Executive performance of depressed suicide attempters: the role of suicidal ideation.

OBJECTIVE: Suicidal ideation has been related to cognitive rigidity whereas suicidal behaviour itself was associated with specific executive deficits. Yet it remains unclear if a distinct cognitive suicidal phenotype does exist. The aim of the present study was to further investigate the role of suicidal thinking for the neuropsychological performance in depressive suicide attempters. METHOD: Depressive inpatients after a recent suicide attempt, who either had present suicidal ideation (n=14) or not (n=15) and healthy controls (n=29) were recruited. The groups were assessed by means of executive tasks designed to capture impulsive decision-making, and with verbal memory and attention tests. Self-rating measures of impulsivity and aggression were further applied. RESULTS: Only patients with current suicidal ideation showed executive dysfunctions with impaired decision-making being the most salient. Verbal memory and attention were reasonably intact in all patients. All patients reported increased aggression. CONCLUSION: Suicidal ideation is clearly associated with impaired cognitive performance. Our results suggest that executive deficits seen in depressive suicide attempters have a state-dependent component.

Clinical features of heparin-induced thrombocytopenia including risk factors for thrombosis. A retrospective analysis of 408 patients.

Immune mediated heparin induced thrombocytopenia (HIT) is a prothrombotic adverse effect of heparin. However, only a subgroup of patients with HIT develops thromboembolic complications. We aimed to identify risk factors for developing HITassociated thrombosis. We analyzed a registry of patients with clinical suspicion of HIT who tested positive using a sensitive functional assay. Patient information was obtained by a standardized questionnaire. By multivariate analysis the association of age, gender, type of patient population, and magnitude of the platelet count decline with the frequency, type (venous or arterial), and temporal pattern of thrombotic events was assessed. In 408 HIT patients we observed predominance of venous thrombosis (2.4:1), with 40% of patients developing a pulmonary embolism. However, in the subgroup of post-cardiovascular surgery patients there was predominance of arterial thrombosis (1:8.5). The type of arterial thrombosis (limb artery thrombosis > thrombotic stroke > myocardial infarction) was the converse of that observed with typical atherothrombotic clots in non-HIT populations. In 59.8% of patients HIT-related thrombosis manifested either on the same day a platelet count decrease >50% was documented (26.3%) or before the decrease in platelet counts (33.5%). The most important risk factors for thrombosis were orthopedic/trauma surgery and the magnitude of platelet count decrease. HIT-associated thrombosis occurs in a considerable proportion of patients before platelet counts decrease by more than 50%.

Platelet receptor and clotting factor polymorphisms as genetic risk factors for thromboembolic complications in heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is an immune mediated adverse reaction to heparin treatment often associated with limb- and/or life-threatening thromboembolic complications (TECs). Presently, no prognostic marker has been identified that allows differentiation between mildly (isolated thrombocytopenia) and severely (TECs) affected patients. This study assesses the impact of platelet glycoprotein- and clotting factor polymorphisms in HIT-patients with isolated thrombocytopenia compared to HIT-patients with TECs. Sixty-three HIT-patients with isolated thrombocytopenia and 79 HIT-patients with HIT-related TECs were genotyped for GPIIb-IIIa polymorphisms (HPA-1, HPA-3), GPIa-IIa polymorphisms (HPA-5, GPIaC807T), GPIb-IX-V polymorphisms (HPA-2, Kozak-5, VNTR), and clotting factor polymorphisms (FV-Leiden R506Q, prothrombin PT-G20210A and MTHFR C677T). Women more often presented with TECs than men (P = 0.04). No differences in genotype frequencies could be seen on comparing HIT-patients with and without TECs. Analysing men and women separately, the C allele of the Kozak polymorphism was overrepresented in men who developed TECs (P = 0.034). The enhanced risk of women to develop HIT-associated TECs remains unexplained but it is potentially important in view of recent data on sex-hormone related changes of haemostasis. There was no correlation between platelet glycoprotein- and clotting factor polymorphisms and the risk to develop HIT-associated TECs. An association between the development of TECs and the Kozak-5C allele could be seen among male patients. However, this would need to be assessed in further larger studies. Most likely, the high levels of thrombin generation during acute HIT are so procoagulant that less pronounced risk factors such as polymorphisms are overshadowed.

Heparin-induced thrombocytopenia: temporal pattern of thrombocytopenia in relation to initial use or reexposure to heparin.

STUDY OBJECTIVES: Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse drug reaction associated with a decrease of platelet counts that usually begins after at least 5 days of heparin treatment. Uncertainty exists about the risk of early onset of HIT (ie, < 5 days) in relation to previous heparin exposure. We therefore analyzed the temporal pattern of thrombocytopenia in patients with laboratory-confirmed HIT to assess whether patients with previous heparin exposure have an increased risk of early onset of HIT. DESIGN: Platelet count patterns in patients with a laboratory-confirmed diagnosis of HIT were examined in a retrospective chart review of a clinical study database. The onset of thrombocytopenia < 100 x 10(9)/L associated with the current heparin treatment (mainly unfractionated heparin) was analyzed using nonparametric maximum likelihood estimation. RESULTS: A total of 119 patients with 125 treatment episodes were assessed: HIT developed in 79 patients during initial exposure to heparin, and in 46 patients during reexposure. Early onset (< 5 days) of thrombocytopenia was associated with very recent heparin exposure. Patients reexposed to heparin within 3 months had an earlier onset of thrombocytopenia as compared to patients reexposed to heparin after 3 months (4.9 +/- 4.4 days vs 11.5 +/- 5.5 days [mean +/- SD], p = 0.001). There was no difference between onset on thrombocytopenia < 100 x 10(9)/L in patients reexposed to heparin within 3 to 12 months and after 1 year (9.7 +/- 6.4 days vs 12.3 +/- 5.2 days, p = 0.41). Whether platelet counts were obtained daily or less regularly did not affect the analysis. CONCLUSION: Early onset of thrombocytopenia in HIT is associated with recent heparin treatment (< 3 months). In contrast, for patients who did not receive heparin within the previous 3 months, HIT is an unlikely explanation for thrombocytopenia that occurs within the first 5 days.

Heparin-induced thrombocytopenia and cardiopulmonary bypass: perioperative argatroban use.

Heparin-induced thrombocytopenia (HIT), a serious complication of heparin therapy, mandates heparin cessation and alternative anticoagulation. We report a patient with a history of HIT who successfully underwent cardiopulmonary bypass (CPB) using short-term reexposure to heparin and perioperative therapy with argatroban. No bleeding complications or HIT-related problems occurred. The pharmacokinetics of argatroban, especially its hepatic rather than renal elimination, makes it the drug of choice for some HIT patients in whom other alternative anticoagulants (eg, danaparoid and hirudin) are less well suited. Because of interference with the international normalized ratio (INR), switching from argatroban to oral anticoagulants is not straightforward.

Low-dose danaparoid sodium catheter flushes in an intensive care infant suffering from heparin-induced thrombocytopenia.

OBJECTIVE: Despite controversy about whether peripheral and central venous catheters should be locked with heparin to prevent catheter-associated clotting, the practice is widespread. We describe a severe side effect of the practice: a case of heparin-induced thrombocytopenia occurring with catheter flushes using unfractionated heparin (UFH) in a 10-month-old boy successfully treated with danaparoid. Patient: A preterm-born patient (33 wks gestational age, birth weight 1200 g) suffering from VACTERL syndrome was repeatedly treated with UFH in the context of several invasive procedures. On day 310 of age, a central venous catheter was inserted to provide total parenteral nutrition. The central catheter was flushed with a continuous infusion of UFH at 100 U/day, and a decrease in platelet counts from 150,000/&mgr;L (on day 310 of age) to 45,000/&mgr;L (on day 319 of age) was observed. Clinically suspected heparin-induced thrombocytopenia (HIT) was serologically confirmed by demonstrating HIT antibodies with platelet factor 4/heparin complex specificity. Main Result: Catheter flushing was switched to low-dose danaparoid sodium as a continuous infusion at 15 anti-factor Xa units per day. Two days later, platelet counts recovered. Neither catheter thrombosis nor systemic thromboembolic complications occurred during the follow up period. CONCLUSIONS: Even continuous infusion of low-dose heparin to provide patency of central venous port catheters may trigger the primary immune response of HIT. Low-dose danaparoid sodium, a heparinoid, can prevent in-catheter thrombus formation and allows normalization of platelet counts in acute HIT.

Fc(gamma) receptors IIa on cardiomyocytes and their potential functional relevance in dilated cardiomyopathy.

OBJECTIVES: The purpose of this study was to investigate how cardiac autoantibodies might contribute to cardiac dysfunction in patients suffering from dilated cardiomyopathy (DCM). BACKGROUND: In the majority of DCM patients, it is possible to detect antibodies with negative inotropic effect on cardiomyocytes. The manner in which these antibodies impair cardiac function is poorly understood. METHODS: Immunoglobulin (Ig)G was prepared from plasma of 11 DCM patients containing antibodies that induced a negative inotropic effect on cardiomyocytes. We analyzed the effects of antibodies/IgG fragments on calcium transients and on systolic cell shortening of adult rat cardiomyocytes and investigated the dependency of these effects on potential cardiomyocyte Fc receptors. RESULTS: In contrast to control subjects, intact IgG from DCM patients reduced calcium transients and cell shortening of cardiomyocytes. The F(ab')2 fragments of these antibodies did not induce these effects but inhibited the functional effects of DCM-IgG of the respective patients' IgG. These effects were also inhibited by Fc fragments of normal IgG. Reconstitution of the Fc part by incubation of cardiomyocytes with DCM-F(ab')2 fragments followed by goat-anti-human-F(ab')-IgG again induced reduction of cell shortening and of calcium transients. In rat and human ventricular cardiomyocytes, Fc(gamma) receptors IIa (CD32) were demonstrated by immunofluorescence. CONCLUSIONS: Our findings indicate that DCM-IgG-F(ab')2 bind to their cardiac antigen(s), but the Fc part might trigger the negative inotropic effects via the newly detected Fc(gamma) receptor on cardiomyocytes. These results point to a novel potential mechanism for antibody-induced impairment of cardiac function in DCM patients.

Very severe thrombocytopenia and fragmentation hemolysis mimicking thrombotic thrombocytopenic purpura associated with a giant intracardiac vegetation infected with Staphylococcus epidermidis: role of monocyte procoagulant activity induced by bacterial supernatant.

The pathogenesis of very severe thrombocytopenia in bacterial endocarditis is uncertain. We report a 50-year-old male with platelet counts < 10 x 10(9)/l and fragmentation hemolysis complicating Staphylococcus epidermidis pacemaker endocarditis with a giant vegetation. Antibiotics, corticosteroids, high-dose intravenous gammaglobulin, and plasmapheresis (for initially-suspected thrombotic thrombocytopenic purpura) failed to produce significant platelet count increase. However, therapeutic-dose heparin anticoagulation was associated with a platelet count increase from <10 to approximately 40 x 10(9)/l, with parallel reduction in thrombin-antithrombin complexes (from 8.9 to 3.5 microg/l), facilitating surgical intervention. The thrombocytopenia promptly resolved following surgical removal of the vegetation. Culture supernatant from S. epidermidis isolated from the patient's blood induced monocytes to express procoagulant activity (assessed by factor Xa generation) equivalent to lipopolysaccharide (1 microg/ml), with half-maximal activation seen with culture supernatant diluted to 1:12,800. These data are consistent with previous animal models of endocarditis demonstrating staphylococci-induced procoagulant changes in monocytes. This case demonstrates that heparin anticoagulation can be therapeutic in infective endocarditis-associated severe thrombocytopenia in a non-bleeding patient, and that such therapy may ameliorate the platelet count enough to permit surgical intervention.

Gender imbalance and risk factor interactions in heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is caused by antibodies against a "self" protein-platelet factor 4-bound to heparin. We observed an overrepresentation of the female gender in 290 patients who developed HIT after cardiac or orthopedic surgery compared with the representation found in national databases (study 1). Therefore, we investigated gender imbalance in HIT by logistic regression analysis of a randomized controlled trial of unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) (study 2), and we analyzed individual patient data from 7 prospective studies comparing HIT frequency between UFH and LMWH, evaluating effects of gender, heparin (UFH vs LMWH), and patient type (surgical vs medical) (study 3). All 3 studies showed female overrepresentation, which for study 3 was a common odds ratio (OR) of 2.37 (95% confidence interval [95% CI], 1.37-4.09; P = .0015). Study 3 also showed an interaction between gender, heparin, and patient type. Although UFH was more likely than LMWH to cause HIT (P < .0001), this effect was predominantly seen in women compared with men (common OR, 9.22 vs 1.83; P = .020) and in surgical patients compared with medical patients (common OR, 13.93 vs 1.75; P = .005). We conclude that females are at greater risk for HIT and that using LMWH to prevent HIT may have greatest absolute benefit in females undergoing surgical thromboprophylaxis.

Incidence and clinical significance of anti-PF4/heparin antibodies of the IgG, IgM, and IgA class in 755 consecutive patient samples referred for diagnostic testing for heparin-induced thrombocytopenia.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is usually caused by anti-platelet factor 4 (PF4)/heparin antibodies, leading to intravascular platelet activation. These antibodies can be detected by PF4/polyanion antigen assays or platelet activation assays. While antigen assays are very sensitive and recognize immunoglobulin (Ig)G, IgA, and IgM antibodies, the role of IgM and IgA HIT-antibodies is debated. Platelet activation assays recognize IgG and are more specific for clinical HIT. METHODS: We analyzed sera from 755 consecutive patients referred for diagnostic testing for HIT using a PF4/heparin enzyme-linked immunosorbent assay (ELISA) for IgG, IgA, and IgM and by the heparin-induced platelet activation (HIPA) test. Clinical information was provided by the treating physicians. RESULTS: A total of 108 of 755 (14.3%) patients tested positive, 105 (13.9%) in the PF4/heparin IgG/A/M ELISA [28 (26.7%) only for IgM/A]; 53 (7.0%) sera were positive in the HIPA, of those 50 tested also positive in the ELISA. In 77 patients sufficient clinical information was provided. Available clinical information for 17 of the 28 patients who had only IgM and/or IgA detected showed plausible alternative (non-HIT) explanations in four of seven who had thromboembolic complications and in nine of 10 who had isolated HIT. CONCLUSION: Detection of IgG, IgM and IgA class antibodies by PF4/heparin ELISA yields a positive test result about twice as often as does a platelet activation assay, with only a minority of the additional patients detected likely having HIT. Thus, there is a potential for considerable over-diagnosis of HIT by laboratories that utilize only an ELISA for diagnostic testing.

Staphylococcus aureus carriers neutralize superantigens by antibodies specific for their colonizing strain: a potential explanation for their improved prognosis in severe sepsis.

Staphylococcus aureus is one of the most common causes of hospital-acquired infections. At the same time, 25% of healthy persons are symptom-free S. aureus carriers, and they have an increased risk of developing nosocomial S. aureus septicemia. Paradoxically, their prognosis is much better than that of noncarriers. We compared the antibody profiles for carriers and noncarriers toward S. aureus superantigens. In carriers, we found high titers of neutralizing antibodies specific for those superantigens that are expressed by their colonizing strain. The results show that carriage status confers strain-specific humoral immunity, which may contribute to protection during S. aureus septicemia.

Heparin-induced thrombocytopenia in patients receiving mechanical circulatory support.

OBJECTIVES: Patients receiving mechanical circulatory support are at risk for the development of heparin-induced thrombocytopenia due to the prolonged postoperative use of heparin. We evaluated their antibody status and outcome. METHODS: Between 2003 and 2004, 115 patients received mechanical circulatory support for more than 5 days. Blood samples from postoperative day 7 were retrospectively analyzed for anti-platelet factor 4/heparin antibodies and heparin-induced platelet activation. RESULTS: Overall, 12 (10.6%) patients had heparin-induced thrombocytopenia as defined by in vitro platelet activation, 28 (24.8%) had nonactivating antibodies, and 73 (64.6%) were classified as negative for antibodies. Patients positive for heparin-induced thrombocytopenia had the highest levels of anti-platelet factor 4/heparin immunoglobulin G antibodies. Freedom from thromboembolism was 33%, 33%, and 16% at 1, 3, and 6 months for positive patients, 77%, 68%, and 55% for negative patients (P < .001), and 70%, 53%, and 53% for patients with nonactivating antibodies (P = .068), respectively. The relative risk for thromboembolism in antibody positive patients peaked in the first month of support (odds ratio 7.46, P = .002). Independent risk factors for thromboembolic events included higher anti-platelet factor 4/heparin antibody titers, female gender, and higher fibrinogen levels. CONCLUSION: Heparin-induced thrombocytopenia was more prevalent in patients receiving mechanical circulatory support than in other cardiac patients. Frequent antibody screening is recommended due to the increased risk of thromboembolism. Heparin alternatives should be subjected to clinical trials in these high-risk patients.

Effect of fondaparinux on platelet activation in the presence of heparin-dependent antibodies: a blinded comparative multicenter study with unfractionated heparin.

Heparin-induced thrombocytopenia (HIT) is a complication of heparin therapy caused by antibodies against a complex of platelet factor 4 and heparin. Fondaparinux (Arixtra) is a new synthetic selective factor Xa inhibitor. We performed a serologic study to determine the cross-reactivity of HIT sera with fondaparinux. Using a prospective, blinded study design, 39 clinically and serologically confirmed sera from patients with HIT and 15 control sera were sent to 3 different laboratories, each of which specialized in a particular HIT assay. These include the serotonin release assay, heparin-induced platelet agglutination assay, and platelet aggregation assay. Two of 82 assays (2.4%) performed in the presence of control sera were positive, both with unfractionated heparin. In the presence of HIT sera, 75 of 94 (79.8%) evaluable assays were positive with unfractionated heparin; fondaparinux was significantly (P < .001) less reactive than unfractionated heparin, only 3 of 91 evaluable assays (3.3%) being positive. Using flow cytometry, unlike unfractionated heparin, fondaparinux did not induce the binding of PAC1 and anti-CD62 monoclonal antibodies or of annexin V to platelets with HIT sera. Together, these results suggest that fondaparinux is nonreactive to HIT sera and raise the possibility that the drug may be used for prophylaxis and treatment of thrombosis in patients with a history of HIT.

Antibodies against lepirudin are polyspecific and recognize epitopes on bivalirudin.

Bivalirudin is a synthetic antithrombin sharing a sequence of 11 amino acids with the recombinant hirudin lepirudin. We investigated whether antilepirudin antibodies recognize epitopes on bivalirudin. Antilepirudin antibody-positive sera of 43 patients, treated with lepirudin for heparin-induced thrombocytopenia, were analyzed. Lepirudin- and bivalirudin-coated microtiter plates were used for antibody testing in an enzyme-linked immunosorbent assay (ELISA) system. Of the 43 sera-containing antibodies binding to lepirudin, 22 (51.2%) contained antibodies that also recognized bivalirudin. Binding of these antibodies to bivalirudin was inhibited by more than 70% by preincubation with high doses of bivalirudin. However, if lepirudin-coated microtiter plates were used, high concentrations of bivalirudin inhibited only 2 of the 43 positive sera by more than 30%. Therefore antihirudin antibodies must be polyspecific. The clinical consequences of this cross-reactivity are unknown but bivalirudin, targeted by antibodies of patients treated with lepirudin previously, could potentially boost antibody titers in such patients or even trigger an immune response by itself. Clinically significant antibody formation in response to bivalirudin monotherapy has not been observed, however. Yet, as lepirudin and antilepirudin antibodies have recently been implicated in severe anaphylactic reactions, caution is warranted when using bivalirudin in patients previously treated with lepirudin.

The new ID-heparin/PF4 antibody test for rapid detection of heparin-induced antibodies in comparison with functional and antigenic assays.

Heparin-induced thrombocytopenia (HIT) is an immune-mediated complication of heparin treatment. Several in vitro assays are available to detect the causative HIT antibodies: functional assays, usually requiring freshly prepared platelets and immunological tests based on the enzyme-linked immunosorbent assay (ELISA) principle. We compared a new, simple and rapid test based on the ID-microtyping particle agglutination system with 14C-serotonin release assay, heparin-induced platelet activation (HIPA) test and two ELISAs. Sera from 100 confirmed HIT patients, 20 serologically negative suspected HIT patients and 20 healthy blood donors were used. The specificity and sensitivity of the new test was similar to the functional assays. Compared with the ELISAs, specificity was better at the cost of reduced sensitivity. As in all other immunological tests, HIT antibodies against less typical antigens, such as interleukin (IL)-8 or neutrophil-activating peptide (NAP) 2 could not be detected. Thus, although the ID-Heparin/PF4 antibody test seems to be a quick, reliable and robust test to determine the presence of HIT antibodies, it should still be combined with a functional assay if possible. Evaluation of the test in a prospective setting as well as interlaboratory variation should be assessed as a next step.

Lepirudin for prophylaxis of thrombosis in patients with acute isolated heparin-induced thrombocytopenia: an analysis of 3 prospective studies.

This analysis of 3 prospective multicenter trials in patients with laboratory-confirmed acute heparin-induced thrombocytopenia (HIT) without clinically evident thromboembolic complications (TECs), isolated HIT, assessed the combined individual end points of death, new TECs, and limb amputation. Patients with the same inclusion criteria who did not receive lepirudin or danaparoid served as a contemporaneous control group. Ninety-one patients were treated with lepirudin (intravenous infusion 0.10 mg/kg/h, no bolus, activated partial thromboplastin time [aPTT]-adjusted to 1.5-2.5 times baseline) for a median of 11.0 days (range, 1-68 days). During the observation period (median 24 days), 13 (14.3%) deaths, 4 (4.4%) new TECs, 3 (3.3%) limb amputations (combined 18 [19.8%]), and 13 (14.3%) major bleeding events occurred. In comparison to the control group (N = 47), the combined end point (P = .0281) and new TECs (P = .02) were reduced, and major bleeding was not significantly different between groups (P = .5419). In renal impairment, lepirudin did not reach its steady state within 4 hours, and additional monitoring every 4 hours after start of lepirudin until steady state is reached is recommended. Lepirudin seems to be effective in patients with isolated HIT. Dose reductions in renal impairment are important. Keeping the aPTT in the range corresponding to 600 to 700 microg/L lepirudin during treatment may minimize bleeding complications.

Antihirudin antibodies following low-dose subcutaneous treatment with desirudin for thrombosis prophylaxis after hip-replacement surgery: incidence and clinical relevance.

Recombinant hirudin has been found to be immunogenic in patients treated with lepirudin following heparin-induced thrombocytopenia (HIT). We assessed the incidence of immunoglobulin G (IgG) antihirudin antibodies by enzyme-linked immunosorbent assay in 112 patients enrolled in a dose-finding study with desirudin. Patients received desirudin subcutaneously following orthopedic hip surgery at 10 mg twice a day (n = 17), 15 mg twice a day (n = 75), and 20 mg twice a day (n = 20). Of 112 patients, 11 (9.8%) developed antihirudin antibodies independently of the dose. The rate of immunization did not differ from that observed in HIT patients treated with lepirudin (P =.113). Plasma concentrations of desirudin did not differ between antihirudin antibody-positive and -negative patients. Antihirudin antibodies had no impact on incidences of deep vein thrombosis and/or pulmonary embolism, allergic reactions, and hemorrhage. However, the total number of immunized patients observed was low and so infrequent (but severe) effects of antihirudin antibodies cannot be excluded.

Ceftriaxone causes drug-induced immune thrombocytopenia and hemolytic anemia: characterization of targets on platelets and red blood cells.

BACKGROUND: Ceftriaxone, a third-generation cephalosporin, has been reported to occasionally cause fatal drug-induced immune hemolytic anemia (DIHA). A clinical and serologic analysis of the first two patients with severe drug-induced thrombocytopenia (DITP) due to ceftriaxone and one patient with fatal DIHA is reported. STUDY DESIGN AND METHODS: Sera were assessed by the IAT, EIA, glycoprotein (GP)-specific immunoassay, flow cytometry, and immunoprecipitation using transfectants expressing GPIIb/IIIa and GPIb/IX and with different cephalosporins. RESULTS: Sera from Patients 1 and 2 reacted strongly with PLTs in the presence of the drug, but not with RBCs. The binding sites of the drug-dependent antibodies (DDAbs) could be localized to GPIIb/IIIa and GPIb/IX, respectively. Inhibition studies indicated that DDAbs recognized epitopes residing on the GPIIb/IIIa complex and on the GPIX subunit, respectively. No cross-reactivity was observed with other cephalosporin derivatives. Serum 3 showed strong agglutination with RBCs of Rh(null) phenotype in the presence of ex-vivo metabolites of ceftriaxone, but no cross-reactivity with PLTs. CONCLUSIONS: The first two cases of severe DITP and a third patient with DIHA are reported. DDAbs from all patients showed individual reaction patterns and clear cell lineage specificity. In addition, the DDAbs were dependent on the substitution at position 3 of the ceftriaxone molecule. Epitopes on GPIIb/IIIa and GPIX were involved on PLTs. The Rh protein was not the only target of DDAbs on RBCs.

The incidence of heparin-induced thrombocytopenia in hospitalized medical patients treated with subcutaneous unfractionated heparin: a prospective cohort study.

Although heparin-induced thrombocytopenia (HIT) is a known complication of intravenous unfractionated heparin (UFH), its incidence in medical patients treated with subcutaneous UFH is less well defined. To determine the incidence of HIT in this category of patients, the platelet count was performed at baseline and then every 3 +/- 1 days in 598 consecutive patients admitted to 2 medical wards and treated with subcutaneous UFH for prophylactic (n = 360) or therapeutic (n = 238) indications. The diagnosis of HIT was accepted in the case of a platelet drop of 50% or more and either the demonstration of heparin-dependent antibodies or (when this search could not be performed) the combination of the following features: (1) the absence of any other obvious clinical explanation for thrombocytopenia, (2) the occurrence of thrombocytopenia at least 5 days after heparin start, and (3) either the normalization of the platelet count within 10 days after heparin discontinuation or the earlier patient's death due to an unexpected thromboembolic complication. HIT developed in 5 patients (0.8%; 95% CI, 0.1%-1.6%); all of them belonged to the subgroup of patients who received heparin for prophylactic indications. The prevalence of thromboembolic complications in patients with HIT (60%) was remarkably higher than that observed in the remaining 593 patients (3.5%), leading to an odds ratio of 40.8 (95% CI, 5.2-162.8). Although the frequency of HIT in hospitalized medical patients treated with subcutaneous heparin is lower than that observed in other clinical settings, this complication is associated with a similarly high rate of thromboembolic events.

Benefit and risk of heparin for maintaining peripheral venous catheters in neonates: a placebo-controlled trial.

OBJECTIVES: Heparin addition to infusion fluids is used to prolong catheter patency in newborns. Heparin may also induce adverse effects such as bleeding complications and immune-mediated heparin-induced thrombocytopenia (HIT). One objective was peripheral venous catheter patency with heparinization of continuous infusions (0.5 IU/mL). Secondary objectives were incidences of bleeding, clinically manifest HIT, HIT antibodies, and catheter-related complications. STUDY DESIGN: Inclusion criteria were anticipated need for intravenous peripheral infusion (>or=5 days for HIT-related endpoints) and postnatal age <28 days at study entry. Exclusion criteria were bodyweight <1000 g, congenital malformation, need for therapeutic anticoagulation or mechanical ventilation, and severe bleeding. HIT antibodies were assessed by enzyme-linked immunosorbent assay. RESULTS: A total of 145 infants received heparin, and 151 infants received saline. Patient characteristics, number of additional drugs, duration of treatment, and location and size of catheters did not differ. Patency of catheters was 7.4 hours longer in the heparin group (33.8 hours vs 26.4 hours, P<.0001), but the total numbers of catheters did not differ (565 vs 692, P=.3). No infant developed HIT antibodies. Incidences of bleeding complications and thrombocytopenia were comparable between groups. CONCLUSIONS: Balancing the benefits against the risks of heparin addition and the rare complication of HIT, we will not use 0.5 IU/mL heparin addition to parenteral fluids.