11/53. Characterization of factor XII Tenri, a rare CRM-negative factor xii deficiency. Factor XII Tenri (Y34C), a rare cross-reacting material (CRM)-negative factor xii deficiency, was identified in a 71-yr-old Japanese woman with angina pectoris. In the patient's plasma, factor XII activity and antigen levels were only 1.6% and 5.0%, respectively, of those seen in a normal subject. Immunoblot analysis showed that the secreted factor XII Tenri existed not only as a monomer (76 kDa), but also in complexes with apparent molecular weights of approximately 115, 140, 190, 215, and 225 kDa. After reduction with 2-mercaptoethanol, the factor XII Tenri contained in the complexes was completely converted to monomeric form on immunoblot patterns. It appeared that some of the secreted factor XII Tenri formed several types of disulfide-linked complexes, including a factor XII-alpha1-microglobulin complex, through a newly generated Cys residue. The monomeric form of factor XII Tenri, like normal factor XII, was degraded into 2 major fragments with molecular weights of approximately 45 kDa and 30 kDa following mixing with activated partial-thromboplastin-time measuring reagent (cephalin and ellagic acid), whereas the factor XII Tenri that formed the complexes was not. This indicates that the factor XII Tenri present in disulfide-linked complexes with other proteins (and itself) is not converted to active forms, suggesting that attached proteins obstruct or delay the activation of factor XII via an inhibition of its binding to a negatively charged surface in vitro. ( info) |
12/53. Low factor XII level in an individual with sotos syndrome. sotos syndrome is an overgrowth disorder that manifests characteristic dysmorphic features, neurological problems, and an increased risk for cancers and heart defects. Alterations of NSD1 are responsible for this disease. A subset of cases arise from deletions, which is of interest as the factor XII locus lies in close proximity to NSD1. This case report describes an individual with sotos syndrome and factor xii deficiency, providing a potential link between these two genes and, consequently, expanding the clinical phenotype of sotos syndrome. ( info) |
| The outcome of various surgical procedures carried out in patients with severe (homozygote) factor xii deficiency were investigated for the appearance of blood coagulation-related complications with particular emphasis on thrombotic complications. The surgical procedures were total mastectomy, tonsillectomy and adenoidectomy, placement of a hip prosthesis, and double hernia repair. None of the patients slowed any complication. Several other reported cases of surgical procedures carried out in several patients ware found in the literature. Bleeding or thrombotic complications were noted in none of these cases. The surgical procedures in some cases were minor such as adenoidectomy, tonsillectomy, or nasal polyp removal. However several major surgical procedures were carried out in some patients (cholecystectomy, gastrectomy, repair of atrial septal defect, coronary bypass). All patients remained asymptomatic. In some cases whole blood and/or plasma were used as requested by the caring surgeons. In a few patients, the plasma was given prophylactically because of the long partial thromboplastin time. Finally, three patients (two for cardiac surgery and one after hip replacement) received heparin prophylaxis as foreseen by accepted procedures without the undue sequels. These data supply further evidence that factor xii deficiency does not only show any bleeding tendency but also can withstand even major surgical procedures without thrombotic complications. ( info) |
| A 2-year-old Japanese girl with easy bruising and arthropathy was demonstrated to have severe hemophilia a (factor viii activity: less than 0.01 U/ml). She had normal 46XX karyotype. Her brother also had hemophilia a, and her mother and grandmother seem to be hemophiliac carriers. Additionally, activated partial thromboplastin time (APTT) of the patient was disproportionately prolonged and there were reduced levels of coagulation factor XII in the patients and members of the maternal trait which are compatible with heterozygous factor xii deficiency. Her father had both normal factor viii and factor XII levels. Southern blotting analysis of genomic DNA from the propositus and family members with factor viii and factor XII dna probes revealed no gross alterations. This patient represents a female hemophilia a combined with heterozygous factor xii deficiency. Nonrandom inactivation of a normal X-chromosome (extreme lyonization) may be the basis for the expression of hemophilia a in this female patient. ( info) |
| Orbital subperiosteal hemorrhage may develop from the orbital extension of a subgaleal hemorrhage and threaten vision. This article describes the case of a patient with factor viii and factor xii deficiency who had a subgaleal hemorrhage with orbital extension and optic nerve compression following head trauma. ( info) |
16/53. Williams-Beuren syndrome associated with caudal regression syndrome and coagulopathy--a case report. Williams-Beuren syndrome is a genetic disorder caused by a heterozygous deletion at 7q11.23. The present report describes a female patient with Williams-Beuren syndrome combined with caudal regression syndrome and two forms of coagulopathy. Besides the typical developmental abnormalities such as mental and growth retardation, a distinctive facial appearance, and cardiovascular anomalies, our patient showed fusion of fourth and fifth lumbar vertebra and a sacrococcygeal agenesis. blood coagulation tests revealed a deficiency of coagulation factor XI and XII. magnetic resonance imaging angiography showed multiple vascular stenoses mainly in the abdominal aorta and its major branches as a consequence of the insufficient elastin gene. Previous reports identified a deletion of HLXB9 as a possible genetic cause of the caudal regression syndrome, which could not be identified in the present case. This unusual combination of the above-mentioned genetic disorders has not been published so far. ( info) |
17/53. Subdural hematoma in a patient with Hageman trait--case report. A 61-year-old man with severe factor xii deficiency presented with a subdural hematoma appearing as mixed but mainly high density by computed tomography in the left frontotemporoparietal region. No cranial injury was reported in the medical history of the patient. Clotting system study showed less than 1% functional activity of factor XII, whereas the levels of the other clotting factors were within the normal ranges. Partially clotted and hemolyzed subdural hematoma was removed through a craniotomy. The postoperative course was uneventful. The patient later died of severe circulatory-respiratory failure. We believe that the subdural hematoma may have developed as a result of a minor head trauma sustained in the past. We suggest that impairment of fibrinolytic activation related to severe factor xii deficiency might have contributed to the delay of dissolution of the subdural hematoma which, under ordinary circumstances, would have formed chronic subdural hematoma. ( info) |
| Transmission of congenital clotting factor deficiencies after orthotopic liver transplantation is rare. There are published reports of liver donor-to-recipient transmission of protein c deficiency with dysfibrinogenemia, protein s, factor VII and factor XI deficiencies. We report a case of transmission of factor xii deficiency with liver transplantation in a patient with budd-chiari syndrome. There was a persistent elevation of the activated partial thromboplastin time (aPTT), but no evidence of bleeding while the patient was maintained on warfarin. The presence of a persistently abnormal aPTT may raise suspicion for the presence of a clotting factor deficiency; however, deficiencies of other clotting factors may not be readily apparent on routine blood tests performed in a donor. Being aware of the possibilities of transmission of these inherited deficiencies of coagulation factors will aid in their early detection and management in the transplant donor and recipient. ( info) |
19/53. Functional characterization of an abnormal factor XII molecule (F XII Bern). An 18-year-old healthy woman was found to have cross-reacting material (CRM)-positive factor XII (F XII) deficiency, F XII clotting activity was less than 0.01 U/mL, whereas F XII antigen was 0.11 U/mL. An F XII inhibitor was excluded. To partially characterize the molecular defect of the abnormal F XII, immunologic and functional studies were performed on the proposita's plasma. The abnormal F XII was a single chain molecule with the same molecular weight (80 Kd) and the same isoelectric points (pl, 5.9 to 6.8) as normal F XII. dextran sulfate activation of the proposita's plasma showed no proteolytic cleavage of F XII even after 120 minutes, whereas F XII in pooled normal plasma, diluted 1:10 with CRM-negative F XII-deficient plasma, was completely cleaved after 40 minutes. adsorption to kaolin was identical for both abnormal and normal F XII. In the presence of dextran sulfate and exogenous plasma kallikrein, the abnormal F XII was cleaved with the same rate as normal F XII. However, kallikrein-cleaved abnormal F XII was not able to cleave factor XI and plasma prekallikrein, in contrast to activated normal F XII. Thus, these studies show that the functional defect of this abnormal F XII, denoted as F XII Bern, is due to the lack of protease activity of the kallikrein-cleaved molecule. Therefore, the structural defect is likely to be located in the light chain region of F XII, containing the enzymatic active site. ( info) |
| A 19-year-old primigravida with known factor xii deficiency (prepregnant factor XII level of 21%) presented with placental abruption and preterm labor at 26 weeks' gestation. A healthy 925-g female infant was born by spontaneous vaginal delivery. The mother had no postpartum hemorrhage or further complications, and the infant demonstrated no intracranial or other forms of hemorrhage up to 70 days of age. The infant's factor XII level was 34% (normal for her age). There are only two previous reports of factor xii deficiency in pregnancy cited in the English literature, and both were uncomplicated. In view of the risk of thromboembolic complications in nonpregnant individuals with factor xii deficiency, pregnant women with a prolonged activated partial thromboplastin time and no lupus anticoagulant or anticardiolipin antibody syndrome should also be investigated for deficiencies of factors VIII, IX, and XII. These patients should be given the appropriate counseling and should be monitored for features of thromboembolism if factor xii deficiency is confirmed. ( info) |