Elevated Levels Of Platelet-associated IgG Research Articles

Post-renal acute kidney injury complicated by urinary tract obstruction due to massive blood clots and severe thrombocytopenia in a patient with systemic lupus erythematosus: A case report.

Systemic lupus erythematosus (SLE) is often seen with antiphospholipid antibody syndrome (APS), and these conditions may occur concurrently with severe immune thrombocytopenia and even acute kidney injury (AKI); however, post-renal AKI due to bleeding is uncommon. Here, we describe a case of post-renal AKI and anuria in a patient with SLE and APS, which were attributable to urinary tract obstruction due to massive blood clots caused by secondary immune thrombocytopenia. A 50-year-old Japanese woman was admitted to our hospital with anuria, abdominal tenderness, purpura in the trunk and in both legs, and severe thrombocytopenia. She had been receiving medical treatment for APS and SLE till the age of 45 years. Computed tomography revealed a blood clot without extravasation in both urinary tracts and she was diagnosed with post-renal AKI due to complete obstruction of the urinary system. Additionally, based on her medical history, elevated platelet-associated IgG levels, and increased megakaryocyte count, she was diagnosed with secondary immune thrombocytopenia complicated by SLE and APS. She also had elevated APS-related autoantibodies, including antiphosphatidylserine/prothrombin IgM, and IgG. However, concomitant serositis such as lupus enteritis or cystitis was not seen. She was treated with a combination of glucocorticoids, intravenous immunoglobulin, and continuous hemodialysis/hemofiltration, which resulted in rapid improvement of her symptoms and renal dysfunction. Secondary immune thrombocytopenia-induced massive bleeding of urinary tract can cause post-renal AKI. Appropriate diagnosis and aggressive treatment are necessary to improve prognosis in such patients.

Platelet associated IgG and immune thrombocytopenia in lymphoproliferative and autoimmune disorders.

Thrombocytopenia is frequently encountered in patients with lymphoproliferative disorders (LPD) and systemic erythromatosus (SLE) and to a lesser extent in association with other diseases such as rheumatoid arthritis (RA), pernicious anaemia (PA) and autoimmune haemolytic anaemia (AIHA). This report attempts to document the incidence of thrombocytopenia in these disorders, other than that overtly due to malignant infiltration or marrow suppression by drugs and to demonstrate, that in a significant proportion antibody mediated immune destruction of platelets can be confirmed by positive platelet antibody tests. Platelet associated IgG (PAIgG) was measured in all patients by a quantitative enzyme linked assay. Platelet antibodies were found in 11 of 24 (46%) thrombocytopenic patients with LPD, 10 of 16 (62%) patients with SLE and thrombocytopenia, and in all patients with RA and PA who had low platelet counts at the time of study. In addition, elevated PAIgG levels were found in the following non-thrombocytopenic patients: 9 of 43 (21%) patients with LPD, 2 of 12 (17%) with SLE, 2 of 12 (17%) with AIHA, 2 of 39 (5%) with PA and 5 of 61 (8%) patients with RA. The nature and the role of raised PAIgG levels in diseases other than autoimmune thrombocytopenia is controversial. Our reasons for interpreting these as true platelet autoantibodies in this selected group of disorders and the clinical implications of our results are discussed.

Acute myelogenous leukemia with multilineage myelodysplasia, positive direct Coombs test, and elevated levels of platelet-associated IgG

Acute myelogenous leukemia with multilineage myelodysplasia, positive direct Coombs test, and elevated levels of platelet-associated IgG

Immune Thrombocytopenic Purpura Associated with Pulmonary Tuberculosis

A 22-year-old woman was admitted into our hospital because of generalized purpura and abnormalities in her chest X-ray. Isolated thrombocytopenia and elevated platelet-associated IgG levels were detected, while the bone marrow examination was normal. Mycobacterium tuberculosis was detected in the bronchoalveolar lavage fluid, and consequently she was diagnosed as having active tuberculosis. High-dose immunoglobulin therapy combined with anti-tuberculosis drugs not only rapidly and continuously corrected thrombocytopenia but also cured pulmonary tuberculosis. This case suggests a causal association between immune thrombocytopenia and tuberculosis as well as the safety and efficacy of the anti-tuberculosis drugs combined with high-dose immunoglobulin therapy.

An evaluation of intravenous immunoglobulin in the treatment of human immunodeficiency virus‐associated thrombocytopenia

Anecdotal evidence suggests that high-dose intravenous immunoglobulin (IVIG) is useful in the management of human immunodeficiency virus (HIV)-associated thrombocytopenia. To rigorously evaluate this therapy, a crossover study was designed to compare IVIG, given at 1 g per kg per day for 2 consecutive days each week for 4 weeks, with intravenous saline placebo administered according to the same schedule. Subjects were randomly assigned to receive either IVIG or saline during the first 4 weeks; if IVIG was given, there was a 4-week period of no therapy before beginning placebo administration. Criteria for eligibility were platelet count of less than 50,000 per microL (50 x 10(9)/L), elevated platelet-associated IgG levels, increased megakaryocytes in the bone marrow, and positive HIV antibody test. Twelve patients (11 men, 1 woman) were studied. Seven patients completed the full protocol. Four dropped out: after 2, 5 (2 patients), and 8 weeks that included at least 2 weeks of IVIG. All patients sustained an increase in platelet count in response to IVIG, with increments ranging from 15,000 to 358,000 per microL (15 to 350 x 10(9)/L) (mean, 180,000/microL [180 x 10(9)/L]; median, 174,000/microL [174 x 10(9)/L]). No patient had an increase after placebo infusions. There were no adverse effects of treatment, and weekly chemical analyses showed no new abnormalities except for mild elevations in the serum protein. The duration of responses ranged from 2 to 10 weeks. No patient demonstrated refractoriness to IVIG. IVIG consistently raises platelet counts in patients with HIV-associated thrombocytopenia.

Treatment of septic thrombocytopenia with immune globulin

Thrombocytopenia frequently complicates systemic infection and results from multiple possible mechanisms. We and others have demonstrated that platelet-associated IgG (PAIgG) levels are elevated in the majority of patients with septic thrombocytopenia. Corticosteroids may be undesirable as a treatment for thrombocytopenia for patients with severe infection because of their potential for suppressing the immune response. We hypothesized that septic thrombocytopenia is, in most cases, an immune disorder analogous to idiopathic thrombocytopenic purpura (ITP) which might respond to intravenous gamma-globulin as a treatment for increasing the platelet count in this disorder. Intravenous immune globulin (IVIG), 400 mg/kg daily for 3 days, was administered in a randomized double-blind placebo-controlled trial. Twenty-nine patients who developed thrombocytopenia during a documented, septic episode were studied. Patients with disseminated intravascular coagulation (DIC), hypersplenism, or drugs known to cause thrombocytopenia were excluded. Elevated PAIgG levels were documented in 52% of evaluable patients. Mean platelet counts in the IVIG group rose from 43K at study entry to 178K (411% rise) by Day 9. In the placebo group platelets rose from 51K to 125K (261% rise; P = 0.02). Seventy-seven percent of the IVIG group had a minimum peak rise of 35K, vs 56% of the placebo group. Three patients in the placebo group had a serious bleeding episode, vs one in the IVIG group. The use of IVIG to treat septic thrombocytopenia not associated with DIC leads to a more rapid, more sustained, and greater increase in platelet count than placebo. Its use is recommended in the septic patient who is bleeding or is likely to need invasive or surgical procedures.

Platelet-Associated IgG in Pediatric HIV Infection

Hematologic abnormalities, including thrombocytopenia, are seen in HIV infection. We have previously reported elevated platelet-associated IgG (PAIgG) in thrombocytopenia in children associated with human immunodeficiency virus (HIV). In this study we prospectively monitored 40 HIV-infected infants and children to determine the significance of elevated PAIgG levels as they relate to thrombocytopenia. We also examined platelet eluates for the presence of HIV antibody and antigen. Of 16 patients with thrombocytopenia, 15 (93.7%) had elevated PAIgG. Of 24 patients with normal platelet counts, 21 (87.5%) had elevated PAIgG. On follow-up, none of the children with normal platelet counts and elevated PAIgG levels developed thrombocytopenia. Examination of the platelet eluates was negative for HIV antibody or P24 antigen. Although the sensitivity of an elevated PAIgG level in predicting thrombocytopenia is 93%, its specificity is only 13%. Elevated PAIgG levels are therefore not causally related to the development of thrombocytopenia in children.

In Reply: Thrombocytopenia and Pediatric Patients With AIDS

Based upon newly analyzed data, we agree with Dr Weinblatt's well-made point that HIV disease cannot be solely attributed to autoimmune destruction on the basis of elevated levels of platelet-associated IgG. In a recent prospective study of 38 infants and children with HIV infection monitored for as many as 9 years, we demonstrated that, using elevated platelet-associated IgG levels to detect AIDS thrombocytopenia, the sensitivity is 93% but the specificity is 13%. However, when combined with the finding of large circulating platelets as measured by increased mean platelet volume, the specificity is increased to 90%.

A chloroquine elution technique for platelet serology.

The authors describe a prototype elution method employing chloroquine, a quinoline derivative, to elute IgG antibodies from the platelet surface. This chloroquine elution technique is relatively easy to perform and is effective in the removal of alloantibodies from the platelet surface. Eluted alloantibody was immunologically active once the chloroquine was removed from the eluate. The major advantage of this technique is that serologic testing of platelets after elution is possible, as 50 percent of the platelets remain after exposure to hypertonic acid chloroquine solution. Antigens on the platelet surface maintained their antigenicity subsequent to treatment, although measurable reductions in PIA1 reactivity occur. The elution technique was also successful in removing IgG from the platelet surface in patients with diseases involving elevated levels of platelet-associated IgG.

Elevated Levels of PA IgG in Thrombocytopenic Patients Are Not Related to the Presence of Microthrombocytes or Megathrombocytes

Platelet-associated (PA) IgG levels were measured on peripheral blood samples from 63 thrombocytopenic patients with the use of fluorescein isothiocyanate (FITC)-conjugated anti-IgG antibody. Test specificity was investigated by examining the influence of variables such as the platelet count in platelet-rich plasma (PRP), platelet loss after the assay procedure, and platelet size distribution (including the percentage of microthrombocytes and megathrombocytes) on the PA IgG levels. Additionally, PA IgG levels were compared with PA albumin levels and with levels of nonspecific adherence of FITC anti-IgG by the platelets to ascertain if elevated levels were specific. Elevated PA IgG levels showed only significant correlations (P less than 0.05) with a mean platelet size below normal range and to increased PA albumin levels but not to PRP count, platelet loss after assay procedure, the percentage of microthrombocytes and megathrombocytes, and nonspecific adherence of FITC anti-IgG.

111In-Oxine Platelet Survivals in Thrombocytopenic Infants

Thrombocytopenia is a common occurrence (20%) in sick neonates, but the causes have not been well studied. In this report we demonstrate that thrombocytopenia in the neonate is characterized by increased platelet destruction as shown by shortened homologous 111In-oxine-labeled platelet life spans. Thirty-one prospectively studied thrombocytopenic neonates were investigated by measuring the 111In-labeled platelet life span, platelet-associated IgG (PAIgG), and coagulation screening tests. In every infant, the thrombocytopenia was shown to have a destructive component since the mean platelet life span was significantly shortened to 65 +/- 6 (mean +/- SEM) hours with a range of one to 128 hours compared with adult values (212 +/- 8; range, 140 to 260; gamma function analysis). The platelet survival was directly related to the lowest platelet count and inversely related to both the highest mean platelet volume and duration of the thrombocytopenia. In 22 infants the percent recovery of the radiolabeled platelets was less than 50%, which suggested that increased sequestration also contributed to the thrombocytopenia. Infants with laboratory evidence of disseminated intravascular coagulation (n = 8) or immune platelet destruction evidenced by elevated levels of PAIgG (n = 13) had even shorter platelet survivals and a more severe thrombocytopenia compared with the ten infants in whom an underlying cause for the thrombocytopenia was not apparent. Full-body scintigraphic images obtained in 11 infants showed an increased uptake in the spleen and liver, with a spleen-to-liver ratio of 3:1. This study indicates that thrombocytopenia in sick neonates is primarily destructive, with a subgroup having evidence of increased platelet sequestration.

111In-oxine platelet survivals in thrombocytopenic infants

Thrombocytopenia is a common occurrence (20%) in sick neonates, but the causes have not been well studied. In this report we demonstrate that thrombocytopenia in the neonate is characterized by increased platelet destruction as shown by shortened homologous 111In-oxine-labeled platelet life spans. Thirty-one prospectively studied thrombocytopenic neonates were investigated by measuring the 111In-labeled platelet life span, platelet-associated IgG (PAIgG), and coagulation screening tests. In every infant, the thrombocytopenia was shown to have a destructive component since the mean platelet life span was significantly shortened to 65 +/- 6 (mean +/- SEM) hours with a range of one to 128 hours compared with adult values (212 +/- 8; range, 140 to 260; gamma function analysis). The platelet survival was directly related to the lowest platelet count and inversely related to both the highest mean platelet volume and duration of the thrombocytopenia. In 22 infants the percent recovery of the radiolabeled platelets was less than 50%, which suggested that increased sequestration also contributed to the thrombocytopenia. Infants with laboratory evidence of disseminated intravascular coagulation (n = 8) or immune platelet destruction evidenced by elevated levels of PAIgG (n = 13) had even shorter platelet survivals and a more severe thrombocytopenia compared with the ten infants in whom an underlying cause for the thrombocytopenia was not apparent. Full-body scintigraphic images obtained in 11 infants showed an increased uptake in the spleen and liver, with a spleen-to- liver ratio of 3:1. This study indicates that thrombocytopenia in sick neonates is primarily destructive, with a subgroup having evidence of increased platelet sequestration.

The relationship among platelet-associated IgG, platelet lifespan, and reticuloendothelial cell function

Platelet-associated IgG (PAIgG) has been reported to be elevated in nonthrombocytopenic patients who have a normal platelet lifespan. This has been interpreted as indicating that PAIgG is a nonspecific finding in these patients and not a determinant of platelet survival. It is important to recognize that the reticuloendothelial (RE) system plays an important role in the clearance of antibody-sensitized cells. In this study, we related the level of PAIgG and the platelet lifespan to the RE function in patients with: (A) idiopathic thrombocytopenic purpura (ITP), and (B) five patients with elevated levels of PAIgG yet normal or near-normal platelet counts. RE function was assessed by measuring the clearance of autologous chromium-labeled red cells sensitized with a precise amount of alloantibody (2,000–3,600 molecules of IgG/cell). Eight patients with immune thrombocytopenia had significantly shortened platelet survivals (less than 2–113 hr). In contrast, the five patients with elevated PAIgG, yet normal or near- normal platelet counts, all had normal autologous platelet survivals (186–222 hr). These patients also had significantly impaired clearance of IgG-sensitized red cells, with an average of 85% of the infused red cells remaining in the circulation at 60 min (normal 42% +/- 14%, n = 10). In this study, every patient with elevated PAIgG and normal RE function had a shortened platelet lifespan. Those patients with elevated PAIgG and impaired RE function did not invariably have a shortened platelet lifespan. The observation that the PAIgG is elevated in some patients whose platelet survival is normal does not indicate that PAIgG is not biologically relevant. It indicates that these patients may have RE blockade and do not clear IgG-sensitized cells.

The Relationship Among Platelet-Associated IgG, Platelet Lifespan, and Reticuloendothelial Cell Function

Platelet-associated IgG (PAIgG) has been reported to be elevated in nonthrombocytopenic patients who have a normal platelet lifespan. This has been interpreted as indicating that PAIgG is a nonspecific finding in these patients and not a determinant of platelet survival. It is important to recognize that the reticuloendothelial (RE) system plays an important role in the clearance of antibody-sensitized cells. In this study, we related the level of PAIgG and the platelet lifespan to the RE function in patients with: (A) idiopathic thrombocytopenic purpura (ITP), and (B) five patients with elevated levels of PAIgG yet normal or near-normal platelet counts. RE function was assessed by measuring the clearance of autologous chromium-labeled red cells sensitized with a precise amount of alloantibody (2,000-3,600 molecules of IgG/cell). Eight patients with immune thrombocytopenia had significantly shortened platelet survivals (less than 2-113 hr). In contrast, the five patients with elevated PAIgG, yet normal or near-normal platelet counts, all had normal autologous platelet survivals (186-222 hr). These patients also had significantly impaired clearance of IgG-sensitized red cells, with an average of 85% of the infused red cells remaining in the circulation at 60 min (normal 42% +/- 14%, n = 10). In this study, every patient with elevated PAIgG and normal RE function had a shortened platelet lifespan. Those patients with elevated PAIgG and impaired RE function did not invariably have a shortened platelet lifespan. The observation that the PAIgG is elevated in some patients whose platelet survival is normal does not indicate that PAIgG is not biologically relevant. It indicates that these patients may have RE blockade and do not clear IgG-sensitized cells.

Platelet-associated IgG and IgM in myelofibrosis.

Elevated levels of platelet-associated IgG and/or IgM were found in 15 of 18 patients with myelofibrosis (83%). All but 5 patients with elevated PAIg had active disease. The amounts of PAIg were not correlated to either S-Ig, platelet count or spleen size. Levels of PAIgG well above the normal range were especially found in patients with short duration of disease and/or a transitional myeloproliferative state. It is debated whether immune-mediated platelet dysfunction may be of importance for the development of bone marrow fibrosis, mediated by the release of platelet-derived growth factors in the bone marrow. Elevated PAIg may also contribute to abnormal haemostasis and thrombocytopenia in myelofibrosis.

Platelet-associated IgG in patients with lymphoma

Levels of platelet-associated IgG (PA-IgG) were studied in 72 patients with Hodgkin's (HD) and non-Hodgkin's lymphoma (NHL). Thirty-nine percent of patients with HD and 20% of patients with NHL had elevated PA-IgG levels. There was a positive correlation between disease activity and the presence of PA-IgG in HD and NHL. In patients with HD, PA-IgG strongly correlated with extent of disease and may serve as a marker of disease activity. PA-IgG may have facilitated platelet destruction in 5 of 11 thrombocytopenic patients with HD and increased PA-IgG and in 2 patients with HD and increased PA-IgG who developed severe thrombocytopenia when treated with chemotherapy.

Platelet-Associated IgG in Patients With Lymphoma

AbstractLevels of platelet-associated IgG (PA-IgG) were studied in 72 patients with Hodgkin's (HD) and non-Hodgkin's lymphoma (NHL). Thirty-nine percent of patients with HD and 20% of patients with NHL had elevated PA-IgG levels. There was a positive correlation between disease activity and the presence of PA-IgG in HD and NHL. In patients with HD, PA-IgG strongly correlated with extent of disease and may serve as a marker of disease activity. PA-IgG may have facilitated platelet destruction in 5 of 11 thrombocytopenic patients with HD and increased PA-IgG and in 2 patients with HD and increased PA-IgG who developed severe thrombocytopenia when treated with chemotherapy.

Acute idiopathic thrombocytopenic purpura in children.

Acute idiopathic thrombocytopenic purpura (ITP) characteristically follows a viral illness in preschool children. The exact role of viruses in the pathogenesis of this disorder remains uncertain, but the finding of markedly elevated levels of platelet-associated IgG serves to distinguish it from the chronic form of the disease and permits speculation on the mechanisms of platelet destruction. Although the spleen is important in both antibody production and platelet destruction, bone marrow synthesis of IgG has also been shown to be increased. The clinical course may be alarming, but mortality is low and prognosis excellent. Controversy has surrounded the role of steroids in the management of acute childhood ITP in retrospective studies. Controlled studies, however, indicate that thrombocytopenia is reversed sooner in treated patients. New assays for platelet-associated IgG offer new insights into this disorder and will allow delineation of acute and chronic disease at the time of diagnosis.

Platelet-associated IgG in immune thrombocytopenic purpura

A method for the measurement of immunoglobulin G associated with gel- filtered platelets is described and finding in 70 control subjects and 37 patients with immune thrombocytopenic purpura (ITP) are reported. Control platelet-associated IgG (PAIgG) levels (nanograms IgG per 10(9) platelets) averaged (+/-SD) 1231+/-424; samples studied after 24 and 48 hr remained within the control range. PAIgG values of 19 adult and 12 childhood patients with chronic ITP averaged 4711+/-3025 and 4923+/- 3955, respectively, and differed significantly from controls (p less than 0.001). There was an inverse correlation between PAIgG values and the chronic ITP patient's platelet count. Six patients with childhood acute ITP had PAIgG levels ranging from 5588 to 56,250 and appeared to represent a different statistical population from those with chronic ITP. In chronic ITP patients responding to splenectomy, there was an immediate normalization of PAIgG levels; however, a certain percentage of patients studied several months after splenectomy evidenced elevated PAIgG levels in association with normal platelet counts. These data showed that the direct measurement of platelet associated antibody is a useful technique in the diagnosis and follow-up of patients with chronic ITP. Preliminary studies in patients with acute ITP have suggested that this method may be useful in differentiating acute and chronic childhood ITP.

Platelet-associated IgG in Immune Thrombocytopenic Purpura

A method for the measurement of immunoglobulin G associated with gel-filtered platelets is described and finding in 70 control subjects and 37 patients with immune thrombocytopenic purpura (ITP) are reported. Control platelet-associated IgG (PAIgG) levels (nanograms IgG per 10(9) platelets) averaged (+/-SD) 1231+/-424; samples studied after 24 and 48 hr remained within the control range. PAIgG values of 19 adult and 12 childhood patients with chronic ITP averaged 4711+/-3025 and 4923+/-3955, respectively, and differed significantly from controls (p less than 0.001). There was an inverse correlation between PAIgG values and the chronic ITP patient's platelet count. Six patients with childhood acute ITP had PAIgG levels ranging from 5588 to 56,250 and appeared to represent a different statistical population from those with chronic ITP. In chronic ITP patients responding to splenectomy, there was an immediate normalization of PAIgG levels; however, a certain percentage of patients studied several months after splenectomy evidenced elevated PAIgG levels in association with normal platelet counts. These data showed that the direct measurement of platelet associated antibody is a useful technique in the diagnosis and follow-up of patients with chronic ITP. Preliminary studies in patients with acute ITP have suggested that this method may be useful in differentiating acute and chronic childhood ITP.