Management of thrombocytopenic bleeding: is there a role for recombinant coagulation factor VIIa?

The ability of high concentrations of recombinant factor VIIa (rFVIIa) to improve thrombin generation in in vitro and ex vivo models of thrombocytopenia, and to improve bleeding time in thrombocytopenic animal models supports a potential role for rFVIIa in the management of thrombocytopenic bleeding. Anecdotal reports suggest that rFVIIa is effective in the prevention and treatment of bleeding episodes in surgical procedures in a limited number of patients with severe thrombocytopenia. There is a need for clinical trials to determine whether rFVIIa is efficacious and safe in severe thrombocytopenic bleeding, either by itself or in combination with other hemostatic agents such as platelet transfusion. Pending the availability of such data, rFVIIa may be considered in severe thrombocytopenic bleeding that is unresponsive to human leukocyte antigen-compatible platelet transfusions and other standard treatments. If rFVIIa is used, unresolved issues include optional dosage, dosing interval, and whether rFVIIa is best used alone or in conjunction with platelet transfusion.     

Recombinant factor VIIa: use in fatal post partum hemorrhage — Indian experience case series and review of literature

Postpartum hemorrhage is leading cause of maternal mortality and still remains a challenging condition to treat and hysterectomy may be required to control the bleeding once medical interventions fail. These strategies are not always successful and a direct approach in activating the coagulation system can be more effective and life saving. We describe here the mechanism of action of rFVIIa, review of literature and its use in 10 cases with different causes for PPH with good response.     

Vitamin D: a cardioprotective agent?

Vitamin D is a fat-soluble vitamin that is naturally found in very few foods, is added to others, and is available as a dietary supplement. It is produced endogenously when ultraviolet light strikes the skin. Recent epidemiologic and experimental evidence has suggested that low vitamin D levels may play a role in various cardiovascular conditions, including coronary artery disease, congestive heart failure, valvular calcification, stroke, hypertension, and cognitive decline. Low vitamin D may lead to vascular smooth muscle cell proliferation, endothelial cell dysfunction, vascular and myocardial cell calcification, and increased inflammation. However, the data supporting a cardioprotective effect of vitamin D supplementation are very weak, and the large, controlled clinical trials now in progress should resolve this issue.     

Subclinical hypothyroidism: a cardiovascular risk factor?

Although patent hypothyroidism is clearly associated with increased cardiovascular risk, the relationship between infraclinical hypothyroidism and cardiovascular disease remains controversial though probable. This relationship is mediated by the traditional risk factors (lipids, hypertension), by changes in parameters of inflammation and haemostasis, and by a direct effect of thyroid hormones on the vessel wall. The authors review the epidemiological evidence and the mechanisms underlying the association between infraclinical hypothyroidism and cardiovascular risk and the therapeutic implications of this association.     

Bone marrow lesions: a universal bone response to injury?

The ever increasing use of magnetic resonance imaging in clinical practice has led to the recognition of a new entity, bone marrow lesions (BMLs). These lesions are characterized by excessive water signals in the marrow space and have emerged as a central component of many different diseases affecting the musculoskeletal system. BMLs have in particular been associated with a wide variety of inflammatory and non-inflammatory rheumatologic conditions and are not only considered significant sources of pain, but also linked to the worsening of patient prognosis in many disease states. In this review, we summarize the current knowledge on BMLs with an emphasis on the clinical and histological features of this entity in inflammatory and non-inflammatory disease and provide a unifying hypothesis based on the appearance with various imaging technologies. We also try to pair this hypothesis with the apparent beneficial effects of various treatment regimens, mainly within the group of bone antiresorptive drugs (calcitonin, bisphosphonates) on symptoms associated with BMLs.     

Protein Z: a new factor of thrombophilia?

INTRODUCTION: Sometimes, in front of a clinical setting of thrombophilia, the biological findings are helpless. Therefore we suggest to test a protein Z deficiency. EXEGESIS: Protein Z is a vitamin-K dependent protein forming a complex with the Z protein-dependent protease inhibitor for inhibiting the activated factor X; so protein Z acts as a "natural low molecular weight heparin". The prothrombotic phenotype associated with protein Z deficiency includes early fetal losses (before the 20th week of gestation), early and relapsing venous thrombosis in patients with factor V Leiden mutation and somehow ischaemic stroke in young people. CONCLUSION: The protein Z deficiency seems to be associated with a particular prothrombotic phenotype including early fetal losses as well as early and relapsing venous thromboses in patients carrying the factor V Leiden mutation. It is unclear whether or not it plays a role as a thrombophilic factor especially in the arterial vascular field.     

Helicobacter pylori: a new cardiovascular risk factor?

There is increasing evidence that certain microbial agents may have an etiopathogenic role in the development of atherothrombosis. Helicobacter pylori, a bacterium that causes peptic ulcer disease, has been suggested as one of the microbes involved in the development of atherothrombosis. This hypothesis is based on the following observations: a) a higher prevalence of Helicobacter pylori infection in patients with coronary artery disease, myocardial infarction, or cerebrovascular disease; b) the coincidence of Helicobacter pylori infection and cardiovascular risk factors, such as serum cholesterol and triglyceride concentrations and plasma fibrinogen; c) Helicobacter pylori seropositivity correlates with acute-phase proteins associated with higher risk of coronary disease, such as C-reactive protein, and d) controversial PCR studies indicating the presence of Helicobacter pylori in atheromas. Analysis of the scientific evidence suggests that Helicobacter pylori infection could indirectly contribute to the development and severity of atherothrombosis and cardiovascular disease.     

Acylation stimulating protein: a female lipogenic factor?

Acylation stimulating protein (ASP) is a potent lipogenic factor produced from adipocytes. Plasma ASP levels were shown to increase in obesity, diabetes mellitus type II and dyslipidemia, and decrease after weight loss and fasting. Growing evidence suggests that ASP may significantly contribute to subcutaneous fat storage in females. In vitro, ASP stimulated triglyceride synthesis to a larger extent in subcutaneous compared with omental adipocytes. The ASP receptor binding affinity to plasma membranes prepared from adipose tissue showed higher binding affinity to plasma membranes from female adipose tissue compared with male adipose tissue, and was more pronounced to subcutaneous compared with omental plasma membranes. Human studies demonstrated that postprandial triglyceride clearance predicted by ASP levels was more efficient in women than in men. In mice, postprandial triglyceride clearance, with intraperitoneal ASP administration, was faster in females compared with males. The ASP deficient mice were resistant to weight gain and had reduced fat mass that was more pronounced in females. Recent findings in humans and mice point to a significant association between progesterone and ASP variations in females. In this review, we highlight findings, to date, linking ASP to physiological and hormonal alterations that may contribute to subcutaneous fat distribution typical to females.     

Arterial stiffness: a modifiable cardiovascular risk factor?

The subject of arterial stiffness as a modifiable risk factor is controversial and difficult to understand. The best approach here will be to assist readers to understand the issue and the basis of controversy. We also hope to show that the subject is not as overwhelming as it might appear. We believe that new blood is required in this field and that a basic understanding is necessary for researchers to be induced to take on such investigations. Our approach sets out a historic and pathophysiologic background on which modern studies can be based; describes measures and indices of arterial stiffness including pulse wave velocity, augmentation index, ambulatory arterial stiffness index, aortic impedance, and carotid elastic modulus; and finally, addresses the specifics of this interesting and important question. Although aortic stiffening with age is attributable to fracture of elastin lamellae and is largely irreversible, stiffening of muscular arteries can be modified by vasodilator drugs, and by improved endothelial function such as induced by exercise training.     

Thromboelastography and recombinant factor VIIa—hemophilia and beyond

Thromboelastography (TEG), which records the continuous profiles of whole blood (WB) coagulation, can be used to evaluate the effects of hemostatic agents, such as recombinant factor VII (rFVIIa). Our group has developed a revised TEG model, involving activation with minute amounts of tissue factor and subsequent signal processing, and has used this method to evaluate the effects of rFVIIa both in patients with hemophilia and in those receiving vitamin K antagonist (VKA) thromboprophylaxis. We review the early results of our investigations, which suggest that, in clinical situations where rFVIIa has shown benefit, the changes in the profiles obtained by TEG recording appear to correlate with the clinical outcome.