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At least 433 records · Page 24Linked to original sources
PubMed2005

Low brain-derived neurotrophic factor (BDNF) levels in serum of depressed patients probably results from lowered platelet BDNF release unrelated to platelet reactivity.

BACKGROUND: Recent reports have suggested a role for brain-derived neurotrophic factor (BDNF) in psychiatric disorders. Decreased serum BDNF levels have been reported in major depression, but the cause of this decrease has not yet been investigated. The goal of this study was to assess blood BDNF and a platelet activation index, PF4. METHODS: Forty-three drug-free patients (27 female, 16 male) diagnosed with major depression and 35 healthy control subjects (18 female, 17 male) were assessed for plasma, serum, and blood BDNF content. Brain-derived neurotrophic factor and PF4 were assayed with enzyme-linked immunosorbent assay methods, and severity of depression was evaluated with the Montgomery-Asberg Depression Rating Scale. RESULTS: Serum and plasma BDNF levels were decreased in depressed patients compared with control subjects. In whole blood, BDNF levels were unaltered in the depressed subjects compared with control subjects. The serum/blood BDNF ratio was lower in patients with major depression. Increased plasma but not serum PF4 levels were observed in depressed subjects compared with control subjects. CONCLUSIONS: Our results suggest that an alteration of serum or plasma BDNF is not due to the change in blood BDNF but rather is probably related to mechanisms of BDNF release. Secretion of BDNF seems to be independent of platelet reactivity; other mechanisms are therefore probably involved and need to be elucidated.

Adult↗
PubMed2005

Platelet release of beta-thromboglobulin and platelet factor 4 and serotonin in plasma samples.

OBJECTIVES: Platelet release of alpha granule-derived CXC chemokines and dense granule-derived serotonin in plasma samples was evaluated. METHODS: Concentrations of the CXC chemokines beta-TG and PF4 were assayed by an enzyme immunoassay; serotonin was measured by an HPLC method. RESULTS: Beta-TG and PF4 were more easily released than serotonin by in vitro procedures. Use of the anti-platelet cocktail CTAD and preservation of the samples at 4 degrees C were necessary to accurately measure beta-TG and PF4, but not serotonin. CONCLUSIONS: Assaying serotonin may be useful for assessing platelet activation in vivo as a laboratory test because of facile preparation of plasma samples.

Adenosine↗
PubMed2005

Laboratory testing for the antibodies that cause heparin-induced thrombocytopenia: how much class do we need?

Heparin-induced thrombocytopenia (HIT) is usually caused by platelet-activating antibodies of immunoglobulin G class that recognize platelet factor-4 (PF4) bound to heparin or certain other polyanions. Commercial enzyme immunoassays (EIAs) for PF4/polyanion-reactive antibodies detect two immunoglobulin classes (IgA and IgM) besides IgG. To investigate whether the additional detection of these antibody classes improves or worsens assay operating characteristics, we compared the sensitivity and specificity of EIAs that detect these 3 immunoglobulin classes individually with that of a commercial EIA (Genetic Testing Institute, GTI), as well as a platelet-activation assay, the serotonin-release assay (SRA). We compared the operating characteristics of these 5 assays by evaluating 448 patients, in 14 of whom clinical HIT developed, who received either unfractionated or low molecular weight heparin in prospective studies that included systematic platelet-count monitoring and serologic evaluation for anti-PF4/polyanion antibodies. We found that the SRA and IgG and commercial EIAs had similar high sensitivity for HIT; however, diagnostic specificity (for unfractionated and low molecular weight heparin, respectively) varied considerably, as follows: SRA (95.1%, 97.2%) > IgG EIA (89.0%, 93.7%) > GTI EIA (74.2%, 87.6%). Additional detection of IgA and IgM antibodies by the GTI EIA worsened test specificity by detecting numerous nonpathogenic antibodies. Moreover, the frequency and magnitude of IgA and IgM antibody formation in non-HIT immune responses did not differ from that exhibited by patients in whom clinical HIT developed. We conclude that an EIA that detects anti-PF4/polyanion antibodies of only the IgG class has greater diagnostic usefulness in revealing clinical HIT than does an assay that also detects IgA and IgM class antibodies.

Clinical Medicine↗
PubMed2004

Whole blood serotonin and platelet activation in depressed post-myocardial infarction patients.

Depression is an independent risk factor for post myocardial infarction (MI) mortality. Abnormalities in platelet function have been proposed as one of the mechanisms involved in increased cardiovascular risk among patients with depression post-MI. Depression in somatically healthy patients has been associated with increased platelet activation. Some but not all studies showed changes in blood serotonin level. Increased platelet activation and blood serotonin level have been associated with increased risk of cardiac events in patients with MI. The goal of this study was to investigate whether 1) depressed post-MI patients have higher markers of platelet activation as measured by plasma levels of beta-thromboglobulin (betaTG), platelet factor 4 (PF4) and soluble CD40 ligand (sCD40L) and higher serotonin (5-HT) levels than non-depressed post-MI patients and 2) treatment with the antidepressant mirtazapine decreases platelet activation. In this study, 25 depressed post-MI patients were asked for blood collection before start as well as after 8 weeks treatment with mirtazapine or placebo. The control group (n=22) consisted of non-depressed post-MI patients, matched for age, gender and time elapsed since MI. Plasma levels of betaTG, PF4 and sCD40L were not statistically different between the groups, but 5-HT levels were significantly higher in depressed patients. Treatment with mirtazapine resulted in a non-significant decrease in betaTG and PF4 and platelet 5-HT levels. Platelet and whole blood 5-HT, but not platelet activation was significantly increased in depressed post-MI patients. Treatment with mirtazapine showed a non-significant decrease in platelet activation and platelet 5-HT.

Adult↗
PubMed2006

Testing for heparin-induced thrombocytopenia antibodies.

Heparin-induced thrombocytopenia (HIT) has a distinct clinical profile and unique pathogenesis. It is caused by platelet-activating IgG antibodies that recognize multimolecular complexes of platelet factor 4 (PF4) bound to heparin or certain other polyanions. Although an immune response to PF4/heparin associated with heparin treatment is very common, clinical HIT occurs only among the minority of patients whose antibodies are capable of strongly activating platelets. This explains why certain platelet activation assays and anti-PF4/polyanion immunoassays have high sensitivity for HIT and why diagnostic specificity is highest for those assays that preferentially detect pathogenic antibodies, such as the washed platelet activation assays or immunoassays that detect only IgG antibodies. Negative results obtained in a solid-phase PF4/polyanion immunoassay generally exclude HIT (high negative predictive value), especially in a setting of a low pretest probability. In addition, because the magnitude of a positive test result correlates with greater likelihood of HIT, a Bayesian diagnostic approach that combines pretest probability and the magnitude of a positive test result is recommended. Recent studies suggest that presence of anti-PF4/polyanion antibodies in certain clinical settings confers an adverse prognosis, even without clinically evident HIT. Whether such antibodies impart "forme fruste" HIT or are simply a surrogate marker for a non-HIT adverse risk factor such as inflammation is unresolved.

Anticoagulants↗
PubMed2000

Immediate effect of balloon valvuloplasty on hemostatic changes in mitral stenosis.

This study was conducted to assess right and left atrial hemostatic function in patients with mitral stenosis (MS) and to investigate the immediate effect of balloon mitral valvuloplasty (BMV) on hemostatic function. BMV was performed in 28 patients with MS (age 29 +/- 8 years) who had sinus rhythm and no left atrial (LA) thrombus. Right and left atrial biochemical markers of platelet activity (platelet factor 4 [PF4] and B thromboglobulin [BTG]), coagulation (thrombin-antithrombin III complex [TAT]), and fibrinolytic activity (D-dimer) were measured before and 30 minutes after BMV. Right atrial levels of these markers were also measured in 20 control subjects. Compared with control subjects, patients with MS had higher right atrial levels of PF4 (30 +/- 15 vs 5 +/- 2 IU/ml), BTG (231 +/- 53 vs 30 +/- 8 IU/ml), TAT (7 +/- 4 vs 2 +/- 0.3 microg/L), and D-dimer (380 +/- 145 vs 160 +/- 35 ng/ml, p < 0.0001 in all). TAT levels were higher in the left atrium than in the right atrium of patients before BMV (8 +/- 4 vs 7 +/- 4 microg/L, p < 0.0001). BMV was successful (final mitral valve area > or = 1.5 cm2 and > or = 50% increase of the initial valve area) in all patients. There was a significant reduction of LA levels of PF4 (35 +/- 8 to 26 +/- 9 IU/ml, p < 0.0001), BTG (225 +/- 41 to 196 +/- 28 IU/ml, p < 0.001), and TAT (10 +/- 5 to 7 +/- 1 microg/L, p < 0.05) in the 16 patients with LA pressure < 10 mm Hg after BMV, whereas these markers were not reduced in the 12 patients with left atrial pressure > or = 10 mm Hg after BMV. These data indicate that platelet function, coagulation status, and fibrinolytic activity are increased regionally in the left atrium and in the systemic circulation in patients with MS and sinus rhythm in the absence of LA thrombus. Successful BMV induces a significant reduction of prethrombotic status in patients with low LA pressure after the procedure. Patients with high LA pressure after BMV maintain a high prethrombotic state and may be considered at an increased risk of thromboembolism after the procedure.

Adolescent↗
PubMed1999

Schedule-induced polydipsia: gender-specific effects and consequences of prenatal cocaine and postnatal handling.

The impact of gestational cocaine in conjunction with postnatal handling on schedule-induced polydipsia (SIP) was examined. Rat offspring were derived from Sprague-Dawley dams injected subcutaneously with 40 mg/kg/3 cc cocaine hydrochloride (C40) on gestational days 8-20, dams injected with vehicle and pair fed 4 (PF4) days to mimic the acute anorexic effects of cocaine administration, and nontreated (NT) control dams. In adulthood, offspring were food deprived and given 13 daily 30-min SIP sessions, with water intake recorded during the scheduled (fixed time 60 s-FT60) food delivery. For 4 days thereafter, animals received saline, 5 or 10 mg/kg of cocaine in counterbalanced order prior to SIP testing. Acquisition and maintenance of SIP, but not cocaine-induced suppression of SIP performance, were observed to be dependent upon prenatal treatment, handling, and gender. Females acquired SIP faster and exhibited notably higher levels of polydipsia than males. Early handling increased levels of established SIP in NT offspring, while enhancing SIP acquisition in both PF4 and C40 offspring. In nonhandled animals, NT offspring exhibited less SIP than PF4 and C40 offspring, differences that were attenuated by early handling. These effects are discussed in relation to previously reported neurohormonal characteristics of these gender and treatment variables.

Analysis of Variance↗
PubMed2001

Identification of T cells responding to a self-protein modified by an external agent.

An interesting class of immune responses is that in which an environmental agent modifies a self-protein. Heparin induced thrombocytopenia (HIT) is associated with an antibody response in which the immunogen is a self-protein, platelet factor 4 (PF4), modified by an external agent, heparin. We tested the hypothesis that a T cell component exists in HIT, which like the humoral response, also requires the combination of heparin and PF4 to be activated. We identify here, a subset of T cells derived from a subject with severe HIT, which were expanded preferentially in 14-day in vitro cultures specifically in the presence of PF4:heparin complexes. A combination of T cell receptor spectratyping, CDR3 sequencing, and clonotype-specific probe hybridization were used to identify the responding T cells. The three BV17 T cell "clonotypes" thus identified had a CDR3 length of 10 amino acids, used BJ1.2, and displayed a conserved CDR3 sequence motif. These T cells are an example of a cellular response to environmentally altered self and are likely to be directly involved in HIT by functioning as T helper cells. The results are discussed in terms of the possible role of modification of antigen presentation by the external agent in this response.

Aged↗
PubMed1997

Growth factors released into the coronary circulation after vascular injury promote proliferation of human vascular smooth muscle cells in culture.

OBJECTIVES: This study sought to 1) assess in vivo release of platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) into the coronary circulation after vascular injury in human subjects; and 2) evaluate mitogenic effects of PDGF and bFGF on the patient's own vascular smooth muscle cells (VSMCs). BACKGROUND: Circumstantial evidence suggests involvement of PDGF and bFGF peptides in the neointimal response to vascular injury. To date, no study has shown biologically active growth factors within the coronary circulation after vascular injury in human subjects. METHODS: In 18 patients, plasma PDGF AB, platelet factor 4 (PF4) and beta-thromboglobulin (beta-TG) levels were measured in coronary sinus blood obtained before and up to 30 min after angioplasty. In five patients undergoing atherectomy, coronary sinus serum was added to cultured VSMCs derived from atherectomy tissue to assess the mitogenic potential of the serum. Mitogenicity attributable to PDGF and bFGF was determined using neutralizing antibodies to these factors. PDGF A, PDGF B and bFGF were localized within the atherectomy tissue using immunocytochemical analysis. RESULTS: Before angioplasty, PDGF AB, PF4 and beta-TG levels were elevated threefold in patients scheduled for angioplasty compared with those in control patients (p < 0.01). Within 5 min of angioplasty, PDGF AB levels increased twofold and returned toward preangioplasty levels at 30 min; PF4 and beta-TG levels remained elevated. Serum obtained at 30 min after atherectomy showed a sixfold increase in mitogenicity compared with preatherectomy serum (p = 0.01). This increase in mitogenicity was reduced by 20%, 40% and 65% in the presence of neutralizing antibodies to PDGF, bFGF and PDGF + bFGF, respectively. PDGF A, PDGF B and bFGF were visualized within the intima of the atherectomy tissue. CONCLUSIONS: The change in plasma PDGF level is consistent with first-phase release of PDGF after vascular injury. The increase in mitogenicity of serum suggests that PDGF and bFGF are biologically active.

Adult↗
PubMed1997

Relation between mitral regurgitation and platelet activation.

OBJECTIVES: This study sought to examine the effect of mitral regurgitation (MR) on platelet activation in patients with mitral valve prolapse (MVP) or rheumatic MR. BACKGROUND: MVP and rheumatic MR are associated with an increased incidence of thromboembolic events. Although the underlying causes are not clear, increased platelet activation has been suggested as one of the pathogenic mechanisms. Results of previous studies that have investigated the relation between MVP and platelet activation are controversial. Whether the presence of MR in patients with mitral valve disease is associated with platelet activation remains unclear. METHODS: We studied platelet activation by measuring the plasma level of platelet factor 4 (PF4) and beta-thromboglobulin (BTG) in 16 patients with MVP, 12 patients with rheumatic MR and 25 control subjects. A detailed echocardiographic examination, including M-mode measurement and color Doppler flow mapping to detect the presence and severity of MR was performed. RESULTS: Patients and control subjects were matched for gender, age and left ventricular ejection fraction. Eight (50%) of 16 patients with MVP had MR. Patients with MVP and MR and patients with rheumatic MR had a significantly larger left atrial diameter. Mean log plasma levels of PF4 and BTG were significantly higher in patients with MVP and MR and patients with rheumatic MR than in control subjects (1.17 +/- 0.22 and 0.93 +/- 0.23 IU/ml vs. 0.52 +/- 0.34 IU/ml, p < 0.01; 1.70 +/- 0.21 and 1.53 +/- 0.15 IU/ml vs. 1.37 +/- 0.15 IU/ml, p < 0.05, respectively) but were comparable in patients with MVP and no MR and control subjects. Plasma levels of PF4 and BTG were positively correlated with the severity of MR, as assessed by a semiquantitative method (r = 0.59, p = 0.0001; r = 0.60, p = 0.0001, respectively). Increasing age and left atrial enlargement were not related to platelet activation. CONCLUSIONS: MR in mitral valve disease was associated with systemic platelet activation. MVP itself was not associated with increased platelet activation. The degree of platelet activation was positively correlated with the severity of MR and was independent of the underlying etiology of mitral valve disease, age and left atrial size. The possibility of a higher incidence of thromboembolism and the role of antiplatelet agents in such patients will require further studies to determine.

Adult↗
PubMed1991

Human platelet factor 4 subunit association/dissociation thermodynamics and kinetics.

Platelet factor 4 (PF4) monomers (7800 daltons) form dimers and tetramers in varying molar ratios under certain solution conditions [Mayo, K. H., & Chen, M. J. (1989) Biochemistry 28, 9469]. The presence of a simplified aromatic region (one Tyr and two His) and resolved monomer, dimer, and tetramer Y60 3,5 ring proton resonances makes study of PF4 aggregate association/dissociation thermodynamics and kinetics possible. PF4 protein subunit association/dissociation equilibrium thermodynamic parameters have been derived by 1H NMR (500MHz) resonance line-fitting analysis of steady-state Y60 3,5 ring proton resonance monomer-dimer-tetramer populations as a function of temperature from 10 to 40 degrees C. Below 10 degrees C and above 40 degrees C, resonance broadening and overlap severely impaired analysis. Enthalpic and entropic contributions to dimer association Gibb's free energy [-5.1 kcal/mol (30 degrees C)] are +2.5 +/- 1 kcal/mol and +26 +/- 7 eu, respectively, and for tetramer association Gibb's free energy [-5.7 kcal/mol (30 degrees C)], they are -7.5 +/- 1 kcal/mol and -7 +/- 3 eu, respectively. These thermodynamic parameters are consistent with low dielectric medium electrostatic/hydrophobic interactions governing dimer formation and hydrogen bonding governing tetramer formation. Association/dissociation kinetic parameters, i.e., steady-state jump rates, have been derived from exchange-induced line-width increases and from 1H NMR (500 MHz) saturation-transfer and spin-lattice (Tl) relaxation experiments. From dissociation jump rates and equilibrium constants, association rate constants were estimated. For dimer and tetramer equilibria at 30 degrees C, unimolecular dissociation rate constants are 35 +/- 10 s-1 for dimer dissociation and 6 +/- 2 s-1 for tetramer dissociation.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1989

Human platelet factor 4 monomer-dimer-tetramer equilibria investigated by 1H NMR spectroscopy.

As a function of protein concentration, proton NMR spectra of human platelet factor 4 (PF4) differ. Correlation with low-angle laser light scattering data has allowed identification of concentration-dependent NMR spectral changes to PF4 aggregation, with tetramers being the largest aggregates formed. Well-resolved aromatic ring proton NMR resonances were assigned to Tyr-60, His-I, and His-II in monomer, dimer, and tetramer states. Since Tyr-60 3.5 ring proton resonances are well resolved from state to state, estimation of fractional populations in each state was possible. By varying the PF4 concentration, changes in these populations when plotted according to the Hill equation show a bimolecular mechanism of aggregation which proceeds from monomers to tetramers through a dimer intermediate. Equilibrium constants for dimer association (KD) and tetramer association (KT) have been estimated as a function of pH and ionic strength. At pH 4, where KD and KT approach the same value, resonances associated with all three aggregate states are observed. Lowering the pH shifts the equilibrium to the monomer state, while raising the pH shifts the equilibrium to dimer and tetramer states. Analysis of the pH dependence of KD and KT suggests that electrostatic interactions, probably arising from Glu/Asp and Lys/Arg side chains, play a role in the binding process. Increasing the solvent ionic strength stabilizes the tetramer state especially at low pH, suggesting that intersubunit, repulsive electrostatic interactions probably between/among cationic side chains (Lys/Arg) attenuate the aggregation process. Information based primarily on histidine pKa values and photo-CIDNP 1H NMR data suggests that Tyr-60 and His-I, but not His-II, are significantly affected by the aggregation process.

Histidine↗
PubMed1999

Vascular endothelial growth factor measured in platelet poor plasma allows optimal separation between cancer patients and volunteers: a key to study an angiogenic marker in vivo?

BACKGROUND: Serum VEGF levels are elevated in cancer patients and are used as a tumor marker in different malignancies. We have measured VEGF levels in different blood compartments in cancer patients and healthy volunteers in order to assess the most suitable way of processing blood for measuring VEGF as a marker of tumor-angiogenesis. PATIENTS AND METHODS: VEGF concentrations were analyzed by an enzyme-linked immunosorbent assay in serum (VEGFS), EDTA plasma (VEGFEDTA), citrated plasma (VEGFC), CTAD-plasma (VEGFCTAD), platelet poor plasma (VEGFPPP), platelet rich plasma after induction of platelet activation (VEGFPRP). Platelet activation was assessed by measuring PF4 concentrations in different plasma samples. RESULTS: We observed higher VEGFS (P = 0.0027), VEGFEDTA (P = 0.003) and VEGFPPP (P = 0.0007) levels in cancer patients than in volunteers; VEGFPRP concentrations showed no significant difference (P = 0.208). Analysis of the correlation between VEGFplt and VEGFS in cancer patients showed a similar correlation in a comparable VEGFS concentration range as in the volunteers. When comparing VEGFC to VEGFCTAD, we find significantly higher VEGF and PF4 levels in citrated plasma (VEGF: P = 0.00019; PF4: P = 0.00023). CONCLUSIONS: It is likely that VEGFS in cancer patients encompass platelet-delivered VEGF and VEGF from other sources, notably from (neo)-angiogenesis in tumoral tissue. The best discrimination between volunteers and cancer patients was observed in PPP. As generating plasma can induce platelet activation, with consequent VEGF release from platelets, we suggest that to assess free circulating VEGF, CTAD plasma should be used.

Adult↗
PubMed1995

Multiple native-like conformations trapped via self-association-induced hydrophobic collapse of the 33-residue beta-sheet domain from platelet factor 4.

Native platelet factor 4 (PF4) (70 residues) has a hydrophobic three-stranded anti-parallel beta-sheet domain on to which is folded an amphipathic C-terminal alpha-helix and an aperiodic N-terminal domain. The 33-amino acid beta-sheet domain from PF4 (residues 23-55) has been synthesized and studied by c.d. and n.m.r. At 10 degrees C and low concentration, peptide 23-55 appears to exist in aqueous solution in a random-coil distribution of highly flexible conformational states. Some preferred conformation, however, is observed, particularly within a relatively stable chain reversal from Leu-45 to Arg-49. As the peptide concentration and/or temperature is increased, a new conformational state(s) appears and intensifies as slowly exchanging (600 MHz 1H-n.m.r. chemical-shift time scale) random-coil resonances disappear. Hill plots of the concentration-dependence indicated mostly tetramer formation as found in native PF4. Although apparent resonance linewidths in aggregate state(s) are of the order of 100 Hz, sequence-specific assignments for most resonances could be made. N.m.r./nuclear Overhauser effect structural analysis indicates the formation of multiple native-like anti-parallel beta-sheet conformations, kinetically trapped via subunit-association-induced hydrophobic collapse and stabilized by low-dielectric electrostatic interactions among/between Gly-28 and Lys-50 in opposing subunits. Results are discussed in terms of protein folding.

Amino Acid Sequence↗
PubMed1985

Fibrinogen derivatives and platelet activation products in acute and chronic liver disease.

1. The concentration in plasma of fibrinogen derivatives fibrinopeptide A (FPA) and B beta 1-42 and the platelet release products beta-thromboglobulin (beta TG) and platelet factor 4 (PF4) have been determined in patients with acute and chronic liver disease. 2. In 21 patients with fulmiant hepatic failure on admission in grade III or IV coma the plasma FPA, B beta 1-42, beta TG and PF4 levels were significantly increased compared with those in normal control subjects. On heparinization before haemoperfusion the FPA levels returned to the normal range and during resin and charcoal haemoperfusion there were no significant changes in the coagulation or platelet factors, except for a small increase in FPA with charcoal haemoperfusion. 3. In ten patients with compensated chronic liver disease there was a significant increase in B beta 1-42 and beta TG levels but not FPA and PF4 as compared with normal controls. 4. Interpretation of the results is complicated by the possible reduced clearance of these proteins as a result of renal failure in some of the patients with fulminant hepatic failure and also by the damaged liver itself. However, these results have confirmed that disseminated intravascular coagulation can occur in both acute and chronic liver disease.

Acute Disease↗
PubMed2001

Determination of heparin-platelet factor 4-IgG antibodies improves diagnosis of heparin-induced thrombocytopenia.

Only a few patients with heparin-induced antibodies develop heparin-induced thrombocytopenia (HIT). In this study, we investigated whether different immunglobulin classes can be used to differentiate between antibody-positive patients with and without HIT. Four different patient populations were investigated: 32 patients with the immune type of HIT with thromboembolic complications, 13 patients with HIT without thromboembolism, 24 patients with heparin-platelet factor 4 (PF4) antibodies without clinical symptoms of HIT, and 20 heparin-treated patients with thrombocytopenia caused by other reasons. In all patients the immunglobulin mixture of IgG, IgM and IgA, and the single immunglobulin classes of heparin-PF4 antibodies, were investigated. No significant differences between HIT patients with thromboembolic complications and patients with isolated HIT were found concerning the different immunglobulin classes. Antibody-positive patients with HIT had significantly higher levels of IgG antibodies than those without HIT (P < 0.05), while they did not differ concerning IgM and IgA antibodies. By determining IgG antibodies, the specificity of the enzyme-linked immunosorbent assay (ELISA) system was increased without loss of sensitivity. Heparin-PF4-IgG antibodies can identify patients at risk of developing life-threatening HIT. Future ELISAs should only include this immunglobulin class, as the determination of the antibody mixture may lead to overestimation of HIT.

Aged↗
PubMed1997

Assays for heparin-induced thrombocytopenia.

Tests for the presence of heparin-dependent antibodies (heparin-Ig) have evolved in parallel with improved understanding of the pathophysiology of heparin-induced thrombocytopenia (HIT). The first group of tests relied upon platelet aggregation or activation. Among tests in this group, the serotonin release assay has been reported to demonstrate the best performance characteristics. However, this test has not been widely adopted outside a few specialized laboratories owing to its complexity and need for radioactive materials. As a result, the less sensitive and specific platelet aggregation test is more commonly used for the diagnosis of heparin-Ig. The literature suggests that test sensitivity can be improved by the use of the patient's own platelets, platelets from selected donors known to be reactive in the assay, or washed platelets. Test specificity has been enhanced by the use of two point assays that include neutralization of the reaction by a high dose of heparin. A second group of assays have focused on detection of heparin-dependent binding of immunoglobulins to the platelet membrane. Most of these tests are hampered by the fact that platelets in patients with suspected HIT and in conditions that are in the differential diagnosis of HIT frequently express high levels of platelet-associated immunoglobulin. The most recent tests for heparin-Ig are based on the recognition that patient antibodies are directed against the heparin-PF4 complex. This has led to the development of the PF4/ heparin EIA assay. Because whole platelets are not used in this assay, problems related to under-reactivity or nonspecific reactivity are avoided. In addition, the ability of the test to predict clinical complications may be improved because the test can distinguish IgM from IgG heparin-Ig. Currently the laboratory diagnosis of heparin-Ig remains inexact. The sensitivity and specificity of laboratory assays cannot be firmly established. Much like the diagnosis of the phospholipid syndrome-where use of both the cardiolipin EIA and the lupus anticoagulant test offer overlapping advantages-the combination of the heparin-PF4 EIA plus either a test of platelet activation or a heparin-dependent antibody binding assay may prove to be a more sensitive and specific approach to the diagnosis of heparin-Ig. Despite the progress that has been made in the area of laboratory diagnosis of heparin-Ig, further improvement is needed. Heparin-induced thrombocytopenia is not rare and may be associated with devastating morbidity as well as mortality. Low-molecular-weight heparins usually cross-react with heparin-Ig. Therapy with Org 10172 appears to be the most promising alternative for patients with HIT. Because the clinical diagnosis is uncertain in sick hospitalized patients, further improvements in laboratory assays for heparin-Ig allowing earlier and more accurate diagnosis of patients at risk for HIT will be welcome.

Anticoagulants↗
PubMed1986

Platelet activity in cluster headache.

Platelets are known to be activated in common or classic migraine both during the attack and in headache-free periods. Platelet behavior is less well known in cluster headache. We have investigated beta-thromboglobulin (beta-TG) and platelet factor four (PF4) plasma levels, markers of in vivo platelet activation, in patients during remission and during bouts of cluster headache with and without pain. The results indicated that statistically significantly higher levels of beta-TG and PF4 occur in the patients during the remission period when compared with the control subjects. Such high levels seemed to persist between paroxysmal episodes in cluster periods. However, during the attacks of cluster headache beta-TG and PF4 plasma levels decreased by 42% and 50%, respectively, in comparison with plasma concentrations measured outside of attack. Thus, although platelet activation also occurs in patients with cluster headache, the attack as such seems to be characterized by a marked reduction in platelet activation.

Adult↗