Treatment of refractory thrombotic thrombocytopenic purpura with N-acetylcysteine: a case report.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease resulting in systemic microvascular thrombosis. The disease is caused by excessive platelet (PLT) adhesion to ultra-large (UL) von Willebrand factor (VWF) multimers inadequately cleaved by the processing enzyme ADAMTS-13. While many cases respond to plasma exchange performed with or without concurrent corticosteroids, treatment of the 10% to 20% of patients with refractory disease is difficult. Experimental studies demonstrating that N-acetylcysteine (NAC) inhibits PLT binding to endothelial cell-secreted and anchored UL VWF multimers suggest that NAC may be useful in the treatment of TTP. CASE REPORT: A 44-year-old woman presented with malaise, confusion, chest and abdominal pain, and transient visual loss. Laboratory results and peripheral blood smear were consistent with TTP. The patient was begun on plasma exchange and corticosteroid treatment, but after 10 days the PLT count was still less than 10.0 × 10(9) /L and she developed a fever. Rituximab was initiated, but the patient's condition worsened and she became comatose. Antibiotics were initiated, but cultures remained sterile. After 3 days of coma and further clinical deterioration, treatment with NAC was begun. The patient received a loading dose of 150 mg/kg NAC intravenously (IV) over 1 hour. Within 18 hours the patient awakened abruptly and began communicating with medical personnel. Plasma exchange, corticosteroids, rituximab, and NAC infusion (150 mg/kg IV over 17 hr daily × 10 days) were continued and by Day 17 the PLT count was more than 50 × 10(9) /L. The patient fully recovered and was discharged on Day 31. CONCLUSION: This is the first complete report of a TTP patient treated with NAC. NAC was a safe and effective supplementary treatment for refractory TTP in this patient.

A rare case of acyclovir-induced thrombocytopenia.

Acyclovir is used for its potent antiviral properties for the mucocutaneous herpes, herpes zoster, herpes encephalitis, and genital herpes simplex. The drug has a very wide distribution involving almost every organ of the body, with excretion into the urine. Urine analysis, kidney function, liver function, and complete blood counts are some of the monitoring parameters. The active triphosphate form of the drug inhibits DNA synthesis and viral replication by competing with deoxyguanosine triphosphate for viral DNA polymerase and being incorporated into viral DNA. Because the drug is only absorbed by the cells that are virus infected, acyclovir has minimal side effects at therapeutic doses. However, at high intravenous infusions, severe central nervous system (malaise), gastrointestinal (nausea/vomiting), renal (elevated blood urea nitrogen/creatinine), hepatic (elevated liver enzymes), and skin dyscrasias have been found to occur. There have been few case reports of bone marrow suppression and only one case report so far of acyclovir-related isolated thrombocytopenia. Whether there is any further association between acyclovir and thrombotic thrombocytopenic purpura/hemolytic uremic syndrome is the next dilemma if such an association is established. Here, the authors present a case report of a 58-year-old man with acquired immune deficiency syndrome on highly active antiretroviral therapy who went into severe thrombocytopenia on starting acyclovir.

Using Federal, State, and Grassroots Advocacy to Effect Change in Cancer Care Delivery and Patient Outcomes in the United States.

Health policy influences health and well-being for patients with cancer. Advocating for evidence-based health policies that aim to prevent cancer, promote health, and improve efficiencies in the health care system is crucial to improving care delivery and cancer outcomes nationwide. The role of the ASCO's Government Relations Committee (GRC) is to advocate for policies at a federal and state level that promote high-quality and equitable cancer care, and ASCO volunteer engagement is critical for the success of creating, changing, and adopting policies that support patients with cancer and their care team. Cancer care professionals are uniquely positioned to advocate at all levels of government, local, state, and federal and to serve as invaluable resources for lawmakers as they work to implement policy changes. Lawmakers are highly responsive to cancer care providers as most lawmakers have family or friends who have been diagnosed with cancer. Multiple advocacy strategies that are effective and efficient in their approach have been used, making advocating feasible for cancer care professionals' busy schedule. To improve patient care, ASCO's GRC and ASCO volunteers advocate for increased federal funding for research, greater health care access, value in cancer care, and payment reform. ASCO's GRC has many programs in place to support ASCO members interested in engaging in advocacy to improve the quality of care for their patients and the support for cancer care professionals to thrive in the field.

Direct thrombin inhibitors: a case indicating benefit from 'plasmapheresis' in toxicity: a call for establishing "guidelines" in overdose and to find an "antidote"!

Patient presented with passage of fresh blood mixed with clots per rectum. In the ER, she was found to have bright red blood per rectum with clots, with frank blood on nasogastric tube. She was on dabigatran for atrial fibrillation and aspirin, with intermittent intake of ibuprofen. Vitals were positive for orthostatic hypotension. The pertinent findings in the physical examination were altered mental status with orientation*1, weak peripheral pulses, irregularly irregular heart rate, and bilateral pitting edema 2+ in bilateral lower extremities. Patient was intubated and put on mechanical ventilation. A massive transfusion protocol was followed. Laboratories and imaging: hemoglobin/hematocrit, 7.2/22.1; white blood cells, 7.7, platelet, 210; international normalized ratio, 2.5; prothrombin time, 19.2; activated partial thromboplastin time, 88.2; CMP was WNL; BNP, 621; fibrinogen, 500 mg/dL. Electrocardiogram showed atrial fibrillation with inferolateral ischemia. Ultrasonography of the liver and gallbladder showed no acute pathology. Echocardiogram showed an EF of 70% with hyperdynamic LV. Patient was transferred to the intensive care unit. Dabigatran, aspirin, and nonsteroidal anti-inflammatory drugs were discontinued, and antihypertensives were held. She was given blood and FFPs. Hemoglobin, hematocrit, and coagulation profile was monitored every 6 hours. Gastroenterology, general surgery, interventional radiology, and hematology services were called stat. IR placed a double-lumen, power central venous catheter. In gastroenterology, EGD and colonoscopy was performed, which showed active bleed at distal esophagus, stopped with local epinephrine. No active bleed seen on colonoscopy. The patient was put on Nexium drip. Hematology service recommended thrombin time (>200) and factors 2, 5, 7, 9, 10-41(l), 80, 68, 48(l), 61. Prothrombin time and activated partial thromboplastin time mixing studies were done, which indicated the presence of thrombin inhibition. Prothrombin complex concentrate at 50 U/kg was started to reverse the effect of dabigatran, and platelets were transfused to reverse the effect of aspirin. They also discussed that the half-life of dabigatran being 17 hours, and the drug would not be toxic at this point, as the patient was already 24-hour inpatient by now. The hemoglobin trend: 7.4→6.4→8.2→7.5→6.6. At this point, the need for further intervention in form of hemodialysis or plasmapheresis was considered. The patient was given plasmapheresis and hemoglobin and hematocrit stabilized. The patient was kept on continued mechanical ventilator support for the night and extubated next day. The hemodynamics stabilized and the patient was transferred to the general medical floors after 1 day of observation, after extubation.

Chemotherapy-related cardiotoxicity.

Cardiovascular toxicity caused by cancer therapy is a challenging area which needs thorough evaluation and research. Numerous studies, meta-analyses and reviews have been published in the past discussing cardiotoxicity caused by chemotherapeutic agents. A brief review of the on-target and off-target cardiotoxicities caused by chemotherapeutic agents is presented here. Cardiotoxicities are broadly outlined in terms of left ventricular dysfunction, hypertension and thromboembolic events. The mechanisms leading to the cardiotoxicity profiles of various chemotherapeutic agents are discussed. The management of various cardiotoxicities of chemotherapeutic agents is also discussed.

A success story leading us to think big!

Immune dysregulation is the hallmark of all autoimmune diseases. It is extremely interesting to study the associations and pathogenesis of the various autoimmune diseases, like the link between the AIHA and CLL. This link is well established and is based on the fact that there is loss of tolerance to the self-antigen, which in turn leads to immunebased hemolytic anemia. Around 30% of the patients with CLL are at the risk of developing AIHA, and 11% eventually develop AIHA. Whether there is any definite linkup between the corrupted immune system and "acute" leukemias/lymphomas is yet to be established. Needless to say, if there was an association between the pathogenesis of the ALLs and AIHA, it would be a landmark in the field of oncology as it would enforce early diagnosis and treatment for the disease which is much more aggressive and found in a comparatively younger age group (predominantly in children and a mean age of 40 years in adults) as compared to its chronic counterparts. The AIHA would serve as a "tip to the underlying iceberg" in these situations, warning us of the cryptic diagnosis.