spindle cell variant of cutaneous B-cell lymphoma is a rare entity which poses a diagnostic difficulty. The differential diagnosis of cutaneous spindle cell lesions is broad, and often includes sarcoma, carcinoma, and melanoma. Lymphoma with spindle cell morphology is frequently only considered after exclusion of more common etiologies.

Senile transthyretin cardiac amyloidosis in patients with plasma cell dyscrasias: importance of cardiac biopsy for making the correct diagnosis.

Amyloidosis refers to a group of widely diverse conditions characterized by the deposition of insoluble protein within the extracellular space, leading to disruption of normal organ function. AL primary amyloidosis is associated with plasma cell dyscrasias and is caused by the deposition of insoluble kappa or lambda light chains. Cardiac involvement by AL primary amyloidosis has a very poor prognosis, and patients are treated with systemic chemotherapy.

Recombinant Human Antithrombin in Pregnant Patients with Hereditary Antithrombin Deficiency: Integrated Analysis of Clinical Data.

Objectives: The purpose of this analysis was to evaluate the use of recombinant human antithrombin (rhAT) in preventing venous thromboembolism (VTE) in pregnant patients with hereditary AT deficiency (HATD).

Study Design: Data from two clinical trials were pooled. Dosing of rhAT was based on body weight and baseline AT activity, started up to 24 hours before scheduled induction or cesarean delivery, or at the onset of labor.

Plasma Cell Granuloma: An Entity within the Spectrum of IgG4-Related Disease.

Plasma cell granuloma (PCG) is a relatively rare, mass-forming lesion comprised of polyclonal plasma cells set in a background of storiform fibrosis and spindle cell proliferation. While uncommon, this lesion may occur within any site and should be included in the list of differential diagnoses for plasma cell neoplasms. As this entity can be mistaken for a plasma cell neoplasm, surgical pathologists should consider ancillary studies to assess clonality of plasma cell proliferations, especially during intraoperative consultation.

Evaluation of heparin-induced thrombocytopenia (HIT) laboratory testing and the 4Ts scoring system in the intensive care unit.

Background: Over-diagnosis of heparin-induced thrombocytopenia (HIT) results in costly and unnecessary laboratory screening and treatment with direct thrombin inhibitors. Our aim was to evaluate the utility of the 4Ts scoring system to predict HIT in multiple ICU settings and to characterize our treatment of these cases.

Methods: Eighty-two patients from multiple ICU settings who underwent laboratory testing for HIT were classified as low-, intermediate-, or high-risk patients based on retrospectively adjudicated 4Ts scores.

Proteomic analysis of murine bone marrow niche microenvironment identifies thioredoxin as a novel agent for radioprotection and for enhancing donor cell reconstitution.

Hematopoiesis is regulated by the bone marrow (BM) niche microenvironment. We recently found that posttransplant administration of AMD3100 (a specific and reversible CXCR4 antagonist) enhanced donor cell engraftment and promoted recovery of all donor cell lineages in a congeneic mouse transplant model. We hypothesized that AMD3100 enhances donor cell reconstitution in part by modulating the levels and constitution of soluble factors in the niche microenvironment.

Evaluation of the role of secretory sphingomyelinase and bioactive sphingolipids as biomarkers in hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a rare systemic inflammatory syndrome that results from unrestrained immune cell activation. Despite significant advances in the understanding of the pathophysiology of HLH, interventions remain limited for this often-fatal condition. Secretory sphingomyelinase (S-SMase) is a pro-inflammatory lipid hydrolase that is upregulated in several inflammatory conditions, including HLH.

Pancytopenia after allogeneic bone marrow transplant due to copper deficiency.

Pancytopenia occurring 1 year or later after allogeneic bone marrow transplantation typically prompts a primary consideration for relapse. We present the case of a 15-year old-girl who underwent transplantation for therapy-related myelodysplasia secondary to Ewing sarcoma treatment who developed pancytopenia with myelodysplasia 1 year after transplant due to copper deficiency. Copper deficiency is an important consideration in the evaluation of pancytopenia and myelodysplasia in pediatric patients.

Cutaneous presentation of T-cell prolymphocytic leukemia.

T-cell prolymphocytic leukemia (T-PLL) is the most common mature T-cell leukemia (MTCL). Cutaneous involvement is a characteristic symptom of T-PLL and appears in up to one-third of cases; however, T-PLL is a relatively unknown disease in the field of dermatology. In this article, we seek to increase awareness and educate physicians about the clinical manifestations of T-PLL.

Neuroblastoma in an adult: case presentation and literature review.

Neuroblastoma is the most common malignancy in children less than one year of age, but is rare in adults. Adult neuroblastoma differs from pediatric cases by lacking classical features including low incidence of MYCN amplification, elevated urinary catecholamimes, and MIBG avidity. The diagnosis may not be initially considered because of the rarity, which emphasizes the importance of immunohistochemical staining and cytogenetic testing in aiding the diagnosis.

Clinically silent massive fetomaternal hemorrhage: important lessons from an illustrative case.

Massive fetomaternal hemorrhage (FMH) >150 mL is rare and may occur in the absence of high-risk obstetrical events. The significance of FMH in Rh D-negative women is alloimmunization with an increased risk of hemolytic disease of the newborn in subsequent Rh D-positive pregnancies and adverse outcomes for the fetus/neonate. The Kleihauer-Betke (KB) acid elution test is used to quantify fetal erythrocytes in the circulation of Rh D-negative women postpartum and to calculate the dose of Rh immune globulin (RhIG) needed for prophylaxis against alloimmunization.

The incidence and clinical significance of lymph node micrometastases determined by immunohistochemical staining in stage I - lymph node negative endometrial cancer.

Objective: Determine the incidence and clinical relevance of lymph node micrometastases found with immunohistochemical (IHC) staining in patients diagnosed with stage I lymph node-negative endometrial adenocarcinoma.

Methods: Eligible patients with endometrioid-type histology and negative lymph nodes by H&E were identified by a computerized database. After histologic confirmation, all paraffin-embedded pathologic specimens were freshly sliced and stained with IHC stains for pancytokeratin.