ORGAN TRANSPLANTATION:

PERSONS WITH CLOTTING DISORDERS

Margaret Ragni, MD

University of Pittsburgh

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

Organ Transplant in Hemophilia

1. Bleeding Risk

2. Hepatotoxicity

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

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)

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

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

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

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) (%)(x105 Eq/ml)

Hemophilic men 152 84.2% 64.02n = 19

Homosexual men 78 5.9% 3.5n = 21 p<.05 p < .001

Hepatotoxocity: Antiviral TherapyPittsburgh, Blood 1995;85:2337

Subjects: 126 HIV+, CD4 > 200Rx: AZT + ddI

LFT >5XUL Time to LFT >5XULSubjects 1 year 2 yearHemophilic Men 13/40 (32%) 25% 34%Nonhemophilic Men 8/86 (9%) 11% 11%

p = .0009 p = .008

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