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1

&NA;. "Heparin/low molecular weight heparins." Reactions Weekly &NA;, no. 1414 (August 2012): 28–29. http://dx.doi.org/10.2165/00128415-201214140-00091.

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&NA;. "Heparin/low-molecular-weight heparins." Reactions Weekly &NA;, no. 1198 (April 2008): 22. http://dx.doi.org/10.2165/00128415-200811980-00068.

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&NA;. "Heparin/low molecular weight heparins." Reactions Weekly &NA;, no. 1210 (July 2008): 18. http://dx.doi.org/10.2165/00128415-200812100-00051.

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&NA;. "Heparin/low molecular weight heparins." Reactions Weekly &NA;, no. 1211 (July 2008): 17–18. http://dx.doi.org/10.2165/00128415-200812110-00053.

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&NA;. "Heparin/low molecular weight heparins." Reactions Weekly &NA;, no. 1211 (July 2008): 18. http://dx.doi.org/10.2165/00128415-200812110-00056.

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&NA;. "Heparin/low molecular weight heparins." Reactions Weekly &NA;, no. 1277 (November 2009): 23. http://dx.doi.org/10.2165/00128415-200912770-00068.

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7

&NA;. "Heparin/low molecular weight heparins." Reactions Weekly &NA;, no. 1231 (December 2008): 16–17. http://dx.doi.org/10.2165/00128415-200812310-00049.

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8

&NA;. "Heparin/low molecular weight heparins." Reactions Weekly &NA;, no. 989 (February 2004): 10. http://dx.doi.org/10.2165/00128415-200409890-00030.

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9

Mulloy, Barbara, Trevor Barrowcliffe, and Elaine Gray. "Heparin and low-molecular-weight heparin." Thrombosis and Haemostasis 99, no. 11 (2008): 807–18. http://dx.doi.org/10.1160/th08-01-0032.

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SummaryHeparin is one of the oldest biological medicines, and has an established place in the prevention and treatment of venous thrombosis. Low-molecular-weight heparins (LMWH) have been developed by several manufacturers and have advantages in terms of pharmacokinetics and convenience of administration. They have been shown to be at least as effective and safe as unfractionated heparin and have replaced the latter in many indications. In this article the chemistry, mechanisms of action, measurement of anticoagulant activities, and clinical status of heparin and LMWH are reviewed.
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10

Hoppensteadt, Debra, Jeanine M. Walenga, Jawed Fareed, and Rodger L. Bick. "Heparin, low–molecular-weight heparins, and heparin pentasaccharide." Hematology/Oncology Clinics of North America 17, no. 1 (February 2003): 313–41. http://dx.doi.org/10.1016/s0889-8588(02)00091-6.

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11

&NA;. "Heparin/low molecular weight heparins/warfarin." Reactions Weekly &NA;, no. 1321 (October 2010): 20. http://dx.doi.org/10.2165/00128415-201013210-00061.

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12

Hirsh, Jack. "Heparin and low-molecular weight heparins." Coronary Artery Disease 3, no. 11 (November 1992): 990–1002. http://dx.doi.org/10.1097/00019501-199211000-00002.

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13

&NA;. "Heparin/low-molecular weight heparin." Reactions Weekly &NA;, no. 1216 (August 2008): 19. http://dx.doi.org/10.2165/00128415-200812160-00049.

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14

Mulloy, B., C. Gee, S. F. Wheeler, R. Wait, E. Gray, and T. W. Barrowcliffe. "Molecular Weight Measurements of Low Molecular Weight Heparins by Gel Permeation Chromatography." Thrombosis and Haemostasis 77, no. 04 (1997): 668–74. http://dx.doi.org/10.1055/s-0038-1656031.

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SummaryThe molecular weight profiles of low molecular weight heparin samples have been measured by high-performance gel permeation chromatography using as calibrant the heparinase-degraded material (90/686) now established as the 1st International Reference Preparation (IRP) Low Molecular Weight Heparin for Molecular Weight Calibration. Use of the calibrant as a broad molecular weight standard is described and a calibration table provided based on data collected over several years in one laboratory.In order to confirm the assignment of degree of polymerisation to resolved oligosaccharide peaks in the calibrant, molecular weights of oligosaccharides fractionated from the 1st IRP were independently determined by fast atom bombardment mass spectrometry (FAB MS).The molecular weight distributions of commercial low molecular weight heparins have been characterized. Measurements of molecular weight parameters of heparin molecular weight standards from several sources provide comparisons between the molecular weight scales of this and other studies.
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15

Martinez-Salas, José, Richard Mendelssohn, William M. Abraham, Bernard Hsiao, and Tahir Ahmed. "Inhibition of allergic airway responses by inhaled low-molecular-weight heparins: molecular-weight dependence." Journal of Applied Physiology 84, no. 1 (January 1, 1998): 222–28. http://dx.doi.org/10.1152/jappl.1998.84.1.222.

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Martinez-Salas, José, Richard Mendelssohn, William M. Abraham, Bernard Hsiao, and Tahir Ahmed. Inhibition of allergic airway responses by inhaled low-molecular-weight heparins: molecular-weight dependence. J. Appl. Physiol. 84(1): 222–228, 1998.—Inhaled heparin prevents antigen-induced bronchoconstriction and inhibits anti-immunoglobulin E-mediated mast cell degranulation. We hypothesized that the antiallergic action of heparin may be molecular weight dependent. Therefore, we studied the effects of three different low-molecular-weight fractions of heparin [medium-, low-, and ultralow-molecular-weight heparin (MMWH, LMWH, ULMWH, respectively)] on the antigen-induced acute bronchoconstrictor response (ABR) and airway hyperresponsiveness (AHR) in allergic sheep. Specific lung resistance was measured in 22 sheep before and after airway challenge with Ascaris suum antigen, without and after pretreatment with inhaled fractionated heparins at doses of 0.31–5.0 mg/kg. Airway responsiveness was estimated before and 2 h postantigen as the cumulative provocating dose of carbachol in breath units that increased specific lung resistance by 400%. All fractionated heparins caused a dose-dependent inhibition of ABR and AHR. ULMWH was the most effective fraction, with the inhibitory dose causing 50% protection (ID50) against ABR of 0.5 mg/kg, whereas ID50values of LMWH and MMWH were 1.25 and 1.8 mg/kg, respectively. ULMWH was also the most effective fraction in attenuating AHR; the ID50values for ULMWH, LMWH, and MMWH were 0.5, 2.5, and 4.7 mg/kg, respectively. These data suggest that 1) fractionated low-molecular-weight heparins attenuate antigen-induced ABR and AHR; 2) there is an inverse relationship between the antiallergic activity of heparin fractions and molecular weight; and 3) ULMWH is the most effective fraction preventing allergic bronchoconstriction and airway hyperresponsiveness.
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16

&NA;. "Danaparoid sodium/heparin/low molecular weight heparins." Reactions Weekly &NA;, no. 1269 (September 2009): 15–16. http://dx.doi.org/10.2165/00128415-200912690-00042.

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17

&NA;. "Low molecular weight heparins challenge standard heparin." Inpharma Weekly &NA;, no. 805 (September 1991): 22–23. http://dx.doi.org/10.2165/00128413-199108050-00057.

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18

Hirsh, Jack, and Robert Raschke. "Heparin and Low-Molecular-Weight Heparin." Chest 126, no. 3 (September 2004): 188S—203S. http://dx.doi.org/10.1378/chest.126.3_suppl.188s.

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19

Hirsh, Jack, Theodore E. Warkentin, Robert Raschke, Christopher Granger, E. Magnus Ohman, and James E. Dalen. "Heparin and Low-Molecular-Weight Heparin." Chest 114, no. 5 (November 1998): 489S—510S. http://dx.doi.org/10.1378/chest.114.5_supplement.489s.

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20

&NA;. "Low molecular weight heparin." Reactions Weekly &NA;, no. 1148 (April 2007): 25. http://dx.doi.org/10.2165/00128415-200711480-00081.

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21

Whang, Peter G., and Jay R. Lieberman. "Low-Molecular-Weight Heparin." Journal of the American Academy of Orthopaedic Surgeons 10, no. 5 (September 2002): 299–302. http://dx.doi.org/10.5435/00124635-200209000-00001.

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22

&NA;. "Low-molecular-weight heparin." Reactions Weekly &NA;, no. 683 (January 1998): 10. http://dx.doi.org/10.2165/00128415-199806830-00027.

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23

&NA;. "Low molecular weight heparin." Reactions Weekly &NA;, no. 378 (November 1991): 6. http://dx.doi.org/10.2165/00128415-199103780-00028.

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24

&NA;. "Low molecular weight heparin." Reactions Weekly &NA;, no. 417 (September 1992): 10. http://dx.doi.org/10.2165/00128415-199204170-00038.

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25

&NA;. "Low molecular weight heparin." Reactions Weekly &NA;, no. 341 (March 1991): 7. http://dx.doi.org/10.2165/00128415-199103410-00040.

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26

&NA;. "Low molecular weight heparin." Reactions Weekly &NA;, no. 357 (June 1991): 8. http://dx.doi.org/10.2165/00128415-199103570-00035.

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27

Hirsh, J., and MN Levine. "Low molecular weight heparin." Blood 79, no. 1 (January 1, 1992): 1–17. http://dx.doi.org/10.1182/blood.v79.1.1.1.

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28

Hirsh, J., and MN Levine. "Low molecular weight heparin." Blood 79, no. 1 (January 1, 1992): 1–17. http://dx.doi.org/10.1182/blood.v79.1.1.bloodjournal7911.

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29

Hirsh, Jack. "Low Molecular Weight Heparin." Thrombosis and Haemostasis 70, no. 01 (1993): 204–7. http://dx.doi.org/10.1055/s-0038-1646191.

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30

Hirsh, Jack. "Low-Molecular-Weight Heparin." Circulation 98, no. 15 (October 13, 1998): 1575–82. http://dx.doi.org/10.1161/01.cir.98.15.1575.

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31

Heit, John A. "Low-Molecular-Weight Heparin." Regional Anesthesia and Pain Medicine 23, Sup 2 (November 1998): 135–39. http://dx.doi.org/10.1097/00115550-199823062-00002.

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32

Routledge, P. A., and R. R. West. "Low molecular weight heparin." BMJ 305, no. 6859 (October 17, 1992): 906. http://dx.doi.org/10.1136/bmj.305.6859.906.

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33

Horlocker, Terese T., and John A. Heit. "Low Molecular Weight Heparin." Anesthesia & Analgesia 85, no. 4 (October 1997): 874–85. http://dx.doi.org/10.1097/00000539-199710000-00031.

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34

Hunt, B. J. "Low Molecular Weight Heparin." Blood Coagulation & Fibrinolysis 3, no. 5 (October 1992): 683. http://dx.doi.org/10.1097/00001721-199210000-00030.

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35

Schmitt, Y., and H. Schneider. "Low molecular weight heparin." Blood Coagulation & Fibrinolysis 7, no. 3 (April 1996): 385. http://dx.doi.org/10.1097/00001721-199604000-00051.

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36

Horlocker, Terese T., and John A. Heit. "Low Molecular Weight Heparin." Anesthesia & Analgesia 85, no. 4 (October 1997): 874–85. http://dx.doi.org/10.1213/00000539-199710000-00031.

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37

Wolf, Helmut. "Low-molecular-weight heparin." Medical Clinics of North America 78, no. 3 (May 1994): 733–43. http://dx.doi.org/10.1016/s0025-7125(16)30155-9.

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38

Nunnelee, Janice D. "Low-molecular-weight heparin." Journal of Vascular Nursing 15, no. 3 (September 1997): 94–96. http://dx.doi.org/10.1016/s1062-0303(97)90057-1.

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39

Vanpee, Dominique, Jean-Bernard Gillet, and Christian Swine. "Low Molecular Weight Heparin." Annals of Emergency Medicine 36, no. 3 (September 2000): 277. http://dx.doi.org/10.1067/mem.2000.109264.

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40

Salzman, Edwin W. "Low-Molecular-Weight Heparin." New England Journal of Medicine 315, no. 15 (October 9, 1986): 957–59. http://dx.doi.org/10.1056/nejm198610093151509.

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41

Gough, S. "Low molecular weight heparin." BMJ 303, no. 6805 (September 28, 1991): 784. http://dx.doi.org/10.1136/bmj.303.6805.784-a.

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42

Brack, M. J. "Low molecular weight heparin." International Journal of Cardiology 38, no. 2 (February 1993): 207–8. http://dx.doi.org/10.1016/0167-5273(93)90193-k.

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43

Barrowcliffe, T. W., A. D. Curtis, E. A. Johnson, and D. P. Thomas. "An International Standard for Low Molecular Weight Heparin." Thrombosis and Haemostasis 60, no. 01 (1988): 001–7. http://dx.doi.org/10.1055/s-0038-1647623.

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SummaryAn international collaborative study has been carried out with the aim of establishing an international standard for low molecular weight (LMW) heparin. Three preparations of LMW heparin were assayed against the International Standard for unfractionated heparin (UFH) by 25 laboratories in 13 countries, using nine different assay methods. The results confirmed previous findings of non-parallel assays, wide interlaboratory variability and differences between methods when LMW heparins are assayed against a UFH standard. Use of one of the LMW heparins as a standard for the other two gave parallel assays and much closer agreement between laboratories. The preparation in ampoules coded 85/600 was selected as likely to give the best agreement with the largest number of LMW heparins; potencies were assigned by taking the mean of all the anti-Xa assays, and the mean of the thrombin and APTT assays, to represent the two major groups of activities. Preparation 85/600 has been established by WHO as the 1st International Standard for LMW heparin, with potencies of 1,680 iu/ampoule by anti-Xa assays and 665 iu/ampoule by thrombin inhibition and APTT assays.
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44

Chen, Jianle, Yanlei Yu, Jawed Fareed, Debra Hoppensteadt, Walter Jeske, Ahmed Kouta, Caijuan Jin, et al. "Comparison of Low-Molecular-Weight Heparins Prepared From Ovine Heparins With Enoxaparin." Clinical and Applied Thrombosis/Hemostasis 25 (January 1, 2019): 107602961984070. http://dx.doi.org/10.1177/1076029619840701.

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Heparin and its low-molecular-weight heparin derivatives are widely used clinical anticoagulants. These drugs are critical for the practice of medicine in applications, including kidney dialysis, cardiopulmonary bypass, and in the management of venous thromboembolism. Currently, these drugs are derived from livestock, primarily porcine intestine and less frequently bovine intestine and bovine lung. The worldwide dependence on the pig as a single dominant animal species has made the supply chain for this critical drug quite fragile, leading to the search for other sources of these drugs, including the expanded use of bovine tissues. A number of laboratories are now also examining the similarities between heparin and low-molecular-weight heparins prepared from porcine and ovine tissues. This study was designed to compare low-molecular-weight heparin prepared from ovine heparin through chemical β-elimination, a process currently used to prepare the low-molecular-weight heparin, enoxaparin. Using top-down, bottom-up, and compositional analyses as well as bioassays, low-molecular-weight heparin derived from ovine intestine was shown to closely resemble enoxaparin. Moreover, the compositions of daughter low-molecular-weight heparins prepared from three unfractionated ovine parent heparins were compared. Ovine enoxaparins had similar molecular weight and in vitro anticoagulant activities as Lovenox. Some disaccharide compositional, oligosaccharide composition at the reducing and nonreducing ends and intact chain compositional differences could be observed between porcine enoxaparin and ovine low-molecular-weight heparin. The similarity of these ovine and porcine heparin products suggests that their preclinical evaluation and ultimately clinical assessment is warranted.
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45

Fareed, Jawed, Walter Jeske, Daniel Fareed, Melaine Clark, Rakesh Wahi, Cafer Adiguzel, and Debra Hoppensteadt. "Are All Low Molecular Weight Heparins Equivalent in the Management of Venous Thromboembolism?" Clinical and Applied Thrombosis/Hemostasis 14, no. 4 (December 26, 2007): 385–92. http://dx.doi.org/10.1177/1076029608319881.

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Low molecular weight heparins are replacing unfractionated heparin in a number of clinical indications because of their improved subcutaneous bioavailability and more predictable antithrombotic response. Clinical trials have demonstrated that low molecular weight heparins are at least as safe and effective as unfractionated heparin for the initial treatment of venous thromboembolism, and unfractionated heparin and warfarin for primary and secondary thromboprophylaxis. The mechanism behind the antithrombotic action of low molecular weight heparins is not fully understood but is likely to involve inhibition of coagulation factors Xa and IIa (thrombin), release of tissue-factor-pathway inhibitor, and inhibition of thrombin activatable fibrinolytic inhibitor. Different low molecular weight heparins have been shown to have various effects on coagulation parameters. Seven low molecular weight heparins are currently marketed worldwide, each demonstrated distinct chemical entities with unique pharmacokinetic and pharmacodynamic profiles. Each low molecular weight heparin is approved for specific indications based on the available efficacy and safety data for that product. The relative efficacy and safety of the low molecular weight heparins are unclear because there have been very few direct comparisons in randomized clinical trials. While recommending low molecular weight heparins for the prevention and treatment of venous thromboembolism, clinical guidelines have not specified individual agents. National and international organizations recognize that low molecular weight heparins are distinct entities and that they should not be used interchangeably in clinical practice. Each low molecular weight heparin should be used at the recommended dose when efficacy and safety data exist for the condition being treated. When these data are not available, the dosing and administration of low molecular weight heparins must be adapted from existing data and recommendations.
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46

Barrowcliffe, T. W., A. D. Curtis, T. P. Tomlinson, A. R. Hubbard, E. A. Johnson, and D. P. Thomas. "Standardization of Low Molecular Weight Heparins : A Collaborative Study." Thrombosis and Haemostasis 54, no. 03 (1985): 675–79. http://dx.doi.org/10.1055/s-0038-1660095.

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SummaryA collaborative study was carried out, in which eight laboratories each assayed eight low molecular weight (LMW) heparins against the International Standard (IS) for heparin. APTT assays and three types of anti-Xa method were used. The results of this study showed that:1. LMW heparins cannot be validly assayed against the IS by APTT or anti-Xa methods.2. Potencies of LMW heparins vs. the IS differed considerably between the four types of assay method used and also between different laboratories using the same type of method.3. Adoption of a single LMW heparin standard would improve validity, improve inter-laboratory variation, and largely abolish the differences between the three types of anti-Xa method. However, since calibration of a LMW heparin standard against the IS would give potencies that differ widely by the different assay methods, a single assay method such as the anti-Xa amidolytic, plasma, would need to be chosen for this calibration.
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47

Mammen, Eberhard F. "Low Molecular Weight Heparins and Heparin-Induced Thrombocytopenia." Clinical and Applied Thrombosis/Hemostasis 5, no. 1_suppl (October 1999): S72—S75. http://dx.doi.org/10.1177/10760296990050s113.

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48

Ambrosioni, E., and E. Strocchi. "Pharmacokinetics of Heparin and Low Molecular Weight Heparins." Pathophysiology of Haemostasis and Thrombosis 20, no. 1 (1990): 94–97. http://dx.doi.org/10.1159/000216165.

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49

Stefoni, Sergio, Giuseppe Cianciolo, Gabriele Donati, Luigi Colì, Gaetano La Manna, Concettina Raimondi, Vittorio Dalmastri, Valentina Orlandi, and Francesca D’Addio. "Standard Heparin versus Low-Molecular-Weight Heparin." Nephron 92, no. 3 (2002): 589–600. http://dx.doi.org/10.1159/000064086.

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50

Raskob, Gary E. "Low molecular weight heparin, heparin, and warfarin." Current Opinion in Hematology 2, no. 5 (1995): 372–79. http://dx.doi.org/10.1097/00062752-199502050-00008.

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