PubMed Health⌕ Search

Biomedical subjects

S Panzer

Publications and source records attributed to S Panzer.

At least 19 recordsLinked to original sources
PubMed2006

Influence of clinical factors on the haemolysis marker haptoglobin.

BACKGROUND: Plasma haptoglobin determination is clinically used as parameter for haemolysis. To date, however, the influence of the mode of haemolysis (extravascular vs. intravascular) and of nonhaemolytic conditions on haptoglobin concentration and its reliability as a haemolysis marker remain poorly defined. MATERIALS AND METHODS: In a total of 479 individuals, the influence of haemolytic and nonhaemolytic conditions on plasma haptoglobin levels was investigated. RESULTS: All studied types of haemolytic disease (n = 16) were associated with markedly decreased plasma haptoglobin levels, without significant differences between intravascular vs. predominantly extravascular haemolysis. Diminished haptoglobin values were also observed in patients with liver cirrhosis, which normalized after liver transplantation. In contrast, markedly increased haptoglobin levels were found in patients with inflammation. In patients with haemolysis and a concomitant acute-phase response, however, haemolysis-dependent haptoglobin depletion was not attenuated. Interestingly, patients with a strongly positive direct antiglobulin test or high cold agglutinin titre but no further evidence for haemolysis had normal haptoglobin values. Likewise, anaemia owing to bone marrow failure, acute gastrointestinal or chronic diffuse blood loss, and end-stage kidney disease were associated with normal haptoglobin levels. CONCLUSIONS: Plasma haptoglobin depletion is a reliable marker for the instant diagnosis of accelerated red cell destruction irrespective of the site of haemolysis or the presence of inflammation. The capacity of this parameter to predict haemolysis appears to be limited in patients with liver cirrhosis and decreased haptoglobin production only.

Acute-Phase Reaction↗
PubMed2006

Monitoring survival and function of transfused platelets in Glanzmann thrombasthenia by flow cytometry and thrombelastography.

Patients with Glanzmann thrombasthenia (GT) may form isoantibodies which induce refractoriness or inhibition of function of transfused platelets. We monitored the survival and function of transfused platelets by flow cytometry and thrombelastography in a patient with GT. Gating on CD42a+ allowed identification of even a few transfused platelets. Only by gating on these CD41+ CD42a+ cells were we able to demonstrate their capability to bind fibrinogen and PAC-1 upon activation. Platelets were rapidly cleared from the circulation as a result of boosted isoantibodies. The contribution of transfused platelets to clot formation was also demonstrated by thrombelastography by blocking their function with abciximab.

Adolescent↗
PubMed2006

Specificities of platelet autoantibodies and platelet activation in lupus anticoagulant patients: a relation to their history of thromboembolic disease.

Lupus anticoagulants (LA) prolong in vitro phospholipid-dependent coagulation tests, but are associated with thromboembolic disease (TE). However, a subgroup of individuals with LA has no TE, and it is therefore desirable to distinguish those at risk for TE from those without. Whether platelets have a primary role in the development of TE is not clear yet. We determined platelet autoantibodies to identify a specific platelet target which is associated with platelet activation in 97 patients with a long history of detectable LA, 65 patients with TE (LA/TE+), and 32 individuals without TE (LA/TE-). Thrombocytopenia was more common in the LA/TE- than in the LA/TE+ group (P < 0.05). Both groups had platelet antibodies, but the frequency of antibodies was lower in LA/TE+ than LA/TE- patients (P < 0.01), who had higher antibody titres against glycoprotein IIb/IIIa and glycoprotein Ib/IX (P < 0.05). Also, their platelets were more activated, as determined by PAC-1 binding (P < 0.01). These differences were also noted if patients with arterial thrombosis were evaluated separately. These findings in LA/TE- individuals were similar to those in patients with chronic autoimmune thrombocytopenia. However, there was no autoantibody target identifiable to distinguish between LA/TE- from LA-TE+ individuals. We therefore conclude that the presence of platelet antibodies, even if associated with platelet activation, is not sufficient to dispose LA patients to thromboembolic disease.

Adolescent↗
PubMed2005

Short- and long-term effects of therapy with interferon-alpha and pegylated interferon-alpha/ribavirin on platelet plug formation and von Willebrand factor release in patients with chronic hepatitis C.

BACKGROUND: A pegylated interferon-alpha-induced decrease in platelet counts may become a limiting factor for continuation of therapy. AIM: To evaluate the effect of pegylated interferon-alpha administration on platelet plug formation and von Willebrand factor antigen release in patients with chronic hepatitis C. METHODS: Thirty patients with chronic hepatitis C (genotype 1; fibrosis 1-3: n = 16, cirrhosis: n = 14) received a single dose of 9 MU interferon-alpha2a, followed by weekly administration of 180 mug of pegylated interferon-alpha2a/ribavirin for 48 weeks. Platelet counts, platelet function (collagen-epinephrine-induced closure time) and von Willebrand factor antigen were measured. RESULTS: Platelet counts and collagen-epinephrine-induced closure time decreased by 13% and 16%, respectively, 24 h after the first dose of interferon-alpha2a, and von Willebrand factor antigen levels increased by 31% (P < 0.01) compared with baseline. During a 48-week observation period, platelet counts decreased by a maximum of 33% (P < 0.001), von Willebrand factor antigen levels increased by 69% (P < 0.001) whereas collagen-epinephrine-induced closure time did not change. In noncirrhotic patients, the increase of von Willebrand factor antigen levels was maintained throughout therapy without a change in collagen-epinephrine-induced closure time. In contrast, in cirrhotics, von Willebrand factor antigen levels did not increase, while collagen-epinephrine-induced closure time was prolonged. CONCLUSION: Single-dose interferon-alpha decreases platelet counts but improves platelet function, possibly by the release of von Willebrand factor antigen. Accordingly, long-term antiviral treatment had no effect on collagen-epinephrine-induced closure time, despite the decrease in platelet count in noncirrhotic patients. Such a compensation of decreased platelet counts by increased von Willebrand factor antigen level did not occur in cirrhotics.

Adult↗
PubMed2005

Frequencies of maternal platelet alloantibodies and autoantibodies in suspected fetal/neonatal alloimmune thrombocytopenia, with emphasis on human platelet antigen-15 alloimmunization.

BACKGROUND AND OBJECTIVES: Serological evaluation of maternal sera for platelet antibodies in suspected fetal/neonatal alloimmune thrombocytopenia (FNAITP) discloses in only approximately 30% of individuals a platelet-specific antibody. Transfusion-induced alloimmunization against human platelet antigen-15 (HPA-15) has been reported to be about as common as against HPA-5, the second most common platelet antibody. Thus, anti-HPA-15 may also contribute significantly to yet-unclear cases of FNAITP. MATERIALS AND METHODS: In this retrospective analysis, we provide data on maternal platelet antibodies from 309 mothers who delivered an offspring with suspected FNAITP. RESULTS: Genotyping maternal and paternal samples (together n = 573) revealed a gene frequency of 0.496 for HPA-15a and a gene frequency of 0.504 for HPA-15b. HPA-15 antibodies were detected in 2% of all samples. Anti-HPA-15a and -15b were detected in two and three samples, respectively. One serum reacted equally with HPA-15a and -15b platelets. The most frequent platelet-specific antibodies were anti-HPA-1a (22%), but anti-HPA-5b (8.4%) were more frequent than anti-HPA-15. In addition, panreactive (5.5%) or autoreactive (5.2%) anti-GPIIb/IIIa or anti-GPIb/IX were detectable in maternal samples. CONCLUSIONS: These data indicate that HPA-15 alloimmunization needs only to be considered in subjects with suspected FNAITP if no other platelet-specific antibody is detectable. The presence of panreactive or autoreactive antibodies should also be considered in neonatal thrombocytopenia.

Antigens, CD↗
PubMed2005

Severe thrombocytopenia due to host-derived anti-HPA-1a after non-myeloablative allogeneic haematopoietic stem cell transplantation for multiple myeloma: a case report.

BACKGROUND AND OBJECTIVES: Host- or donor-derived alloimmune thrombocytopenia can develop after non-myeloablative allogeneic haematopoietic stem cell transplantation (HSCT). We report the first case of host-derived HPA-1a antibodies. CASE REPORT: A 52-year-old male patient received HSCT from his human leucocyte antigen (HLA)-A, -B, -C, -DR identical brother after reduced intensity conditioning. Bilinear engraftment around day 12 was accompanied by a continuous decrease of platelet counts. We investigated for platelet antibodies because of a progressive decline of platelet counts and refractoriness to platelet transfusions. METHODS: The patient's serum was tested by enzyme-linked immunosorbent assay (ELISA), a solid phase assay and monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay. Recipient's DNA from the time before HSCT and donor's DNA were genotyped for human platelet antigens. RESULTS: Serum obtained on day 15 after HSCT reacted strongly with the donor's platelets due to host-derived anti-HPA-1a- and anti-HLA I antibodies. Serum samples from days 39, 45 and 65 after HSCT contained only anti-HLA I; no antibodies were detectable on day 149. Platelet counts increased on day 20 spontaneously. The decrease of the antibodies accompanied by the increase of the platelet counts suggests progressive elimination of residual host cells. CONCLUSIONS: The HPA-1a antibodies affected thrombopoietic engraftment and the success of platelet transfusions.

Antigens, Human Platelet↗
PubMed2005

Light chain phenotypes of HLA antibodies in cases with suspected neonatal alloimmune thrombocytopenia.

BACKGROUND AND OBJECTIVES: Platelet-specific antibodies are detectable in only about 30% in suspected neonatal alloimmune thrombocytopenia (NAIT). Human leucocyte antigen (HLA) class I antibodies are often detectable, and as platelets express the corresponding antigens, it has been suggested that these antibodies can be responsible for NAIT. Light chain phenotyping may assist in the diagnosis of HLA antibodies-induced NAIT. MATERIALS AND METHODS: We determined light chain phenotypes of platelet reactive HLA antibodies in 17 sera from mothers who delivered offspring with suspected NAIT. Ten sera also contained platelet-specific antibodies: HPA-1a (n = 5, one with HPA-15b), HPA-5b (n = 4) and autoantibodies (n = 1). Sera were tested for kappa or lambda restriction by monoclonal antibody-specific immobilization of platelet antigens (MAIPA). RESULTS: The cross-match with paternal platelets was positive in all cases due to HLA antibodies. We identified 5, 3 and 3 sera to contain lymphocytotoxic antibodies of single, two or multiple specificities, respectively. In six cases, HLA antibodies were only detectable by MAIPA. Light chain restriction (n = 9) was not associated with HPA containing antibodies or to any pattern of the HLA antibodies. Similarly, polyclonal antibodies (n = 8) were seen in all categories. CONCLUSION: We show that pregnancy-associated HLA antibodies can be clonal or polyclonal, irrespective of a diagnosis of NAIT. ONE-SENTENCE SUMMARY: Pregnancy associated HLA antibodies can be clonal or polyclonal, irrespective a diagnosis of NAIT.

Antigens, Human Platelet↗
PubMed2003

Idiopathic autoimmune thrombocytopenia: evidence for redistribution of platelet antibodies into the circulation after immunoadsorption treatment.

Platelet antibodies are detectable in only about 50% of patients with chronic autoimmune thrombocytopenia (AITP). We determined platelet antibodies against GPIa/IIa, GPIb/IX, GPIIb/IIIa, and GPV and reticulated platelets in three female patients with AITP, before and after immunoadsorption treatment. None of the three patients' sera contained platelet antibodies prior to treatment. Thereafter, anti-GPIIb/IIIa, anti-GPIb/IX (n = 3), and anti-GPV (n = 1) were detectable in the patients' sera. These antibody specificities were also found in the eluates from the immunoadsorption columns. Only one patient had elevated levels of reticulated platelets. Immunoadsorption treatment did not induce a sustained increase of platelet counts in any patient. Immunoadsorption treatment in AITP can induce redistribution of antibodies into the circulation.

Adolescent↗
PubMed2003

Influence of human platelet antigen match on the success of stem cell transplantation after myeloablative conditioning.

Mismatches between donor and recipient for human platelet antigens (HPA) may affect the success of transplantation due to: (a) serving as minor histocompa-tibility antigens and therefore render recipients at risk for graft-versus-host disease (GvHD), (b) inhibition of thrombopoiesis due to platelet antibodies. We therefore evaluated the occurrence of GvHD and need of platelet support by prospective analysis of donor-recipient pairs (n=53) for HPA-1, -2, -3, and -5 allotypes and screening for platelet antibodies prior to transplantation and in weekly intervals until day 100 after transplantation. Neither the incidence of GvHD nor the onset of thrombopoiesis, nor the CCI after platelet transfusions, nor the frequency of platelet transfusions was affected by HPA mismatches. Settings of homozygous donors vs heterozygous recipients or homozygous recipients vs heterozygous donors were not associated with any adverse effects on the outcome of the transplantation. Thus, the HPA-match does not affect the success of transplantation.

Adolescent↗
PubMed2001

Presence of N regions in the clonotypic DJ rearrangements of the immunoglobulin heavy-chain genes indicates an exquisitely short latency in t(4;11)-positive infant acute lymphoblastic leukemia.

Childhood acute lymphoblastic leukemia (ALL) is frequently initiated in utero at a time of developmentally regulated insertion of N regions into the DJ(H) rearrangements of immunoglobulin heavy-chain (Ig(H)) genes. Here it is shown that N regions are present in the clonotypic DJ(H) rearrangements in 11 of 12 infant ALLs with t(4;11). These data are compared with the 122 previously published DJ(H) sequences and were found to have a pattern similar to that of ALL in children older than 3 years at diagnosis but were unlike that in children younger than 3 years who predominantly lack N regions. These findings, therefore, indicate that t(4;11)-positive infant ALL is initiated later in fetal development than most B-cell precursor ALL from children younger than 3 years and that they have a shorter latency period already in utero.

Base Sequence↗
PubMed2001

A common C-->T polymorphism at nt 46 in the promoter region of coagulation factor XII is associated with decreased factor XII activity.

Coagulation factor XII (FXII) deficiency is rarely found to be associated with bleeding, but single reports demonstrated thromboembolic events in FXII-deficient patients. Currently, the biological role of FXII is still discussed controversially. It is well known that plasma levels of FXII show great interindividual variability. Recently, it has been demonstrated that a frequently occurring C-->T polymorphism in the FXII promoter region at nucleotide (nt) 46 is associated with lower plasma FXII activity levels in Orientals. In our study, we evaluated the frequency of this polymorphism in a randomly selected sample of newborns and investigated whether this C-->T polymorphism also contributes to the frequently observed moderate FXII deficiency in Europeans. We developed a new mutagenically separated polymerase chain reaction assay (MS PCR), which allows mutation detection without the use of restriction enzymes. Among 100 healthy newborns, we found 64% homozygous carriers of the wildtype FXII 46C allele, 29% were heterozygous for FXII C46T, and 7% homozygous for FXII 46T. Evaluation of plasma FXII activity and genotype in 80 randomly selected and unrelated individuals revealed a highly statistically significant (P<.001) association of the FXII 46T allele with reduced FXII plasma activity. Individuals carrying the homozygous FXII 46C genotype had a mean of 1.17 U/ml (+/-0.31 U/ml), individuals heterozygous for FXII C46T showed a mean of 0.70 U/ml (+/-0.31 U/ml), and subjects homozygous for FXII 46T had only 0.44 U/ml (+/-0.10 U/ml) plasma FXII activity.

Alleles↗
PubMed2001

Red cell antibodies in frequently transfused patients with myelodysplastic syndrome.

Therapy for myelodysplastic syndrome (MDS) is often restricted to lifelong support with red blood cell units (RBCU). A variety of immune phenomena associated with antibody production have been reported in MDS patients. Therefore, we hypothesized that red cell antibodies are more frequent in patients with MDS compared to other regularly transfused patients. Red cell antibodies were determined in 42 MDS patients, in 28 patients with other hematological disorders, and in a historical group of 129 patients with end-stage renal failure. All of these patients received frequent red cell substitution therapy, at least two RBCU in biweekly intervals. Red cell antibodies were detected in 9 of 42 patients with MDS, in 3 of 28 patients with other hematological disorders, and in 4 of 129 patients with end-stage renal failure. Evidence of red cell antibodies was displayed by 6 of 27 MDS patients treated with prestorage leukocyte-depleted RBCU and 3 of 15 MDS patients transfused with bedside leukocyte-filtered RBCU. Red cell antibodies are frequent in patients with hematological disorders who require repetitive red cell transfusions. The formation of alloantibodies to red cell antigens is as frequent in MDS patients as in other patients with hematological disorders.

Adult↗
PubMed2001

Amantadine in Parkinson's disease: lymphocyte subsets and IL-2 secreting T cell precursor frequencies.

The antiviral drug amantadine, that is effective in idiopathic Parkinson's disease (PD), may affect the composition and function of peripheral blood lymphocytes. In an explorative study, we therefore compared lymphocyte subpopulations and IL-2 secreting T cell precursors frequencies (HTLp-frequencies) in 15 PD patients without amantadine and six patients on long-term treatment. Five patients were investigated before and three months after the start of treatment. Group comparisons for long-term amantadine treatment showed no differences in subpopulations of B-, T-, and NK cells, and HTLp-frequencies. However, three months after initiation of treatment we noted in all five patients an increase of CD3+CD4+ and decrease of CD3+CD8+ cells, associated with an increase of the CD3+CD4+/CD3+CD8+ ratio. These changes had no effect on the HTLp-frequencies. Thus, at least for a short period of time, amantadine improves the T cell mediated immune system in PD patients.

Aged↗
PubMed2001

Human platelet antigen-1a antibodies induce the release of the chemokine RANTES from human platelets.

BACKGROUND AND OBJECTIVE: Binding of human platelet antigen-1a (HPA-1a)-specific antibodies to target platelets can trigger platelet activation and mediator release. Here we tested the effect of HPA-1a antibody-containing sera on platelet release of the chemokine RANTES (regulated on activation, normal, T-cell expressed, and presumably secreted) in vitro. PATIENTS AND METHODS: HPA-1a-containing sera obtained from 11 mothers delivered of an infant with neonatal alloimmune thrombocytopenia (NAIT) and from six patients with post-transfusion purpura (PTP) were incubated with HPA-1a/a target platelets. Antibody-induced release of soluble RANTES was determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: A significant release of soluble RANTES was induced by four out of the 17 sera. Two out of the four reactive sera were obtained from mothers who were delivered of a baby with NAIT and the remaining two sera were from patients with PTP. Chemokine release was specific for binding of anti-HPA-1a to the platelet membrane, as none of the reactive sera induced the release of soluble RANTES when incubated with HPA-1b/b platelets. The blockade of platelet-expressed Fc gamma receptor type II (FcgammaRII) inhibited anti-HPA-1a-mediated RANTES release when incubated with the reactive sera of patients with NAIT, but not when platelets were incubated with sera of patients with PTP. CONCLUSION: Our findings suggest that anti-HPA-1a antibody-induced release of platelet-derived RANTES can play a role in adverse reactions in alloimmunized patients.

Adult↗
PubMed2001

High levels of reticulated platelets and thrombopoietin characterize fetal thrombopoiesis.

To characterize fetal thrombopoiesis, we determined plasma thrombopoietin (TPO) and glycocalicin levels, platelet counts and reticulated platelets (RP) of fetuses and compared them with the respective values of their mothers. Percutaneous umbilical vein sampling in abnormal pregnancies revealed twofold higher thrombopoietin levels and 20-fold higher reticulated platelet counts, but lower levels of glycocalicin in fetuses compared with their mothers (P < 0.05). Neither the expression of platelet glycoprotein Ib and IIb on platelets nor the platelet counts were different between mothers and their fetuses. These data indicate enhanced thrombopoiesis and/or increased platelet turnover in fetuses.

Adult↗