Pulmonary thrombotic arteriopathy in patients with sickle cell disease.

BACKGROUND: Shortened life expectancy due to pulmonary hypertension (PH) is seen in 5% to 10% of patients with sickle cell disease. The principal factors suspected of causing PH are pulmonary thromboemboli (PE) and in situ arterial thrombosis. OBJECTIVE: To investigate the possible role that PE or in situ arterial thrombosis play in the development of PH in sickle cell disease. METHODS: Autopsies of 12 patients with sickle cell disease were correlated with clinical data from medical records. RESULTS: Right ventricular hypertrophy was present in 9 of 12 patients. Six patients with right ventricular hypertrophy had thrombi in large elastic pulmonary arteries. All patients with elastic artery thrombi had fresh or organized thrombi in small muscular pulmonary arteries. Hypertensive small arterial changes were present in 5 of these 6 patients. Six patients showed no thrombi in elastic arteries. Among these 6 patients, 3 had right ventricular hypertrophy and recent and organized thrombi, as well as hypertensive changes in small arteries. One of these 3 patients demonstrated plexiform-like lesions and fibrinoid necrosis of small arteries. Three patients without right ventricular hypertrophy had pneumonia or pulmonary edema with no identifiable pulmonary artery pathology. CONCLUSIONS: Arterial thrombosis with PH and cor pulmonale was regarded as the cause of death among most of these patients. Elastic artery thrombi are pulmonary thromboemboli, but pulmonary thromboemboli are always associated with widespread thrombosis of small arteries. Widespread thrombosis of small arteries alone was associated with PH in some cases. This finding suggests that pulmonary thromboemboli may be a late complication of PH and cor pulmonale and that an in situ thrombotic arteriopathy underlies the development of PH in most patients with sickle cell disease.     

Severe anemia: a risk factor for glomerular injury in sickle cell disease.

Approximately 15% to 20% of patients with sickle cell disease have proteinuria. Proteinuria, particularly albuminuria, is the hallmark of glomerular injury. This study examines risk factors for glomerular injury as indicated by urinary albumin excretion (UAE) 30 microgram/minute, directly related to sickle cell disease. A total of seven patients were enrolled between September 1992 and March 1993. Fasting blood chemistries, complete blood cell count, 24-hour urine for protein and creatinine clearance, and glomerular filtration rate determined by 125 I-iothalamate were obtained for each patient. The results indicated that the lower the hematocrit, the higher the UAE rate. Low hematocrits have served as a protective mechanism in sickle cell disease by reducing blood viscosity and thus decreasing the number of vaso-occlusive crises. However, severe anemia appears to have an indirect adverse effect on the kidney in sickle cell disease.     

Clinical assessment of the risk for sudden cardiac death in patients with sickle cell anemia

BACKGROUND: Previous studies suggest that patients with sickle cell anemia (SCA) have an increased risk of sudden cardiac death; however, its etiology and mechanism are not well defined. Left ventricular hypertrophy (LVH), ventricular tachycardia (VT) and poor left ventricular systolic function are known risk factors for sudden cardiac death. An abnormal microvolt T-wave alternans (TWA) test is also a predictor of sudden cardiac death risk, but it has not been applied to this patient population. METHODS: We performed a 12-lead electrocardiogram, 24-hour Holter monitor, two-dimensional echocardiogram, nuclear stress test and microvolt TWA test to determine whether markers of sudden cardiac death could be identified. RESULTS: Twenty-six patients were evaluated with a mean age of 40 +/- 12 years. The two-dimensional echocardiogram revealed a normal ejection fraction in 23 patients and LVH in 17 (65%), whereas hypertension was noted in only five (19%). Microvolt TWA testing was abnormal in six of 22 patients (27%). Holter monitor revealed VT in two patients. Among the clinical variables tested, only LVH was predictive of an abnormal TWA test. The sensitivity, specificity, positive and negative predictive value of LVH for and abnormal TWA test was 100, 56, 46 and 100%. CONCLUSION: LVH was common in patients with SCA and disproportional to the number of patients with hypertension. Microvolt TWA tests were abnormal in 27% of patients; however, LVH was the only clinical variable that predicted an abnormal TWA test. Risk stratification of SCA patients may require echocardiographic detection of LVH and an abnormal TWA test due to the high negative predictive value. The significance of an abnormal TWA test should be further evaluated in a large study, with a longer follow-up period.     

Pulmonary hypertension in sickle cell hemoglobinopathy: a clinicopathologic study of 20 cases

Pulmonary hypertension is one of the major causes of morbidity and mortality of patients with sickle cell hemoglobinopathy (SCH). Although a clinically recognized complication of sickle cell disease (SCD), there are few published pathologic studies of pulmonary findings in these patients. The aim of this study was to define the pulmonary pathologic changes and to investigate correlation between the pathologic changes, the antemortem diagnosis of pulmonary hypertension, and the severity of SCH. Cases of SCH were identified from the autopsy database using Snomed codes. Clinical and echocardiograph data were collected for correlation with the pathologic data. A total of 20 adult patients (12 males and 8 females) were identified. Hemoglobin electrophoresis results were available for 16 patients, with hemoglobin S fraction percentages ranging from 23% to 97.8%. Eleven patients had SCD, 5 patients had sickle cell trait (SCT), and the remaining 4 patients without hemoglobin electrophoresis were included in the SCT group. The mean age of the SCT group was higher than that of the SCD group (P = 0.03). Histologically, all 20 patients demonstrated changes in pulmonary vasculature considered diagnostic of pulmonary hypertension grade I to grade IV, associated with plexiform lesions in 60% of patients. Medial hypertrophy and intimal hyperplasia/fibrosis, considered potentially reversible lesions, were seen in all patients. A weak association was found between SCD and plexiform lesions. Fibroelastic degeneration of small arteries, arterioles, and venules was identified in almost all (95%) cases. Clinically, tricuspid regurgitation was detected by echocardiogram in 10 of 20 (50%) patients; 6 of these 10 had significant regurgitation to allow estimation of systolic pressure. Sudden death occurred in 8 patients, with males having a significantly higher incidence. Cardiomegaly was present in 95% of patients, however, autosplenectomy and hepatic cirrhosis/hemochromatosis were observed almost exclusively in patients with SCD. Cirrhosis was found to have a strong positive association with SCD. This study demonstrates pulmonary hypertensive changes in all 20 autopsied patients who had SCH but died from various causes. We conclude that a high prevalence of pulmonary hypertension is associated with SCH with consequent high mortality. Therefore, patients with SCH would benefit from a regular periodic assessment for pulmonary hypertension regardless of age, sex, and severity of hemoglobinopathy.     

Obstructive sleep apnoea as a risk factor for hypertension

SUMMARY  It is controversial whether obstructive sleep apnoea (OSA) is a risk factor for hypertension as previous reviews of the subject have emphasized the confounding effect of obesity. We examined evidence from recent studies to reassess this debate. Cross-sectional studies from sleep clinic population (Sydney Sleep Cohort, Gothenburg Sleep Clinic Cohort), community sample (Busselton Sleep Survey, Wisconsin Sleep Cohort) and obese population (Swedish Obese Subjects Study) provide stronger evidence that the relationship between sleep apnoea and hypertension is an independent one. Moreover recent studies looking at the effect of sleep apnoea treatment have demonstrated a fall in blood pressure independent of weight change. More definitive studies are required but recent data provide increasing evidence that OSA is an independent risk factor for hypertension.     

Preeclampsia as a female-specific risk factor for chronic hypertension

Preeclampsia is a complication of pregnancy that has also long term effects on maternal health. Several epidemiologic studies have shown an increased risk for cardiovascular morbidity (relative risk [RR] 2.3) and mortality (RR 2.3) in women after a history of preeclampsia. The chance to develop chronic hypertension afterwards is twofold to 10 times higher in affected women, compared with women after normotensive pregnancies. As hypertension is a major cardiovascular risk factor, early detection and treatment is mandatory to reduce the risk of future cardiovascular disease. Data on (cost)-effectiveness of cardiovascular screening programs in women after preeclampsia are currently lacking and there are no recommendations yet for prevention in the guidelines. We recommend regularly preventive blood pressure measurements after high risk pregnancies. More research is needed to identify women who will profit most of early intervention.     

Dysphagia as a risk factor for sudden unexplained death in infancy

The TRIAD of encephalopathy, subdural haemorrhages, and retinal haemorrhages is commonly considered diagnostic of Shaken Baby Syndrome, but the original paper describes a statistically linked QUADRAD of features, the fourth of which is a previous history of feeding difficulties (dysphagia). Recent reviews of giving pacifiers (dummies) to infants during sleeping periods have found a significant reduction in the incidence of Sudden Infant Death Syndrome. Stimulation of swallowing is a possible connection with dysphagia, which is examined here, illustrated by a well documented case. Although amniotic fluid passes freely through the larynx of fetal mammals during fetal breathing, application of pure water to the laryngeal epithelium in infants causes choking and laryngeal closure. "Water sensors" in the surface respond to lack of chloride ions and adapt very slowly or not at all. Others have found in puppies that following application of pure water only 32% resume breathing in less than 30-40s. The rest needed at least one saline flush, and some required artificial ventilation in addition. These receptors also respond to high potassium concentrations and acid or alkaline solutions. Normally, airway closure during swallowing or vomiting prevents entry of feed or oesophageal reflux, but in some forms of dysphagia leakage can occur, causing paroxysmal coughing, reflex laryngeal closure, and so prolonged apnoea. Recently, it has been realised that the TRIAD injuries can also result from high intracranial vascular pressures transmitted from intra-thoracic pressure surges during paroxysmal coughing, choking, etc. Triggering of such pressure surges by dysphagic accidents provides a physiological link to injuries commonly considered diagnostic of Shaken Baby Syndrome, completing the statistically identified QUADRAD of features. Further dysphagic research might reveal predictive factors, and preventative measures such as feeds of optimal pH.     

Is pain crisis a cause of death in sickle cell disease?

It has been a matter of controversy as to whether patients with sickle cell disease die of crisis or merely in crisis. The authors reviewed the 74 patients with sickle cell disease autopsied at The Johns Hopkins Hospital. From clinical review, there were 20 (27%) who died with pain crisis, 51 (69%) who died without pain crisis, and 3 (4%) for whom documentation was insufficient. On pathology review, death was attributable to infection in 19 (26%), uremia in 9 (12%), sequestration crisis in 9 (12%), necrotic bone marrow emboli in 7 (9%), and miscellaneous causes in 14 (19%); in 16 (22%) patients no cause of death could be identified. Death was explained in 47/51 (92%) patients without pain crisis; but only in 11/20 (55%, P less than 0.01) patients dying in pain crisis. The disproportionately large number of patients dying in pain crisis with an unexplained cause of death suggests that pain crisis may account for the death of some patients with sickle cell disease.     

Radiation as a risk factor for cardiovascular disease

Abstract population are ubiquitous background radiation and medical exposure of patients. From the early 1980s to 2006, the average dose per individual in the United States for all sources of radiation increased by a factor of 1.7-6.2?mSv, with this increase due to the growth of medical imaging procedures. Radiation can place individuals at an increased risk of developing cardiovascular disease. Excess risk of cardiovascular disease occurs a long time after exposure to lower doses of radiation as demonstrated in Japanese atomic bomb survivors. This review examines sources of radiation (atomic bombs, radiation accidents, radiological terrorism, cancer treatment, space exploration, radiosurgery for cardiac arrhythmia, and computed tomography) and the risk for developing cardiovascular disease. The evidence presented suggests an association between cardiovascular disease and exposure to low-to-moderate levels of radiation, as well as the well-known association at high doses. Studies are needed to define the extent that diagnostic and therapeutic radiation results in increased risk factors for cardiovascular disease, to understand the mechanisms involved, and to develop strategies to mitigate or treat radiation-induced cardiovascular disease.     

Electrocardiogram analysis in adult patients with sickle cell disease

This study is an analysis of the electrocardiograms (ECGs) of 87 adult patients taken during hospital admission for sickle cell disease (homozygous S). The age range was 18 to 55 years: 38 were men and 49 were women. Seventy-two percent of all patients had abnormal ECGs. Nonspecific ST-T (NS-ST-T) wave abnormalities (53 percent) and QT interval prolongation (12 percent) were frequent. Seventy-five percent of the normal ECGs occurred in women (P < .05); and 74 percent of those with left ventricular hypertrophy (LVH) were men (P < .05). Fifteen of 21 (71 percent) patients with arrhythmias had NS-ST-T abnormalities. Systemic hypertension and ECG evidence for right-sided heart disease were rare, as was the incidence of LVH by ECG.     

Chronic granulomatous disease as a risk factor for autoimmune disease

Chronic granulomatous disease (CGD) is characterized by recurrent infections and granuloma formation. In addition, we have observed a number of diverse autoimmune conditions in our CGD population, suggesting that patients with CGD are at an elevated risk for development of autoimmune disorders. In this report, we describe antiphospholipid syndrome, recurrent pericardial effusion, juvenile idiopathic arthritis, IgA nephropathy, cutaneous lupus erythematosus, and autoimmune pulmonary disease in the setting of CGD. The presence and type of autoimmune disease have important treatment implications for patients with CGD.