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Thromb Haemost 1995; 73(02): 194-202
DOI: 10.1055/s-0038-1653750
Original Article
Clinical Studies
Schattauer GmbH Stuttgart

Definition of the Bleeding Tendency in Factor XI-Deficient Kindreds–A Clinical and Laboratory Study

P H B Bolton-Maggs
1   The Department of Haematology, Royal Liverpool University Hospital, Liverpool, UK
,
D A Patterson
1   The Department of Haematology, Royal Liverpool University Hospital, Liverpool, UK
,
R T Wensley
2   The Department of Clinical Haematology, Manchester Royal Infirmary, Manchester, UK
,
E G D Tuddenham
3   The Haemostasis Research Group, MRC Clinical Sciences Centre, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK
› Author Affiliations
Further Information

Publication History

Received 26 April 1994

Accepted after resubmission 28 October 1994

Publication Date:
09 July 2018 (online)

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Summary

Individuals with severe factor XI deficiency are prone to excessive bleeding after injury or surgery, but the existence of a haemorrhagic tendency in partial factor XI deficiency is controversial. In this study, 172 members of 30 kindreds (20 non-Jewish) transmitting factor XI deficiency in North West England were interviewed and a bleeding history questionnaire completed. Blood was taken for coagulation assays. The questionnaires were categorised independently by two assessors to determine presence or absence of a bleeding tendency, in the absence of information about the factor XI level or family history. Analysis shows that 48% of heterozygotes have a bleeding tendency. Eighteen (60%) families came to attention because of bleeding problems in heterozygotes. Comparison of histories between partially deficient and non-deficient individuals demonstrated a higher incidence of menstrual problems, an increase in significant bruising, and an increased likelihood of excessive bleeding after tonsillectomy and dental extractions.

The incidence of von Willebrand’s disease was not increased, but individuals with heterozygous factor XI deficiency who were bleeders tended to have lower levels of factor VIIIc and von Willebrand factor, and were more commonly of blood group 0. These features may contribute to the bleeding tendency. There was no evidence of alteration in factor VII activity (as defined by the ratio of activity to antigen) between the bleeders and non-bleeders.

This is convincing evidence for abnormal bleeding in factor XI deficiency which is not confined to severely deficient patients.

 

  • References

  • 1 Rosenthal RL, Dreskin OH, Rosenthal N. New Hemophilia-like disease caused by deficiency of a third plasma thromboplastin factor. Proc Soc Exp Biol Med 1953; 82: 171-174
    CrossrefPubMedSearch in Google Scholar
  • 2 Seligsohn U. High gene frequency of factor XI (PTA) deficiency in Ashkenazi jews. Blood 1978; 51: 1223-1228
    CrossrefPubMedSearch in Google Scholar
  • 3 Saito H, Ratnoff OD, Bouma BN, Seligsohn U. Failure to detect variant (CRM+) plasma thromboplastin antecedent (factor XI) molecules in hereditary plasma thromboplastin antecedent deficiency: a study of 125 patients of several ethnic backgrounds. J Lab Clin Med 1985; 106: 718-722
    PubMedSearch in Google Scholar
  • 4 Hancock JF, Wieland K, Pugh RE, Martinowitz U, Schulman S, Kakkar VV, Kernoff PB A, Cooper DN. A molecular genetic study of factor XI deficiency. Blood 1991; 77: 1942-1948
    PubMedSearch in Google Scholar
  • 5 Leiba H, Ramot B, Many A. Heredity and coagulation studies in ten families with factor XI (plasma thromboplastin antecedent) deficiency. Br J Haematol 1995; 11: 654-665
    PubMedSearch in Google Scholar
  • 6 Rapaport SI, Proctor RR, Patch MJ, Yettra M. The mode of inheritance of PTA deficiency: evidence for the existence of major PTA deficiency and minor PTA deficiency. Blood 1961; 18: 149-165
    PubMedSearch in Google Scholar
  • 7 Mammen EF. Congenital coagulation disorders – Factor XI deficiency. Semin Thromb Haemost 1983; 9 (01) 34-35
    Thieme ConnectPubMedSearch in Google Scholar
  • 8 Edson JR, White JG, Krivit W. The enigma of severe factor XI deficiency without hemorrhagic symptoms. Thromb Diath Haemorrh 1967; 18: 324-348
    PubMedSearch in Google Scholar
  • 9 Egeberg O. A family with antihemophilic C factor (AHC = Plasma thromboplastin antecedent) deficiency without bleeding tendency. Scand J Clin Lab Invest 1962; 14: 478-486
    CrossrefPubMedSearch in Google Scholar
  • 10 Ragni MV, Sinha D, Seaman F, Lewis JH, Spero JA, Walsh PN. Comparison of bleeding tendency, factor XI coagulant activity, and factor XI antigen in 25 factor Xl-deficient kindreds. Blood 1985; 65: 719-724
    PubMedSearch in Google Scholar
  • 11 Bolton-Maggs PH B, Young Wan-Yin B, McGraw AH, Slack J, Kernoff PB A. Inheritance and bleeding in factor XI deficiency. Br J Haematol 1988; 69: 521-528
    CrossrefPubMedSearch in Google Scholar
  • 12 Litz CE, Swaim WR, Dalmasso AP. Factor XI deficiency: genetic and clinical studies of a single kindred. Am J Hematol 1988; 28: 8-12
    CrossrefPubMedSearch in Google Scholar
  • 13 Lian EC-Y, Deykin D, Harkness DR. Combined deficiencies of factor VIII (AHF) and factor XI (PTA). Am J Hematol 1976; 1: 319-324
    CrossrefPubMedSearch in Google Scholar
  • 14 Chediak J, Lambert E, Johnson El, Telfer MC. Combined severe factor XI deficiency and von Willebrand’s disease. Am J Clin Pathol 1980; 74: 108-114
    CrossrefPubMedSearch in Google Scholar
  • 15 Tavori S, Brenner B, Tatarsky I. The effect of combined factor XI deficiency with von Willebrand factor abnormalities on haemorrhagic diathesis. Thromb Haemost 1990; 63: 36-38
    Thieme ConnectPubMedSearch in Google Scholar
  • 16 Brody JI. Prolonged bleeding times with factor IX and XI deficiency (von Willebrand syndromes). Am J Med Sci 1975; 269: 19-24
    CrossrefPubMedSearch in Google Scholar
  • 17 Karaca M, Nilsson IM. PTA (Factor XI) deficiency and prolonged bleeding time. Act Med Scand 1972; 192: 171-176
    PubMedSearch in Google Scholar
  • 18 Winter M, Needham J, Barkhan P. Factor XI deficiency and a platelet defect. Haemostasis 1983; 13: 83-88
    PubMedSearch in Google Scholar
  • 19 Mannhalter C, Hellstem P, Deutsch E. Identification of a defective factor XI cross-reacting material in a factor XI deficient patient. Blood 1987; 70: 31-37
    PubMedSearch in Google Scholar
  • 20 Asakai R, Chung DW, Davie EW, Seligsohn U. Factor XI deficiency in Ashkenazi jews in Israel. N Engl J Med 1991; 325: 153-158
    CrossrefPubMedSearch in Google Scholar
  • 21 Miller BC, Hultin MB, Jesty J. Altered factor VII activity in hemophilia. Blood 1985; 65: 845-849
    PubMedSearch in Google Scholar
  • 22 Rosenthal RL, Dreskin OH, Rosenthal N. Plasma thromboplastin antecedent (PTA) deficiency: clinical, coagulation, therapeutic and hereditary aspects of a new hemophilia-like disease. Blood 1955; 10: 120-131
    PubMedSearch in Google Scholar
  • 23 Cavins JA, Wall RL. Clinical and laboratory studies of plasma thromboplastin antecedent deficiency (PTA). Am J Med 1960; 444-448
    PubMedSearch in Google Scholar
  • 24 Conrad FG, Breneman WL, Grisham DB. A clinical evaluation of plasma thromboplastin antecedent (PTA) deficiency. Ann Int Med 1965; 62: 885-898
    CrossrefPubMedSearch in Google Scholar
  • 25 Forbes CD, Madhok R. Genetic disorders of blood coagulation: clinical presentation and management. In: Disorders of Hemostasis. Ratnoff OD, Forbes CD. eds. WB Saunders; Philadelphia: 1991. Ch 5: pp 141-202
    Search in Google Scholar
  • 26 Kelly TE. Autosomal dominant and recessive traits. In: Clinical Genetics and Genetic Counselling, 2nd Edition. Year Book Medical Publishers Inc.; Chicago: 1986. Ch 4: p 67
    Search in Google Scholar
  • 27 Ohkubo Y, O’Brien DP, Kanehiro T, Fukui H, Tuddenham EG D. Characterization of a panel of monoclonal antibodies to human coagulation factor XI and detection of factor XI in Hep G2 cell conditioned medium. Thromb Haemost 1990; 63: 417-423
    Thieme ConnectPubMedSearch in Google Scholar
  • 28 Machin SJ, Mackie IJ. Von Willebrand factor assay. In: Laboratory Haematology. An account of laboratory techniques Chanarin I. (ed). Churchill-Livingstone; 1989. pp 309-310
    Search in Google Scholar
  • 29 Campbell MJ, Machin D. Relative (receiver) operating characteristics. In: Medical Statistics. A commonsense approach John Wiley and Sons, Chichester; UK: 1990. pp 36-38
    Search in Google Scholar
  • 30 Bolton-Maggs PH B, Lloyd J, Wensley RT, Tuddenham EG D. Genetic analysis of 27 kindreds with factor XI deficiency from North West England. International Society of Haematology 1992. Abstract 511. p 131 Blackwell Scientific Publications;
    Search in Google Scholar
  • 31 Phillips LL, Hyman GA, Rosenthal RL. Prolonged post-operative bleeding in a patient with factor XI (PTA) deficiency. Ann Surg 1995; 162: 37-42
    PubMedSearch in Google Scholar
  • 32 Bolton-Maggs PH B, Wensley RT, Kernoff PB A, Kasper CK, Winkelman L, Lane RS, Smith JK. Production and therapeutic use of a factor XI concentrate from plasma. Thromb Haemost 1992; 67: 314-319
    Thieme ConnectPubMedSearch in Google Scholar
  • 33 Eikenboom JC J, Rosendaal FR, Briët E. History taking in the diagnosis of bleeding disorders. Thromb Haemost 1991; 65 (08) 1047
    PubMedSearch in Google Scholar
  • 34 Pearson RW, Triplett DA. Factor XI assay results in the CAP survey. 1981; Am J Clin Path 1982; 78 S 615-620
    PubMedSearch in Google Scholar
  • 35 Henry AI, Rosenthal RL. Spontaneous hemorrhages caused by plasma thromboplastin antecedent deficiency. JAMA 1956; 162: 727-729
    CrossrefPubMedSearch in Google Scholar
  • 36 Fraser IS, McCarron G, Markham R. A preliminary study of factors influencing perception of menstrual blood loss volume. Am J Obstet Gynecol 1984; 149: 788-793
    CrossrefPubMedSearch in Google Scholar
  • 37 Rees MC P, Turnbull AC. Menstrual disorders – an overview. Clin Obstet Gynaecol 1989; 13: 217-226
    PubMedSearch in Google Scholar
  • 38 Iles S, Gath S. Psychological problems and uterine bleeding. Clin Obstet Gynaecol 1989; 3: 375-389
    PubMedSearch in Google Scholar
  • 39 Cox Gill J, Endres-Brooks. Bauer PJ, Marks WJ, Montgomery RR. The effect of ABO blood group on the diagnosis of von Willebrand disease. Blood 1997; 69: 1691-1695
    PubMedSearch in Google Scholar
  • 40 Rodeghiero F, Castaman G, Dini E. Epidemiological investigation of the prevalence of von Willebrand’s disease. Blood 1987; 69: 454-459
    PubMedSearch in Google Scholar
  • 41 Berliner SA, Seligsohn U, Zivelin A, Zwang E, Sofferman G. A relatively high frequency of severe (type III) von Willebrand’s disease in Israel. Brit J Haematol 1986; 62: 535-543
    CrossrefPubMedSearch in Google Scholar
  • 42 Wildgoose P, Nemerson Y, Hansen LL, Nielsen FE, Glazer S, Hedner U. Measurement of basal levels of factor VIIa in hemophilia A and B patients. Blood 1992; 80: 25-28
    PubMedSearch in Google Scholar