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Semin Thromb Hemost 2014; 40(05): 592-599
DOI: 10.1055/s-0034-1384767
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The Old and the New in Prekallikrein Deficiency: Historical Context and a Family from Argentina with PK Deficiency due to a New Mutation (Arg541Gln) in Exon 14 Associated with a Common Polymorphysm (Asn124Ser) in Exon 5[*]

Antonio Girolami
1   Department of Medicine, University of Padua Medical School, Padua, Italy
,
Josè Vidal
2   Department of Clinical Biochemistry and San Roque Hospital, Faculty of Chemical Sciences, National University of Cordoba, Cordoba, Argentina
,
Marcela Salagh
2   Department of Clinical Biochemistry and San Roque Hospital, Faculty of Chemical Sciences, National University of Cordoba, Cordoba, Argentina
,
Nora Gervan
2   Department of Clinical Biochemistry and San Roque Hospital, Faculty of Chemical Sciences, National University of Cordoba, Cordoba, Argentina
,
Maria Parody
2   Department of Clinical Biochemistry and San Roque Hospital, Faculty of Chemical Sciences, National University of Cordoba, Cordoba, Argentina
,
Edoardo Peroni
1   Department of Medicine, University of Padua Medical School, Padua, Italy
,
Luisa Sambado
1   Department of Medicine, University of Padua Medical School, Padua, Italy
,
Hugo Guglielmone
2   Department of Clinical Biochemistry and San Roque Hospital, Faculty of Chemical Sciences, National University of Cordoba, Cordoba, Argentina
› Author Affiliations
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Publication Date:
30 July 2014 (online)

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The Old and the New in Prekallikrein Deficiency: Historical Context and a Family from Argentina with PK Deficiency due to a New Mutation (Arg541Gln) in Exon 14 Associated with a Common Polymorphysm (Asn124Ser) in Exon 5Semin Thromb Hemost 2014; 40(06): 712-712
DOI: 10.1055/s-0034-1389566

Abstract

Prekallikrein (PK) is one of the clotting factors involved in the contact phase of blood. PK has an important historical role as its deficiency state represents the second instance of a clotting defect without bleeding manifestations, the first one being factor XII deficiency. PK deficiency is a rare clotting disorder. Moreover, only 11 patients have been investigated so far by molecular biology techniques. In this article, we briefly review some of the history around PK and also present some recent data on a newly identified family from Argentina suffering from PK deficiency. Two patients are homozygous whereas other family members are heterozygous. PK activity and antigen are 1% of normal in the homozygotes and around 60 to 70% of normal in the heterozygotes. As expected, all patients are asymptomatic of bleeding or thrombosis presentations. However, the two homozygotes showed essential hypertension. The PK deficiency in this family is due to a new mutation (Arg541Gln) in exon 14. The defect segregates together with a known polymorphism, Asn124Ser, in exon 5. The significance of the presence of hypertension in the two homozygotes is discussed in view of the extra coagulation effects of PK on vasodilation, vessel permeability, and the control of blood pressure. Structure function analysis indicates that the substitution of Arg with Gln probably impedes the transmembrane diffusion of the molecule, which therefore cannot be secreted in the homozygotes. The presence of hypertension in patients with PK deficiency has been previously reported in some but not all patients. Future research activities will probably concentrate on the effect of PK and other contact phase factors on the vascular system.

Keywords

prekallikrein deficiency - contact phase - hypertension - blood coagulation

* Dedicated to the memory of Alfredo Pavlovsky and Pietro De Nicola, who, during the years 1945–1965, pioneered research on blood coagulation disorders in Argentina and Italy.


 

  • References

  • 1 Hathaway WE, Belhasen LP, Hathaway HS. Evidence for a new plasma thromboplastin factor. I. Case report, coagulation studies and physicochemical properties. Blood 1965; 26 (5) 521-532
    PubMedSearch in Google Scholar
  • 2 Girolami A, Scarparo P, Candeo N, Lombardi AM. Congenital prekallikrein deficiency. Expert Rev Hematol 2010; 3 (6) 685-695
    CrossrefPubMedSearch in Google Scholar
  • 3 Ratnoff OD, Colopy JE. A familial hemorrhagic trait associated with a deficiency of a clot-promoting fraction of plasma. J Clin Invest 1955; 34 (4) 602-613
    CrossrefPubMedSearch in Google Scholar
  • 4 Colman RW. Contact Activation (Kallikrein-Kinin) pathway: Involving inflammatory, fibrinolytic, anticoagulant physiologic and pathophisiologic activities. In: Colman RW, Marder VJ, Clowes AW, George JN, Goldhaber SZ, , eds. Hemostasis and Thrombosis, 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2006: 107-130
    Search in Google Scholar
  • 5 Hattersley PG, Hayse D. Fletcher factor deficiency: a report of three unrelated cases. Br J Haematol 1970; 18 (4) 411-416
    CrossrefPubMedSearch in Google Scholar
  • 6 Goodnough LT, Saito H, Ratnoff OD. Thrombosis or myocardial infarction in congenital clotting factor abnormalities and chronic thrombocytopenias: a report of 21 patients and a review of 50 previously reported cases. Medicine (Baltimore) 1983; 62 (4) 248-255
    PubMedSearch in Google Scholar
  • 7 Wuillemin WA, Furlan M, von Felten A, Lämmle B. Functional characterization of a variant prekallikrein (PK Zürich). Thromb Haemost 1993; 70 (3) 427-432
    PubMedSearch in Google Scholar
  • 8 Bouma BN, Kerbiriou DM, Baker J, Griffin JH. Characterization of a variant prekallikrein, prekallikrein Long Beach, from a family with mixed cross-reacting material-positive and cross-reacting material-negative prekallikrein deficiency. J Clin Invest 1986; 78 (1) 170-176
    CrossrefPubMedSearch in Google Scholar
  • 9 Lombardi AM, Sartori MT, Cabrio L, Fadin M, Zanon E, Girolami A. Severe prekallikrein (Fletcher factor) deficiency due to a compound heterozygosis (383Trp stop codon and Cys529Tyr). Thromb Haemost 2003; 90 (6) 1040-1045
    PubMedSearch in Google Scholar
  • 10 Shigekiyo T, Fujino O, Kanagawa Y, Matsumoto T. Prekallikrein (PK) Tokushima: PK deficiency caused by a Gly401—>Glu mutation. J Thromb Haemost 2003; 1 (6) 1314-1316
    CrossrefPubMedSearch in Google Scholar
  • 11 François D, Trigui N, Leterreux G , et al. Severe prekallikrein deficiencies due to homozygous C529Y mutations. Blood Coagul Fibrinolysis 2007; 18 (3) 283-286
    CrossrefPubMedSearch in Google Scholar
  • 12 Wynne Jones D, Russell G, Allford SL , et al. Severe prekallikrein deficiency associated with homozygosity for an Arg94Stop nonsense mutation. Br J Haematol 2004; 127 (2) 220-223
    CrossrefPubMedSearch in Google Scholar
  • 13 Katsuda I, Maruyama F, Ezaki K, Sawamura T, Ichihara Y. A new type of plasma prekallikrein deficiency associated with homozygosity for Gly104Arg and Asn124Ser in apple domain 2 of the heavy-chain region. Eur J Haematol 2007; 79 (1) 59-68
    CrossrefPubMedSearch in Google Scholar
  • 14 Maak B, Kochhan L, Heuchel P, Jenderny J. Severe prekallikrein deficiency due to a compound heterozygosis in the KLKB1-gene [in German]. Hamostaseologie 2009; 29 (2) 187-189
    PubMedSearch in Google Scholar
  • 15 Nakao T, Yamane T, Katagami T , et al. Severe prekallikrein deficiency due to a homozygous Trp499Stop nonsense mutation. Blood Coagul Fibrinolysis 2011; 22 (4) 337-339
    CrossrefPubMedSearch in Google Scholar
  • 16 Girolami A, Marun S, Vettore S , et al. A large family from Argentina with prekallikrein deficiency due to a compound heterozygosis (T insertion in intron 7 and Asp558Glu in exon 15): prekallikrein Cordoba. Am J Hematol 2010; 85 (5) 363-366
    PubMedSearch in Google Scholar
  • 17 Dasanu CA, Alexandrescu DT. A case of prekallikrein deficiency resulting in severe recurrent mucosal hemorrhage. Am J Med Sci 2009; 338 (5) 429-430
    CrossrefPubMedSearch in Google Scholar
  • 18 Nagaya S, Morishita E, Takami A , et al. An elderly case of congenital prekallikrein deficiency [in Japanease]. Nippon Ronen Igakkai Zasshi 2009; 46 (4) 348-351
    CrossrefPubMedSearch in Google Scholar
  • 19 Girolami A, Molaro G, Lazzarin M, Scarpa R, Brunetti A. A “new” congenital haemorrhagic condition due to the presence of an abnormal factor X (factor X Friuli): study of a large kindred. Br J Haematol 1970; 19 (2) 179-192
    CrossrefPubMedSearch in Google Scholar
  • 20 Chung DW, Fujikawa K, McMullen BA, Davie EW. Human plasma prekallikrein, a zymogen to a serine protease that contains four tandem repeats. Biochemistry 1986; 25 (9) 2410-2417
    CrossrefPubMedSearch in Google Scholar
  • 21 McMullen BA, Fujikawa K, Davie EW. Location of the disulfide bonds in human plasma prekallikrein: the presence of four novel apple domains in the amino-terminal portion of the molecule. Biochemistry 1991; 30 (8) 2050-2056
    CrossrefPubMedSearch in Google Scholar
  • 22 Yu H, Anderson PJ, Freedman BI, Rich SS, Bowden DW. Genomic structure of the human plasma prekallikrein gene, identification of allelic variants, and analysis in end-stage renal disease. Genomics 2000; 69 (2) 225-234
    CrossrefPubMedSearch in Google Scholar
  • 23 Govers-Riemslag JW, Smid M, Cooper JA , et al. The plasma kallikrein-kinin system and risk of cardiovascular disease in men. J Thromb Haemost 2007; 5 (9) 1896-1903
    CrossrefPubMedSearch in Google Scholar
  • 24 Pantos A, Tsogas I, Paleos CM. Guanidinium group. Guanidinium group: a versatile moiety inducing transport and multicompartmentalization in complementary membranes. Biochim Biophys Acta 2008; 1778 (4) 811-823
    CrossrefPubMedSearch in Google Scholar
  • 25 Saito H, Goodnough LT, Soria J, Soria C, Aznar J, España F. Heterogeneity of human prekallikrein deficiency (Fletcher trait): evidence that five of 18 cases are positive for cross-reacting material. N Engl J Med 1981; 305 (16) 910-914
    CrossrefPubMedSearch in Google Scholar
  • 26 Currimbhoy Z, Vinciguerra V, Palakavongs P, Kuslansky P, Degnan TJ. Fletcher factor deficiency and myocardial infarction. Am J Clin Pathol 1976; 65 (6) 970-974
    PubMedSearch in Google Scholar
  • 27 De Stefano V, Leone G, Teofili L , et al. Association of Graves' disease and prekallikrein congenital deficiency in a patient belonging to the first CRM+ prekallikrein-deficient Italian family. Thromb Res 1990; 60 (5) 397-404
    CrossrefPubMedSearch in Google Scholar
  • 28 Girolami A, Allemand E, Bertozzi I, Candeo N, Marun S, Girolami B. Thrombotic events in patients with congenital prekallikrein deficiency: a critical evaluation of all reported cases. Acta Haematol 2010; 123 (4) 210-214
    CrossrefPubMedSearch in Google Scholar
  • 29 Harris MG, Exner T, Rickard KA, Kronenberg H. Multiple cerebral thrombosis in Fletcher factor (prekallikrein) deficiency: a case report. Am J Hematol 1985; 19 (4) 387-393
    CrossrefPubMedSearch in Google Scholar
  • 30 Kyrle PA, Niessner H, Deutsch E, Lechner K, Korninger C, Mannhalter C. CRM+ severe Fletcher factor deficiency associated with Graves' disease. Haemostasis 1984; 14 (4) 302-306
    PubMedSearch in Google Scholar
  • 31 Cichon S, Martin L, Hennies HC , et al. Increased activity of coagulation factor XII (Hageman factor) causes hereditary angioedema type III. Am J Hum Genet 2006; 79 (6) 1098-1104
    CrossrefPubMedSearch in Google Scholar
  • 32 Zuraw BL, Christiansen SC. Pathogenesis and laboratory diagnosis of hereditary angioedema. Allergy Asthma Proc 2009; 30 (5) 487-492
    CrossrefPubMedSearch in Google Scholar
  • 33 Bork K, Wulff K, Meinke P, Wagner N, Hardt J, Witzke G. A novel mutation in the coagulation factor 12 gene in subjects with hereditary angioedema and normal C1-inhibitor. Clin Immunol 2011; 141 (1) 31-35
    CrossrefPubMedSearch in Google Scholar
  • 34 Gómez-Traseira C, López-Lera A, Drouet C , et al. Hereditary angioedema caused by the p.Thr309Lys mutation in the F12 gene: a multifactorial disease. J Allergy Clin Immunol 2013; 132 (4) 986-989 , e1–e5
    CrossrefPubMedSearch in Google Scholar
  • 35 Girolami A, Agostino D, Cliffton EE. The effect of ellagic acid on coagulation in vivo. Blood 1966; 27 (1) 93-102
    PubMedSearch in Google Scholar
  • 36 Girolami A, Cliffton EE. Hypercoagulable state induced in humans by the intravenous administration of purified ellagic acid. Thromb Diath Haemorrh 1967; 17 (1-2) 165-175
    PubMedSearch in Google Scholar
  • 37 Lu X, Zhao W, Huang J , et al. Common variation in KLKB1 and essential hypertension risk: tagging-SNP haplotype analysis in a case-control study. Hum Genet 2007; 121 (3-4) 327-335
    CrossrefPubMedSearch in Google Scholar