Download PDF
Semin Thromb Hemost 2007; 33(5): 524-533
DOI: 10.1055/s-2007-982084
Copyright © 2007 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Heparin, Low Molecular Weight Heparin, and Derivatives in Thrombosis, Angiogenesis, and Inflammation: Emerging Links

Shaker A. Mousa1
  • 1The Pharmaceutical Research Institute at Albany College of Pharmacy, Albany, New York
Further Information

Publication History

Publication Date:
16 July 2007 (online)

    Permissions and Reprints

ABSTRACT

The key reason behind the success of heparin in thrombosis and beyond is its polypharmacological sites of action for the prevention and treatment of multifactorial diseases that will only benefit slightly with single pharmacological mechanism-based agents. Thromboembolic disorders are driven by hypercoagulable, hyperactive platelet, proinflammatory, endothelial dysfunction, and proangiogenesis states. Heparin can effectively modulate all of those multifactorial components, as well as the interface among those components.

KEYWORDS

Heparin - low molecular weight heparin - glycosaminoglycans - thrombosis - angiogenesis - inflamation - tissue factor - tissue factor pathway inhibitor - anti-factor Xa - anti-factor IIa

REFERENCES

  • 1 Weitz J I. Low-molecular-weight heparin.  N Engl J Med. 1997;  337 688-698
    CrossrefPubMedGoogle Scholar
  • 2 Aguilar D, Goldhaber S Z. Clinical uses of low molecular weight heparin.  Chest. 1999;  115 1418-1423
    CrossrefPubMedGoogle Scholar
  • 3 Mousa S A, Fareed J. Overview: from heparin to low molecular weight heparin: beyond anticoagulation.  Curr Opin Investig Drugs. 2001;  2(8) 1077-1080
    PubMedGoogle Scholar
  • 4 Mousa S A. Comparative efficacy of different low-molecular-weight heparins (LMWHs) and drug interactions with LMWH: implications for management of vascular disorders.  Semin Thromb Hemost. 2000;  26(suppl 1) 39-46
    PubMedGoogle Scholar
  • 5 Taheri S A, Lazar L, Haddad G, Castaldo R, Wilson M, Mousa S. Diagnosis of deep venous thrombosis by use of soluble necrosis factor receptor.  Angiology. 1998;  49 537-541
    PubMedGoogle Scholar
  • 6 Nelson R M, Cecconi O, Roberts W G, Aruffo A, Linhardt R J, Bevilacqua M P. Heparin oligosaccharides bind L- and P-selectin and inhibit acute inflammation.  Blood. 1993;  82 3253-3258
    PubMedGoogle Scholar
  • 7 Lantz M, Thysell H, Nilsson E, Olsson I. On the binding of tumor necrosis factor (TNF) to heparin and the release in vivo of the TNF-binding protein I by heparin.  J Clin Invest. 1991;  88 2026-2031
    PubMedGoogle Scholar
  • 8 Tyrell D J, Kilfeather S, Page C P. Therapeutic uses of heparin beyond its traditional role as an anticoagulant.  Trends Pharmacol Sci. 1995;  16 198-204
    CrossrefPubMedGoogle Scholar
  • 9 Hocking D, Ferro T J, Johnson A. Dextran sulfate and heparin sulfate inhibit platelet-activating factor-induced pulmonary edema.  J Appl Physiol. 1992;  72 179-185
    PubMedGoogle Scholar
  • 10 Darien B J, Fareed J, Centgraf K S et al.. Low molecular weight heparin prevents the pulmonary hemodynamic and pathomorphologic effects of endotoxin in a porcine acute lung injury model.  Shock. 1998;  9 274-281
    PubMedGoogle Scholar
  • 11 Meyer J, Cox C S, Herndon D N et al.. Heparin in experimental hyperdynamic sepsis.  Crit Care Med. 1993;  21 84-89
    PubMedGoogle Scholar
  • 12 Hiebert L M, Liu J M. Heparin protects cultured arterial endothelial cells from damage by toxic oxygen metabolites.  Atherosclerosis. 1990;  83 47-51
    CrossrefPubMedGoogle Scholar
  • 13 Matzner Y, Marx G, Drexler R, Eldor A. The inhibitory effect of heparin and related glycosaminoglycans on neutrophil chemotaxis.  Thromb Haemost. 1984;  52 134-137
    PubMedGoogle Scholar
  • 14 Bazzoni G, Beltran Nunez A, Mascellani G, Bianchini P, Dejana E, Del Maschio A. Effect of heparin, dermatan sulfate, and related oligo-derivatives on human polymorphonuclear leukocyte functions.  J Lab Clin Med. 1993;  121 268-275
    PubMedGoogle Scholar
  • 15 Buller H R, Agnelli G, Hull R D, Hyers T M, Prins M H, Raskob G E. Antithrombotic therapy for venous thromboembolic disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.  Chest. 2004;  126 401S-428S
    CrossrefPubMedGoogle Scholar
  • 16 Hutten B A, Prins M H, Gent M et al.. Incidence of recurrent thromboembolic and bleeding complications among patients with venous thromboembolism in relation to both malignancy and achieved international normalized ratio: a retrospective analysis.  J Clin Oncol. 2000;  18 3078-3083
    PubMedGoogle Scholar
  • 17 Palareti G, Legnani C, Lee A et al.. A comparison of the safety and efficacy of oral anticoagulation for the treatment of venous thromboembolic disease in patients with or without malignancy.  Thromb Haemost. 2000;  84 805-810
    Article in Thieme ConnectPubMedGoogle Scholar
  • 18 Prandoni P, Lensing A WA, Piccioli A et al.. Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis.  Blood. 2002;  100 3484-3488
    CrossrefPubMedGoogle Scholar
  • 19 Lee A Y, Levine M N, Baker R I et al.. Randomized comparison of low-molecular-weight heparin versus oral anticoagulant therapy for the prevention of recurrent venous thromboembolism in patients with cancer.  N Engl J Med. 2003;  349 146-153
    CrossrefPubMedGoogle Scholar
  • 20 Meyer G, Marjanovic Z, Valcke J et al.. Comparison of low-molecular-weight heparin and warfarin for the secondary prevention of venous thromboembolism in patients with cancer.  Arch Intern Med. 2002;  162 1729-1735
    CrossrefPubMedGoogle Scholar
  • 21 The Columbus Investigators . Low-molecular-weight heparin in the treatment of patients with venous thromboembolism.  N Engl J Med. 1997;  337 657-662
    CrossrefPubMedGoogle Scholar
  • 22 Simonneau G, Sors H, Charbonnier B et al.. A comparison of low-molecular-weight heparin with unfractionated heparin for acute pulmonary embolism.  N Engl J Med. 1997;  337 663-669
    CrossrefPubMedGoogle Scholar
  • 23 Quinlan D J, McQuillan A, Eikelboom J W. Low-molecular-weight heparin compared with intravenous unfractionated heparin for treatment of pulmonary embolism: a meta-analysis of randomized, controlled trials.  Ann Intern Med. 2004;  140 175-183
    PubMedGoogle Scholar
  • 24 Goldhaber S Z, Visani L, De Rosa M. Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER).  Lancet. 1999;  353 1386-1389
    CrossrefPubMedGoogle Scholar
  • 25 Grifoni S, Olivotto I, Cecchini P et al.. Short-term clinical outcome of patients with acute pulmonary embolism, normal blood pressure, and echocardiographic right ventricular dysfunction.  Circulation. 2000;  101 2817-2822
    CrossrefPubMedGoogle Scholar
  • 26 Agnelli G, Becattini C, Kirschstein T. Thrombolysis vs heparin in the treatment of pulmonary embolism.  Arch Intern Med. 2002;  162 2537-2541
    CrossrefPubMedGoogle Scholar
  • 27 Thabut G, Thabut D, Myers R P et al.. Thrombolytic therapy of pulmonary embolism: a meta-analysis.  J Am Coll Cardiol. 2002;  40 1660-1667
    CrossrefPubMedGoogle Scholar
  • 28 Konstantinides S, Gebel A, Heusel G et al.. Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism.  N Engl J Med. 2002;  347 1143-1150
    CrossrefPubMedGoogle Scholar
  • 29 Ten Wolde M, Sohne M, Quak E, Mac Gillavry M R, Buller H R. Prognostic value of echocardiographically assessed right ventricular dysfunction in patients with pulmonary embolism.  Arch Intern Med. 2004;  164 1685-1689
    CrossrefPubMedGoogle Scholar
  • 30 Prandoni P, Lensing A WA, Cogo A et al.. The long-term clinical course of acute deep venous thrombosis.  Ann Intern Med. 1996;  125 1-7
    CrossrefPubMedGoogle Scholar
  • 31 Prandoni P, Villalta S, Bagatella P et al.. The clinical course of deep-vein thrombosis. Prospective long-term follow-up of 528 symptomatic patients.  Haematologica. 1997;  82 423-428
    PubMedGoogle Scholar
  • 32 Hansson P O, Sorbo J, Eriksson H. Recurrent venous thromboembolism after deep vein thrombosis: incidence and risk factors.  Arch Intern Med. 2000;  160 769-774
    CrossrefPubMedGoogle Scholar
  • 33 Heit J A, Mohr D N, Silverstein M D, Petterson T M, O'Fallon W M, Melton III L J. Predictors of recurrence after deep vein thrombosis and pulmonary embolism: a population-based cohort study.  Arch Intern Med. 2000;  160 761-768
    CrossrefPubMedGoogle Scholar
  • 34 Schulman S, Rhedin A S, Lindmarker P et al.. A comparison of six weeks with six months of oral anticoagulant therapy after a first episode of venous thromboembolism.  N Engl J Med. 1995;  332 1661-1665
    CrossrefPubMedGoogle Scholar
  • 35 Kearon C, Gent M, Hirsh J et al.. A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism.  N Engl J Med. 1999;  340 901-907
    PubMedGoogle Scholar
  • 36 Agnelli G, Prandoni P, Santamaria M G et al.. Three months versus one year of oral anticoagulant therapy for idiopathic deep venous thrombosis.  N Engl J Med. 2001;  345 165-169
    PubMedGoogle Scholar
  • 37 Pinede L, Ninet J, Duhaut P et al.. Comparison of 3 and 6 months of oral anticoagulant therapy after a first episode of proximal deep vein thrombosis or pulmonary embolism and comparison of 6 and 12 weeks of therapy after isolated calf deep vein thrombosis.  Circulation. 2001;  103 2453-2460
    CrossrefPubMedGoogle Scholar
  • 38 Agnelli G, Prandoni P, Becattini C et al.. Extended oral anticoagulant therapy after a first episode of pulmonary embolism.  Ann Intern Med. 2003;  139 19-25
    CrossrefPubMedGoogle Scholar
  • 39 Schulman S, Granqvist S, Holmstrom M et al.. The duration of oral anticoagulant therapy after a second episode of venous thromboembolism.  N Engl J Med. 1997;  336 393-398
    CrossrefPubMedGoogle Scholar
  • 40 Ridker P M, Goldhaber S Z, Danielson E et al.. Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism.  N Engl J Med. 2003;  348 1425-1434
    CrossrefPubMedGoogle Scholar
  • 41 Kearon C, Ginsberg J S, Anderson D R et al.. Comparison of 1 month with 3 months of anticoagulation for a first episode of venous thromboembolism associated with a transient risk factor.  J Thromb Haemost. 2004;  2 743-749
    CrossrefPubMedGoogle Scholar
  • 42 Vancheri C, Mastruzzo C, Armato F et al.. Intranasal heparin reduces eosinophil recruitment after nasal allergen challenge in patients with allergic rhinitis.  J Allergy Clin Immunol. 2001;  108 703-708
    CrossrefPubMedGoogle Scholar
  • 43 Diamant Z, Timmers M C, van der Veen H, Page C P, van der Meer F J, Sterk P J. Effect of inhaled heparin on allergen-induced early and late asthmatic responses in patients with atopic asthma.  Am J Respir Crit Care Med. 1996;  153 1790-1795
    PubMedGoogle Scholar
  • 44 Garrigo J, Danta I, Ahmed T. Time course of the protective effect of inhaled heparin on exercise-induced asthma.  Am J Respir Crit Care Med. 1996;  153 1702-1707
    PubMedGoogle Scholar
  • 45 Gaffney A, Gaffney P. Rheumatoid arthritis and heparin.  Br J Rheumatol. 1996;  35 808-809
    CrossrefPubMedGoogle Scholar
  • 46 Bowler S D, Smith S M, Lavercombe P S. Heparin inhibits the immediate response to antigen in the skin and lungs of allergic subjects.  Am Rev Respir Dis. 1993;  147 160-163
    PubMedGoogle Scholar
  • 47 Dwarakanath A D, Yu L G, Brookes C, Pryce D, Rhodes J M. Sticky neutrophils, pathergic arthritis, and response to heparin in pyoderma gangrenosum complicating ulcerative colitis.  Gut. 1995;  37 585-588
    PubMedGoogle Scholar
  • 48 Petitou M, Hérault J-P, Bernat A et al.. Synthesis of thrombin-inhibiting heparin mimetics without side effects.  Nature. 1999;  398 417-422
    CrossrefPubMedGoogle Scholar
  • 49 Tyrrel D J, Horne A P, Holme K R, Preuss J MH, Page C P. Heparin in inflammation: potential therapeutic applications beyond anticoagulation.  Adv Pharmacol. 1999;  46 151-208
    PubMedGoogle Scholar
  • 50 Salas A, Sans M, Soriano A et al.. Heparin attenuates TNF-induced inflammatory response through a CD11b dependent mechanism.  Gut. 2000;  47 88-96
    CrossrefPubMedGoogle Scholar
  • 51 Panés J, Perry M, Granger D N. Leukocyte-endothelial cell adhesion: avenues for therapeutic intervention.  Br J Pharmacol. 1999;  126 537-550
    CrossrefPubMedGoogle Scholar
  • 52 Lever R, Hoult J RS, Page C P. The effects of heparin and related molecules upon the adhesion of human polymorphonuclear leukocytes to vascular endothelium in vitro.  Br J Pharmacol. 2000;  129 533-540
    CrossrefPubMedGoogle Scholar
  • 53 Gaffney P R, Doyle C T, Gaffney A, Hogan J, Hayes D P, Annis P. Paradoxical response to heparin in 10 patients with ulcerative colitis.  Am J Gastroenterol. 1995;  90 220-223
    PubMedGoogle Scholar
  • 54 Gaffney P, Gaffney A. Heparin therapy in refractory ulcerative colitis-an update.  Gastroenterology. 1996;  110 A913 , (abst)
    PubMedGoogle Scholar
  • 55 Evans R C, Rhodes J M. Treatment of corticosteroid-resistant ulcerative colitis with heparin. A report of nine cases.  Gut. 1995;  37 A49 , (abst)
    PubMedGoogle Scholar
  • 56 Brazier F, Yzet T, Duchmann J C et al.. Effect of heparin treatment on extra intestinal manifestations associated with inflammatory bowel diseases.  Gastroenterology. 1996;  110 A872 , (abst)
    PubMedGoogle Scholar
  • 57 Brazier F, Yzet T, Boruchowicz A et al.. Treatment of ulcerative colitis with heparin.  Gastroenterology. 1996;  110 A872 , (abst)
    PubMedGoogle Scholar
  • 58 Dupas J L, Brazier F, Yzet T et al.. Treatment of active Crohn's disease with heparin.  Gastroenterology. 1996;  110 A900 , (abst)
    PubMedGoogle Scholar
  • 59 Folwaczny C, Spannagl M, Wiebecke W et al.. Heparin in the treatment of highly active inflammatory bowel disease (IBD).  Gastroenterology. 1996;  110 A908 , (abst)
    PubMedGoogle Scholar
  • 60 Dwarakanath A D, Yu L G, Brookes C, Pryce D, Rhodes J M. “Sticky” neutrophils, pathergic arthritis, and response to heparin in pyoderma gangrenosum complicating ulcerative colitis.  Gut. 1995;  37 585-588
    PubMedGoogle Scholar
  • 61 Teixeira M M, Hellewell P G. Suppression by intradermal administration of heparin of eosinophil accumulation but not edema formation in inflammatory reactions in guinea-pig skin.  Br J Pharmacol. 1993;  110 1496-1500
    PubMedGoogle Scholar
  • 62 Carr J. The anti-inflammatory action of heparin: heparin as an antagonist to histamine, bradykinin and prostaglandin E1.  Thromb Res. 1979;  16 507-516
    CrossrefPubMedGoogle Scholar
  • 63 Koenig A, Norgard-Sumnicht K, Linhardt R, Varki A. Differential interactions of heparin and heparan sulfate glycosaminoglycans with the selectins: implications for the use of unfractionated and low molecular weight heparins as therapeutic agents.  J Clin Invest. 1998;  101 877-889
    CrossrefPubMedGoogle Scholar
  • 64 Diamond M S, Alon R, Parkos C A, Quinn M T, Springer T A. Heparin is an adhesive ligand for the leukocyte integrin Mac-1 (CD11b/CD18).  J Cell Biol. 1995;  130 1473-1482
    CrossrefPubMedGoogle Scholar
  • 65 Benimetskaya L, Loike J D, Khaled Z et al.. Mac-1 (CD11b/CD18) is an oligodeoxy-nucleotide-binding protein.  Nat Med. 1997;  3 414-420
    CrossrefPubMedGoogle Scholar
  • 66 Emanuele R M, Fareed J. The effect of molecular weight on the bioavailability of heparin.  Thromb Res. 1987;  48 591-596
    CrossrefPubMedGoogle Scholar
  • 67 Brieger D, Dawes J. Production method affects the pharmacokinetic and ex vivo biological properties of low molecular weight heparins.  Thromb Haemost. 1997;  77 317-322
    PubMedGoogle Scholar
  • 68 Mousa S A, Mohamed S. Inhibition of endothelial cell tube formation by the low molecular weight heparin, tinzaparin, is mediated by tissue factor pathway inhibitor.  Thromb Haemost. 2004;  92 627-633
    Google Scholar
  • 69 Mousa S A, Kaiser B. Tissue factor pathway inhibitor in thrombosis and beyond: role of heparin.  Drugs Future. 2004;  29 751-766
    CrossrefPubMedGoogle Scholar
  • 70 Boneu B, Caranobe C, Cadroy Y et al.. Pharmacokinetic studies of standard unfractionated heparin, and low molecular weight heparins in the rabbit.  Semin Thromb Hemost. 1988;  14 18-27
    PubMedGoogle Scholar
  • 71 Sutor A H, Massicotte P, Leaker M, Andrew M. Heparin therapy in pediatric patients.  Semin Thromb Hemost. 1997;  23 303-319
    Article in Thieme ConnectPubMedGoogle Scholar
  • 72 Majerus P, Broze J G, Miletich J. Anticoagulant, thrombolytic and antiplatelet drugs. In: Hardman J, Limbird L, Molinoff P, Ruddon R, Goodman A Goodman & Gilman's, The Pharmacological Basis of Therapeutics. 9th ed. New York; McGraw-Hill 1996: 1341-1359
    Google Scholar
  • 73 Silverstein R. Drugs affecting hemostosis. In: Munson P, Mueller R, Breeze G Munson's Principles of Pharmacology. New York; Chapman & Hall 1995: 1123-1143
    Google Scholar
  • 74 Theroux P, Waters D, Qiu S, McCans J, de Guise P, Juneau M. Aspirin versus heparin to prevent myocardial infarction during the acute phase of unstable angina.  Circulation. 1993;  88 2045-2048
    PubMedGoogle Scholar
  • 75 Itoh K, Nakao A, Kishimoto W, Takagi H. Heparin effects on superoxide production by neutrophils.  Eur Surg Res. 1995;  27 184-188
    PubMedGoogle Scholar
  • 76 Attanasio M, Gori A M, Giusti B et al.. Cytokine gene expression in human LPS- and IFNgamma-stimulated mononuclear cells is inhibited by heparin.  Thromb Haemost. 1998;  79 959-962
    PubMedGoogle Scholar
  • 77 Dandona P, Qutob T, Hamouda W, Bakri F, Aljada A, Kumbkarni Y. Heparin inhibits reactive oxygen species generation by polymorphonuclear and mononuclear leucocytes.  Thromb Res. 1999;  96 437-443
    CrossrefPubMedGoogle Scholar
  • 78 Friedrichs G S, Kilgore K S, Manley P J, Gralinski M R, Lucchesi B R. Effects of heparin and N-acetyl heparin on ischemia/reperfusion-induced alterations in myocardial function in the rabbit isolated heart.  Circ Res. 1994;  75 701-710
    PubMedGoogle Scholar
  • 79 Black S C, Gralinski M R, Friedrichs G S, Kilgore K S, Driscoll E M, Lucchesi B R. Cardioprotective effects of heparin or N-acetylheparin in an in vivo model of myocardial ischaemic and reperfusion injury.  Cardiovasc Res. 1995;  29 629-636
    CrossrefPubMedGoogle Scholar
  • 80 Lucchesi B R, Kilgore K S. Complement inhibitors in myocardial ischemia/reperfusion injury.  Immunopharmacology. 1997;  38 27-42
    CrossrefPubMedGoogle Scholar
  • 81 Hawari F I, Shykoff B E, Izzo Jr J L. Heparin attenuates norepinephrine-induced venoconstriction.  Vasc Med. 1998;  3 95-100
    PubMedGoogle Scholar
  • 82 De Caterina R, Libby P, Peng H B et al.. Nitric oxide decreases cytokine-induced endothelial activation: nitric oxide selectively reduces endothelial expression of adhesion molecules and pro-inflammatory cytokines.  J Clin Invest. 1995;  96 60-68
    PubMedGoogle Scholar
  • 83 Merwin R M, Algire G H. Induction of plasma-cell neoplasms and fibrosarcomas in BALB/c mice carrying diffusion chambers.  Proc Soc Exp Biol Med. 1959;  101(3) 437-439
    PubMedGoogle Scholar
  • 84 Kerbel R S. Tumor angiogenesis: past, present and the near future.  Carcinogenesis. 2000;  21 505-515
    CrossrefPubMedGoogle Scholar
  • 85 Folkman J. Proceedings: tumor angiogenesis factor.  Cancer Res. 1974;  34(8) 2109-2113
    PubMedGoogle Scholar
  • 86 Folkman J, Langer R, Linhardt R, Haudenschild C, Taylor S. Angiogenesis inhibition and tumor regression caused by heparin or a heparin fragment in the presence of cortisone.  Science. 1983;  221 719-725
    PubMedGoogle Scholar
  • 87 Folkman J, Shing Y. Control of angiogenesis by heparin and other sulfated polysaccharides.  Adv Exp Med Biol. 1992;  313 355-364
    PubMedGoogle Scholar
  • 88 Mousa S A, Mohamed S. Anti-angiogenic mechanisms and efficacy of the low molecular weight heparin, tinzaparin: anti-cancer efficacy.  Oncol Rep. 2004;  12 683-688
    PubMedGoogle Scholar
  • 89 Hull R D, Raskob G E, Pineo G F et al.. Subcutaneous LMWH compared with continuous intravenous heparin in the treatment of proximal-vein thrombosis.  N Engl J Med. 1992;  326 975-982
    CrossrefPubMedGoogle Scholar
  • 90 Simonneau G, Sors H, Charbonnier B et al.. A comparison of LMWH with unfractionated heparin for acute pulmonary embolism.  N Engl J Med. 1997;  337 663-669
    CrossrefPubMedGoogle Scholar
  • 91 Dahlback B. Blood coagulation.  Lancet. 2000;  355 1627-1632
    CrossrefPubMedGoogle Scholar
  • 92 Bajaj M S, Bajaj S P. Tissue factor pathway inhibitor: potential therapeutic applications.  Thromb Haemost. 1997;  78 471-477
    PubMedGoogle Scholar
  • 93 Von Tempelhoff G-F, Hareberg J, Niemann F, Hommel G, Kirkpatrik C J, Heilmann L. Subcutaneous heparin treatment increases survival in small cell lung cancer.  Int J Oncol. 2000;  16 815-824
    PubMedGoogle Scholar
  • 94 Kakkar A K, Williamson R C. Antithrombotic therapy in cancer.  BMJ. 1999;  318(7198) 1571-1572
    PubMedGoogle Scholar
  • 95 Kohanna F H, Sweeny J, Hussey S, Zacharski L, Salzman E W. Effect of perioperative low-dose heparin on the course of colon cancer.  Surgery. 1983;  93 433-438
    PubMedGoogle Scholar
  • 96 Leonard W J, Lin J X. Cytokine receptor signaling pathways.  J Allergy Clin Immunol. 2000;  105 877-888
    CrossrefPubMedGoogle Scholar
  • 97 Mousa S A, Linhardt R, Francis J L, Amirkhosravi A. Anti-metastatic effect of a non-anticoagulant low-molecular-weight heparin versus the standard low-molecular-weight heparin, enoxaparin.  Thromb Haemost. 2006;  96 816-821
    Google Scholar

Shaker MousaPh.D. M.B.A. F.A.C.C. F.A.C.B. 

Pharmaceutical Research Institute at Albany College of Pharmacy

PRI, 106 New Scotland Avenue, Albany, NY 12208

Email: mousas@acp.edu

      >