Pharmacotherapy of Coagulation Disorders

Coagulation Disorders Overview

• Hemostasis maintains blood fluidity, repairs vascular injury, limits blood loss, and prevents thrombosis.
• Understanding the coagulation cascade and its components is essential for diagnosing and treating disorders.

Clotting Factors & Their Role

• Factor VI is not involved in blood coagulation.
• Clotting factors are crucial in the coagulation cascade, each fulfilling a specific function.

Anticoagulant Drugs

• Aspirin inhibits thromboxane A2 to prevent platelet aggregation.
• Clopidogrel acts as an ADP inhibitor to reduce thrombus formation.
• Abciximab is a GP IIb/IIIa receptor inhibitor.
• Warfarin inhibits Vitamin K Epoxide reductase affecting factors II, VII, IX, and X.
• Heparin and Dalteparin activate Antithrombin III.
• Dabigatran inhibits thrombin (Factor IIa).
• Rivaroxaban targets Factor Xa.
• Alteplase functions as a Tissue Plasminogen Activator for clot lysis.

Hemophilia Types

• Hemophilia is known as "Royal Disease" due to its prevalence among royals; characterized by severe bleeding.
• Hemophilia A is due to factor VIII deficiency, 4 times more common than Hemophilia B (factor IX deficiency).
• Incidence of hemophilia is approximately 1 in 5000 male births.
• Symptoms include easy bruising and spontaneous hemorrhage after injuries.

Hemophilia A Specifics

• X-linked recessive disorder; traced to defective factor VIII.
• Symptoms: Anemia, weakness, tachycardia, and various types of hemorrhage, including hematuria.
• Diagnosis involves CBC, PT, aPTT, and specific factor VIII assays.
• Treatment focuses on managing bleeding episodes, factor replacement, and anti-fibrinolytics.

Desmopressin

• Analog of vasopressin, acts mostly through V2 receptors.
• Induces exocytosis of von Willebrand Factor (VWF), enhancing clotting function.

Acquired Hemophilia

• Rare, life-threatening condition with autoantibodies against factor VIII.
• Symptoms include diverse bleeding manifestations; diagnosis shows prolonged aPTT and decreased factor VIII.
• Treatment combines factor VIII infusion and immunosuppression, using corticosteroids and monoclonal antibodies like Rituximab.

Hemophilia B Specifics

• Caused by factor IX deficiency; referred to as "Christmas disease."
• Symptoms primarily involve joint bleeding (hemarthrosis) and hematomas.
• Diagnosis includes platelet count and specific assays for factor IX.
• Treatment involves factor IX replacement and anti-fibrinolytics.

Clotting Factor Deficiencies

• Factor II deficiency: Leads to hypoprothrombinemia; can be inherited, autoimmune, or drug-induced. Symptoms may include severe bleeding.
• Factor V deficiency (Owren’s disease): Extremely rare, characterized by prolonged PT and aPTT; treatment involves fresh frozen plasma.
• Factor VII deficiency: Prolonged PT with normal aPTT; management includes specific factor replacement and anti-fibrinolytics.
• Factor X deficiency: Related to vitamin K metabolism; shows prolonged PT and aPTT; treatment involves vitamin K and factor replacement.

von Willebrand Disease (VWD)

• Three types exist, with Type 1 being the most common.
• Type 2 has subtypes; Type 2A leads to low VWF affecting platelet function.
• Type 3 is the most severe form, characterized by an almost complete absence of VWF.
• Inherited through mutations; treatments include desmopressin for Type 1 and replacement therapy for severe cases.

Key Diagnostic Tests for VWD

• CBC, VWF antigen test, ristocetin co-factor test, and specific factor assays are critical for diagnosis.
• Prolonged bleeding and excessive bleeding during procedures are common symptoms.

Treatment and Contraindications

• Desmopressin is effective for Type 1 and some Type 2 variants but contraindicated in Type 2B due to low platelet counts.
• Aminocaproic acid and tranexamic acid are used in management; NSAIDs and blood thinners should be avoided in VWD patients.

This quiz focuses on the pharmacotherapy associated with coagulation disorders, covering their pathophysiology, inducing factors, and clinical presentations. Students will explore diagnostic methods and therapeutic outcomes in the context of hemostasis and coagulation management.