Vessel Wall

Vitamin K is a generic name for a group of fat-soluble compounds commonly referred to as vitamin K1 (or phylloquinone) and vitamin K2 (menaquinones, Figure #). Vitamin K1 is mainly found in leafy green vegetables like spinach, kale, sprouts and broccoli, with each kilogram of vegetable containing approximately 1 to 8 mg of vitamin K1. The menaquinones are synthesised by bacteria and mainly occur in fermented foods like cheeses and other dairy products. Very high concentrations of MK-7 (ranging from 9 to 12 mg/kg) are found in fermented soybeans (natto). Since vitamin K is fat-soluble, consuming spinach with butter results in higher absorption of vitamin K from the gastrointestinal tract than spinach alone. 

The biological function of vitamin K is to act as a co-factor for the enzyme 𝛾-glutamyl carboxylase, which adds additional negative charge (in the form of carboxy groups) to the so-called vitamin K-dependent proteins during post-translational modification. The extra negative charge helps the vitamin K-dependent proteins bind calcium ions, thereby enhancing their biological activity. For instance, the coagulation factors II, VII, IX, and X acquire enhanced membrane-binding characteristics, whereas other proteins, such as the MGP, require the additional negative charge to inhibit vascular calcification. 

Coagulation Profile BV offers a variety of assays for assessing the vitamin K status of individual subjects, including differentiating between carboxylated and uncarboxylated proteins such as prothrombin and PIVKA-II. Please contact us for more details or to discuss specific requirements. 

After long being considered a passive process, vascular calcification has recently been shown to be an active disorder, resulting from an imbalance between promoters and inhibitors favouring the former. A major contributor to vascular calcification is the matrix Gla protein (MGP), which relies on vitamin K for activation. The importance of MGP has been demonstrated in experiments reported by Luo et al, who found that while MGP knockout mice were born at term, they all died around 6-8 weeks after birth from ruptures of severely calcified aortas. 

Clinical implications of vitamin K deficiency
Vitamin K deficiency leads to release of the inactive form of MGP, which is both dephosphorylated and uncarboxylated (dp-ucMGP), into the systemic circulation. In vitro cell culture experiments and animal studies have shown that dp-ucMGP tends to accumulate at sites of arterial calcification. Furthermore, clinical studies have repeatedly shown an association between circulating plasma dp-ucMGP levels on the one hand and rates of atherosclerosis, arterial stiffness, cardiovascular disease, and mortality on the other, especially in chronic kidney disease and haemodialysis patients. 

Coagulation Profile BV offers assays for assessment of full carboxylated MGP levels, as well as for partially inactivated MGP, including dp-ucMGP. Please contact us for more details or to discuss specific requirements. 

As the term suggests, vitamin K-dependent proteins such as prothrombin (Factor II) and MGP depend on vitamin K in their synthesis for optimal biological activity. In the absence of vitamin K, or in the presence of a vitamin K antagonist (warfarin and coumarin derivatives), the vitamin K-dependent proteins will still be synthesised, but with less or no activity – these are referred to as proteins induced by vitamin K absence/antagonist (PIVKA). Hence, prothrombin synthesised in the absence of vitamin K or in the presence of an antagonist is called PIVKA-II. 

Coagulation Profile BV offers an enzyme-linked immunosorbent assay (ELISA) for quantifying PIVKA-II, as well as various ELISAs for determining partially inactivated MGP, including dp-ucMGP. Please contact us for more details or to discuss specific requirements. 

Bone is a dynamic tissue which undergoes constant remodelling by osteoblasts and osteoclasts. With ageing, the balance between bone resorption and formation tends to shift towards resorption exceeding formation, increasing the risk of pathological conditions such as osteoporosis and bone fractures. 

Bone marker tests are blood and urine tests that detect products of bone remodelling to estimate the rate of bone resorption and/or formation. 

Coagulation Profile BV offers assays for quantifying bone markers, including bone-specific alkaline phosphatase and collagen degradation products such as the C-terminal telopeptide of type I collagen (CTX-I). Please contact us for more details or to discuss specific requirements.