Comparison of the effect of a conventional heparin and a low molecular weight heparinoid on platelet function.

Mikhailidis, DP; Barradas, M.A.; Mikhailidis, A M; Magnani, H.N.; Dandona, Paresh

doi:10.1111/j.1365-2125.1984.tb04997.x

Cited by 60 publications

(50 citation statements)

References 25 publications

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“…There is considerable evidence that therapeutic concentrations of conventional high molecular weight heparins (HMWHs) can activate platelets Brace etal., 1985;Eika, 1972;Mikhailidis et al, 1984Mikhailidis et al, , 1985bMikhailidis et al, ,c, 1986Mikhailidis et al, , 1987. Thus HMWHs, added in vitro, enhance submaximal platelet aggregation induced by conventional agonists (e.g.…”

Section: Introductionmentioning

confidence: 99%

“…Thus HMWHs, added in vitro, enhance submaximal platelet aggregation induced by conventional agonists (e.g. ADP, adrenaline and collagen) (Mikhailidis et al, 1984). HMWHs alone have also been shown to induce aggregation in vitro especially in samples prepared from patients with hyperaggregable platelets (Mikhailidis et al, 1985b(Mikhailidis et al, , 1986(Mikhailidis et al, , 1987.…”

Section: Introductionmentioning

confidence: 99%

“…Finally, there is evidence that HMWHs activate platelets in vivo (Gollub & Ulin, 1962;Leroy et al, 1985). In contrast, low molecular weight heparins (LMWHs) and a heparinoid, Org 10172, appear to be largely devoid of this platelet-activating capacity, at least at therapeutic concentrations (Mikhailidis et al, 1984(Mikhailidis et al, , 1985b. It has also been generally assumed that prior use of aspirin in bleeding patients receiving heparin for urgent anticoagulation would exacerbate the risk of blood loss.…”

Section: Introductionmentioning

confidence: 99%

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Platelet activation following intravenous injection of a conventional heparin: absence of effect with a low molecular weight heparinoid (Org 10172).

Mikhailidis

Fonseca

Barradas

et al. 1987

Brit J Clinical Pharma

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1 The effects of an intravenous injection of a conventional high molecular weight heparin (HMWH) were compared with those of a low molecular weight heparinoid (Org 10172). A bolus injection of HMWH (5000 iu) was associated with: (a) a small but significant prolongation of bleeding time (BT); (b) a significant fall in PRP platelet count; (c) significantly enhanced platelet aggregation; and (d) significantly increased platelet thromboxane A2 (TXA2) release. These changes were not observed following the intravenous injection of Org 10172 (3200 anti Xa U). 2 These experiments were repeated following the oral administration of acetylsalicylic acid (ASA). HMWH again caused some enhancement of platelet aggregation despite the ASA-mediated inhibition of platelet aggregation and TXA2 release. Administration of Org 10172 to subjects taking ASA did not alter any of the platelet function indices. 3 In additional control experiments the injection of 5000 iu of HMWH was associated with a significant fall in PRP but not whole blood platelet counts. This finding suggests that the fall in PRP platelet count is a methodological artefact. 4 The HMWH also induced a significantly greater increase in serum non-esterified fatty acid (NEFA) concentrations than Org 10172. 5 The present findings indicate that Org 10172 is a less potent stimulator of platelet aggregation and lipolysis than HMWH. 6 The minor prolongation of the BT after HMWH is not compatible with enhanced aggregation but may be a consequence of alterations in the activity of coagulation factors and vascular-platelet interactions or of ongoing platelet activation accompanied by granule depletion. 7 The different effects of the two anticoagulants assessed suggests a therapeutic advantage in favour of Org 10172, especially in patients with hyperactive platelets.Keywords heparin low molecular weight heparinoid platelet count platelet aggregation thromboxane A2 non-esterified fatty acids

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Platelet activation following intravenous injection of a conventional heparin: absence of effect with a low molecular weight heparinoid (Org 10172).

Mikhailidis

Fonseca

Barradas

et al. 1987

Brit J Clinical Pharma

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“…Because caffeine consumption is very common, we investigated whether consumption of caffeine-rich beverages, such as coffee, black, or green tea, affects the risk of SLE. Caffeine is most commonly used as a probe drug for NAT2 phenotype determinations (28) and excellent NAT2 genotype-phenotype association has been reported (16). Furthermore, we investigated risk modification by the NAT2 polymorphisms in the association of alcohol use, coffee, and other caffeine-rich beverages and SLE risk in Japanese women.…”

Section: Introductionmentioning

confidence: 99%

Modifying Effect of N‐Acetyltransferase 2 Genotype on the Association Between Systemic Lupus Erythematosus and Consumption of Alcohol and Caffeine‐Rich Beverages

Kiyohara

Washio

Horiuchi

et al. 2014

Arthritis Care & Research

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Objective. N-acetyltransferase 2 (NAT2) is involved in the metabolism of various environmental substances, both with and without carcinogenic potential. Alcoholic and nonalcoholic caffeine-rich beverages may be associated with markers of inflammation. Systemic lupus erythematosus (SLE) is a chronic, multifaceted inflammatory disease. We investigated the effects of alcoholic and nonalcoholic caffeine-rich beverages on risk of SLE and determined whether the effects were modified by NAT2 status. Methods. The NAT2 polymorphism was genotyped in 152 SLE cases and 427 healthy controls, all women and Japanese. We assessed effect modification by testing an interaction term for the NAT2 polymorphism and consumption of beverages. Results. Consumption of black tea (odds ratio [OR] 1.88, 95% confidence interval [95% CI] 1.03-3.41) and coffee (OR 1.57, 95% CI 0.95-2.61), but not green tea, was associated with an increased risk of SLE, while alcohol use (OR 0.33, 95% CI 0.20 -0.55) was associated with a decreased risk of SLE. There were significant interactions between the NAT2 polymorphism and either alcohol use (P interaction ‫؍‬ 0.026) or consumption of black tea (P interaction ‫؍‬ 0.048). Conclusion. The NAT2 polymorphism significantly modified the effects of alcohol use and black tea consumption on SLE, emphasizing the importance of incorporating genetic and metabolic information in studies on management of SLE. Additional studies are warranted to confirm the findings suggested in this study.

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“…[9] Danaparoid would be then a promising antico- control. [8] PRP was pre-incubated for one minute in the incubating hole of the aggregometer.…”

Section: Introductionmentioning

confidence: 99%

Availability of Danaparoid, an Anticoagulant, for Routine Hematological Tests.

Tatsumi

Nishioka

Yokota

et al. 2003

HEP

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In the Multiphasic Health Check-up System, medical laboratory testing has been changing lately to utilize a small and compact type of testing systems. The system uses heparinized blood for chemistry tests to reduce laboratory's workload and sample volume. The danaparoid, a mixture of glycosamino-glycans (Heparan sulfate), has been used clinically for treatment of patients with disseminated intravascular coagulopathy instead of heparin sulfate. Heparin has been used for routine laboratory tests, although it has a strong activity of platelet aggregation. This study aimed to examine availability of Danaparoid for routine hematology tests as a substitute of heparin. Although Danaparoid induced platelet aggregation directly, the reaction was weaker than that of heparin. The platelet count of Danaparoid blood was decreased after five minutes of mixing. Addition of MgSO4 or of kanamycin sulfate to Danaparoid blood was able to prevent this decrease. When Danaparoid blood was applied to chemistry tests, major chemistry test data showed acceptable results, although level differences were observed slightly. It was concluded that Danaparoid would be a good candidate for a universal anticoagulant for both chemical and hematological laboratory tests.

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Comparison of the effect of a conventional heparin and a low molecular weight heparinoid on platelet function.

Cited by 60 publications

References 25 publications

Platelet activation following intravenous injection of a conventional heparin: absence of effect with a low molecular weight heparinoid (Org 10172).

Platelet activation following intravenous injection of a conventional heparin: absence of effect with a low molecular weight heparinoid (Org 10172).

Modifying Effect of N‐Acetyltransferase 2 Genotype on the Association Between Systemic Lupus Erythematosus and Consumption of Alcohol and Caffeine‐Rich Beverages

Availability of Danaparoid, an Anticoagulant, for Routine Hematological Tests.

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