Subject(s)
Drug Substitution , Heparin/supply & distribution , African Swine Fever , Animals , Intestinal Mucosa/chemistry , SwineABSTRACT
Most of the unfractionated and low-molecular-weight heparins available worldwide are produced by Chinese companies from porcine mucosa. China is the world's largest producer of pork and thus has plenty of raw material to produce heparins. However, the deadly African Swine Fever (ASF) outbreaks afflicting China since August 2018 may cause extensive losses to the pig herd, with serious consequences for the global supply of heparins. In 2008, a sudden shortage of heparin's raw material resulting from a viral disease in Chinese pigs prompted adulterations responsible for 80 deaths and hundreds of adverse events. This incident revealed the fragility of such a supply chain, which is mostly based on raw material from a single animal from a single country. A worldwide introduction of bovine mucosa heparins manufactured in different countries certainly is a feasible way to mitigate eventual shortages of these life-saving anticoagulants caused by local veterinary problems such as the ASF threatening China now.
Subject(s)
African Swine Fever Virus/pathogenicity , African Swine Fever/virology , Anticoagulants/supply & distribution , Disease Outbreaks/veterinary , Heparin/supply & distribution , Intestinal Mucosa/metabolism , Animals , Anticoagulants/isolation & purification , China , Heparin/isolation & purification , Sus scrofa , SwineABSTRACT
OBJECTIVE: Unfractionated heparin is a mixture of glycosaminoglycans with different pharmacologic and pharmacokinetic properties. The literature suggests that blood loss after cardiac surgery is related to both elevated postoperative heparin concentrations and the potency of different heparin brands. DESIGN: An audit of the observed increase in the incidence of cardiac surgery-related bleeding after change in heparin supplier. Patient characteristics were compared between groups before and after a change in heparin brands. SETTING: Tertiary cardiothoracic center. PARTICIPANTS: All patients undergoing cardiac surgery between August 1, 2011, and April 30, 2012. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two hundred eighty patients underwent surgery before a change in heparin brands and 216 after a change. Their preoperative and intraoperative characteristics were similar. Postoperative chest tube drainages and blood transfusions were significantly greater after the change in heparin brands (postoperative chest drainage 476.8 ± 393.1 v 344.8 ± 323.2 mL/6 h and 1,062.2 ± 738.8 v 841.8 ± 567.4 mL/24 h, respectively; both p < 0.001) despite the administration of larger amounts of protamine, fresh frozen plasma/platelet transfusions, and cryoprecipitate. Heparin recirculation within 24 hours of bypass was noted in about 70% of the samples tested using either anti-factor X activity or the thromboelastography ratio between nonheparinase R and heparinase-modified R and was not associated with the heparin brand. The likelihood ratio chi-square test for nested models identified an added predictive value of the heparin brand when included as a predictor of bleeding (chest drainage >800 mL/6 h) in a model comprising recirculation, assessed using either an elevated anti-factor X activity or ratio between nonheparinase R and heparinase-modified R. CONCLUSION: It is likely that the observed increase in postoperative bleeding was related to the pharmacologic properties of the new heparin brand rather than a higher incidence of heparin recirculation.
Subject(s)
Cardiac Surgical Procedures/adverse effects , Drug Substitution/adverse effects , Heparin/adverse effects , Heparin/supply & distribution , Postoperative Hemorrhage/chemically induced , Postoperative Hemorrhage/diagnosis , Aged , Anticoagulants/adverse effects , Anticoagulants/supply & distribution , Cardiac Surgical Procedures/trends , Cohort Studies , Drug Substitution/trends , Female , Follow-Up Studies , Humans , Male , Middle Aged , Postoperative Hemorrhage/epidemiology , Retrospective StudiesSubject(s)
Anticoagulants/adverse effects , Heparin/adverse effects , Postanesthesia Nursing/methods , Postoperative Care/methods , Safety Management/methods , Adverse Drug Reaction Reporting Systems , Anticoagulants/supply & distribution , Drug Contamination/prevention & control , Drug Contamination/statistics & numerical data , Drug Hypersensitivity/etiology , Drug Monitoring , Hemorrhage/chemically induced , Heparin/supply & distribution , Humans , Nursing Assessment , Partial Thromboplastin Time , Postoperative Care/nursing , Thrombocytopenia/chemically induced , United States , United States Food and Drug Administration , Whole Blood Coagulation TimeSubject(s)
Anticoagulants , Bacteremia/etiology , Bacteremia/prevention & control , Catheterization, Central Venous/adverse effects , Cross Infection/etiology , Cross Infection/prevention & control , Heparin , Infection Control/methods , Anticoagulants/supply & distribution , Drug Approval , Heparin/supply & distribution , Humans , United KingdomSubject(s)
Brain Ischemia/drug therapy , Brain Ischemia/etiology , Stroke/drug therapy , Stroke/etiology , Thrombolytic Therapy , Animals , Arterial Occlusive Diseases/complications , Arterial Occlusive Diseases/drug therapy , Europe/epidemiology , Fibrinolytic Agents/standards , Fibrinolytic Agents/therapeutic use , Forecasting , Heparin/supply & distribution , Heparin/therapeutic use , Humans , Infusions, Intra-Arterial , Infusions, Intravenous , Middle Cerebral Artery/pathology , Practice Guidelines as Topic , Thrombolytic Therapy/standards , Tissue Plasminogen Activator/standards , Tissue Plasminogen Activator/therapeutic use , Treatment Outcome , United States/epidemiology , United States Food and Drug AdministrationABSTRACT
Heparin inhibits smooth-muscle cell (SMC) growth in vitro and inhibits the development of hypoxic pulmonary hypertension and vascular remodeling in vivo. We wondered whether preparations of heparin with different antiproliferative potency in vitro would differ in their ability to inhibit the development of hypoxic pulmonary hypertension in vivo. Two such heparins, a weakly antiproliferative lot of Elkins-Sinn (E-S) (% inhibition of SMC growth at 10 micrograms/ml = 13 +/- 9% [mean +/- SEM, n = 24]) and a more active lot from Upjohn (UJ) (% inhibition = 71 +/- 12% [n = 12, p < 0.05 versus E-S]), were infused subcutaneously (300 U.S.P. units/day; E-S 300 versus UJ 300) via an osmotic pump into guinea pigs exposed to hypoxia (10% O2) for 10 d, after which pulmonary artery pressure (PAP; mm Hg) and cardiac index (CI; ml/min/kg) were measured in room air. Hypoxic controls (HC) received saline. PAP increased from 11 +/- 1 mm Hg in normoxic controls (NC) (n = 5) to 24 +/- 1 mm Hg in HC (n = 8, p < 0.05). The PAP was lower in the E-S 300 (21 +/- 1; n = 7, p < 0.05 versus HC and NC) and even lower in the UJ 300-treated group (18 +/- 0.5; n = 7, p < 0.05 versus HC and NC). Total pulmonary vascular resistance (TPR; mm Hg/ml/min/kg) increased significantly from 0.038 +/- 0.002 in NC to 0.076 +/- 0.003 (p < 0.05) in HC. There was no difference in TPR between the HC and the E-S 300-treated group.(ABSTRACT TRUNCATED AT 250 WORDS)