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Chapter 54

Drugs for Hemophilia

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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

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Basic Considerations

Pathophysiology Failure of hemostasis Normal process

• Formation of a platelet plug followed by production of fibrin

Hemophilia • Fibrin production does not proceed normally

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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

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Basic Considerations

Overview of therapy Pain management

• Mild pain: Tylenol • Moderate to severe pain: opioids• Avoid NSAIDs and aspirin• More research needed for COX-2 use

Immunization Normal immunization schedule

• SubQ rather than IM injections Vaccinated for hepatitis A and B

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Fig. 54–1. Outline of the coagulation cascade showing clotting factors used to treat hemophilia.

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Preparations Used to Treat Hemophilia

Factor VIII concentrates Production methods and product safety

• Plasma-derived factor VIII (low risk of viral contaminants) • Recombinant factor VIII

Adverse effects: allergic reactions Dosage and administration

• On-demand therapy• Prophylactic therapy

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Preparations Used to Treat Hemophilia

Factor IX concentrates Nearly identical pharmacology to that of

factor VIII• No risk of HIV/AIDS transmission• Small risk of hepatitis A transmission

On-demand therapy Prophylactic therapy

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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)

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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)• Anti-inhibitor coagulant complex (AICC)• Porcine factor VIII

Factor IX inhibitors• Limited options• Immune tolerance therapy (ITT) often fails