Heparin-Induced Thrombocytopenia

Warkentin, Theodore E.

doi:10.1161/01.cir.0000147537.72829.1b

Cited by 171 publications

(117 citation statements)

References 21 publications

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“…Also, it is likely that the HITassociated antibody of another type (such as the complexes formed between the heparin molecule and with other chemokines of the C-X-C super family such as IL-8 or NAP-2), may have been present. The literature also suggests that a wide variation in the prevalence, seroconversion and functionality of HITassociated antibodies exists and is largely dependent on the patient population, type/route/dosage/duration of heparin used and the diagnostic tests employed [18] . Occurrence of polymorphism in Indians was observed to be higher than studies in the east, e.g Japan, where it is 51% but comparable to that in the west (78%).…”

Section: Am J Immunology 1 (1): 55-59 2005mentioning

confidence: 99%

Heparin-PF4 Antibodies in Heparin Induced Thrombocytopenia: Its Relationship with FcgRIIa Polymorphism

Kannan¹,

Ahmad²,

Ahmad³

et al. 2005

American J. of Immunology

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Abstract:We did the pilot study, in an attempt to determine the prevalence of HIT in Indians and determine its relationship, if any, to FcγRIIa polymorphism, the occurrence of heparin-induced thrombocytopenia (HIT) was investigated in 33 Indian patients undergoing cardiovascular surgery (CVS) who received unfractionated heparin (UFH). Platelet counts were performed prior to the initiation of UFH therapy and 5-16 days, post-therapy. The fall in patients' platelet count >35% of the baseline value or <100,000 µL 1 was considered to be suggestive of HIT syndrome. Heparin-induced platelet aggregation (HIPA), Enzyme Linked Immunosorbant assay (ELISA) and Serotonin Release Assay (SRA) tests were performed in all the patients to detect the antibodies formed against the heparin and platelet factor 4 complex (H-PF4). DNA analysis for FcγRIIa polymorphism was done by allele specific PCR. Thrombocytopenia was found to be present in 10 (30%) patients. Of these, 5 patients were found to be positive by HIPA, ELISA and SRA tests. These 5 patients were considered to have classic HIT syndrome. One of these patients had bleeding while the others were asymptomatic. One of the HIT positive patients was found to be homozygous for FcγRIIa His/ His polymorphism and others were heterozygous, had one defective allele with single amino acid change (Arg 131 His) at FcγRIIa platelet receptor. Frequency of occurrence of homozygous (FcγRIIa His/ His) and heterozygous (FcγRIIa Arg/ His ) polymorphism was higher in patients with HIT (100%) than in the normal population (68%). The prevalence of HIT in the pilot study (15%) was higher than that in the west (5%) but comparable to that from Japan (12%) (14). However, the Occurance of FcγRIIa polymorphism in Indian (68%) was higher than in the east (51%) and comparable to that in the west (78%). Thus it appears that the FcγRIIa polymorphism may have some relation to occurrence of HIT. Higher prevalence of FcγRIIa polymorphism in Indian may predispose to higher prevalence of HIT in India. Thus, it is recommended that, heparin-treated patients should be routinely tested for not only aPTT but also for platelet count, HPF4 antibodies and FcγRIIa polymorphism analysis. From the pilot study, it shows that absence of FcγRIIa receptor polymorphism may suggest low or negligible risk of development of HIT antibodies. However, further studies required with more patients using the same protocol.

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Section: Am J Immunology 1 (1): 55-59 2005mentioning

confidence: 99%

Heparin-PF4 Antibodies in Heparin Induced Thrombocytopenia: Its Relationship with FcgRIIa Polymorphism

Kannan¹,

Ahmad²,

Ahmad³

et al. 2005

American J. of Immunology

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“…3 In addition, CXCL4 has a role in heparin-induced thrombocytopenia (HIT), a common immune-mediated disorder characterized by an immune response against epitopes within circulating heparin-CXCL4 complexes, which leads to a reduction of circulating platelets counts and is recognized as a risk factor for thromboembolic complications. 4,5 Subsequent studies have defined an array of apparently unrelated CXCL4 activities. CXCL4 exhibits antiangiogenic properties in vitro and in vivo and inhibits tumor neovascularization through a variety of mechanisms.…”

Section: Introductionmentioning

confidence: 99%

PF-4/CXCL4 and CXCL4L1 exhibit distinct subcellular localization and a differentially regulated mechanism of secretion

Lasagni

Grépin

Mazzinghi

et al. 2007

Blood

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PF-4/CXCL4 is a member of the CXC chemokine family, which is mainly produced by platelets and known for its pleiotropic biological functions. Recently, the proteic product of a nonallelic variant gene of CXCL4 was isolated from human platelets and named as CXCL4L1. CXCL4L1 shows only 4.3% amino acid divergence in the mature protein, but exhibits a 38% amino acid divergence in the signal peptide region. We hypothesized that this may imply a difference in the cell type in which CXCL4L1 is expressed or a difference in its mode of secretion. In different types of transfected cells, CXCL4 and CXCL4L1 exhibited a distinct subcellular localization and a differential regulation of secretion, CXCL4 being stored in secretory granules and released in response to protein kinase C activation, whereas CXCL4L1 was continuously synthesized and secreted through a constitutive pathway. A protein kinase C-regulated CXCL4 secretion was observed also in lymphocytes, a cell type expressing mainly CXCL4 mRNA, whereas smooth muscle cells, which preferentially expressed CXCL4L1, exhibited a constitutive pathway of secretion. These results demonstrate that CXCL4 and CXCL4L1 exhibit a distinct subcellular localization and are secreted in a differentially regulated manner, suggesting distinct roles in inflammatory or homeostatic processes. IntroductionPF-4/CXCL4 is a member of the CXC chemokine family produced by cells of the megakaryocytic lineage. In megakaryocytes CXCL4 is synthesized, enclosed in vesicles, and transferred to the ␣ granules from which it is secreted following platelet activation. 1 More recently, CXCL4 expression was also found in monocytes. 2 The first biological function described for CXCL4 is its antiheparin activity, responsible for the important role of CXCL4 in the regulation of coagulation processes. 3 In addition, CXCL4 has a role in heparin-induced thrombocytopenia (HIT), a common immune-mediated disorder characterized by an immune response against epitopes within circulating heparin-CXCL4 complexes, which leads to a reduction of circulating platelets counts and is recognized as a risk factor for thromboembolic complications. 4,5 Subsequent studies have defined an array of apparently unrelated CXCL4 activities. CXCL4 exhibits antiangiogenic properties in vitro and in vivo and inhibits tumor neovascularization through a variety of mechanisms. [6][7][8] First, CXCL4 is able to interact directly with angiogenic growth factors, such as fibroblast growth factors (FGFs) and vascular endothelial growth factor (VEGF), and inhibits their interaction with the cell surface receptor. 6,9 Second, CXCL4 may bind proteoglycans and interfere with the proteoglycan-bystander effect on growth factor activity. 10 Furthermore, a cell surface receptor that is expressed by human endothelial cells (ECs) in a cell cycle-dependent manner 11 and mediates the antiangiogenic effects of CXCL4 has been recently identified and named as Besides the antiangiogenic properties, CXCL4 expresses immunomodulatory activities, such as down-regulatio...

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“…tokių ligonių, neseniai gydytų heparinu, turi cirkuliuojančių HIT antikūnų (1,3,7,10,14). Jei, adekvačiai gydant heparinais, įvyksta trombozės, reikėtų įtarti prasidėjusį HIT (25,26).…”

Section: Diagnostika Ir Diferencinė Diagnostikaunclassified

“…Papildomos gydymo priemonės (7,8,15,19,26) Priešembolinio filtro įstatymas į apatinę tuščiąją veną (plaučių arterijos tromboembolijos profilaktikai) nerekomenduojamas, nes ši procedūra ligoniams, kuriems pasireiškė HIT, gali sukelti trombinių komplikacijų.…”

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