DISORDERS OF SECONDARY HEMOSTASIS (COAGULATION DEFECTS)

22 DISORDERS OF SECONDARY HEMOSTASIS (COAGULATION DEFECTS)



1 What is secondary hemostasis, and what are associated tests?


Secondary hemostasis is the sequential activation of coagulation proteins (factors) resulting in conversion of soluble fibrinogen to insoluble fibrin. For convenience, the coagulation proteins are grouped into the intrinsic, extrinsic, and common coagulation pathways.


Prothrombin time (PT) tests for quantitative and qualitative adequacy of proteins in the extrinsic and common coagulation pathways. Activated partial thromboplastin time (aPTT) tests for qualitative and quantitative adequacy of proteins in the intrinsic and common pathways. Thrombin time (TT) tests for quantitative and qualitative aspects of fibrinogen. Depending on the affected pathway, the appropriate test will be prolonged if a single factor or factors are inadequate quantitatively or qualitatively.



2 What are the clinical signs of secondary (coagulation) defects?


Bleeding into tissues or body cavities is most characteristic of coagulation defects. Coagulation defects often result in hematoma formation; pleural, peritoneal, or retroperitoneal hemorrhage; hemarthrosis; and hemorrhage between the planes of large muscle groups. Delayed bleeding or rebleeding is also characteristic. Usually, venipuncture is uncomplicated. Mucosal or frictional area bleeding is uncommon.



3 How are acquired coagulation defects differentiated from inherited defects?


Inherited coagulation defects often occur in animals at a young age and with a history of previous hemorrhage. Siblings (especially male) and other relatives probably will also have bleeding defects. Inherited coagulation defects usually are associated with a single coagulation protein. Acquired coagulation defects occur at any age, and there is no history of previous bleeding or affected relatives. Acquired coagulation defects often affect multiple coagulation proteins.



4 What is the most common acquired coagulopathy?


Toxicosis with anticoagulant rodenticides is the most common acquired secondary hemostatic disorder. This toxicosis is sometimes difficult to diagnose because bleeding is often occult, occurring in body cavities or between planes of large muscle groups. No specific and relatively easy laboratory test can corroborate this diagnosis, although tests can strongly suggest rodenticide toxicosis. The most common clinical treatment errors are inadequate dosages of vitamin K1 and inadequate duration of treatment.



5 What are the vitamin K–dependent coagulation proteins?


The four major vitamin K–dependent coagulation proteins involved in functional clotting activity are factor II (also known as prothrombin), factor VII, factor IX, and factor X. Proteins C and S are also vitamin K–dependent proteins but have anticoagulant activity.



6 What does vitamin K dependence mean?


Factors II, VII, IX, and X are produced by hepatocytes in an inactive or precursor form. To become functional, glutamic acid in the precursor protein must be carboxylated. This is called gamma-carboxyglutamic acid. The carboxylation process requires the presence of vitamin K. In the absence of vitamin K, these proteins are only present in nonfunctional forms.



7 How do anticoagulant rodenticides affect coagulation?


The active hydroquinone form of vitamin K is necessary for the carboxylation and epoxidation required to change the precursor proteins into the functional forms of factors II, VII, IX, and X. Hydroquinone is converted into the inactive epoxide form of vitamin K as these factors are activated. The active form, hydroquinone, must be regenerated by enzymatic reductions. Anticoagulant rodenticides act by inhibiting the reduction reaction. This quickly reduces the concentration of the hydroquinone form of vitamin K and thus the concentration of functional vitamin K–dependent proteins.



8 How can vitamin K be inhibited without involving rodenticides?


Because vitamin K is fat soluble and is taken up by the intestinal tract with fatty acids, conditions that lead to maldigestion or malabsorption of fats in the diet can also cause reduction in vitamin K concentration. Conditions to rule out include infiltrative bowel disease, lymphangiectasia, exocrine pancreatic deficiency, and biliary obstruction. Bile acids facilitate intestinal absorption of fat. Prolonged oral antibiotic therapy with second-generation and third-generation cephalosporins may lead to mild vitamin K deficiency as the result of decreased bacterial synthesis. These conditions should be considered clinically for completeness but are infrequent causes of severe vitamin K depletion.

Related posts:

  1. ERYTHROCYTE DISORDERS
  2. OVERVIEW: HEMOSTATIC COMPONENTS AND DISORDERS
  3. LABORATORY TESTING FOR THYROID DISEASE
  4. METABOLIC ACID-BASE ABNORMALITIES

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Aug 26, 2016 | Posted by in INTERNAL MEDICINE | Comments Off on DISORDERS OF SECONDARY HEMOSTASIS (COAGULATION DEFECTS)

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