HIV Thrombocytopenia

2/23/2005

Question:  What is HIV Thrombocytopenia?

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15774614.ui or 12944242.ui or 11913995.ui or 11604565.ui or 10981487.ui or 8565280.ui or 7892259.ui or 9422122.ui or 8249910.ui or 8329555.ui or 1483592.ui or 1938991.ui

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15774614[PMID] OR 12944242[PMID] OR 11913995[PMID] OR 11604565[PMID] OR 10981487[PMID] OR 8565280[PMID] OR 7892259[PMID] OR 9422122[PMID] OR 8249910[PMID] OR 8329555[PMID] OR 1483592[PMID] OR 1938991[PMID]

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<1>

Unique Identifier [PMID]: 15774614

Authors: Li Z. Nardi MA. Karpatkin S.

Institution: New York University School of Medicine, 550 First Ave, New York, NY 10016, USA.

Title: Role of molecular mimicry to HIV-1 peptides in HIV-1-related immunologic thrombocytopenia.

Source: Blood. 106(2):572-6, 2005 Jul 15.

Abstract: Patients with early HIV-1 infection develop an autoimmune thrombocytopenia in which antibody is directed against an immunodominant epitope of the beta3 (glycoprotein IIIa [GPIIIa]) integrin, GPIIIa49-66. This antibody induces thrombocytopenia by a novel complement-independent mechanism in which platelets are fragmented by antibody-induced generation of H2O2 derived from the interaction of platelet nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and 12-lipoxygenase. To examine whether sharing of epitope between host and parasite may be responsible for this immunodominant epitope, we screened for antibody-reactive peptides capable of inhibiting platelet lysis and oxidation in vitro, using a filamentous phage display 7-mer peptide library. Fourteen of these phage-peptide clones were identified. Five shared close sequence similarity with GPIIIa49-66, as expected. Ten were molecular mimics with close sequence similarity to HIV-1 proteins nef, gag, env, and pol. Seven were synthesized as 10-mers from their known HIV-1 sequence and found to inhibit anti-GPIIIa49-66-induced platelet oxidation/fragmentation in vitro. Three rabbit antibodies raised against these peptides induced platelet oxidation/fragmentation in vitro and thrombocytopenia in vivo when passively transferred into mice. One of the peptides shared a known epitope region with HIV-1 protein nef and was derived from a variant region of the protein. These data provide strong support for molecular mimicry in HIV-1-immunologic thrombocytopenia within polymorphic regions of HIV-1 proteins. A known epitope of nef is particularly incriminated.

Publication Type: Journal Article.

<2>

Unique Identifier [PMID]: 12944242

Authors: Gyongyossy-Issa MI. Bussel JB. Carter CJ. Devine DV.

Institution: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC Canada. missa@unixg.ubc.ca

Title: Comparison of thrombopoiesis during ITP and HIV-ITP and response to intravenous gammaglobulin treatment.

Source: Platelets. 14(5):267-76, 2003 Aug.

Abstract: Immune thrombocytopenic purpura's diagnosis (ITP) is based on low platelet count and exclusion of clinical conditions rather than a specific diagnostic test. We used the reticulated platelet (RP) assay to study ITP and thrombocytopenia associated with HIV infection (HIV-ITP). Data from 96 ITP and 23 HIV-ITP patients showed low platelet counts (PC) with both high or low %RP suggesting that individuals have different degrees of thrombopoiesis. About 20% of ITP and 46% of HIV-ITP patients had %RP in the 'low' or 'normal' ranges. Grouped by platelet count <30x10(9)/L, 24% ITP and 36% HIV-ITP patients had 'low' to 'normal' %RP. The patient population did not show correlation between PC and %RP, but individuals showed an inverse relationship. Within a week of receiving IVIG, 18 ITP and 9 HIV-ITP patients' PC increased, %RP decreased. Patients with %RP measured within 24 h of IVIG treatment had lower %RP than expected, suggesting dilution by an older platelet population. ITP and HIV-ITP patients' responses to i.v. gammaglobulins were similar. Thrombopoietin levels of ITP patients did not correlate with PC, %RP, or RP count. Estimation of thrombopoiesis by RP assay provides useful information for differentiation among thrombocytopenias.

Publication Type: Journal Article.

<3>

Unique Identifier [PMID]: 11913995

Authors: Rosse WF.

Institution: Division of Hematology, Department of Medicine, Duke University Medical Center, Durham, NC 27707, USA. rosse001@mc.duke.edu

Title: Clinical management of adult ITP prior to splenectomy: a perspective. [Review] [12 refs]

Source: Blood Reviews. 16(1):47-9, 2002 Mar.

Abstract: A philosophy of management of adult immune thrombocytopenic purpura (ITP) prior to splenectomy is presented. The initial action is to determine whether the condition is hyperacute, acute, or chronic. In symptomatic cases, initial remission usually requires steroids and the administration of intravenous immunoglobulin (i.v.Ig), followed by platelet transfusion if the patient is actively hemorrhaging. Once initial remission is achieved, a rapid reduction to minimal maintenance therapy should be made. The options include steroids, immunotherapy, and chemotherapy. Adjustments to maintenance therapy must be made with the understanding that response rates vary for each agent. Copyright 2002, Elsevier Science Ltd. All rights reserved. [References: 12]

Publication Type: Journal Article. Review.

<4>

Unique Identifier [PMID]: 11604565

Authors: Leissinger CA.

Institution: Tulane University School of Medicine, Section of Hematology and Medical Oncology, New Orleans, Louisiana 70112-2699, USA. cleissi@tulane.edu

Title: Platelet kinetics in immune thrombocytopenic purpura and human immunodeficiency virus thrombocytopenia. [Review] [42 refs]

Source: Current Opinion in Hematology. 8(5):299-305, 2001 Sep.

Abstract: Platelet kinetics studies are capable of measuring in vivo platelet survival and platelet turnover rates. These studies can be helpful in elucidating mechanisms of thrombocytopenia, particularly in complicated clinical situations. Numerous studies over the past 30 years have established the abnormalities in platelet kinetics associated with immune thrombocytopenic purpura (ITP). It is now well known that many patients infected with HIV type-1 will develop thrombocytopenia, and that at least 10% will develop a thrombocytopenic disorder clinically indistinguishable from immune thrombocytopenic purpura. Platelet kinetics studies in this group of patients may prove of great benefit in understanding the mechanisms underlying thrombocytopenia and in making accurate diagnoses. For all patients with ITP-like disorders, these studies may also prove helpful in understanding and improving current therapies. [References: 42]

Publication Type: Journal Article. Review.

<5>

Unique Identifier [PMID]: 10981487

Authors: Aboulafia DM. Bundow D. Waide S. Bennet C. Kerr D.

Institution: Division of Hematology and Oncology, Virginia Mason Medical Center, Seattle, Washington 98111, USA.

Title: Initial observations on the efficacy of highly active antiretroviral therapy in the treatment of HIV-associated autoimmune thrombocytopenia.

Source: American Journal of the Medical Sciences. 320(2):117-23, 2000 Aug.

Abstract: BACKGROUND: Immune thrombocytopenic purpura (ITP) occurs in as many as 40% of patients infected with the human immunodeficiency virus (HIV). We sought to evaluate the effect of highly active antiretroviral therapy (HAART) on platelet counts in such patients. METHODS: Data collected from 11 homosexual men with HIV-associated ITP and < or = 50 x 10(9) platelets were analyzed after they were placed on HAART. At initial evaluation, 7 patients were antiretroviral naive, 2 were taking zidovudine alone, and 2 were receiving combination antiretroviral therapy for known HIV infection. For 6 patients with <30 x 10(9) platelets, prednisone was initially coadministered with HAART. The primary outcome measure was the platelet count response to HAART, which was measured weekly until counts had normalized on 3 consecutive occasions, then every 3 months while on HAART. Secondary outcome measures were HIV-viral RNA levels and CD4+ cell counts. RESULTS: One month after the initiation of HAART, 10 evaluable patients had an increase in mean platelet count. This improvement was sustained at 6 and 12 months' follow-up for 9 of 10 evaluable patients. Increases in mean platelet count at 6 and 12 months of the 9 responders were statistically significant. The range of follow-up in the 9 responders is 21 to 46 months (median, 30 months), with no thrombocytopenic relapses. The 9 long-term platelet responders have been maintained on HAART and at 12 months had a mean reduction of > 1.5 log10 in HIV viral RNA serum levels and a marked improvement in CD4+ T-lymphocyte cell count. CONCLUSION: HAART seems to be effective in improving platelet counts in the setting of HIV-associated ITP, enhancing CD4+ cell counts, and reducing HIV viral loads.

Publication Type: Journal Article.

<6>

Unique Identifier [PMID]: 8565280

Authors: Bettaieb A. Oksenhendler E. Duedari N. Bierling P.

Institution: Laboratoire d'Immunologie Leuco-Plaquettaire, Centre de Transfusion, Creteil, France.

Title: Cross-reactive antibodies between HIV-gp120 and platelet gpIIIa (CD61) in HIV-related immune thrombocytopenic purpura.

Source: Clinical & Experimental Immunology. 103(1):19-23, 1996 Jan.

Abstract: We have previously demonstrated that immune platelet destruction observed in an AIDS-free HIV-infected patient was associated with the presence of a cross-reactive antibody recognizing both HIV-glycoprotein (gp)120 and platelet gpIIIa (CD61). We have now investigated the presence of such antibodies in other HIV-infected patients, together with the molecular structure of the cross-reactive epitope. Platelet gpIIb/IIIa antibodies were characterized in sera from HIV-infected patients with immune thrombocytopenic purpura by means of an ELISA and a radio-immunoprecipitation procedure (RIP). The platelet antibodies were purified and tested for their ability to recognize HIV-gp. We also tried to characterize the antibody target epitope on HIV-gp120 using recombinant gp and synthetic peptides. IgG with anti-gpIIb/IIIa activity were detected, by means of an ELISA with purified gpIIb/IIIa, in 101/138 (73%) sera from HIV-infected patients with immune thrombocytopenic purpura. The platelet antibodies were purified from 23 sera by absorption/elution on purified immobilized platelet gpIIb/IIIa, and recognition of gpIIIa was confirmed in eight cases with a RIP. Furthermore, the presence of a cross-reactive antibody between HIV-gp120 and platelet gpIIIa was demonstrated in 18/18 patients (including the eight with a confirmed gpIIIa antibody) by the ability of the serum HIV-gp160/120 antibodies to bind to purified gpIIb/IIIa. The cross-reactive epitope was shown to be independent of the carbohydrate moieties of gp120, since deglycosylation of two recombinant (r)-gp120s did not abolish antibody binding. However, the antibody did not recognize synthetic gp120 peptides spanning 355 of the 516 amino acids of gp120, particularly the four regions exhibiting sequences of four or five consecutive amino acids that are identical between r-gp120 and gpIIIa. Our results thus support the hypothesis that the cross-reactive antibody recognizes the conformational structure of gp120. These results strongly suggest that molecular mimicry between HIV-gp120 and platelet gpIIIa may be important in the pathogenesis of immune thrombocytopenia in AIDS-free HIV-infected patients.

Publication Type: Journal Article.

<7>

Unique Identifier [PMID]: 7892259

Authors: Karpatkin S. Nardi MA. Hymes KB.

Institution: Department of Medicine, New York University Medical School, NY 10016.

Title: Sequestration of anti-platelet GPIIIa antibody in rheumatoid factor immune complexes of human immunodeficiency virus 1 thrombocytopenic patients.

Source: Proceedings of the National Academy of Sciences of the United States of America. 92(6):2263-7, 1995 Mar 14.

Abstract: Human immunodeficiency virus 1-related idiopathic thrombocytopenic purpura (HIV-1-ITP) patients have a 4-fold increased percentage of CD5+ B cells and a 4.8-fold increased percentage of serum immune complexes precipitated by polyethylene glycol (PEG-ICs) compared to control subjects, as reported previously. Since CD5+ B cells produce predominantly IgM rheumatoid factor (RF) vs. Fc of IgG and PEG-ICs contain high levels of IgM, we looked for the presence of RF in the immune complexes of HIV-1-ITP patients. PEG-ICs were adsorbed to protein A and dissociated with acid, and IgM and IgG were purified by gel filtration and affinity chromatography. Solid-phase ELISA was used to measure antibody specificity vs. platelets, Fc, and HIV-1 gp120, p24, and CD4. Dissociated IgG antibody reacted with platelets, HIV-1 gp120, p24, and CD4, but not with Fc. Serum IgG did not react with platelets or Fc but did react with HIV-1 gp120, p24, and CD4. Both PEG-IC IgM and serum IgM reacted with Fc as well as the other four antigens. Control IgM and IgG were unreactive. Isolated IgM from PEG-ICs relocated approximately 50% of the IgG preincubated with IgM to the Vo region of a G200 gel-filtration column. Anti-platelet IgG but not IgM could be affinity-purified from fixed platelets. Both F(ab')2 fragments of anti-platelet IgG and the total PEG-IC bound to platelets in a saturation-dependent manner. F(ab')2 of anti-platelet IgG inhibited 50% binding of PEG-IC to platelets at an F(ab')2/complex ratio of 3:1 (wt/wt). Scatchard analysis revealed two classes of binding sites: high-affinity Kd values of 0.8-1.8 nM and lower-affinity Kd values of 6.6-12.3 nM with respective numbers of binding sites of 44,000-57,000 and 122,000-256,000 (n = 4). Anti-platelet IgG of 6/6 patients precipitated GPIIIa from platelet lysates of surface 125I-labeled platelets. Platelet count correlated inversely with anti-platelet IgG (r = -0.73; P < 0.01; n = 27). Thus, PEG-ICs of HIV-1-ITP patients contain IgM RF, which sequesters serum anti-platelet IgG containing anti-GPIIIa. Anti-platelet IgG contributes to binding of immune complexes to platelets and correlates with thrombocytopenia.

Publication Type: Clinical Trial. Controlled Clinical Trial. Journal Article.

<8>

Unique Identifier [PMID]: 9422122

Authors: Kretschmer V. Huss B. Weber S. Bewarder S. Schulzki T. Koppler H. Heimanns J.

Institution: Department of Transfusion Medicine and Hemostaseology, University Hospital, Marburg, Germany.

Title: Determination of bleeding risk in thrombocytopenic patients with platelet transfusion therapy.

Source: Beitrage zur Infusionstherapie und Transfusionsmedizin. 32:434-6, 1994.

Abstract: In a clinical study (50 thrombocytopenic patients) we determined the bleeding risk and the platelet transfusion efficacy by a special modification of the in vitro bleeding test (IVBT, Thrombostat 4000). Additionally, cell count, hematocrit, body temperature, platelet volume and distribution width, Simplate bleeding time and a bleeding score were investigated. The use of the modified IVBT proved to be promising to find a clearer indication of platelet transfusion and to estimate its efficacy.

Publication Type: Journal Article.

<9>

Unique Identifier [PMID]: 8249910

Authors: Marti M. Feliu E. Campo E. Palacin A. Berga L. Casals FJ. Urbano Ispizua A. Cardesa A. Rozman C.

Institution: Departamento de Anatomia Patologica, Hospital Clinic i Provincial, University of Barcelona, Spain.

Title: Comparative study of spleen pathology in drug abusers with thrombocytopenia related to human immunodeficiency virus infection and in patients with idiopathic thrombocytopenic purpura. A morphometric, immunohistochemical, and ultrastructural study.

Source: American Journal of Clinical Pathology. 100(6):633-42, 1993 Dec.

Abstract: A morphometric and immunohistochemical study was performed to assess the spleen's alterations in patients with autoimmune thrombocytopenia and in drug abusers with thrombocytopenia (DAT) related to human immunodeficiency virus (HIV) infection. A total of 34 patients were included in the study: 20 DAT patients and 14 with idiopathic thrombocytopenic purpura (ITP). Twenty HIV-negative splenectomy patients without thrombocytopenia were included as controls. Spleen weight in DAT patients (323.25 +/- 149.96 g, mean + standard deviation) was significantly increased compared with the ITP (164.28 +/- 29.79 g, P < 0.0001) and control (175.50 +/- 49.14 g, P < 0.0001) groups. The mean diameter of lymphoid follicles in the spleens of DAT patients (446.83 +/- 99.16 microns, was significantly higher than in those of the control patients (370.87 +/- 55.30 microns, P = 0.019). In control patients' spleens, the number of platelets in Billroth's cords was significantly higher (59.54 +/- 32.72/10(4) microns 2) than in those of the DAT (2.13 +/- 1.42/10(4) microns 2, P < 0.0001) and ITP (P < 0.0001) patients. The number of macrophages and ceroid histiocytes per 10(4) microns 2 of red pulp was significantly increased in both DAT (5.14 +/- 1.90) and ITP (7.48 +/- 4.38) patients compared with the control patients (3.66 +/- 1.10, P < 0.0001) and P = 0.06, respectively), and in ITP patients compared with DAT patients (P = 0.0136). The number of granulopoietic precursors per 10(4) microns 2 of red pulp was higher in the spleens of DAT (1.41 +2- 1.46, P < 0.0001) and ITP (0.92 +/- 0.75, P < 0.0001) patients compared with those of the control group. Transmission electron microscopy studies demonstrated platelet phagocytosis by macrophages of Billroth's cords and presence of myeloid metaplasia in spleens of DAT and ITP patients. Immunohistochemical studies showed a depletion of CD4+ lymphocytes in the T zone of splenic white pulp and an increased number of CD8+ lymphocytes in red pulp of DAT patients' spleens compared with those of ITP and control patients. There were no significant alterations in dendritic reticular cell network in the DAT group compared with the ITP and control groups.

Publication Type: Journal Article.

<10>

Unique Identifier [PMID]: 8329555

Authors: Fabris F. Sgarabotto D. Zanon E. Francavilla F. Zaggia F. Cadrobbi P. Girolami A.

Institution: Fourth Chair of Internal Medicine, University of Padua Medical School, Italy.

Title: The effect of a single course of alpha-2B-interferon in patients with HIV-related and chronic idiopathic immune thrombocytopenia.

Source: Autoimmunity. 14(3):175-9, 1993.

Abstract: 13 patients with HIV-related immune thrombocytopenia (HIV-ITP) and 10 patients with chronic idiopathic thrombocytopenic purpura (C-ITP) were treated with a single course of alpha-2b-Interferon (IFN 3 x 10(6) IU subcutaneously for 12 d). The patients had platelet counts lower than 40 x 10(9)/L and thrombocytopenia persisting for over 1 year (range 1-22 years); 7 patients were refractory to previous conventional therapy, 5 were responsive, and 11 had not been previously treated. The response to IFN was complete in 8 patients (platelets > 100 x 10(9)/L), partial in 7 (platelets 50-100 x 10(9)/L); 8 patients showed no response. The treatment with IFN was stopped after 4 d in one patient due to a fall in platelet count. The maximal platelet count (median peak 116 +/- 55 SD x 10(9)/L platelets) was obtained after 13.7 +/- 2.98 d and the improvement in platelet count was maintained for 22.8 +/- 8.6 d. No difference in platelets response was observed between HIV-ITP and C-ITP. The response to IFN seems to be related to the one obtained with previous treatments. Indeed 80% of the patients who were responsive to previous steroids, high dose immunoglobulins or azidothymidine (HIV-ITP) showed a complete or partial response while only 43% of the refractory patients showed a partial response; the positive response rate in previously untreated patients was 73%.

Publication Type: Journal Article.

<11>

Unique Identifier [PMID]: 1483592

Authors: Stellini R. Rossi G. Paraninfo G.

Institution: I Divisione di Malattie Infettive, Spedali Civili di Brescia, Italy.

Title: Interferon therapy in intravenous drug users with HIV-associated idiopathic thrombocytopenic purpura.

Source: Haematologica. 77(5):418-20, 1992 Sep-Oct.

Abstract: BACKGROUND. There is no generally accepted treatment for human immunodeficiency virus (HIV)--associated idiopathic thrombocytopenic purpura (ITP). recombinant alpha interferon (rIFN) has been used in classic ITP with conflicting results. We have tested its activity in a group of intravenous drug users (IVDUs) with HIV-associated ITP, who also had a high prevalence of chronic liver disease. METHODS. Nine patients were treated with a short course of rIFN-2b (3 MU s.c. three times a week for four weeks), and their hematological and biochemical parameters were monitored before (t0), at the end (t1), and one month after discontinuation of rIFN therapy (t2). RESULTS. Platelet counts increased significantly from 15.9 +/- 7.3 x 10(9)/L at t0 up to 67.0 +/- 38.8 x 10S(9)/L at t1 (p < 0.005), but returned to 24.7 +/- 12.7 x 10(9)/L at t2 (t1 vs t2: p < 0.005). The other parameters did not change, with the exception of the alanine aminotransferase levels, which decreased from 105 IU/L at t0 to 42 IU/L at t1 (p < 0.05). CONCLUSIONS. A short course of rIFN is an effective treatment for HIV-associated ITP in IVDUs and may also be beneficial for the frequently concomitant chronic liver disease. Since the efficacy of rIFN on the platelet count is short-lived, long-term rIFN administration would be worth testing.

Publication Type: Journal Article.

<12>

Unique Identifier [PMID]: 1938991

Authors: Stricker RB.

Institution: Department of Medicine, Children's Hospital of San Francisco, California.

Title: Hematologic aspects of HIV disease: diagnostic and therapeutic considerations. [Review] [20 refs]

Source: Journal of Clinical Apheresis. 6(2):106-9, 1991.

Publication Type: Journal Article. Review.