Thrombosis in subjects with homozygous and heterozygous factor XII deficiency.
Explore the source record for details and available documents.
Factor XII Deficiency↗
Biomedical subjects
F Rodeghiero
Publications and source records attributed to F Rodeghiero.
The bleeding time in normal subjects is mainly determined by platelet von Willebrand factor and is independent from blood group.
Bleeding time (BT) is the most important test "in vivo" evaluating the primary hemostasis. No relationship between plasma von Willebrand factor (vWF) and BT has been found in normal subjects, whereas no data are available on the relationship between platelet vWF and blood group or BT in normal subjects. To clarify the reciprocal relationship between blood group, vWF and BT, we studied 177 normal subjects. The influence of blood group on BT was analyzed in 116 subjects and the distribution of platelet and plasma vWF between different blood groups in 111 subjects. Furthermore, in a subgroup of 50 subjects, a multivariate regression model, including age, platelet count, plasma and platelet vWF:Ag and Ristocetin Cofactor (RiCof), hematocrit, sex and O or non-O blood group was used to assess the joint influence of these variables on BT. BT was similar in O and non-O group (P = 0.310) and, although plasma vWF was significantly lower in O group (P less than 0.0001), platelet vWF content was similarly distributed (P = 0.873 vWF:Ag and P = 0.322 RiCof). Furthermore, platelet vWF was not correlated with plasma vWF (r = 0.06, P = 0.526). In the multivariate regression analysis, only platelet vWF, age and platelet count showed a significant, inverse correlation with BT (P = 0.004), explaining 25% of the total variation of this test. Platelet vWF resulted therefore the main determinant of BT.
Adolescent↗
A new variant of von Willebrand disease (type II I) with a normal degree of proteolytic cleavage of von Willebrand factor.
A variant of type II von Willebrand disease (vWd) is described in a young woman and her mother with severe lifelong bleeding histories. On electrophoresis with low-resolution agarose gels the plasma of the proband lacked large and intermediate-size multimers of von Willebrand factor (vWF) but the platelet multimeric structure was normal. On high-resolution gels, smaller multimers could be resolved into a broader central band and four satellite bands, which were much fainter than in normal plasma. In the proband plasma, the relative concentrations of proteolytic fragments of the vWF subunit were within the normal laboratory range. Since this variant of vWd appears to differ from those reported hitherto, the designation of type II I is proposed.
Adolescent↗
Subunit composition of plasma von Willebrand factor (vWF) in two uremic patients with acquired vWF abnormalities.
Explore the source record for details and available documents.
Humans↗
In vivo experiments indicate that relatively high platelet deposition in von Willebrand's disease 'Vicenza' is caused by normal platelet-VWF levels rather than by high VWF-multimers in plasma.
Von Willebrand's disease (vWD) 'Vicenza' is characterized by low plasma von Willebrand Factor antigen (vWF:Ag) and very low levels of Ristocetin Cofactor activity (RiCof). The hemorrhagic tendency in vWD 'Vicenza' is, however, mild and bleeding times in this rare vWD-subtype are only slightly prolonged (1). Larger than normal multimers of plasma-vWF and normal levels of platelet-vWF have both been suggested to compensate the defects that are normally present in vWD. To elucidate the mechanisms involved, whole blood of four patients with vWD 'Vicenza' was circulated through a rectangular perfusion chamber (2) with fibrillar collagen as adhesive surface. Under these conditions, both plasma and platelet vWF participate to platelet adhesion. Compared to perfusion results with blood of normal donors, platelet adhesion of 'Vicenza' patients was decreased. However, the Vicenza defect was less than was observed in parallel experiments with blood of vWD type 1 subtype platelet-low patients and blood of a severe vWD patient. Adhesion was not increased in perfusions with only plasma of the 'Vicenza' vWD-patients. Equal vWF:Ag concentrations of normal multimeric composition were just as effective as the high multimeric 'Vicenza' vWF. Therefore, the abnormal plasma-vWF in 'Vicenza' patients does not cause the relatively high adhesion obtained with whole blood. In contrast, platelets of vWD 'Vicenza' patients resuspended in human albumine solution (HAS) showed far better adhesion than (vWF-poor) platelets of a patient with severe vWD. The values were at least comparable and tended to be higher than those obtained with normal platelets or with platelets of patients with vWD type I subtype platelet normal.(ABSTRACT TRUNCATED AT 250 WORDS)
Biopolymers↗
Effectiveness of high-dose intravenous immunoglobulin in a case of acquired von Willebrand syndrome with chronic melena not responsive to desmopressin and factor VIII concentrate.
A patient with benign monoclonal IgG lambda paraproteinemia, acquired von Willebrand syndrome (AVWS), and chronic melena successfully responding to high-dose intravenous immunoglobulin (lvlg) is reported. Coagulation parameters at admission were APTT (ratio) 1.68; VIII:C 11 IU/dL; vWF:Ag 7 IU/dL:Ricof less than 3 IU/dl. RIPA was greater than 1.8 mg/ml, and bleeding time (BT) was prolonged (18 min). No evidence for an in vitro inhibitor against the VIII/vWF complex was observed. VIII/vWF measurements showed a short-lived increase after both DDAVP and Hemate P, and BT was transiently normalized. After intravenous Ig (1 g/kg for 2 days), VIII/vWF measurements, hemostatic parameters and multimeric pattern were completely corrected (VIII/C 106 IU/dl, vWF:Ag 168 IU/dl, RiCof 147 IU/dl, APTT ratio 0.89, BT 5'), with a return to pre-infusion values after 15 days. Hemoccult test became negative and packed red cell transfusions, of which 130 units were administered during the last year, were no longer required. After 18 months the patient is on maintenance treatment with repeated courses of Ig, at 3 to 4-week intervals based on VIII/vWF and BT monitoring.
Bleeding Time↗
EDTA-dependent pseudothrombocytopenia.
Explore the source record for details and available documents.
Adult↗
Fibrin glue from single-donation autologous plasmapheresis.
A method is described for preparing fibrin glue from fibrinogen obtained by double cryoprecipitation of plasma collected by plasmapheresis. Plasma (average volume, 528.8 +/- 86 mL), collected from 12 plasmapheresis donors was cryoprecipitated twice. When the cryoprecipitated pellet was resuspended in 0.5 to 2 mL of saline (total volume of saline-resuspended fibrinogen: 5 mL), the average yield of fibrinogen was 78.4 +/- 18.3 mg per mL. This is comparable to commercial preparations, is suitable for clinical use, and offers greater safety at a reduced cost.
Electrophoresis, Polyacrylamide Gel↗
Replacement therapy with virus-inactivated plasma concentrates in von Willebrand disease.
In von Willebrand disease, the goal of treatment is to correct the two laboratory hallmarks of abnormal hemostasis, i.e. the deficiency of factor VIII (FVIII) and the prolonged bleeding time (BT). Since desmopressin (DDAVP) is able to achieve both these goals in the majority of patients, it is the treatment of choice. Some patients, however, are not responsive or become refractory to DDAVP. In these, blood products maintain an important therapeutic role, and there is a need to assess the efficacy of the recently available virus-inactivated plasma concentrates, which contain both FVIII and von Willebrand factor and carry a low risk of transmitting blood-borne viruses. Our survey of the data reported in the literature indicates that all available concentrates are similarly effective in attaining high and sustained levels of FVIII after infusion. Although they often shorten or normalize the prolonged BT, that effect is less uniform. Since concentrates appear efficacious in the majority of clinical situations that require the use of blood products, they should be preferred, because of their greater safety, to cryoprecipitate produced by blood banks, which cannot be virus inactivated.
Bleeding Time↗
Clinical pharmacokinetics of a placenta-derived factor XIII concentrate in type I and type II factor XIII deficiency.
Limited data are available about the pharmacokinetics of placenta-derived factor XIII (FXIII) concentrate in patients with FXIII deficiency. This concentrate contains only the active subunit A but not the carrier subunit B of the factor, and perplexities have been raised about its clinical use. Moreover, no data are available on its use in the rare patients completely lacking both subunit A and subunit B. Therefore, we evaluated the pharmacokinetics of a commercial placenta concentrate in three patients with FXIII deficiency: two lacking subunit A (type II) and one lacking both subunits (type I). The elimination half-life of the infused placenta subunit A in the three patients was very similar (280, 283, and 272 hr) and was also consistent with the previously reported data for plasma-derived FXIII. No thrombin-independent activity was observed in our concentrate batches. The recovery was significantly lower in the type I patient, in whom infusion of subunit A was not able to elicit a monthly increment of subunit B, as usually observed in type II patients. Monthly infusions of placenta concentrate (at higher dosage in type I patient) have been administered to our patients for two to three years and no evidence of inhibitor against factor XIII activity has been observed. We conclude that placenta concentrates may be as effective as plasma derivatives in replacement therapy of factor XIII deficiency, even in patients who lack subunit B.
Adult↗
Hepatocellular carcinoma in hemophilia.
A questionnaire-based survey involving 11,801 hemophiliacs from 54 hemophilia centers in the USA and Europe documented the occurrence of hepatocellular carcinoma (HCC) in 10 patients. The crude rate of HCC was 3.2/100,000 patients/year, at least 30 times higher than the background incidence of this tumor in the countries of origin of the patients. All patients were Caucasians with hemophilia A, 39 to 74 years of age, and had liver cirrhosis. All had one or more risk factor for cirrhosis and HCC: 5 were positive for serum hepatitis B surface antigen, 4 had the antibody to hepatitis C virus, and 4 had histories of alcohol abuse. Serum alpha-fetoprotein, measured in 6 patients, was significantly elevated in 4 (range: 807-1399 ng/ml), and only moderately elevated in 2 (25 and 171 ng/ml). The onset of HCC was asymptomatic in 5 patients, whereas it was accompanied by jaundice, abdominal pain, or ascites in the remaining patients. Thus, HCC seems to be a more important secondary disease for hemophiliacs than formerly recognized. Since HCC is often asymptomatic, screening hemophiliacs with chronic liver disease with periodic ultrasound scans might increase the changes of detecting HCC at a stage amenable to surgical treatment.
Adult↗
Clinical indications for desmopressin (DDAVP) in congenital and acquired von Willebrand disease.
In the majority of patients with congenital and acquired von Willebrand disease (vWD), desmopressin (DDAVP) is able to increase circulating factor VIII coagulant (VIII: C) to levels sufficient to secure satisfactory hemostasis. The bleeding time (BT) is also often normalized. In this review, all cases of vWD treated with DDAVP for the prevention or control of hemorrhage and reported in the literature for whom at least basal and peak values of VIII:C were available have been analysed. When reported, the effect on the BT was also considered. It appears that, in keeping with clinical experience gained with blood products, the correction of VIII:C defect is often sufficient to secure normal hemostasis. The only significant exception is mucosal bleeding, for which the correction of BT also appears to be necessary. Several patients (mainly with type I vWD) with basal VIII:C levels of 5-10% have been successfully treated to prevent bleeding after tooth extractions and minor surgery and to control spontaneous and post-traumatic bleeding. Experience with DDAVP in major surgery is still limited, so that the compound cannot be recommended for routine use. In acquired vWD, a trial with DDAVP is advised before resorting to substitutive therapy with blood derivatives. Since side effects to DDAVP treatment are limited and no major complications have been consistently demonstrated, DDAVP can be proposed as the treatment of first choice for most patients with vWD. The recent availability of concentrated preparations of DDAVP for intranasal administration and the demonstration that the subcutaneous route is an effective and simpler alternative to the intravenous route should further facilitate its use and make home-therapy feasible.
Deamino Arginine Vasopressin↗
Parallel line bioassay in a coagulation laboratory. A program for personal computer use and an example application to Ristocetin Cofactor assay.
The authors review the statistical principles of parallel line bioassay and describe a computer program written to facilitate a correct approach to most coagulation assays. This program should be especially useful for those assays in which linearization of dose-response curves may prove difficult, or in which careful analysis of assay validity is required. How the knowledge of bioassay theory can be applied to von Willebrand factor Ristocetin Cofactor activity measurement is shown as a general example.
Biological Assay↗
[Essential thrombocythemia: clinical aspects].
Explore the source record for details and available documents.
Adult↗
Fibrinogen assays: a collaborative study of six different methods. C.I.S.M.E.L. Comitato Italiano per la Standardizzazione dei Metodi in Ematologia e Laboratorio.
This collaborative study, organized by the Hemostasis Subcommittee of C.I.S.M.E.L., evaluated the accuracy, precision, and comparability of the following six widely used fibrinogen assays: total clottable fibrinogen (Blombäck and Blombäck), clotting time (Von Clauss), turbidimetry (Ellis and Stransky), Chromotime System, prothrombin time (PT)-derived, and radial immunodiffusion (RID). The same frozen samples, with normal and high contents of fibrinogen, were examined in four laboratories. The methods were calibrated with an internal standard whose fibrinogen content was determined gravimetrically. Both the Von Clauss and the RID methods were reliable, accurate, and precise, if adequate calibration was used. The PT-derived method was highly reproducible, but had some problems with accuracy. We demonstrate that an adequate calibration procedure is indispensable for reliable fibrinogen measurements whatever method is used. Because neither the calibration procedures proposed by the manufacturers nor the use of lyophilized commercial plasmas is adequate for this purpose, we urge that an international standard for fibrinogen measurement be promptly established.
Calibration↗
von Willebrand factor antigen is less sensitive than ristocetin cofactor for the diagnosis of type I von Willebrand disease--results based on an epidemiological investigation.
Recently, in an epidemiological investigation involving 1,218 children aged 11-14, we demonstrated that the prevalence of von Willebrand's disease, based on a low ristocetin cofactor activity (RiCof) in children with a personal and/or family history of hemorrhage, was at least 1% (Blood 1987; 69: 454). All the diagnosed cases had multimeric patterns typical of type I von Willebrand's disease (vWd). Since standardization of RiCof is difficult and the test is not easily performed in a clinical laboratory, we measured von Willebrand factor antigen (vWf:Ag) in all available unthawed plasma samples of previously investigated children by ELISA, to assess the relative sensitivity of this more simple test for diagnosing vWd. Separate normal ranges were calculated by non-parametric methods for 0 and non-0 subjects, and for children and adults, since values were higher in non-0 subjects and in children. Taking into account the 90% confidence interval around the lower limit of the normal range, 7 (50%) of the 14 cases diagnosed by RiCof were detected by vWf:Ag. Furthermore, two new cases would have been diagnosed by vWf:Ag, leading to a relative Ag/RiCof global sensitivity of 64%. A similar figure was obtained when the two tests were compared in the group of relatives of the affected children. In conclusion, measurement of vWf:Ag seems to be definitely less sensitive than the RiCof assay for detecting patients with vWd, even in type I patients, and RiCof remains the test of choice for screening for vWd in hemorrhagic patients.
Adult↗
Platelet adhesion to collagen in subtypes of type I von Willebrand's disease is dependent on platelet von Willebrand factor.
Von Willebrand's disease type I, characterized by low levels of factor VIII coagulant activity (VIII: C), von Willebrand factor antigen (vWF:Ag) and ristocetin cofactor activity (RiCof) (1), can be subdivided on the basis of platelet von Willebrand factor into subtype platelet normal, platelet discordant, and platelet low (2). We have investigated the contribution of platelet von Willebrand factor in these various subtypes to platelet adhesion using the rectangular perfusion chamber of Sakariassen et al. (3) with fibrillar collagen or a fibroblast matrix as adhesive surfaces. Platelet adhesion to fibrillar collagen was decreased in all subtypes of von Willebrand's disease, but not as low as in severe von Willebrand's disease. A close correlation was observed between platelet adhesion to collagen and plasma vWF:Ag in severe von Willebrand's disease, subtype platelet low, subtype platelet discordant, and normal controls. The platelet adhesion in subtype platelet normal was higher than expected from the plasma vWF:Ag level. Perfusions in which washed platelets were added to a human albumin solution together with red blood cells gave similar adhesion values in subtype platelet normal and normal controls; adhesion was decreased in subtype platelet discordant, and the lowest values were found in subtype platelet low and in severe von Willebrand's disease. These data indicate that platelet von Willebrand factor may contribute to platelet adhesion, when plasma von Willebrand factor is low. Perfusion studies over a fibroblast matrix gave similar low adhesion values for subtype platelet low and platelet normal, indicating that the contribution of platelet von Willebrand factor can only be observed on a strongly activating surface such as fibrillar collagen.
Antigens↗