10 Factor XI deficiency

doi:10.1016/S0950-3536(96)80068-0

Baillière's Clinical Haematology

Volume 9, Issue 2, June 1996, Pages 355-368

https://doi.org/10.1016/S0950-3536(96)80068-0 Get rights and content

Summary

That factor XI has a role in normal blood coagulation is evidenced by the fact that patients with deficiency are prone to excessive bleeding after haemostatic challenge. The role of factor XI in physiological processes has become clearer since the discovery that it is activated by thrombin; this fact has contributed to a revised model of blood coagulation.

Factor XI deficiency is particularly common in Ashkenazi Jews. Bleeding is typically provoked by surgery in areas of increased fibrinolysis, and is not restricted to individuals with severe deficiency. The bleeding tendency is variable and the reasons for this are not fully understood, although in severe deficiency there is some correlation between phenotype and genotype.

The factor XI gene is 23 kb long, and two mutations are responsible for most factor XI deficiency in the Ashkenazi population. A total of 13 mutations have thus far been published.

Factor XI deficient patients may need specific therapy to cover surgery and dental extractions. Although a factor XI concentrate is available there have been recent reports of coagulation activation and thrombosis indicating that it should be used cautiously. Fresh frozen plasma may be an acceptable alternative in some situations.

References (72)

BauerKA et al.
Factor IX is activated in vivo by the tissue factor mechanism
Blood
(1990)
Bolton-MaggsPHB et al.
Thrombogenic potential of factor XI concentrate
Lancet
(1994)
BoumaBN et al.
Coagulation factor XI: isolation and activation by factor XIIa
Journal of Biological Chemistry
(1977)
BrunneeT et al.
Activation of factor XI in plasma is depending on factor XII
Blood
(1993)
CavinsJA et al.
Clinical and laboratory studies of plasma thromboplastin antecedent deficiency (PTA)
American Journal of Medicine
(1960)
FraserIS et al.
A preliminary study of factors influencing perception of menstrual blood loss volume
American Journal of Obstetrics and Gynecology
(1984)
HancockJF et al.
A molecular genetic study of factor XI deficiency
Blood
(1991)
MandleRJ et al.
Hageman-factor-dependent fibrinolysis: generation of fibrinolytic activity by the interaction of human activated factor XI and plasminogen
Blood
(1979)
MannhalterC et al.
Identification of a defective factor XI cross-reacting material in a factor XI-deficient patient
Blood
(1987)
MannucciPM et al.
Activation of the coagulation cascade after infusion of a factor XI concentrate in congenitally deficient patients
Blood
(1994)

MealsRA

Paradoxical frequencies of recessive disorders in Ashkenazic jews

Journal of Chronic Diseases

(1971)

MeijersJCM et al.

Expression of human blood coagulation factor XI: Characterisation of the defect in factor XI type III deficiency

Blood

(1992)

PughRE et al.

Six point mutations that cause factor XI deficiency

Blood

(1995)

RagniMV et al.

Comparison of bleeding tendency, factor XI coagulant activity, and factor XI antigen in 25 factor XI-deficient kindreds

Blood

(1985)

RapaportSI et al.

The mode of inheritance of PTA deficiency; evidence for the existence of major PTA deficiency and minor PTA deficiency

Blood

(1961)

RimonA et al.

Factor XI activity and factor XI antigen in homozygous and heterozygous factor XI deficiency

Blood

(1976)

RosenthalRL et al.

Plasma thromboplastin antecedent (PTA) deficiency: clinical, coagulation, therapeutic and hereditary aspects of a new hemophilia-like disease

Blood

(1955)

ShpilbergO et al.

One of the two common mutations causing factor XI deficiency in Ashkenazi Jews (Type II) is also prevalent in Iraqi Jews, who represent the ancient pool of Jews

Blood

(1995)

SidiA et al.

Factor XI deficiency: detection and management during urological surgery

Journal of Urology

(1978)

AghaiE et al.

Factor XI deficiency in an arab moslem family in Israel

Scandinavian Journal of Haematology

(1984)

AsakaiR et al.

Organisation of the gene for human factor XI

Biochemistry

(1987)

AsakaiR et al.

Factor XI deficiency in Ashkenazi jews is a bleeding disorder that can result from three types of point mutations

AsakaiR et al.

Factor XI deficiency in Ashkenazy Jews in Israel

New England Journal of Medicine

(1991)

BaireyO et al.

Haemarthrosis in patients with mild coagulation factor deficiency

Blood Coagulation and Fibrinolysis

(1991)

BerlinerS et al.

Dental surgery in patients with severe factor XI deficiency without plasma replacement

Blood Coagulation and Fibrinolysis

(1992)

Bolton-MaggsPHB

Factor XI deficiency: a review

Haemophilia

(1995)

Bolton-MaggsPHB et al.

Inheritance and bleeding in factor XI deficiency

British Journal of Haematology

(1988)

Bolton-MaggsPHB et al.

Production and therapeutic use of a factor XI concentrate from plasma

Thrombosis and Haemostasis

(1992)

Bolton-MaggsPHB et al.

Definition of the bleeding tendency in factor XI deficient kindreds: a clinical and laboratory study

Thrombosis and Haemostasis

(1995)

BrennerB et al.

Von Willebrand factor antigen and factor XI activity levels predict bleeding tendency in Israeli patients with von Willebrand's disease

Clinical and Applied Thrombosis and Hemostasis

(1995)

BrennerB et al.

Predictors of bleeding in factor XI deficient patients

Thrombosis and Haemostasis

(1995)

BrozeGJ

The role of tissue factor pathway inhibitor in a revised coagulation cascade

BrozeGJ et al.

The role of factor XI in coagulation

Thrombosis and Haemostasis

(1993)

CampbellEW et al.

Plasma thromboplastin antecedent (PTA) deficiency

Archives of Internal Medicine

(1957)

CollinsPW et al.

Clinical experience of factor XI deficiency: the role of fresh frozen plasma and factor XI concentrate

Haemophilia

(1995)

ColmanRW et al.

Factor XI deficiency and hemostasis

American Journal of Hematology

(1994)

Cited by (36)

Thrombogenic potential of picomolar coagulation factor XIa is mediated by thrombin wave propagation
2023, Blood Advances
Inhibitors of coagulation factor XIa (FXIa) are currently being investigated as potential anticoagulant therapies. We hypothesize that circulating FXIa could be a potential target for these therapies. Using previous analyses of FXIa impurities in immune globulin products involved in thrombotic adverse events, we estimated that picomolar levels of FXIa can be thrombogenic. In an in vitro clot-growth assay, 0.1-3 pM of FXIa did not, by itself, activate clotting but increased the size of growing clots. Spatio-temporal reconstruction of thrombin activity inside the clot revealed that FXIa’s effect was limited to the clot-plasma interface, in which FXIa produced a taller than standard wave of thrombin. Factor-depleted plasma and a panel of selective anti-FXIa antibodies showed that exogenous FXIa effects are (1) blocked by anti-FXIa antibodies, (2) independent of FXI activation inside the clot, and (3) larger than the contribution of in situ FXIa. In a thrombin generation (TG) assay, picomolar FXIa did not initiate TG but rather promoted TG triggered by tissue factor or thrombin, suggesting that the effect of FXIa on the thrombin wave is mediated by the elevation of thrombin-triggered TG. In circulating bovine blood, low doses of human FXIa did not initiate clotting but increased the size of stenosis-triggered thrombi. FXIa injection in mice enhanced TG in plasma for at least 6 hours ex vivo, confirming the persistence of circulating FXIa. Our findings suggest that picomolar levels of circulating FXIa may not be able to initiate thrombosis but can facilitate thrombus growth through the facilitation of TG inside the clot.
Evaluation of thrombin generation assay in factor XI deficiency
2021, Clinica Chimica Acta
Citation Excerpt :
Patients with severe deficiency may not present a hemorrhagic syndrome, even during surgery, while patients with moderate deficiency may develop hemorrhagic complications outside of invasive procedures [21]. Moreover, aPTT is not correlated with clinical bleeding risk [8]. Our results confirm previous descriptions.
Factor XI (FXI) deficiency is characterized by a lack of correlation between FXI plasma levels and the occurrence of hemorrhagic events. The main objective of our study was to determine whether thrombin generation assay (TGA) could be used to assess the hemorrhagic phenotype of patients with FXI deficiency.
All patients had confirmed laboratory measurement of FXI < 50% in two plasma samples. Relevant bleeding history was evaluated by a senior physician. TGA was performed with Calibrated Automated Thrombography, in platelet poor plasma, from patients and healthy controls. The assay was performed with PPP low reagent (1 pM of human tissue factor).
Seventy-six patients with FXI deficiency were included between 2011 and 2020. Among them, eight patients had severe deficiency (FXI < 15%). Mean age was 34 years [range: 9–77]. Endogenous thrombin potential (ETP) was significantly lower in patients with FXI deficiency and bleeding (573 nM·min [225–1214]) or no bleeding (732 nM·min [222–1435]), compared to healthy controls (1184 nM·min [933–1518]). No difference was observed for ETP and peak between patients with FXI deficiency and bleeding and patients with FXI deficiency and no bleeding. No difference was observed for ETP (923 nM·min [377–1497] vs 1063 nM·min [252–2529]), peak (82 nM [28–154] vs 131 nM [20–330]) or velocity (13.7 nM/min [3.6–29.6] vs 26.5 nM/min [2.5–90]) in women with (n = 4) and without history (n = 17) of post-partum bleeding. No difference of thrombin generation was observed in pregnant women with FXI deficiency (ETP: 1395 nM·min [351–2529]; peak: 154 nM [26–330]; velocity: 29.6 nM/min [4.1–90.0]), compared to healthy controls and a control group of healthy pregnant women.
In conclusion, under our experimental condition, a non-significant decrease of thrombin generation was observed in plasma samples of patients with FXI deficiency and bleeding. Our results suggest an increase of coagulation parameters during pregnancy in women with FXI deficiency. A larger sample size or other experimental conditions are required to evaluate the use of TGA in FXI deficiency.
Surface loops of trypsin-like serine proteases as determinants of function
2019, Biochimie
Citation Excerpt :
Factor XI is encoded on chromosome 4, and genetic deficiencies lead to the recessive bleeding disorder hemophilia C, also known as Rosenthal syndrome, which for gynecological reasons affects more women than men. Hemophilia C does usually not lead to spontaneous bleeding, but can result in excessive blood loss by physical traumata or surgery [37]. The architecture of factors IX and X from the intrinsic pathway differs significantly from fXII and fXI, comprising two EGF-like domains and an N-terminal Gla domain, which contains up to 12 γ-carboxyglutamates, forming four Ca2+ and four Mg2+ sites that allow for binding phospholipids of vascular cell membranes [38].
Trypsin and chymotrypsin-like serine proteases from family S1 (clan PA) constitute the largest protease group in humans and more generally in vertebrates. The prototypes chymotrypsin, trypsin and elastase represent simple digestive proteases in the gut, where they cleave nearly any protein. Multidomain trypsin-like proteases are key players in the tightly controlled blood coagulation and complement systems, as well as related proteases that are secreted from diverse immune cells. Some serine proteases are expressed in nearly all tissues and fluids of the human body, such as the human kallikreins and kallikrein-related peptidases with specialization for often unique substrates and accurate timing of activity. HtrA and membrane-anchored serine proteases fulfill important physiological tasks with emerging roles in cancer. The high diversity of all family members, which share the tandem β-barrel architecture of the chymotrypsin-fold in the catalytic domain, is conferred by the large differences of eight surface loops, surrounding the active site. The length of these loops alters with insertions and deletions, resulting in remarkably different three-dimensional arrangements. In addition, metal binding sites for Na⁺, Ca²⁺ and Zn²⁺ serve as regulatory elements, as do N-glycosylation sites. Depending on the individual tasks of the protease, the surface loops determine substrate specificity, control the turnover and allow regulation of activation, activity and degradation by other proteins, which are often serine proteases themselves. Most intriguingly, in some serine proteases, the surface loops interact as allosteric network, partially tuned by protein co-factors. Knowledge of these subtle and complicated molecular motions may allow nowadays for new and specific pharmaceutical or medical approaches.
Arrayed Primer Extension Microarrays for Molecular Diagnostics
2009, Molecular Diagnostics: Second Edition
This chapter provides an introduction to Arrayed Primer Extension (APEX), which is a microarray-based approach. This method is well suited for testing known disease-causing mutations and analyzing single nucleotide polymorphisms (SNPs) in candidate regions where tens to thousand of markers need to be tested using custom-made arrays. The size of the deletions and insertions can be determined if analysis is carried out simultaneously from both DNA strands, since this gives the starting and ending points of the deletion or insertion in the known DNA sequence. More than 600-plex reactions can be routinely performed in one tube, reducing the pipetting time and consumables needed substantially. For the TP53 gene, a resequencing microarray has been developed, which also allows analyzing de novo mutations. It can be used for testing of somatic mutations directly from the tumor sample, with as little as 6 percent of mutated DNA on the background of normal sequence from the normal tissue. An updated version of the method, namely, APEX-2, has been introduced, which has increased the degree of multiplexing for SNP testing. It opens up new frontiers for utilizing the microarrays in custom genotyping applications. The future applications of the APEX microarrays are discussed, which include copy-number variation testing.
Labour epidural analgesia for a woman with a factor XI deficiency: An illconsidered risk?
2009, Annales Francaises d'Anesthesie et de Reanimation
Les troubles congénitaux de la coagulation contre-indiquent l’analgésie péridurale en raison du risque d’hématome périmédullaire. Il n’existe cependant pas de consensus sur le taux limite de facteur de coagulation permettant sa réalisation. Nous rapportons une observation d’analgésie péridurale obstétricale chez une femme souffrant d’un déficit modéré et symptomatique en facteur XI (FXI), malgré cette contre-indication théorique. En effet, le déficit en FXI entraîne un risque hémorragique variable difficilement prévisible. Aucune séquelle neurologique ou saignement anormal n’a été déploré malgré l’absence de prophylaxie spécifique.
Inherited bleeding disorders contraindicate epidural analgesia because of the risk of epidural haematoma. However, there is no consensus about a minimal rate of factor XI required for its performance. We report here a case of epidural analgesia in a pregnant woman with a moderate and symptomatic factor XI deficiency, despite this theoretical contraindication. Indeed, the factor XI deficiency results in a haemorrhagic risk which is variable and not easily foreseeable. Nevertheless, no neurological after-effect or excessive bleeding occurred although no specific prophylaxis had been performed.
Comprehensive arrayed primer extension array forthe detection of 59 sequence variants in 15 conditions prevalent among the (Ashkenazi) Jewish population
2007, Journal of Molecular Diagnostics
In the Ashkenazi Jewish population, serious and lethal genetic conditions occur with relatively high frequency. A single test that encompasses the majority of population-specific mutations is not currently available. For comprehensive carrier screening and molecular diagnostic purposes, we developed a population-specific and inclusive microarray. The arrayed primer extension genotyping microarray carries 59 sequence variant detection sites, of which 53 are detectable bi-directionally. These sites represent the most common variants in Tay-Sachs disease, Bloom syndrome, Canavan disease, Niemann-Pick A, familial dysautonomia, torsion dystonia, mucolipidosis type IV, Fanconi anemia, Gaucher disease, factor XI deficiency, glycogen storage disease type 1a, maple syrup urine disease, nonsyndromic sensorineural hearing loss, familial Mediterranean fever, and glycogen storage disease type III. Several mutations in the selected disorders that are not prevalent per se in the Ashkenazi Jewish populations, as well pseudodeficiency alleles, are also included in the array. The initial technical evaluation of this microarray demonstrates that it is comprehensive, robust, sensitive, specific, and easily modifiable. This cost-effective array is based on a diversely applied platform technology and is suitable for both carrier screening and disease detection in Ashkenazi and Sephardic Jewish populations.

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10 Factor XI deficiency

Summary

Blood

Lancet

Journal of Biological Chemistry

Blood

American Journal of Medicine

American Journal of Obstetrics and Gynecology

Blood

Blood

Blood

Blood

Journal of Chronic Diseases

Blood

Blood

Blood

Blood

Blood

Blood

Blood

Journal of Urology

Factor XI deficiency in an arab moslem family in Israel

Scandinavian Journal of Haematology

Organisation of the gene for human factor XI

Biochemistry

Factor XI deficiency in Ashkenazi jews is a bleeding disorder that can result from three types of point mutations

Factor XI deficiency in Ashkenazy Jews in Israel

New England Journal of Medicine

Haemarthrosis in patients with mild coagulation factor deficiency

Blood Coagulation and Fibrinolysis

Dental surgery in patients with severe factor XI deficiency without plasma replacement

Blood Coagulation and Fibrinolysis

Factor XI deficiency: a review

Haemophilia

Inheritance and bleeding in factor XI deficiency

British Journal of Haematology

Production and therapeutic use of a factor XI concentrate from plasma

Thrombosis and Haemostasis

Definition of the bleeding tendency in factor XI deficient kindreds: a clinical and laboratory study

Thrombosis and Haemostasis

Von Willebrand factor antigen and factor XI activity levels predict bleeding tendency in Israeli patients with von Willebrand's disease

Clinical and Applied Thrombosis and Hemostasis

Predictors of bleeding in factor XI deficient patients

Thrombosis and Haemostasis

The role of tissue factor pathway inhibitor in a revised coagulation cascade

The role of factor XI in coagulation

Thrombosis and Haemostasis

Plasma thromboplastin antecedent (PTA) deficiency

Archives of Internal Medicine

Clinical experience of factor XI deficiency: the role of fresh frozen plasma and factor XI concentrate

Haemophilia

Factor XI deficiency and hemostasis

American Journal of Hematology