Measurement of platelet-associated IgG in animal models of immune and nonimmune thrombocytopenia.

Platelet-associated IgG (PAIgG) is elevated in idiopathic thrombocytopenic purpura (ITP), but it also is elevated in other thrombocytopenic disorders traditionally considered to be nonimmune. Consequently it is possible that elevated PAIgG is a nonspecific finding secondary to thrombocytopenia. To study this issue we developed a rabbit model of immune and nonimmune mediated thrombocytopenia.

Clinical impact of neonatal thrombocytopenia.

In a 1-year prospective study, the outcome in infants with a platelet count less than 100 X 10(9)/L (n = 97) was compared with the outcome in an age-, weight-, and disease-matched nonthrombocytopenic control group (n = 80). The hemostatic impact of the thrombocytopenia was assessed by modified template bleeding time, hemorrhage score, and determination of the presence and extent of intraventricular hemorrhage (IVH) in thrombocytopenic infants weighing less than 1500 at birth (n = 39) compared with all nonthrombocytopenic infants less than 1500 g (n = 122) admitted during the study period. The development outcome in infants less than 1500 g was compared at 12 months after delivery.

Studies investigating platelet aggregation and release initiated by sera from patients with thrombotic thrombocytopenic purpura.

Many patients with thrombotic thrombocytopenic purpura (TTP) have a platelet aggregating factor in their serum that may be pathologically linked with the disease process. To help characterize the type of platelet aggregation and platelet release induced by the sera from seven TTP patients, we measured the ability of a variety of inhibitors of platelet function as well as the ability of monoclonal antibodies (MoAbs) against platelet glycoproteins to inhibit TTP sera-induced platelet aggregation and release. These results were compared with the ability of the same inhibitors to block platelet aggregation induced by ristocetin, collagen, ADP, thrombin, and IgG-immune complexes.

Frequency and mechanism of neonatal thrombocytopenia.

We performed a 1-year prospective study of 807 consecutive infants admitted to a regional neonatal intensive care unit to determine the frequency, natural history, mechanism(s), and cause of thrombocytopenia. Thrombocytopenia developed in 22% of the infants. The platelet count nadir usually occurred by day 4 and resolved by day 10.

Bleeding time in hemophilia A: potential mechanisms for prolongation.

Prolongation of bleeding time has been previously observed in hemophilia, although no cause has been elucidated. We measured bleeding time, platelet aggregation, nucleotide release, and thromboxane B2 (TXB2), plasma 6-keto-PGF 1 alpha, platelet-associated IgG (PAIgG), and circulating immune complexes in 31 unselected patients with severe hemophilia A and in 17 controls. In 85% of patients with hemophilia A, the bleeding time was greater than 2 SD above the control level (greater than 8 minutes).

A diagnostic test for heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia can be a serious and difficult-to-diagnose complication of heparin therapy. Serum from patients with heparin-induced thrombocytopenia can cause heparin-dependent platelet aggregation, but the low sensitivity and specificity of this test limit its clinical usefulness. In this report we describe an assay for heparin-induced thrombocytopenia that is both sensitive and specific.

Heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia is the most frequent and the most important idiosyncratic haematological drug reaction. It is important for several reasons: first, because heparin is used so often, and the frequency of heparin-induced thrombocytopenia is high, the risk of a hospitalized patient developing heparin-induced thrombocytopenia is high. Second, heparin-induced thrombocytopenia poses a major therapeutic dilemma for the clinician - continue the heparin and risk a worsening of the thrombocytopenia, or stop the heparin and risk extension or embolism of the thrombus.

Platelet fragments do not contribute to elevated levels of platelet associated IgG.

Most assays that measure platelet associated IgG (PAIgG) relate the IgG associated with the test platelets to the platelet count. This could lead to a systematic error if platelet fragments were present in the washed platelet sample but not counted. To address this issue, we studied platelets from patients with idiopathic thrombocytopenic purpura (ITP), thrombocytopenia complicating cardiopulmonary bypass, and laboratory synthesized platelet fragments (freeze-thawed) using electron microscopy.

Granulocytes do not have surface ABO antigens.

There is disagreement whether granulocytes have ABO antigens on their surfaces. We investigated this issue using pure populations of washed granulocytes from healthy individuals of known ABO, Lewis, and secretor phenotypes. The presence of ABO antigens on granulocytes was sought using four different techniques: a granulocyte-red cell mixed agglutination assay; a microleukoagglutination assay; a microgranulocyte cytotoxicity assay; and an immunoradiometric assay for granulocyte-associated IgG.

Impaired reticuloendothelial function in patients treated with methyldopa.

In about 20 per cent of patients taking the antihypertensive agent methyldopa, IgG autoantibodies form against red cells, but most such patients do not have hemolysis. The reason for this is uncertain; it does not appear to be explained by known characteristics of the autoantibody. Since antibody-dependent reticuloendothelial function is an important determinant of cell clearance, we measured reticuloendothelial function in nine patients taking methyldopa.

The concentration of IgG in the serum is a major determinant of Fc-dependent reticuloendothelial function.

Defective Fc receptor-specific reticuloendothelial (RE) function has been reported in certain patients with a variety of immunologic and nonimmunologic diseases. The mechanism responsible for the impaired RE function is uncertain, but it could be caused by immune complexes that are present in many of these disorders. Alternatively, the impaired RE function could be a secondary effect of the high concentrations of monomeric IgG in the serum of these patients, since monomeric IgG can compete with complexed IgG for macrophage receptors in vitro.

Correlation of a quinidine-induced platelet-specific antibody with development of thrombocytopenia.

The rapidity by which drug-dependent antiplatelet antibodies can develop is not known, since patients are only studied during or after the episode of thrombocytopenia. This report describes the development of quinidine-induced immune thrombocytopenia in a healthy volunteer during a drug study. The thrombocytopenia developed within two weeks of initiation of quinidine therapy.

Comparison of the measurement of surface or total platelet-associated IgG in the diagnosis of immune thrombocytopenia.

Platelet-associated IgG (PAIgG) can be measured on intact platelets or following platelet lysis. Measurement of PAIgG following platelet lysis may provide different or additional information compared to PAIgG measured on intact platelets. The PAIgG of lysed platelets represents "total" PAIgG, ie, IgG on the surface of platelets plus any IgG that was inside the platelet.

A platelet function defect in preeclampsia.

A prospective study was performed on 26 preeclamptic patients and 17 pregnant control subjects relating the platelet count to in vivo platelet function as assessed by the bleeding time and in vitro platelet function as assessed by collagen-stimulated thromboxane B2 biosynthesis. The results of these tests were normal in all control subjects. Nine of the 26 preeclamptic patients (34%) showed thrombocytopenia, and five of these patients had a prolonged bleeding time.

Quantitation of red cell-associated IgG using an immunoradiometric assay.

In this report, we describe a sensitive immunoradiometric assay (IRMA) for quantitating IgG on the surface of red cells. Washed red cells were prepared to a purity of greater than 99.9 percent.

The detection of a platelet-agglutinating factor in thrombotic thrombocytopenic purpura.

A sensitive and specific test was used to identify a platelet-agglutinating factor in sera from patients with thrombotic thrombocytopenic purpura. Serum from patients plus a preparation rich in large multimers of factor VIII: von Willebrand factor were added to target platelets, and agglutination occurred in 41 of 48 samples. Edetic acid, heparin, or heating, but not aspirin, monomeric IgG, or dansylarginine N-(3-ethyl-1,5-pentanediyl)amide inhibited the platelet-agglutinating factor.

Blood component therapy.

Human blood has been transfused for about 60-70 years. Over this time, the practice of blood transfusion has changed dramatically. One major change is the separation of blood into its various components.