Sticky Platelet Syndrome: An Underrecognized Cause of Graft Dysfunction and Thromboembolic Complications in Renal Transplant Recipients

Sticky platelet syndrome (SPS) leads to hyperaggregabilty of platelets in response to physiologic stimuli. In this report we describe three patients with clinical symptoms of SPS after renal transplantation. The first patient developed an infarction of her transplant kidney with additional, subsequent renal microinfarctions. The second patient suffered multiple strokes and deep vein thrombosis with episodes of pulmonary embolism and ischemic bowel disease due to colonic microinfarctions. The third patient experienced a long episode of unexplained respiratory and graft dysfunction immediately after transplantation until therapy for SPS was initiated, at which point symptoms resolved quickly. Kidney transplant recipients with SPS may be at increased risk of developing thrombosis, given that most immunosuppressive drugs are known to induce either endothelial cell damage or augment platelet aggregation. All patients awaiting renal transplantation should be screened for a history of thrombosis and, if appropriate, tested for SPS. Affected patients should receive dose-adjusted acetylsalicylic acid.     

Developing Organ Offer and Acceptance Measures: When 'Good' Organs Are Turned Down

Turndowns of offers of deceased donor kidneys for transplantation can contribute to inefficiencies in the organ distribution system and inequality in access to donated organs. Match run data were obtained for 4967 'good' kidneys placed and transplanted in 2005 after fewer than 50 offers. These kidneys were not recovered from donation after cardiac death or expanded criteria donors, or from donors with a history of substance abuse. On average, these good kidneys were not accepted until after seven offers to candidates and after offers to 2.4 programs. Models for the likelihood of acceptance found several donor and candidate characteristics to be significantly related to acceptance rates (p < 0.05). After accounting for these variables, there remained 2- to 3-fold differences among transplant programs in acceptance rates. These models could be used to identify kidney transplant centers with exceptional acceptance practices. Several strategies might be employed to increase acceptance rates for good organs.     

Genetic association studies of interleukin-13 receptor alpha1 subunit gene polymorphisms in asthma and atopy.

Interleukin (IL)-13 plays a central role in asthma pathogenesis by binding to the IL-13 receptor, which is a heterodimer composed of the IL-13 receptor alpha1 subunit (IL-13Ralpha1) and IL-4Ralpha. The genetic diversity at the IL-13Ralpha1 gene (IL13RA1) locus on chromosome Xq24 was characterised and the association of identified polymorphisms with asthma and atopy phenotypes examined. The promoter and coding region of IL13RA1 were screened for common genetic variants, and polymorphisms found were genotyped in a large cohort of 341 asthmatic Caucasian families (each containing at least two asthmatic siblings) and 182 nonasthmatic control subjects. Genetic association was determined using case-control and transmission disequilibrium test analyses. Two common polymorphisms were identified, a newly found thymidine (T) to guanine (G) transition of nucleotide -281 (-281T>G) single nucleotide polymorphism in the IL13RA1 promoter and the previously described 1365A>G variant in the IL13RA1 proximal 3' untranslated region. No significant association of either -281T>G or 1365A>G with risk of asthma or atopy phenotypes was found, apart from a suggestive association between the IL13RA1 -281T/1365A haplotype and raised total serum immunoglobulin E levels in adult female asthmatics. These findings indicate that the interleukin-13 receptor alpha1 subunit gene -281T>G and 1365A>G polymorphisms do not contribute to asthma susceptibility or severity, although the interleukin-13 receptor alpha1 subunit gene locus might be involved in the control of immunoglobulin E production.     

Pulmonary hypertension in patients with pulmonary fibrosis awaiting lung transplant.

Pulmonary hypertension (PH) may complicate idiopathic pulmonary fibrosis (IPF) but the prevalence of PH in IPF remains undefined. The present authors sought to describe the prevalence of PH in IPF. The lung transplant registry for the USA (January 1995 to June 2004) was analysed and IPF patients who had undergone right heart catheterisation (RHC) were identified. PH was defined as a mean pulmonary arterial pressure ((Ppa)) > or =25 mmHg and severe PH as a (Ppa) >40 mmHg. Independent factors associated with PH were determined. Of the 3,457 persons listed, 2,525 (73.0%) had undergone RHC. PH affected 46.1% of subjects; approximately 9% had severe PH. Variables independently associated with mild-to-moderate PH were as follows: need for oxygen, pulmonary capillary wedge pressure (P(pcw)) and forced expiratory volume in one second (FEV(1)). Independent factors related to severe PH included the following: carbon dioxide tension, age, FEV(1), P(pcw), need for oxygen and ethnicity. A sensitivity analysis in subjects with P(pcw) <15 mmHg did not appreciably alter the present findings. Pulmonary hypertension is common in idiopathic pulmonary fibrosis patients awaiting lung transplant, but the elevations in mean pulmonary arterial pressure are moderate. Lung volumes alone do not explain the pulmonary hypertension. Given the prevalence of pulmonary hypertension and its relationship with surrogate markers for quality of life (e.g. activities of daily living), future trials of therapies for this may be warranted.     

Definition, epidemiology and natural history of COPD.

Chronic obstructive pulmonary disease (COPD) is the fifth cause of morbidity and mortality in the developed world and represents a substantial economic and social burden. Patients experience a progressive deterioration up to end-stage COPD, characterised by very severe airflow limitation, severely limited and declining performance status with chronic respiratory failure, advanced age, multiple comorbidities and severe systemic manifestations/complications. COPD is frequently underdiagnosed and under-treated. Today, COPD develops earlier in life and is less gender specific. Tobacco smoking is the major risk factor for COPD, followed by occupation and air pollution. Severe deficiency for alpha(1)-antitrypsin is rare; several phenotypes are being associated with elevated risk for COPD in the presence of risk factor exposure. Any patient presenting with cough, sputum production or dyspnoea should be assessed by standardised spirometry. Continued exposure to noxious agents promotes a more rapid decline in lung function and increases the risk for repeated exacerbations, eventually leading to end-stage disease. Without major efforts in prevention, there will be an increasing proportion of end-stage patients who can live longer through long-term oxygen therapy and assisted ventilation, but with elevated suffering and huge costs. Smoking prevention and smoking cessation are the most important epidemiological measurements to counteract chronic obstructive pulmonary disease epidemics.