Thrombosis in Suspected Heparin-induced Thrombocytopenia Occurs More Often with High Antibody Levels (original) (raw)
Related papers
Turkish journal of haematology : official journal of Turkish Society of Haematology, 2009
Heparin-induced thrombocytopenia (HIT) is a life threatening complication of heparin therapy, causing thrombosis. The aim of our study was to find out the frequencies of HIT antibody seroconversion and clinical HIT in Turkish medical patients on different forms of heparins. Our study included 61 patients who were on unfractionated heparin (UFH) (n: 37) and low molecular weight heparin (LMWH) (n: 24) therapies. The frequency of HIT antibody formation was determined by means of antigenic (ELISA), and functional assays (serotonin release assay-SRA). The seroconversion rates in UFH and LMWH groups were found to be 18.9% and 4.1% (ELISA), and 8.1% and 4.1% (SRA), respectively. One patient (2.1%) on UFH therapy developed deep vein thrombosis. No thromboembolic event was observed in patients taking LMWH. Seroconversion rates by means of antigenic and functional assays and clinical HIT were more common in patients on UFH than patients on LMWH therapy.
Cureus, 2018
Heparin-induced thrombocytopenia (HIT) is an adverse reaction to the administration of heparin due to the activation of the platelets by the immunoglobulin G (IgG) antibody-platelet factor 4 (PF4)/heparin immune complex. Since the clinical outcome is uncertain (as it could be associated with significant morbidity and sometimes death), an early diagnosis and appropriate treatment are necessary. The 4Ts pretest clinical scoring system and testing for all anti-PF4/heparin antibodies can markedly improve the diagnosis and prompt adequate treatment. Our study was undertaken to retrospectively evaluate the appropriateness of ordering the PF4 enzyme-linked immunosorbent assay (ELISA) test by using the 4Ts scoring system in a tertiary institution. We examined a database of 118 patients who had the PF4 ELISA test and calculated their 4Ts scores retrospectively. A total of 107 patients were evaluated; 95 patients (88.79%) had a negative PF4 ELISA assay and 12 patients tested positive (11.21%). Only one patient tested weakly positive in the low probability group (negative predictive value 98%). In the intermediate group, six patients were strongly positive (optical density (OD) > 1.0). In this latter group, further confirmatory testing using serotonin release assays (SRAs) could have been done. We also evaluated the setting where the tests were performed and found that the majority of patients (63.55%) were tested in the intensive care unit (ICU) where thrombocytopenia is multifactorial. We concluded that the large majority of patients were not appropriately evaluated prior to testing, which incurred unnecessary expense and patient distress. For the proper identification of patients suspected of HIT who should undergo PF4/heparin antibody testing, further education of the ordering physicians is recommended.
2009
Objective: Heparin-induced thrombocytopenia (HIT) is a life threatening complication of heparin therapy, causing thrombosis. The aim of our study was to find out the frequencies of HIT antibody seroconversion and clinical HIT in Turkish medical patients on different forms of heparins. Materials and Methods: Our study included 61 patients who were on unfractionated heparin (UFH) (n: 37) and low molecular weight heparin (LMWH) (n: 24) therapies. The frequency of HIT antibody formation was determined by means of antigenic (ELISA), and functional assays (serotonin release assay-SRA). Results: The seroconversion rates in UFH and LMWH groups were found to be 18.9% and 4.1% (ELISA), and 8.1% and 4.1% (SRA), respectively. One patient (2.1%) on UFH therapy developed deep vein thrombosis. No thromboembolic event was observed in patients taking LMWH. Conclusion: Seroconversion rates by means of antigenic and functional assays and clinical HIT were more common in patients on UFH than patients o...
Journal of Clinical Investigation, 1994
Heparin-induced thrombocytopenia/thrombosis (HITP) is thought to be mediated by immunoglobulins that activate platelets in the presence of pharmacologic concentrations of heparin, but the molecular basis for this relatively common and often serious complication of heparin therapy has not been established. We found that plasma from each of 12 patients with HITP contained high titer (. 1:200) antibodies that reacted with immobilized complexes of heparin and platelet factor 4 (PF4), a heparin-binding protein contained in platelet alphagranules. Recombinant human PF4 behaved similarly to PF4 isolated from platelets in this assay system. Complexes formed at an apparent heparin/PF4 molecular ratio of -1:2 (fresh heparin) and -1:12 (outdated heparin) were most effective in binding antibody. Immune complexes consisting of PF4, heparin, and antibody reacted with resting platelets; this interaction was inhibited by a monoclonal antibody specific for the FcyRII receptor and by excess heparin. Human umbilical vein endothelial cells, known to express heparin-like glycosaminoglycan molecules on their surface, were recognized by antibody in the presence of PF4 alone; this reaction was inhibited by excess heparin, but not by anti-Fc'yRII. Antibodies reactive with heparin/PF4 were not found in normal plasma, but IgG and 1gM antibodies were detected at dilutions of 1:10 (IgG) and 1:50 (IgM) in 3 of 50 patients (6%) with other types of immune thrombocytopenia. These findings indicate that antibodies associated with HITP react with PF4 complexed with heparin in solution or with glycosaminoglycan molecules on the surface of endothelial cells and provide the basis for a new hypothesis to explain the development of thrombocytopenia with thrombosis or disseminated intravascular coagulation in patients sensitive to heparin. (J. Clin. Invest. 1994. 93:81-88.)
Anticoagulation drugs - the Current State of the Art [Working Title]
Heparin-induced thrombocytopenia (HIT) is the most life-threatening adverse effect of heparin therapy and is provoked by the development of drug-dependent antibodies. It occurs more frequently in patients with cardiac or orthopedic surgery or severe circulatory diseases, and the risk depends on the patient pathological status. As heparin is an anticoagulant used for treating thrombotic events or their risk, this iatrogenic complication has a paradoxal effect as it can induce thromboembolic diseases, frequently associated to severe morbidity or fatal outcomes. Diagnosis involves clinical evaluation of disease probability and laboratory tools for testing the presence of heparin-dependent antibodies with immunoassays or their capability to activate platelets with functional assays. Antibodies developed when stoichiometric complexes of platelet factor 4 (PF4) with heparin are formed during therapy. In few cases non-platelet factor 4 antigens can be involved. Antibodies can remain asymptomatic, but pathogenicity occurs in the presence of high concentrations of IgG isotype antibodies, with high avidity: they target and activate platelets or endothelial cells exposing heparin-PF4 (HPF4) complexes and produce thrombocytopenia and sometimes thrombosis. Risk factors which favor the development of antibodies and their pathological effect are discussed. The present understanding of mechanisms underlying disease development and diagnostic strategies of this heparin adverse effect is presented.
Journal of Blood Medicine, 2020
Heparin-induced thrombocytopenia (HIT) is a recognized clinical entity in patients receiving unfractionated heparin and low-molecular weight heparin. Currently, diagnosing HIT includes the combination of a physician's clinical suspicion based on a clinical scoring system and a series of laboratory tests. In the present article, we discuss challenges in suspecting and diagnosing HIT in consideration of the turnaround time of available tests and recent advances in techniques and methodologies of newer immunoassays and functional assays.
Thrombosis and haemostasis, 2010
Heparin-induced thrombocytopenia (HIT) is a life-threatening complication of heparin treatment; the prognosis depends on early and accurate diagnosis, and prompt start of alternative anticoagulants. Because of high sensitivity, the commercially available immunologic assays are widely used, though not suited to be run on single samples and with a turnaround time of 2-3 hours. We evaluated two new, rapid, automated, semi-quantitative chemiluminescent immunoassays in HIT suspected patients: HemosIL AcuStar HIT-IgG(PF4-H) (specific for IgG anti-PF4/heparin antibodies) and HemosIL AcuStar HIT-Ab(PF4-H) (detecting IgG, IgM and IgA anti-PF4/heparin antibodies) (both from Instrumentation Laboratory). A total of 102 patients with suspected HIT were included; HIT was diagnosed in 17 (16.7%). No false negative cases were observed using either the HemosIL AcuStar HIT-IgG(PF4-H) or the HIT-Ab(PF4-H) assay (sensitivity and negative predictive values = 100%; negative likelihood ratios <0.01). T...
Thrombosis Research, 2002
Antibodies to heparin -platelet factor 4 (PF4) complexes have been observed in patients with heparin-induced thrombocytopenia (HIT) syndrome. These antibodies may be of various isotypes and differ with respect to their ability to activate platelets/endothelial cells. This study determined the isotypes and functionality of antiheparin -platelet factor 4 (AHPF4) antibodies in 111 patients treated with heparin and clinically suspected for HIT. In this patient population, 50% had detectable AHPF4 cumulative IgA, IgG, and IgM (determined by enzyme-linked immunosorbent assay, ELISA), but only 35% was positive when tested with the 14 C-serotonin release assay (SRA). Using antihuman Ig specific for different isotypes, we found that 50% of the 111 samples was positive for IgG, 45% for IgM, and 37% for IgA. In 50 normal human serum (NHS) samples, only two were positive for IgG, but 33 were positive for IgM, indicating a potential humoral response to the heparin -PF4 complex prior to heparin administration. Patients that were ELISA + for AHPF4 antibody titer were subdivided into SRA-positive (+) and SRA-negative ( À ) groups. The SRA + group had a mean ELISA optical density (OD) for AHPF4 IgA/IgG/IgM of 2.1, while the SRA À group had a mean OD of 0.8 ( P < .001). The SRA + group had greater mean OD values for all three individual isotypes. Using flow cytometry, we determined the ability of different patient samples to activate platelets. Samples that contained IgG and were SRA + activated platelets (as measured by microparticle generation and P-selectin expression) in the presence of therapeutic concentrations of heparin. NHS and samples containing IgA and/or IgM that were SRA À were not able to produce microparticles nor were they able to increase expression of P-selectin. Together, these data indicate that IgG is the principal mediator of platelet activation in patients with HIT, with IgA and IgM playing a less significant role in the pathophysiology of this syndrome. D