Coagulation Studies

Overview

Definition

Coagulation studies are a group of hematologic studies that reflect the function of blood vessels, platelets, and coagulation factors, which all work in harmony to achieve hemostasis.

Uses of coagulation studies

• Evaluation of abnormal bleeding or thrombosis
• Preoperative testing
• Management of anticoagulation therapy
• Assist in resuscitation management during massive transfusions

Review: phases of the hemostatic process

The following is a summary of the hemostatic process:

• Constriction of the blood vessel: limits blood flow to the area
• Formation of the platelet plug: the initial, temporary plug formed via the following steps:
  • Adhesion: exposed von Willebrand factor (VWF) binds to the glycoprotein (Gp) Ib receptors on platelets
  • Aggregation: GpIIb/IIIa receptors on platelets bind fibrinogen
  • Secretion: Substances are released that stimulate further platelet activation and aggregation and initiate the coagulation cascade.
• Activation of the coagulation cascade: forms a more stable fibrin clot
  • Extrinsic pathway: 
    • Primarily responsible for initiation of the cascade
    • Involves (in order): tissue factor, factor VII, and factor X
  • Intrinsic pathway: 
    • Primarily involved in amplification of the cascade
    • Can be directly activated by vessel injury
    • Involves (in order): factors XII, XI, IX, VIII, and X
  • Common pathway: 
    • The extrinsic and intrinsic pathways join together when factor X is activated to form the final common pathway.
    • Involves (in order): factors X, V, II (thrombin), I (fibrin), and XIII
• Inhibition of clotting and fibrinolytic phase: 
  • Stops clotting and breaks down the clot once it is no longer necessary
  • Involves: 
    • Plasmin
    • Antithrombin
    • Proteins C and S

Clinical Relevance: Hypocoagulable Conditions

Hypocoagulable conditions are a group of diseases that result in abnormal hemostasis. They manifest with minor bleeding (petechiae, mucocutaneous bleeding) or more severe internal bleeding (hemarthrosis, intracranial bleeding).

Disorders of formation of the platelet plug

Patients with these disorders will most likely have an increased bleeding time but normal PT and aPTT.

• Glanzmann thrombasthenia: an autosomal recessive bleeding syndrome characterized by a deficiency of the GpIIb/IIIa receptor, resulting in a lack of platelet aggregation
• Bernard–Soulier syndrome: an autosomal recessive bleeding syndrome characterized by deficiency of the GpIb receptor, resulting in failure of platelet adhesion: Bernard–Soulier syndrome can be diagnosed with a ristocetin assay. Ristocetin activates VWF to allow binding to the platelet GpIb receptor; however, in Bernard–Soulier syndrome, platelets will fail to adhere with the assay.
• Thrombocytopenia: When platelet levels are low, formation of the platelet plug may be impaired. Thrombocytopenia is usually diagnosed with a CBC with platelet count and morphology assessment. Causes may include immune thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), HIV, drug-induced thrombocytopenia, or other bone marrow disorders (including malignancy).

Disorders of the coagulation cascade

Hemophilia: a rare blood clotting disorder in which the body lacks blood-clotting factors (factor VIII in hemophilia A and factor IX in hemophilia B). Affected individuals present with abnormal bleeding that occurred spontaneously or after minor trauma. Patients can bleed into joint spaces and can develop life-threatening internal bleeding. Coagulation studies typically reveal a prolonged aPTT due to the abnormalities in the intrinsic pathway, but the PT and platelet counts are normal. Mixing studies will correct, and the level of the specific factor activity in which the patient is deficient will be low.

Mixed disorders affecting both platelets and coagulation factors

• Von Willebrand disease (VWD): the most commonly inherited disorder of hemostasis, caused by a qualitative or quantitative deficiency in VWF: The three primary types of VWD differ in severity, though all tend to present with bleeding abnormalities. Von Willebrand factor is required for both initial platelet adhesion, and it helps stabilize factor VIII in the intrinsic pathway. Testing shows a normal platelet count, but the aPTT may be prolonged (depending on the reduction of factor VIII activity). A VWF antigen test, specific functional assays, and genetic testing can aid in the diagnosis.
• Disseminated intravascular coagulation: a serious medical condition in which the coagulation cascade is activated systemically, leading to multiple clots that can lead to permanent end-organ damage and in the process, coagulation factors are used up: Disseminated intravascular coagulation always has a secondary cause. Infections, burns, and malignancies are among the most common causes, but DIC can also occur during severe postpartum hemorrhage. Laboratory findings include thrombocytopenia, prolongation of the PT and aPTT, and elevation of D-dimer.
• Cirrhosis: The liver is the primary site of synthesis for a majority of the clotting factors. In addition to impaired synthesis of clotting factors, cirrhosis also may independently result in thrombocytopenia due to splenic sequestration of platelets and decreased thrombopoietin production. Platelets themselves may also be dysfunctional. The platelet count may be low and the PT and aPTT may both be prolonged.