Definitions of the phenotypic manifestations of sickle cell disease.

Sickle cell disease (SCD) is a pleiotropic genetic disorder of hemoglobin that has profound multiorgan effects. The low prevalence of SCD ( approximately 100,000/US) has limited progress in clinical, basic, and translational research. Lack of a large, readily accessible population for clinical studies has contributed to the absence of standard definitions and diagnostic criteria for the numerous complications of SCD and inadequate understanding of SCD pathophysiology. In 2005, the Comprehensive Sickle Cell Centers initiated a project to establish consensus definitions of the most frequently occurring complications. A group of clinicians and scientists with extensive expertise in research and treatment of SCD gathered to identify and categorize the most common complications. From this group, a formal writing team was formed that further reviewed the literature, sought specialist input, and produced definitions in a standard format. This article provides an overview of the process and describes 12 body system categories and the most prevalent or severe complications within these categories. A detailed Appendix provides standardized definitions for all complications identified within each system. This report proposes use of these definitions for studies of SCD complications, so future studies can be comparably robust and treatment efficacy measured. Use of these definitions will support greater accuracy in genotype-phenotype studies, thereby achieving a better understanding of SCD pathophysiology. This should nevertheless be viewed as a dynamic rather than final document; phenotype descriptions should be reevaluated and revised periodically to provide the most current standard definitions as etiologic factors are better understood, and new diagnostic options are developed.

Pain management in sickle cell disease: palliative care begins at birth?

People with sickle cell disease (SCD) are living longer, but their lives are impacted even more by the unpredictable intermittent or constant pain that is often poorly managed over a lifetime. To address this problem, an interdisciplinary team approach is needed that brings the medical professionals together for optimal compassionate care that is coordinated from the beginning of life and throughout the patient's lifespan.The hematologist, whenever possible, should take the lead. Effective models that have been developed to address SCD pain, such as the Day Hospital, The Recidivism Project and various Home Care models, need to be integrated into an overarching plan on a continuum with an underpinning philosophy that will sustain such a program. While the focus of palliative care has been end of life, its philosophies fit the chronic disease model and support an integrated team approach to the SCD pain management dilemma. The patient-focused and family-oriented interventions can be modeled to fit "any place, any time," outpatient, inpatient or the home, with homecare and other support systems. Such are the needs in SCD: appropriate, timely and compassionate care to prevent or relieve suffering and to preserve dignity, meaning, value and quality of life with improvement that is translational from birth until the end of life.

Secretory phospholipase A2 levels in patients with sickle cell disease and acute chest syndrome.

In a multicenter study (eight centers), we determined secretory phospholipase A(2) (sPLA(2)) levels in patients with sickle cell disease and acute chest syndrome (ACS). The diagnosis of ACS was made according to established criteria. The sPLA2 levels were determined in blood samples collected at baseline (time of diagnosis) and serially thereafter up to day 22-35 follow-up visits. Thirty-four of 43 (80%) patients with ACS had enzyme levels > or =1.00 AU at baseline. The enzyme levels decreased significantly on Days 2 through Days 25-35 after baseline. Nine of 43 (20%) patients had baseline sPLA2 values of <1.00 AU with six of them never exceeding 1.00 AU at any point in time during follow-up. The data indicate that the reliability of sPLA(2( for predicting the development of ACS is not perfect (100%) as was previously reported but occurs in about 80% of the patients.

Managing pain: The Challenge in Underserved Populations: Appropriate Use Versus Abuse and Diversion.

ISSUE: Inadequate pain management is a serious public health problem that affects a wide cross-section of Americans. Patients are often denied sufficient medication, because physicians lack training and fear scrutiny from federal and state regulatory agencies. In addition, even the state-financed system of care, Medicaid, has been increasingly denying payment for the best treatment for pain management. These factors are complicated by physician bias about various subgroups and poor physician-patient communication. Comprehensive patient assessment plays a crucial role in determining appropriate treatment and identifying potential abuse problems. Physicians must routinely document medications analgesic effects and screen for potential ill effects and drug abuse. OBJECTIVE: To examine the prevalence of the undertreatment of pain, particularly among African Americans, and to recommend relevant proactive policy and practice changes to aid in eliminating this health problem. CONSENSUS PROCESS: In July 2002, the NMA convened the "Managing Pain: The Challenge in Underserved Populations: Appropriate Use versus Abuse and Diversion" Consensus Meeting in Washington, DC. The country's most renowned experts in the area of pain management and substance abuse reviewed substantial information regarding pain management and substance abuse including the following: --A draft summary paper on pain management and substance abuse that served as briefing material for consensus members; --Annotated bibliographies; --Articles on pain management and substance abuse; and --Key presentations on pain management and substance abuse.

Safety of purified poloxamer 188 in sickle cell disease: phase I study of a non-ionic surfactant in the management of acute chest syndrome.

Acute chest syndrome (ACS) is the most common cause of death in patients with sickle cell anemia. Its management is primarily palliative. We performed a Phase I evaluation of purified poloxamer 188 (a non-ionic surfactant) in the management of ACS. Forty-three patients with sickle cell disease and ACS were treated with doses as high as 2960 mg/day by continuous intravenous (IV) infusion. The maximum tolerated dose has not been identified. No evidence of renal toxicity or other limiting adverse events were found. One adult patient died due to sepsis and adult respiratory distress syndrome, which were unrelated to treatment. Poloxamer 188 is safe to administer to patients with ACS, and preliminary data suggest that it may shorten its duration and the length of hospitalization in a dose related manner. Children appeared to benefit more than adults. The data and safety profile justify further studies with purified poloxamer 188 in the treatment of ACS.

Chlamydia pneumoniae and acute chest syndrome in patients with sickle cell disease.

UNLABELLED: PURPOSE Few studies address the association of Chlamydia pneumoniae infection with pulmonary disease and outcome in patients with underlying pathology such as sickle cell disease (SCD). SCD patients are susceptible to the pulmonary disorder known as acute chest syndrome (ACS), where the etiology remains ill defined. The purpose of this study was to analyze the clinical course and outcome of C. pneumoniae-associated ACS among SCD patients as part of the National Acute Chest Syndrome Study. PATIENTS AND METHODS: This was a longitudinal study of SCD patients presenting with ACS to multiple U.S. medical centers. Two hundred ninety-six SCD patients who developed ACS were tested by PCR for C. pneumoniae and by standard techniques for other respiratory pathogens. These infections were evaluated for association with ACS, clinical course, and complications. RESULTS: Forty-one (14%) patients with first episodes of ACS were PCR positive for C. pneumoniae. Compared with other infections, C. pneumoniae-infected patients were older, were more likely to present with chest pain, and had higher hemoglobin levels at diagnosis. Both groups had similar rates of respiratory failure and prolonged hospitalization. Of the 89 patients with single-pathogen infections, 27 (30%) were due to C. pneumoniae, 21% to Mycoplasma pneumoniae, 10% to RSV, 4% to Staphylococcus aureus, and 3% to Streptococcus pneumoniae. CONCLUSIONS: C. pneumoniae was the most prevalent pathogen in this study of ACS and was responsible for significant morbidity. Additional research is required to develop effective treatment guidelines for ACS.

Breathing patterns during vaso-occlusive crisis of sickle cell disease.

STUDY OBJECTIVES: To determine the effect of sickle cell pain and its treatment on patients' breathing patterns, and to compare the effect of thoracic cage pain to pain at other sites. DESIGN: Prospective, observational study. SETTING: Sickle Cell Center Day Hospital. PATIENTS: Twenty-five patients with sickle cell disease admitted to the Sickle Cell Center Day Hospital for treatment of vaso-occlusive crisis (VOC) [10 patients with chest (thoracic cage) pain]. INTERVENTIONS: Breathing patterns were measured by respiratory inductive plethysmography. Tidal breathing data, including respiratory rate, tidal volume (VT), minute ventilation, and the rib cage contribution to VT, were collected at baseline and then following treatment with opioid analgesia. MEASUREMENTS AND RESULTS: The patients with chest pain had smaller V(Ts) at baseline than those with pain at other sites (355 +/- 37 mL vs 508 +/- 141 mL, p = 0.003), and higher respiratory rates (23.2 +/- 8.2 breaths/min vs 17.6 breaths/min, p = 0.03). These differences became insignificant following opioid treatment. Six patients had respiratory alternans (four patients in the chest pain group, and two patients with pain at other sites). All cases of respiratory alternans resolved following opioid administration. CONCLUSIONS: Patients with VOC and chest pain have more shallow, rapid breathing than patients with pain elsewhere. Analgesia reduces these differences. As pain-associated shallow breathing and maldistribution of ventilation may contribute to the pathogenesis of acute chest syndrome, these results support the need for adequate pain relief and monitoring of ventilatory patterns during the treatment of VOC.