Vitamin Information and Courses from MediaLab, Inc.

Although the procedure is simple to perform, accurate results depend on careful adherence to manufacturer’s directions and adequate quality control. Normal and abnormal controls should be tested whenever a new lot of strips is opened, and at the frequency defined by the laboratory's procedure. If quality control results do not correspond to the published control values, the problem must be resolved before patient samples are tested. High levels of ascorbic acid (Vitamin C) in the urine may inhibit some reagent strip reactions, such as glucose, blood, bilirubin, nitrate and leukocyte esterase. The urine dipstick's package insert will provide information about potential interfering substances, including ascorbic acid. Intensely colored urine may make it difficult to correctly interpret color reactions on the dipstick. The affected tests should not be reported from the dipstick. It would be necessary to use an alternative method of testing if available.

A lack of Vitamin K can cause a loss of functionality in Vitamin K dependant coagulation factors, specifically, factors II, VII, IX and X. Most often associated with a diet lacking in Vitamin K, it may also present in situations of broad spectrum antibiotic use, where normal flora in the gut have been eliminated. As one might expect, treatment involves a diet rich in Vitamin K containing foods, and judicious use of broad spectrum antibiotics.

The therapeutic use of oral anticoagulants is typically the long-term solution for the patient in terms of managing situations of thrombosis. Warfarin, a dicumarol derivative, is one of the most popular oral anticoagulants used today. While heparin is administered intravenously and acts to inhibit thrombin, warfarin is given orally, taken in pill form, and functions as a Vitamin K antagonist. In earlier discussions, it was mentioned that certain clotting factors are considered to be vitamin K dependant. They require vitamin K molecules for their action to occur. Vitamin K dependant factors include factor II, VII, IX, and X. Vitamin K dependant metabolic processes involved with these coagulation factors are inhibited by drugs such as warfarin. The chemical structure of warfarin and similar anticoagulants enables them to bind competitively with free vitamin K. The prothrombin time (PT/INR) is used to monitor oral anticoagulant therapy.

The genes involved in warfarin metabolism are CYP2C9 and vitamin K epoxide reductase complex subunit 1 (VKOR). Warfarin owes its anticoagulant action to its inhibition of VKOR. This enzyme recycles vitamin K, a critical element for the clotting factors II, VII, IX, and X, as well as for proteins C, S, and Z. There are six CYP2C9 alleles that are known to cause prolonged metabolism of warfarin: CYP2C9 *2, *3, *4, *5, *6, and *11. (Polymorphisms in CYP450 genes are denoted with asterisks.)One-third of the patients that receive warfarin metabolize it differently than expected and experience a higher risk of bleeding.Genetic testing for the two most common polymorphisms (CYP2C9*2 and *3) as well as for VKOR may be able to reduce the variability associated with warfarin dosing response. Labs performing PGx testing can provide general warfarin dosing recommendations based on the patient's genotype analysis. The lab report will indicate whether a patient has a normal, mild, moderate, high, or very high sensitivity to warfarin. For example, a patient who has one CYP2C9 normal wild-type allele (CYP2C9 *1), one polymorphism (CYP2C9*3), and also a VKOR polymorphism is predicted to have a moderate sensitivity to warfarin. This patient should have frequent INR monitoring and possible warfarin dose reduction. It is important to recognize that knowing a genotype does not necessarily guarantee accurate dose prediction; other drugs and/or environmental or disease factors can also alter CYP2C9 activity. Therefore, monitoring the INR is still very important.

The focus of these photographed fields is on the occasional large oval macrocyte,and the large, hypersegmented neutrophils representing either vitamin B-12 or folic acid deficiency, or both. The distinct hypochromia of many of the erythrocytes reflects low iron stores.

Another example of macrocytes is seen in this slide. This patient had pernicious anemia, which results from an inability to absorb the vitamin B12 needed for DNA synthesis. Since many cells are destroyed in the bone marrow, decreased numbers of red cells are present in the circulating blood causing low hemoglobin(anemia).