Pathophysiology of HIV related thrombocytopenia: an analysis of 41 patients.

Domínguez, A.; G, Gamallo; Garcı́a, R.; López-Pastor, Andrea R.; Peña, José M.; Vázquez, Juan José

doi:10.1136/jcp.47.11.999

Cited by 30 publications

(27 citation statements)

References 19 publications

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“…Clearance of Ab-coated 5 or immune complex-coated [43][44][45] platelets through Fc␥-mediated endocytosis by phagocytotic cells in the reticular endothelial system may be one of the major mechanisms of immune-mediated platelet depletion in HIV-1-ITP. In particular, the low-affinity Fc␥RIII on macrophages may play an important role in the clearance of autoantibody-platelet immune complexes as shown in a murine model of ATP.…”

Section: Discussionmentioning

confidence: 99%

Identification of talin head domain as an immunodominant epitope of the antiplatelet antibody response in patients with HIV-1-associated thrombocytopenia

Koefoed

Ditzel

2004

Blood

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HIV-1-associated thrombocytopenia (HIV-1-ITP) is a common complication of HIV-1 infection, frequently caused by increased peripheral platelet destruction mediated by antiplatelet antibodies (Abs) and/or platelet-bound immune complexes. Little is known about the specificity of the antiplatelet Abs at a molecular level. Here, we used immunoglobulin G (IgG) phagedisplay libraries generated from 3 HIV-1-ITP patients to isolate a large panel of human monoclonal antiplatelet Abs by selection on unfixed platelets. The platelet antigen recognized by all the cloned Abs was identified to be the talin head domain (talin-H), a cleavage product of talin that can be generated by platelet activation or HIV-1 protease. Talin IntroductionHIV-1-associated thrombocytopenia (HIV-1-ITP) is a common complication of HIV-1 infection 1,2 and sometimes one of the first clinical signs. 3 In individuals where HIV-1-ITP develops in the early stage of HIV-1 infection prior to the development of AIDS, the low platelet counts are often caused by increased peripheral destruction due to sequestration of antibody (Ab)-coated platelets via Fc receptor-or complement-mediated phagocytosis in the spleen 4,5 and/or complementindependent, peroxide-induced, Ab-mediated platelet lysis. 6 Impaired platelet production due to direct effects of HIV-1 infection on megakaryocyte production and platelet release from the bone marrow also plays an important role and is thought to contribute to the platelet depletion in the later stages of HIV-1 infection. Reduction of the viral load by highly active antiretroviral therapy (HART) therapy has reduced the problem of decreased platelet production and lowered the frequency of patients with HIV-1-ITP. 7 Clinically, immune-mediated HIV-1-ITP is indistinguishable from classic autoimmune thrombocytopenia purpura (ATP); however, the characteristics of the Abs involved in the peripheral platelet destruction in HIV-1-ITP are thought to be distinctly different. HIV-1-ITP patients exhibit significantly higher levels of circulating immune complexes (ICs) and platelet-associated immunoglobulin G (IgG), IgM, and complement proteins C3 and C4 than patients with classic ATP. 8 The ICs have been proposed to contain anti-idiotypic Abs, complement factors C3 and C4, and platelet surface membrane fragments, including surface proteins such as the ␤ 3 integrin glycoprotein IIIa (GPIIIa). 6,9 The Ab specificities in the ICs have been reported to include anti-HIV-1 gp120, anti-CD4, anti-GPIb/IX, and anti-GPIIb/GPIIIa, particularly Abs to an immunodominant epitope (amino acids [aa's] 49-66) within GPIIIa. 9,10 However, these reports were based on characterization of whole or affinity-purified serum and since HIV-1 sera generally have elevated levels of polyreactive antibodies of both IgM and IgG subclasses, 11,12 normal serologic analysis can be difficult to interpret. Thus, analysis of the Ab specificities involved in HIV-1-ITP at a molecular level by generating monoclonal Abs is desirable.In this study, we used phage-display repertoire c...

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Section: Discussionmentioning

confidence: 99%

Identification of talin head domain as an immunodominant epitope of the antiplatelet antibody response in patients with HIV-1-associated thrombocytopenia

Koefoed

Ditzel

2004

Blood

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“…This woman was severely immunocompromised and had a low Hb and total WCC both at baseline and 6 weeks after delivery. She was not receiving any ART, in the context of Dominguez et al 's [10] finding that untreated HIV-infected thrombocytopenic individuals had lower platelet turnover than those treated with zidovudine. The TCP in the other 2 women was probably immunemediated HIV-associated TCP, since both had relatively high CD4 counts.…”

Section: Discussionmentioning

confidence: 99%

“…Immunologically competent HIV-infected individuals (as opposed to those who are immunosuppressed) would be expected to produce more antiplatelet antibodies, leading to increased platelet destruction; among 41 HIV-infected individuals with TCP, platelet destruction was more prominent in patients with high CD4 counts. [10] It could be argued that the TCP in the HIV-infected participants (patients 1 -3 in Table 4) that was detected both in the antenatal period and at 6 weeks was also immunologically induced. If that is so, the prevalence of HIVrelated TCP during pregnancy in the present study would be 0.9%, and while low platelet counts occurred mainly among women with CD counts of >200 cells/µL, the TCP was mild.…”

Section: Discussionmentioning

confidence: 99%

“…[8] Individuals with HIVassociated TCP have a clinical presentation and response to therapy similar to that of idiopathic (immune) thrombocytopenic purpura (ITP). [10] Apart from the severity and the time of onset of TCP in pregnant women with ITP (being more severe and occurring in earlier gestation), there is as yet no diagnostic test to differentiate gTCP from ITP, as circulating antibodies may be found in both conditions. [11] There are limited data on the prevalence of gTCP in HIV-infected women.…”

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confidence: 99%

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Thrombocytopenia during pregnancy in women with HIV infection receiving no treatment

Sebitloane

2016

S Afr Med J

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Background. Thrombocytopenia (TCP) complicates 5 -8% of pregnancies. Most cases of TCP are gestational, and the condition is usually mild and occurs in the latter part of pregnancy. Apart from pregnancy-associated medical complications such as pre-eclampsia, HIV infection is a recognised cause of TCP, and a relatively high prevalence of TCP during pregnancy would be expected in a setting with a high antenatal seroprevalence of HIV. Methods. This was a sub-analysis of the data from a prospective trial in which the incidence of postpartum sepsis in HIV-infected women was compared with that in HIV-uninfected women. Women who were considered at low risk and eligible for vaginal delivery were recruited at 36 weeks' gestation, and followed up for 6 weeks after delivery. Full blood counts and CD4 counts of HIV-infected women were obtained at baseline and repeated 6 weeks after delivery. Results. The prevalence of TCP was 5.3% during pregnancy and 1.2% 6 weeks after delivery. The prevalence was similar among HIVinfected (6.0%) and HIV-uninfected women (4.7%) (p=0.292). Among the HIV-infected women, who were not receiving antiretroviral therapy (mean CD4 cell count of 453 cells/µL), there was no significant association between immunosuppression and the severity of TCP. Conclusions. Most of the TCP seen during pregnancy is of the gestational variety, and in this study HIV infection did not increase its prevalence or its severity.

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“…This is probably true for bone marrow sampling, although over the past few years there has been increasing evidence to support the value of this investigation for HIV infected patients, in particular for those who also have fever, haematological malignancy, and thrombocytopenia. [1][2][3][4][5][6][7][8] There are, however, few reports that examine the diagnostic utility of bone marrow (BM) sampling in unselected populations of HIV positive patients and the few studies that are published involve relatively small numbers of patient.490 We have therefore reviewed BM samples taken from HIV infected patients over a period of nine years in order to provide an overall assessment of the diagnostic value of this investigation.…”

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confidence: 99%