**7.2. Vitamin K deficiency and warfarin therapy**

Vitamin K is an essential cofactor needed for carboxylation of glutamate residues of Gla domain containing proteins [95]. Dietary deficiency of vitamin K leads to acquired bleeding disorders. Vitamin K oral supplementation is recommended to treat the vitamin K deficiency [95]. Vitamin K deficiency is diagnosed by prolonged prothrombin time, detection of non-carboxylated proteins and measuring the plasma vitamin K by high performance liquid chromatography [129].

clotting factors II, VII, IX and X prevents the risk of thrombosis, thereby Warfarin is used as an efficient oral anticoagulant/ blood thinner. Over dosage of Warfarin is lethal as it can cause severe bleeding. 2% of the warfarin consumers are prone to the risk of major hemorrhage

Understanding the Clotting Cascade, Regulators, and Clinical Modulators of Coagulation

http://dx.doi.org/10.5772/intechopen.75141

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Platelet activation and aggregation is essential for clot formation and fibrinolysis [131]. Decrease in platelet number or inhibition of platelet activation impairs blood clotting. Infections such as dengue virus, chickenpox, rubella and bacteria effect the circulating platelet number in the blood [132]. Antiplatelet drugs like aspirin impairs platelet aggregation therefore over dosage of aspirin can cause hemorrhage [133]. Acquired platelet disorders are

[130]. Vitamin K is administered as an antidote for warfarin.

analyzed by platelet count and their aggregation properties.

**7.3. Acquired disorders of platelet function**

**Figure 3.** Schematic representation of DIC and its phenotypes.

**Table 2.** DIC phenotypes, diagnosis and treatment.

Warfarin is a coumarin-based anticoagulant and it is used as an oral anticoagulant. It inhibits vitamin K epoxide reductase (VKOR) thereby prevents vitamin K recycling which in turn limits the availability of vitamin K. Limitation in Vitamin K prevents carboxylation of glutamate residues of Gla domain containing proteins. Preventing Gla domain carboxylation of


**Table 2.** DIC phenotypes, diagnosis and treatment.

defined DIC as *"an acquired syndrome characterized by the intravascular activation of coagulation with loss of localization arising from different causes. It can originate from and cause damage to microvasculature, which if severe, can produce organ dysfunction"* [125–127]. DIC occurs in all ages, races and all genders. DIC is classified as acute DIC, developed due to sudden exposure of procoagulants [125–127]. In acute DIC compensatory hemostatic mechanisms are quickly overwhelmed and leads to hemorrhage development. Chronic DIC is develops due to constant or intermittent exposure of small amounts of tissue factor (TF) [125–127]. DIC is acquired due to several reasons which include external agents such as infections, snake bite, trauma, severe transfusion reactions and environmental changes that cause hemocytopenia [125–127]. Disease conditions leading to DIC include malignancy, organ disfunctions such as hepatic failure and pancreatitis, vascular abnormalities. The phenotypes of DIC include non-symptomatic, bleeding, massive bleeding and organ failure type. If there is no observed phenotype in the patients, whereas the abnormalities were observed in clinical laboratory only, the diagnosis is known as Non-symptomatic DIC [125–127]. In the bleeding type is more predominantly observed phenotype in DIC, the primary symptom is bleeding due to hyperfibrinolysis [125–127]. This phenotype is observed in patients with leukemia, aortic aneurysm and obstetric diseases. Organ failure phenotype is observed in the patients with hypercoagulation, this phenotype is observed in patients with infections. Massive bleeding is observed when the fibrinolysis and

hypercoagulation are remarkable. Massive bleeding often leads to death [125–127].

[128] (**Figure 3**).

chromatography [129].

**7.2. Vitamin K deficiency and warfarin therapy**

142 Hematology - Latest Research and Clinical Advances

DIC is diagnosed by global tests such as platelet count, prothrombin time (PT), aPTT and the amount of fibrinogen, fibrin and fibrin degradation products. Other diagnostic markers include antithrombin, Protein C, Thrombin-Antithrombin (TAT) complex, VWF propeptide and plasminogen activator inhibitor-1 (PAI-1) (**Table 2**). Treatment of DIC depends on the type of phenotype (**Table 2**) [128]. Heparin treatment is recommended for the treatment of non-symptomatic type whereas, antifibrinolytic treatment is not recommended. The recommended treatment for the organ failure type DIC is natural protease inhibitor whereas, antifibrinolytic treatment is not recommended [128]. Recommended treatments for the bleeding phenotype DIC include blood transfusion, synthetic protease inhibitors and a fibrinolytic treatment, the non-recommended treatments include heparin and anti-Xa

Vitamin K is an essential cofactor needed for carboxylation of glutamate residues of Gla domain containing proteins [95]. Dietary deficiency of vitamin K leads to acquired bleeding disorders. Vitamin K oral supplementation is recommended to treat the vitamin K deficiency [95]. Vitamin K deficiency is diagnosed by prolonged prothrombin time, detection of non-carboxylated proteins and measuring the plasma vitamin K by high performance liquid

Warfarin is a coumarin-based anticoagulant and it is used as an oral anticoagulant. It inhibits vitamin K epoxide reductase (VKOR) thereby prevents vitamin K recycling which in turn limits the availability of vitamin K. Limitation in Vitamin K prevents carboxylation of glutamate residues of Gla domain containing proteins. Preventing Gla domain carboxylation of

**Figure 3.** Schematic representation of DIC and its phenotypes.

clotting factors II, VII, IX and X prevents the risk of thrombosis, thereby Warfarin is used as an efficient oral anticoagulant/ blood thinner. Over dosage of Warfarin is lethal as it can cause severe bleeding. 2% of the warfarin consumers are prone to the risk of major hemorrhage [130]. Vitamin K is administered as an antidote for warfarin.

#### **7.3. Acquired disorders of platelet function**

Platelet activation and aggregation is essential for clot formation and fibrinolysis [131]. Decrease in platelet number or inhibition of platelet activation impairs blood clotting. Infections such as dengue virus, chickenpox, rubella and bacteria effect the circulating platelet number in the blood [132]. Antiplatelet drugs like aspirin impairs platelet aggregation therefore over dosage of aspirin can cause hemorrhage [133]. Acquired platelet disorders are analyzed by platelet count and their aggregation properties.
