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Bleeding vs Coagulation Disorder: Components of Hemostasis, Types of Bleeding Disorders, and Laboratory Evaluation

• Hemostasis is a regulated process that maintains blood in a liquid state inside vessels and arrests bleeding at the site of vascular injury by forming a hemostatic clot.

• Five components, including platelets, blood vessel wall, coagulation system, coagulation regulatory system, and fibrinolytic system, participate in both hemostasis and thrombosis.

• Platelets are anuclear cellular fragments derived from bone marrow megakaryocytes and play a crucial role in forming the primary hemostatic plug, releasing platelet activating and procoagulant molecules, providing a procoagulant surface, and activating the coagulation system.

• Blood vessel walls, specifically endothelial cells, have antithrombotic systems that limit coagulation, but under inflammatory conditions or injury, they can become procoagulant and expose a highly thrombogenic subendothelial extracellular matrix, leading to platelet adherence and activation.

• The coagulation system has two pathways, the extrinsic and intrinsic, and can be assessed with laboratory tests like prothrombin time and partial thromboplastin time.

• The coagulation regulatory mechanism includes antithrombin, proteins C and S, and tissue factor pathway inhibitor, which inhibit the activity of thrombin and other factors.

• The fibrinolytic system involves plasminogen activation and plays a role in removing the hemostatic plug when healing is complete.

• Hemostasis disorders can lead to either hemorrhage or thrombosis, and bleeding disorders are more common than thrombotic disorders.

• Bleeding disorders can be classified based on terminologies like petechiae, purpura, ecchymoses, hematoma, and easy bruisability.

• Laboratory tests for hemostatic and thrombotic disorders include platelet count, platelet aggregation test, clot retraction test, capillary fragility test, and bleeding time.

• Vascular purpura is a group of disorders of blood vessels that result in bleeding, induce small hemorrhages in the skin or mucous membranes, and usually do not cause serious bleeding.

• Platelet disorders can be quantitative or qualitative in nature, and thrombocytopenia is a platelet disorder characterized by a platelet count of less than 100 x 10^9/L and can lead to cutaneous and mucosal bleeding. Idiopathic (immune) thrombocytopenic purpura is a common cause of thrombocytopenia, which involves the destruction of platelets by antibodies.Overview of Platelet Disorders and Coagulation Disorders

• Immune thrombocytopenic purpura (ITP) is an autoimmune disorder that results in the formation of antiplatelet antibodies, leading to thrombocytopenia.

• ITP is more common in children and women, with a F:M ratio of 3:1.

• Laboratory findings in ITP include a markedly reduced platelet count, prolonged bleeding time, and normal PT and APTT.

• Evans syndrome is a term used for autoimmune hemolytic anemia (AIHA) along with immune thrombocytopenia.

• Secondary immune thrombocytopenic purpura includes all forms of immune thrombocytopenias except primary ITP.

• Thrombotic microangiopathy is a spectrum of clinical syndromes characterized by widespread formation of platelet-fibrin thrombi in the microcirculation.

• Thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS) are two closely related entities included under thrombotic microangiopathy.

• The classic five symptoms of TTP include microangiopathic hemolytic anemia, thrombocytopenia, transient neurologic symptoms, fever, and renal failure.

• Glanzmann thrombasthenia is an autosomal recessive disorder characterized by a deficiency of glycoprotein IIb-IIIa, resulting in defective platelet aggregation.

• Hereditary disorders of platelet function include defective adhesion of platelets, disorders of platelet secretion, and defective platelet aggregation.

• Acquired platelet function disorders include drug-induced platelet dysfunction, paraproteinemias, and myeloproliferative neoplasms.

• Screening coagulograms are the baseline tests used to assess hemostasis, including platelet count, prothrombin time (PT), and activated partial thromboplastin time (aPTT).

• Hemophilia A is a sex-linked recessive disease caused by a deficiency in factor VIII.Overview of Hemostasis and Bleeding Disorders

• Hemophilia A is a rare bleeding disorder caused by deficiency of Factor VIII, which has two components: VIII C and vWF. Males are affected while females are carriers, and bleeding time is usually normal while APTT is increased in laboratory findings.

• Hemophilia B, also known as Christmas Disease, is caused by deficiency of Factor IX and is inherited in an X-linked recessive manner. Clinical features are usually milder than Hemophilia A, but hemarthrosis is a common presentation. Lab findings are similar to Hemophilia A.

• Von Willebrand Disease is a bleeding disorder characterized by a platelet function defect and a coagulation defect. It has multiple variants with varying clinical presentations and modes of inheritance. Lab findings include prolonged bleeding time and APTT, and diagnosis is confirmed by vWF assays and genetic studies.

• Rare hereditary bleeding disorders include hypofibrinogenemia and afibrinogenemia, dysfibrinogenemia, Factor XIII deficiency, and Factor V deficiency. Lab findings vary but all show prolonged clotting times that get corrected with the addition of normal plasma.

• Disseminated Intravascular Coagulation (DIC) is an acquired pathological state caused by the presence of excessive thrombin in the systemic circulation. It is associated with various disorders such as obstetric complications and malignancies, and lab findings include decreased platelet count, increased PT and APTT, and decreased fibrinogen.

• Vitamin K deficiency results in incomplete and inactive coagulation factors, and can develop when absorption is defective due to liver disease or small bowel disease. Bleeding manifestations show a dramatic response to parenteral vitamin K therapy.

• Thrombophilia refers to hereditary and acquired conditions associated with a tendency for arterial and venous thrombosis. The five major ones in order of frequency in the general population are Factor V Leiden, Prothrombin 20210A mutation, Protein S deficiency, Protein C deficiency, and Antithrombin III deficiency.

• Antithrombin III deficiency is an autosomal dominant condition that results in thrombus formation. Protein C and S deficiency promote thrombosis by not neutralizing activated factor V and VIII. Factor V Leiden is the most common genetic disorder associated with familial thrombophilia.

• Acquired hypercoagulable states include Antiphospholipid Antibody Syndrome (APLA/APS), which is characterized by the presence of antiphospholipid antibodies in the plasma and is associated with hypercoagulable state and repeated spontaneous abortions. Homocysteinemia, which is an increased plasma concentration of homocysteine, also predisposes to atherosclerosis and thrombosis.

• Approach to investigation of a bleeding disorder depends on the laboratory findings. Bleeding disorder with normal PT and APTT requires further investigation such as platelet function tests, while bleeding disorder with prolonged

Bleeding vs Coagulation Disorder: Components of Hemostasis, Types of Bleeding Disorders, and Laboratory Evaluation

• Hemostasis is a regulated process that maintains blood in a liquid state inside vessels and arrests bleeding at the site of vascular injury by forming a hemostatic clot.

• Five components, including platelets, blood vessel wall, coagulation system, coagulation regulatory system, and fibrinolytic system, participate in both hemostasis and thrombosis.

• Platelets are anuclear cellular fragments derived from bone marrow megakaryocytes and play a crucial role in forming the primary hemostatic plug, releasing platelet activating and procoagulant molecules, providing a procoagulant surface, and activating the coagulation system.

• Blood vessel walls, specifically endothelial cells, have antithrombotic systems that limit coagulation, but under inflammatory conditions or injury, they can become procoagulant and expose a highly thrombogenic subendothelial extracellular matrix, leading to platelet adherence and activation.

• The coagulation system has two pathways, the extrinsic and intrinsic, and can be assessed with laboratory tests like prothrombin time and partial thromboplastin time.

• The coagulation regulatory mechanism includes antithrombin, proteins C and S, and tissue factor pathway inhibitor, which inhibit the activity of thrombin and other factors.

• The fibrinolytic system involves plasminogen activation and plays a role in removing the hemostatic plug when healing is complete.

• Hemostasis disorders can lead to either hemorrhage or thrombosis, and bleeding disorders are more common than thrombotic disorders.

• Bleeding disorders can be classified based on terminologies like petechiae, purpura, ecchymoses, hematoma, and easy bruisability.

• Laboratory tests for hemostatic and thrombotic disorders include platelet count, platelet aggregation test, clot retraction test, capillary fragility test, and bleeding time.

• Vascular purpura is a group of disorders of blood vessels that result in bleeding, induce small hemorrhages in the skin or mucous membranes, and usually do not cause serious bleeding.

• Platelet disorders can be quantitative or qualitative in nature, and thrombocytopenia is a platelet disorder characterized by a platelet count of less than 100 x 10^9/L and can lead to cutaneous and mucosal bleeding. Idiopathic (immune) thrombocytopenic purpura is a common cause of thrombocytopenia, which involves the destruction of platelets by antibodies.Overview of Platelet Disorders and Coagulation Disorders

• Immune thrombocytopenic purpura (ITP) is an autoimmune disorder that results in the formation of antiplatelet antibodies, leading to thrombocytopenia.

• ITP is more common in children and women, with a F:M ratio of 3:1.

• Laboratory findings in ITP include a markedly reduced platelet count, prolonged bleeding time, and normal PT and APTT.

• Evans syndrome is a term used for autoimmune hemolytic anemia (AIHA) along with immune thrombocytopenia.

• Secondary immune thrombocytopenic purpura includes all forms of immune thrombocytopenias except primary ITP.

• Thrombotic microangiopathy is a spectrum of clinical syndromes characterized by widespread formation of platelet-fibrin thrombi in the microcirculation.

• Thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS) are two closely related entities included under thrombotic microangiopathy.

• The classic five symptoms of TTP include microangiopathic hemolytic anemia, thrombocytopenia, transient neurologic symptoms, fever, and renal failure.

• Glanzmann thrombasthenia is an autosomal recessive disorder characterized by a deficiency of glycoprotein IIb-IIIa, resulting in defective platelet aggregation.

• Hereditary disorders of platelet function include defective adhesion of platelets, disorders of platelet secretion, and defective platelet aggregation.

• Acquired platelet function disorders include drug-induced platelet dysfunction, paraproteinemias, and myeloproliferative neoplasms.

• Screening coagulograms are the baseline tests used to assess hemostasis, including platelet count, prothrombin time (PT), and activated partial thromboplastin time (aPTT).

• Hemophilia A is a sex-linked recessive disease caused by a deficiency in factor VIII.Overview of Hemostasis and Bleeding Disorders

• Hemophilia A is a rare bleeding disorder caused by deficiency of Factor VIII, which has two components: VIII C and vWF. Males are affected while females are carriers, and bleeding time is usually normal while APTT is increased in laboratory findings.

• Hemophilia B, also known as Christmas Disease, is caused by deficiency of Factor IX and is inherited in an X-linked recessive manner. Clinical features are usually milder than Hemophilia A, but hemarthrosis is a common presentation. Lab findings are similar to Hemophilia A.

• Von Willebrand Disease is a bleeding disorder characterized by a platelet function defect and a coagulation defect. It has multiple variants with varying clinical presentations and modes of inheritance. Lab findings include prolonged bleeding time and APTT, and diagnosis is confirmed by vWF assays and genetic studies.

• Rare hereditary bleeding disorders include hypofibrinogenemia and afibrinogenemia, dysfibrinogenemia, Factor XIII deficiency, and Factor V deficiency. Lab findings vary but all show prolonged clotting times that get corrected with the addition of normal plasma.

• Disseminated Intravascular Coagulation (DIC) is an acquired pathological state caused by the presence of excessive thrombin in the systemic circulation. It is associated with various disorders such as obstetric complications and malignancies, and lab findings include decreased platelet count, increased PT and APTT, and decreased fibrinogen.

• Vitamin K deficiency results in incomplete and inactive coagulation factors, and can develop when absorption is defective due to liver disease or small bowel disease. Bleeding manifestations show a dramatic response to parenteral vitamin K therapy.

• Thrombophilia refers to hereditary and acquired conditions associated with a tendency for arterial and venous thrombosis. The five major ones in order of frequency in the general population are Factor V Leiden, Prothrombin 20210A mutation, Protein S deficiency, Protein C deficiency, and Antithrombin III deficiency.

• Antithrombin III deficiency is an autosomal dominant condition that results in thrombus formation. Protein C and S deficiency promote thrombosis by not neutralizing activated factor V and VIII. Factor V Leiden is the most common genetic disorder associated with familial thrombophilia.

• Acquired hypercoagulable states include Antiphospholipid Antibody Syndrome (APLA/APS), which is characterized by the presence of antiphospholipid antibodies in the plasma and is associated with hypercoagulable state and repeated spontaneous abortions. Homocysteinemia, which is an increased plasma concentration of homocysteine, also predisposes to atherosclerosis and thrombosis.

• Approach to investigation of a bleeding disorder depends on the laboratory findings. Bleeding disorder with normal PT and APTT requires further investigation such as platelet function tests, while bleeding disorder with prolonged