ライフサイエンスコーパス: HIT

1 HIT antibodies reduced the ability of PF4 to augment aPC

2 HIT develops in temporal association with heparin therap

3 HIT in humans is directly mirrored in a murine genetic m

4 HIT is a prothrombotic disorder that typically presents

5 HIT is caused by antibodies that preferentially recogniz

6 HIT is necessary for improved quality of care but it inc

7 HIT is propagated by activated platelets, monocytes, end

8 HIT pathophysiology is dynamic and complex.

9 HIT pathophysiology is initiated by four essential compo

10 HIT requires treatment with alternative anticoagulants.

11 HIT was defined as a 4Ts score >/= 4 and positive (14)C-

12 HIT'nDRIVE aims to solve the "random walk facility locat

13 HIT-positive plasma demonstrated greater mean inhibition

14 ransfusions were reported in 10.1% TTP, 7.1% HIT, and 25.8% ITP admissions.

15 aged 7-13 years were randomly assigned to a HIT or an active control group matched for enjoyment and

16 tients treated with rivaroxaban during acute HIT (group A, n = 25; group B, n = 21); major hemorrhage

17 patients who received DOAC therapy for acute HIT as either primary therapy (group A) or secondary the

18 rting efficacy and safety of DOACs for acute HIT is increasing, with the most experience reported for

19 ted thrombosis during DOAC therapy for acute HIT.

20 nux is effective and safe in suspected acute HIT; no HIT-specific complications occurred in the fonda

21 urred in all 10 Hamilton patients with acute HIT treated with rivaroxaban.

22 per 10 000 admissions (P< .001), adjudicated HIT decreased 79% from 10.7 to 2.2 per 10 000 admissions

23 Rates of suspected HIT, adjudicated HIT, and HITT, along with HIT-related expenditures were

24 The findings suggest that although all HIT antibodies recognize PF4 in a complex with heparin,

25 ence of HIT, HIT with thrombosis (HITT), and HIT-related costs.

26 Beyond PF4 and HIT, the methods applied in the current study may be rel

27 erial thrombosis and mortality among TTP and HIT patients.

28 frequency of management failures defined as HIT-positive participants with a low 4Ts score (irrespec

29 rombocytopenia (HIT) syndrome (or autoimmune HIT), defined as a transient prothrombotic thrombocytope

30 strated by a case of persisting (autoimmune) HIT (>2-month platelet recovery with inversely parallel

31 between PF4/CS complexes and those that bind HIT antibodies.

32 lic dysfunction, which was prevented by both HIT and MIT.

33 The Syk inhibitor PRT318 thus prevented both HIT immune complex-induced thrombocytopenia and thrombos

34 e-bound platelet factor 4 (PF4) activated by HIT antibodies contribute to the prothrombotic state in

35 e assay that measures cellular activation by HIT antibodies via FcgammaRIIA using DT40 cells.

36 le blood of 131RR donors after activation by HIT antibodies, with increased phospholipid procoagulant

37 combination of direct platelet activation by HIT immune complexes through FcgammaRIIA and transactiva

38 eration, but its activity was not blocked by HIT antibodies.

39 maRIIA-dependent activation of DT40 cells by HIT antibodies as well as platelet activation, as measur

40 Recognition of these complexes by HIT antibodies reverses the PF4-dependent enhancement in

41 hypersensitivity (DTH) reactions and not by HIT or other rare conditions.

42 bivalrudin has the advantage of not causing HIT, a major concern is lack of an antidote for this dru

43 CD-HIT is a widely used program for clustering and comparin

44 CD-HIT is a widely used program for clustering biological s

45 The enhanced CD-HIT is capable of handling very large datasets in much s

46 ing technologies, we have developed a new CD-HIT program accelerated with a novel parallelization str

47 utilizes the powerful clustering program CD-HIT to cluster similar MITEs into MITE families.

48 l advantages over the widely used program CD-HIT, including higher speed, lower memory use, improved

49 portantly, we developed a new web server, CD-HIT Suite, for clustering a user-uploaded sequence datas

50 In order to further assist the CD-HIT users, we significantly improved this program with m

51 nship between age, race, or sex and clinical HIT status was found.

52 teristics, laboratory findings, and clinical HIT status.

53 ients, even among those with a high clinical HIT probability.

54 with HIT, an at least intermediate clinical HIT-risk (4Ts score >/=4 points), and received treatment

55 osorbent assay were classified as clinically HIT-positive or HIT-negative, followed by confirmation w

56 Aggregation tests performed with collagen, HIT plasma, and monoclonal antibodies cross-linking Fcga

57 f thromboembolic and bleeding complications, HIT, and pregnancy outcome).

58 argatroban = 47) for suspected or confirmed HIT.

59 sing rivaroxaban for serologically confirmed HIT (4Ts score >/=4 points; positive platelet factor 4 [

60 having this property could explain "delayed HIT" seen in some individuals after discontinuation of h

61 nts with anti-PF4-heparin antibodies develop HIT, implying that only a subset of these antibodies is

62 d antibody production in patients developing HIT.

63 utility of the confirmatory test to diagnose HIT.

64 Diagnosing HIT in hospitalized patients is often challenging becaus

65 ry, as well as for 15 other serially-diluted HIT sera.

66 We observed that post-TPE/diluted HIT sera-when first testing SRA-negative-continue to tes

67 The propensity for thrombosis distinguishes HIT from other common drug-induced thrombocytopenias.

68 ticoagulant with transition to a DOAC during HIT-associated thrombocytopenia).

69 Ts score plus negative PaGIA result excluded HIT, whereas any other combination of results justified

70 re appears to be a robust means of excluding HIT.

71 n MPPs, Pcid2 interacts with the Zinc finger HIT-type containing 1 (ZNHIT1) to block Snf2-related CRE

72 Approved for HIT are 2 direct thrombin inhibitors (DTI; lepirudin, ar

73 nosis and widely used immunologic assays for HIT results in frequent overdiagnosis.

74 idered, as well as laboratory evaluation for HIT.

75 on assay and a PF4-dependent immunoassay for HIT antibodies indicates that patients with subacute HIT

76 ay have the potential to reduce the risk for HIT during treatment with heparin.

77 ted our prospective study of rivaroxaban for HIT), using rivaroxaban for serologically confirmed HIT

78 stics and non-anticoagulant therapeutics for HIT.

79 First-line therapies for HIT are argatroban or lepirudin.

80 clinical practice, its predictive value for HIT in diverse settings and patient populations is unkno

81 bound to peri-injury endothelium and formed HIT antigenic complexes that were dissociated by heparin

82 FR-HIT is slower than the fastest SOAP2, BWA and BWA-SW, bu

83 We implemented an efficient algorithm, FR-HIT, for fragment recruitment.

84 We applied FR-HIT and several other tools including BLASTN, MegaBLAST,

85 On average, FR-HIT and BLASTN recruited significantly more reads than o

86 tly more reads than other programs, while FR-HIT is about two orders of magnitude faster than BLASTN.

87 xposure serologically indistinguishable from HIT, is controversial.

88 ersists for weeks in patients recovered from HIT.

89 Furthermore, HIT'nDRIVE, when applied to a large panel of pan-cancer

90 hm could distinguish patients likely to have HIT from those who do not.

91 or avoiding heparin on the incidence of HIT, HIT with thrombosis (HITT), and HIT-related costs.

92 Hospital HIT-related expenditures decreased by $266 938 per year

93 4 tetramerization and inhibits KKO and human HIT IgG-induced platelet activation and platelet aggrega

94 d heparin is specifically inhibited by human HIT antibodies that activate platelets, whereas inhibiti

95 bosis in vivo, demonstrating its activity in HIT.

96 s, may provide a novel treatment approach in HIT.

97 ostic criteria, and management approaches in HIT.

98 treatment of thromboembolic complications in HIT.

99 48 276P or 326Q alleles was less frequent in HIT patients, suggesting a protective effect of these po

100 breadth of molecular and cellular players in HIT.

101 cell tolerance may play an important role in HIT pathogenesis.

102 es contributes to the prothrombotic state in HIT and showed that HIT antibodies bind to monocyte Fcga

103 ategies, directed at the initiating steps in HIT pathophysiology and with potential combinations stag

104 48 (Q276P, R326Q, and D872E) were studied in HIT patients and 2 control groups, with or without antib

105 erived thrombin contributes to thrombosis in HIT and identifies potential new targets for lessening t

106 n the pathogenesis of arterial thrombosis in HIT and suggest that therapies targeting these cells mig

107 found to increase the risk of thrombosis in HIT patients (odds ratio: 5.9; 95% confidence interval:

108 The mechanism of thrombosis in HIT remains poorly understood.

109 Platelet transfusions in HIT were associated with higher odds of arterial thrombo

110 Government incentives to increase HIT will likely result in a more computerized clinical e

111 A-mediated platelet reactivity and influence HIT susceptibility.

112 PRT318 completely inhibited HIT immune complex-induced aggregation of both human and

113 Here we introduce HIT'nDRIVE, a computational method that integrates genom

114 entary lifestyle or 8-10 weeks of isocaloric HIT or MIT.

115 mation of delayed-onset (or autoimmune-like) HIT antibodies that activate platelets even in the absen

116 After a few minutes, HIT antigen was detected within the thrombus itself at t

117 ce were treated with KKO, a mouse monoclonal HIT-like antibody, and heparin.

118 etramer/KKO-Fab complex (a murine monoclonal HIT-like antibody) and (3) PF4 monomer/RTO-Fab complex (

119 ffective and safe in suspected acute HIT; no HIT-specific complications occurred in the fondaparinux-

120 ) and (3) PF4 monomer/RTO-Fab complex (a non-HIT anti-PF4 monoclonal antibody).

121 arranted, as achievement of full benefits of HIT requires addressing significant challenges.

122 e by characterizing PF4-dependent binding of HIT antibodies to intact platelets and found that most a

123 telet count, the most feared complication of HIT is thrombosis.

124 unity to prevent thrombotic complications of HIT, while sparing systemic hemostatic pathways.

125 izing heparin exposure to the development of HIT is 5 days irrespective of the patient's previous hep

126 Risk factors for the development of HIT related to heparin administration are well described

127 lifestyle, we report a very modest effect of HIT and no effect of resistance training on AHN in adult

128 The composite endpoint of HIT-specific complications (thromboembolic events, amput

129 40 to 100 days (median) after an episode of HIT, depending on the assay performed.

130 improving the specificity and feasibility of HIT laboratory testing.

131 ions that involve patients with a history of HIT (eg, treatment of venous thromboembolism or acute co

132 at among patients with a previous history of HIT who are reexposed to intraoperative (but not postope

133 nticoagulation in patients with a history of HIT.

134 evious heparin exposure status or history of HIT.

135 egy for avoiding heparin on the incidence of HIT, HIT with thrombosis (HITT), and HIT-related costs.

136 Main outcome measures were the incidences of HIT-specific complications (thromboembolic venous/arteri

137 cessful outpatient rivaroxaban management of HIT-associated thrombosis.

138 ility to individual and combined measures of HIT.

139 studies using our transgenic mouse model of HIT have shown that antibodies reactive with heparin-pla

140 These data provide a model of HIT wherein a combination of direct FcgammaRIIA-mediated

141 carotid artery in a modified murine model of HIT while paradoxically exacerbating thrombocytopenia.

142 uses thrombocytopenia in an in vivo model of HIT, whereas RTO does not.

143 used to analyze the murine genetic model of HIT.

144 ay contribute to the prothrombotic nature of HIT.

145 ivation via FcgammaRIIa, the sine qua non of HIT, has become much better appreciated.

146 However, the B-cell origin of HIT antibody production is not known.

147 ntibodies are central to the pathogenesis of HIT.

148 f epitope specificity in the pathogenesis of HIT.

149 dic system that simulate the pathogenesis of HIT.

150 de new tools to probe the pathophysiology of HIT.

151 y responsible for scoring, the prevalence of HIT, or the composition of the study population.

152 IA result reduced the pretest probability of HIT from 1.9% to 0% (95% CI, 0-1.3%), 6.7% to 0% (95% CI

153 /H-PaGIA result increased the probability of HIT in the low score group to 15.4% (95% CI, 5.9-30.5).

154 hed data on drug efficacy and probability of HIT-related thromboembolism and major bleeding.

155 by 4Ts score as having a low probability of HIT.

156 date the intrinsic PF4-binding properties of HIT-like monoclonal antibody (KKO) versus non-pathogenic

157 We also performed a literature review of HIT treatment using DOACs (rivaroxaban, apixaban, dabiga

158 bly exert a protective effect on the risk of HIT in patients with antibodies to PF4/Hs.

159 ombus endothelium is the predominant site of HIT antigen assembly.

160 When there is clinical suspicion of HIT, heparin should be discontinued and alternative anti

161 valuate the importance of absolute titers of HIT antibodies as a risk factor for clinical occurrence.

162 studied and approved drugs for treatment of HIT.

163 will summarize our current understanding of HIT by reviewing pathogenesis, essential clinical and la

164 Progress in our understanding of HIT has translated to improvements in treatment and pati

165 the challenges that limit meaningful use of HIT, there is a high chance that institutions will conve

166 d aerobic capacity and reduced obesity, only HIT improved glucose tolerance.

167 ogic feature characteristic of delayed-onset HIT (ie, where heparin use precedes HIT but is not requi

168 ie, no sooner than observed in typical-onset HIT.

169 ere classified as clinically HIT-positive or HIT-negative, followed by confirmation with excess hepar

170 Overall, HIT'nDRIVE may help clinicians contextualize massive mul

171 The annual rate of patients with a positive HIT assay decreased 63% from 16.5 to 6.1 per 10 000 admi

172 T reexposed to heparin 4.4 years (mean) post-HIT; 17 patients were given heparin intraoperatively (wi

173 OS was superior compared with the precedent HIT '91 trial.

174 ed-onset HIT (ie, where heparin use precedes HIT but is not required for subsequent development or wo

175 tory positive status independently predicted HIT in multivariate analysis.

176 At present, HIT remains an underdiagnosed and undertreated condition

177 [73%]) suggests that patients with previous HIT may be especially predisposed to forming recurrent a

178 f recurrent HIT in 20 patients with previous HIT reexposed to heparin 4.4 years (mean) post-HIT; 17 p

179 atment of patients with suspected and proven HIT.

180 In proven HIT, approved treatments reduce but do not eliminate thr

181 Suspected HIT is more frequent than proven HIT, because of the widespread use of Hep and the inadeq

182 One patient developed recurrent HIT beginning 7 days after cardiac surgery, with newly r

183 The risk of recurrent HIT 1 to 2 weeks after heparin reexposure is approximate

184 ostoperative) heparin, the risk of recurrent HIT appears to be low, but is possible if antibodies wit

185 assay [EIA]), and the frequency of recurrent HIT in 20 patients with previous HIT reexposed to hepari

186 fter cardiac surgery, with newly regenerated HIT antibodies exhibiting strong heparin-independent pla

187 se that a rigorous definition of spontaneous HIT syndrome should include otherwise unexplained thromb

188 ve serologically-confirmed acute or subacute HIT; for this situation, a negative platelet activation

189 bodies indicates that patients with subacute HIT undergoing repeated TPE before heparin reexposure sh

190 samples in a patient with recent (subacute) HIT who underwent serial TPE precardiac surgery, as well

191 Suspected HIT is more frequent than proven HIT, because of the wid

192 The annual rate of suspected HIT decreased 42%, from 85.5 per 10 000 admissions in th

193 fondaparinux for the treatment of suspected HIT from the institutional perspective.

194 Rates of suspected HIT, adjudicated HIT, and HITT, along with HIT-related e

195 f fondaparinux in the treatment of suspected HIT.

196 ) in samples from 58 patients with suspected HIT and circulating anti-PF4/heparin antibodies.

197 Consecutive cases with suspected HIT from 2003 through 2012 were reviewed.

198 tudies that included patients with suspected HIT, who were evaluated by both the 4Ts and a reference

199 an and danaparoid in patients with suspected HIT.

200 value of the 4Ts in patients with suspected HIT.

201 Health information technology (HIT) is perceived as an essential component for addressi

202 5-point improvement in Headache Impact Test (HIT)-6.

203 greater mean inhibition of KKO binding than HIT-negative plasma (78.9% vs 26.0%; P < .0001) and indu

204 These results demonstrate that HIT patients homozygous for the FcgammaRIIA 131R allele

205 We have shown previously that HIT is associated with antibodies to complexes that form

206 We now show that HIT antibodies are able to inhibit generation of activat

207 e prothrombotic state in HIT and showed that HIT antibodies bind to monocyte FcgammaRIIA, which activ

208 The HIT immune response is remarkably transient, with hepari

209 communication and workflow patterns into the HIT application.

210 We investigated the effects of the HIT Ab complex on tissue factor (TF) expression and rele

211 receptor IIA (FcgammaRIIA), infusion of the HIT-like monoclonal antibody KKO increased fibrin and pl

212 sures the effect of plasma on binding of the HIT-like monoclonal antibody KKO to platelet factor 4 (P

213 4 (PF4)/heparin complex, which is termed the HIT Ab complex.

214 We found that the HIT Ab complex induced TF expression in monocytes and th

215 nd desirudin have recently been added to the HIT armamentarium.

216 ura (TTP), heparin-induced thrombocytopenia (HIT) and immune thrombocytopenic purpura (ITP).

217 siology of heparin-induced thrombocytopenia (HIT) and in applying this knowledge to the treatment of

218 sential in heparin-induced thrombocytopenia (HIT) and other immune-mediated thrombocytopenia and thro

219 f previous heparin-induced thrombocytopenia (HIT) can be appropriate if platelet-activating antibodie

220 f treating heparin-induced thrombocytopenia (HIT) focus on treatment and prevention of thrombotic com

221 results in heparin-induced thrombocytopenia (HIT) from cellular activation involving Fc receptors.

222 esting for heparin-induced thrombocytopenia (HIT) has important shortcomings.

223 to remove heparin-induced thrombocytopenia (HIT) IgG antibodies before cardiac/vascular surgery in p

224 Heparin-induced thrombocytopenia (HIT) is a life- and limb-threatening thrombotic disorder

225 Heparin-induced thrombocytopenia (HIT) is a major cause of morbidity and mortality resulti

226 Heparin-induced thrombocytopenia (HIT) is a potentially devastating form of drug-induced t

227 Heparin-induced thrombocytopenia (HIT) is a prothrombotic complication of heparin therapy

228 Heparin-induced thrombocytopenia (HIT) is a prothrombotic disorder initiated by antibodies

229 Heparin-induced thrombocytopenia (HIT) is a relatively common prothrombotic adverse drug r

230 Heparin-induced thrombocytopenia (HIT) is a significant cause of morbidity and mortality i

231 Heparin-induced thrombocytopenia (HIT) is a thrombotic complication of heparin therapy med

232 Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction occurring in up to 5% o

233 Heparin-induced thrombocytopenia (HIT) is an autoimmune thrombotic disorder caused by immu

234 Heparin-induced thrombocytopenia (HIT) is an immune complication of heparin therapy caused

235 Heparin-induced thrombocytopenia (HIT) is an immune-mediated disorder that can cause fatal

236 Heparin-induced thrombocytopenia (HIT) is an immune-mediated hypercoagulable disorder caus

237 Heparin-induced thrombocytopenia (HIT) is an important, increasingly recognized antibody-m

238 Heparin-induced thrombocytopenia (HIT) is caused by antibodies that recognize complexes be

239 Heparin-induced thrombocytopenia (HIT) is characterized by a high incidence of thrombosis,

240 Heparin-induced thrombocytopenia (HIT) is due primarily to IgG antibodies specific to plat

241 essment of heparin-induced thrombocytopenia (HIT) is important for disease recognition and management

242 clusion of heparin-induced thrombocytopenia (HIT) is needed to determine which patients can continue

243 hreatening heparin-induced thrombocytopenia (HIT) is treated with the alternative nonheparin anticoag

244 elines for heparin-induced thrombocytopenia (HIT) management recommend heparin cessation and switchin

245 ients with heparin-induced thrombocytopenia (HIT) remain at risk for recurrent thromboembolic complic

246 agnosis of heparin-induced thrombocytopenia (HIT) requires detection of antibodies to the heparin/pla

247 pontaneous heparin-induced thrombocytopenia (HIT) syndrome (or autoimmune HIT), defined as a transien

248 a (TTP) or heparin-induced thrombocytopenia (HIT), and Trousseau syndrome, but some patients present

249 eatment of heparin-induced thrombocytopenia (HIT), few data are available comparing the cost-effectiv

250 atran) for heparin-induced thrombocytopenia (HIT),and also outline aHIT prevention strategy through d

251 ly cause a heparin-induced thrombocytopenia (HIT)-like prothrombotic disorder.

252 effect of heparin-induced thrombocytopenia (HIT).

253 genesis of heparin-induced thrombocytopenia (HIT).

254 ion called heparin-induced thrombocytopenia (HIT).

255 disorder, heparin-induced thrombocytopenia (HIT).

256 system for heparin-induced thrombocytopenia (HIT).

257 g reaction heparin-induced thrombocytopenia (HIT).

258 eatment of heparin-induced thrombocytopenia (HIT).

259 assays for heparin-induced thrombocytopenia (HIT).

260 eding, and heparin-induced thrombocytopenia [HIT]).

261 rin-induced thrombocytopenia and thrombosis (HIT) patients homozygous for arginine (R) at position 13

262 rin-induced thrombocytopenia and thrombosis (HIT), but many antibody-positive patients have normal pl

263 f the tyrosine kinase Syk, as an approach to HIT treatment.

264 with the HR and HH genotypes in response to HIT plasma or 5B9, a recently developed humanized monocl

265 -brain barrier; it affects susceptibility to HIT by altering the brain concentration of haloperidol.

266 ABCB5 alleles alter susceptibility to HIT in mouse and humans.

267 enetic factors that affect susceptibility to HIT, but it is likely that additional pharmacogenetic su

268 ansporter (Abcb5) affected susceptibility to HIT.

269 se strains are differentially susceptible to HIT.

270 onded with a >/=5-point improvement in total HIT-6 during treatment cycles 1, 2 and 3, respectively.

271 toms caused by haloperidol-induced toxicity (HIT), which limits its clinical utility.

272 effect of a 6 week high-intensity training (HIT) regimen on measures of cognitive control and workin

273 te whether high-intensity interval training (HIT) is superior to moderate-intensity training (MIT) in

274 effects of high-intensity interval training (HIT) or of purely anaerobic resistance training on AHN.

275 g (ET) and high intensity interval training (HIT), generally regarded as a time-efficient alternative

276 Whether high-intensity interval training (HIT), referring to alternating short bouts of very inten

277 Transgenic HIT model mice were treated with KKO, a mouse monoclonal

278 ced aggregation of both human and transgenic HIT mouse platelets.

279 din and fondaparinux have been used to treat HIT in small case series.

280 agulants should next be studied for treating HIT.

281 of the different anticoagulants for treating HIT.

282 cently completed prospective clinical trial (HIT [for heparin-induced thrombocytopenia] 5801 study; n

283 cal and laboratory features confirmed "true" HIT in at least 74 of 195 (38.0%) patients; 35 of 74 (47

284 to 2200 tumors from four major cancer types, HIT'nDRIVE revealed many potentially clinically actionab

285 Insights into the unique HIT antibody response continue to emerge, but without co

286 the use of alternative anticoagulants until HIT could be excluded.

287 ry, if the operation cannot be delayed until HIT antibodies have become negative, alternative anticoa

288 e prediction for tumor samples by only using HIT'nDRIVE-seeded driver gene modules from gene interact

289 The 6-week HIT regimen resulted in improvements on measures of cogn

290 ran voluntarily on a running wheel, whereas HIT on the treadmill had a smaller, statistically non-si

291 e success and feasibility of a hospital-wide HIT prevention strategy.

292 10 624 hospitalizations with TTP; 6332 with HIT and 79 980 with ITP.

293 d HIT, adjudicated HIT, and HITT, along with HIT-related expenditures were compared in the pre-interv

294 ospitalized patients who were diagnosed with HIT, an at least intermediate clinical HIT-risk (4Ts sco

295 y, share a number of serologic features with HIT Abs, including platelet activation, and may pose hea

296 gies are recommended, although patients with HIT are at a greater risk for adverse outcomes.

297 Patients with HIT develop autoantibodies to the platelet factor 4 (PF4

298 nd/or plasma exchange, whereas patients with HIT need an alternative anticoagulant to replace heparin

299 For patients with HIT, alternative anticoagulation is available, but for c

300 (KKO), as well as plasma from patients with HIT.

301 e development of thrombosis in patients with HIT.