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We have described an abnormal fibrinogen in 6 patients with liver disease who had prolonged plasma thrombin times due to impaired fibrin monomer aggregation. To investigate the role of sialic acid in this functional abnormality, fibrinogen was purified from normal and patient plasmas by the glycine precipitation method. Sialic acid content of the fibrinogens was measured by the thriobarbituric acid assay after acid hydrolysis. Normal fibrinogen had 6.1 ± 0.5 residues per molecule of fibrinogen, whereas patient fibrinogen sialic acid content ranged between 7.5 and 10 residues per molecule. The reduced fibrinogen demonstrated normal mobility of Aα, B3 and γ chains on SDS Polyacrylamide gel electrophoresis when stained for protein and, similar to normal fibrinogen, only the Bβ and γ chains stained with PAS. The degree of prolongation of the thrombin times of the purified patient fibrinogens appeared to correlate with the increase in the fibrinogen sialic acid. The effect on fibrin monomer aggregation of decreasing patient fibrinogen sialic acid content was studied. Partially desialated patient fibrinogen was prepared by treating the protein with Vibrio cholerae neuraminidase for varying periods of time. Partial removal of sialic acid from patient fibrinogen resulted in normalization of the thrombin time and improvement in fibrin monomer aggregation. Thrombin times ranged from 31.5 to 49.5 seconds prior to removal of excess sialic acid compared to 20.5 to 25.5 seconds post removal. These findings indicate that the dysfibrinogenemia associated with liver disease is biochemically characterized by increased sialic acid content and removal of this sialic acid results in a functional normalization of the protein.

This review seeks to highlight the pathophysiologic phenomena implicated in vascular and valvular calcification and summarize the literature available regarding the use of bisphosphonates in animal and human models. We also discuss novel treatment approaches for vascular calcification, with emphasis on chronic kidney disease and calciphylaxis.

Previous work from our laboratory had demonstrated attenuation of systemic vasoreactivity to pressor agents in rats after acute or chronic exposure to hypoxia. Therefore we hypothesized that hemorrhage of acutely hypoxic (12% O2) or chronically hypoxic (barometric pressure 380 mmHg for 3 wk) rats would deter the normal increase in total peripheral resistance (TPR) and thus decrease the ability to maintain blood pressure. Progressive hemorrhage (2% of blood volume per min) was performed under conditions of either normoxia or acute hypoxia in conscious rats. In control animals, the increase in TPR observed during normoxic hemorrhage was absent when hemorrhage was performed in acute hypoxia. Furthermore, the amount of blood removal required to achieve hypotension was reduced under conditions of acute hypoxia. In contrast, chronically hypoxic rats exhibited no difference in the threshold for hypotension between conditions of acute normoxia and hypoxia and demonstrated an increased hypotensive threshold under both normoxic and hypoxic conditions compared with control animals. We next hypothesized that the prolonged threshold for hypotension observed in chronically hypoxic rats might be due to hypoxia-induced right ventricular hypertrophy. Such ventricular hypertrophy may minimize stimulation of ventricular volume receptors thought to elicit the reflex fall in heart rate and TPR occurring in extreme underfill conditions. Therefore we compared the cardiovascular responses to hemorrhage in rats with right ventricular hypertrophy resulting from administration of monocrotaline with those from rats treated with vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)

Purpose Aberrant thyroid function causes dysregulated metabolic homeostasis. Literature has demonstrated hypercoagulability in hypothyroidism, suggesting a risk for thromboembolic events (TEE). We hypothesize that individuals with hypothyroidism will experience more clinically-diagnosed TEE than euthyroid individuals. Methods De-identified patient data from the University of New Mexico Health Sciences Center were retrieved using thyrotropin (TSH; thyroid-stimulating hormone) for case-finding from 2005 to 2007 and ICD billing codes to identify TEE during the follow-up period of 10 to 12 years. Diagnoses affecting coagulation were excluded and 12 109 unique enrollees were categorized according to TSH concentration as Hyperthyroid (n = 510), Euthyroid (n = 9867), Subclinical Hypothyroid (n = 1405), or Overtly Hypothyroid (n = 327). Analysis with multiple logistic regression provided the odds of TEE while adjusting for covariates. Results There were 228 TEEs in the cohort over 5.1 ± 4.3 years of follow-up. Risk of TEE varied significantly across study groups while adjusting for sex, race/ethnicity, levothyroxine, oral contraceptive therapy, and visit status (outpatient vs non-outpatient), and this risk was modified by age. Overt Hypothyroidism conferred a significantly higher risk of TEE than Euthyroidism below age 35, and Hyperthyroidism conferred an increased risk for TEE at age 20. Analysis also demonstrated a higher age-controlled risk for a subsequent TEE in men compared with women (odds ratio [OR] = 1.36; 95% confidence interval [CI], 1.02–1.81). Subanalysis of smoking status (n = 5068, 86 TEE) demonstrated that smokers have 2.21-fold higher odds of TEE relative to nonsmokers (95% CI, 1.41–3.45). Conclusions In this retrospective cohort study, Overt Hypothyroidism conferred increased risk of TEE over the next decade for individuals younger than 35 years of age, as compared with Euthyroidism.