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Heparin-induced Thrombocytopenia (heparin-induced + thrombocytopenia)
Selected AbstractsPrevalence of heparin-induced antibodies in patients with chronic renal failure undergoing hemodialysisJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 5 2005Iván Palomo Abstract Heparin-induced thrombocytopenia (HIT) type II is a serious complication of heparin therapy. It presents initially as thrombocytopenia, and is associated with thrombosis in 20,50% of the cases. HIT is related to the presence of heparin-induced antibodies (HIA), which show specificity for the PF4-heparin (PF4-H) complex. The Fc,RIIa receptor has been suggested to participate in the pathogenic mechanism of HIA. Since patients undergoing chronic hemodialysis (HD) are exposed repeatedly to heparin, we studied the prevalence of HIA and their eventual relationship with thrombocytopenia and/or thrombosis, and the possible participation of the Fc,RIIa polymorphism. We studied 207 patients with chronic renal failure (CRF) undergoing HD. As a control we included 130 blood donors and 28 patients with CRF without HD. The HIA patients were studied with the use of a PF4-H ELISA. Additionally, in some positive cases for the previous test, a 14C- serotonin release assay (14C-SRA) was performed. The polymorphism Fc,RIIa H/R131 was studied by polymerase chain reaction (PCR) with allele-specific primers. Thirty-seven patients (17.9%) undergoing HD presented with HIA. The majority of these antibodies were IgG, IgM, and IgA. The HIA investigated presented specificity against the PF4-H complex, but not against PF4 alone (P<0.001). Twelve out of 22 (54.5%) PF4-H antibodies were positive when tested with the 14C-SRA. The distribution of the Fc,RIIa polymorphism in patients and healthy controls was 42.6% and 41.6% for H/H131, 41% and 48.9% for the H/R131 isoform, and 16.4% and 9.5% for the R/R131 isoform, respectively. No statistically significant difference in the Fc,RIIa isoform distribution was found. Twenty-nine out of 156 patients (18.5%) presented thrombocytopenia, and 21/207 (12.4%) had thrombosis of the native vein arterio-venous fistula (AVF). We did not find any statistically significant between HIA and thrombocytopenia or thrombosis. An important proportion of patients with CRF undergoing HD developed HIA, but these cases were not associated with thrombocytopenia or thrombosis of AVF. The frequency of the Fc,RIIa polymorphism did not statistically differ between HIT type II and normal controls. J. Clin. Lab. Anal. 19:189,195, 2005. © 2005 Wiley-Liss, Inc. [source] Heparin-induced thrombocytopenia: a prospective study on the incidence, platelet-activating capacity and clinical significance of antiplatelet factor 4/heparin antibodies of the IgG, IgM, and IgA classesJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 8 2007A. GREINACHER Summary.,Introduction:,Platelet-activating antiplatelet factor 4/heparin (anti-PF4/heparin) antibodies are the major cause of heparin-induced thrombocytopenia (HIT). However, the relative utility of functional (platelet activation) vs. antigen [enzyme-immunoassay (EIA)] assays, and the significance of assay discrepancies remain unresolved.Methods:,Consecutive patient sera (n = 1650) referred for diagnostic HIT testing were screened prospectively by both the heparin-induced platelet activation (HIPA) test and anti-PF4/heparin EIA , including individual classes (IgG, IgA, IgM) , with clinical correlations studied. Platelet microparticle and annexin-V-binding properties of the sera were also investigated.Results:,Only 205 (12.4%) sera tested positive in either the HIPA and/or EIA: 95 (46.3%) were positive in both, 109 (53.1%) were only EIA-positive, and, notably, only one serum was HIPA-positive/EIA-negative. Of 185 EIA-positive sera, only 17.6% had detectable IgM and/or IgA without detectable IgG. Among sera positive for EIA IgG, optical density values were higher when the sera were HIPA-positive (1.117 vs. 0.768; P < 0.0001), with widely overlapping values. Two HIPA-positive but EIA-IgG-negative sera became HIPA-negative following IgG depletion, suggesting platelet-activating antibodies against non-PF4-dependent antigens. Clinical correlations showed that HIPA-negative/EIA-positive patients did not develop thrombosis and had reasons other than HIT to explain thrombocytopenia. IgM/A antibodies did not increase microparticle penetration, but increased annexin-V binding.Conclusions:,The anti-PF4/heparin EIA has high (,99%) sensitivity for HIT. However, only about half of EIA-positive patients are likely to have HIT. Anti-PF4/heparin antibodies of IgM/A class and non-PF4-dependent antigens have only a minor role in HIT. [source] Diagnostic score for heparin-induced thrombocytopenia after cardiopulmonary bypassJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 11 2004A. Lillo-Le Louet Summary. Heparin-induced thrombocytopenia (HIT) occurs in nearly 3% of patients treated with heparin after cardiopulmonary bypass (CPB). HIT carries a risk of severe thrombotic complications, and must be diagnosed rapidly. To identify simple criteria for estimating the probability of HIT after CPB, we retrospectively analyzed the files of 84 patients with suspected HIT after CPB and we analyzed the usefulness of several variables collected at the time of HIT suspicion to estimate HIT probability. HIT was confirmed in 35 cases and ruled out in 49 cases, on the basis of a platelet increment after heparin withdrawal, detection of heparin-dependent antibodies, and absence of other clear cause of thrombocytopenia. A biphasic platelet count from CPB to the first day of suspected HIT, an interval of ,,5 days from CPB to the first day of suspected HIT, and a CPB duration of ,,118 min were independent risk factors for HIT. These variables were combined to create a post-CPB HIT probability score. The score correctly identified 34/35 HIT patients and 28/49-non-HIT patients. This score, which can be applied as soon as HIT is suspected after CPB, has very good negative predictive value (97%). Prospective studies are required to confirm these findings. [source] Heparin-induced thrombocytopenia and warfarin-induced skin necrosis in a child with severe protein C deficiency: successful treatment with dermatan sulfate and protein C concentrateJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 2 2003L. Gatti No abstract is available for this article. [source] Heparin-induced thrombocytopenia: Current status and diagnostic challenges,AMERICAN JOURNAL OF HEMATOLOGY, Issue 9 2010Stavroula A Otis Heparin-induced thrombocytopenia (HIT) is a fairly common and potentially catastrophic complication of heparin therapy. Diagnosing HIT remains a challenge, as the patients at risk often have other reasons for thrombocytopenia and/or thrombosis. HIT is considered a clinicopathologic disorder whose diagnosis is generally made on the basis of both clinical criteria and the presence of "HIT antibodies" in the patient's serum or plasma. There are two basic laboratory approaches to detect HIT antibodies. The immunoassays detect antibodies based on their binding properties, whereas the functional assays detect antibodies based on their platelet-activating properties. Prompt and accurate diagnosis of HIT is imperative, as overdiagnosis exposes patients to alternative anticoagulants and their associated bleeding risks, whereas under- or delayed diagnosis leaves patients vulnerable to the thromboembolic sequelae of HIT, which can be life threatening. A critical interpretation of laboratory results by the clinician is an essential component of diagnosing HIT. This requires a keen understanding of the current concepts in the pathophysiologic mechanisms of the disease, and the application of these concepts when interpreting the results of both the functional and immunoassays. Equally important is an awareness of the strengths and weaknesses, as well as the current lack of standardization and proficiency testing, of these assays. Am. J. Hematol., 2010. © 2010 Wiley-Liss, Inc. [source] Heparin-induced thrombocytopenia with multiple organized thrombi accompanied by unusual cholesterin deposition: Autopsy case after long-term follow upPATHOLOGY INTERNATIONAL, Issue 10 2009Masaaki Ichinoe Heparin-induced thrombocytopenia (HIT) is characterized by a reduction in the platelet count and systemic thromboembolism during heparin therapy. Herein is reported a case of HIT with characteristic thrombus formation. A 68-year-old man who had been treated for hypertension for 27 years suffered a brain infarction and was treated with heparin. After this treatment, other new infarctions occurred in multiple organs. Because serum antibodies against heparin/PF4 complex were detected, he was diagnosed as having HIT, and warfarin and argatroban were administered instead of heparin. He died, however, 119 days after the first onset. At autopsy infarction due to organized thrombi with cholesterin deposition in multiple organs were found, similar to usual atherosclerotic emboli, but different to them with regard to clinical course and distribution of thrombi. This case in which organization and frequent cholesterin deposition were found in thromboembolized lesions of multiple organs after relatively long-term follow up, is unusual. The findings suggest that HIT accompanied by marked hypercholesterolemia of long duration contributes to a characteristic form of thromboembolism that needs careful management. [source] Utility of consecutive repeat HIT ELISA testing for heparin-induced thrombocytopeniaAMERICAN JOURNAL OF HEMATOLOGY, Issue 3 2008Maren Chan Heparin-induced thrombocytopenia (HIT) is a serious complication of heparin therapy. Limited data are available regarding repeat HIT antibody testing after an initial negative test. We conducted a retrospective study to determine the utility of repeat testing. Heparin antibodies were detected using the GTI-PF4 enzyme-linked immunoabsorbent assay, ELISA (GTI Diagnostics, Waukesha, WI). Patients (n = 137) were assigned to one of three groups based upon the initial negative test optical density (OD) range of low = 0,0.132, medium = 0.133,0.267, and high = 0.268,0.399. A pretest clinical score was retrospectively determined using the "4T's" (Thrombocytopenia, Timing of platelet fall, Thrombosis, and the absence of oTher causes of thrombocytopenia). A subsequent positive ELISA was found in 16% (22/137) of patients who underwent repeat testing. Most of these patients had a low pretest clinical score (62%). Four patients had an interval change in the pretest score between the initial negative and subsequent positive tests. Only these four patients developed HIT with thrombosis (HITT). Eighty percent of patients with a high initial negative test OD value had a positive ELISA on repeat testing; however, the initial negative test OD value could not predict whether a patient developed HITT. In contrast, an increase in the pretest clinical probability between initial and repeat testing better predicted HITT. Consecutive repeat ELISA testing for heparin antibodies may be warranted in patients with an increase in their pretest clinical score after an initial negative test as an adjunct to confirm the diagnosis of HIT. Am. J. Hematol., 2008. © 2007 Wiley-Liss, Inc. [source] Heparin-induced thrombocytopenia: pathogenesis and managementBRITISH JOURNAL OF HAEMATOLOGY, Issue 2 2003Rasheed A Saad No abstract is available for this article. [source] Heparin-induced thrombocytopenia: pathogenesis and management , Response to Rasheed SaadBRITISH JOURNAL OF HAEMATOLOGY, Issue 2 2003Theodore E. Warkentin No abstract is available for this article. [source] Biological and clinical features of low-molecular-weight heparin-induced thrombocytopeniaBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2003Yves Gruel Summary. Heparin-induced thrombocytopenia (HIT) is a common adverse effect of unfractionated heparin (UFH) therapy. In contrast, only a few patients have been reported with HIT following low-molecular-weight heparin (LMWH) therapy (LMW-HIT). To define the clinical and biological characteristics of LMW-HIT, 180 patients treated for suspected HIT at 15 French centres were investigated. Clinical history was recorded and HIT was confirmed in 59 patients with positive serotonin release assay results: 57 of them had high levels of antibodies (Abs) to heparin,platelet factor 4 complexes (H/PF4) and two had Abs to interleukin 8. Eleven patients were treated exclusively with LMWH (LMW-HIT) and 48 with UFH either alone (UF-HIT, n = 34) or combined with LMWH (UF/LMW-HIT, n = 14). The LMW-HIT and UF-HIT groups were similar with respect to sex, age, platelet count before heparin therapy, frequency of bleeding and occurrence of disseminated intravascular coagulation. The interval to onset of HIT was longer in LMW-HIT patients compared with UF-HIT patients (P = 0·03). Severe thrombocytopenia (platelets <,15 × 109/l) was more frequent in the LMW-HIT group (P = 0·04). Thrombosis occurred in three of 11 LMW-HIT patients, i.e. as frequently as in UF-HIT patients. LMW-HIT is potentially severe and may be observed after longer heparin treatment compared with UF-HIT. It is highly recommended, therefore, that platelet counts be monitored carefully whenever LMWH is administered. [source] Heparin-induced thrombocytopenia (HIT) causing pulmonary emboli during coronary intervention,CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS, Issue 6 2008Ronny S. Jiji MD Abstract Thrombotic complications of heparin-induced thrombocytopenia (HIT) can be devastating if not recognized and treated promptly. We describe an unusual case of rapid-onset HIT resulting in massive-bilateral pulmonary emboli in a 70 year-old man who developed chest pain during elective percutaneous coronary intervention (PCI). The diagnosis was made the following day after persistent chest pain and laboratory work demonstrating a new thrombocytopenia, a mildly elevated troponin, and positive DIC panel led to confirmatory imaging tests. HIT-related thrombosis should be considered in the differential diagnosis of chest pain in patients undergoing PCI. © 2008 Wiley-Liss, Inc. [source] Heparin-induced thrombocytopenia and thrombosisCLINICAL CARDIOLOGY, Issue 9 2004Georges Chahoud M.D. No abstract is available for this article. [source] Should patients be informed about the risk of heparin-induced thrombocytopenia before prolonged low-molecular-weight heparin thromboprophylaxis post-trauma/orthopedic surgery?EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2007Norbert Lubenow Abstract Objectives:, Heparin-induced thrombocytopenia (HIT) is an immune-mediated prothrombotic adverse drug effect that occurs less frequently with low-molecular-weight heparin (LMWH) than with unfractionated heparin (UFH) in post-trauma/orthopedic surgery patients. The life-threatening nature of HIT raises the question whether informed consent for this treatment-induced adverse effect should be obtained, particularly as LMWH is often continued during the outpatient period when clinical and platelet count monitoring become problematic. Paradoxically, refusal of thromboprophylaxis as a result of seeking informed consent could increase risk for thrombosis. Methods:, We evaluated in patients undergoing routine LMWH thromboprophylaxis post-trauma/orthopedic surgery the feasibility of obtaining informed consent, using a standardized questionnaire to determine patient preferences. We also identified the proportion of HIT patients in our laboratory comprised of trauma/orthopedic surgery patients from 1995,1997 and 2002,2004 (time periods characterized, respectively, by UFH and LMWH thromboprophylaxis for this patient population). Results:, None of 460 patients in whom informed consent was administered rejected LMWH thromboprophylaxis. The patients' perception of the informed consent process and the written information provided about the risk of HIT and its risk due to clinical consequences were highly favorable. From 1995,1997 to 2002,2004, the proportion of HIT identified among trauma/orthopedic surgery patients declined from 30.3% to 1.2% (P < 0.0001). Conclusions:, Obtaining informed consent about HIT is feasible in written form and does not cause refusal of LMWH thromboprophylaxis. Despite the uncommon occurrence of HIT during LMWH thromboprophylaxis, informed consent increases patient's awareness of this potentially life-threatening adverse drug effect, an outcome that could increase outpatient recognition of the diagnosis. [source] Etiology of thrombocytopenia in all patients treated with heparin productsEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2 2005Damian A. Laber Abstract:,Purpose:,To characterize the cause of thrombocytopenia in all patients treated with heparin products, to determine the incidence of heparin-induced thrombocytopenia (HIT) in unselected hospitalized patients, and to have modern data of the magnitude of this problem. Methods:,Retrospective hospital-based cohort study. During a random 2-month period, we reviewed the medical records of all patients treated with heparin agents, screened them for thrombocytopenia, and determined the cause of it. Results:,Out of 674 patients who received heparin products, 110 (16%) had thrombocytopenia. The most common causes included cancer chemotherapy, surgery, sepsis, and medications. Three patients met the clinical criteria for HIT. One had antibodies for heparin-platelet factor-4, and received a direct thrombin inhibitor. The other two individuals had a clinical syndrome that resembled immune HIT, but were not tested for HIT antibodies. One suffered a thrombotic episode that led to the death of her fetus. The other died of a possible thromboembolism. Conclusions:,This study provides evidence-based data for the differential diagnosis of thrombocytopenia after treatment with heparin products. Our findings suggest that increased awareness of the HIT syndrome might reduce morbidity and mortality. Patients exposed to heparin products, who develop thrombocytopenia, should not be overlooked. [source] Acute cardiorespiratory collapse from heparin: a consequence of heparin-induced thrombocytopeniaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2004Martha P. Mims Abstract: Background:, Heparin has rarely been reported to cause acute cardiorespiratory reactions or collapse. Some reports relate this to underlying heparin-induced thrombocytopenia. Objective:, To confirm and increase awareness of acute life-threatening cardiopulmonary events when patients with heparin-induced thrombocytopenia are re-exposed to heparin. Design:, Retrospective observational case series. Patients/setting:, Four cardiovascular surgery patients were identified in two adjacent large urban hospitals over a 2-yr-period who experienced eight episodes of cardiorespiratory collapse immediately following heparin administration. All had underlying heparin-induced thrombocytopenia. Results:, Intravenous boluses of unfractionated heparin were given to four patients with known or previously unrecognized heparin-induced thrombocytopenia. Two patients experienced severe respiratory distress within 15 min for which they required endotracheal intubation. Two other patients experienced cardiac arrest or a lethal arrhythmia within minutes of receiving intravenous heparin. Serologic tests for heparin-induced antibodies were positive in all patients. In three cases, the platelet count was normal or near normal but fell dramatically (71%) immediately following the heparin bolus. Three cases had prior diagnoses of heparin-induced thrombocytopenia, but health care workers administered heparin either unaware of the diagnosis or ignorant of its significance. No patients died, but all required some form of cardiopulmonary resuscitation and subsequent intensive care. Conclusions:, Heparin administration to patients with heparin-induced antibodies can result in life-threatening pulmonary or cardiac events. Appreciation of this phenomenon can unmask cases of heparin-induced thrombocytopenia and strengthens the mandate to avoid any heparin exposure in affected patients. Recognition is crucial to avoiding disastrous outcomes. [source] An evaluation of monitoring possibilities of argatroban using rotational thromboelastometry and activated partial thromboplastin timeACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 1 2010M. ENGSTRÖM Background: Rotational thrombelastometry/thrombelastography with ROTEM® and TEG® is becoming available bedside in an increasing number of intensive care units, where many patients with heparin-induced thrombocytopenia (HIT) are treated. The study has been performed in an effort to find out whether ROTEM® could be an alternative to activated partial thromboplastin time (aPTT) when argatroban is used for anticoagulation. Methods: Argatroban was added in vitro to a series of citrated whole-blood samples from 10 healthy volunteers to obtain whole-blood concentrations of 0, 0.125, 0.25, 0.5, 1.0, 2.0, 4.0 and 8.0 mg/l. ROTEM® and whole-blood aPTT analyses were performed at each argatroban concentration. Correlation analyses were performed using the Spearman correlation analysis. Results: There was a significant and strong correlation between argatroban concentrations and clotting time (CT in ROTEM® analysis with INTEM) (P<0.0001 and r=0.98). Also, the ROTEM® time to maximum clot formation velocity (MAXV-t) appeared to have a very strong and highly significant correlation to argatroban concentrations (P<0.0001 and r=0.95). When we studied the correlation between aPTT and CT, we found a highly significant and strong correlation between these two analyses (P<0.0001 and r=0.97), especially so in the clinically relevant therapeutic range up to 100 s aPTT prolongation for HIT patients. Conclusion: A significant and strong correlation was found between argatroban concentrations and several ROTEM® parameters. Rotational thrombelastometry/thrombelastography has a potential role in increasing the safety of argatroban anticoagulation in critically ill patients. [source] Hypothermic cardiopulmonary bypass as a determinant of late thrombocytopenia following cardiac operations in pediatric patientsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 8 2009M. RANUCCI Background: Thrombocytopenia after cardiac operations is a common event in both adult and pediatric patients. Late thrombocytopenia (LTCP) is a less common event that is still without a well-recognized cause. This study explores the role of heparin-induced thrombocytopenia (HIT) and other factors (complexity of the operation, temperature management, and drug use) in determining LTCP. Methods: We conducted an observational study of 63 consecutive patients aged <36 months operated with or without cardiopulmonary bypass (CPB). LTCP was defined as a platelet count <100,000 cells/,l or <50% of the pre-operative count at any point in time between post-operative days 5 and 10. A diagnostic test for heparin-platelet factor 4 (PF4) antibodies was performed in patients with LTCP. Other pre- and post-operative factors were investigated for their association with LTCP. Results: LTCP occurred in 15 (24%) patients. No patient had positive heparin-PF4 antibodies. The lowest temperature on CPB was an independent predictor of LTCP, with a cut-off value at 29 °C (sensitivity 80%, specificity 70%). Other factors associated with LTCP were prolonged post-operative use of unfractionated heparin and milrinone. LTCP was associated with increased post-operative morbidity. Conclusion: LTCP was related to a combination of factors (operation severity, degree of hypothermia during CPB, prolonged use of unfractionated heparin, and milrinone). The individual contribution of each factor seems difficult to establish. However, the degree of hypothermia during CPB and drug-associated effects were identified. HIT could be excluded in all cases. [source] Thrombocytopenia in Patients Treated with Heparin, Combination Antiplatelet Therapy, and Intra-Aortic Balloon Pump CounterpulsationJOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 4 2008B.C.P.S., HEATHER R. BREAM-ROUWENHORST Pharm D. Objectives:Determine the incidence and timing of intra-aortic balloon pump (IABP)-associated thrombocytopenia, if concomitant antiplatelet agents increase the incidence of thrombocytopenia, and the incidence of heparin-induced thrombocytopenia (HIT) in a contemporary IABP population. Background:Previous studies predate the current practice of treating acute coronary syndrome patients with heparin and aspirin plus thienopyridines and glycoprotein IIb/IIIa receptor antagonists such that data are unavailable to determine if their co-administration worsens IABP-associated thrombocytopenia. Methods:A retrospective cohort study of adult IABP patients (n = 107) from 2002 to 2006 was performed to determine the indication for and duration of counterpulsation, platelet counts during and for 7 days postcounterpulsation, medications potentially contributing to thrombocytopenia, and HIT antibody results if obtained. Results:Thrombocytopenia, defined as platelets <150,000/mL or >50% decrease from baseline, occurred in 57.9% of patients. Overall, platelets declined to 60.2 ± 22.8% of baseline with the mean (± standard deviation) nadir on day 2.8 ± 2.0. Comparing patients who received heparin, aspirin, thienopyridines, and glycoprotein IIb/IIIa antagonists (n = 44) versus heparinized patients ± aspirin (n = 45), platelet nadirs were 62.7 ± 20.9% versus 58.3 ± 23.9% of baseline levels, respectively (P = 0.42). The incidence of HIT was 2.8% in the entire cohort. Conclusions:IABP-associated thrombocytopenia occurred in 57.9% of this cohort. HIT was diagnosed in 2.8% and should be considered as a diagnosis if platelet counts do not stabilize or continue to fall after 3,4 days of counterpulsation. Increased use of antiplatelet therapy does not impact the degree of thrombocytopenia although the current practice of prompt IABP removal may offset this effect. [source] Early-onset and persisting thrombocytopenia in post-cardiac surgery patients is rarely due to heparin-induced thrombocytopenia, even when antibody tests are positiveJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 1 2010S. SELLENG See also Gruel Y, Pouplard C. Post-operative platelet count profile: the most reliable tool for identifying patients with true heparin-induced thrombocypenia after cardiac surgery. This issue, pp 27,29. Summary.,Background:,The high frequency of thrombocytopenia in post-cardiac surgery patients makes it challenging to diagnose heparin-induced thrombocytopenia (HIT). Two platelet count profiles are reported as indicating possible HIT in these patients: profile 1 describes a platelet count fall that begins between postoperative days 5 and 10, whereas profile 2 denotes early-onset thrombocytopenia that persists beyond day 5. Objectives: To examine how these platelet count profiles correlate with antibody status and HIT post-cardiac surgery. Methods: We prospectively screened 581 cardiac surgery patients for heparin-dependent antibodies by platelet factor 4 (PF4),heparin immunoassay and platelet-activation test, and performed daily platelet counts (until day 10) with 30-day follow-up. Results: All three patients with platelet count profile 1 tested positive for platelet-activating anti-PF4,heparin IgG antibodies [odds ratio (OR) 521.7, 95% confidence interval (CI) 3.9,34 000, P = 0.002], and were judged to have HIT. In contrast, none of 25 patients with early-onset and persisting thrombocytopenia (profile 2) was judged to have HIT, including five patients testing positive for platelet-activating anti-PF4,heparin IgG antibodies. In these patients, the frequency of heparin-dependent antibodies did not differ from that in non-thrombocytopenic controls, either for anti-PF4,heparin IgG (OR 1.7, 95% CI 0.7,4.1, P = 0.31) or for platelet-activating antibodies (OR 1.9, 95% CI 0.6,5.7, P = 0.20). Multivariate analysis revealed that type of cardiac surgery, but not HIT antibody status, predicted early-onset and persisting thrombocytopenia. Together, these findings show that HIT was uncommon in this study population [overall frequency, 3/581 (0.5%), 95% CI 0.1,1.5%]. Conclusions: Thrombocytopenia that begins between 5 and 10 days post-cardiac surgery is highly predictive for HIT. In contrast, early-onset and persisting thrombocytopenia is usually caused by non-HIT factors with coinciding heparin-dependent antibody seroconversion. [source] The costs of heparin-induced thrombocytopenia: a patient-based cost of illness analysisJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 5 2009T. WILKE Summary.,Background and objectives:,Due to the complexity of heparin-induced thrombocytopenia (HIT), currently available cost analyses are rough estimates. The objectives of this study were quantification of costs involved in HIT and identification of main cost drivers based on a patient-oriented approach. Methods:,Patients diagnosed with HIT (1995,2004, University-hospital Greifswald, Germany) based on a positive functional assay (HIPA test) were retrieved from the laboratory records and scored (4T-score) by two medical experts using the patient file. For cost of illness analysis, predefined HIT-relevant cost parameters (medication costs, prolonged in-hospital stay, diagnostic and therapeutic interventions, laboratory tests, blood transfusions) were retrieved from the patient files. The data were analysed by linear regression estimates with the log of costs and a gamma regression model. Mean length of stay data of non-HIT patients were obtained from the German Federal Statistical Office, adjusted for patient characteristics, comorbidities and year of treatment. Hospital costs were provided by the controlling department. Results and conclusions:,One hundred and thirty HIT cases with a 4T-score ,4 and a positive HIPA test were analyzed. Mean additional costs of a HIT case were 9008 ,. The main cost drivers were prolonged in-hospital stay (70.3%) and costs of alternative anticoagulants (19.7%). HIT was more costly in surgical patients compared with medical patients and in patients with thrombosis. Early start of alternative anticoagulation did not increase HIT costs despite the high medication costs indicating prevention of costly complications. An HIT cost calculator is provided, allowing online calculation of HIT costs based on local cost structures and different currencies. [source] Quantitative interpretation of optical density measurements using PF4-dependent enzyme-immunoassaysJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 8 2008T. E. WARKENTIN Summary.,Background:,Many laboratories test for heparin-induced thrombocytopenia (HIT) using a PF4-dependent enzyme-immunoassay (EIA). An advantage of the EIA is its simplicity; a disadvantage is that it only indirectly detects heparin-dependent, platelet-activating antibodies (,HIT antibodies'). Objectives:,To determine whether the magnitude of a positive EIA result, expressed in optical density (OD) units, predicts risk of HIT antibodies, defined as a strong-positive platelet serotonin-release assay (SRA) result (,50% serotonin release). Patients/methods:,We determined the risk of a strong-positive SRA result for five categories of OD reactivity (<0.40, 0.40,<1.00, 1.00,<1.40, 1.40,<2.00, and ,2.00 OD units) using two EIAs (commercial anti-PF4/polyanion IgG/A/M and in-house anti-PF4/heparin,IgG). Results:,For patient sera investigated for HIT antibodies, a weak-positive result (0.40,<1.00 OD units) in either EIA indicated a low probability (,5%) of a strong-positive SRA; the risk increased to ,90% with an OD , 2.00 units. Quantifying the EIA,SRA relationship for 1553 referred patient sera, we found that for every increase of 0.50 OD units in the EIA,IgG, the risk of a strong-positive SRA result increased by OR = 6.39 [95% confidence interval (CI), 5.13, 7.95; P < 0.0001]. For every increase of 1.00 OD units in the EIA,IgG, the risk increased by OR = 40.81 (95% CI, 26.35, 63.20; P < 0.0001). Conclusions:,The probability of HIT antibodies (strong-positive SRA result) inferred by a positive PF4-dependent EIA varies considerably in relation to the magnitude of the EIA result, expressed as OD values. In our laboratory, the probability of HIT antibodies being present reached ,50% only when the OD level was ,1.40 units. [source] Heparin-induced thrombocytopenia: a prospective study on the incidence, platelet-activating capacity and clinical significance of antiplatelet factor 4/heparin antibodies of the IgG, IgM, and IgA classesJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 8 2007A. GREINACHER Summary.,Introduction:,Platelet-activating antiplatelet factor 4/heparin (anti-PF4/heparin) antibodies are the major cause of heparin-induced thrombocytopenia (HIT). However, the relative utility of functional (platelet activation) vs. antigen [enzyme-immunoassay (EIA)] assays, and the significance of assay discrepancies remain unresolved.Methods:,Consecutive patient sera (n = 1650) referred for diagnostic HIT testing were screened prospectively by both the heparin-induced platelet activation (HIPA) test and anti-PF4/heparin EIA , including individual classes (IgG, IgA, IgM) , with clinical correlations studied. Platelet microparticle and annexin-V-binding properties of the sera were also investigated.Results:,Only 205 (12.4%) sera tested positive in either the HIPA and/or EIA: 95 (46.3%) were positive in both, 109 (53.1%) were only EIA-positive, and, notably, only one serum was HIPA-positive/EIA-negative. Of 185 EIA-positive sera, only 17.6% had detectable IgM and/or IgA without detectable IgG. Among sera positive for EIA IgG, optical density values were higher when the sera were HIPA-positive (1.117 vs. 0.768; P < 0.0001), with widely overlapping values. Two HIPA-positive but EIA-IgG-negative sera became HIPA-negative following IgG depletion, suggesting platelet-activating antibodies against non-PF4-dependent antigens. Clinical correlations showed that HIPA-negative/EIA-positive patients did not develop thrombosis and had reasons other than HIT to explain thrombocytopenia. IgM/A antibodies did not increase microparticle penetration, but increased annexin-V binding.Conclusions:,The anti-PF4/heparin EIA has high (,99%) sensitivity for HIT. However, only about half of EIA-positive patients are likely to have HIT. Anti-PF4/heparin antibodies of IgM/A class and non-PF4-dependent antigens have only a minor role in HIT. [source] IgG classification of anti-PF4/heparin antibodies to identify patients with heparin-induced thrombocytopenia during mechanical circulatory supportJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 2 2007S. SCHENK Summary., Commercial immunoassays frequently detect anti-PF4/heparin antibodies during mechanical circulatory support (MCS), but only a small minority of patients develops heparin-induced thrombocytopenia (HIT). Whereas platelet functional tests can distinguish between platelet-activating and non-platelet-activating antibodies, commercial PF4-dependent immunoassays do not. Between 2003 and 2004, 113 patients were placed on MCS. Blood samples were obtained on postimplant day 5,7 for analyses by antibody assays and the functional heparin-induced platelet activation (HIPA) assay. Three distinct groups of patient sera were identified: platelet-activating anti-PF4/heparin antibodies (n = 10), non-platelet-activating anti-PF4/heparin antibodies (n = 53), and anti-PF4/heparin antibody negative (n = 50). Patients with platelet-activating antibodies had the highest risk for thromboembolic events (P < 0.005), whereas those with non-platelet-activating antibodies did not differ from antibody negative patients (P = 0.369). The enzyme-immunoassay and column agglutination assays, which cover all immunoglobulin classes, demonstrated adequate sensitivity and negative predictive value; yet, both lacked specificity with respect to the platelet-activating antibodies. If all antibody positive patients were further classified by an IgG-specific anti-PF4/heparin enzyme-immuno assay, specificity for platelet-activating antibodies increased. Whereas IgG-specific optical density (OD) values below 1.0 were likely for non-platelet-activating anti-PF4/heparin antibodies, higher values were progressively predictive for pathogenic platelet activation. The probability of the development of clinical HIT also increased steeply. In conclusion, platelet-activating anti-PF4/heparin antibodies are relatively common (about 9%) in patients on MCS and are associated with significantly higher thrombotic event rates. Low IgG-specific OD values (< 1.0) in the enzyme-immunoassay indicate low likelihood for the presence of platelet-activating antibodies. These results justify further validation so that anticoagulation during MCS becomes safer and adequate. [source] IN FOCUS: Activation of platelets by heparin-induced thrombocytopenia antibodies in the serotonin release assay is not dependent on the presence of heparinJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 10 2005M. M. PRECHEL Summary., The serotonin release assay (SRA) tests for antibodies responsible for heparin-induced thrombocytopenia (HIT). By definition, SRA-positive antibodies cause platelet serotonin release in vitro, in the presence of low concentrations of heparin, but not with excess heparin. Many SRA-positive sera activate platelets in the presence of saline without drug, either as a result of residual heparin in the specimen, or because of intrinsic features of the HIT antibodies. The present experiments show that neither exhaustive heparinase treatment, nor chromatographic removal of heparin abrogates the spontaneous platelet activation caused by these HIT antibodies. This is the first study to systematically demonstrate that in vitro activity of HIT antibodies can be independent of heparin. In addition, T-gel chromatography demonstrated differences among fractions of enzyme-linked-immunosorbent assay (ELISA)-positive HIT antibodies within individual specimens. Certain ELISA-positive fractions had SRA activity while others did not, and the SRA activity was not proportional to HIT antibody ELISA titer. These data suggest that antibodies formed as a result of heparin treatment are heterogeneous, and that some can contribute to the pathogenesis of HIT even when heparin is no longer present. [source] Diagnostic score for heparin-induced thrombocytopenia after cardiopulmonary bypassJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 11 2004A. Lillo-Le Louet Summary. Heparin-induced thrombocytopenia (HIT) occurs in nearly 3% of patients treated with heparin after cardiopulmonary bypass (CPB). HIT carries a risk of severe thrombotic complications, and must be diagnosed rapidly. To identify simple criteria for estimating the probability of HIT after CPB, we retrospectively analyzed the files of 84 patients with suspected HIT after CPB and we analyzed the usefulness of several variables collected at the time of HIT suspicion to estimate HIT probability. HIT was confirmed in 35 cases and ruled out in 49 cases, on the basis of a platelet increment after heparin withdrawal, detection of heparin-dependent antibodies, and absence of other clear cause of thrombocytopenia. A biphasic platelet count from CPB to the first day of suspected HIT, an interval of ,,5 days from CPB to the first day of suspected HIT, and a CPB duration of ,,118 min were independent risk factors for HIT. These variables were combined to create a post-CPB HIT probability score. The score correctly identified 34/35 HIT patients and 28/49-non-HIT patients. This score, which can be applied as soon as HIT is suspected after CPB, has very good negative predictive value (97%). Prospective studies are required to confirm these findings. [source] Minimizing the incidence of heparin-induced thrombocytopenia: to heparinize or not to heparinize vascular access?PEDIATRIC ANESTHESIA, Issue 12 2005JOHN L. CHOW MD MS First page of article [source] Utility of consecutive repeat HIT ELISA testing for heparin-induced thrombocytopeniaAMERICAN JOURNAL OF HEMATOLOGY, Issue 3 2008Maren Chan Heparin-induced thrombocytopenia (HIT) is a serious complication of heparin therapy. Limited data are available regarding repeat HIT antibody testing after an initial negative test. We conducted a retrospective study to determine the utility of repeat testing. Heparin antibodies were detected using the GTI-PF4 enzyme-linked immunoabsorbent assay, ELISA (GTI Diagnostics, Waukesha, WI). Patients (n = 137) were assigned to one of three groups based upon the initial negative test optical density (OD) range of low = 0,0.132, medium = 0.133,0.267, and high = 0.268,0.399. A pretest clinical score was retrospectively determined using the "4T's" (Thrombocytopenia, Timing of platelet fall, Thrombosis, and the absence of oTher causes of thrombocytopenia). A subsequent positive ELISA was found in 16% (22/137) of patients who underwent repeat testing. Most of these patients had a low pretest clinical score (62%). Four patients had an interval change in the pretest score between the initial negative and subsequent positive tests. Only these four patients developed HIT with thrombosis (HITT). Eighty percent of patients with a high initial negative test OD value had a positive ELISA on repeat testing; however, the initial negative test OD value could not predict whether a patient developed HITT. In contrast, an increase in the pretest clinical probability between initial and repeat testing better predicted HITT. Consecutive repeat ELISA testing for heparin antibodies may be warranted in patients with an increase in their pretest clinical score after an initial negative test as an adjunct to confirm the diagnosis of HIT. Am. J. Hematol., 2008. © 2007 Wiley-Liss, Inc. [source] Heparin-induced skin necrosis associated with thrombocytopenia and acquired protein C and protein S deficiencyAMERICAN JOURNAL OF HEMATOLOGY, Issue 12 2007H. Keshava Prasad We have described a patient with colon cancer and liver metastases who developed heparin-induced thrombocytopenia and skin necrosis. We believe that the skin necrosis caused by the heparin/platelet factor 4 antibody was exacerbated by the acquired protein C and protein S deficiency. After the heparin was discontinued and infection treated, the skin necrosis and thrombocytopenia resolved. This case illustrates the fact that, in patients with heparin-induced skin necrosis, a search must be undertaken for an underlying pro-thrombotic state, which may precipitate the microthrombosis responsible for skin necrosis. We could not find any previous case reports of heparin-induced skin necrosis associated with isolated protein C deficiency, or combined protein C and protein S deficiency. Am. J. Hematol., 2007. © 2007 Wiley-Liss, Inc. [source] Latest news and product developmentsPRESCRIBER, Issue 6 2008Article first published online: 24 APR 200 Government responds to NICE report The Government has published its response to the Health Select Committee's report into NICE, broadly arguing that the Committee's recommendations are either already being dealt with or are not appropriate. The Committee recommended appraisals for all new drugs, shorter, rapid appraisals to coincide with their launch, and improved mechanisms for setting drug prices. The Government says its negotiations on the PPRS preclude a detailed response but suggests a rapid system may not be transparent or legally robust. It is exploring how high-cost drugs can be brought within the payment-by-results tariff. While defending NICE's reliance on QALYs, the Government accepts the need to explore how wider economic factors can be considered. As for the threshold cost per QALY by which NICE defines cost effectiveness, it says this is being validated scientifically and NICE will continue to determine the threshold. More topically, the Committee criticised the quality of clinical trial data available to NICE. The Government sees no need to compel pharmaceutical companies to disclose information and says NICE is already becoming more involved with research programmes. All clinical trials must be registered (confidentially) with the EU and the Government believes mandatory registration in the UK would be ineffective and illegal. Prescription charge up again from April The Government has raised the prescription charge by 25p to £7.10 per item with effect from 1 April. Prescription prepayment certificates will cost £27.85 for three months and £102.50 for 12 months. The increase, below the annual rate of inflation for the 10th successive year, will be levied on the 12 per cent of prescriptions that are liable for the charge: 5 per cent via prepayment certificates and 7 per cent from other prescriptions. The charge will generate £435 million in England in 2008/09; this excludes money from prescriptions written by dispensing doctors, which is retained by the PCT. Following criticism of the charge by the Health Select Committee, the Government says it has reviewed the charge and is now consulting on ,cost-neutral' options. MHRA safety update The MHRA warns of possible dose errors associated with Boots Medisure Domiciliary Dosage System in its latest issue of Drug Safety Update (2008;1:issue 8). One case has been reported in which incomplete sealing allowed tablets to mix between compartments. No other cases are known and the MHRA says no harm was reported but the risk is serious. The system should be carefully sealed and inspected visually and physically. The MHRA reaffirms its plans to reclassify all pseudoephedrine and ephedrine products to prescription-only status in 2009 if the new restrictions on sales do not reduce misuse. Other topics in this month's Update include revised indications for oral ketoconazole (Nizoral), restricting its use to selected conditions unresponsive to topical therapy; reformulation of the injectable antibiotic Tazocin (piperacillin plus tazobactum); the risk of peripheral neuropathy associated with pegylated interferon and telbivudine (Sebivo) in the treatment of hepatitis B; and serious adverse events associated with modafinil (Provigil). First oral anticoagulant since warfarin In January this year the EMEA issued a positive opinion to recommend marketing authorisation of the oral, fixed-dose, direct thrombin inhibitor dabigatran etexilate (Pradaxa) for the primary prevention of venous thromboembolism (VTE) in adult patients that have undergone elective knee or hip replacement surgery. Marketing authorisation for the EU (including the UK) is expected from the European Commission in the next few weeks, making dabigatran the first oral anticoagulant since warfarin was introduced in 1954. Dabigatran etexilate has been shown to be as safe and effective as enoxaparin (Clexane) with a similar adverse event profile in the noninferiority phase III RENOVATE (Lancet 2007;370: 949-56) and RE-MODEL (J Throm Haemost 2007;5:217885) trials, which investigated the efficacy and safety of dabigatran compared to enoxaparin in reducing the risk of VTE after total hip and knee surgery respectively. Dabigatran has the practical advantage over low-molecular-weight heparin of oral postoperative administration and no risk of heparin-induced thrombocytopenia and, unlike warfarin, does not require monitoring or dose titration. Risk scale predicts anticholinergic effects US investigators have developed a scale for predicting the risk of anticholinergic side-effects from older patients' medicines (Arch Intern Med 2008;168: 508-13). The scale assigns a score from 1 (low) to 3 (high) for the risk of anticholinergic effects such as dry mouth, constipation and dizziness associated with commonly prescribed medicines. Checking the scale retrospectively in older patients in residential care, a higher score was associated with a 30 per cent increased risk of side-effects after adjustment for age and number of medicines. When this was repeated prospectively in a primary-care cohort, the increased risk was 90 per cent. HRT cancer risk persists The latest analysis of the Women's Health Initiative (WHI) trial of HRT shows that the small increase in the risk of cancer persists for up to three years after stopping treatment (J Am Med Assoc 2008;299:1036-45). WHI was stopped after 5.6 years' follow-up when it became clear the risks of HRT outweighed its benefits. This follow-up after a further three years (mean 2.4) involved 15 730 women. The annual risk of cardiovascular events was similar for HRT (1.97 per cent) and placebo (1.91 per cent). Cancers were more common among women who had taken HRT (1.56 vs 1.26 per cent), in particular breast cancer (0.42 vs 0.33 per cent). All-cause mortality was higher, but not statistically significantly so, with HRT (1.20 vs 1.06 per cent). Tight glycaemic control may increase falls Maintaining HbA1C at or below 6 per cent with insulin is associated with an increased risk of falls, a US study suggests (Diabetes Care 2008;31:391-6). The Health, Aging and Composition study involved 446 older people with type 2 diabetes (mean age 74) followed up for approximately five years. The incidence of falls ranged from 22 to 30 per cent annually. Comparing subgroups with HbA1C of ,6 per cent and >8 per cent, an increased risk of falls was associated with insulin use (odds ratio 4.4) but not oral hypoglycaemic drugs. Copyright © 2008 Wiley Interface Ltd [source] Immediate Posttransplantation Cotrimoxazole-Induced Immune ThrombocytopeniaAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2010R. Caluwé Drug-induced immune thrombocytopenia (DITP) can be caused by numerous drugs. When this condition develops, platelet destruction results from binding of antibodies to normal platelets only in the presence of a sensitizing drug. A recently proposed model suggests that these drug-dependent antibodies are derived from a pool of naturally occurring antibodies with weak affinity for specific epitopes on certain platelet membrane glycoproteins. We describe here a case of DITP secondary to cotrimoxazole exposure in the immediate posttransplantation phase in a renal transplant recipient. Apart from heparin-induced thrombocytopenia, DITP posttransplantation has to the best of our knowledge never been described, perhaps because of its immune-mediated origin. Our case demonstrates that DITP can occur posttransplantation, that cotrimoxazole due to its intensive use in the transplanted population is one of the most likely causative agents and that a timely recognition and treatment might have important consequences for both graft and patient. [source] | |||||||||||||||||||||||||