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Biomedical subjects

T S Kickler

Publications and source records attributed to T S Kickler.

At least 73 records · Page 4Linked to original sources

Post-transfusion purpura: a report of five patients and a review of the pathogenesis and management.

We report five cases of post-transfusion purpura. Despite having profound thrombocytopenia, their management consisted only of steroid administration if serious bleeding was present. In one patient without bleeding, no specific therapy was given. This patient recovered uneventfully. Two patients died. One of these died from complicating illnesses rather than bleeding. The other suffered brain death, the result of a ruptured cerebral aneurysm. Four patients were PLA1 negative. The fifth patient had an antibody to an unidentified platelet-specific antigen.

Adult↗

In utero cerebral hemorrhage in alloimmune thrombocytopenia.

Central nervous system hemorrhage is a well-recognized complication of neonatal alloimmune thrombocytopenia attributed to perinatal trauma from passage through the birth canal. That central nervous system (CNS) hemorrhage can occur in utero is not as well recognized, and congenital CNS lesions have only circumstantially been linked to thrombocytopenia. We report two cases of intrauterine CNS hemorrhage shown to have occurred prenatally, resulting in porencephaly. The second case is unique in that the necropsy finding of a porencephalic cyst arising from an old hemorrhagic site pathologically confirms that the etiology of congenital CNS lesions in alloimmune thrombocytopenia is due to hemorrhage. This second case received close prenatal monitoring and yet died as a result of hemorrhage that was not detected until emergency operative delivery. A review of the literature revealed 10 cases, including two other pairs of siblings, who had CNS damage attributable to intrauterine hemorrhage. These findings indicate that congenital CNS lesions in alloimmune thrombocytopenia are due to intrauterine hemorrhage that careful obstetric and prenatal care may not identify or prevent. This fact should be included when genetic counseling is offered to alloimmunized mothers.

Blood Platelets↗

The resolution of platelet serologic problems using Western blotting.

Serologic identification of anti-PLAl and other platelet specific antibodies is difficult because other platelet reactive antibodies (e.g. anti-HLA) are commonly found in the samples. We have developed and evaluated a method using Western blotting to identify platelet specific antibodies. Since anti-PLAl is the most frequently encountered antibody, we used this antibody to validate the method. The PLAl antigen was found on a 95,000 Dalton protein, confirmed as glycoprotein IIIa by two-dimensional electrophoresis. The usefulness of Western blotting in resolving difficult platelet serologic problems was compared to a radiolabeled antiglobulin test using intact platelets. Our results showed that all sera with anti-PLAl identified by serology were confirmed by Western blotting. In addition, one anti-PLAl was detectable only by the proposed method. Western blotting was also as useful as a serologic method to PLAl type platelets. HLA antibodies were not demonstrable by this technique. In summary, Western blotting is a highly specific and sensitive way of identifying anti-PLAl in a variety of clinical situations. This approach may be used to identify antibodies to other platelet specific antigens and to standardize platelet antigen typing sera.

Antibody Specificity↗

The diagnostic usefulness of measuring antineutrophil antibodies in neutropenic patients.

We prospectively evaluated the usefulness of measuring antineutrophil (PMN) antibodies in patients with neutropenia by a sensitive immunoassay. The result of the immunoassay were compared to a standard leukoagglutination test. Thirty-two patients with neutropenia were studied. The mean value (+/- 1 SD) for PMN-bound IgG for 43 normal controls was 121 +/- 29 fg/PHN. All fifteen patients with immune neutropenia had elevated plasma levels of anti-PMN antibody (191-2,000 fg/PMN). The leukoagglutination assay was positive in 10 of these 15 patients. In 17 patients with nonimmune neutropenia, the mean value (+/- 1 SD) for PMN-bound IgG was 120 +/- 22 fg. Seventeen patients with sero-positive rheumatoid arthritis but normal PMN counts were also studied. These patients' plasmas bound 447 +/- (1 SD) 201 fg IgG/PMN. The leukoagglutination test was negative in these patients. Our study shows that the immunoassay is more sensitive than leukoagglutination testing for diagnosing immune neutropenia. Nonimmune, neutropenic patients' plasmas showed no increased reactivity. In nonneutropenic patients who have high titers of rheumatoid factor, immunoreactivity against PMN is measured by the immunoassay, but not by leukoagglutination testing. Binding assays may be more sensitive than leukoagglutination testing for measuring anti-PMN antibodies; however, in some cases, specificity of such testing may be increased with leukoagglutination testing.

Agglutination Tests↗

Studies on the pathophysiology of posttransfusion purpura.

Posttransfusion purpura typically occurs in PLA1 negative blood recipients who have been previously immunized to the PLA1 antigen. Following transfusion, severe thrombocytopenia develops with the formation of anti-PLA1. Since the patients' platelets lack the PLA1 antigen, one would not expect this antibody to destroy autologous platelets. In this study we show that PLA1 antigen exists in stored blood and can absorb to PLA1 negative platelets making them PLA1 reactive. Incubating PLA1 (-) platelets with ultracentrifuged plasma from PLA1 (+) blood donors allowed anti-PLA1 to bind to PLA1 (-) platelets. Control plasma from PLA1 (-) blood donors did not lead to anti-PLA1 binding. Using an inhibition assay, we showed that stored blood contains PLA1 material that was not removed by ultracentrifugation. The material absorbing to PLA1 (-) platelets represented the PLA1 antigen, which was confirmed by Western blotting. After incubating plasma containing PLA1 antigen with PLA1 (-) platelets, reactivity at 95,000 D was observed. Native PLA1 (+) platelets showed a similar band. When PLA1 (-) platelets were incubated with plasma from a PLA1 (-) donor, this band was not present. These studies show that a soluble form of PLA1 antigen exists in stored blood that can absorb to PLA1 (-) platelets. Consequently, anti-PLA1 can bind to these platelets leading to thrombocytopenia. These observations may explain the autologous destruction of platelets in posttransfusion purpura.

Antigens, Human Platelet↗

Probenecid induced immune hemolytic anemia.

We report a patient who, while receiving probenecid and colchicine for acute gouty arthritis, developed severe hemolytic anemia in association with a generalized rash. The hemolysis was immune mediated as shown by a positive direct Coombs' test. In vitro hematologic studies showed that a probenecid dependent antibody was present.

Anemia, Hemolytic, Autoimmune↗

A simplified radioimmunoassay for antibodies causing immune cytopenia.

A two-step, solid-phase radioimmunoassay for the measurement of antibodies directed against platelets, neutrophils, and red blood cells is described. Cells to be tested or standard solutions of human IgG (HIgG) first are incubated with excess 125I goat anti-human IgG. Unbound 125I anti-IgG is adsorbed in a second step to polystyrene balls (PB) coated with excess human IgG. Inhibition of binding in this second step is related directly to the level of cell associated IgG. The amount of cell bound IgG is determined by comparison to a inhibition curve for standard IgG solution. The method was evaluated by quantitating antibody levels in patients with clinical evidence of immune cytopenias.

Antibodies↗

Plasmapheresis for the treatment of repeated early pregnancy wastage associated with anti-P.

It has been proposed that the blood group antibody, anti-P, produced by p or Pk individuals may cause abortion early in pregnancy. The authors have studied and successfully treated a Pk woman with anti-P who had 13 consecutive first-trimester miscarriages. Anti-P was implicated as the cause of repeated pregnancy loss after extensive clinical, endocrinologic, immunologic, and chromosomal evaluations. To remove P blood group antibodies, plasmapheresis was begun at five weeks' gestation during the 14th pregnancy with one plasma volume exchange two to three times per week. This therapy resulted in a reduction in the titer of anti-P, and the patient was delivered of a viable female infant after 33 weeks' gestation. The management and outcome indicate that habitual abortion presumably due to anti-P can be successfully treated with plasmapheresis. This case provides additional evidence that anti-P is responsible for abortions in p or Pk women, and that these abortions are immunologically mediated.

Abortion, Habitual↗

Immunoglobulin class heterogeneity of platelet alloantibodies.

The immunoglobulin classes of platelet alloantibodies were studied using monospecific antisera in a radiolabeled technique. 14 of 28 consecutively studied multiply transfused oncology patients demonstrated platelet antibodies. These 14 patients were also refractory to random donor platelets. The immunoglobulin classes of these platelet antibodies were found to be: IgG alone 4, IgM alone 4, IgG and IgM 5, IgM plus IgA1. The results in this study suggest that using monospecific antisera other than anti-IgG alone, one can detect additional antibodies involved in the immune destruction of platelets.

Blood Platelets↗

Arthritis and autoimmune pancytopenia.

We report a patient who developed arthritis and pancytopenia without an underlying systemic disease. Autoantibodies to all lines were demonstrated using an 125I-anti human IgG assay. Elution studies documented cross reactivity of an antibody between erythrocytes and platelets, a pathogenetic variation not previously reported.

Adult↗

Unexplained hemolytic anemia associated with pregnancy.

Unexplained hemolytic anemia in pregnancy is a rare condition. Striking anemia beginning in the first (38%) or second (38%) trimester, resolving within 5 months of delivery (18 of 19 patients, 95%) and recurring in a subsequent pregnancy (six of 12 patients, 50%) was noted in a total of 19 pregnancies in 12 women. Transient hemolysis was present in four of 19 (22%) infants. The etiology of this problem is unknown, and the only factor clearly associated with the anemia is the gravid state. Characteristic of this problem is the absence of any identifiable immune mechanism or intracorpuscular or extracorpuscular defects despite the use of specific and sensitive complement-fixation antibody consumption techniques and assay of all red blood cell enzymes. Important in the management of these patients is the clinical observation that they do respond (seven of seven patients) to corticosteroid therapy and can experience a normal delivery. Although not frequent, this problem can be life threatening to both mother and child. With early recognition and appropriate treatment with corticosteroids the hazards of this condition can be avoided.

Adult↗

Serial determinations of antiplatelet antibodies in a patient with Hodgkin's disease and autoimmune thrombocytopenia.

This case report describes a patient who presented with Stage IV B Hodgkin's disease and autoimmune thrombocytopenia. Prior to the institution of therapy the presence of platelet-associated IgG was documented. When the patient was treated with steroids and chemotherapy, the thrombocytopenia resolved and platelet-associated IgG disappeared. Splenectomy alone did not correct the thrombocytopenia. The literature on Hodgkin's disease and autoimmune thrombocytopenia is reviewed.

Adult↗

A radiolabeled antiglobulin test for crossmatching platelet transfusions.

Despite the use of HLA-matched platelets for alloimmunized recipients, transfusion failures occur. In order to reduce these failures, we investigated the use of a radiolabeled antiglobulin technique for platelet crossmatching. The principle of the test is that of an indirect Coombs test using 125I labeled goat anti-human IgG. Incompatibility is determined by calculating a radioactivity antiglobulin test (RAGT) index. Using this technique, we performed 89 crossmatches on 19 leukemic or aplastic patients who were refractory to random donor platelets and receiving varying degrees of HLA-matched platelets. Effectiveness of the transfusion was assessed from the posttransfusion corrected platelet count increment (CCI) determined at 1 and 20 hr. When the RAGT index was 1.9 or less, the mean CCI at 1 lhr was 17,570 +/- 7003/cu mm, n = 55. When the RAGT index was 2.0 or greater, the mean CCI was 4237 +/- 4100/cu mm, n = 34. At 20 hr when the RAGT index was 1.9 or less, the mean CCI was 8722 +/- 3143/cu mm, n = 33, and when the index was 2.0 or greater, the mean CCI was 571 +/- 1286/cu mm, n = 23. Using this technique, one false negative resulted. Nine positive crossmatches with good increments at 1 hr were found; at 20 hr, however, the survival of these units was zero. These data suggest that this method is a useful adjunct in the selection of platelets in the refractory patient.

Adolescent↗

Kinetic determination of serum haptoblobin with a centrifugal analyzer.

We describe a method for determining haptoglobin with a centrifugal analyzer that is based on haptoglobin combining stoichiometrically with hemoglobin to form a complex that has peroxidase-like activity proportional to the quantity of haptoglobin present. Under assay conditions, unbound hemoglobin exhibits only a small fraction of the total peroxidase activity. Activity is measured colorimetrically at 405 nm after reaction with o-dianisdine and ethyl hydrogen peroxide. The procedure is standardized by saturating aknown amount of hemoglobin with a serum whose hemoglobin binding capacity exceeds the amount of hemoglobin in the assay system. The mean and mean within-run precision of our method, determined by performing 17 replicate assays of both a pooled normal serum and a 10-fold dilution of the serum, was 1.13 g/liter (CV, 2.9%), and 106 mg/liter (cv, 5.8%), respectively. The 95 percentile estimate of the normal range by our method is 0.45-1.85 g/liter hemoglobin binding capacity. When results by our automated method were compared to those by a manual method [Scand. J. Clin. Lab. 2nvest. 18, 80 (1965)], the slope of the unweighted linear least-squares regression line was .970 the y-intercept 26 mg/liter, and the correlation coefficient .995.

Autoanalysis↗

Devastating sequelae of alloimmune thrombocytopenia: an entity that deserves more attention.

UNLABELLED: In alloimmune thrombocytopenia, maternal sensitization to a fetal platelet alloantigen results in fetal thrombocytopenia. Even in primipara, 20% of offspring can suffer intracranial hemorrhage, half of which occur in utero. Ninety percent of subsequent pregnancies will be equally or more severely affected. We describe two patients whose previous pregnancies were complicated by neonatal alloimmune thrombocytopenia (NAIT). As expected, NAIT recurred, with devastating sequelae in both cases. One case presented with hydrops fetalis, a previously unreported association; the other fetus developed extensive intracranial hemorrhages in utero. Because both previous obstetrical histories had gone unrecognized, no preventative strategies had been undertaken. CONCLUSION: Better recognition of this disease through a positive obstetrical history is needed in order to properly counsel patients and institute appropriate prenatal treatment regimens.

Adult↗