Major Haemorrhage during Vitamin K Antagonist Treatment: The Influence of Thyroid Hormone Levels.

BACKGROUND: Annually, approximately 1-3% of patients treated with vitamin K antagonists (VKA) suffer from major haemorrhage. Since high levels of free thyroxine (fT4) are associated with increased thrombosis risk, the aim was to assess whether low levels of fT4 contribute to major haemorrhage in patients under VKA treatment. METHODS: The FACTORS (Factors in Oral Anticoagulant Safety) study is a case-control study on patients receiving VKA treatment, including 110 cases with major haemorrhage. Controls were 220 matched participants treated with VKA without major haemorrhage. Odds ratios (OR) and 95% confidence intervals (95% CI) for the association of fT4 levels with major haemorrhage were calculated for different fT4 cutoffs by conditional logistic regression. RESULTS: In patients with an fT4 level below 13 pmol/l, the risk of major haemorrhage was 5-fold increased (OR = 5.1; 95% CI: 0.9-28.6) compared with patients with an fT4 level above 13 pmol/l. At a cutoff of 14 pmol/l, the risk was 3-fold increased (OR = 2.9; 95% CI: 1.0-8.5). High levels of fT4 did not affect bleeding risk. No clear effect of thyroid-stimulating hormone and thyroid peroxidase antibodies was seen on the risk of major haemorrhage. CONCLUSIONS: These results indicate that fT4 levels below 14 pmol/l play a role in the aetiology of major haemorrhage in VKA users.

Comparative study of blood collection tubes and thromboplastin reagents for correction of INR discrepancies: a proposal for maximum allowable magnesium contamination in sodium citrate anticoagulant solutions.

International normalized ratio (INR) discrepancies were noted between clinical laboratories using various prothrombin time (PT) systems. We studied the influence of different commercial blood collection tubes and different PT systems on INR measurements. INRs of fresh patient samples were determined by 3 laboratories, each using different PT systems. In the first part of the study, samples were drawn with Vacutainer tubes and in the second part with Monovette tubes. In the first part of the study, the maximum bias for all patients amounted to 0.46 INR (14%), and in the second part, to 0.14 INR (4.9%). The maximum bias for all patients could be reduced further by local system calibration using frozen pooled plasma specimens. The sodium citrate solutions in the blood collection tubes were contaminated with magnesium ions (approximately 2.7 mmol/L and 0.3 mmol/L in the Vacutainer and Monovette, respectively). INR discrepancies could be explained largely by this influence of blood collection tubes. The maximum allowable magnesium contamination in sodium citrate anticoagulant solutions should be less than 1 mmol/L.

Differential impact of impaired fasting glucose versus impaired glucose tolerance on cardiometabolic risk factors in multi-ethnic overweight/obese children.

We aimed to investigate the prevalence of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), and their associations with cardiometabolic risk factors, according to ethnicity in a large obese paediatric cohort. A 75-g oral glucose tolerance test was performed in 1,007 overweight/obese Dutch children of multi-ethnic origin, referred to the obesity outpatient clinics of two Dutch hospitals in Amsterdam (mean age, 11.4 ± 3.2 years; 50.7% boys). Anthropometric parameters and blood samples were collected, and cardiometabolic risk factors were assessed. The cohort consisted of Dutch native (26.0%), Turkish (23.7%), Moroccan (18.8%) and children of 'other' (31.5%) ethnicity. The prevalence of IFG was significantly higher in Moroccan and Turkish children as compared to Dutch native children (25.4% and 19.7% vs. 11.8%, respectively, P < 0.05). IGT was most frequently present in Turkish and Dutch native children, relative to Moroccan children (6.3% and 5.3% vs. 1.6%, P < 0.05). Besides pubertal status and ethnicity, components of 'metabolic syndrome' (MetS) which were associated with IGT, independent of hyperinsulinaemia, were hypertension [odds ratio (OR), 2.3; 95% CI, 1.1-4.9] while a trend was seen for high triglycerides (OR, 2.0; 95% CI, 0.9-4.3). When analyzing components of MetS which were associated with IFG, only low high-density lipoprotein cholesterol was significantly associated (OR, 1.7; 95% CI, 1.2-2.5) independent of hyperinsulinaemia. In conclusion, in a Dutch multi-ethnic cohort of overweight/obese children, a high prevalence of IFG was found against a low prevalence of IGT, which differed in their associations with cardiometabolic risk factors.

Prolactin and venous thrombosis: indications for a novel risk factor?

OBJECTIVE: Several acquired risk factors for venous thrombosis (VT) are associated with high prolactin levels. Our goal was to investigate VT risk for different levels of prolactin. METHODS AND RESULTS: We used data of a case-control study on leg vein thrombosis conducted between September 1999 and August 2006 at the Academic Medical Center, Amsterdam, the Netherlands. Prolactin was assessed in 187 cases (mean age, 57 years; range, 19 to 90) and 374 gender-matched controls (mean age, 57 years; range, 18 to 93). Odds ratios and 95% CI for VT risk were estimated based on several cutoff levels derived from prolactin levels in controls. Odds ratios for VT risk clearly increased with higher prolactin levels. For prolactin levels above the 75th percentile (8 µg/L), we found an odds ratio of 1.7 (95% CI 1.0 to 2.7) as compared with levels below the 50th percentile (6 µg/L). This further increased up to an odds ratio of 4.7 (95% CI 1.8 to 11.8) for prolactin levels above the 97.5th percentile (16 µg/L). The risk was most pronounced in premenopausal women. CONCLUSIONS: Our data suggest that prolactin levels are associated with VT in a dose-dependent fashion. Future studies are needed to evaluate the causality of this relationship.

Urinary markers of bone resorption, pyridinoline and deoxypyridinoline, are increased in sickle cell patients with further increments during painful crisis.

The painful crisis is the hallmark of sickle-cell disease (SCD). Bone resorption, as part of physiological bone turnover, results in release into the circulation with subsequent urinary excretion of the collagen cross-links pyridinoline (PYD) and deoxypyridinoline (DPD). Urinary PYD and DPD concentrations could reflect the extent of bone infarction during painful sickle-cell crisis. Urinary concentrations of PYD and DPD, adjusted for urine creatinine, were measured in sickle-cell patients (38 clinically asymptomatics and 27 during painful crisis) and healthy controls (n 5 25) using high-performance liquid chromatography(HPLC). PYD and DPD concentrations were higher in asymptomatic HbSS/HbSb0-thalassemia patients compared to controls (P <0.05) with further increments during painful crisis in both HbSS/HbSb0-thalassemia and HbSC/HbSb1-thalassemia patients (P < 0.05). In the asymptomatic HbSS/HbSb0-thalassemia patients, there was a statistically significant positive correlation between DPD and hemolytic rate.Based on urinary PYD and DPD concentrations, bone degradation is increased in asymptomatic sickle-cell patients, with further increments during painful crisis. Urinary PYD and DPD concentrations are potentially diagnostic and prognostic tools in SCD.

Increasing levels of free thyroxine as a risk factor for a first venous thrombosis: a case-control study.

A hypercoagulable state exists in hyperthyroidism, but the association with venous thrombosis (VT) is not fully explored. We aimed to investigate VT risk for different plasma levels of thyroid hormones and thyroid antibodies. We used a case-control study on leg vein thrombosis conducted between September 1999 and August 2006 at the Academic Medical Center, Amsterdam, The Netherlands. Parameters of thyroid function were assessed in 190 cases (mean age, 57 years; range, 19-90 years) and 379 sex-matched controls (mean age, 56 years; range, 18-93 years). Odds ratios (ORs) and 95% confidence intervals (CIs) for VT risk were estimated according to several cutoff levels derived from plasma levels observed in controls. We found the risk of VT to gradually rise with increasing levels of free thyroxine (FT(4)). In the absence of traditional acquired risk factors, FT(4) levels above 17 pmol/L yielded a sex- and age-adjusted OR of 2.2 (95% CI, 1.2-4.2) for deep VT, which further increased up to an OR of 13.0 (95% CI, 1.1-154.1) for FT(4) levels above reference range. Our data suggest increasing levels of FT(4) to be a risk factor for VT and may have implications for both the prevention and management of this disease.

Anti-inflammatory and anticoagulant effects of pravastatin in patients with type 2 diabetes.

OBJECTIVE: Type 2 diabetes is associated with increased plasma concentrations of coagulation and inflammation markers. Different studies have shown that treatment with hydroxymethylglutaryl-CoA reductase inhibitors (statins) is associated with antithrombotic and anti-inflammatory effects in addition to a cholesterol-lowering effect. Our objective was to evaluate the effect of pravastatin (40 mg/day) on coagulation and inflammation markers in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: This was an open, randomized, crossover study designed with an 8-week intervention period. The study group was comprised of 50 patients with type 2 diabetes (median HbA(1c) 7.1%) and serum total cholesterol of 5-10 mmol/l. We evaluated plasma levels of fibrinogen, F1 + 2, D-dimer, soluble tissue factor (sTF), von Willebrand Factor antigen (vWFag), and C-reactive protein (CRP) in blood samples drawn after fasting on day 1 and after 8 and 16 weeks. RESULTS: Significant reductions of total cholesterol (-22%; P < 0.001), LDL cholesterol (-32%; P < 0.001), and triglycerides (-10%; P < 0.05) were achieved after 8 weeks of treatment with pravastatin. In addition, significant reductions of plasma levels of F1 + 2 (-4.4%; P < 0.05), vWFag (-5.3%; P < 0.05), and sTF (-3.4%; P < 0.05) were observed after treatment with pravastatin. Furthermore, plasma levels of CRP were also significantly reduced (-13%; P < 0.05). Levels of fibrinogen and D-dimer did not decrease after treatment with pravastatin. CONCLUSIONS: The results indicated that pravastatin reduces levels of coagulation and inflammation markers in type 2 diabetic patients. These antithrombotic and anti-inflammatory effects of treatment with statins could play a role in reducing cardiovascular complications in type 2 diabetic patients.