Heparins from porcine and bovine intestinal mucosa: Are they similar drugs?
Increasing reports of bleeding and peri- or post-operative blood dyscrasias in Brazil were possibly associated with the use of heparin from bovine instead of porcine intestine. These two pharmaceutical grade heparins were analysed for potential differences. NMR analyses confirmed that porcine heparin is composed of mainly trisulfated disaccharides -->4-alpha-IdoA2S-1-->4-alpha-GlcNS6S-1-->. Heparin from bovine intestine is also composed of highly 2-sulfated alpha-iduronic acid residues, but the sulfation of the alpha-glucosamine units vary significantly: approximately 50% are 6- and N -disulfated, as in porcine heparin, while approximately 36% are 6-desulfated and approximately 14% N -acetylated. These heparins differ significantly in their effects on coagulation, thrombosis and bleeding. Bovine heparin acts mostly through factor Xa. Compared to porcine heparin on a weight basis, bovine heparin exhibited approximately half of the anticoagulant and antithrombotic effects, but similar effect on bleeding. These two heparins also differ in their protamine neutralisation curves. The doses of heparin from bovine intestine required for effective antithrombotic protection and the production of adverse bleeding effects are closer than those for porcine heparin. This observation may explain the increasing bleeding observed among Brazilian patients. Our results suggest that these two types of heparin are not equivalent drugs.
Aquino
Rafael S
RS
Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho, Programa de Glicobiologia, Instituto de Bioquímica Médica, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Caixa Postal 68041, Rio de Janeiro, RJ, 21941-590, Brazil.
Pereira
Mariana S
MS
Vairo
Bruno C
BC
Cinelli
Leonardo P
LP
Santos
Gustavo R C
GR
Fonseca
Roberto J C
RJ
Mourão
Paulo A S
PA
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D002417:Cattle; D004187:Disaccharides / Q000737:chemistry*; D015951:Factor Xa / Q000378:metabolism; D006470:Hemorrhage / Q000209:etiology; D006493:Heparin / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D007413:Intestinal Mucosa / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D011479:Protamines / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013552:Swine; D013925:Thromboplastin / Q000008:administration & dosage; D020246:Venous Thrombosis / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*
D004187:Disaccharides; D011479:Protamines; C030101:protamine heparin aggregate; D006493:Heparin; D013925:Thromboplastin; D015951:Factor Xa