Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 54 Drugs for Hemophilia

2Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Hemophilia  Genetically based bleeding disorder  Almost exclusively seen in males  70% of cases result from inheriting defective gene from mother  30% of cases result from spontaneous gene mutation  Hemophilia A and hemophilia B  Prognosis is good with good management

3Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Basic Considerations  Pathophysiology  Failure of hemostasis  Normal process Formation of a platelet plug followed by production of fibrin Formation of a platelet plug followed by production of fibrin  Hemophilia Fibrin production does not proceed normally Fibrin production does not proceed normally

4Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Basic Considerations  Inheritance pattern  Recessive gene (both factors VIII and IX)  Carried on the X chromosome  Females can have hemophilia in some cases  Clinical features  Severe hemophilia  Moderate hemophilia  Mild hemophilia

5Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Basic Considerations  Overview of therapy  Pain management Mild pain: Tylenol Mild pain: Tylenol Moderate to severe pain: opioids Moderate to severe pain: opioids Avoid NSAIDs and aspirin Avoid NSAIDs and aspirin More research needed for COX-2 use More research needed for COX-2 use  Immunization  Normal immunization schedule SubQ rather than IM injections SubQ rather than IM injections  Vaccinated for hepatitis A and B

6Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Fig. 54–1. Outline of the coagulation cascade showing clotting factors used to treat hemophilia.

7Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Preparations Used to Treat Hemophilia  Factor VIII concentrates  Production methods and product safety Plasma-derived factor VIII (low risk of viral contaminants) Plasma-derived factor VIII (low risk of viral contaminants) Recombinant factor VIII Recombinant factor VIII  Adverse effects: allergic reactions  Dosage and administration On-demand therapy On-demand therapy Prophylactic therapy Prophylactic therapy

8Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Preparations Used to Treat Hemophilia  Factor IX concentrates  Nearly identical pharmacology to that of factor VIII No risk of HIV/AIDS transmission No risk of HIV/AIDS transmission Small risk of hepatitis A transmission Small risk of hepatitis A transmission  On-demand therapy  Prophylactic therapy

9Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Preparations Used to Treat Hemophilia  Desmopressin  Stops or prevents bleeding (mild hemophilia)  Antifibrinolytic agents  Used to prevent recurrent bleeding, less useful to stop ongoing bleeding  Aminocaproic acid (Amicar), tranexamic acid (Cyklokapron)

10Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Managing Patients Who Develop Inhibitors  Inhibitors: antibodies that develop against factor VIII or IX  Drugs for patients with inhibitors  Factor VIII inhibitors Activated factor VII (factor VIIa) Activated factor VII (factor VIIa) Anti-inhibitor coagulant complex (AICC) Anti-inhibitor coagulant complex (AICC) Porcine factor VIII Porcine factor VIII  Factor IX inhibitors Limited options Limited options Immune tolerance therapy (ITT) often fails Immune tolerance therapy (ITT) often fails