Download Truthtelling and Making Mistakes

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
(IU/ml)
Hemophilic men
n = 19
Homosexual men
n = 21
HCV Ab(+) HCV RNA
(%)
(x105 Eq/ml)
152
84.2%
64.02
78
5.9%
3.5
p<.05
p < .001
Hepatotoxocity: Antiviral Therapy
Pittsburgh, Blood 1995;85:2337
Subjects: 126 HIV+, CD4 > 200
Rx: AZT + ddI
LFT >5XUL
Subjects
Hemophilic Men
Nonhemophilic Men
13/40 (32%)
8/86 (9%)
p = .0009
Time to LFT >5XUL
1 year 2 year
25%
34%
11%
11%
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