Pharmacological control of blood coagulation by synthetic, low-molecular-weight inhibitors of clotting enzymes

Background Hydroxyethyl starches (HES) with lower impact on blood coagulation but longer intravascular persistence are of clinical interest. The current study aimed to investigate in vivo the isolated effect of molecular weight on blood coagulation during progressive acute normovolemic hemodilution. Methods Twenty-four pigs were normovolemically hemodiluted up to a total exchange of 50 ml . kg . body weight of HES 650/0.42 or HES 130/0.42. Serial blood sampling was performed to measure HES plasma concentration and to assess blood coagulation. Concentration-effect relations were analyzed by linear regression, followed by the Student t test on regression parameters. Results Blood coagulation was increasingly compromised toward hypocoagulability by acute normovolemic hemodilution with both treatments (P < 0.01). Significantly greater impact on activated partial thromboplastin time (P = 0.04) and significantly stronger decrease of maximal amplitude (P = 0.04), angle alpha (P = 0.02), and coagulation index (P = 0.02) was seen after acute normovolemic hemodilution with HES 650/0.42 as compared with HES 130/0.42. Except for factor VIII (P = 0.04), no significant differences between both treatments were observed when relating antihemostatic effects to HES plasma concentrations (P > 0.05). A significantly lesser decrease of hemoglobin concentration has been found with HES 650/0.42 as compared with HES 130/0.42 (P < 0.01) in relation to HES plasma concentrations. Conclusion High-molecular-weight HES (650/0.42) shows a moderately greater antihemostatic effect than low-molecular-weight HES (130/0.42) during acute normovolemic hemodilution. However, similar effects on hemostasis were observed with both treatments when observed antihemostatic effects were related to measured HES plasma concentrations. In addition, HES 650/0.42 may have a lower efficacy in immediately restoring plasma volume.

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Anti Factor Xa Activity In Plasma Following Oral, Pulmonary, Subcutaneous And Intravenous Administration Of Cd5000 Low Molecular Weight Heparin And Commercial Heparin To Rats, Rabbits And Dogs

10.1055/s-0038-1652700 ◽

1981 ◽

Author(s):

L I Harrison ◽

C R Kehe ◽

R E Ober

Keyword(s):

Molecular Weight ◽

Oral Administration ◽

Blood Coagulation ◽

Intravenous Administration ◽

Plasma Levels ◽

Low Molecular Weight Heparin ◽

Factor Xa ◽

Low Molecular Weight ◽

Dog Plasma ◽

Antifactor Xa

CD5000 heparin (LMWH) is a low molecular weight heparin fraction, ave. mol wt. ∼ 5100. Plasma levels of antiFactor Xa activity (XaA) after iv, pulmonary, sc and oral administration of LMWH and commercial heparin (CH) were examined in rats, rabbits and dogs. Overall, LMWH maintained higher levels of XaA in plasma than did a similar mg dose of CH. When the heparins were given iv, plasma XaA after LMWH had a t1/2 ∼ 2X as long as that after CH. When similar mg doses were given sc, the average plasma XaA following LMWH was significantly higher than that following CH during 0-6 hrs postdose. When equal USP unit doses (four times as much LMWH on a mg basis) were administered into the lungs of dogs, LMWH showed plasma XaA significantly higher than after CH. LMWH also showed higher plasma XaA on oral administration of equal USP unit doses in rats, but the fraction of the dose absorbed and the plasma levels were low. About 4X as much LMWH on a mg basis as CH had to be given to achieve similar APTT values in dog plasma. LMWH may have significant therapeutic advantages in man if pharmacokinetic differences and different blood coagulation effects of the various mol wt. heparins described here in animals also occur in man. Studies in humans are planned.

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Effects of Unfractionated Heparin, Low-Molecular-Weight Heparin, and Heparinoid on Thromboelastographic Assay of Blood Coagulation

American Journal of Clinical Pathology ◽

10.1309/q4ae-bmcw-cq7j-nuvt ◽

2000 ◽

Vol 113 (5) ◽

pp. 725-731 ◽

Cited By ~ 51

Author(s):

Karen Zmuda ◽

Demetra Neofotistos ◽

Chung-hsin Ts’ao

Keyword(s):

Molecular Weight ◽

Unfractionated Heparin ◽

Blood Coagulation ◽

Low Molecular Weight Heparin ◽

Low Molecular Weight

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THE EFFECT OF LOW MOLECULAR WEIGHT DEXTRAN ON BLOOD COAGULATION IN OPEN HEART SURGERY USING EXTRACORPOREAL CIRCULATION, WITH SPECIAL REFERENCE TO THROMBELASTOGRAPHIC FINDINGS

Journal of the Japan Society of Blood Transfusion ◽

10.3925/jjtc1958.13.97 ◽

1966 ◽

Vol 13 (4) ◽

pp. 97-111

Author(s):

Takashi MIYAMOTO

Keyword(s):

Molecular Weight ◽

Special Reference ◽

Blood Coagulation ◽

Extracorporeal Circulation ◽

Heart Surgery ◽

Open Heart Surgery ◽

Low Molecular Weight ◽

Open Heart

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A high-performance oil-free backing pump for electron microscopes

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100107691 ◽

1978 ◽

Vol 36 (1) ◽

pp. 110-111

Author(s):

G.K.W. Balkau ◽

E. Bez ◽

J.L. Farrant

Keyword(s):

Molecular Weight ◽

Electron Microscope ◽

Hot Spots ◽

High Performance ◽

Carbonaceous Material ◽

Contamination Rate ◽

Low Molecular Weight ◽

Principal Source ◽

Rotary Pumps ◽

Electron Microscopes

The earliest account of the contamination of electron microscope specimens by the deposition of carbonaceous material during electron irradiation was published in 1947 by Watson who was then working in Canada. It was soon established that this carbonaceous material is formed from organic vapours, and it is now recognized that the principal source is the oil-sealed rotary pumps which provide the backing vacuum. It has been shown that the organic vapours consist of low molecular weight fragments of oil molecules which have been degraded at hot spots produced by friction between the vanes and the surfaces on which they slide. As satisfactory oil-free pumps are unavailable, it is standard electron microscope practice to reduce the partial pressure of organic vapours in the microscope in the vicinity of the specimen by using liquid-nitrogen cooled anti-contamination devices. Traps of this type are sufficient to reduce the contamination rate to about 0.1 Å per min, which is tolerable for many investigations.

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