Cross-reactivity study of low molecular weight heparins and heparinoid in heparin-induced thrombocytopenia

Vun, Chee M.; Evans, Sue; Chong, Beng H.

doi:10.1016/0049-3848(96)00027-8

Cited by 74 publications

(26 citation statements)

References 19 publications

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“…In agreement with previous in vitro studies (Greinacher et al, 1992;Vun et al, 1996), we found an overall cross-reactivity rate of 10% (5/50) which was confirmed in ELISA with a significant increase in A 492 varying between 0 . 3 and 0 .…”

Section: Discussionsupporting

confidence: 80%

Differences in specificity of heparin‐dependent antibodies developed in heparin‐induced thrombocytopenia and consequences on cross‐reactivity with danaparoid sodium

Pouplard¹,

Amiral²,

Borg

et al. 1997

Br J Haematol

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Summary. Heparin-induced thrombocytopenia (HIT) is frequently associated with antibodies (Abs) to heparin-PF4 complexes (H-PF4). In order to investigate whether there are variations in specificity of Abs, we studied 63 samples from patients with suspected HIT. Two groups of samples were separated after comparing their reactivity against H-PF4 or recombinant PF4 (r-PF4) using ELISA. In group Ab1 (n ¼ 46), Abs only or mainly bound to H-PF4 complexes and thus most of the epitopes recognized probably involved both heparin and PF4. In group Ab2 (n ¼ 17), Abs exhibited similar reactivity to r-PF4 and H-PF4, and the antigens recognized were possibly neoepitopes mainly expressed by modified PF4 and by H-PF4 complexes. Platelet activation tests were positive with 56 samples containing high titres of Abs to H-PF4. Most samples (n ¼ 59) contained IgG antibodies, often associated with IgA antibodies which were more frequently found in group Ab2, and/or IgM. With unfractionated heparin treatment, HIT was associated with Ab1 or Ab2 antibodies, whereas only Ab1 antibodies were detected after low-molecular-weight heparin (LMWH). Furthermore, cross-reactivity with danaparoid sodium was present only in group Ab1 and mainly involved LMWHtreated patients.

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Section: Discussionsupporting

confidence: 80%

Differences in specificity of heparin‐dependent antibodies developed in heparin‐induced thrombocytopenia and consequences on cross‐reactivity with danaparoid sodium

Pouplard¹,

Amiral²,

Borg

et al. 1997

Br J Haematol

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“…Aggregrometry was performed using human citrated PRP, adjusted to a platelet count of 200 · 10 9 /l, by the method of Born using a four-channel aggregometer at 37°C (ChronoLog) with PPP as the reference, as previously described (Born, 1962;Vun et al, 1996). Control PRP from a healthy volunteer was tested in parallel with each patient sample.…”

Section: Platelet Aggregationmentioning

confidence: 99%

A familial platelet function disorder associated with abnormal signalling through the glycoprotein VI pathway

et al. 2007

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SummaryThe platelet collagen receptor, glycoprotein (GP)VI, of the immunoreceptor family forms a complex with the von Willebrand factor (VWF) receptor, GPIb‐IX‐V, critical for initiating thrombus formation. GPVI is co‐associated with Fc receptor γ‐chain (FcRγ), which contains a cytoplasmic immunoreceptor tyrosine‐based activation motif domain, involved in activation of Syk, and a signalling cascade leading to (i) activation of αIIbβ3, which binds VWF and fibrinogen and mediates platelet aggregation, and (ii) metalloproteinase‐mediated shedding of the GPVI ectodomain (blocked by Syk inhibitors), a key mechanism for regulating GPVI surface expression. In this study, we report a familial case of abnormal platelet aggregation with dysfunctional signalling through GPVI that uniquely demonstrates divergent αIIbβ3‐activating and GPVI‐shedding pathways. The patient is a 60‐year‐old female with a history of immune disorders, excessive bleeding from childhood and a life‐threatening haemorrhage post‐trauma. Platelet aggregation to ADP, thrombin receptor‐agonist peptide or ristocetin/VWF was normal (indicating normal expression and function of αIIbβ3), but platelet aggregation to GPVI agonists, collagen, collagen‐related peptide, or convulxin, was defective. Both GPVI/FcRγ expression and ligand‐induced GPVI ectodomain shedding were normal, confirming expression of functional GPVI/FcRγ, but suggesting a signalling defect downstream of Syk. A genetic defect in GPVI/Fcγ signalling compromising platelet function is hypothesised in this family.

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“…The antigenic efficiency of a specific heparin is directly dependent on its molecular weight. The rate of complex formation with platelet factor 4 and the activation of platelet factor 4 release rise with increasing molecular size and number of sulfate groups on the glucosaminoglycans [19]. In a meta-analysis, Warkentin [17] demonstrated that the risk of antibody formation in response to heparin/platelet factor-4 complexes was significantly higher (7.8%) following administration of UHF than after application of LMW-H (2.2%).…”

Section: Discussionmentioning

confidence: 99%

Complications during Inpatient Thrombosis Prophylaxis – Experience from 40 Patients with Heparin-Induced Thrombocytopenia Type II (HIT II)

Hensel¹,

Dresing²,

Zierott³

et al. 2000

Eur J Trauma

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Heparin-induced thrombocytopenia Type II (HIT II) is based on a hypersensitivity to heparin and results in serious thromboembolic complications with a lethality of up to 23%. Due to its various manifestations -with or without thrombosis and/or a reduced number of thrombocytes -, a reliable diagnosis proves difficult and can only be made by a combination of clinical signs, thrombocytic behavior and antibody screening.

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Cross-reactivity study of low molecular weight heparins and heparinoid in heparin-induced thrombocytopenia

Cited by 74 publications

References 19 publications

Differences in specificity of heparin‐dependent antibodies developed in heparin‐induced thrombocytopenia and consequences on cross‐reactivity with danaparoid sodium

Differences in specificity of heparin‐dependent antibodies developed in heparin‐induced thrombocytopenia and consequences on cross‐reactivity with danaparoid sodium

A familial platelet function disorder associated with abnormal signalling through the glycoprotein VI pathway

Complications during Inpatient Thrombosis Prophylaxis – Experience from 40 Patients with Heparin-Induced Thrombocytopenia Type II (HIT II)

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