Identification

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Name
Lonoctocog alfa
Accession Number
DB13998  (DBSALT002411)
Type
Biotech
Groups
Approved, Investigational
Description
Not Available
Synonyms
Not Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AfstylaKit; Powder, for solution3000 unitIntravenousCsl BehringNot applicableNot applicableCanada
AfstylaKit; Powder, for solution500 unitIntravenousCsl BehringNot applicableNot applicableCanada
AfstylaKit; Powder, for solution2500 unitIntravenousCsl BehringNot applicableNot applicableCanada
AfstylaKit; Powder, for solution250 unitIntravenousCsl BehringNot applicableNot applicableCanada
AfstylaKit; Powder, for solution2000 unitIntravenousCsl BehringNot applicableNot applicableCanada
AfstylaKit; Powder, for solution1500 unitIntravenousCsl BehringNot applicableNot applicableCanada
AfstylaKit; Powder, for solution1000 unitIntravenousCsl BehringNot applicableNot applicableCanada
AFSTYLA Antihemophilic Factor (Recombinant), Single ChainKit3000 [iU]/5mLCsl Behring Recombinant Facility Ag2016-05-25Not applicableUs
AFSTYLA Antihemophilic Factor (Recombinant), Single ChainKit2000 [iU]/5mLCsl Behring Recombinant Facility Ag2016-05-25Not applicableUs
AFSTYLA Antihemophilic Factor (Recombinant), Single ChainKit1000 [iU]/2.5mLCsl Behring Recombinant Facility Ag2016-05-25Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories
UNII
VQ723R7O8R
CAS number
1388129-63-2

Pharmacology

Indication

For the treatment of hemophilia A, von Willebrand disease and Factor XIII deficiency.

Associated Conditions
Pharmacodynamics

Antihemophilic Factor binds factor IXa along with calcium and phospholipid, This complex converts factor X to factor Xa to facilitate clotting cascade.

Mechanism of action

Antihemophilic factor (AHF) is a protein found in normal plasma which is necessary for clot formation. The administration of AHF provides an increase in plasma levels of AHF and can temporarily correct the coagulation defect of patients with hemophilia A (classical hemophilia).

TargetActionsOrganism
ACoagulation factor X
activator
Humans
UPhytanoyl-CoA dioxygenase, peroxisomal
antagonist
Humans
ACoagulation factor IX
cofactor
Humans
UAsialoglycoprotein receptor 2
binder
Humans
U78 kDa glucose-regulated protein
chaperone
Humans
UCalreticulin
chaperone
Humans
UCalnexin
chaperone
Humans
UProtein ERGIC-53
chaperone
Humans
UProlow-density lipoprotein receptor-related protein 1
modulator
Humans
UMultiple coagulation factor deficiency protein 2
modulator
Humans
Avon Willebrand factor
binder
Humans
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life

8.4-19.3 hrs

Clearance
  • 4.1 mL/h•kg [Previously treated pediatric patients]
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Titheradge MA, Coore HG: Initial rates of pyruvate transport in mitochondria determined by an "inhibitor-stop" technique. Biochem J. 1975 Sep;150(3):553-6. [PubMed:2157]
External Links
Not Available
AHFS Codes
  • 20:28.16 — Hemostatics

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Kit; powder, for solutionIntravenous1000 unit
Kit; powder, for solutionIntravenous1500 unit
Kit; powder, for solutionIntravenous2000 unit
Kit; powder, for solutionIntravenous250 unit
Kit; powder, for solutionIntravenous2500 unit
Kit; powder, for solutionIntravenous3000 unit
Kit; powder, for solutionIntravenous500 unit
Kit1000 [iU]/2.5mL
Kit1500 [iU]/5mL
Kit2000 [iU]/5mL
Kit250 [iU]/2.5mL
Kit2500 [iU]/5mL
Kit3000 [iU]/5mL
Kit500 [iU]/2.5mL
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available

Taxonomy

Classification
Not classified

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Activator
General Function
Serine-type endopeptidase activity
Specific Function
Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting.
Gene Name
F10
Uniprot ID
P00742
Uniprot Name
Coagulation factor X
Molecular Weight
54731.255 Da
References
  1. BLATRIX C, SOULIER JP: [Preparation of a fraction rich in prothrombin, proconvertin, Stuart factor and antihemophilic factor B (P.P.B. fraction)]. Pathol Biol (Paris). 1959 Dec;7:2477-86. [PubMed:13801371]
  2. LUNDBLAD RL, DAVIE EW: THE ACTIVATION OF STUART FACTOR (FACTOR X) BY ACTIVATED ANTIHEMOPHILIC FACTOR (ACTIVATED FACTOR 8). Biochemistry. 1965 Jan;4:113-20. [PubMed:14285227]
  3. Radnoff OD, Saito H: Inhibition of Hageman factor, plasma thromboplastin antecedent, thrombin and other clotting factors by phenylglyoxal hydrate (38500). Proc Soc Exp Biol Med. 1975 Jan;148(1):177-82. [PubMed:236567]
  4. Orthner CL: Characterization of proteases in AHF concentrates: effect on factor VIII:von Willebrand protein as assessed by high-pressure gel permeation chromatography. J Lab Clin Med. 1984 Nov;104(5):816-28. [PubMed:6436416]
  5. Freedman J, Mody M, Lazarus AH, Dewar L, Song S, Blanchette VS, Garvey MB, Ofosu FA: Platelet activation and hypercoagulability following treatment with porcine factor VIII (HYATE:C). Am J Hematol. 2002 Mar;69(3):192-9. [PubMed:11891806]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
Phytanoyl-coa dioxygenase activity
Specific Function
Converts phytanoyl-CoA to 2-hydroxyphytanoyl-CoA.
Gene Name
PHYH
Uniprot ID
O14832
Uniprot Name
Phytanoyl-CoA dioxygenase, peroxisomal
Molecular Weight
38538.065 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Chen C, Wang Q, Fang X, Xu Q, Chi C, Gu J: Roles of phytanoyl-CoA alpha-hydroxylase in mediating the expression of human coagulation factor VIII. J Biol Chem. 2001 Dec 7;276(49):46340-6. [PubMed:11574539]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Cofactor
General Function
Serine-type endopeptidase activity
Specific Function
Factor IX is a vitamin K-dependent plasma protein that participates in the intrinsic pathway of blood coagulation by converting factor X to its active form in the presence of Ca(2+) ions, phospholi...
Gene Name
F9
Uniprot ID
P00740
Uniprot Name
Coagulation factor IX
Molecular Weight
51778.11 Da
References
  1. Hule V: [Factor IX inhibitor (antihemophilic factor B, PTC) in a woman]. Vnitr Lek. 1975 Mar;21(3):274-7. [PubMed:1119107]
  2. Yoshitake S, Schach BG, Foster DC, Davie EW, Kurachi K: Nucleotide sequence of the gene for human factor IX (antihemophilic factor B). Biochemistry. 1985 Jul 2;24(14):3736-50. [PubMed:2994716]
  3. LUNDBLAD RL, DAVIE EW: THE ACTIVATION OF ANTIHEMOPHILIC FACTOR (FACTOR 8) BY ACTIVATED CHRISTMAS FACTOR (ACTIVATED FACTOR9 9). Biochemistry. 1964 Nov;3:1720-5. [PubMed:14240634]
  4. Hoofnagle JH, Gerety RJ, Thiel J, Barker LF: The prevalence of hepatitis B surface antigen in commercially prepared plasma products. J Lab Clin Med. 1976 Jul;88(1):102-13. [PubMed:932529]
  5. Prince AM, Horowitz B, Brotman B, Huima T, Richardson L, van den Ende MC: Inactivation of hepatitis B and Hutchinson strain non-A, non-B hepatitis viruses by exposure to Tween 80 and ether. Vox Sang. 1984;46(1):36-43. [PubMed:6422634]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Carbohydrate binding
Specific Function
Mediates the endocytosis of plasma glycoproteins to which the terminal sialic acid residue on their complex carbohydrate moieties has been removed. The receptor recognizes terminal galactose and N-...
Gene Name
ASGR2
Uniprot ID
P07307
Uniprot Name
Asialoglycoprotein receptor 2
Molecular Weight
35092.04 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Bovenschen N, Rijken DC, Havekes LM, van Vlijmen BJ, Mertens K: The B domain of coagulation factor VIII interacts with the asialoglycoprotein receptor. J Thromb Haemost. 2005 Jun;3(6):1257-65. [PubMed:15946216]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Chaperone
General Function
Unfolded protein binding
Specific Function
Probably plays a role in facilitating the assembly of multimeric protein complexes inside the endoplasmic reticulum. Involved in the correct folding of proteins and degradation of misfolded protein...
Gene Name
HSPA5
Uniprot ID
P11021
Uniprot Name
78 kDa glucose-regulated protein
Molecular Weight
72332.425 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Kaufman RJ, Pipe SW, Tagliavacca L, Swaroop M, Moussalli M: Biosynthesis, assembly and secretion of coagulation factor VIII. Blood Coagul Fibrinolysis. 1997 Dec;8 Suppl 2:S3-14. [PubMed:9607108]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Chaperone
General Function
Zinc ion binding
Specific Function
Calcium-binding chaperone that promotes folding, oligomeric assembly and quality control in the endoplasmic reticulum (ER) via the calreticulin/calnexin cycle. This lectin interacts transiently wit...
Gene Name
CALR
Uniprot ID
P27797
Uniprot Name
Calreticulin
Molecular Weight
48141.2 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Pipe SW, Morris JA, Shah J, Kaufman RJ: Differential interaction of coagulation factor VIII and factor V with protein chaperones calnexin and calreticulin. J Biol Chem. 1998 Apr 3;273(14):8537-44. [PubMed:9525969]
  4. Srour MA, Grupp J, Aburubaiha Z, Albert T, Brondke H, Oldenburg J, Schwaab R: Modified expression of coagulation factor VIII by addition of a glycosylation site at the N terminus of the protein. Ann Hematol. 2008 Feb;87(2):107-12. Epub 2007 Sep 26. [PubMed:17899080]
  5. Kaufman RJ, Pipe SW, Tagliavacca L, Swaroop M, Moussalli M: Biosynthesis, assembly and secretion of coagulation factor VIII. Blood Coagul Fibrinolysis. 1997 Dec;8 Suppl 2:S3-14. [PubMed:9607108]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Chaperone
General Function
Poly(a) rna binding
Specific Function
Calcium-binding protein that interacts with newly synthesized glycoproteins in the endoplasmic reticulum. It may act in assisting protein assembly and/or in the retention within the ER of unassembl...
Gene Name
CANX
Uniprot ID
P27824
Uniprot Name
Calnexin
Molecular Weight
67567.695 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Pipe SW, Morris JA, Shah J, Kaufman RJ: Differential interaction of coagulation factor VIII and factor V with protein chaperones calnexin and calreticulin. J Biol Chem. 1998 Apr 3;273(14):8537-44. [PubMed:9525969]
  4. Becker S, Simpson JC, Pepperkok R, Heinz S, Herder C, Grez M, Seifried E, Tonn T: Confocal microscopy analysis of native, full length and B-domain deleted coagulation factor VIII trafficking in mammalian cells. Thromb Haemost. 2004 Jul;92(1):23-35. [PubMed:15213841]
  5. Srour MA, Grupp J, Aburubaiha Z, Albert T, Brondke H, Oldenburg J, Schwaab R: Modified expression of coagulation factor VIII by addition of a glycosylation site at the N terminus of the protein. Ann Hematol. 2008 Feb;87(2):107-12. Epub 2007 Sep 26. [PubMed:17899080]
  6. Kaufman RJ, Pipe SW, Tagliavacca L, Swaroop M, Moussalli M: Biosynthesis, assembly and secretion of coagulation factor VIII. Blood Coagul Fibrinolysis. 1997 Dec;8 Suppl 2:S3-14. [PubMed:9607108]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Chaperone
General Function
Unfolded protein binding
Specific Function
Mannose-specific lectin. May recognize sugar residues of glycoproteins, glycolipids, or glycosylphosphatidyl inositol anchors and may be involved in the sorting or recycling of proteins, lipids, or...
Gene Name
LMAN1
Uniprot ID
P49257
Uniprot Name
Protein ERGIC-53
Molecular Weight
57548.665 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Cunningham MA, Pipe SW, Zhang B, Hauri HP, Ginsburg D, Kaufman RJ: LMAN1 is a molecular chaperone for the secretion of coagulation factor VIII. J Thromb Haemost. 2003 Nov;1(11):2360-7. [PubMed:14629470]
  4. Miao HZ, Sirachainan N, Palmer L, Kucab P, Cunningham MA, Kaufman RJ, Pipe SW: Bioengineering of coagulation factor VIII for improved secretion. Blood. 2004 May 1;103(9):3412-9. Epub 2004 Jan 15. [PubMed:14726380]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Modulator
General Function
Receptor activity
Specific Function
Endocytic receptor involved in endocytosis and in phagocytosis of apoptotic cells. Required for early embryonic development. Involved in cellular lipid homeostasis. Involved in the plasma clearance...
Gene Name
LRP1
Uniprot ID
Q07954
Uniprot Name
Prolow-density lipoprotein receptor-related protein 1
Molecular Weight
504601.695 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Franchini M, Montagnana M: Low-density lipoprotein receptor-related protein 1: new functions for an old molecule. Clin Chem Lab Med. 2011 Jun;49(6):967-70. doi: 10.1515/CCLM.2011.154. Epub 2011 Mar 11. [PubMed:21391865]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Modulator
General Function
Calcium ion binding
Specific Function
The MCFD2-LMAN1 complex forms a specific cargo receptor for the ER-to-Golgi transport of selected proteins. Plays a role in the secretion of coagulation factors.
Gene Name
MCFD2
Uniprot ID
Q8NI22
Uniprot Name
Multiple coagulation factor deficiency protein 2
Molecular Weight
16390.175 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Zhang B, Kaufman RJ, Ginsburg D: LMAN1 and MCFD2 form a cargo receptor complex and interact with coagulation factor VIII in the early secretory pathway. J Biol Chem. 2005 Jul 8;280(27):25881-6. Epub 2005 May 10. [PubMed:15886209]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Binder
General Function
Protein n-terminus binding
Specific Function
Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surf...
Gene Name
VWF
Uniprot ID
P04275
Uniprot Name
von Willebrand factor
Molecular Weight
309261.83 Da
References
  1. Shord SS, Lindley CM: Coagulation products and their uses. Am J Health Syst Pharm. 2000 Aug 1;57(15):1403-17; quiz 1418-20. [PubMed:10938981]
  2. Lillicrap D, Poon MC, Walker I, Xie F, Schwartz BA: Efficacy and safety of the factor VIII/von Willebrand factor concentrate, haemate-P/humate-P: ristocetin cofactor unit dosing in patients with von Willebrand disease. Thromb Haemost. 2002 Feb;87(2):224-30. [PubMed:11858481]
  3. Gill JC, Ewenstein BM, Thompson AR, Mueller-Velten G, Schwartz BA: Successful treatment of urgent bleeding in von Willebrand disease with factor VIII/VWF concentrate (Humate-P): use of the ristocetin cofactor assay (VWF:RCo) to measure potency and to guide therapy. Haemophilia. 2003 Nov;9(6):688-95. [PubMed:14750934]
  4. Smith KJ, Lusher JM, Cohen AR, Salzman P: Initial clinical experience with a new pasteurized monoclonal antibody purified factor VIIIC. Semin Hematol. 1990 Apr;27(2 Suppl 2):25-9. [PubMed:2128855]
  5. Altieri DC, Capitanio AM, Mannucci PM: von Willebrand factor contaminating porcine factor VIII concentrate (Hyate:C) causes platelet aggregation. Br J Haematol. 1986 Aug;63(4):703-11. [PubMed:2942172]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Activator
General Function
Thrombospondin receptor activity
Specific Function
Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostas...
Gene Name
F2
Uniprot ID
P00734
Uniprot Name
Prothrombin
Molecular Weight
70036.295 Da
References
  1. Alberio L, Safa O, Clemetson KJ, Esmon CT, Dale GL: Surface expression and functional characterization of alpha-granule factor V in human platelets: effects of ionophore A23187, thrombin, collagen, and convulxin. Blood. 2000 Mar 1;95(5):1694-702. [PubMed:10688826]
  2. Ratnoff OD, Lewis JH: Heckathorn's disease: variable functional dificiency of antihemophilic factor (factor VIII). Blood. 1975 Aug;46(2):161-73. [PubMed:1139038]
  3. Anderson DM, Shelley S, Crick N, Buraglio M: No effect of the novel antidiabetic agent nateglinide on the pharmacokinetics and anticoagulant properties of warfarin in healthy volunteers. J Clin Pharmacol. 2002 Dec;42(12):1358-65. [PubMed:12463731]
  4. Piet MP, Chin S, Prince AM, Brotman B, Cundell AM, Horowitz B: The use of tri(n-butyl)phosphate detergent mixtures to inactivate hepatitis viruses and human immunodeficiency virus in plasma and plasma's subsequent fractionation. Transfusion. 1990 Sep;30(7):591-8. [PubMed:2402772]
  5. Lazarchick J, Ashby MA, Lazarchick JJ, Sens DA: Mechanism of factor VIII inactivation by human antibodies. IV. Antibody binding prevents factor VIII proteolysis by thrombin. Ann Clin Lab Sci. 1986 Nov-Dec;16(6):497-501. [PubMed:3099625]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inactivator
General Function
Serine-type endopeptidase activity
Specific Function
Protein C is a vitamin K-dependent serine protease that regulates blood coagulation by inactivating factors Va and VIIIa in the presence of calcium ions and phospholipids (PubMed:25618265). Exerts ...
Gene Name
PROC
Uniprot ID
P04070
Uniprot Name
Vitamin K-dependent protein C
Molecular Weight
52070.82 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Bereczky Z, Kovacs KB, Muszbek L: Protein C and protein S deficiencies: similarities and differences between two brothers playing in the same game. Clin Chem Lab Med. 2010 Dec;48 Suppl 1:S53-66. doi: 10.1515/CCLM.2010.369. Epub 2010 Nov 5. [PubMed:21054189]

Drug created on March 20, 2018 11:52 / Updated on July 20, 2019 12:16