Hemarthrosis revealing congenital factor XI deficiency.

Congenital factor XI deficiency (also known as the Rosenthal syndrome or hemophilia C) manifests as minor bleeding, usually after trauma or surgery. We report a case in which bilateral knee hemarthrosis was the first manifestation. The patient presented at 32 years of age with a 2-year history of mechanical pain and intermittent swelling in both knees. Knee aspiration recovered blood-tinged fluid. The laboratory workup showed severe factor XI deficiency. Replacement therapy with fresh frozen plasma was effective. Tests in the family showed factor XI deficiency in the patient's sister.

Successful use of recombinant factor VIIa (NovoSeven) during cardiac surgery in a pediatric patient with congenital factor XI deficiency.

We report our experience with the use of recombinant activated factor VII (rFVIIa) during cardiac surgery in a 4.5-year-old boy with severe congenital FXI deficiency and a congenital heart disease. After weaning the patient from cardiopulmonary bypass, the first intravenous dose of rFVIIa (90 microg/kg) was administered. This same dosage was repeated eight more times, at 2- to 4-hour intervals postoperatively. There was no bleeding during and after surgery. rFVIIa treatment may be used successfully in children with severe FXI deficiency in major operations such as open heart surgery.

Percutaneous coronary intervention in a patient with congenital factor XI deficiency and acquired inhibitor.

BACKGROUND: Factor XI deficiency has been associated with bleeding diathesis mostly secondary to trauma and post-operatively depending on the severity of deficiency. Cases with factor XI deficiency having undergone cardiac surgery and coronary intervention after appropriate replacement therapy have been reported in the past. The presence of inhibitor in factor XI deficiency poses a hematological challenge and literature regarding coronary intervention in such patients is limited. Immunosuppressive therapy, plasma exchange and factor VII product transfusions have been used prior to cardiac interventions in few such reported cases. METHOD: We report our approach in such a case of Percutaneous Transluminal Coronary Angioplasty in a 72-year-old male of Jewish origin who has congenital factor XI deficiency complicated with acquired inhibitor. RESULTS: In some cases, the acuity of the coronary syndrome may mandate immediate coronary intervention. However, patient's history of factor XI deficiency and acquired inhibitor pose a major dilemma of further course of action. We performed percutaneous balloon angioplasty in this case with no anti-coagulant and with favorable outcome. CONCLUSION: Under these circumstances of significant coagulation disorder and based on the case report, we recommend that balloon angioplasty be undertaken with no additional anti-coagulation other than Aspirin.

An illustrative case and a review on the dosing of recombinant factor VIIa in congenital factor XI deficiency.

Recombinant activated factor VII (rFVIIa) has been used in a very limited number of patients with severe factor XI (FXI) deficiency. The dose and duration of treatment has varied greatly between these case reports. In a few of these cases there was also evidence of thrombotic complications. We present here a report on one additional patient with congenital FXI deficiency. For two major orthopaedic procedures in this patient we used rFVIIa as a single bolus dose followed by continuous infusion at a low rate. The data from these treatment episodes, together with those from a review of the published cases, lend support to the concept of using much lower doses than in haemophilia with inhibitors. A bolus dose of 20 microg kg(-1) and thereafter maintenance of the FVII activity at approximately 3 IU mL(-1) appears effective and safe.

[Identification of two novel factor XI non-sense mutation Trp228stop and Trp383stop in a Chinese pedigree of congenital factor XI deficiency].

OBJECTIVE: To identify the factor XI gene mutation in a Chinese pedigree of congenital factor XI deficiency. METHODS: The peripheral blood samples were collected from the proband and her family members and the plasma FXI:C and FXI:Ag were assayed. All the exons and their adjacent intron sequences of factor XI were amplified with PCR and sequenced thereafter. RESULTS: Two novel nonsense mutations TGG-->TGA (Trp228stop) and TGG-->TAG (Trp383stop) were identified in the family. CONCLUSION: The compound heterozygous Trp228stop and Trp383stop may attribute to the pathogenesis of the congenital factor deficiency.

[Postoperative haemorrhagia in a girl with congenital factor XI deficiency - successful treatment with desmopressin (DDAVP, Minirin(R))]. / Postoperative Blutung bei einem Mädchen mit angeborenem Faktor-XI-Mangel - erfolgreiche Therapie mit Desmopressin (DDAVP, Minirin(R)).

UNLABELLED: The rare factor XI deficiency is associated with different profuse bleeding without correlation to the severity of reduction of factor XI. Accordingly, traumata or surgical procedures may cause unexpected excessive bleeding in asymptomatic patients. After surgery of a nine-year-old girl with factor XI deficiency (8 per cent) profuse bleeding occurred which could only be stopped after infusion of desmopressin. After administration the factor XI activity was increased to 31 per cent, the factor VIII even to 290 per cent over the normal range. We suppose that the favorable clinical effectiveness is not only related to the increasing factor XI activity but also to the elevation of the factor VIII/von-Willebrand-complex. CONCLUSION: It is recommended to give desmopressin as firstline therapy of bleeding by factor XI deficiency since the only effective alternative such as substitution of factor XI by transfusion of fresh frozen plasma is associated with the risk of transmission of virus infections.

The role of factor XI in thrombin generation induced by low concentrations of tissue factor.

Thrombin generation has been studied in the plasma of severely factor XI deficient patients under conditions in which contact activation did not play a role. In platelet-rich as well as platelet-poor plasma, thrombin generation was dependent upon the presence of factor XI at tissue factor concentrations of between 1 and 20 pg/ml i.e. approximately 0.01 to 0.20% of the concentration normally present in the thromboplastin time determination. The requirement for factor XI is low; significant thrombin generation was seen at 1% factor XI; at 10%, thrombin formation was nearly normalised. A suspension of normal platelets in severely factor XI deficient plasma did not increase thrombin generation. This implies that there is no significant factor XI activity carried by normal platelets, although the presence of factor XI and factor XI inhibitors in platelets cannot be ruled out.

Management of factor XI inhibitor for cardiac intervention: successful treatment with immunosuppressive therapy and plasma exchange.

Two cases with congenital homozygous factor XI deficiency developed a factor XI inhibitor following repeated plasma transfusions. Case 1 was given cyclophosphamide, intravenous immunoglobulin, and steroids. The factor XI inhibitor disappeared on day 103 and cardiac catheterization was performed without complications after giving fresh frozen plasma. Case 2 was effectively managed by plasma exchange for cardiac catheterization and surgery. However, after five plasma exchange procedures, the same plasma volume exchange was not effective in shortening the activated partial thromboplastin time (APTT). A significant heparin rebound occurred 4 h after heparin neutralization with protamine sulphate for which the patient needed to have a blood clot evacuated from around the heart.

A novel mutation that leads to a congenital factor XI deficiency in a Japanese family.

We have identified a novel mutation leading to a congenital deficiency of the coagulation factor XI (FXI) in a Japanese family. A propositus was a 42-year-old female patient without bleeding tendency. Coagulant activity and the antigen level of FXI in her plasma were below the detectable range. The nucleotide sequences of the FXI gene of this patient were determined by a direct sequence method established in this study. A novel nonsense mutation (CAA; Gly263 --> TAA; stop) was identified in exon 8 of the FXI gene. Her parents are first cousins, and a polymerase chain reaction-restriction-fragment length polymorphism analysis revealed that her parents were heterozygous at this nucleotide position. This patient inherited mutant alleles from her parents and is homozygous at this nucleotide position. The nonsense mutation in the FXI gene is responsible for her deficiency of FXI.

[A successful surgical case of atrial septal defect with congenital factor XI deficiency].

We experienced a successful surgical case, who was a 16-year-old boy suffered from atrial septal defect with congenital factor XI deficiency. This disorder is an inherited disorder of blood coagulation characterized by a defect of the intrinsic pathway of thrombin formation and a mild to moderate bleeding tendency, but it can result in severe bleeding in surgical procedures. Open heart surgery in this disorders is rare. Preoperatively we prepared 4000 cc of fresh frozen plasma, but operated without using it. It would appear that the possibility of open heart surgery with congenital factor XI deficiency suggest in this case.

Deficiencia genética del factor XI en familia con antecedentes de trastornos hemorrágicos / Genetic deficiency of factor XI in a family with history of bleeding disorders

Se realizó un estudio prospectivo con el objetivo de identificar la deficiencia genética del factor XI (PTA) en una familia con antecedentes de trastornos hemorrágicos. La población estudiada contó de 13 pacientes, que fue el número de descendientes localizados; a los cuales se les aplicó un cuestionario y luego les fue realizado un perfil de coagulación. De los 13 pacientes, sólo 3 presentaron antecedentes hemorrágicos. La edad de inicio del sangrado osciló entre los 11 y 13 años de edad. De los pacientes estudiados, 8 son de sexo femenino y 5 de sexo masculino. Con relación a las pruebas de hemostasia, la TDT estuvo alargada en solo 2 pacientes y la TT estuvo prolongada en 4 pacientes. Con relación a la cuantificación del factor XI se puede observar que 4 pacientes resultaron con niveles del factor XI por debajo del 20 por ciento , locual se consideró como la deficiencia mayor

Combined factor VIII and factor XI congenital deficiency: a case report.

Combined congenital defect involving both Factor VIII and XI is a very rare disorder. We describe a case of combined Factor VIII and XI deficiency in which the propositus has a mild hemophilia A and inherited a Factor XI deficiency from the father. Moreover, we report on the benefit of DDAVP administration to the patient during a bleeding episode.

Cardiovascular surgery in patients with congenital plasma coagulopathies.

From 1978 to 1986, fifteen cardiovascular operations were performed on 13 patients with known congenital bleeding disorders. The patients (10 men and 3 women) had a mean age of 51.1 +/- 3.4 years. Four were seen with cardiovascular lesions and documented hemophilia A (Factor VIII deficiency); 3 had hemophilia B (Factor IX deficiency); 3 had Factor XI deficiency; 2 had von Willebrand's disease, and 1 had dysfibrinogenemia. All patients had a history of major hemorrhage after dental extractions or general surgical procedures, and had clearly documented coagulation disorders on hematological evaluation. Elective cardiovascular procedures performed in these patients included aortocoronary bypass grafting (eight), cardiac valve replacement or repair (five), aortic graft placement (one), and carotid endarterectomy (one). The mainstay of perioperative management included appropriate replacement therapy with blood components. Coagulation factor levels were measured routinely to guide therapy. There were no deaths. Two hemorrhagic complications necessitated reexploration. We conclude that in patients known to have congenital coagulation disorders, cardiovascular operations using systemic heparinization can be performed with minimal morbidity and mortality when carried out with preoperative and perioperative support from the hematology service, adequate replacement therapy using blood components, and careful monitoring of the coagulation status.

Acquired antibody to factor XI in a patient with congenital factor XI deficiency.

The results of studies in a patient with congenital deficiency of Factor XI who developed an inhibitor are presented. The patient presented with a severe, apparently spontaneous bleed into the thigh, which progressed despite infusion of fresh frozen plasma, but which responded promptly to activated prothrombin complex. During therapy with plasma his clotting time and Factor XI level were unresponsive and a Factor XI inhibitor titer of 6,000 U/ml was attained. The inhibitor was isolated and found to be polyclonal immunoglobulin G (IgG), predominantly of subclass 4. The specificity of the antibodies for Factor XI was shown by the ability of isolated inhibitor bound to polyacrylamide beads to remove Factor XI selectively from normal plasma. The binding of (125)I-labeled factor XI to the inhibitor was studied and an affinity constant of 1.65 x 10(10) liter/mol was found. Complexing of the antibodies with Factor XI was shown to block multiple activities of the clotting factor. Factor XI complexed with antibody did not bind to high molecular weight kininogen or undergo activation and cleavage by two-chain Factor XII. The complex of activated Factor XI with inhibitor prevented the cleavage and activation of Factor IX. Hence the inhibitor appears to act by binding to multiple sites on the Factor XI molecule and preventing its interaction with other molecules. Clinically these interactions of the inhibitor with Factor XI result in a state of severe Factor XI deficiency. The clinical circumstances of the case, with severe hemorrhage refractory to plasma infusion but readily responsive to an alternate clot-promoting agent, suggest that a defect of intrinsic system activation was critical, supporting the inference that Factor XI does participate in normal hemostasis. The clinical course of this patient, who has only had two documented hemorrhages in the presence of the inhibitor, is not as severe as that of patients with severe Factor VIII or IX deficiency. This suggests that physiologic activation of Factors XI and IX does not occur exclusively in series because deficiency of factors XII, XI, VIII, and IX should then have similar hemostatic consequences. We propose that independent mechanisms for bypass of Factors XII and XI are important in physiologic activation of coagulation.