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ORGAN TRANSPLANTATION: PERSONS WITH CLOTTING DISORDERS Margaret Ragni, MD

ORGAN TRANSPLANTATION: PERSONS WITH CLOTTING DISORDERS Margaret Ragni, MD University of Pittsburgh. HEMOPHILIA X-Linked Bleeding Disorder - Antiquity Deficiency of Factor VIII, IX - 1930s

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ORGAN TRANSPLANTATION: PERSONS WITH CLOTTING DISORDERS Margaret Ragni, MD

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

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

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

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

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

  6. Management of Bleeding Disorder • Bleeding History: factor levels • Drug History: ASA, NSAIDs • Factor levels, PT, APTT, platelet count • 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 • Liver Function – Site of production of factor VIII or IX • Greater liver dysfunction – Multiple hepatitis exposures • More frequent drug interactions

  8. Organ Transplant in Hemophilia 2. Hepatotoxicity • Greater toxicity with antiviral drugs, faster liver dysfunction • Potential for antiviral drug intolerance Hepatitis A, B, C, HIV Chronic analgesic, antiviral treatment • 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 DiagnosisSGOTHCV Ab(+) HCV RNA (IU/ml) (%) (x105 Eq/ml) Hemophilic men 152 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 Subjects1 year2 year Hemophilic Men 13/40 (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

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