scholarly journals MO871HEPARIN INDUCED THROMBOCYTOPENIA AND HEMODIALYSIS - SINGLE CENTRE EXPERINCE

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Ana Bulatovic ◽  
Vesna Maslarevic Radovic ◽  
Katarina Markovic ◽  
Jelena Bjedov ◽  
Petar Djuric ◽  
...  
Keyword(s):  
Unfractionated Heparin ◽  
Medical Center ◽  
Hemodialysis Patients ◽  
Elisa Test ◽  
Platelet Factor ◽  
Heparin Administration ◽  
Heparin Anticoagulation ◽  
Alternative Anticoagulation ◽  
Patients At Risk ◽  
Clinical Scoring

Abstract Background and Aims Heparin-induced thrombocytopenia (HIT) is a potentially fatal adverse reaction after administration of unfractionated or fractionated heparin, which underlies the generation of antibodies to the heparin complex and platelet factor 4 (PF4). It occurs in 5% of patients treated with unfractionated heparin and 0.5 - 1.5% fractionated heparin. The aim of the study is to determine the incidence and outcome of hemodialysis patients with HIT over 4-years period. Method This retrospective study analyzed patients who were tested for evidence of positive anti-heparin antibody in the period from 2015 to 2020 in Zvezdara University Medical Center. The diagnosis was confirmed by the 4T clinical scoring system, a positive antiheparin-PF4 ELISA test and a positive platelet aggregation test with heparin. Results During observation period, total of 64 tests were performed, out of which 23 patients were positive. Out of them, 14 patients were on HD, 7 patients (geriatric, surgery and cardiology departments) received therapy due to peripheral thrombosis, AIM or arrhythmia and 2 patients during 2020 due to SARS-CoV-2 bilateral pneumonia. All patients treated at nephrology, started hemodialysis (HD) with unfractionated heparin, while others were treated with LMWH. 4T scoring showed that 64% of patients had a moderate risk of developing HIT, while high risk was assessed in 36% of patients. Thrombotic complications in the form of deep venous thrombosis had 53% of patients and pulmonary thromboembolism had 17,5 % of patients. The greatest decrease in Tr was the most commonly observed between 10th and 14th day (61% of patients) and 39% from 4th to 10th day from start of heparin administration. In addition to heparin withdrawal and treatment with alternative non-heparin anticoagulation (fondaparinoux), 7 patients needed plasma treatment. 11 patients on HD were transferred to peritoneal dialysis (PD), and 3 patients recovered renal function. Overall mortality was 52%, and it was below 30% in hemodialysis patients. Conclusion HIT should be considered in patients at risk. It is necessary to abolish heparin treatment and use alternative method (PD) or alternative anticoagulation. Hemodialysis patients have better prognosis than other comparable patients

scholarly journals P1510INCIDENCE AND OUTCOME HEMODIALYSIS PATIENCE WITH HEPARIN INDUCED THROMBOCYTOPENIA - FOUR YEAR EXPERIENCE ZVEZDARA UNIVERSITY MEDICAL CENTER

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Ana Bulatovic ◽  
Vesna Maslarevic Radovic ◽  
Katarina Markovic ◽  
Petar Djuric ◽  
Jelena Tosic Dragovic ◽  
...  
Keyword(s):  
Unfractionated Heparin ◽  
Medical Center ◽  
Hemodialysis Patients ◽  
Elisa Test ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Heparin Administration ◽  
Alternative Anticoagulation ◽  
Patients At Risk ◽  
Clinical Scoring

Abstract Background and Aims Heparin-induced thrombocytopenia (HIT) is a potentially fatal adverse reaction after administration of unfractionated or fractionated heparin, which underlies the generation of antibodies to the heparin complex and platelet factor 4 (PF4). It occurs in 5% of patients treated with unfractionated heparin and 0.5 - 1.5% fractionated heparin. The aim of the study is to determine the incidence and outcome of hemodialysis patients with HIT over 4 years period. Method Our retrospective study analyzed patients who were tested for evidence of positive anti-heparin antibody in the period from 2015 to 2019 in Zvezdara University Medical Center. The diagnosis was confirmed by the 4T clinical scoring system, a positive antiheparin-PF4 ELISA test and a positive platelet aggregation test with heparin. Results During observation period, total of 54 tests were performed on HIT suspected patients, out of which 21 patients were positive. Out of them, 14 patients were on HD, and other 7 (geriatric, surgery and cardiology departments) received therapy due to peripheral thrombosis, AIM or arrhythmia. All patients treated at nephrology, started hemodialysis (HD) with unfractionated heparin, while others were treated with LMWH. 4T scoring showed that 64% of patients had a moderate risk of developing HIT, while high risk was assessed in 36% of patients. Thrombotic complications in the form of deep venous thrombosis had 50% of patients, pulmonary thromboembolism had 11% of patients. The greatest decrease in Tr was most commonly observed between 10th and 14th day (61% of patients) and 39% from 4th to 10th day from start of heparin administration. In addition to heparin withdrawal and treatment with alternative nonheparin anticoagulation (fondaparinoux), 5 patients needed plasma treatment. 11 patients on HD were transferred to peritoneal dialysis (PD), and 2 patients recovered renal function. Overall mortality was 52%, while in nephrology patients was below 30%. Conclusion HIT should be considered in patients at risk. It is necessary to abolish heparin treatment and use alternative method (PD) or alternative anticoagulation. Hemodialysis patients have better prognosis than other comparable patients.

scholarly journals Incidence and Outcomes of Heparin-Induced Thrombocytopenia Associated with a Heparin Shortage at a Large Academic Medical Center

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 10-10
Author(s):  
Stephanie L. Seto ◽  
Megan E. Barra ◽  
Russel J. Roberts ◽  
Rachel P. Rosovsky
Keyword(s):  
Unfractionated Heparin ◽  
Massachusetts General Hospital ◽  
Medical Center ◽  
Academic Medical Center ◽  
The United States ◽  
Mitigation Strategies ◽  
Drug Shortage ◽  
Bleeding Events ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is a life-threatening complication associated with significant morbidity and mortality in hospitalized patients. The 2019 African swine fever outbreak in China resulted in a critical national shortage of porcine-derived heparin products in the United States. As a result, our institution implemented a multitude of mitigation strategies to reduce heparin utilization by >80% and optimize safe and effective alternative therapies. The aim of this study was to determine whether this change in clinical practice impacted the incidence of HIT and associated outcomes. A single-center, retrospective cohort study was performed on patients admitted to Massachusetts General Hospital who were ≥ 18 years of age and had a positive platelet factor 4 (PF4) drawn between February 2019 and January 2020. Patient demographics, comorbidities, baseline labs, serotonin release assay results, timing and magnitude of platelet count fall, and characteristics of heparinoid and non-heparinoid anticoagulant use were collected from the medical record. Thrombotic and hemorrhagic outcomes were characterized. Seventy-five patients were included in the final analysis, of which 56 (75%) were critically-ill. Baseline characteristics were similar between groups including median age 66.8 years, 49% male, 80% Caucasian. Forty-four (59%) patients underwent surgery, 23 (31%) required continuous renal replacement therapy, and 13 (17%) underwent extracorporeal membrane oxygenation. Incidence of HIT with any exposure to heparinoid product was 0.3% and 0.15% (p=0.002) in the pre-shortage and shortage periods, respectively. In those who received therapeutic dose unfractionated heparin, incidence of HIT was 1.26% and 1.05% (p=0.63) in the pre-shortage and shortage groups, respectively. Thrombotic complications were observed in 19 (41%) patients in the pre-shortage group and 11 (38%) in the post-shortage group (p=0.77). Bleeding events were observed in 8 (17%) and 5 (17%) (p=0.99). We observed a lower incidence of HIT resulting from our institution's efforts to conserve unfractionated heparin supply and utilize alternative anticoagulants during a critical national drug shortage. There were no significant differences in associated thrombotic and bleeding events. Disclosures Rosovsky: Bristol-Myers Squibb, Dova, Janssen, Portola: Consultancy; Bristol-Myers Squibb, Janssen: Research Funding.

The Effect of Lysed Platelets on Neutralization of Heparin In Vitro with Protamine as Measured by the Activated Coagulation Time (ACT)

1991 ◽  
Vol 66 (02) ◽  
pp. 213-217 ◽  
Author(s):  
Arthur P Bode ◽  
William J Castellani ◽  
Edna D Hodges ◽  
Susan Yelverton
Keyword(s):  
Platelet Rich Plasma ◽  
Coagulation Time ◽  
Platelet Factor ◽  
Platelet Suspension ◽  
Antiheparin Activity ◽  
Unit Increase ◽  
Heparin Anticoagulation ◽  
Heparin Activity ◽  
Activated Coagulation Time

SummaryThe effect of lysed platelets on the activated coagulation time (ACT) was studied in heparinized whole blood during titration with protamine. Frozen-thawed washed platelet suspension, or a chromatography fraction thereof, or autologous frozen-thawed platelet-rich plasma was added in various dilutions to freshly drawn blood anticoagulated with 3,000 USP units/1 heparin. After a 10 min incubation, the amount of protamine needed to restore the ACT to baseline ("protamine titration dose") was determined. We found that the protamine titration dose decreased in proportion to the amount of lysed platelet material added; expressed as a percentage of the total number of platelets present, each unit increase in lysed platelets produced a 1.7% ±0.8 (SD) reduction in the protamine dose needed to normalize the ACT. A heparin activity assay showed that this effect was not due to antiheparin activity of lysed platelets such as platelet factor 4 (PF4). Our data indicate that the procoagulant activity of platelet membranes reduced the sensitivity of the ACT to heparin. These findings suggest that membranous platelet microparticles may cause an inaccurate calculation, based on the ACT, of a protamine dose to reverse heparin anticoagulation in cardiopulmonary bypass procedures.

Effects of Unfractionated and Low Molecular Weight Heparins on Platelet Thromboxane Biosynthesis “In Vivo”

1994 ◽  
Vol 72 (06) ◽  
pp. 942-946 ◽  
Author(s):  
Raffaele Landolfi ◽  
Erica De Candia ◽  
Bianca Rocca ◽  
Giovanni Ciabattoni ◽  
Armando Antinori ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Unfractionated Heparin ◽  
Low Molecular Weight Heparin ◽  
Primary Source ◽  
In Vivo Studies ◽  
Low Molecular Weight ◽  
Heparin Administration ◽  
To Receive

SummarySeveral “in vitro” and “in vivo” studies indicate that heparin administration may affect platelet function. In this study we investigated the effects of prophylactic heparin on thromboxane (Tx)A2 biosynthesis “in vivo”, as assessed by the urinary excretion of major enzymatic metabolites 11-dehydro-TxB2 and 2,3-dinor-TxB2. Twenty-four patients who were candidates for cholecystectomy because of uncomplicated lithiasis were randomly assigned to receive placebo, unfractionated heparin, low molecular weight heparin or unfractionaed heparin plus 100 mg aspirin. Measurements of daily excretion of Tx metabolites were performed before and during the treatment. In the groups assigned to placebo and to low molecular weight heparin there was no statistically significant modification of Tx metabolite excretion while patients receiving unfractionated heparin had a significant increase of both metabolites (11-dehydro-TxB2: 3844 ± 1388 vs 2092 ±777, p <0.05; 2,3-dinor-TxB2: 2737 ± 808 vs 1535 ± 771 pg/mg creatinine, p <0.05). In patients randomized to receive low-dose aspirin plus unfractionated heparin the excretion of the two metabolites was largely suppressed thus suggesting that platelets are the primary source of enhanced thromboxane biosynthesis associated with heparin administration. These data indicate that unfractionated heparin causes platelet activation “in vivo” and suggest that the use of low molecular weight heparin may avoid this complication.

Detection of Enhanced In Vivo Platelet α-Granule Release in Different Patient Groups - Comparison of β-Thromboglobulin, Platelet Factor 4 and Thrombospondin Assays

1984 ◽  
Vol 52 (02) ◽  
pp. 183-187 ◽  
Author(s):  
D A Lane ◽  
H Ireland ◽  
S Wolff ◽  
E Ranasinghe ◽  
J Dawes
Keyword(s):  
Platelet Factor 4 ◽  
Renal Elimination ◽  
Elevated Plasma ◽  
Platelet Factor ◽  
Release Reaction ◽  
Heparin Anticoagulation ◽  
Patient Groups ◽  
Granule Release ◽  
Sensitive Marker

SummaryDuring the platelet release reaction β-thromboglobulin (βTG), platelet factor 4 (PF4) and thrombospondin (TSP) are released from the platelet into plasma and assays of these proteins can be used to monitor in vivo platelet activation. We have assessed their relative merits as markers of the in vivo platelet α-granule release reaction in a number of patient groups which have previously been shown to have elevated plasma βTG and/or PF4 levels. It is concluded that in diseases or conditions not complicated by its reduced clearance, βTG is the most sensitive marker of in vivo platelet α-granule release. However, the TSP assay may be the least ambiguous when monitoring the platelet α-granule release reaction in patients with renal failure who are undergoing haemodialysis with heparin anticoagulation. Under these circumstances plasma βTG, but not PF4 or TSP, levels are elevated because of impaired renal catabolism, and the presence of a heparin-releasable reservoir of PF4 on the endothelium complicates the use of the PF4 assay. In liver failure none of these assays may accurately reflect platelet α-granule release because of impaired hepatic or renal elimination of the proteins.

Relative risk for cardiovascular morbidity in hemodialysis patients regarding gene polymorphism for IL-10, IL-6, and TNF

2016 ◽  
Vol 94 (10) ◽  
pp. 1106-1109 ◽  
Author(s):  
J. Tosic Dragovic ◽  
J. Popovic ◽  
P. Djuric ◽  
A. Jankovic ◽  
A. Bulatovic ◽  
...  
Keyword(s):  
Gene Polymorphism ◽  
Cerebrovascular Accident ◽  
Gene Polymorphisms ◽  
Cardiovascular Events ◽  
Medical Center ◽  
Hemodialysis Patients ◽  
Left Ventricular ◽  
Cardiovascular Morbidity ◽  
Number Of Patients ◽  
Tnf Gene

Uremia-related inflammation is prone to be a key factor to explain high cardiovascular morbidity in hemodialysis patients. Genetic susceptibility may be of importance, including IL-10, IL-6, and TNF. The aim was to analyze IL-10, IL-6, and TNF gene polymorphisms in a group of hemodialysis patients and to correlate the findings with cardiovascular morbidity. This study included 169 patients on regular hemodialysis at Zvezdara University Medical Center. Gene polymorphisms for IL-10, IL-6 and TNF were determined using PCR. These findings were correlated with the cardiovascular morbidity data from patient histories. Heterozygots for IL-10 gene showed significantly lower incidence of cardiovascular events (p = 0.05) and twice lower risk for development of myocardial infarction, but experienced twice higher risk for left ventricular hypertrophy. Regarding TNF gene polymorphism, patients with A allele had 1.5-fold higher risk for cerebrovascular accident and cardiovascular events and 2-fold higher risk for hypertension and peripheral vascular disease. Patients with G allele of IL-6 gene experienced 1.5-fold higher risks for cerebrovascular accident. We need studies with larger number of patients for definitive conclusion about the influence of gene polymorphisms on cardiovascular morbidity in hemodialysis patients and its importance in everyday clinical practice.

scholarly journals Heparin-induced thrombocytopenia: in vitro studies on the interaction of dabigatran, rivaroxaban, and low-sulfated heparin, with platelet factor 4 and anti-PF4/heparin antibodies

Blood ◽  
2012 ◽  
Vol 119 (5) ◽  
pp. 1248-1255 ◽  
Author(s):  
Krystin Krauel ◽  
Christine Hackbarth ◽  
Birgitt Fürll ◽  
Andreas Greinacher
Keyword(s):  
Factor Xa ◽  
Platelet Factor 4 ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Alternative Anticoagulation ◽  
Heparin Complexes ◽  
History Of

Abstract Heparin is a widely used anticoagulant. Because of its negative charge, it forms complexes with positively charged platelet factor 4 (PF4). This can induce anti-PF4/heparin IgG Abs. Resulting immune complexes activate platelets, leading to the prothrombotic adverse drug reaction heparin-induced thrombocytopenia (HIT). HIT requires treatment with alternative anticoagulants. Approved for HIT are 2 direct thrombin inhibitors (DTI; lepirudin, argatroban) and danaparoid. They are niche products with limitations. We assessed the effects of the DTI dabigatran, the direct factor Xa-inhibitor rivaroxaban, and of 2-O, 3-O desulfated heparin (ODSH; a partially desulfated heparin with minimal anticoagulant effects) on PF4/heparin complexes and the interaction of anti-PF4/heparin Abs with platelets. Neither dabigatran nor rivaroxaban had any effect on the interaction of PF4 or anti-PF4/heparin Abs with platelets. In contrast, ODSH inhibited PF4 binding to gel-filtered platelets, displaced PF4 from a PF4-transfected cell line, displaced PF4/heparin complexes from platelet surfaces, and inhibited anti-PF4/heparin Ab binding to PF4/heparin complexes and subsequent platelet activation. Dabigatran and rivaroxaban seem to be options for alternative anticoagulation in patients with a history of HIT. ODSH prevents formation of immunogenic PF4/heparin complexes, and, when given together with heparin, may have the potential to reduce the risk for HIT during treatment with heparin.

P1321PLASMATIC OSTEOPONTIN: A PREDICTOR OF VASCULAR ACCESS DYSFUNCTION IN HEMODIALYSIS PATIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Nirvana Sadaghianloo ◽  
CONTENTI Julie ◽  
Vido Sandor ◽  
Carboni Joseph ◽  
Bonnet Sophie ◽  
...  
Keyword(s):  
Biological Marker ◽  
Duplex Ultrasound ◽  
Hemodialysis Patients ◽  
Control Group ◽  
Strongly Correlated ◽  
Arteriovenous Fistulas ◽  
Significant Difference ◽  
Patients At Risk ◽  
Elisa Technique

Abstract Background and Aims Despite recommendations for a close follow-up of arteriovenous fistulas (AVF), thombosis rate reaches 10% each year. Conventional follow-up modalities remain a burden for hemodialysis patients. We tested the hypothesis that osteopontin (OPN), a pro-inflammatory molecule related to intimal hyperplasia, could be a biological marker of stenosis, and could thereby allow a screening of patients at risk for AVF dysfunction. Method Our prospective study (NCT03270358) compared the rate of plasmatic OPN between patients with a good-functioning AVF (control group, N= 39) and patients who required surgical or endovascular revision of their AVF because of a stenosis (stenosis group, N= 37). Blood samples were taken in the AVF, at the time of AVF cannulation in control patients, and at the time of AVF revision in stenosis patients. For each patient, blood from the contralateral arm was also analyzed as a between-subject control (paired t test). Cardiovascular risk factors, ongoing medications, and OPN rates (ELISA technique) were compared among the groups (uni- and multivariate analysis). The ROC curve determined sensitivity and specificity of the marker for the detection of stenosis. Results Patients' characteristics were similar between the 2 groups (mean age, 70 years; men, 63%; AVF duration; 39 months), apart from diabetes (control group, 33%; stenosis group, 57%; p=0.04). The rate of OPN was similar between the AVF arm and the contralateral arm (p=0.11), but significantly increased in the stenosis group compared to the control group (655 vs. 452 ng/mL, respectively, p=0.02). There was no statistically significant difference in OPN rate for diabetics and non diabetics (two-way ANOVA, p= 0.50). Sensitivity was 89% for a threshold &gt;293ng/mL and specificity was 80% for a threshold &gt;567ng/mL (AUC: 0.70; 95%CI: 0.57-0.81; p=0.004). Patients with an OPN rate ≥293ng/mL and those with an OPN rate ≥567ng/mL had respectively 8.87 and 15.62 higher odds to have a stenosis than patients with an OPN rate &lt;293ng/mL (binomial regression, p&lt;0.01). Conclusion Plasmatic OPN rate in hemodialysis patients can be measured simply, in a blood sample taken at the time of AVF cannulation, and is strongly correlated to the presence of a symptomatic AVF stenosis. This biomarker could help the physician choose which patient need a comprehensive examination of his/her AVF with duplex ultrasound or fistulogram.

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