D-dimers are formed by the breakdown of fibrinogen and fibrin during fibrinolysis. D-dimer analysis is critical for the diagnosis of deep vein thrombosis, pulmonary embolism, and disseminated intravascular coagulation. Modern assays for D-dimer are monoclonal antibody based. The enzyme-linked immunosorbent assay (ELISA) is the reference method for D-dimer analysis in the central clinical laboratory, but is time consuming to perform. Recently, a number of rapid, point-of-care D-dimer assays have been developed for acute care settings that utilize a variety of methodologies. In view of the diversity of D-dimer assays used in central laboratory and point-of-care settings, several caveats must be taken to assure the proper interpretation and clinical application of the results. These include consideration of preanalytical variables and interfering substances, as well as patient drug therapy and underlying disease. D-dimer assays should also be validated in clinical studies, have established cut-off values, and reported according to the reagent manufacturers recommendations.

A RIA for human brain natriuretic peptide (BNP) was developed. Both BNP and atrial natriuretic peptide (ANP) were extracted from human plasma with Vycor glass powder (71% recovery for BNP). The assay had a minimum detection limit of 0.45 fmol/tube and an IC50 of 9 fmol/tube. The within-assay coefficients of variation were 11.4% at 4 pmol/L and 3.2% at 22 pmol/L, and the between-assay coefficient of variation was 11% at 24 pmol/L. There was no significant loss of immunoreactive (IR)-BNP in plasma samples stored at -80 C for 4 weeks. Low rates of labeled BNP and IR-BNP degradation occurred in EDTA plasma incubated at 37 C. The mean venous plasma IR-BNP (6.3 +/- 0.3 pmol/L) in normal subjects (n = 48) was significantly lower than plasma ANP (8.4 +/- 0.6 pmol/L). In contrast to ANP, IR-BNP did not increase when normotensive or hypertensive subjects changed from erect to supine posture. Markedly elevated levels were found in patients with congestive heart failure (mean IR-BNP, 87 +/- 11 pmol/L; ANP, 87 +/- 12 pmol/L; n = 35), recent myocardial infarction (mean IR-BNP, 60 +/- 9 pmol/L; ANP, 33 +/- 6 pmol/L; n = 7), and chronic renal failure. High pressure liquid chromatography of plasma extracts from heart failure subjects revealed both high (mol wt, 10,000) and low (mol wt, 4,000) mol wt IR-BNP. High mol wt BNP was the major component (mean ratio, 1.9:1) and was linearly correlated with low mol wt BNP (r = 0.99). HPLC of plasma extracts from three normal subjects receiving constant infusions of human BNP (2 pmol/kg.min) showed a single major peak eluting in the position of hBNP-32, with no evidence of high mol wt material. These results show that whereas marked elevations in BNP occur in circulatory disorders, a major (> 50%) and consistent contribution to immunoreactivity is due to precursor forms. Further, compared to ANP, there is no IR-BNP response to supine posture in normal and hypertensive subjects.

Since making its debut on the global stage in December 2019, Coronavirus Disease 2019 (COVID-19) has afflicted nearly four million people and caused hundreds of thousands of deaths. Case reports and case series depicting the clinical effects of the causative virus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) have been published, yet few demonstrate the cytopathologic alterations of this disease. We present a clinical-pathological correlation report of a previously healthy Hispanic woman with laboratory-confirmed COVID-19 who had typical features of acute respiratory distress syndrome (ARDS), and also showed cardiac abnormalities thought to represent fulminant viral myocarditis. Congruent with the ARDS clinical impression, autopsy findings were remarkable for extensive and markedly severe acute lung injury consistent with viral pneumonia, characterized by diffuse alveolar damage, pulmonary infarction, severe pulmonary edema, desquamation of pneumocytes with intraalveolar aggregation, and pneumocyte morphological alterations suspicious for viral cytopathic effect. However, there was incongruence between the clinical impression and the cardiovascular pathology findings in that viral myocarditis was not detected on histopathologic evaluation. This case highlights the importance of pathologic corroboration of the clinical impression and, in addition, illuminates the key role autopsy plays during a pandemic by providing valuable insight into viral pathology in tissues.

Context: This study represents the largest compilation to date of clinical and postmortem data from decedents with coronavirus disease 2019 (COVID-19). It will augment previously published small series of autopsy case reports, refine clinicopathologic considerations, and improve the accuracy of future vital statistical reporting. Objective: To accurately reflect the pre-existing diseases and pathologic conditions of decedents with Sars-CoV-2 infection through autopsy. Design: Comprehensive data from 135 autopsy evaluations of COVID-19-positive decedents is presented, including histologic assessment. Postmortem examinations were performed by 36 pathologists at 19 medical centers or forensic institutions in the United States and Brazil. Data from each autopsy were collected through the online submission of multiple choice and openended survey responses. Results: Patients dying of or with COVID-19 had an average of 8.89 pathologic conditions documented at autopsy, spanning a combination of prior chronic disease and acute conditions acquired during hospitalization. Virtually all decedents were cited as having more than one preexisting condition, encompassing an average of 2.88 such diseases each. Clinical conditions during terminal hospitalization were cited 395 times for the 135 autopsied decedents and predominantly encompassed acute failure of multiple organ systems and/or impaired coagulation. Myocarditis was rarely cited. Conclusions: Cause-of-death statements in both autopsy reports and death certificates may not encompass the severity or spectrum of co-morbid conditions in those dying of or with COVID-19. If supported by additional research, this finding may have implications for public health decisions and reporting moving forward through the pandemic.