scholarly journals Lupus anticoagulants: improved diagnosis with a kaolin clotting time using rabbit brain phospholipid in standard and high concentrations

Blood ◽  
1986 ◽  
Vol 68 (2) ◽  
pp. 472-478 ◽  
Author(s):  
MH Rosove ◽  
M Ismail ◽  
BJ Koziol ◽  
A Runge ◽  
CK Kasper
Keyword(s):  
Lupus Erythematosus ◽  
Coagulation Factor ◽  
Rabbit Brain ◽  
Bleeding Tendency ◽  
Clotting Time ◽  
Lupus Anticoagulants ◽  
Normal Limits ◽  
Brain Phospholipid ◽  
High Concentrations ◽  
Kaolin Clotting Time

Abstract We utilized a kaolin-activated partial thromboplastin time (APTT) using rabbit brain phospholipid, in which the capacity of a fourfold increased “high” phospholipid concentration (PC) to normalize the abnormal “standard” PC-APTT in patients with lupus anticoagulants is assessed. This system was also used to measure factors VIIIC, IX, and XI. The tissue thromboplastin inhibition test (TTI), a prothrombin time system in which the activity of a lupus anticoagulant is unmasked by the use of dilute thromboplastin, was simultaneously evaluated. Test sensitivity was defined by results on 31 consecutive patients with standard PC-APTT inhibitors and no bleeding tendency. Specificity was based on 94 patients with various other coagulopathies, including coagulation factor inhibitors, severe congenital factor deficiencies, hepatic insufficiency, and warfarin and heparin treatment. Twenty-one patients with lupus erythematosus and standard PC-APTT results within normal limits were also tested. Sensitivity of the APTT system was superior to that of the TTI (97% v 58%); high PC normalized clotting time ratios and factor levels. Positive results were common with both assays in the group of 20 heparinized patients. The APTT system had superior specificity in remaining cases; there were no positive tests among 74 patients. The lupus erythematosus group had a significant decrease in the clotting time ratio with high PC, indicating that low- level lupus anticoagulants are quite prevalent in this group. The kaolin clotting time using rabbit brain phospholipid in standard and high concentrations is a simple, sensitive, and specific technique for diagnosis of lupus anticoagulants.

scholarly journals Lupus anticoagulants: improved diagnosis with a kaolin clotting time using rabbit brain phospholipid in standard and high concentrations

Blood ◽  
1986 ◽  
Vol 68 (2) ◽  
pp. 472-478
Author(s):  
MH Rosove ◽  
M Ismail ◽  
BJ Koziol ◽  
A Runge ◽  
CK Kasper
Keyword(s):  
Lupus Erythematosus ◽  
Coagulation Factor ◽  
Rabbit Brain ◽  
Bleeding Tendency ◽  
Clotting Time ◽  
Lupus Anticoagulants ◽  
Normal Limits ◽  
Brain Phospholipid ◽  
High Concentrations ◽  
Kaolin Clotting Time

We utilized a kaolin-activated partial thromboplastin time (APTT) using rabbit brain phospholipid, in which the capacity of a fourfold increased “high” phospholipid concentration (PC) to normalize the abnormal “standard” PC-APTT in patients with lupus anticoagulants is assessed. This system was also used to measure factors VIIIC, IX, and XI. The tissue thromboplastin inhibition test (TTI), a prothrombin time system in which the activity of a lupus anticoagulant is unmasked by the use of dilute thromboplastin, was simultaneously evaluated. Test sensitivity was defined by results on 31 consecutive patients with standard PC-APTT inhibitors and no bleeding tendency. Specificity was based on 94 patients with various other coagulopathies, including coagulation factor inhibitors, severe congenital factor deficiencies, hepatic insufficiency, and warfarin and heparin treatment. Twenty-one patients with lupus erythematosus and standard PC-APTT results within normal limits were also tested. Sensitivity of the APTT system was superior to that of the TTI (97% v 58%); high PC normalized clotting time ratios and factor levels. Positive results were common with both assays in the group of 20 heparinized patients. The APTT system had superior specificity in remaining cases; there were no positive tests among 74 patients. The lupus erythematosus group had a significant decrease in the clotting time ratio with high PC, indicating that low- level lupus anticoagulants are quite prevalent in this group. The kaolin clotting time using rabbit brain phospholipid in standard and high concentrations is a simple, sensitive, and specific technique for diagnosis of lupus anticoagulants.

Relative Sensitivity of Different Tests in the Detection of Low Titer Lupus Anticoagulants

1988 ◽  
Vol 60 (02) ◽  
pp. 217-219 ◽  
Author(s):  
B Lesperance ◽  
M David ◽  
J Rauch ◽  
C Infante-Rivard ◽  
G E Rivard
Keyword(s):  
Relative Sensitivity ◽  
Fetal Outcome ◽  
Anticardiolipin Antibodies ◽  
Lupus Anticoagulants ◽  
Normal Plasma ◽  
Coagulation Tests ◽  
High Dilutions ◽  
Tissue Thromboplastin ◽  
High Concentrations ◽  
Kaolin Clotting Time

SummaryLupus anticoagulants (LA) and anticardiolipin antibodies have been strongly associated with recurrent abortion and fetal death. Because steroids have been reported to improve the fetal outcome of LA associated pregnancies, presumably by decreasing the levels of LA, it becomes desirable to have a simple and reliable test to monitor the levels of the putative antibody. To this effect, we assessed the capacity of the following coagulation tests to detect the presence of LA in serial dilutions of patient plasma with pooled normal plasma: kaolin clotting time (KCT), tissue thromboplastin inhibition test (TTIT), dilute Russell Viper venom time (DRVVT) and activated partial thromboplastin time with standard and high concentrations of phospholipids (SC and HCAPTT). All samples were also evaluated for the presence of anticardiolipin antibodies with an ELISA. The KCT was able to detect LA at a much greater dilution in normal plasma than any of the other clotting assays. The ELISA was comparable to KCT in its ability to detect high dilutions of LA.

dRVVT Is more Sensitive than KCT or TTI for Detecting Lupus Anticoagulant Activity of Anti-β2-glycoprotein I Autoantibodies

1999 ◽  
Vol 81 (02) ◽  
pp. 256-258 ◽  
Author(s):  
A. Biasiolo ◽  
P. Rampazzo ◽  
T. Brocco ◽  
V. Pengo
Keyword(s):  
Lupus Anticoagulant ◽  
Anticoagulant Activity ◽  
Test System ◽  
Clotting Time ◽  
Lupus Anticoagulants ◽  
Glycoprotein I ◽  
Tissue Thromboplastin ◽  
The Mean ◽  
Kaolin Clotting Time ◽  
Antibody Preparations

SummaryAnti-β2-glycoprotein I (β2-GPI) antibodies behave as classical Lupus Anticoagulants (LA), as they inhibit phospholipid-dependent coagulation reactions and their activity disappears in the presence of excess exogenous phospholipids (PLs). We have recently shown that a certain amount of PLs in the dilute Russell Viper Venom Time (dRVVT) test system is required to express LA activity of anti β2-GPI antibodies. We have now extended this observation to two other tests, i.e., Kaolin Clotting Time (KCT) in which PLs are not added, and Tissue Thromboplastin Inhibition test (TTI) in which PLs are extremely diluted. In fact, affinity-purified antibody preparations from 5 patients with antiphospholipid syndrome did not express or only weakly expressed anticoagulant activity in both tests; the mean ratios of coagulation times obtained with purified antibodies and that of control buffer were 1.11 and 1.0 for KCT and TTI, respectively. On the contrary, the mean ratios in dRVVT were 1.31 and 1.49 at a PLs dilution of 1:8 and 1:64, respectively. Therefore, the presence of LA activity due to autoantibodies to β2-GPI is characterized by a positive dRVVT and negative or only weakly positive KCT and TTI.

COMPARISION OF THE DETECTION OF LUPUS ANTICOAGULANTS USING THREE DIFFERENT METHODS AND THE PRESENCE OF ANTI-CARDIOLIPIN ANTIBODIES

1987 ◽  
Author(s):  
A Criel ◽  
B Gilbert ◽  
A Van Hoof ◽  
M Hidajat ◽  
A Louwagie
Keyword(s):  
Elisa Test ◽  
Activated Partial Thromboplastin Time ◽  
Detection Methods ◽  
Recurrent Abortion ◽  
Clotting Time ◽  
Lupus Anticoagulants ◽  
Cardiolipin Antibodies ◽  
Tissue Thromboplastin ◽  
Kaolin Clotting Time

Lupus anticoagulant (LAC) is an antibody directed against phospholipids which prolongs in vitro clotting assays. Several detection methods have been described; however all give some different results. Recently ELISA and RIA assays have been developed which detect IgG and IgM anti-cardiolipin antibodies. The aim of our study was to compare three different LAC tests with an ELISA anti-cardiolipin test. The tests used were : kaolin clotting time (KCT or Exnertest), tissue thromboplastin inhibition test (TTI or Schleider test), activated partial thromboplastin time using a 50, 100, 200 fold dilution of the phospholipid preparation (APTT dilution test), and an IgG and IgM anti-cardiolipin ELISA test. 114 samples of patients suffering from diseases known to be accompanied with LAC antibodies (auto-immune diseases, recurrent abortion, thromboembolism, etc.) were studied. Positivity with one of the tests was found in 45 patients (39%). Patients with the diagnosis of SLE or otherimmune diseases showed the highest positivity (56%) whereas those with thromboembolism, recurrent abortion etc. were only positive in 27%.Among these 45 positive patients the TTI was positive in 41 cases (91 %);however in 10 cases (24 %) this was the only positivity found. The KCT test and the APTT dilution test were both positive in 18 cases (40 %). Anti-cardiolipin antibodies were found in 21 patients (47 %): IgG only in 12 (27 %), IgM only in 5 (11 %), both IgG and IgM in 2 (4 %); in 19 of these 21 patientsthe TTI was also positive.In our study the TTI test seems to be the most sensitive test but possibly also the test with the highest aspecific positivities. IgG and IgM anti-cardiolipin antibodies were less frequently found than expected.

Similar Mechanism of Various Lupus Anticoagulants

1985 ◽  
Vol 53 (01) ◽  
pp. 015-018 ◽  
Author(s):  
Thomas Exner
Keyword(s):  
Partial Thromboplastin Time ◽  
Clinical Symptoms ◽  
Activated Partial Thromboplastin Time ◽  
The Other ◽  
Coagulation Test ◽  
Sensitive Test ◽  
Clotting Time ◽  
Lupus Anticoagulants ◽  
Activated Platelets ◽  
Kaolin Clotting Time

SummaryPotent lupus inhibitors from various patients were mixed with platelet free normal plasma and were compared in activated partial thromboplastin time (APTT), dilute prothrombin time (dil. PT), kaolin clotting time (KCT), contact product clotting time (CPCT), and Russell viper venom clotting time (RWCT) tests. In the last three tests platelets and platelet lipid substitutes were avoided to enhance the sensitivities of these tests for the lupus anticoagulant. Correlations between the KCT and the other tests were mostly good, indicating that different lupus inhibitors functioned by a similar mechanism. There was no significant trend between particular clinical symptoms and individual coagulation test combinations. The KCT was found to be the most sensitive test for the lupus inhibitor, followed by the CPCT, RWCT, dil. PT and APTT tests. Activated platelets tended to correct the APTT lupus inhibitor defect in all except the strongest inhibitor cases.

scholarly journals Further Studies on the Abnormal Factor X (Factor X Friuli) Coagulation Disorder: A Report of Another Family

Blood ◽  
1971 ◽  
Vol 37 (5) ◽  
pp. 534-541 ◽  
Author(s):  
A. GIROLAMI ◽  
M. LAZZARIN ◽  
R. SCARPA ◽  
A. BRUNETTI
Keyword(s):  
Normal Serum ◽  
Factor Vii ◽  
White Female ◽  
Coagulation Disorder ◽  
Recessive Trait ◽  
Bleeding Tendency ◽  
Factor X ◽  
Clotting Time ◽  
Serum Factors ◽  
Normal Limits

Abstract Another patient with a congenital coagulation disorder due to the presence of an abnormal factor X (factor X Friuli) is presented. The proposita was a 43-yr-old white female who had a bleeding tendency from early childhood (epistaxes, monorrhagias, bleeding after tooth extractions and other surgical procedures, posttraumatic hemarthroses, bleeding from the gums and postpartum hemorrhages). The coagulation work-up demonstrated a prolonged prothrombin time, prolonged partial thromboplastin time, abnormal prothrombin consumption, and abnormal thromboplastin generation corrected by normal serum. Factors II, V, VII, IX, and XII were within normal limits. Platelets, vascular tests and fibrinolysis were normal. Mr. Stuart’s plasma failed to correct the defect of the proposita’s plasma, but a known factor VII deficient plasma was able to correct the abnormality. The factor X assay was low (6-9%) only when tissue thromboplastin, whole or partial, was used. When Factor X was assayed with a Stypven-cephalin mixture, normal or near normal values were observed. Likewise, the Stypven-cephalin clotting time, the Stypven clotting time and the factor II + factor X level using a Stypven-cephalin mixture were normal. The presence of the abnormal factor X was demonstrated immunologically. The defect, like classical factor X deficiency, is transmitted as an autosomal incompletely recessive trait. The mother and the two children of our proposita had factor X levels varying from 38 to 56% of normal and were considered to be heterozygotes.

Lupus Anticoagulants and Thrombosis: Clinical Association of Different Coagulation and Immunologic Tests

2000 ◽  
Vol 84 (12) ◽  
pp. 1012-1016 ◽  
Author(s):  
Jeffrey Dlott ◽  
Francesca Norbis ◽  
Luisa Ruggeri ◽  
Linda Cler ◽  
Douglas Triplett ◽  
...  
Keyword(s):  
At Risk ◽  
Venous Thrombosis ◽  
Arterial Thrombosis ◽  
Colloidal Silica ◽  
Anticardiolipin Antibodies ◽  
Clotting Time ◽  
Lupus Anticoagulants ◽  
Glycoprotein I ◽  
Patients At Risk ◽  
Kaolin Clotting Time

SummaryThe dilute Russell’s viper venom time (dRVVT) and the kaolin clotting time (KCT) are two among the most commonly used coagulation tests for the detection of lupus anticoagulants. The dRVVT seems superior to the KCT in identifying LA-positive patients at risk of thrombosis. However, this relationship is greatly influenced by both the source of reagents and the instrumentation employed to carry out the assays. Therefore, 4 dRVVTs (“home-made” dRVVT, DVV test, Bioclot LA, LA Screen), and one KCT (Kaoclot) were performed in two centers and compared for their retrospective correlation with the thrombotic complications of 72 patients with a previously established diagnosis of lupus anticoagulants. Two other assays (“home-made” KCT, and Colloidal Silica Clotting Time, CSCT) were performed in one of the two centers, and compared with Kaoclot for their clinical correlations in the same population of patients, 44 of whom (61%) had suffered from arterial and/or venous thrombosis. A rather good degree of inter-laboratory and inter-assay correlations of the different tests was found. However, a statistically significant association with thrombosis was found only with the coagulation profile generated using the “homemade” dRVVT. When the commercially available dRVVTs were used, none of the coagulation profiles remained associated with thrombosis. When the assays were analyzed separately, the association with thrombosis was statistically significant for LA screen (p = 0.0019), DVV test (p = 0.0043), and Bioclot (p = 0.0255), and of borderline significance for the “home-made” dRVVT (p = 0.0503) in one center. This last assay was also significantly associated with thrombosis in the other center (p = 0.0139). When venous and arterial thrombosis were considered separately, DVV test was statistically associated with venous thrombosis in both centers (p = 0.0076 and p = 0.0187, respectively), and LA screen in one center (p = 0.0303). No dRVVT was found to correlate with arterial thrombosis. Kaoclot, Colloidal Silica Clotting Time, and the “home-made” KCT did not correlate with thrombosis. The prevalence of IgG and/or IgM antibodies to cardiolipin, β2-glycoprotein I and prothrombin were 74%, 86% and 85%, respectively. Increased titers of IgG anticardiolipin antibodies were associated with arterial thrombosis (p = 0.0375), whereas IgM anti-β2-glycoprotein I antibodies were associated with venous thrombosis (p = 0.0433). In conclusion, these retrospective data support the notion that the dRVVT, rather than other coagulation or ELISA tests, are able to identify lupus anticoagulant-positive patients at risk of thrombosis. This property appears common to several commercially available dRVVT kits, making this type of assay the ideal target of future efforts of laboratory standardization.

Scientific and Standardization Committee Communications Comparison of Test Methods for the Lupus Anticoagulant: International Survey on Lupus Anticoagulants-I (ISLA-1)

1990 ◽  
Vol 64 (03) ◽  
pp. 478-484 ◽  
Author(s):  
Thomas Exner ◽  
Douglas A Triplett ◽  
David A Taberner ◽  
Margaret A Howard ◽  
E Nigel Harris
Keyword(s):  
Lupus Anticoagulant ◽  
Test Methods ◽  
Positive Sample ◽  
Direct Proportion ◽  
Clotting Time ◽  
Preliminary Screening ◽  
Activated Platelets ◽  
Tissue Thromboplastin ◽  
Kaolin Clotting Time ◽  
Induced Defects

SummarySix lyophilized plasma samples were sent to 20 “expert” laboratories for assessment of lupus anticoagulant (LA). Four samples contained pooled LA of graded potency mixed with aged normal plasma. One contained LA plus cephalin phospholipid and one contained a nonspecific venom anticoagulant. Sixteen methods were used overall with some participants using up to 8 methods. Results were scored in regard to the known potencies of LA in the samples and other known induced defects.Activated partial thromboplastin time (APTT) tests used by most participants for preliminary screening were relatively sensitive, but non-specific. Platelet or phospholipid neutralization procedures (PNP) appeared to be sensitive and specific but showed a non-linear response to increased LA content. Kaolin clotting time (KCT) tests showed the most sensitive response to increased LA content but the weaker LA were not scored as abnormal by most laboratories as the samples may have contained platelet fragments. Other commonly used tests such as the tissue thromboplastin inhibition (TTI) test and the dilute Russell’s viper venom test (DRVVT) were carried out somewhat inconsistently. The variability in performance of tests in different laboratories indicates that standardization of methodology is urgently required.Generally it seemed that most clotting tests were “bypassed” by the addition of phospholipid to a known LA-positive sample in apparently direct proportion to their sensitivity. Sample preparation, especially prevention of contamination with activated platelets is a vital preliminary part in the assay of LA.

Characterization of Recombinant Human Coagulation Factor XFriuli

1996 ◽  
Vol 75 (02) ◽  
pp. 313-317 ◽  
Author(s):  
D J Kim ◽  
A Girolami ◽  
H L James
Keyword(s):  
Catalytic Domain ◽  
Coagulation Factor ◽  
Molecular Size ◽  
Binding Pocket ◽  
Site Directed Mutagenesis ◽  
Bleeding Tendency ◽  
Factor X ◽  
Amino Terminal ◽  
Normal Plasma ◽  
Plasma Factor

SummaryNaturally occurring plasma factor XFriuli (pFXFr) is marginally activated by both the extrinsic and intrinsic coagulation pathways and has impaired catalytic potential. These studies were initiated to obtain confirmation that this molecule is multi-functionally defective due to the substitution of Ser for Pro at position 343 in the catalytic domain. By the Nelson-Long site-directed mutagenesis procedure a construct of cDNA in pRc/CMV was derived for recombinant factor XFriuli (rFXFr) produced in human embryonic (293) kidney cells. The rFXFr was purified and shown to have a molecular size identical to that of normal plasma factor X (pFX) by gel electrophoretic, and amino-terminal sequencing revealed normal processing cleavages. Using recombinant normal plasma factor X (rFXN) as a reference, the post-translational y-carboxy-glutamic acid (Gla) and (β-hydroxy aspartic acid (β-OH-Asp) content of rFXFr was over 85% and close to 100%, respectively, of expected levels. The specific activities of rFXFr in activation and catalytic assays were the same as those of pFXFr. Molecular modeling suggested the involvement of a new H-bond between the side-chains of Ser-343 and Thr-318 as they occur in anti-parallel (3-pleated sheets near the substrate-binding pocket of pFXFr. These results support the conclusion that the observed mutation in pFXFr is responsible for its dysfunctional activation and catalytic potentials, and that it accounts for the moderate bleeding tendency in the homozygous individuals who possess this variant procoagulant.

Rapid Screening Methods for Bleeding Disorders. A Three Year Survey

1964 ◽  
Vol 11 (02) ◽  
pp. 506-512 ◽  
Author(s):  
V. A Lovric ◽  
J Margolis
Keyword(s):  
Laboratory Tests ◽  
Capillary Blood ◽  
Screening Tests ◽  
Rapid Screening ◽  
Screening Methods ◽  
Bleeding Disorders ◽  
Routine Laboratory ◽  
Clotting Time ◽  
Kaolin Clotting Time ◽  
In Infants And Children

SummaryAn adaptation of “kaolin clotting time” and prothrombin time for use on haemolysed capillary blood provided simple and sensitive screening tests suitable for use in infants and children. A survey of three year’s experience shows that these are reliable routine laboratory tests for detection of latent coagulation disorders.

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