The Heparin-Mobilisable Pool of Platelet Factor 4: A Comparison of Intravenous and Subcutaneous Heparin and Kabi Heparin Fragment 2165

O'Brien, Vincent; Etherington,; Ma, P.T.S.

doi:10.1055/s-0038-1660121

Cited by 16 publications

(6 citation statements)

References 9 publications

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“…2) Binding of UFH (and to a much lesser extent of LMWH) to platelet-and plasmaderived proteins such as platelet factor 4 (PF 4 ) and histidin-rich glycoprotein may lead to a reduction of their antithrombotic activity in vivo (13,14). 3) Both UFH and LMWH release from the endothelium various agents such as the tissue factor pathway inhibitor, PF 4 or lipase enzymes, thereby indirectly affecting coagulation (15)(16)(17)(18)(19). 4) LMWH inhibits Xa that is incorporated into the prothrombinase complex to a much lesser extent than free circulating Xa (20,21).…”

Section: Discussionmentioning

confidence: 99%

Effects of a Low Molecular Weight Heparin (Fragmin®) and of Unfractionated Heparin on Coagulation Activation at the Site of Plug Formation In Vivo

Eichinger¹,

Wolz²,

Nieszpaur-Los³

et al. 1994

Thromb Haemost

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SummaryThe clinical benefits of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) have been shown in many trials. However, the mode of action of heparin has not been fully elucidated. Thus, we wanted to study the effects of UFH and LMWH in vivo by measuring coagulation activation markers in blood obtained directly from a vascular injury site. In a double-blind, randomized, 3-way, cross-over study 18 healthy volunteers were given UFH (150 U/kg s.c.) and 2 doses of LMWH [35 U/kg s.c. (low dose, Id), 75 U/kg s.c. (high dose, hd)]. Prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT) and fibrinopeptide A (FPA) were measured in bleeding time blood and in venous blood before and after drug application. In addition, the effects of UFH and LMWH on in vitro coagulation tests were studied. Compared to base line, UFH and both IdLMWH and hdLMWH caused significant reductions of F1+2, TAT and FPA in bleeding time blood at 2 h. A marked effect of UFH and of hdLMWH was also seen at 5 h. The inhibition of FPA generation was more pronounced after hdLMWH compared to IdLMWH. In venous blood, UFH and LMWH caused reductions of F1+2, but not of TAT and FPA. In vitro, UFH predominantly affected the anti-IIa assays (activated partial thromboplastin time, thrombin time) and LMWH mainly the anti-Xa test system. Using a technique that investigates the activated coagulation system in vivo, a time- and dose dependent inhibitory effect of heparin on coagulation activation was detectable. Therefore, in our experimental setting a preferential inhibition of a particular portion of the coagulation system by one of the two heparin preparations was not detectable.

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Section: Discussionmentioning

confidence: 99%

Effects of a Low Molecular Weight Heparin (Fragmin®) and of Unfractionated Heparin on Coagulation Activation at the Site of Plug Formation In Vivo

Eichinger¹,

Wolz²,

Nieszpaur-Los³

et al. 1994

Thromb Haemost

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“…The binding specificity of heparin is determined by its negative charge, molecular size, molecular weight, and chain length [ 34 ••]. Heparin binding to the platelet surface can trigger the release of PF4, a positively charged chemokine secreted from the α granules of activated platelets [ 35 ]. PF4 readily binds negatively charged proteins on the endothelium and also to soluble proteins such as heparin [ 36 ].…”

Section: Pathogenesismentioning

confidence: 99%

Heparin Induced Thrombocytopenia for the Perioperative and Critical Care Clinician

Moreno-Duarte

Ghadimi

2020

Curr Anesthesiol Rep

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Purpose of Review This review will illustrate the importance of heparin-induced thrombocytopenia in the intraoperative and critical care settings. Recent Findings Heparin-induced thrombocytopenia (HIT) occurs more frequently in surgical patients compared with medical patients due to the inflammatory release of platelet factor 4 and perioperative heparin exposure. Recognition of this disease requires a high index of suspicion. Diagnostic tools and therapeutic strategies have been expanded and refined in recent years. Summary HIT is a condition where antibodies against the heparin/platelet factor 4 complex interact with platelet receptors to promote platelet activation, aggregation, and thrombus formation. Our review will focus on intraoperative and postoperative considerations related to HIT to help the clinician better manage this rare but often devastating hypercoagulable disease process.

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“…Polysaccharides with a higher degree of sulfation than heparan, e.g. heparin, can displace PF4 from endothelial bound heparan sulfate (69). The interaction between heparin or other polysaccharides and PF4 has been extensively studied (70).…”

Section: Heparin‐induced Thrombocytopeniamentioning

confidence: 99%

DRUG‐INDUCEDAND DRUG‐DEPENDENT IMMUNE THROMBOCYTOPENIAS

Greinacher¹,

Eichler²,

Lübenow³

et al. 2001

Rev Clin Exp Hematol

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Thrombocytopenia is a frequent comorbid condition in many in hospital patients. In some patients, drugs are the cause of low platelet counts. While cytotoxic effects of anti-tumor therapy are the most frequent cause, immune mechanisms should also be considered. This review addresses thrombocytopenias in four groups. Heparin-dependent thrombocytopenia (HIT), by far the most frequent drug-induced immune-mediated type of thrombocytopenia, has a unique pathogenesis and clinical consequences. HIT is a clinicopathological syndrome in which antibodies mostly directed against a multimolecular complex of platelet factor 4 and heparin cause paradoxical thromboembolic complications. The mechanisms through which heparin can enhance thrombin generation are discussed and treatment alternatives for affected patients are presented in detail. It is of primary importance to recognize these patients as early as possible and to substitute heparin with a compatible anticoagulatory drug, such as hirudin, danaparoid or argatroban. Patients seem to benefit from therapeutic doses of alternative treatment rather than from low-dose prophylactic doses. With the increasing use of glycoprotein (GP) IIb/IIIa inhibitors in patients with acute coronary syndromes, thrombocytopenias are increasingly recognized as an adverse effect of these drugs. Up to 4% of treated patients are affected. Most important, pseudothrombocytopenia, a laboratory artefact, is as frequent as real drug-induced thrombocytopenia and must be excluded before changes in treatment are considered. The pathogenesis of these thrombocytopenias is still debated; an immune mechanism involving preformed antibodies is likely. However, since these antibodies are also detectable in a high percentage of normal controls and of patients not developing thrombocytopenia, their impact is still unclear. Patients with real thrombocytopenia are at an increased risk of bleeding; treatment consists of cessation of the GP IIb/IIIa inhibitor and platelet transfusions in cases of severe hemorrhage. Classic immune thrombocytopenia can be induced by some drugs, e.g. gold, which trigger anti-platelet antibodies indistinguishable from platelet autoantibodies found in autoimmune thrombocytopenia. Drug-induced and drug-dependent immune thrombocytopenia is induced by antibodies recognizing an epitope on platelet GP formed after binding of a drug to a platelet glycoprotein. Still unresolved is whether antibody binding is the consequence of a conformational change of the antigen, the antibody, or both. These antibodies typically react with monomorphic epitopes on platelet GP, but only in the presence of the drug or a metabolite. Although several platelet GP have been identified as antibody target (GPIb/IX, GPV, GP IIb/IIIa), antibodies in an individual patient are highly specific for a single GP. Clinically, these patients present with very low platelet counts and acute, sometimes severe, hemorrhage. Treatment is restricted to withdrawal of the drug and symptomatic treatment of bleeding.

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The Heparin-Mobilisable Pool of Platelet Factor 4: A Comparison of Intravenous and Subcutaneous Heparin and Kabi Heparin Fragment 2165

Cited by 16 publications

References 9 publications

Effects of a Low Molecular Weight Heparin (Fragmin®) and of Unfractionated Heparin on Coagulation Activation at the Site of Plug Formation In Vivo

Effects of a Low Molecular Weight Heparin (Fragmin®) and of Unfractionated Heparin on Coagulation Activation at the Site of Plug Formation In Vivo

Heparin Induced Thrombocytopenia for the Perioperative and Critical Care Clinician

DRUG‐INDUCEDAND DRUG‐DEPENDENT IMMUNE THROMBOCYTOPENIAS

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