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Factor XI deficiency (FXID) is a rare bleeding disorder caused by mutations in the F11 gene. Spontaneous bleeding in patients with factor XI deficiency is rare, but major bleeding may occur after surgery or trauma. The basic method for hemostatic treatment is replacement of the missing factor using FXI concentrate or fresh frozen plasma (FFP). We report the case of a 72-year-old male with severe FXID who underwent a laminoplasty under sufficient, but minimal, FFP transfusion. Through detailed monitoring of activated partial thromboplastin time (APTT) and FXI activity at the perioperative period, we succeeded in hemostatic management of major surgery without significant blood loss and fluid overload. From the course of this case, we found that measuring FXI activity is superior to measuring APTT. Furthermore, we identified a novel homozygous mutation in F11 [NM_000128.3:c.1041C > A:p.(Tyr347*)] by whole exome sequencing.

We report a death from transfusion-transmitted anaplasmosis in a 78-year-old man. The patient died of septic shock 2 weeks after a perioperative transfusion with erythrocytes harboring Anaplasma phagocytophilum. The patient's blood specimens were positive for A. phagocytophilum DNA beginning 7 days after transfusion; serologic testing remained negative until death.

Asthma is associated with activation of coagulation in the airways. The coagulation system can be initiated via the extrinsic tissue factor-dependent pathway or via the intrinsic pathway, in which the central player factor XI (FXI) can be either activated via active factor XII (FXIIa) or via thrombin. We aimed to determine the role of the intrinsic coagulation system and its possible route of activation in allergic lung inflammation induced by the clinically relevant human allergen house dust mite (HDM). Wild-type (WT), FXI knockout (KO), and FXII KO mice were subjected to repeated exposure to HDM via the airways, and inflammatory responses were compared. FXI KO mice showed increased influx of eosinophils into lung tissue, accompanied by elevated local levels of the main eosinophil chemoattractant eotaxin. Although gross lung pathology and airway mucus production did not differ between groups, FXI KO mice displayed an impaired endothelial/epithelial barrier function, as reflected by elevated levels of total protein and IgM in bronchoalveolar lavage fluid. FXI KO mice had a stronger systemic IgE response with an almost completely absent HDM-specific IgG 1 response. The phenotype of FXII KO mice was, except for a higher HDM-specific IgG 1 response, similar to that of WT mice. In conclusion, FXI attenuates part of the allergic response to repeated administration of HDM in the airways by a mechanism that is independent of activation via FXII., (Copyright © 2017 the American Physiological Society.)

Orthotopic liver transplantation for other diseases typically results in a coincidental cure for hemophilia A and B; however, long-term outcomes of liver transplant in hemophilia C are not very well described. Herein, the authors report a patient of severe congenital factor XI (FXI) deficiency who received an orthotopic liver transplant. The authors discuss the perioperative management and long-term outcomes. The normalization of his FXI levels confirms that the liver is the most clinically relevant site of synthesis of FXI.

Introduction: Factor XI (FXI) deficiency is the commonest of the rare bleeding disorders, affecting 2079 individuals in the United Kingdom. Treatment options for bleeding or surgery include antifibrinolytics, fresh frozen plasma or plasma-derived (pd) FXI concentrates. There were a number of reports of thrombosis following treatment with FXI concentrates prior to changes in their manufacturing processes made in the mid-1990's., Aims: The aim of the study was to determine the occurrence of adverse events (haemorrhagic and thrombotic) following usage of pd-FXI concentrates at two large UK haemophilia centres. Retrospective chart review of all consecutively treated patients with BPL Factor XI(®) or Hemoleven(®) over a 5-year period (11/06-11/11) was performed., Results: Twenty-nine patients (median age = 57.1 years) received treatment over 64 treatment episodes (surgery = 56, bleeding = 5, other = 3), using 126 000 U of concentrate. Median baseline FXI:C was 9 U dL(-1) (range = <1-51), with 21 having severe and eight partial deficiency. BPL Factor XI(®) was used in 39 episodes (79 110 U) and Hemoleven(®) 25 episodes (46 890 U). There were six clinically significant bleeding events, managed either with a single additional dose of FXI concentrate (n = 4) or requiring no further intervention (n = 2). One patient required blood transfusion and one oral iron replacement. Two thrombotic events (transient ischaemic attack and pulmonary emboli), occurred in two patients with severe FXI deficiency, despite cautious FXI concentrate usage in the perioperative period., Conclusions: FXI concentrate use is efficacious and safe in the majority of cases although physicians should remain mindful of the possibility of thrombotic complications., (© 2015 John Wiley & Sons Ltd.)

Factor XI (FXI) deficiency is a rare hematologic disease, and shows a less severe bleeding tendency compared with what is generally observed in patients with hemophilia A and B. FXI has received a lot of attention in recent years as a new therapeutic target. Here, we present a case of 59-year-old male patient with chronic renal failure. The patient was found to have a markedly prolonged activated partial thromboplastin time (aPTT) during routine preoperative blood test before an arteriovenous fistula surgery. Finally, he was diagnosed with FXI deficiency. More than 6 months after the start of hemodialysis, no sign of blood clotting in the extracorporeal circuit has been observed. Of note, the patient did not receive any anticoagulant during hemodialysis, and he did not show any bleeding tendency even with aPTT more than 120 s and FXI activity below 3% of normal in a patient with renal failure. To our knowledge, this is the first case report to demonstrate FXI deficiency exhibiting anticoagulant effect equivalent to heparin in dialysis.

Adalimumab is a drug used in the treatment of refractory psoriasis. We present a case of a 55-year-old male patient who developed petechiae and purpura after the ninth dose of adalimumab therapy. The results of laboratory investigations revealed factor XI (F.XI) deficiency. It should be recognized that F XI deficiency may develop in patients using long-term adalimumab, leading to increased risk of bleeding.

Factor XI (FXI) deficiency is a rare bleeding disorder, resulting in a wide range of bleeding manifestations, from asymptomatic bleeding to injury-related bleeding. First in this review, we give an overview of the basic pathophysiology, clinical manifestations, and management of FXI deficiency. Finally, we describe 34 members of 16 FXI-deficient kindreds from south Italy, diagnosed and followed at the Haemophilia, Haemostasis and Thrombosis Centre of Pugliese-Ciaccio Hospital, Catanzaro, during the past 20 years. In our patients, bleeding tendency did not appear to be correlated with FXI levels. Furthermore, we describe 24 pregnancies in 11 patients with FXI deficiency. In all the pregnancies, no bleeding manifestations were reported.

Recurrent hemarthrosis following a revision total knee arthroplasty is a rare complication. The likelihood of encountering bleeding complications in patients with hemophilia C following major surgery is unpredictable. Although the use of postoperative chemotherapeutic agents to prevent deep venous thrombosis (DVT) is considered the standard of care for most patients, its use in the hemophiliac population is unknown. This case describes a woman with Hemophilia C who presented with recurrent hemarthrosis 9 days after her revision total knee arthroplasty. Initial treatment efforts were directed towards treating the patient's underlying coagulopathy. Repeated transfusions of fresh frozen plasma and desmopressin were given in an attempt to achieve hemostasis. However the hemarthrosis did not resolve and 36 days postoperatively, a pseudoaneurysm of the left superior geniculate artery was found by angiography and percutaneously embolized. This article presents the first case, to our knowledge, of recurrent hemarthrosis in a hemophiliac patient after revision total knee arthroplasty. It further highlights the importance of considering all possible causes of postoperative bleeding to make a timely diagnosis in the face of a confounding clinical picture., (Copyright 2010, SLACK Incorporated.)

Factor IX is a key component of the plasma system that forms a fibrin clot at a site of vascular injury. Activation of factor IX by factor XIa is required in certain situations to prevent bleeding from premature clot degradation. Factor XIa is a coagulation protease comprised of two identical subunits. The biochemical and physiologic implications of this unusual structural feature are being actively investigated. Congenital factor XI deficiency causes a mild-to-moderate bleeding disorder, with hemorrhage typically involving the oral/nasal cavities and the urinary tract. Current treatment recommendations take this tissue-specific bleeding pattern into account and target factor replacement to certain types of procedures and clinical situations. Results from animal models and human population studies indicate that factor XI contributes to thromboembolic disease. This protease may therefore be a legitimate therapeutic target.

In this paper, we report an inhibitor antibody to factor XI (FXI) in a woman with severe inherited FXI deficiency, induced by FXI present in an Rh immune globulin preparation. The patient is homozygous for the Glu117Stop mutation, associated with a FXI level of less than 1 U/dL. Unlike all previously described patients with severe FXI deficiency and an inhibitor, the patient had never been exposed to blood products. Following 3 injections of Rh immune globulin during pregnancy, she developed an inhibitor to FXI (8 Bethesda units) that was shown to bind specifically to FXI and inhibit factor IX cleavage by purified FXIa. The administered Rh immune globulin and 2 other similar products were shown to contain FXI. Clinicians should be aware of the potential for immunization of severely FXI-deficient patients by FXI present in Rh immune globulin preparations.

Factor XII (FXII), a clotting enzyme that can initiate coagulation in vitro, has long been considered dispensable for normal blood clotting in vivo because hereditary deficiencies in FXII are not associated with spontaneous or excessive bleeding. However, new studies show that mice lacking FXII are protected against arterial thrombosis (obstructive clot formation) and stroke. Thus, FXII could be a unique drug target that could be blocked to prevent thrombosis without the side effect of increased bleeding.

Formation of fibrin is critical for limiting blood loss at a site of blood vessel injury (hemostasis), but may also contribute to vascular thrombosis. Hereditary deficiency of factor XII (FXII), the protease that triggers the intrinsic pathway of coagulation in vitro, is not associated with spontaneous or excessive injury-related bleeding, indicating FXII is not required for hemostasis. We demonstrate that deficiency or inhibition of FXII protects mice from ischemic brain injury. After transient middle cerebral artery occlusion, the volume of infarcted brain in FXII-deficient and FXII inhibitor-treated mice was substantially less than in wild-type controls, without an increase in infarct-associated hemorrhage. Targeting FXII reduced fibrin formation in ischemic vessels, and reconstitution of FXII-deficient mice with human FXII restored fibrin deposition. Mice deficient in the FXII substrate factor XI were similarly protected from vessel-occluding fibrin formation, suggesting that FXII contributes to pathologic clotting through the intrinsic pathway. These data demonstrate that some processes involved in pathologic thrombus formation are distinct from those required for normal hemostasis. As FXII appears to be instrumental in pathologic fibrin formation but dispensable for hemostasis, FXII inhibition may offer a selective and safe strategy for preventing stroke and other thromboembolic diseases.

Factor XI (FXI) and factor IX (FIX) are zymogens of plasma serine proteases required for normal hemostasis. The purpose of this work was to evaluate FXI and FIX as potential therapeutic targets by means of a refined ferric chloride (FeCl(3))-induced arterial injury model in factor-deficient mice. Various concentrations of FeCl(3) were used to establish the arterial thrombosis model in C57BL/6 mice. Carotid artery blood flow was completely blocked within 10 min in C57BL/6 mice by application of 3.5% FeCl(3). In contrast, FXI- and FIX-deficient mice were fully protected from occlusion induced by 5% FeCl(3), and were partially protected against the effect of 7.5% FeCl(3). The protective effect was comparable to very high doses of heparin (1000 units kg(-1)) and substantially more effective than aspirin. While FXI and FIX deficiencies were indistinguishable in the carotid artery injury model, there was a marked difference in a tail-bleeding-time assay. FXI-deficient and wild-type mice have similar bleeding times, while FIX deficiency was associated with severely prolonged bleeding times (>5.8-fold increase, P < 0.01). Given the relatively mild bleeding diathesis associated with FXI deficiency, therapeutic inhibition of FXI may be a reasonable strategy for treating or preventing thrombus formation.

Objective: To identify gene defect in a Chinese pedigree of hereditary coagulation factor XI (FXI) deficiency., Methods: The peripheral blood samples were collected from the proband and her family members. The plasma PT, APTT, FXI:C and FXI:Ag were assayed. The FXI gene exons and exon-intron boundaries of the proband were amplified by PCR and then sequenced directly. The mRNA of FXI in the peripheral blood was analyzed with RT-PCR., Results: The proband and some of her family members had prolonged APTT. The plasma FXI:C and FXI:Ag of the proband, her brother and her parents were lower than 10% and 50% of the normal values, respectively. Nucleotide sequence analysis revealed that the proband and her brother had a homozygous mutation of IVS J-4delgttg in FXI gene. The mutation was inherited from her parents who were heterozygotes. The mutation was not found in 60 normal subjects. No FXI mRNA was detected in peripheral blood sample of the proband., Conclusion: The IVS J-4delgttg is a novel mutation causing FXI deficiency, which may interfere with mRNA splicing.

Bernard Soulier syndrome (BSS) is an autosomal recessive disorder of platelet function. Factor XI deficiency leads to a variable bleeding tendency and the defect is also inherited in an autosomal recessive manner. In this paper we describe a case of BSS with severe deficiency of factor XI. The patient had both BSS and factor XI deficiency. The sister and both the parents were heterozygous for BSS and had factor XI deficiency. The brother is normal for both BSS and factor XI levels. Apart from the patient, no other family members had any history of bleeding in spite of having a deficiency of factor XI, which suggests that low level of factor XI in this family was not responsible for bleeding. Curiously, although the index patient inherited both Bernard Soulier syndrome and factor XI deficiency (FXI: C = 1.3%), he had mild bleeding symptoms restricted only to ecchymoses and petechiae. Detailed review of the pedigree showed that all the members who inherited the BSS phenotype, also inherited abnormal factor XI gene. Karyotype of the affected members of the family using standard Giemsa banding technique showed a normal picture. Considering the fact that the genes causing both BSS and factor XI are both on widely different chromosomes, their coinheritance in four members of the family without any unusual translocation suggest a unified pathology probably on the basis of a common transcription factor defect or a common post translational processing defect. This is the first case of coinheritance of BSS and factor XI deficiency reported in the English literature.

Background and Objectives: In patients with factor XI(FXI) deficiency the bleeding tendency is poorly correlated with plasma factor levels. The purpose of this study was to evaluate whether or not this discrepancy is also present in a large series of patients from Iran, a previously unexplored ethnic group., Design and Methods: In 28 FXI - deficient patients bleeding symptoms and their relation to FXI levels were compared with those of 100 patients with factor VIII (FVIII)deficiency (classic hemophilia), matched for severity of factor deficiency., Results: Spontaneous bleeding was definitely less frequentin FXI deficiency than in hemophilia, whereas postoperative and post-traumatic bleeding occurred with comparable frequencies. Among FXI-deficient patients the severity of symptoms was poorly correlated with FXI levels, mildly deficient patients bleeding almost as frequently as those severely deficient. In contrast, in patients with classic hemophilia there was a close relation between the severity of bleeding and degree of FVIII deficiency., Interpretation and Conclusions: As in other ethnic groups, in Iranians factor XI deficiency is less severe than classic hemophilia and the bleeding tendency is poorly correlated to plasma factor levels., (©2002, Ferrata Storti Foundation)

A survey of 169 Holstein-Friesian cattle showed 21 heterozygous for Factor XI activity having activities of .43 +/- .10 units per milliliter compared with the normal .99 +/- .32 units per milliliter. The frequency of the mutant gene was .06; the 95% confidence limits for the frequency of homozygotes in the population were .1 to .8%, and for heterozygotes the frequency was 7.0 to 16.0%. Test matings indicated this disorder is transmitted as an autosomal recessive gene.

A multiple clotting defect in a 3 month old Arab colt foal associated with a deficiency in Factors VIII, IX, and XI is described. No abnormalities in clotting factors were detected in the colt's sire, dam, half-sister and half-brother.

The authors report on a kin affected with PTA deficiency. The person with homozygous features and a factor XI content below 1% is solely characterized by prolongations of ART and PTT, which were clinically correlated as severe secondary hemorrhages after injuries and surgical treatments. Three heterozygous persons had normal results in global and group tests at 40-50% of factor XI with objectively unambiguous bleeding episodes being absent. As a peculiarity of the recessive heredity of this kin the marriage of two descendants in the fourth generation deserves to be mentioned.