Coagulation Studies

Overview

Definition

Coagulation studies are a group of hematologic studies that reflect the function of blood vessels, platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets, and coagulation factors, which all work in harmony to achieve hemostasis Hemostasis Hemostasis refers to the innate, stepwise body processes that occur following vessel injury, resulting in clot formation and cessation of bleeding. Hemostasis occurs in 2 phases, namely, primary and secondary. Primary hemostasis involves forming a plug that stops the bleeding temporarily. Secondary hemostasis involves the activation of the coagulation cascade. 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 Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets
  • Aggregation: GpIIb/IIIa receptors on platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. 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 Hypocoagulable conditions Hypocoagulable conditions, also known as bleeding disorders or bleeding diathesis, are a diverse group of diseases that result in abnormal hemostasis. Physiologic hemostasis is dependent on the integrity of endothelial cells, subendothelial matrix, platelets, and coagulation factors. The hypocoagulable states result from abnormalities in one or more of these contributors, resulting in ineffective thrombosis and bleeding. Hypocoagulable Conditions are a group of diseases that result in abnormal hemostasis Hemostasis Hemostasis refers to the innate, stepwise body processes that occur following vessel injury, resulting in clot formation and cessation of bleeding. Hemostasis occurs in 2 phases, namely, primary and secondary. Primary hemostasis involves forming a plug that stops the bleeding temporarily. Secondary hemostasis involves the activation of the coagulation cascade. 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 Autosomal recessive Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited. Autosomal Recessive and Autosomal Dominant Inheritancebleeding syndrome characterized by a deficiency of the GpIIb/IIIa receptor, resulting in a lack of platelet aggregation
• Bernard–Soulier syndrome: an autosomal recessive Autosomal recessive Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited. Autosomal Recessive and Autosomal Dominant Inheritancebleeding 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 Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. 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 ITP Immune thrombocytopenic purpura (ITP), formerly known as idiopathic thrombocytopenic purpura, is a condition that develops secondary to immune-mediated destruction of platelets, resulting in thrombocytopenia (platelet count < 100,000/mm³). Immune thrombocytopenic purpura can be either primary or secondary due to drugs or underlying disease. Immune Thrombocytopenic Purpura), thrombotic thrombocytopenic purpura (TTP), HIV, drug-induced thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia, or other bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow disorders (including malignancy).

Disorders of the coagulation cascade

Hemophilia Hemophilia The hemophilias are a group of inherited, or sometimes acquired, disorders of secondary hemostasis due to deficiency of specific clotting factors. Hemophilia A is a deficiency of factor VIII, hemophilia B a deficiency of factor IX, and hemophilia C a deficiency of factor XI. Patients present with bleeding events that may be spontaneous or associated with minor or major trauma. 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 Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets and coagulation factors

• Von Willebrand disease Von Willebrand disease Von Willebrand disease (vWD) is a bleeding disorder characterized by a qualitative or quantitative deficiency of von Willebrand factor (vWF). Von Willebrand factor is a multimeric protein involved in the plate adhesion phase of hemostasis by forming a bridge between platelets and damaged portions of the vessel wall. Von Willebrand Disease (VWD): the most commonly inherited disorder of hemostasis Hemostasis Hemostasis refers to the innate, stepwise body processes that occur following vessel injury, resulting in clot formation and cessation of bleeding. Hemostasis occurs in 2 phases, namely, primary and secondary. Primary hemostasis involves forming a plug that stops the bleeding temporarily. Secondary hemostasis involves the activation of the coagulation cascade. 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 Disseminated intravascular coagulation Disseminated intravascular coagulation (DIC) is a condition characterized by systemic bodywide activation of the coagulation cascade. This cascade results in both widespread microvascular thrombi contributing to multiple organ dysfunction and consumption of clotting factors and platelets, leading to hemorrhage. 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 Disseminated intravascular coagulation Disseminated intravascular coagulation (DIC) is a condition characterized by systemic bodywide activation of the coagulation cascade. This cascade results in both widespread microvascular thrombi contributing to multiple organ dysfunction and consumption of clotting factors and platelets, leading to hemorrhage. Disseminated Intravascular Coagulation always has a secondary cause. Infections, burns Burns A burn is a type of injury to the skin and deeper tissues caused by exposure to heat, electricity, chemicals, friction, or radiation. Burns are classified according to their depth as superficial (1st-degree), partial-thickness (2nd-degree), full-thickness (3rd-degree), and 4th-degree burns. Burns, and malignancies are among the most common causes, but DIC DIC Disseminated intravascular coagulation (DIC) is a condition characterized by systemic bodywide activation of the coagulation cascade. This cascade results in both widespread microvascular thrombi contributing to multiple organ dysfunction and consumption of clotting factors and platelets, leading to hemorrhage. Disseminated Intravascular Coagulation can also occur during severe postpartum hemorrhage Postpartum hemorrhage Postpartum hemorrhage is one of the most common and deadly obstetric complications. Since 2017, postpartum hemorrhage has been defined as blood loss greater than 1,000 mL for both cesarean and vaginal deliveries, or excessive blood loss with signs of hemodynamic instability. Postpartum Hemorrhage. Laboratory findings include thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia, prolongation of the PT and aPTT, and elevation of D-dimer.
• Cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. 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 Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia due to splenic sequestration of platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. 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.