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Factor XI (FXI) deficiency (hemophilia C or Rosenthal disease) was first described in the 1950s in a multigenerational family experiencing bleeding related to surgery and dental procedures. Managing patients with FXI deficiency presents several challenges, including a lack of correlation of bleeding symptoms with FXI activity levels, the large volume of fresh frozen plasma required to achieve hemostatic FXI levels, lack of availability of FXI concentrate in certain regions of the world, and the inherent thrombotic risk associated with replacement therapy. This article summarizes presentation, diagnosis, and management of patients with FXI deficiency in a variety of clinical settings.

SummaryPlasma thromboplastin antecedent is a beta-globulin which is essential to normal coagulation. Its deficiency results in a hemorrhagic disease which is relatively less severe than either AHG or PTC deficiency. Transmitted as an autosomal dominant gene with variable expression and penetrance, the disease occurs in both males and females. The incidence of PTA deficiency seems to be high in comparison with the other hereditary clotting protein abnormalities. At present, our series numbers 39 cases (29 families). Since PZA is a catalytic, stable factor, which is present in serum, it is well corrected by both fresh or stored blood or plasma (15% replacement). The correction gradually disappears over the period of one week.

We report a 74-year-old woman presenting with vaginal bleeding and hepatomegaly and was found to have plasma thromboplastin antecedent deficiency and alpha 1 antitrypsin deficiency. She also had liver and lung disease of the type associated with the antiprotease deficiency. The relative rarity of the two deficient states led to family and genetic studies. The possibility of a new genetic syndrome is entertained.

Factor XI (plasma thromboplastin antecedent) deficiency is a blood coagulation abnormality occurring in high frequency in Ashkenazi Jews. Three independent point mutations that result in a blood coagulation abnormality have been identified in the factor XI gene of six unrelated Ashkenazi patients. These mutations either disrupt normal mRNA splicing (type I), cause premature polypeptide termination (type II), or result in a specific amino acid substitution (type III). The three different genotypes were present in the six patients as type I/II, type II/III, and type III/III. Thus far no correlation was found between the three genotypes and the bleeding tendency in these patients.

A total of 10 patients with factor XI deficiency underwent prostatectomy: 3 who underwent suprapubic prostatectomy and 3 who underwent transurethral resection received fresh frozen plasma preoperatively, while 4 received fresh frozen plasma only in response to bleeding. We conclude that all patients who present with partial or severe factor XI deficiency should receive fresh frozen plasma preoperatively and for at least 10 to 14 days postoperatively. We believe that all Ashkenazi Jews who are about to undergo a urological operation should be screened for factor XI deficiency even when a history of a bleeding tendency is not present.

Publisher Summary Factor XI is a plasma glycoprotein that participates in the early stage of intrinsic blood coagulation. It is absent, or present as an inert protein, in plasma of individuals with a congenital bleeding disorder called plasma thromboplastin antecedent deficiency. In normal plasma, factor XI is present in a precursor form and is converted to an active form (factor XIa) by another coagulation factor(s). The purification of factor XI has been difficult by conventional methods of protein fractionation since its concentration in plasma is low and it is also very sensitive to protease degradation. This chapter describes the isolation method in which, heparin-agarose column chromatography and benzamidine–agarose column chromatography play an important role in the procedure. It also details each purification step which is performed in the presence of several protease inhibitors, making it possible to isolate a highly purified preparation in a precursor form. It describes the purification process and the general properties of Factor XI.

• A patient had bilateral cataracts and severe plasma thromboplastin antecedent deficiency (factor XI deficiency). This patient underwent successful cataract extraction in both eyes without complication. The problems inherent in performing eye surgery with factor XI deficiency are discussed.

In Reply.— Dr Soloway presents a number of pertinent questions and comments, certain of which were spoken to in the original editorially scrutinized manuscript, later contracted for publication. Answers to his specific questions are as follows: (1) 45 seconds; (2) kaolin; (3) no, specific factor analyses were performed, and only factor XI was below the generally accepted norms for the several factors; (4) no; and (5) no. In 1953, Rosenthal described a type of hemophilia owing to plasma thromboplastin antecedent deficiency (PTA), or hemophilia C.1Following elucidation of this defect, other cases were reported in the literature. Two types of patients were defined. The first group was severely affected with multiple episodes of bleeding and hemorrhage; a second group was much less symptomatic, often only identifiable by clotting factor analysis. The severely affected group on clotting factor analysis was noted to have a factor XI level of 20% of