Clotting impaired

One major mechanism for endothelial dysfunction in hyperhomocysteinemic animals appears to be mediated by the oxidative inactivation of nitric oxide, a diffusible gas that relaxes blood vessels and prevents blood clotting. Impairment of NO-mediated dilation of blood vessels also has been observed in human subjects with chronic or acute hyperho-mocysteinemia (Lentz, 2001). 

K Green leafy vegetables and microorganisms in the intestine Coenzyme in formation of carboxyglutamate in enzymes for blood clotting Impaired clotting, haemorrhagic disease... 

K Phylloquinone, menaquinones Coenzyme in formation of y-carboxyglutamate in enzymes of blood clotting and bone matrix Impaired blood clotting, hemorrhagic disease... 

The other factor deficiencies are rare genetic disorders. Mutations in the gene for the respective clotting factors results in impaired functionality or production of the factor (Table 64-7). 

Several substances that contribute to the blood coagulation process are formed in the liver. These include fibrinogen, prothrombin, and several of the blood clotting factors (II, VII, IX, and X). Deficiency in any of these substances leads to impaired blood coagulation. 

A (very rare) genetic deficiency in the production of factor XIII also results in impaired clotting efficacy in affected persons. In this case, covalent links that normally characterize transformation of a soft clot into a hard clot are not formed. Factor XIII preparations, partially purified from human blood, are used to treat individuals with this condition to date, no recombinant version of the product has been commercialized. 

Progressive liver damage (shock liver) manifests as elevated serum hepatic transaminases and unconjugated bilirubin. Impaired synthesis of clotting factors may increase prothrombin time (PT), international normalized ratio, and activated partial thromboplastin time (aPTT). 

Tissue substrate (i.e., lipid-rich plaque) Fibrinogen, impaired fibrinolysis (i.e., PMI-1), activated platelets and clotting (i.e., factor VII, thrombin generation, FI + 2)... 

Stroke A stroke occurs when there is an interruption of blood supply to the brain. An ischemic stroke occurs when a clot prevents blood flow in the brain. A hemorrhagic stroke is when there is a rupture of a blood vessel in the brain. In either case, the brain cells in the affected area die. This area is called an infarct. Medical treatment is required to arrest the damage. More effective treatment can be administered within 6 hours of the onset of stroke. A stroke may result in weakness, paralysis, impairment of speech and memory, or even death. Medical treatment includes the use of anticoagulants to treat stroke victims. 

In the absence of the vitamin, the blood-clotting time increases, since the post-translational carboxylation of several glutamate residues in prothrombin and other factors involved in blood clotting is impaired. In humans, this disorder is unknown except in cases of faulty vitamin K absorption, since the normal diet covers the need generously. 

The physiological role of vitamin K is in blood clotting and is essential for the synthesis of at least four of the proteins (including prothrombin) involved in this process. Vitamin K also plays a role in the synthesis of a protein (osteocalcin) in bone. Vitamin K deficiency is rare but can result from impaired absorption of fat. Vitamin K levels in the body are also reduced if the intestinal flora is killed (e.g. by antibiotics). Vitamin K toxicity is rare but can be caused by excessive intake of vitamin K supplements. Symptoms include erythrocyte haemolysis, jaundice, brain damage and reduced effectiveness of anticoagulants. 

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