Disorders of coagulation (Proceedings)


Disorders of coagulation (Proceedings)

Aug 01, 2010

The primary hemostatic system alone is not sufficient to provide hemostasis if a large vessel is injured, or if there is significant vascular wall injury. Fibrin needs to be generated in order to form a stable clot, and this occurs through secondary hemostasis, or the coagulation cascade.

The extrinsic coagulation cascade is triggered when tissue factor (TF) is exposed. TF activates factor VII to make FVIIa, which then activates factors VIII, IX, and X. A small amount of thrombin is generated through this process, and this in turn activates the intrinsic cascade by activating factors XI, IX, and VIII. Through this circular process enough thrombin is generated to make fibrin from fibrinogen and to stabilize the clot. This process is controlled by both anticoagulants and fibrinolytics, preventing vessel closure or uncontrolled coagulation from occurring.

Most of the coagulation proteins are created in the liver, and factors II, VII, IX, and X require carboxylation in order to function (a vitamin K-dependent process). Therefore, hepatic dysfunction, vitamin K deficits or antagonism, or congenital or acquired factor deficiencies can lead to compromise of the secondary hemostatic system.

Diagnosing Disorders of Secondary Hemostasis

Disorders of secondary hemostasis often result in hematomas or cavitary hemorrhage, however gastrointestinal, respiratory and other hemorrhage may occur. Common presentations include hemoarthrosis, hemomediastinum, hemoperitoneum, hemothorax, and/or hematomas. Early cases may go undetected, as spontaneous hemorrhage does not occur until approximately 70% of clotting factors are gone. The patient should be examined carefully for signs of underlying disease.

Diagnostic tests for hemostatic disorders should be well understood by the clinician. If the disorder is primarily of the secondary hemostatic system, platelet count and function tests, vWF analysis and buccal mucosal bleeding time would all be expected to be normal. Keep in mind that with significant hemorrhage secondary to a secondary hemostatic disorder, platelet count may be decreased secondary to consumption. It is important to distinguish thrombocytopenia secondary to hemorrhage from thrombocytopenia as the primary cause of hemorrhage. Generally, platelet count must drop below 40,000/µl before bleeding occurs, and it often must drop below 10-20,000/µl before there is significant hemorrhage. It is very rare for platelet count to drop this low secondary to consumption. Therefore, if the platelet count is greater than 30-40,000/µl in a hemorrhaging patient, it is likely a consumptive process and not the primary problem.

Specific tests for secondary hemostasis should be run to narrow down the area along the coagulation cascade that is affected. Many of these tests are now available in-house using citrated whole blood. The prothrombin time (PT) and the Protein Induced by Vitamin K Antagonism (PIVKA) are both used to evaluate the extrinsic and common pathway. There is very little difference in these tests, and the PIVKA is not specific for rodenticide poisoning, so the PT is sufficient and is the recommended test at this time to evaluate the extrinsic and common pathways.

The activated Partial Thromboplastin Time (aPTT) and Activated Clotting Time (ACT) both test the intrinsic and common pathways. The aPTT is more sensitive than the ACT, and its increasing availability as an in-house test makes the aPTT the test of choice when evaluating the intrinsic system. The ACT can also be prolonged with severe thrombocytopenia.

The Thrombin Time (TT) specifically assesses the conversion of fibrinogen to fibrin, so this test is prolonged in situations of fibrinogen deficiencies (hepatic disease, consumption, inherited).

To further narrow down the deficiency, specific factor analyses can be performed. There are also DNA tests available for specific mutations that have been identified for several inherited coagulopathies.