HYPOTHYROIDISM AND ACQUIRED VON WILLEBRAND'S DISEASE

1987 ◽  
Author(s):  
F E Preston ◽  
M Greaves ◽  
B Sampson ◽  
P B A Kernoff ◽  
G Savidge ◽  
...  
Keyword(s):  
Factor Viii ◽  
Inverse Correlation ◽  
Factor Ix ◽  
Bleeding Tendency ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Thyroxine Therapy ◽  
Type Ia ◽  
The Relationship ◽  
Normal Controls

A diagnosis of type IA von Willebrand's disease was made in three patients presenting with a mild bleeding tendency. Previously unrecognised hypothyroidism was also confirmed in two patients. In the third, hypothyroidism was diagnosed four years after initial presentation. In all three patients, thyroxine therapy was associated with correction of the haemostatic defect and resolution of the bleeding tendency.The association of von Willebrand's disease and hypothyrodism prompted us to examine the relationship between thyrotrophin (TSH), T3, T4 and components of the factor VIII complex in 12 patients with clinical and biochemical hypothyroidism. Factor IX was also studied. Mean VIII:C (measured by 2 stage assay) was 0.90 u/ul (range 0.55 - 1.14); mean vWF:Ag 0-83 u/ul (range 0.44 - 1.64); mean VIII:Rcof 0.75 (range 0.45 - 1.55); mean factor IX 0.72 (range 0.39 - 1.19). Multimeric analysis of vWF:Ag performed in samples from 8 patients was normal. VIII:Rcof levels were significantly lower than those of normal controls. A significant inverse correlation was obtained between TSH and factor IX and T4 and vWF:Ag. Although there is a definite inverse relationship between TSH and factor IX, this is not evident with respect to factor VIII and a different mechanism is probably responsible for the modest reduction of vWF:Ag and the occurrence of clinically-evident von Willebrand's disease which we have demonstrated in a small proportion of hypothyroid patients.

scholarly journals Immunologic Studies in Patients with Von Willebrand’s Disease

1977 ◽  
Author(s):  
D. Böttcher ◽  
K. Hasler ◽  
A.H. Sutor
Keyword(s):  
Factor Viii ◽  
Electrophoretic Mobility ◽  
Clinical Symptoms ◽  
Common Finding ◽  
Bleeding Tendency ◽  
Factor Viii Activity ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Ristocetin Cofactor ◽  
Ristocetin Cofactor Activity

An abnormal electrophoretic mobility of factor VIII related antigen(VIIIRAg) is a well known finding in patients with variants of von Willebrand’s disease (vWd), but it has also been described in patients with typical vWd. We have studied 12 patients with vWd and 5 members of a family with a variant of the disease, characterized by normal factor VIII activity and normal VIIIRAg but low or absent ristocetin cofactor activity. The electrophoretic mobility of VIIIRAg as measured by two dimensional immunelectrophoresis at pH 8.6 was grossly abnormal in all patients with a variant of vWd corresponding to the bleeding tendency. This correlation between clinical symptoms and abnormal electrophoretic mobility of VIIIRAg was not found in those patients with vWd, in whom the mobility of VIIIRAg was also grossly abnormal. Chromatography of cryoprecipitate from patients with the described variant of vWd revealed a delayed elution of VIIIRAg with a characteristic pattern, whereas the patients with typical vWd but abnormal electrophoretic mobility of VIIIRAg had normal elution patterns. It is suggested that an abnormal electrophoretic mobility of VIIIRAg is a common finding also in patients with typical vWd.

Influence Of High Molecular Weight Factor VIII On The Expression Of Factor VIII Procoagulant Activity

1981 ◽  
Author(s):  
W Muntean ◽  
W E Hathaway ◽  
R R Montgomery
Keyword(s):  
Molecular Weight ◽  
Factor Viii ◽  
High Molecular Weight ◽  
Procoagulant Activity ◽  
Two Stage ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
The One ◽  
Relationship Of ◽  
The Relationship

The relationship of the high molecular weight (HMW) moiety and low molecular weight (LMW) moiety of factor VIII in expressing procoagulant activity (VIII C) was studied. LMW VIII C was prepared by immunoadsorbent chromatography; HMW VIII was prepared by chromatographing hemophilic cryo- precipitate in 4% agarose. The LMW VIII C obtained by immunoadsorbent chromatography gave higher VIII C values when tested in the one stage partial thromboplastin time (PTT) system using von Willebrand’s disease plasma as substrate than using hemophilic plasma as substrate. This finding was shown to be due to the VIII related antigen (VIIIR:Ag) in the substrate plasmas. When the VIIIR:Ag was removed from the hemophilic substrate plasma by immuno-adsorption, the VIII C values obtained for the LMW VIII C were higher. Also, adding purified HMW VIII to the von Willebrand’s disease substrate plasma resulted in lower VIII C values for the LMW VIII C in the PTT system.When the LMW VIII C was tested in the two stage assay, all VIII C was adsorbed to A1(0H)3. The adsorption of the LMW VIII C was prevented by mixing it with hemophilic plasma. From normal undiluted plasma only 5-21% of VIII C and no VIII related antigen were adsorbed to A1(OH)3, but after activation of the factor VIII of normal plasma by small amounts of thrombin, most of the VIII C was adsorbed. No VIII related antigen was adsorbed after activation.Nevertheless, when unadsorbed LMW VIII C was assayed by the two stage method both with and without HMW VIII or VIIIR:Ag, the results were the same.Our studies suggest that VIIIR:Ag prevents to some extent the activation of LMW VIII C. LMW VIII C that is not bound or protected by VIIIRiAg is adsorbed from plasma by A1(0H)3. These findings may help explain the differences for VIII C found in some patients and certain clinical circumstances with the one and two stage assays.

Genetic disorders of coagulation

2020 ◽  
pp. 5532-5546
Author(s):  
Eleanor S. Pollak ◽  
Katherine A. High
Keyword(s):  
Endothelial Cells ◽  
Factor Viii ◽  
Soft Tissues ◽  
Factor Ix ◽  
Autosomal Dominant Disorder ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Clinical Procedures ◽  
Joint Deformity ◽  
Prolonged Aptt

Haemophilia is a familial X-linked disorder due to deficiency of either factor VIII (haemophilia A) or factor IX (haemophilia B), components of the intrinsic enzymatic complex that activates factor X. Clinical features and diagnosis—the main manifestations are bleeding into joints and soft tissues, with haemophilic arthropathy and joint deformity being inevitable complications in untreated patients. Other features include pseudotumours, bleeding into the urinary system, and bleeding following clinical procedures. Laboratory diagnosis is based on a modification of the classic activated partial thromboplastin time (APTT) assay, with inhibitor screening used to exclude other causes of prolonged APTT. Treatment—involves the administration of the deficient factor VIII or factor IX, most commonly ‘on demand’ in response to bleeding, with prophylactic treatment given before surgery. Von Willebrand’s disease is a common autosomal dominant disorder of platelet function caused by a functional deficiency of von Willebrand factor (VWF). VWF, normally synthesized by megakaryocytes, prevents degradation of factor VIII; VWF, also made by endothelial cells, enhances platelet activation and recruitment at sites of tissue damage. Treatment—mild von Willebrand’s disease is treated with desmopressin 1-deamino-8-d-arginine vasopressin (DDAVP), which releases factor VIII and VWF from endothelial cells. Other treatments include ε‎-aminocaproic acid, oestrogens, and factor VIII concentrates. Other hereditary disorders of coagulation, including (1) hereditary deficiency of the plasma metalloproteinase ADAMTS13; (2) combined deficiency of coagulation factors V and VIII; (3) factor XI deficiency; (4) inherited deficiencies of factors II, V, VII, and X; and (5) deficiency of the contact activating factors, factor XIII, and fibrinogen, and hypercoagulable diseases due to deficiencies of anticoagulants or propensity to thrombosis are discussed in this chapter.

Factor VIII-Related Activities in Normal, Haemophilic and von Willebrand’s Disease Platelet Fractions

1978 ◽  
Vol 40 (02) ◽  
pp. 288-301 ◽  
Author(s):  
P Meucci ◽  
I R Peake ◽  
A L Bloom
Keyword(s):  
Factor Viii ◽  
Electrophoretic Mobility ◽  
Concanavalin A ◽  
Freezing And Thawing ◽  
Von Willebrand's Disease ◽  
Factor Viii Related Antigen ◽  
Von Willebrand’S Disease ◽  
Normal Plasma ◽  
Significant Difference ◽  
Ristocetin Cofactor

SummaryFactor VIII-related activities have been studied in platelet fractions in order to try to reconcile the conflicting findings of other workers, and to extend the studies. In platelets from 16 normal subjects procoagulant factor VIII was not detected. The amount of factor VIII-related antigen (FVIIIR: AG) in the cytosol per mg of protein was about twice that in the membrane fraction and about ten times that in the debris fraction. There was no significant difference between the amount of FVIIIR: AG and ristocetin cofactor (RistCof) activity in each fraction. The findings in haemophilic platelets were similar. In von Willebrand’s disease (vWd) one serverely affected patient had no detectable factor VIII related activities in any platelet fraction. In 5 patients with intermediate vWd results were normal. In a further 5, with more prolonged bleeding times, no FVIIIR: RistCof was detected in platelets, despite a normal amount of FVIIIR: AG in the cytosol and debris. The electrophoretic mobility of cytosol FVIIIR: AG was increased in all normals and patients, while that in the membrane and debris fractions had normal mobility. Cytosol FVIIIR: AG eluted later than normal FVIIIR: AG on gel filtration on Sepharose 2B, and also showed reduced antibody binding in an immunoradiometric assay. Precipitation of FVIIIR: AG by concanavalin A was incomplete in all platelet fractions from normals, and even more reduced in vWd platelet fractions. The results suggest the possibility of two types of platelet FVIIIR: AG.A factor VIII-related antigen was shown to be associated with normal washed platelets by immunofluorescence techniques (Bloom et al. 1973). Since then, several studies have been reported on the localisation of factor VIII related antigen (FVIIIR: AG), factor VIII procoagulant activity (FVIII: C) and factor VIII related ristocetin cofactor activity (FVIIIR: RistCof) within the platelets. Initially, Howard et al. (1974) indicated that FVIIIR: AG was firmly bound to the platelet membrane, and noted that in lysed platelets the level of FVIIIR: AG as measured by electroimmunodiffusion was higher than that in whole platelet suspensions. However, further studies by Nachman and Jaffe (1975) showed that FVIIIR: AG was also present to a considerable extent in the granules, and they detected none in the platelet cytosol. Bouma and colleagues (1975) were, however, able to find FVIIIR: AG and FVIIIR: RistCof in the cytosol upon freezing and thawing platelets. This FVIIIR: AG had an electrophoretic mobility comparable to that of normal plasma. They also noted that platelets which were air dried apparently had a granular FVIIIR:AG localisation by immunfluorescence; however, intact platelets in suspension did not stain by this method.Recently Ruggeri et al. (1977) and Sultan et al. (1977) have also found FVIIIR: AG in the cytosol, and the former authors reported it to have increased electrophoretic mobility when compared to normal plasma FVIIIR:AG. Results concerning the localisation of FVIIIR: AG in normal platelets have thus been conflicting. Similarly, in the few reports available concerning platelet FVIIIR: AG in von Willibrand’s disease variable results have also been obtained (Ruggeri et al. 1977, Howard et al. 1974, Shearn et al. 1974 and Bouma et al. 1975).In this study we report on the localisation of factor VIII-related activities in normal, haemophilic and von Willebrand’s disease platelets using available standard techniques as well as precipitation of FVIIIR: AG with the plant lectin concanavalin A, a procedure which has been shown to detect abnormal forms of FVIIIR:AG in certain types of von Willebrand’s disease (Peake and Bloom 1977).

Studies on the Characterization of Factor VIII and a Co-factor VIII

1974 ◽  
Vol 31 (02) ◽  
pp. 328-338
Author(s):  
M. M. P Paulssen ◽  
H. L. M. A Vandenbussche-Scheffers ◽  
P. B Spaan ◽  
T de Jong ◽  
M. C Planje
Keyword(s):  
Molecular Weight ◽  
Factor Viii ◽  
The Body ◽  
Haemophilia A ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Polysaccharide Content ◽  
Plasma Factor ◽  
Two Factors

SummaryFactor VIII occurs in the body in two different forms. In lymph factor VIII is bound to chylomicra. In plasma, factor VIII is bound to a protein.After delipidation of chylomicra we obtained a glycoprotein with a high polysaccharide content and a molecular weight of approx. 160,000.In plasma, factor VIII is attached to a protein which is present in normal concentrations in plasma of patients with haemophilia A and in serum (co-factor VIII).This factor is deficient in both the plasma and the serum of patients with von Willebrand’s disease.The binding between factor VIII and co-factor VIII is reversible.Some properties of these two factors are described.

The Spectrum of von Willebrand’s Disease

1967 ◽  
Vol 18 (01/02) ◽  
pp. 040-056 ◽  
Author(s):  
E. J Walter Bowie ◽  
P Didisheim ◽  
J. H Thompson ◽  
C. A Owen
Keyword(s):  
Factor Viii ◽  
Bleeding Time ◽  
Severe Bleeding ◽  
Platelet Adhesiveness ◽  
Platelet Activity ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
The Third ◽  
Generation Test

SummaryPatients (from 5 kindreds) with variants of von Willebrand’s disease are described. In one kindred the depression of factor VIII was moderate (20 to 40% of normal) and transfusion of 500 ml of normal plasma led to an increase higher than anticipated and to an almost normal level of factor VIII 17 to 24 hrs later. This represents the usual type of von Willebrand’s disease.In the second kindred the concentration of factor VIII was less than 2 % of normal in the son and daughter, who had severe bleeding and hemarthroses.The third kindred was characterized by reduction of factor VIII and a long bleeding time as well as by a serum defect in the thromboplastin-generation test comparable to that seen in patients with hemophilia B, yet with normal levels of factors IX, X, and VII. The severity of the serum defect, the positive result with the Rumpel-Leede test, and the reduced platelet activity in the thromboplastin-generation test are all compatible with the diagnosis of thrombopathy or ‘‘thrombopathic hemophilia.” In two other kindreds, one patient had a long bleeding time and normal levels of factor VIII and another had a normal bleeding time and decrease of factor VIII. The last patient had the type of response to transfusion usually seen in von Willebrand’s disease.In four kindreds, platelet adhesiveness in vivo was found to be strikingly abnormal (virtually absent).It would appear, therefore, that von Willebrand’s disease forms a spectrum, and whether the kindreds reported simply reflect variations of a single genetic disease state or represent separate entities will be answered only by clarification of the underlying etiology of that disease.

A Simple Enzyme-Immunoassay (EIA) Test for Factor VIII-Related Antigen (VIIIAGN)

1979 ◽  
Vol 42 (03) ◽  
pp. 848-854 ◽  
Author(s):  
Paul M Ness ◽  
Herbert A Perkins
Keyword(s):  
Factor Viii ◽  
Enzyme Immunoassay ◽  
Hemophilia A ◽  
Single Sample ◽  
Healthy Controls ◽  
Von Willebrand's Disease ◽  
Factor Viii Related Antigen ◽  
Von Willebrand’S Disease ◽  
Increased Sensitivity

SummaryAn enzyme immunoassay (EIA) system has been developed to measure factor VIII- related antigen (VIIIAGN). This assay gives similar results to the commonly used Laurell electroimmunodiffusion (EID) assay for VIIIAGN as shown by comparison of both techniques with samples from healthy controls, patients with hemophilia A, and patients with von Willebrand’s disease. The assay also has a greater precision than the EID technique as demonstrated by multiple assays of aliquots of a single sample. The use of this EIA test for VIIIAGN is simple and employs inexpensive reagents and equipment. The use of expensive antisera is minimized. EIA for VIIIAGN has the advantage of increased sensitivity compared to Laurell EIA.

Factor VIII Antigen in the Vessel Walls in Von Willebrand's Disease and Haemophilia A

2009 ◽  
Vol 13 (1) ◽  
pp. 33-38 ◽  
Author(s):  
L. Holmberg ◽  
P. M. Mannucci ◽  
I. Turesson ◽  
Z. M. Ruggeri ◽  
I. M. Nilsson
Keyword(s):  
Factor Viii ◽  
Haemophilia A ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Factor Viii Antigen ◽  
Vessel Walls

Comparison of the O’Brien Filter Test and the PFA-100 Platelet Analyzer in the Laboratory Diagnosis of von Willebrand’s Disease

2000 ◽  
Vol 84 (07) ◽  
pp. 88-92 ◽  
Author(s):  
Agota Schlammadinger ◽  
Adrienne Kerenyi ◽  
Laszlo Muszbek ◽  
Zoltan Boda
Keyword(s):  
Bleeding Time ◽  
Second Phase ◽  
Bleeding Tendency ◽  
High Shear ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Time Determination ◽  
Filter Test ◽  
Type 3

SummaryVon Willebrand’s disease (vWD) is the most common congenital haemorrhagic diathesis, characterized by the quantitative or qualitative disorder of von Willebrand factor (vWF). A number of methods have been used for the diagnosis of the disease, and the bleeding time determination is widely accepted as a screening test in spite of its low sensitivity. Our aim was to evaluate and compare the performance of two high shear systems (the O’Brien filter test and the PFA-100 device) in the screening and diagnosis of vWD. Thirty patients (n=13 type 1 with mild symptoms, n = 9 type 1 with severe symptoms, n = 2 type 2A, n = 3 type 2B and n = 3 type 3 vWD) and twenty controls were investigated. In mild vWD the platelet retention in the second phase of the filter test with citrated blood showed the highest sensitivity (91.6%). The sensitivity of the PFA-100 method with collagen-epinephrine cartridges in this group was 76.9%, while the bleeding time was prolonged only in 15.4% of the cases. In severe type 1, in type 2A and type 3 all functional tests reflected the bleeding tendency of the patients. In type 2B disease the bleeding time was prolonged only when the patient was thrombocytopenic, but both high shear systems revealed the disease independently of the presence of thrombocytopenia. The overall sensitivity of the bleeding time determination was 50% compared to the 80-90% sensitivity of the O’Brien filter test and the PFA-100 system. The sensitivity values of the filter test and the PFA-100 device with collagen-epinephrine cartridges were in the same range, but the collagen-ADP cartridges showed a lower (65.5%) sensitivity, though the results were specific and had high positive predictive value. We conclude that both high shear systems are suitable for the screening of vWD, and that they are superior to the traditional bleeding time determination in case of mild disease or type 2B vWD.

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