1. ORGAN TRANSPLANTATION: PERSONS WITH CLOTTING DISORDERS Margaret Ragni, MD University of Pittsburgh

2. HEMOPHILIA l X-Linked Bleeding Disorder - Antiquity l Deficiency of Factor VIII, IX - 1930s l Clotting Factor Treatment - 1960s, 1970s l Hepatitis B, C - 1970s, 1980s l Chronic Liver Disease - 1970s l HIV Infection - 1980s

3. Organ Transplant in Hemophilia 1. Bleeding Risk 2. Hepatotoxicity

4. Organ Transplant in Hemophilia 1. Bleeding Risk l Poor Fibrin Clot - Lack of Coagulation factor VIII or IX - Decreased synthesis of clotting factors (liver) l PoorPlatelet Plug - Thrombocytopenia due to portal hypertension l Platelet Defects - Analgesics, antibiotics

5. Organ Transplant in Hemophilia 1. Bleeding Risks Transjugular Percutaneous l < 1% (1/178) bleeding complications with biopsy (Ewenstein, 1998) l < 1% overall complication rate with transjugular bx (Little, Zajko, 1996) l < 1% bleeding complications in hemophilia (Wong et al, 1997)

6. Management of Bleeding Disorder l Bleeding History: factor levels l Drug History: ASA, NSAIDs l Factor levels, PT, APTT, platelet count l Treatment: Factor Concentrate for factor deficiency Platelets for portal hypertension DDAVP, Platelets for platelet dysfunction FFP for hepatic synthetic defect

7. Organ Transplant in Hemophilia 2. Hepatotoxicity l Liver Function – Site of production of factor VIII or IX l Greater liver dysfunction – Multiple hepatitis exposures l More frequent drug interactions

8. Organ Transplant in Hemophilia 2. Hepatotoxicity l Greater toxicity with antiviral drugs, faster liver dysfunction l Potential for antiviral drug intolerance Hepatitis A, B, C, HIV Chronic analgesic, antiviral treatment l Liver transplant cures hemophilia

9. SGOT, HCV RNA in HIV(+) Subjects Pittsburgh, Thromb Haemostas 1995;73:1458 Subjects: HIV+ Matched: Age, Date of AIDS Diagnosis At AIDS Diagnosis SGOT HCV Ab(+) HCV RNA (IU/ml) (%)(x10 5 Eq/ml) Hemophilic men152 84.2%64.02 n = 19 Homosexual men 78 5.9%3.5 n = 21 p<.05 p <.001

10. Hepatotoxocity: Antiviral Therapy Pittsburgh, Blood 1995;85:2337 Subjects: 126 HIV+, CD4 > 200 Rx: AZT + ddI LFT >5XULTime to LFT >5XUL Subjects 1 year 2 year Hemophilic Men13/40 (32%) 25% 34% Nonhemophilic Men 8/86 (9%) 11% 11% p =.0009 p =.008

11. Subjects with Hemophilia 1. Bleeding risk: adequate treatment reduces risk to “usual risk” 2. Hepatotoxicity: monitoring and avoiding potential hepatotoxins reduces risk to “usual risk” 3. Potential Benefit: transplant cures hemophilia Conclusion: No reason to exclude individuals with hemophilia