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Organ Transplantation in Persons with Clotting Disorders: Understanding Risks and Benefits

This article explores the history and challenges of organ transplantation in individuals with clotting disorders, specifically focusing on hemophilia. It discusses the bleeding risks, hepatotoxicity, and management strategies associated with organ transplants in these patients. The potential benefits of organ transplantation in curing hemophilia are also highlighted.

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Organ Transplantation in Persons with Clotting Disorders: Understanding Risks and Benefits

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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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