Crizanlizumab in sickle cell disease.

Vaso-occlusion in sickle cell disease (SCD) leads to a myriad of manifestations driving morbidity and mortality in patients with SCD. Increased leucocyte adhesion and P-selectin expression on platelets and endothelial cells is an inciting event that leads to obstruction of microcirculation by adhesion with rigid sickled red blood cells. Crizanlizumab is a first-in-class monoclonal antibody that inhibits P-selectin and has been shown to decrease the frequency of vaso-occlusive pain crises in patients with SCD in clinical trials. The role of crizanlizumab in other manifestations of SCD still needs further investigation.

There are more than 100,000 people in the USA living with sickle cell anemia, which is a form of the inherited blood disorder, sickle cell disease. Patients with sickle cell anemia are typically diagnosed through newborn screening programs. They are also diagnosed during times of vaso-occlusive pain crisis, where patients present with severe pain without an obvious cause, and also through hemolytic anemia, a disorder in which red blood cells are destroyed faster than they can be made. While children typically survive into adulthood, the life expectancy of those with sickle cell remains shorter secondary to the after-effects of chronic sickling, where the hemoglobin inside red blood cells sticks or clumps together, causing the cell to become fragile. The associated complications of chronic sickling include pulmonary hypertension (high blood pressure in the arteries of the lung and the right side of the heart), heart failure, stroke, liver dysfunction and splenic infarction, where the blood flow to the spleen is compromised. Crizanlizumab is a new therapy targeting P-selectin, a protein that blocks interaction with p-selectin glycoprotein ligand, and has shown promise in reducing vaso-occlusive crises.

Spontaneous Tumor Lysis Syndrome Secondary to Metastatic Small Cell Lung Cancer.

Tumor lysis syndrome (TLS) is an oncology emergency caused by the lysis of tumor cells that releases cell contents into the blood. TLS is typically associated with leukemia following the initiation of chemotherapy. Spontaneous TLS has been seen in hematologic malignancies, but the incidence of spontaneous TLS in solid tumors is rare, and only nine cases have been reported in small cell lung carcinoma. We present a case of a patient who presented with severe metabolic acidosis and electrolyte abnormalities consistent with TLS. At presentation, our patient was found to have small cell lung carcinoma with metastasis to the liver. This patient was managed with bicarbonate, rasburicase, allopurinol, and calcium replacement and started on continuous renal replacement therapy, but unfortunately was transitioned to comfort care and passed away. Risk factors for spontaneous TLS include bulky disease, elevated lactate dehydrogenase, elevated white blood cell counts, renal compromise, and abdominal organ involvement. The most common laboratory findings for TLS include metabolic acidosis and hyperuricemia, hyperphosphatemia, hyperkalemia, and hypocalcemia. Cases of spontaneous TLS, however, have been noted to have smaller elevations in phosphate levels. Spontaneous TLS is a rare but potentially fatal complication that can be seen in small cell lung carcinoma.

Aggressive End-of-Life Care in the Veterans Health Administration versus Fee-for-Service Medicare among Patients with Advanced Lung Cancer.

Background: Unlike fee-for-service Medicare, the Veterans Health Administration (VHA) allows for the provision of concurrent care, incorporating cancer treatment while in hospice. Methods: We compared trends of aggressive care at end of life between Medicare and VHA decedents with advanced nonsmall cell lung cancer from 2006 to 2012, and the relation between regional level end-of-life care between Medicare and VHA beneficiaries. Results: Among 18,371 Veterans and 25,283 Medicare beneficiaries, aggressive care at end of life decreased 15% in VHA and 4% in SEER (Surveillance, Epidemiology, and End Results)-Medicare (p < 0.001). Hospice use significantly increased within both cohorts (VHA 28%-41%; SM 60%-73%, p < 0.001). Veterans receiving care in regions with higher hospice admissions among Medicare beneficiaries were significantly less likely to receive aggressive care at end of life (adjusted odds ratio: 0.13, 95% confidence interval: 0.08-0.23, p < 0.001). Conclusions: Patients receiving lung cancer care in the VHA had a greater decline in aggressive care at end of life, perhaps due to increasing concurrent care availability.

A case of acquired hemophilia A in an elderly female.

Acquired Hemophilia A (AHA) is a bleeding diathesis related to the development of factor VIII inhibitor, which can frequently go undetected. It commonly manifests as spontaneous mucosal bleeds without any known history of a bleeding disorder, but has the potential to cause life threatening bleeding especially in elderly patients with underlying comorbidities. Here we describe a case of AHA in a 78 year old female presenting with spontaneous mucocutaneous bleeding as tongue hematoma and recurrent gastrointestinal (GI) bleeding. Underlying etiology remained unclear in this case. While she did not require any reversal agents to control bleeding, the patient received steroids and rituximab as inhibitor eradication therapy.