HUMAN IMMUNODEFICIENCY VIRUS (HIV) & HEMOPHILIA

Margaret V. Ragni, M.D., Director
Hemophilia Center Of Western Pennsylvania

INTRODUCTION

Of all the complications of hemophilia, perhaps the most tragic is that of HIV infection and AIDS.  Over half of the 20,000 individuals with hemophilia in the U.S. were infected with HIV during the early to mid-1980s (median year, 1982).  Now, over 20 percent of those with hemophilia have developed AIDS.  An additional 10 percent are expected to meet the new CDC AIDS case definition.  Clotting factor concentrates revolutionized the lives of hemophiliacs, improving the quality of life and bringing their life expectancy toward normal.  Unfortunately, clotting factor concentrates, prior to donor screening and viral inactivation technologies, were also the route of HIV transmission. 

Septic arthritis is an uncommon complication of join hemorrhages in HIV (-) hemophiliacs.  However, septic arthritis may complicate the occurrence of sepsis in HIV (+) hemophiliacs, with seeding of the infection into joints, which have undergone recurrent hemarthroses, with synovial inflammation and proliferation, and make an ideal growth medium for bacteria.  The key to management is early detection, distinguishing the several exquisitely painful affected multiple joints of septic arthritis from the typical moderately painful singly affected joint of uncomplicated hemarthrosis.  Early aspiration for diagnosis and empiric antibiotics are essential to prevent disabling joint destruction. 

Immune thrombocytopenic purpura (ITP) in hemophiliacs with HIV infection and fewer than 50,000/mm³ platelets has been associated with an increase in the frequency of hemorrhages, and bleeding especially in the central nervous system.  In contrast to HIV (+) nonhemophilic subjects with ITP who rarely, if ever, bleed, the enhanced bleeding tendency of HIV (+) hemophiliacs with ITP likely relates to the underlying coagulation defect, hemophilia, and the coexistence of chronic transfusion-induced liver disease.  Prevention and treatment of severe thrombocytopenia is accomplished by the use of AZT (azidothymidine, zidovudine), and if necessary, IVIG to maintain platelets above 50,000/mm³ .

ANTI-VIII INHIBITORS

Anti-VIII inhibitors typically develop in 5 to 10 percent of hemophilia A patients and result in loss of response to standard clotting factor VIII concentrates.  In hemophiliacs with HIV infection, anti-VIII inhibitors, if present, may disappear as immunodeficiency worsens and/or advanced HIV disease progresses.  By frequent, careful screening for the presence of an inhibitor, patients who lose an anti-VIII inhibitor and thereby regain response to infused factor VIII may be identified and treatment resumed with the more dependable factor VIII concentrate. 

In contrast to HIV (+) gay men, in whom there has been a steady increase in HIV-associated lymphomas, there has been no increase in the lymphoma incidence in HIV (+) hemophiliacs.  The initially reported 36-fold increased risk above that in HIV (-) hemophiliacs appears to remain constant.  Lymphomas in hemophilic subjects may present as unusual superficial masses or hematomas, which are refractory to usual factor replacement.  Management requires early suspicion, biopsy, diagnosis, and treatment.  For intrathecal prophylaxis or primary treatment of CNS lymphomas, factor concentrate is crucial to avoid life-threatening bleeding. 

The absence of Kaposi’s sarcoma (KS) in the HIV (+) hemophilic population contrasts sharply with the experience in HIV (+) gay men, in whom KS represents one of the more common AIDS diagnoses.  Several investigators have suggested that various growth factors, cytokines, or viral co-factors may be involved in the development of KS.  

It may well be that differences between hemophilic and homosexual men in the activity and/or level of such “growth factors” or in exposure to viruses or viral “co-factor” may account for the absence of KS in the hemophilia population.  This is an area of intense research. 

Adverse drug reactions (ADR) are very common in the HIV-infected patients, including hemophiliacs.  In the HIV (+) hemophilia population, over half develop ADR, primarily those with advanced HIV infection.  These adverse drug reactions typically occur to more than one drug, most commonly antibiotics, analgesics, and anti-viral drugs.  The frequency and intensity of ADR vary with the severity of immune dysfunction.  ADR may also result from alterations in drug metabolism associated with their chronic transfusion-induced liver disease. 

Finally, individuals with hemophilia fare worse than non-hemophilic subjects in clinical trials of antiretroviral therapy.  This is likely related to their chronic immunosuppression due to chronic transfusion therapy. 

In summary, the manifestations of HIV infection in the hemophilic population may differ from that in non-hemophilic risk groups.  By studying the differences between HIV-infected hemophilic and other non-hemophilic cohorts, and the factors underlying them, we may better understand the pathogenesis of HIV infection.

Copies of the Transfusion Medicine Update can be obtained by contacting Deborah Small at (412) 209-7320 or
by e-mail:  dsmall@itxm.org.