by Lee Shun Keung. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1988. / Bibliography: leaves 73-91.

206 leaves : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (M.D.)--Dept. of Medicine, University of Adelaide, 1974

Thesis (Ph. D.)--University of New South Wales, 1999. / Also available online.

A patient had spurious thrombocytopenia resulting from a mechanism not previously described. Whereas in prior reports the in vitro phenomenon of platelet clumping has been effected by either EDTA‐dependent or temperature‐dependent antibodies capable of direct platelet agglutination, neither the IgG nor the IgM fractions of this patient's serum demonstrated such activity. However, agglutination was produced by incubating allogeneic platelets with the IgG fraction followed by a room temperature incubation with the rheumatoid factor‐positive IgM fraction. The data support a new mechanism for spurious thrombocytopenia resulting from the interaction of a cold‐reactive rheumatoid factor with antiplatelet antibody.

Rheumatoid Arthritis (RA) is an autoimmune disease characterized by inflammation and eventual destruction of the synovial joints. The role of platelets in the pathophysiology of arthritis has only recently been established. Because antibodies to CD44 can deplete platelets, we hypothesized that these antibodies might be effective in arthritis through a platelet-depletion mechanism. We examined the K/BxN passive transfer mouse model of arthritis and found that most antibodies against CD44 were capable of depleting platelets. However, anti-CD44 treatment is effective when administered during developing arthritis, while anti-platelet treatment was not. While CD44 antibodies may be therapeutic through platelet-dependant and independent mechanisms, the ability of CD44 antibodies to decrease platelet counts does not seem to be the critical factor in resolving arthritis in the K/BxN model.

Rheumatoid Arthritis (RA) is an autoimmune disease characterized by inflammation and eventual destruction of the synovial joints. The role of platelets in the pathophysiology of arthritis has only recently been established. Because antibodies to CD44 can deplete platelets, we hypothesized that these antibodies might be effective in arthritis through a platelet-depletion mechanism. We examined the K/BxN passive transfer mouse model of arthritis and found that most antibodies against CD44 were capable of depleting platelets. However, anti-CD44 treatment is effective when administered during developing arthritis, while anti-platelet treatment was not. While CD44 antibodies may be therapeutic through platelet-dependant and independent mechanisms, the ability of CD44 antibodies to decrease platelet counts does not seem to be the critical factor in resolving arthritis in the K/BxN model.

We report here the first case of severe Immune thrombocytopenia induced by a secondgeneration cephalosporin antibiotic, Loracarbef. A 56-year old white female developed acute severe thrombocytopenia associated with acute respiratory symptoms following administration of Loracarbef. She responded to Loracarbef withdrawal and systemic corticosteroid administration. Loracarbef-dependent platelet-reactive antibodies were demonstrable in her serum by flow cytometry.

Cytomegalovirus (CMV) is the most common congenitally acquired infection. It is of major concern due to the long-term neurodevelopmental morbidity in both symptomatic and asymptomatic newborns. While CMV infection is less commonly diagnosed in infancy to adulthood, mostly due to its asymptomatic presentation, it is still an important differential to consider. A missed diagnosis could lead to visual impairments and neurological complications. Infants can acquire CMV by encountering bodily secretions from those who have an active infection. Symptoms of infection include fever, fatigue, pharyngitis, and hepatitis. Laboratory abnormalities include thrombocytopenia, elevated transaminases, and abnormal lymphocyte count. We investigated a clinical case of a previously healthy 5-month-old whose only symptoms were petechial rash and thrombocytopenia. They presented to the ED with a worsening petechial rash for 11 days. The patient’s mother had prenatal care and an uncomplicated pregnancy. In the ED IgM for CMV was positive and platelet count on admission was 35K. The patient was discharged without intervention because platelet count remained above 20K. Outpatient hematology workup ruled out other potential causes of thrombocytopenia. There is no family history of bleeding disorders. The patient was prescribed valganciclovir for 2 months and urine CMV PCR was ordered for the patient and the patient’s mother. The patient’s urine CMV was positive, but the mother’s urine CMV was negative. The patient’s petechiae and thrombocytopenia improved while on valganciclovir treatment. In this case, since the patient’s mother was negative for CMV, it is unlikely that the infection was maternally acquired. Our case illustrates that CMV infection in infancy can be acquired through horizontal transmission and its only presentation can be thrombocytopenia. Since the CMV infection was diagnosed early the patient did not have any neurological symptoms, such as sensorineural hearing loss or delayed developmental milestones.

No description available.

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder characterized by a low platelet count (less than 100 x 10^9 platelets/L) and an increased risk of bleeding. ITP is difficult to diagnose and manage due to the deficiencies in our understanding of the pathophysiological mechanisms leading to thrombocytopenia. Anti-platelet autoantibodies are believed to be the primary mechanism of thrombocytopenia in ITP. In this thesis, I demonstrate that autoantibodies can only be detected in half of all ITP patients; therefore, other mechanisms should be investigated. CD8+ T cells have been implicated as a mechanism of disease in ITP, but platelet-specific CD8+ T cells have yet to be identified. I have characterized CD8+ T cells in ITP patients and found that platelet-specific CD8+ T cells can be detected in ITP patients. These platelet-specific CD8+ T cells can also be detected in healthy individuals, so they are not specific to ITP. However, regulatory defects were observed in ITP patients and CD8+ T cell activity was elevated in ITP patients relative to healthy individuals and thrombocytopenic non-ITP patients. Investigating whether platelet-specific CD8+ T cells can actively participate in platelet destruction and underproduction will be an essential step towards better understanding the role of CD8+ T cells as a disease mechanism in ITP, which will lead to improvements in the management of ITP. / Thesis / Doctor of Philosophy (PhD) / Platelets are small blood cells that are involved in minimizing blood loss at the site of a wound by forming a plug. In a disease called immune thrombocytopenia (ITP), patients have a low platelet count, which can result in bleeding. The bleeding symptoms of ITP decrease the quality of life for ITP patients and can be life-threatening in rare cases. It is believed that ITP is caused by proteins produced by the immune system called antibodies. I found that the antibodies that cause ITP can only be detected in half of all ITP patients. Therefore, there are probably additional causes of ITP. It is suspected that CD8+ T cells might cause ITP in some patients. CD8+ T cells are part of the immune system and they typically destroy other cells that are cancerous or infected by viruses. CD8+ T cells might also destroy healthy cells, like platelets. My goal was to characterize CD8+ T cells in order to determine their role in ITP. I found that CD8+ T cells from ITP patients can target platelets, and that healthy people have these CD8+ T cells as well. In regard to CD8+ T cells that target platelets, the difference between ITP patients and healthy people appears to be related to immune system regulation and CD8+ T cell activity. In the future, we should focus on understanding how platelet-specific CD8+ T cells can cause a low platelet count in order to improve the clinical management of ITP.