Spurious Prolongation of the Activated Partial Thromboplastin Time

1977 ◽  
Vol 38 (04) ◽  
pp. 0900-0908 ◽  
Author(s):  
Robert A. Okpara ◽  
Joann Carabello ◽  
H James Day
Keyword(s):  
Partial Thromboplastin Time ◽  
Laboratory Data ◽  
Activated Partial Thromboplastin Time ◽  
Rate Of Change ◽  
Maximal Rate ◽  
Middle Stage ◽  
Normal Plasma ◽  
Prolonged Aptt ◽  
Tissue Thromboplastin ◽  
Abnormal Tissue

SummaryThe clinical and laboratory data of 8 patients (4 males and 4 females) with circulating anticoagulant were presented. Based on prolonged APTT, failure to correct the APTT with 50 % normal plasma and abnormal tissue thromboplastin inhibition test, the inhibitor was identified as “middle stage” – or the “lupus anticoagulant”. Thrombokinetics showed the maximal rate of change in optical density (VmaxΔOD) of plasma, resulting from clot formation to be significantly less in the plasma of patients with the inhibitor than in normal plasma. This was not completely corrected by mixing the patients’ plasma with 50% normal plasma.

Comparison Between a One-Point Dilute Phospholipid APTT and the Dilute Russell Viper Venom Time for Verification of Lupus Anticoagulants

1992 ◽  
Vol 67 (06) ◽  
pp. 672-678 ◽  
Author(s):  
Barbara M Alving ◽  
Charles F Barr ◽  
Lawrence E Johansen ◽  
Douglas B Tang
Keyword(s):  
Partial Thromboplastin Time ◽  
Antiphospholipid Antibodies ◽  
Test System ◽  
Bovine Brain ◽  
Activated Partial Thromboplastin Time ◽  
Clotting Time ◽  
Lupus Anticoagulants ◽  
Normal Plasma ◽  
Prolonged Aptt ◽  
Higher Sensitivity

SummaryIn the present study, the dilute Russell viper venom time (RVVT) and the dilute phospholipid activated partial thromboplastin time (PL-APTT), which are two assays used for the verification of lupus anticoagulants (LA), were modified to increase standardization. The modified assays were then compared with respect to sensitivity and specificity in detecting LA in plasmas from 72 patients with a prolonged APTT. Modifications included utilizing a single dilution of phospholipid that was either bovine brain thromboplastin (Thrombofax) or liposomes comprised of phosphatidylcholine/phosphatidylserine, and expressing the results as a ratio of the clotting times of the mixture of patient and normal plasma/clotting time of normal plasma. In the RWT, the correlation coefficient between assay results for liposomes and Thrombofax was 0.88 and in the PL-APTT, the correlation was 0.68. A positive test for LA was defined as a ratio of ≥1.3 for the PL-APTT with liposomes and ≥1.2 for the PL-APTT with Thrombofax and the RWT with Thrombofax or liposomes. Regardless of the phospholipid source in the test system, the PL-APTT demonstrated higher sensitivity and the RWT showed greater specificity in detecting patient plasmas that contained antiphospholipid antibodies.

INCIDENCE OF PROCAINAMIDE-INDUCED LUPUS ANTICOAGULANT

1987 ◽  
Author(s):  
H J Day ◽  
R Cherrey ◽  
D O'Hara ◽  
J Carabello
Keyword(s):  
Screening Test ◽  
Laboratory Data ◽  
Activated Partial Thromboplastin Time ◽  
Ambulatory Patients ◽  
Hospital Patients ◽  
Prolonged Aptt ◽  
Group A ◽  
Tissue Thromboplastin ◽  
The Difference ◽  
Group B

Isolated cases of lupus anticoagulants (LA) in association with procainamide have been reported. This study was done to estimate the frequency of LA in patients taking procainamide. Two groups of patients were evaluated: Group A: 110 hospitalized patients (84 males, 26 females, ages 51-78, mean age 74.3) and Group B: 80 ambulatory patients (54 males, 26 females, ages 36-89, mean 67.5 years). The latter group of patients was on this drug for a period of two-five years, while the former group hadbeen on drug at least two full days. All patients were screened with baseline laboratory data including activated partial thromboplastin time (APTT) and prothrombin time (PT) which were performed using Auto APTT® and Simplastin® on a Coagulamate X2® (General Diagnostics/Organon Teknika). Patients taking drugs known to alter the APTT and PT were excluded. All patients were followed with daily (hospital patients) or weekly (ambulatory patients) APTT and PT. Prolongation of the APTT of 5 sec or PT of 3 sec over baseline was considered as a positive LA screening test. Patients with a positive screening test were further evaluated with tissue thromboplastin inhibitor assay (TTI), platelet neutralization procedure (PNP, anti-nuclear antibodies (ANA) and blood serology (RPR). In Group A. 11 out of 110 (1096) developed prolonged APTT while on procainamide . Of these, 9 developed abnormal TTI and 2 had positive PNP. The ANA was positive (titers of 1:320-1:2560) in 10 patients with the only positive RPR test, being in the patient with the highest ANA titer. In Group B, 12 out of 80 (1596) developed prolonged APTT, 11 had positive TTI. The ANA titer was elevated in all positive cases, although one patient's titer was 1:30. The PNP was positive in 1/12. All blood serologies were negative in this group. The difference in incidence between Groups A and B may reflect longer exposure to drug in the latter group. This difference is not statistically significant. This study indicates that the incidence of procainamide-induced lupus antocoagulant is between 10-1596 when the APTT (or PT) is used as a screening test. The TTI and ANA seem to have equal sensitivity in this syndrome when taking this drug. The failure of the PNP to be sensitive to LA may be due to the minimal prolongation of the APTT arbitrarily chosen as representing a positive screening test.

Evaluation of Recently Described Tests for Detection of the Lupus Anticoagulant

1994 ◽  
Vol 72 (05) ◽  
pp. 728-733 ◽  
Author(s):  
Ricardo R Forastiero ◽  
Graciela S Cerrato ◽  
Luis O Carreras
Keyword(s):  
Human Placenta ◽  
Partial Thromboplastin Time ◽  
Lupus Anticoagulant ◽  
High Sensitivity ◽  
Activated Partial Thromboplastin Time ◽  
Lupus Anticoagulants ◽  
Coagulation Tests ◽  
Prolonged Aptt ◽  
Tissue Thromboplastin ◽  
Standard Tests

SummaryIt is known that lupus anticoagulants (LA) are antibodies which interfere with phospholipid-dependent coagulation tests, but due to the heterogeneity of LA and the differences in sensitivity of reagents and tests, the diagnosis of LA remains difficult.Recently, Triplett et al. (26) have proposed a new test based on two venoms, Textarin (T) and Ecarin (E), that activate prothrombin but differ in their phospholipid requirements. By testing this new assay we have evaluated 36 patient plasmas containing LA according to standard tests (activated partial thromboplastin time, dilute Russell viper venom time and platelet neutralization procedure) and our results confirm a high sensitivity for LA of the T/E test.In addition, we observed a greater sensitivity of the tissue thromboplastin inhibition test using a recombinant thromboplastin instead of a human placenta thromboplastin.Our study also showed that the T/E test seems to be a useful assay in confirming the diagnosis of LA in patients with an unexplained prolonged APTT.

scholarly journals A Rare Cause of Isolated Prolonged Activated Partial Thromboplastin Time: An Overview of Prekallikrein Deficiency and the Contact System

2021 ◽  
Vol 9 ◽  
pp. 232470962110121
Author(s):  
Ivy Riano ◽  
Klaorat Prasongdee
Keyword(s):  
Partial Thromboplastin Time ◽  
Normal Activity ◽  
Fresh Frozen Plasma ◽  
Activated Partial Thromboplastin Time ◽  
Recessive Trait ◽  
Bleeding Tendency ◽  
Contact Activation ◽  
Asymptomatic Patients ◽  
Prolonged Aptt ◽  
Fresh Frozen

Prekallikrein (PK) deficiency, also known as Fletcher factor deficiency, is a very rare disorder inherited as an autosomal recessive trait. It is usually identified incidentally in asymptomatic patients with a prolonged activated partial thromboplastin time (aPTT). In this article, we present the case of a 52-year-old woman, with no prior personal or family history of thrombotic or hemorrhagic disorders, who was noted to have substantial protracted aPTT through the routine coagulation assessment before a kidney biopsy. The patient had an uneventful biopsy course after receiving fresh frozen plasma (FFP). Laboratory investigations performed before the biopsy indicated normal activity for factors VIII, IX, XI, XII, and von Willebrand factor (vWF) as well as negative lupus anticoagulant (LA) screen. The plasma PK assay revealed low activity at 15% consistent with mild PK deficiency. The deficit of PK is characterized by a severely prolonged aPTT and normal prothrombin time (PT) in the absence of bleeding tendency. PK plays a role in the contact-activated coagulation pathway and the inflammatory response. Thus, other differential diagnoses of isolated prolonged aPTT include intrinsic pathway factor deficiencies and nonspecific inhibitors such as LA. We concluded that the initial evaluation of a prolonged aPTT with normal PT should appraise the measurement of contact activation factors and factor inhibitors. PK deficiency should be considered in asymptomatic patients with isolated aPTT prolongation, which corrects on incubation, with normal levels of the contact activation factors and factor inhibitors.

scholarly journals The use of the dilute Russell viper venom time for the diagnosis of lupus anticoagulants

Blood ◽  
1986 ◽  
Vol 68 (4) ◽  
pp. 869-874 ◽  
Author(s):  
P Thiagarajan ◽  
V Pengo ◽  
SS Shapiro
Keyword(s):  
Partial Thromboplastin Time ◽  
Activated Partial Thromboplastin Time ◽  
Inhibition Test ◽  
Specific Method ◽  
Lupus Anticoagulants ◽  
Tissue Thromboplastin

Abstract We describe here a test for lupus anticoagulants based on a modified Russell viper venom time (RVVT), using limiting amounts of phospholipid and venom. We have studied 29 patients with a prolonged dilute RVVT. Five of the 29 had a normal activated partial thromboplastin time and three of 14 tested by the tissue thromboplastin inhibition test were normal. In 17 of 19 patients tested, the dilute RVVT was completely normal when ionophore-treated platelets were substituted for phospholipid; the remaining two patients, both with very long phospholipid-dependent dilute RVVT's, were nearly completely normalized. The dilute RVVT is not prolonged in the presence of antibodies to factors VIII, IX, or XI. Thus, the dilute RVVT appears to be a simple, reproducible, sensitive, and relatively specific method for the detection of lupus anticoagulants.

The influence of acetaldehyde and glycosaminoglycans upon Factor Xa- and Factor X-deficient plasma

2002 ◽  
Vol 80 (9) ◽  
pp. 879-886 ◽  
Author(s):  
Arthur S Brecher ◽  
Eric L Hommema
Keyword(s):  
Blood Coagulation ◽  
Partial Thromboplastin Time ◽  
Factor Xa ◽  
Activated Partial Thromboplastin Time ◽  
Clotting Factor ◽  
Factor X ◽  
Chondroitin Sulfates ◽  
Prolonged Aptt ◽  
Subsequent Addition ◽  
Three Components

The comparative effects of glycosaminoglycans and acetaldehyde (AcH) – glycosaminoglycan (GAG) mixtures upon Factor Xa- (FXa) and Factor X-deficient plasma (FXDP) have been studied by activated partial thromboplastin time (APTT) studies. Heparin at 0.025, 0.030, 0.04, and 0.05 U statistically prolonged the APTT when pre-incubated with FXa at 37°C for 3 min prior to addition to FXDP and subsequent addition of Ca2+. Upon addition of 0.25, 0.375, and 0.5 µg heparin-6000 (H6k) to FXa, significant increases in APTT were observed. Similarly, profound increases in APTT were observed when 0.5, 0.75, and 1.0 µg heparin-3000 (H3k) was added to FXa. The chondroitin sulfates (CSA, CSB, CSC) had far less impact upon APTT with the FXa–FXDP system. In examining the effects of AcH–GAG mixtures upon the clotting factor, it was observed that 44.3 and 443 mM AcH synergistically prolonged the APTT in a statistically significant manner regardless of the order of premixing the three components. Hence, AcH may play a role in prolonging APTT in alcoholics. It synergistically prolonged APTT in concert with GAGs and FXa at the AcH levels used in this study. The effect of the GAGs upon FXDP is far less than its effect upon FXa.Key words: Factor Xa, acetaldehyde, heparin, glycosaminoglycans, blood coagulation.

scholarly journals Recombinant lipoprotein-associated coagulation inhibitor inhibits tissue thromboplastin-induced intravascular coagulation in the rabbit

Blood ◽  
1990 ◽  
Vol 76 (8) ◽  
pp. 1538-1545 ◽  
Author(s):  
KC Day ◽  
LC Hoffman ◽  
MO Palmier ◽  
KK Kretzmer ◽  
MD Huang ◽  
...  
Keyword(s):  
Body Weight ◽  
Prothrombin Time ◽  
Partial Thromboplastin Time ◽  
Rabbit Model ◽  
Activated Partial Thromboplastin Time ◽  
High Dose ◽  
Intravascular Coagulation ◽  
Coagulation Inhibitor ◽  
Tissue Thromboplastin ◽  
Induced Radioactivity

Lipoprotein-associated coagulation inhibitor produces feed-back inhibition of tissue factor (tissue thromboplastin)-induced coagulation in the presence of factor Xa Recombinant lipoprotein-associated coagulation inhibitor (rLACI) was tested for its ability to modify thromboplastin-induced intravascular coagulation in a rabbit model that allows monitoring of iodine-125 fibrin accumulation/disappearance in the lung and sampling of blood for the measurement of coagulation parameters. Infusion of thromboplastin into the rabbit caused a rapid increase of radioactivity over the lungs, possibly due to the accumulation of 125I fibrin in the lungs, followed by a rapid decline of radioactivity, suggestive of removal of fibrin from the lungs. Thromboplastin also caused a rapid decrease of systemic fibrinogen that was accompanied by a lengthening of the activated partial thromboplastin time and prothrombin time. The effect of coinfusion of rLACI with thromboplastin or bolus injection of rLACI before thromboplastin infusion was studied. At a high dose of rLACI (800 micrograms/kg body weight), the thromboplastin-induced radioactivity increase in the lungs and the systemic fibrinogen decrease were completely suppressed. The activated partial thromboplastin time and prothrombin time of the plasma samples lengthened, possibly due to the presence of thromboplastin in circulation. The thromboplastin-induced radioactivity increase over the lungs was not completely suppressed by lower doses of rLACI (135 to 270 micrograms/kg body weight), but these doses of rLACI prevented systemic fibrinogen decrease. At a bolus dose of 23 micrograms/kg body weight, rLACI provided 50% protection of the fibrinogen consumption (fibrinogen decreased to 82% compared with 65% in rabbits treated with thromboplastin alone). These results show that rLACI is effective in the inhibition of thromboplastin-induced coagulation in vivo.

scholarly journals The use of the dilute Russell viper venom time for the diagnosis of lupus anticoagulants

Blood ◽  
1986 ◽  
Vol 68 (4) ◽  
pp. 869-874 ◽  
Author(s):  
P Thiagarajan ◽  
V Pengo ◽  
SS Shapiro
Keyword(s):  
Partial Thromboplastin Time ◽  
Activated Partial Thromboplastin Time ◽  
Inhibition Test ◽  
Specific Method ◽  
Lupus Anticoagulants ◽  
Tissue Thromboplastin

We describe here a test for lupus anticoagulants based on a modified Russell viper venom time (RVVT), using limiting amounts of phospholipid and venom. We have studied 29 patients with a prolonged dilute RVVT. Five of the 29 had a normal activated partial thromboplastin time and three of 14 tested by the tissue thromboplastin inhibition test were normal. In 17 of 19 patients tested, the dilute RVVT was completely normal when ionophore-treated platelets were substituted for phospholipid; the remaining two patients, both with very long phospholipid-dependent dilute RVVT's, were nearly completely normalized. The dilute RVVT is not prolonged in the presence of antibodies to factors VIII, IX, or XI. Thus, the dilute RVVT appears to be a simple, reproducible, sensitive, and relatively specific method for the detection of lupus anticoagulants.

The Dilute Phospholipid APTT: A Sensitive Assay for Verification of Lupus Anticoagulants

1985 ◽  
Vol 54 (03) ◽  
pp. 709-712 ◽  
Author(s):  
Barbara M Alving ◽  
Phillip E Baldwin ◽  
Roberta L Richards ◽  
Beverly J Jackson
Keyword(s):  
Regression Analysis ◽  
Partial Thromboplastin Time ◽  
Coagulation Factor ◽  
Activated Partial Thromboplastin Time ◽  
Negative Slope ◽  
Sensitive Assay ◽  
Lupus Anticoagulants ◽  
Normal Plasma ◽  
The Mean ◽  
Sensitive Method

SummaryA simple sensitive method for verification of lupus anticoagulants utilizing dilution of phospholipid in the activated partial thromboplastin time (APTT) system is described. Patient plasma, mixed with an equal volume of normal plasma, is activated with micronized silica. To this mixture are added different dilutions of Thrombofax® and then calcium chloride. Clotting times are plotted linearly against the logarithm of the phospholipid dilutions and slopes are calculated by regression analysis. In this assay the mean negative slope of 19 plasmas that contained antiphospholipid activity was five times greater than those of normal plasma or those obtained from patients having single or multiple coagulation factor deficiencies such as those induced by warfarin. The assay can be modified to test heparinized plasmas. Thus, it is a sensitive means by which to verify the presence of lupus anticoagulants in patients who have congenital or acquired factor deficiencies or who are receiving anticoagulant therapy.

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