Platelet GPIIb-IIIa blockers

Topol, Eric J.; Byzova, Tatiana V.; Plow, Edward F.

doi:10.1016/s0140-6736(98)11086-3

Cited by 496 publications

(279 citation statements)

References 37 publications

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“…8,[12][13][14] Tirofiban, however, as a pure antagonist of the ␣ IIb␤3 integrin receptor, has no biological activity beyond the platelet, and thus the near identical survival with these 2 agents in the present study calls into question the clinical relevance of these nonplatelet properties, especially in the face of less myonecrosis with abciximab.…”

Section: Stone Et Al Clinical Syndrome Acuity and Iib/iia Inhibitor Rmentioning

confidence: 75%

Impact of clinical syndrome acuity on the differential response to 2 glycoprotein IIb/IIIa inhibitors in patients undergoing coronary stenting. The TARGET trial

Stone¹,

Moliterno²,

Bertrand³

2002

ACC Current Journal Review

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Background-Although glycoprotein IIb/IIIa inhibitors have been shown to reduce periprocedural and late ischemic events in patients undergoing stent implantation, the relative safety and efficacy of different agents in this class is less established. Also unknown is whether the acuity of the presenting clinical syndrome, which may affect the degree of platelet inhibition required or achieved, influences the response to different antiplatelet agents. Methods and Results-A prospective, multicenter, double-blind, randomized trial was performed in which 4809 patients undergoing planned stenting were randomized to receive abciximab or tirofiban. In patients with acute coronary syndromes (ACS; nϭ3025), abciximab resulted in lower rates of myocardial infarction at 30 days (5.8% versus 8.5%; Pϭ0.004) and 6 months (7.2% versus 9.8%; Pϭ0.013), although 6-month mortality rates were identical (1.39% in both groups; Pϭ0.99). Conversely, in patients without ACS (nϭ1784), myocardial infarction rates were not significantly lower with tirofiban, survival was similar, and target vessel revascularization was reduced, which translated into a trend toward enhanced 6-month event-free survival with tirofiban (89.7% versus 86.6%; Pϭ0.056). Conclusions-In patients with ACS undergoing stent implantation, abciximab use compared with tirofiban results in greater suppression of periprocedural myonecrosis, although a survival benefit has not been demonstrated. Patients with stable coronary syndromes may have equivalent or better outcomes with tirofiban relative to abciximab, with fewer adverse hematologic and hemorrhagic events. These data raise important issues regarding the relative pharmacodynamic inhibition of platelet function required in varying clinical scenarios and have important implications for the cost-effective utilization of glycoprotein IIb/IIIa inhibitors.

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Section: Stone Et Al Clinical Syndrome Acuity and Iib/iia Inhibitor Rmentioning

confidence: 75%

Impact of clinical syndrome acuity on the differential response to 2 glycoprotein IIb/IIIa inhibitors in patients undergoing coronary stenting. The TARGET trial

Stone¹,

Moliterno²,

Bertrand³

2002

ACC Current Journal Review

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“…In contrast, efficient antithrombotic strategies (eg, glycoprotein IIb/IIIa antagonists) appear to be effective in limiting restenosis. 25,26 The similar neointima formation in ␣ 2 -AP ϩ/ϩ and ␣ 2 -AP Ϫ/Ϫ mice also indicates that the physiological plasmin inhibitor does not play a major role. This is somewhat surprising in view of previous studies showing impaired neointima formation in uPA and in plasminogen-deficient mice, 12,13 thus suggesting a key role of plasmin.…”

Section: Discussionmentioning

confidence: 90%

α ₂ -Antiplasmin Gene Deficiency in Mice Does Not Affect Neointima Formation After Vascular Injury

Lijnen

Hoef

Dewerchin

et al. 2000

ATVB

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Abstract-The hypothesis that ␣ 2 -antiplasmin (␣ 2 -AP), the main physiological plasmin inhibitor, plays a role in neointima formation was tested with use of a vascular injury model in wild-type (␣ 2 -AP ϩ/ϩ ) and ␣ 2 -AP-deficient (␣ 2 -AP Ϫ/Ϫ ) mice. The neointimal and medial areas were similar 1 to 3 weeks after electric injury of the femoral artery in ␣ 2 -AP ϩ/ϩ and ␣ 2 -AP Ϫ/Ϫ mice, resulting in comparable intima/media ratios (eg, 0.43Ϯ0.12 and 0.42Ϯ0.11 2 weeks after injury). Nuclear cell counts in cross-sectional areas of the intima of the injured region were also comparable in arteries from ␣ 2 -AP ϩ/ϩ and ␣ 2 -AP Ϫ/Ϫ mice (78Ϯ19 and 69Ϯ8). Fibrin deposition was not significantly different in arteries of both genotypes 1 day after injury, and no mural thrombosis was detected 1 week after injury. Fibrinolytic activity in femoral arterial sections, as monitored by fibrin zymography, was higher in ␣ 2 -AP Ϫ/Ϫ mice 1 week after injury (PϽ0.001) but was comparable in both genotypes 2 and 3 weeks after injury. Staining for elastin did not reveal significant degradation of the internal elastica lamina in either genotype. Immunocytochemical analysis revealed a comparable distribution pattern of ␣-actin-positive smooth muscle cells in both genotypes. These findings indicate that the endogenous fibrinolytic system of ␣ 2 -AP ϩ/ϩ mice is capable of preventing fibrin deposition after vascular injury and suggest that ␣ 2 -AP does not play a major role in smooth muscle cell migration and neointima formation in vivo. (Arterioscler

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“…These agents include RGD peptides and derivatives, monoclonal antibodies to the IIb/IIIa receptor, von Willebrand factor antagonists, serotonin receptor antagonists, thromboxane A2 receptor antagonists, prostacyclin and analogues, synthetic thrombin inhibitors, apyrases, and ticlopidine and clopidogrel (14,15). Many of these antiplatelet agents have shown promise in basic and clinical trials, and several are now approved for clinical use, but their utility has often been hampered by systemic side effects, including hypotension and prolongation of bleeding times (16,17).…”

Section: Discussionmentioning

confidence: 99%

Chrysoptin Is a Potent Glycoprotein IIb/IIIa Fibrinogen Receptor Antagonist Present in Salivary Gland Extracts of the Deerfly

Reddy

Kounga

Mariano

et al. 2000

Journal of Biological Chemistry

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Salivary gland lysates of the deerfly (genus Chrysops) contain chrysoptin, an inhibitor of ADP-induced platelet aggregation, which presumably assists the fly in obtaining a blood meal. Chrysoptin has now been isolated, and its cDNA has been cloned and expressed. Chrysoptin was purified to homogeneity using anion exchange and hydrophobic interaction chromatography and found to be a protein with a molecular mass of 65 kDa as determined by gel electrophoresis. N-terminal amino acid sequencing allowed for the synthesis of degenerate oligonucleotides that led to cloning, from salivary gland specific mRNA, of the cDNA encoding this platelet inhibitor. No RGD sites are present in the predicted sequence. A search of GenBank TM did not reveal significant sequence homology between chrysoptin and other proteins. The molecular mass predicted from the cDNA was 59 kDa. Predicted glycosylation and phosphorylation sites may account for this difference in molecular mass, as recombinant chrysoptin expressed in Sf21 cells had a molecular mass of 65 kDa, matching that of the natural protein. Chrysoptin functions by inhibiting the binding of fibrinogen to the fibrinogen/glycoprotein IIb/ IIIa receptor on platelets with an IC 50 of 95 pmol. These results reveal that insect salivary glands are a source of fibrinogen receptor antagonists.To facilitate blood feeding, hematophagous arthropods produce a number of bioactive substances that overcome the hemostatic mechanisms of the host. Arthropods trigger primary hemostasis by damaging blood vessels while probing the skin. As platelet aggregation is fundamental to hemostasis, some hematophagous arthropods appear to have evolved the ability to secrete platelet inhibitors in their saliva. Previous reports of antiplatelet activity in arthropod saliva include findings of prostacyclin activity in ticks (1, 2); apyrase activity in ticks (3), mosquitoes (4), blood-sucking bugs (5), and tse-tse flies (6); and a nitrosylheme protein from Rhodnius prolixus that has the capacity to release nitric oxide (7). Other than the protein from Rhodnius, these antiplatelet activities have not been well characterized, and it is not clear whether these or other activities account for the platelet inhibitory activity found in salivary gland lysates.Deerflies (genus Chrysops), also referred to as "greenheads" because of their brilliant green eyes, frequent the coast of the northeastern United States for several weeks in midsummer. Because these flies inflict painful bites that sometimes bleed, we reasoned that deerfly salivary gland extract (DFE) 1 might contain an inhibitor of platelet aggregation. We reported previously that DFE inhibits ADP-, thrombin-, and collagen-induced aggregation of human platelets (8). DFE differs from the antiplatelet activities found in other arthropods in two respects. First, it does not alter cAMP levels in platelets, suggesting that it does not contain prostaglandin-like activity. Second, it does not contain apyrase activity. We report the isolation and characterization of chrysopti...

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Platelet GPIIb-IIIa blockers

Cited by 496 publications

References 37 publications

Impact of clinical syndrome acuity on the differential response to 2 glycoprotein IIb/IIIa inhibitors in patients undergoing coronary stenting. The TARGET trial

Impact of clinical syndrome acuity on the differential response to 2 glycoprotein IIb/IIIa inhibitors in patients undergoing coronary stenting. The TARGET trial

α ₂ -Antiplasmin Gene Deficiency in Mice Does Not Affect Neointima Formation After Vascular Injury

Chrysoptin Is a Potent Glycoprotein IIb/IIIa Fibrinogen Receptor Antagonist Present in Salivary Gland Extracts of the Deerfly

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Platelet GPIIb-IIIa blockers

Cited by 496 publications

References 37 publications

Impact of clinical syndrome acuity on the differential response to 2 glycoprotein IIb/IIIa inhibitors in patients undergoing coronary stenting. The TARGET trial

Impact of clinical syndrome acuity on the differential response to 2 glycoprotein IIb/IIIa inhibitors in patients undergoing coronary stenting. The TARGET trial

α 2 -Antiplasmin Gene Deficiency in Mice Does Not Affect Neointima Formation After Vascular Injury

Chrysoptin Is a Potent Glycoprotein IIb/IIIa Fibrinogen Receptor Antagonist Present in Salivary Gland Extracts of the Deerfly

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α ₂ -Antiplasmin Gene Deficiency in Mice Does Not Affect Neointima Formation After Vascular Injury