Heterozygous Factor VII Deficiency Research Articles

The Utility of Thromboelastography As a Screening Test for Bleeding Disorders

Abstract 4352 Introduction:Accurate assessment of bleeding disorders requires a thorough clinical evaluation and appropriate laboratory testing process. These patients comprise a substantial proportion of consultations carried out by hematologists. The limitations of each screening test, and the heterogeneity of these disorders continue to make the diagnosis cumbersome for the practicing clinician. Plasma clotting times, such as the prothrombin time and activated partial thromboplastin time are the most frequently used screening tests to assess adequacy of hemostasis. Thromboelastography (TEG) lends the ability to assess hemostasis globally while also assessing the effects of platelets, leucocytes and red cells on coagulation. Aims:To determine the utility of TEG as an effective screening test for bleeding disorders Methods:Medical records of patients referred to Hematology Service from August 2006 through July 2011 were retrospectively reviewed after institutional review board approval. Results:One hundred ninety-five patients (125 females, 70 males: ages 0.1 to 20 years) were evaluated for a bleeding disorder based on either bleeding symptoms or abnormal routine clotting tests and had TEG performed with low dose tissue factor (1:190 000 concentration). Most common symptoms were epistaxis (83/195), bruising (67/195), menorrhagia (48/195), surgical bleeding (16/195). Twenty-nine patients were diagnosed with a bleeding disorder based on clinical evaluation and laboratory testing. Type 1 vonWillebrand disease (vWD) was diagnosed in 16 patients, heterozygous factor VII deficiency in 6 patients, factor XII deficiency in 3 patients, factor XI deficiency in 2 patients and platelet delta storage pool disease in 1 patient. One patient was a symptomatic hemophilia carrier.Preliminary analysis revealed that among the vWD patients, only 1 patient demonstrated abnormalities in all parameters of TEG [Prolonged Reaction time (R Time), k time (rate of clot formation) and decreased Maximum amplitude (MA)] and 2 showed prolonged R and k time without concomitant decrease in MA. In patients with heterozygous factor VII deficiency, only 2 of 4 patients showed prolonged R and k times. The symptomatic hemophilia carrier, 1 of 3 with factor XII and 1 of 2 patients with factor XI deficiency had prolonged R as their sole abnormality. TEG was completely normal in the patient with platelet delta storage pool disease. The sensitivity of the R time to diagnose a clotting factor (including low factor VIII with vWD) deficiency was only 58% with a specificity of 78%. R time correlated with PTT and PT in up to 50% (vWD: 12%, FVII deficiency: 33%, FXII: 33%, FXI: 50%) of the patients. R time was also prolonged in 46/166 (28%) patients without a definitive bleeding disorder, however 10 of these patients had a lupus anticoagulant. Conclusion:In our study of 195 patients referred for evaluation of bleeding symptoms or abnormal coagulation tests, TEG was of limited value in identifying congenital coagulation defects with both poor sensitivity and specificity. Future studies could examine different agonists or conditions for TEG that may improve its sensitivity for detection of congenital bleeding disorders. Disclosures:No relevant conflicts of interest to declare.

Open-heart surgery in an infant with heterozygous factor VII deficiency

A four-month-old male with Taussig-Bing anomaly and multiple ventricular septal defects underwent an open-heart palliative procedure. He suffered from massive postoperative gastrointestinal bleeding. Heterozygous Arg402Stop-related factor VII deficiency was detected by genomic examinations. When he was 14 months old, a subsequent open-heart surgery with replacement therapy of recombinant factor VIIa was performed without any bleeding or thromboembolic complications. Although heterozygous factor VII deficiency is generally recognized as clinically asymptomatic, this latent bleeding disorder can appear perioperatively or postoperatively in patients who undergo cardiopulmonary bypass procedures. Consequently, the prophylactic replacement therapy with recombinant factor VII is recommended during cardiac operations.

Pregnancy in women with congenital factor VII deficiency

The aim was to review the pregnancy and obstetric outcome in women with factor VII (FVII) deficiency. The study group contained women with FVII deficiency, registered with Haemophilia centre and Haemostasis Unit at the Royal Free Hospital, London. The women were interviewed and case notes were reviewed. The main outcome measures were changes in FVII levels in pregnancy, maternal and perinatal outcome. The FVII levels ranged from 7-36 IU dL(-1) in the 13 women included in the study. There were a total of 14 pregnancies in seven women. Ten pregnancies in four women were prior to the diagnosis of FVII deficiency. Following the diagnosis of FVII deficiency, there were four pregnancies in three women. There was an increase in the FVII level during pregnancy in these women from a mean baseline level of 33 IU dL(-1) to a mean of 73 IU dL(-1). These women received recombinant FVIIa replacement during labour and delivery. There were two early pregnancy losses, both associated with excessive haemorrhage. There was only one postpartum haemorrhage in the study. There is a significant increase in FVII levels in pregnancy in women with heterozygous FVII deficiency. The risk of bleeding in early pregnancy might be higher than that at term, due to inadequate rise in the FVII level in early pregnancy.

Subgaleal Hematoma with Delayed Proptosis and Corneal Ulceration

We report the delayed occurrence in a child of proptosis caused by a subgaleal hematoma. A corneal ulcer resulted from the proptosis, which developed 9 days after mild head trauma. Evaluation revealed a heterozygous factor VII deficiency. The coagulopathy and, more likely, the use of the nonsteroidal antiinflammatory drug ibuprofen may have contributed to the extension of the hematoma into the orbital space. Careful follow-up of patients with subgaleal hematomas is necessary because the development of proptosis may be delayed. [Pomeranz AJ, Ruttum MS, Harris GJ: Subgaleal hematoma with delayed proptosis and corneal ulceration. Ann Emerg Med December 1995;26:752-754.]

Factor VII Verona Coagulation Disorder: Double Heterozygosis With an Abnormal Factor VII and Heterozygous Factor VII Deficiency

A family with a peculiar defect of factor VII is described. The propositi, a brother and sister, were born of a nonconsanguineous marriage and presented a mild to moderate bleeding tendency since childhood (epistaxis, excessive bleeding after tooth extraction). The coagulation pattern was characterized by a mildly prolonged prothrombin time, normal partial thromboplastin time, and normal Stypven-cephalin clotting time. Prothrombin consumption and thromboplastin generation were normal. Factor VII activity was 20%-25% of normal but factor VII antigen was about 50% of normal. The father and other members of his family had factor VII activity of 36%-50% of normal but the factor VII antigen level was 100%. The mother had factor VII activity and antigen levels of about 50% of normal. It appeared that the propositi had inherited an abnormal factor VII from the father and a heterozygous factor VII deficiency from the mother. Therefore, the defect would seem to result from a double heterozygous state. The brother of the propositi had 65% factor VII activity and a normal factor VII antigen, probably the result of the interaction of a paternal abnormal factor VII gene and a normal maternal gene. The condition is referred to as factor VII Verona.