Wounds resulting from non-malignant haematological disease: a case series.

A proactive and systemic approach is imperative to preventing wounds due to disorders of non-malignant haematologic disease. Here, the authors provide several examples of patients with either a known history or acute diagnosis of a coagulation disorder with the aim of reviewing potential cutaneous injuries as well as diagnosis and treatment. A description of the wound and treatment course along with recommendations where appropriate are presented. The article serves as a general review for health professionals who may encounter patients with this disorder and who are involved in treatment decisions. After reviewing the article, the practitioner will be able to identify cutaneous injuries that may be secondary to an underlying haematological disorder, review the diagnosis and treatment recommended, and understand the need for a multidisciplinary approach to patient care.

Defining the role of risk stratification and duplex ultrasound in the diagnosis of acute lower extremity deep vein thrombosis.

OBJECTIVE: Risk stratification using the plasma D-dimer level and Wells score has been proposed as a safe strategy to rule out acute lower extremity deep vein thrombosis (DVT) and limit the use of duplex ultrasound (DUS) for low-risk patients. A widely used diagnostic protocol defining the role of pretest probability and D-dimer testing in lieu of DUS has not been reported. Our aim was to define the risk of DVT in a standard population of emergency department patients who had presented with acute lower extremity symptoms and determine the role of DUS for these patients. METHODS: Outpatients presenting to the emergency department with symptoms concerning for lower extremity DVT were prospectively enrolled. All the patients underwent whole leg DUS and clinical and laboratory assessments for DVT using the Wells criteria and plasma D-dimer testing. The patients were stratified into three groups according to the combination of their Wells score and plasma D-dimer level. The prevalence of DVT and the statistical performance of the combined Wells score and plasma D-dimer were compared. RESULTS: A total of 3087 patients were enrolled. Most of the patients had had a negative plasma D-dimer level and Wells score (n = 2290 patients). A total of 222 patients had had a positive plasma D-dimer level and Wells score. The overall prevalence of acute DVT in the present study was 7.3%. Of the 2290 patients with a negative Wells score and negative plasma D-dimer level, 4 had had a diagnosis of DVT (negative predictive value, 99.8%). In contrast, DVT was present in 181 of 222 patients (81.5%) with a positive Wells score and plasma D-dimer level (positive predictive value, 81.5%). The plasma D-dimer level also correlated with the DVT location, and the D-dimer levels were highest for the patients with proximal DVT. CONCLUSIONS: The combination of a negative Wells score and negative plasma D-dimer level can safely exclude the presence of DVT. Patients with a negative Wells score and negative plasma D-dimer level are unlikely to benefit from DUS. In contrast, patients with a positive D-dimer level and positive Wells score will benefit from whole leg DUS to rule out the presence of high-risk DVT.

The clinical significance of ultra-high D-dimer levels.

OBJECTIVE: Plasma D-dimer levels >5000 ng/mL are encountered in a number of conditions other than venous thromboembolism (VTE). Recent studies have used plasma D-dimer levels as a prognostic indicator for coronavirus disease 2019 (COVID-19) infection. The implications of abnormal levels are less clear for patients diagnosed with COVID-19 with a baseline elevation in plasma D-dimer levels. In the present study, we reviewed the occurrence of plasma D-dimer levels >5000 ng/mL and investigated the clinical significance of this finding before the onset of the COVID-19 pandemic. METHODS: Inpatient records for a 4-year period were screened for laboratory results of plasma D-dimer levels >5000 ng/mL. The patient data were reviewed for the clinical identifiers commonly associated with elevated plasma D-dimer levels, including VTE, cancer, sepsis, pneumonia, other infection, bleeding, and trauma. The patients were then categorized into groups stratified by the plasma D-dimer level to allow for comparisons between the various clinical diagnoses. RESULTS: A total of 671 patients were included in the present study. VTE was the most common diagnosis for patients with a plasma D-dimer level >5000 ng/mL, followed by cancer and pneumonia. Multiple clinical diagnoses were present in 61% of the patients. No clear cause for the ultra-high plasma D-dimer level could be identified in 11.3% of the patients. Among the patients lacking a clinical diagnosis at discharge, mortality was 24% in the 5000- to 10,000-ng/mL group, 28.6% in the 10,000- to 15,000-ng/mL group, and 75% in the >15,000-ng/mL group. CONCLUSIONS: VTE, cancer, and pneumonia were frequently present when ultra-high plasma D-dimer levels were encountered, and mortality was high when the levels were >15,000 ng/mL. The results from our study from a pre-COVID-19 patient population suggest that ultra-high plasma D-dimer levels indicate the presence of severe underlying disease. This should be considered when using the plasma D-dimer level as a screening tool or prognostic indicator for COVID-19 infection.

A Case of Thrombotic Vasculopathy in the Setting of High-Dose Hydroxyurea Use.

This case study describes the presentation of a 76-year-old male with a past medical history that included atrial fibrillation, essential hypertension, coronary artery disease status post cardiac stent placement, heart failure, hyperlipidemia, thyroid cancer (with thyroid resection resulting in hypothyroidism), prostate cancer status post brachytherapy (in remission), and a history of JAK2-positive myeloproliferative disease. He presented with painful areas of hyperpigmentation appearing as purple discoloration to his neck, lower abdominal skinfold, and bilateral groin areas that progressed to painful ulcerations a few weeks after a myocardial infarction. Due to the patient's multiple medical conditions and uncommon presentation of wounds, a multidisciplinary team was involved in his care. Differential diagnosis included antiphospholipid syndrome, symmetrical drug-related intertriginous and flexural exanthema, warfarin-induced necrosis, cutaneous thrombotic vasculopathy, myeloproliferative disorder, and high-dose hydroxyurea therapy. It was determined by the authors that the high-dose hydroxyurea therapy was the cause of the wounds. Because of the patient's initial health status, treatment of the wounds included use of collagenase and sodium hypochlorite solution to reduce the risk of infection and attempt to promote autolytic debridement until surgical wound debridement could be done. The patient required multiple hospital stays, but ultimately his health status improved and the wounds resolved with the assistance of the combined efforts of the multidisciplinary team to diagnose and treat this complex patient and his uncommon wound presentation.

Romidepsin-associated cardiac toxicity and ECG changes: A case report and review of the literature.

Background Romidepsin is a novel histone deacetylase inhibitor that is approved for the treatment of cutaneous and peripheral T-cell lymphoma in patients who have had at least one prior therapy. Romidepsin is generally well tolerated, though it comes with a risk of cardiac toxicities. Objective We report a case of electrocardiogram changes in a 64-year-old male with enteropathy-associated T-cell lymphoma, type 2, treated with salvage romidepsin therapy who relapsed after non-myeloablative allogeneic sibling peripheral blood stem cell transplant. Discussion Although histone deacetylase inhibitors have been investigated for many years, they have only recently been translated to clinical use as a therapy for malignancies. Furthermore, given their approval for a rare disease, clinicians often have limited experience with the dosing and side effects of histone deacetylase inhibitors. Conclusion This case report and literature review investigates the cardiac side effects of histone deacetylase inhibitors and illustrates the importance of cardiac monitoring prior to and during treatment.

Association of osteoprotegerin and bone loss after adjuvant chemotherapy in early-stage breast cancer.

PURPOSE: Chemotherapy induced ovarian failure (CIOF) results in rapid bone loss. Receptor Activator of Nuclear Factor Kappa-B (RANK)-RANK ligand (RANK-L) signaling balances bone resorption and formation. Osteoprotegerin (OPG) acts as a decoy receptor for RANK, interrupting osteoclast activation and bone resorption. This study examined the relationship between OPG and bone loss in women with CIOF. METHODS: Premenopausal women with stage I/II breast cancers receiving adjuvant chemotherapy were evaluated at chemotherapy initiation, 6 and 12 months. Bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN), follicle stimulating hormone (FSH), ionized calcium, osteocalcin, and OPG were serially measured. CIOF was defined as a negative pregnancy test, FSH levels >30 MIU/mL, and ≥3 months of amenorrhea. RESULTS: Forty women were enrolled; 31 (77.5%) met CIOF criteria. BMD significantly decreased (p < 0.001) in the CIOF group at both time points: LS BMD decreased from a median of 0.993 g/cm(2) to 0.976 g/cm(2) and 0.937 g/cm(2) at 6 and 12 months, respectively. OPG was significantly elevated at 6 months (median increase 0.30 pmol/L, p = 0.015) and then decreased at 12 months to levels still above baseline (median difference 0.2 pmol/L, p = 0.70). CONCLUSIONS: In what was likely a compensatory response to rapid bone loss, CIOF patients' OPG levels increased at 6 months and then decreased at 12 months to values greater than baseline assessments. This phenomenon is described in other diseases, but never before in CIOF.

Role of trastuzumab emtansine in the treatment of HER2-positive breast cancer.

Trastuzumab is a monoclonal antibody that is used in the treatment of breast cancer. Trastuzumab targets the human epidermal growth factor receptor 2 (HER2) receptor on breast cancer cells that express this tyrosine kinase receptor. These cancers are referred to as HER2-positive breast cancer. The original studies of trastuzumab showed improved survival in metastatic breast cancer; however, resistance often develops. In the adjuvant setting, women often progress despite therapy that includes trastuzumab. Antibody-drug conjugates are a new class of powerful drugs designed to target high-dose chemotherapy directly to the cancer cells. Trastuzumab emtansine is one of these antibody-drug conjugates and was the first Food and Drug Administration approved drug for a solid tumor. Emtansine is a potent antimicrotubule agent. Trastuzumab is used to target this potent chemotherapy agent directly to the HER2-expressing cancer cells. This review article will summarize the evidence from the preclinical studies, summarize evidence from the clinical trials, discuss current clinical trials, discuss current approval of trastuzumab emtansine, and discuss future directions of research.