Vonicog alfa for the management of von Willebrand disease: a comprehensive review and single-center experience.

Von Willebrand Disease (VWD) is characterized by a qualitative or quantitative defect in von Willebrand factor that results in prolonged bleeding due to the inability to form a stable platelet plug. VWD is the most common inherited bleeding disorder. The mainstay of treatment of VWD includes desmopressin; with plasma-derived von Willebrand Factor concentrates reserved for patients with severe VWD or those with desmopressin intolerability. Although efficacious, plasma-derived factor concentrates can have risks associated with them including minimal risk of pathogenic transmission, potential to contain extraneous plasma proteins and cause severe allergic reactions, and a supply limited by plasma donor availability. Vonicog alfa is a recombinant von Willebrand Factor product. Two phase III trials evaluated the safety and efficacy of vonicog alfa in preventing perioperative bleeding and treating acute bleeding in patients with VWD. Beyond the clinical trials, there has been little real-world experience published regarding experiences with this medication. This article comprehensively reviews the efficacy, safety, pharmacokinetics, and pharmacodynamics of vonicog alfa. These points will be discussed using institutional experiential data from the University of Virginia (UVA) Health System in relation to the clinical studies. The goal of this review article is to offer insights to clinical directions, discuss operational challenges, and offer guidance for future studies and formulary decisions.

Enhancing evaluation of sarcopenia in patients with non-small cell lung cancer (NSCLC) by assessing skeletal muscle index (SMI) at the first lumbar (L1) level on routine chest computed tomography (CT).

PURPOSE: Ongoing cancer cachexia trials evaluate sarcopenia by skeletal muscle index (SMI) at the L3 vertebrae level, commonly used as a standard. Routine chest CT institutional protocols widely differ in including L3. We investigated whether SMI at L1 assessment, rather than L3, would be reliable and more practicable for non-small cell lung cancer (NSCLC). METHODS: NSCLC patients with routine CT chest had SMI measurements performed at L1 using Slice-O-Matic software. Accuracy of including L1 level, imaging quality, and ability to detect sarcopenia was collected and correlation of L1 SMI with body mass index (BMI) was performed. RESULTS: Thirty-seven patients with NSCLC (73 CT assessments) were enlisted at three institutions. Characteristics: 47% female; medians: age 59, KPS 80%; BMI 25.49, weight 72.97 kg, SMI 59.24. Sarcopenia was detected in 14.7% of patients; 20% had sarcopenic obesity. Of the 73 CTs, 94.5% included L1 (95% CI 86.6-98.5%). Three images (4%) were difficult to evaluate. Inclusion of L1 was similar among the three participating institutions (90.4 to 96.7% inclusion). BMI correlation with SMI was weak (r = 0.329). CONCLUSIONS: SMI assessment at L1 is achievable in patients with NSCLC receiving routine chest CT, with 96% having acceptable quality evaluations. Similar to results previously reported at L3, BMI showed poor correlation and low sensitivity to detect muscle mass loss. The use of CT at L1 is reliable and presents the opportunity for easier patient evaluation of sarcopenia in patients with lung cancer without the need for additional testing or radiation exposure.

IVC agenesis: a rare cause of deep vein thrombosis.

We present the case of a healthy, young Caucasian female who presented to an outside hospital with phlegmasia cerulea dolens of both lower extremities. Computed tomography angiography revealed inferior vena cava (IVC) occlusion. She was initiated on heparin infusion and transferred to University of Virginia Medical Center. Our evaluation revealed aplasia of the IVC from the infrahepatic segment to the confluence of the common iliac veins and acute bilateral iliac vein thromboses. An extensive network of collateral veins was noted. These findings were consistent with IVC agenesis. She was not pregnant or using contraception. Primary thrombophilia workup was negative. She underwent bilateral iliac vein thrombolysis and was started on anticoagulation. While IVC agenesis is rare, it carries risk for development of thrombotic sequelae and bears consideration when evaluating young patients with unexplained deep vein thrombosis, especially if extensive and bilateral.

Reversal of cardiomyopathy with tocilizumab in a case of HIV-negative Castleman's disease.

The association between Castleman's disease (CD) and cardiomyopathy has been rarely reported and the optimal therapeutic approach remains unknown. We report a previously healthy 20-year-old African American female who presented with fever, dyspnea, anasarca, and generalized lymphadenopathy. Diagnostic workup, including an axillary lymph node biopsy, revealed that she had human immunodeficiency virus-negative and human herpes virus-8-negative multicentric CD. She had a non-anaphylactoid infusion reaction during her fourth rituximab infusion. A few weeks later, she developed new-onset severe cardiomyopathy requiring inotropic therapy, warranting consideration for left ventricular assist device. Several clinical clues indicated her new-onset heart failure was a manifestation of her CD. Interestingly, a trial of tocilizumab (an anti-interleukin-6 receptor monoclonal antibody) resulted in complete resolution of her cardiomyopathy and other manifestations of CD. Tocilizumab received orphan drug approval for the treatment of CD in Japan, but is not yet approved for this indication in the United States. Clinicians should be aware of its potential clinical utility in CD.

Cardiac complications from multisystem inflammatory syndrome associated with prior COVID-19 infection.

Multisystem inflammatory syndrome in adults (MIS-A) is a systemic inflammatory condition that presents roughly 4-6 weeks after initial COVID-19 infection. Patients typically present with persistent fevers, widespread rash, abdominal pain, vomiting and diarrhoea, and new-onset neurological symptoms. Cardiac dysfunction is a prominent feature of COVID-19 sequelae due to the abundance of ACE2 receptors on cardiac tissue. Delayed diagnosis due to the novelty of MIS-A can lead to cardiac complications like heart failure and shock, which could result in chronic cardiac disease. Avoidance of complications and chronic illness is possible with prompt corticosteroid therapy. Despite patient recovery to baseline level of function, surveillance of cardiac function to screen for chronic cardiac disease in the follow-up period is recommended. We present a case of MIS-A in a young man, compare his presentation with other similar cases and discuss implications of delayed diagnosis.

A Review of the Past, Present and Future of Cancer-associated Thrombosis Management.

Venous thromboembolism (VTE) can have a significant impact on the management, quality of life and mortality of patients with cancer. VTE occurs in 5-20% of patients with cancer, and malignancy is associated with up to 25% of all VTE. It is the second leading cause of death in ambulatory patients with cancer who are receiving chemotherapy. Increased rates of cancer-associated thrombosis are attributed to improved patient survival, increased awareness, surgery, antineoplastic treatments and the use of central venous access devices. Many factors influence cancer-associated thrombosis risk and are broadly categorized into patient-related, cancer-related and treatment-related risks. Direct-acting oral anticoagulants have shown themselves to be at least as effective in preventing recurrent VTE in patients with cancer with symptomatic and incidental VTE. This has led to a change in treatment paradigms so that direct-acting oral anticoagulants are now considered first-line agents in appropriately selected patients. In this article, we review the prior and recent landmark studies that have directed the treatment of cancer-associated thrombosis, and discuss specific factors that affect management as well as future treatment considerations.

A Brief Review of Thrombolytics for Venous Interventions.

Anticoagulation continues to be the mainstay of therapy for the management of venous thromboembolism. However, anticoagulation does not lead to the breakdown or dissolving of the thrombus. In an acute pulmonary embolism, extensive thrombus burden can be associated with a high risk for early decompensation, and in acute deep venous thrombosis, it can be associated with an increased risk for phlegmasia. In addition, residual thrombosis can be associated with chronic thromboembolic pulmonary hypertension and postthrombotic syndrome in a chronic setting. Thrombolytic therapy is a crucial therapeutic choice in treating venous thromboembolism for thrombus resolution. Historically, it was administered systemically and was associated with high bleeding rates, particularly major bleeding, including intracranial bleeding. In the last two decades, there has been a significant increase in catheter-based therapies with and without ultrasound, where lower doses of thrombolytic agents are utilized, potentially reducing the risk for major bleeding events and improving the odds of reducing the thrombus burden. In this article, we provide an overview of several thrombolytic therapies, including delivery methods, doses, and outcomes.

Multidisciplinary Effort to Decrease Time From Admission to Chemotherapy on an Inpatient Oncology Unit.

There are no national standards for time between patient arrival and the initiation of scheduled chemotherapy (time to chemotherapy [TTC]). Delays in this process have a negative impact on patient care and the use of health care resources. At the University of Virginia Cancer Center, mean TTC in 2015 was 12.1 hours and mean length of stay (LOS) was 5.45 days at baseline. We formed a multidisciplinary team that participated in ASCO's Quality Training Program. We aimed to improve TTC by 10% over 6 months. We used Plan-Do-Study-Act (PDSA) cycles as quality improvement (QI) models and used XmR charts to evaluate the interventions. The first PDSA cycle involved amending the chemotherapy consent process; mean TTC and LOS improved to 9.3 hours and 4.65 days, respectively. The second PDSA cycle involved shifting pharmacist review of chemotherapy orders to before admission rather than after patient arrival. Mean TTC remained at 9.4 hours (net 22% improvement from baseline) and LOS improved to 4.33 days (net 21% improvement). Our team surpassed the 10% improvement goal for TTC. This QI project faced a few limitations. Our baseline data set was a retrospective cohort review. In addition, oncology patients have a wide range of individual clinical needs that may have an impact on TTC. Delays in TTC have an impact on oncologic care at many medical centers. Our project highlights the need for guidance on this issue. We recommend that other institutions form multidisciplinary teams and also use QI tools to assess delays and implement changes.

New Therapeutic Strategies in Acute Lymphocytic Leukemia.

Most drugs used in standard regimens for acute lymphoblastic leukemia (ALL) were developed more than 30 years ago. Since that time, several new drugs have been developed and incorporated into ALL treatment. In spite of this, novel therapeutic approaches are still needed to improve outcomes for high-risk or relapsed ALL. This manuscript discusses newer treatment strategies, including purine nucleoside analogs, monoclonal antibodies, antibody drug conjugates, mammalian target of rapamycin (mTOR) inhibitors, proteasome inhibitors, histone deacetylase (HDAC) inhibitors, hypomethylating agents, spleen tyrosine kinase inhibitors, Bruton's tyrosine kinase (BTK) inhibitors, Janus kinase-signal transducer and activator of transcription (JAK-STAT) inhibitors, anti-programmed cell death protein (anti-PD-1) antibodies, mitogen-activated protein kinase (MEK) inhibitors, CXCR4 antagonists, poly (ADP-ribose) polymerase (PARP) inhibitors, and FMS-like tyrosine kinase 3 (FLT3) inhibitors. Additionally, this manuscript discusses the impact of diagnostic approaches on management of ALL. Specifically, minimal residual disease is increasingly felt to be important and will likely dramatically impact the care of ALL patients in the near future.

Body surface area: a predictor of response to red blood cell transfusion.

A current focus of transfusion medicine is a judicious strategy in transfusion of blood products. Unfortunately, our ability to predict hemoglobin (Hgb) response to transfusion has been limited. The objective of this study was to determine variability of response to red blood cell transfusion and to predict which patients will have an Hgb rise higher or lower than that predicted by the long-standing convention of "one and three". This was a retrospective chart review in a single hospital. Data for 167 consecutive patient encounters were reviewed. The dataset was randomly divided into derivation and validation subsets with no significant differences in characteristics. DeltaHgb was defined as posttransfusion Hgb minus pre-transfusion Hgb per red blood cell unit. We classified all the patients in both the subsets as "high responders" (DeltaHgb >1 g/dL) or as "low responders" (DeltaHgb ≤1 g/dL). In univariate analysis, age, sex, body weight, estimated blood volume, and body surface area were significantly associated with response category (P<0.05). Different multivariate regression models were tested using the derivation subset. The probability of being a high responder was best calculated using the logarithmic formula eH / (1 + eH), where H is B0 + (B1 × variable 1) + (B2 × variable 2). Bis are coefficients of the models. On validation, the model H=6.5-(3.3 × body surface area), with the cutoff probability of 0.5, was found to correctly classify patients into high and low responders in 69% of cases (sensitivity 84.6%, specificity 43.8%). This model may equip clinicians to make more appropriate transfusion decisions and serve as a springboard for further research in transfusion medicine.