Commercial Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Molecular Assays: Superior Analytical Sensitivity of cobas SARS-CoV-2 Relative to NxTAG CoV Extended Panel and ID NOW COVID-19 Test.

CONTEXT.­: We implemented multiple nucleic acid amplification test platforms because of the limited availability of test kits for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the early stages of the pandemic. Interpretation of results generated by different platforms and prioritization for testing algorithms required cross-comparison. OBJECTIVE.­: To compare the analytical sensitivity of 3 commercial SARS-CoV-2 molecular assays, selected samples were studied in parallel with Cobas SARS-CoV-2 test, NxTAG CoV Extended Panel, and ID NOW COVID-19 assays. DESIGN.­: A total of 8043 SARS-CoV-2 tests performed from March 22 to April 19, 2020, were included in this study. For all 1794 positive specimens detected by the cobas SARS-CoV-2 assay, the cycle threshold (Ct) values were manually tracked and plotted to demonstrate the distribution of sample viral levels. Additionally, 50 and 63 low-positive specimens (Ct values >32) as well as 50 and 61 consecutive positive specimens by the cobas assay were tested with NxTAG and ID NOW, respectively, to estimate their relative sensitivities. RESULTS.­: The Ct values of cobas SARS-CoV-2-positive samples were evenly distributed throughout ranges of 13.32 to 39.50 (mean, 25.06) and 13.60 to 42.49 (mean, 26.45) for ORF1 and E gene targets, respectively. NxTAG reliably detected only specimens with E gene Ct values lower than 33, and is estimated to detect 89.4% of positive specimens detected by cobas assay. ID NOW had performance variation independent of Ct value and is estimated to detect 83.5% of cobas positives. CONCLUSIONS.­: Clinical specimens exhibit a wide range of viral burden, with a significant portion at low levels. Analytical sensitivity of testing platforms is critical for reliable detection of SARS-CoV-2 and uniform care to patients.

New-onset acute thrombocytopenia in hospitalized patients: pathophysiology and diagnostic approach.

Thrombocytopenia is a hematological finding commonly encountered in daily clinical practice from asymptomatic clinic patients to critically ill intensive care unit patients. A broad spectrum of etiologies and variation in clinical presentation often present a diagnostic challenge. Furthermore, concomitant presence of thrombosis and thrombocytopenia, as in cases of thrombotic thrombocytopenia, complicates the management. In hospitalized patients, new-onset thrombocytopenia is an important reason for hematology consultation. Therefore, it is of utmost importance that the etiology is diagnosed accurately. In addition, a basic understanding of the pathophysiology and the differential diagnosis avoids delay in the diagnosis and leads to rapid initiation of treatment. This review will address causes of thrombocytopenia that arises in hospitalized patients with an emphasis on the pathophysiological basis of each disorder.

Immunoglobulin D Multiple Myeloma, Plasma Cell Leukemia and Chronic Myelogenous Leukemia in a Single Patient Treated Simultaneously with Lenalidomide, Bortezomib, Dexamethasone and Imatinib.

Multiple myeloma (MM) is a neoplastic lymphoproliferative disorder characterized by uncontrolled monoclonal plasma cell proliferation. Among different isotypes of MM, immunoglobulin D (IgD) MM is very rare, representing only 1 to 2% of all isotypes. Chronic myelogenous leukemia (CML) is a neoplastic myeloproliferative disorder of pluripotent hematopoietic stem cell, which is characterized by the uncontrolled proliferation of myeloid cells. An 88-year-old male was diagnosed simultaneously with IgD kappa MM and CML. A distinctive feature in this patient was the progression to plasma cell leukemia without any symptomatic myeloma stage. He was treated simultaneously with lenalidomide, bortezomib and imatinib. Synchronous occurrence of these rare hematological malignancies in a single patient is an exceedingly rare event. Multiple hypotheses to explain co-occurrence of CML and MM have been proposed; however, the exact etiological molecular pathophysiology remains elusive.

Occult gastric cancer presenting as hypoxia from pulmonary tumor thrombotic microangiopathy.

Pulmonary tumor thrombotic microangiopathy (PTTM) causing fatal pulmonary hypertension is a rare presentation of malignancy. In general, patients with PTTM rapidly succumb to death due to severe hypoxia. To date, very few cases of PTTM have been reported in the literature; and most of these cases were from gastric cancer and were diagnosed on post mortem autopsy, as it is extremely challenging to make an ante mortem diagnosis. We here report on a case of undiagnosed diffuse gastric cancer, presenting as worsening hypoxia. The clinical, radiographic, and echocardiographic features, and laboratory and pathological results were consistent with PTTM from gastric cancer. The patient was started on anticoagulation therapy, corticosteroids, and high-flow oxygen. However, her hypoxia worsened to the extent that she required ventilator support, and she died soon after intubation due to cardiac arrest. Since diffuse gastric cancer is associated with hereditary diffuse gastric cancer syndrome, cadherin 1 gene mutation analysis was performed to estimate the risk to her daughters. The test came back negative.

Small cell lung cancer presenting as severe thrombocytopenia and refractory hypokalemia.

A 70-year-old female with a history of mild cirrhosis was referred by her primary care provider for a platelet count of 36,000/ µ L which had dropped from 47,000/ µ L in a week along with mild pain in extremities. Serum potassium was low (2.9 mEq/L) in spite of the patient being recently started on potassium supplement on outpatient for hypokalemia. Initially thrombocytopenia was attributed to cirrhosis. However, platelet counts continued to drop to a nadir of 9000/ µ L in spite of several platelet transfusions. Hypokalemia was refractory to potassium supplements. Subsequent bone marrow biopsy revealed extensive marrow necrosis with a focus of small cell tumor cells of pulmonary origin. CT scan of the chest showed a spiculated left lung mass. The ACTH level was high, with normal rennin and aldosterone levels. The patient likely had ectopic ACTH syndrome from small cell lung cancer. She died within few days of diagnosis. Severe thrombocytopenia and refractory hypokalemia can rarely be initial presentations of small cell lung cancer. Thrombocytopenia should prompt an evaluation for bone marrow metastases and a search for undiagnosed systemic malignancy. In severe cases of metastases, bone marrow necrosis can be present. Refractory hypokalemia can be the sole presentation of ectopic ACTH production.