Coagulation Disorders - Diagnosis - Anticoagulation Therapy

/2005

Question:  How does one diagnose a coagulation disorder if the patient is on anticoagulation therapy?

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12362255.ui or 12008964.ui or 11943938.ui or 11587992.ui or 11414631.ui or 7942443.ui or 8029789.ui or 2678585.ui or 6611586.ui or 7395817.ui or 16174603.ui or 12871411.ui or 12556745.ui or 12362247.ui or 11734670.ui or 10364776.ui or 7740528.ui or 7878649.ui or 7803245.ui

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12362255[PMID] OR 12008964[PMID] OR 11943938[PMID] OR 11587992[PMID] OR 11414631[PMID] OR 7942443[PMID] OR 8029789[PMID] OR 2678585[PMID] OR 6611586[PMID] OR 7395817[PMID] OR 16174603[PMID] OR 12871411[PMID] OR 12556745[PMID] OR 12362247[PMID] OR 11734670[PMID] OR 10364776[PMID] OR 7740528[PMID] OR 7878649[PMID] OR 7803245[PMID]

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<1>

Unique Identifier [PMID]: 12362255

Authors: Perrier A. Bounameaux H.

Title: A rebuttal: withholding anticoagulation in patients with suspected pulmonary embolism and a low probability ventilation perfusion scan: an unacceptable risk.[see comment][comment].

Comments Comment in: Thromb Haemost. 2003 Feb;89(2):407-8; PMID: 12574823, Comment on: Thromb Haemost. 2002 Apr;87(4):772; PMID: 12008964

Source: Thrombosis & Haemostasis. 88(4):702, 2002 Oct.

Publication Type: Comment. Letter.

<2>

Unique Identifier [PMID]: 12008964

Authors: Iles S. Egermayer P. Hlavac M. Turner J. Town GI.

Title: What is the risk of withholding anticoagulation in those with a low probability ventilation perfusion scan in the investigation of pulmonary emboli?[see comment].

Comments Comment in: Thromb Haemost. 2002 Oct;88(4):702; PMID: 12362255

Source: Thrombosis & Haemostasis. 87(4):772, 2002 Apr.

Publication Type: Letter.

<3>

Unique Identifier [PMID]: 11943938

Authors: Couturaud F. Kearon C. Bates SM. Ginsberg JS.

Institution: Hamilton Civic Hospitals Research Centre, and McMaster University, Hamilton, Ontario, Canada.

Title: Decrease in sensitivity of D-dimer for acute venous thromboembolism after starting anticoagulant therapy. [Review] [36 refs]

Source: Blood Coagulation & Fibrinolysis. 13(3):241-6, 2002 Apr.

Abstract: D-dimer testing is useful for the exclusion of acute venous thromboembolism (VTE). Anticoagulant therapy is expected to reduce D-dimer levels in patients with thrombosis and, consequently, it may not be safe to use D-dimer levels to exclude VTE after anticoagulant therapy has been started. The objectives of this study were to estimate the decrease in D-dimer levels after 24 h of heparin therapy and, applying this estimate to the results of a recent study, to calculate the expected reduction in sensitivity. Using pre-defined criteria, we first performed a literature review to determine whether, and by how much, D-dimer levels decrease within 24 h of starting heparin therapy in patients with acute VTE. Using D-dimer levels that were measured in a prospective study of patients with confirmed deep vein thrombosis and/or pulmonary embolism as baselines, we then determined the change in sensitivity (and specificity) that would result from the fall in D-dimer levels that the literature review suggested would have occurred after 24 h of heparin therapy. On the basis of the literature review, we calculated that mean D-dimer levels decrease by 25%, 24 h after starting heparin therapy in patients with acute VTE. This 25% decrease in D-dimer levels resulted in a decrease in sensitivity from 95.6% (95% confidence interval, 90.0-98.6) to 89.4% (95% confidence interval, 83.7-95.1). There is a decrease in D-dimer levels in patients with acute VTE 24 h after starting heparin therapy that is expected to result in a clinically important drop in sensitivity. [References: 36]

Publication Type: Journal Article. Review.

<4>

Unique Identifier [PMID]: 11587992

Authors: Girard P. Decousus M. Laporte S. Buchmuller A. Herve P. Lamer C. Parent F. Tardy B. PREPIC Study Group.

Institution: Departement Thoracique and Departement de Reanimation, Institut Mutualiste Montsouris, Paris, France. philippe.girard@imm.fr

Title: Diagnosis of pulmonary embolism in patients with proximal deep vein thrombosis: specificity of symptoms and perfusion defects at baseline and during anticoagulant therapy.

Source: American Journal of Respiratory & Critical Care Medicine. 164(6):1033-7, 2001 Sep 15.

Abstract: To determine the specificity of pulmonary embolism (PE) symptoms and lung scan perfusion defects in patients with deep vein thrombosis (DVT), we analyzed data on 400 patients with phlebography-proven proximal DVT included in a prospective trial. As the incidence of PE during anticoagulant therapy was the main outcome measure of the trial, all patients underwent lung scanning and/or pulmonary angiography within 48 h of inclusion, and then whenever PE was suspected. Angiography was recommended in patients with nondiagnostic lung scan. At baseline, the presence or absence of PE could be ascertained in 350 patients (87.5%), and 197 (56%) had PE. Sensitivity and specificity of symptoms for PE were 74 and 67%, respectively. Among 37 patients with symptoms and nondiagnostic lung scan, only 8 (22%) had PE at angiography. During anticoagulant therapy (3 mo), there were 29 events suspicious for PE, mostly (53%) within 2 wk of inclusion. Repeated perfusion studies with comparison to baseline tests excluded PE in 21 cases. Cumulated 3-mo risks of suspected and confirmed on-treatment PE were 6.8% (95% CI, 5.4- 8.2%) and 2.0% (95% CI, 0.6-3.4%) respectively. Even in patients with known proximal DVT, PE symptoms are unspecific and careful imaging studies are needed for diagnosis, both at baseline and during anticoagulant therapy.

Publication Type: Clinical Trial. Journal Article. Multicenter Study. Randomized Controlled Trial.

<5>

Unique Identifier [PMID]: 11414631

Authors: Chitolie A. Lawrie AS. Mackie IJ. Harrison P. Machin SJ.

Institution: Haematology Department, University College London Hospitals, UK. a.chitolie@ucl.ac.uk

Title: The impact of oral anticoagulant therapy, factor VIII level and quality of factor V-deficient plasma on three commercial methods for activated protein C resistance.

Source: Blood Coagulation & Fibrinolysis. 12(3):179-86, 2001 Apr.

Abstract: Several methods are now available for the laboratory assessment of activated protein C resistance (APCR). In this study, we evaluated two activated partial thromboplastin time-based assays [Coatest activated protein C (APC) and Diagen protein C activator (PCA)], with and without predilution of test plasma in factor V-deficient plasma (FVdp) and an amidolytic assay (Immuno Ltd, Vienna, Austria). Testing plasmas from normal volunteers who had received 1-deamino-8-D-arginine vasopressin (DDAVP) also assessed the effect of elevated factor VIII on APCR. In the unmodified clotting tests, the Coatest kit gave overlapping results for normal and heterozygous FV:Q506 samples; some FV:Q506 samples on oral anticoagulant therapy (OAT) were misclassified as normal, and some normal samples with high factor VIII levels would be classified as APC resistant. The unmodified Diagen kit correctly classified these three types of sample, but had the disadvantage that prolonged PCA clotting times gave serious problems with instrument end-point detection. Both kits modified by diluting the samples in FVdp correctly classified all the samples, as well as samples from patients with lupus anticoagulant (LA) and patients receiving heparin. The Immunochrom kit correctly classified the normal and FV:Q506 samples, but would have misclassified most normal persons on OAT as well as some patients with LA or receiving heparin therapy as APC resistant.

Publication Type: Journal Article.

<6>

Unique Identifier [PMID]: 7942443

Authors: Becker RC. Cyr J. Corrao JM. Ball SP.

Institution: Coronary Care Unit, University of Massachusetts Medical School, Worcester 01655.

Title: Bedside coagulation monitoring in heparin-treated patients with active thromboembolic disease: a coronary care unit experience.

Source: American Heart Journal. 128(4):719-23, 1994 Oct.

Abstract: Patients with active venous and arterial thromboembolic disorders are known to benefit from systemic anticoagulation with heparin. Clinical studies have shown, however, that therapeutic anticoagulation is rarely achieved rapidly and often is not maintained over time. Prolonged laboratory turnaround time of the activated partial thromboplastin time (aPTT) may contribute directly to these common problems. A total of 272 aPTT determinations were performed on 120 heparin-treated patients admitted to the coronary care unit. The time from sample collection to data availability was 126 +/- 84 minutes with standard laboratory aPTT testing. In contrast, a bedside coagulation device provided an aPTT within 3 minutes (p < 0.001). Subtherapeutic aPTT values (< 65 seconds) were documented in 21% of all patients; in each, the heparin dose was changed and a repeat aPTT was required. In a separate study of 33 heparinized patients randomized to either bedside or central laboratory aPTT testing (264 aPTT determinations), the time to achieve a therapeutic state of systemic anticoagulation was 8.2 hours and 18.1 hours, respectively (p < 0.005). The time from aPTT determination to a decision regarding heparin titration adjustments was 14.5 minutes and 3 hours with bedside and laboratory testing, respectively (p < 0.001). Thus bedside coagulation monitoring provides a convenient, rapid, and accurate assessment of systemic anticoagulation among heparin-treated patients with active thromboembolic disease in the coronary care unit. This technology warrants further clinical investigation.

Publication Type: Clinical Trial. Journal Article. Randomized Controlled Trial.

<7>

Unique Identifier [PMID]: 8029789

Authors: Bohner J. von Pape KW. Blaurock M.

Institution: Institut fur Laboratoriumsmedizin, Stadtisches Klinikum Fulda, Germany.

Title: Thrombin-based antithrombin assays show overestimation of antithrombin III activity in patients on heparin therapy due to heparin cofactor II influence.

Source: Thrombosis & Haemostasis. 71(3):280-3, 1994 Mar.

Abstract: An extensive comparison has been performed on the clinical chemistry automate Hitachi 717 between thrombin- and Factor Xa-based methods for determination of antithrombin III activity. In 460 patients who did not receive any heparin therapy the agreement between assays was in general close although the thrombin-based methods resulted in slightly higher assignments of 0.3-2.6% antithrombin III activity. The discrepancy was, however, substantial in plasmas from patients receiving heparin of > or = 20000 IU/day, resulting in plasma levels of heparin of 0.8-1.2 IU/ml. Thus, analysis of 102 patients showed that the thrombin-based methods resulted in, on average, 7-16% higher assignment of antithrombin III activity as compared to the Factor Xa-based method used. Addition of antibodies to antithrombin III and heparin cofactor II revealed that the discrepancy was primarily due to contribution of heparin cofactor II activity in the thrombin-based methods. The results thus suggest that the Factor Xa-based antithrombin III activity method provides more valid results in patients on heparin therapy.

Publication Type: Journal Article.

<8>

Unique Identifier [PMID]: 2678585

Authors: Bogaty-Yver J. Samama M.

Title: Thrombin-antithrombin III complexes for the detection of postoperative hypercoagulable state in surgical patients receiving heparin prophylaxis.

Source: Thrombosis & Haemostasis. 61(3):538, 1989 Jun 30.

Publication Type: Letter.

<9>

Unique Identifier [PMID]: 6611586

Authors: Ottesen S. Stormorken H. Hatteland K.

Title: The value of activated coagulation time in monitoring heparin therapy during extracorporeal circulation.

Source: Scandinavian Journal of Thoracic & Cardiovascular Surgery. 18(2):123-8, 1984.

Abstract: The anticoagulant effect of heparin was studied in 20 patients undergoing aortocoronary bypass surgery. The protamine dose necessary to reverse heparin after extracorporeal circulation (ECC) was assessed in ten patients from individual heparin dose-response curves (HDR group). The other ten patients received protamine according to a routine protocol (control group). The protamine administration was followed in both groups by injection of 3-5 g tranexamic acid (Cyklokapron). A wide range of sensitivity to heparin was shown by the patients. Although almost twice as much protamine was given to the control group as to the HDR group, the effect on heparin reversal was similar. The variability of protamine dose did not influence the post-bypass levels of fibrinogen, AT-III, activated coagulation time (ACT) or Cephotest, and fibrinolysis was not observed in either of the groups. During ECC there was poor correlation between ACT and plasma heparin levels, and the use of heparin dose-response curves was grossly misleading in regard to true heparin concentration. The postoperative bleeding was not related to the levels of heparin or coagulation parameters after heparin reversal. The concentrations of fibrinogen and AT-III showed variations dependent on the changes in haematocrit. A number of factors other than heparin that influence ACT are discussed.

Publication Type: Journal Article.

<10>

Unique Identifier [PMID]: 7395817

Authors: Bounameaux H. Marbet GA. Lammle B. Eichlisberger R. Duckert F.

Title: Monitoring of heparin treatment. Comparison of thrombin time, activated partial thromboplastin time, and plasma heparin concentration, and analysis of the behavior of antithrombin III.

Source: American Journal of Clinical Pathology. 74(1):68-73, 1980 Jul.

Abstract: Three laboratory methods for monitoring heparin treatment have been compared using 63 plasma samples: the thrombin time, the activated partial thromboplastin time, and the measurement of the heparin concentration using a chromogenic substrate. A good correlation was found between the methods. However, the intensity of anticoagulation was identical in only 27 of the 63 samples (43%) when the thrombin time and the activated partial thromboplastin time were compared. Fully discordant results were recorded for four samples (6%). The thrombin time was found to be more closely related to the plasma heparin concentration than was the activated partial thromboplastin time. Both antithrombin-III activity and immunologic levels were lower in the group with strong heparinization. It is suggested that the thrombin time is a good and safe method for monitoring heparin treatment.

Publication Type: Journal Article.

<11>

Unique Identifier [PMID]: 16174603

Authors: Favaloro EJ. Soltani S. McDonald J. Grezchnik E. Easton L.

Institution: Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, NSW, Australia. emmanuel@icpmr.wsahs.nsw.gov.au

Title: Laboratory identification of familial thrombophilia: do the pitfalls exceed the benefits? A reassessment of ABO-blood group, gender, age, and other laboratory parameters on the potential influence on a diagnosis of protein C, protein S, and antithrombin deficiency and the potential high risk of a false positive diagnosis.

Source: Laboratory Hematology. 11(3):174-84, 2005.

Abstract: Laboratory testing for familial thrombophilia defines a large proportion of the modern hemostasis laboratory workload. As part of an ongoing assessment of our activities, we have re-evaluated our laboratory procedures for antithrombin (AT), Protein C (PC), and Protein S (PS), inclusive of normal reference ranges (NRR), the potential influence of ABO-blood group, gender and age, as well as other laboratory parameters, in order to help assess the effectiveness of testing as an aid to clinical diagnosis. We did not observe a significant influence of ABO-blood group on AT, PC, or PS. However, there were gender-related effects for PS (lower in females) and AT (higher in females), but not for PC. There were also age-related effects for AT, PC, and PS. Data is compared with literature findings. We also audited the positive detection rate for PC and/or PS deficiencies. In a 6-month period of testing, we identified that 18.9% of tested samples yielded low or near-low PC and/or PS levels. However, 33.3% of such samples were potentially derived from patients on oral anticoagulant therapy (ie, potential false positives). Additional pre-analytical variables, intra-assay, inter-assay, and inter-laboratory variability also contribute to the possibility of false positive detection. Thus, whilst NRR can be developed for test parameters, the likelihood of a false-positive test result can still be shown to exceed the likelihood of a true positive result, and this casts a shadow over the clinical value of such testing in some cases. In conclusion, laboratory testing for these markers of familial thrombophilia may or may not assist in the clinical diagnosis of this condition and clinical specialists should be made aware of laboratory test limitations, and consult with laboratories prior to making a definitive diagnosis of AT, PC, or PS deficiency.

Publication Type: Journal Article.

<12>

Unique Identifier [PMID]: 12871411

Authors: Meijer P. Kluft C. Haverkate F. De Maat MP.

Institution: ECAT Foundation, Leiden, the Netherlands. P.Meijer@ecat.nl

Title: The long-term within- and between-laboratory variability for assay of antithrombin, and proteins C and S: results derived from the external quality assessment program for thrombophilia screening of the ECAT Foundation.

Source: Journal of Thrombosis & Haemostasis. 1(4):748-53, 2003 Apr.

Abstract: A stable laboratory performance is important for comparability and transferability of laboratory data both within and between laboratories. The lack of a reference system within hemostasis hampers laboratories in establishing their laboratory performance over a prolonged period of time. Therefore, based on data from an external quality assessment program, we evaluated the between laboratory variation (CVBETWEEN) and the long-term within-laboratory variation (LCVa) for antithrombin, and proteins C and S. We evaluated the CVBETWEEN for the period 1996-2001, including the results of 64-240 laboratories from 23 different surveys (protein S activity 15 surveys). We observed a quite high CVBETWEEN and a broad range for each analyte. The CVBETWEEN was significantly higher for antithrombin and protein S for samples with low levels similar to heterozygous deficiencies. We also evaluated the LCVa, including the results of 136 laboratories. The lowest LCVa[median and 95% content interval (CI)] was observed for antithrombin (7.6%; 3.6-35.5%), intermediate values for protein C activity and antigen (8.6%; 3.5-25.3% and 10.8%; 4.8-33.1%, respectively) and highest values for the protein S variables (13.4%; 6.4-50.6% for total protein S antigen, 14.1%; 6.5-79.1% for free protein S antigen and 17.2%; 7.2-84.3% for protein S activity). We concluded that the main reason for the high CVBETWEEN is the long-term within-laboratory variability. Application of linear regression on data of an external quality assessment program is a useful model to demonstrate per analyte per laboratory the long-term variability (LCVa). It is concluded that improvement of the long-term within-laboratory test performance is the first priority in hemostasis to yield important improvements in the comparability and transferability of laboratory data.

Publication Type: Journal Article.

<13>

Unique Identifier [PMID]: 12556745

Authors: Olin JW.

Institution: Division of Cardiovascular Medicine, Mount Sinai School of Medicine, New York, NY, USA.

Title: Pulmonary embolism. [Review] [37 refs]

Source: Reviews in Cardiovascular Medicine. 3 Suppl 2:S68-75, 2002.

Abstract: The natural history of pulmonary embolism (PE) is incompletely characterized, because most episodes of PE go undetected, the clinical presentation mimics so many other common and uncommon diseases, the sensitivity and specificity of the diagnostic tests are poorly defined, and even detection at autopsy is difficult and requires close examination of the pulmonary arteries. Yet PE is a significant cause of morbidity and mortality in the hospitalized patient, and one reason for its extremely high incidence is the failure of physicians to provide adequate prophylaxis to patients who are at risk of developing venous thromboembolism. The mortality rate for PE is less than 8% when the condition is recognized and treated correctly but approximately 30% when untreated. Pulmonary arteriography is still the gold standard in diagnosing pulmonary emboli, but several other imaging modalities have been used to diagnose pulmonary emboli in recent years, including transthoracic and transesophageal echocardiography, magnetic resonance angiography, spiral computerized tomography, and ventilation-perfusion lung scanning. The treatment modality chosen depends directly on the clinical presentation of the patient. Low molecular weight heparin may be equal or superior in efficacy to unfractionated heparin for the treatment of deep venous thrombosis and PE. Thrombolytic therapy can be considered for patients with hemodynamic instability, those with right ventricular dysfunction, and young patients with a massive PE despite a normal right ventricle on echocardiography. In those patients who cannot receive anticoagulation therapy or thrombolysis, or who remain at high risk, an inferior vena cava filter should be placed. [References: 37]

Publication Type: Journal Article. Review.

<14>

Unique Identifier [PMID]: 12362247

Authors: Tripodi A. Peyvandi F. Chantarangkul V. Menegatti M. Mannucci PM.

Title: Relatively poor performance of clinical laboratories for DNA analyses in the detection of two thrombophilic mutations--a cause for concern.

Source: Thrombosis & Haemostasis. 88(4):690-1, 2002 Oct.

Publication Type: Letter.

<15>

Unique Identifier [PMID]: 11734670

Authors: Gemmati D. Serino ML. Tognazzo S. Ongaro A. Moratelli S. Gilli G. Forini E. De Mattei M. Scapoli GL.

Institution: Centre for the Study of Haemostasis and Thrombosis, University of Ferrara, Italy. cet@unife.it

Title: The reduced sensitivity of the ProC Global test in protein S deficient subjects reflects a reduction in the associated thrombotic risk.

Source: Blood Coagulation & Fibrinolysis. 12(8):691-7, 2001 Dec.

Abstract: To investigate simultaneously a defect affecting the protein C/protein S (PC/PS) anticoagulant pathway is possible thanks to a methodological approach (ProC(R) Global; Dade Behring) based on the activation of endogenous plasma PC by a snake venom extract. Factor V (FV) Leiden, the most frequent cause of hereditary thrombosis, is well detected by the test with sensitivity of 100% irrespective of the presence/absence of thrombosis in the subjects investigated. The test is also suited to detect PC or PS defect, but in this case the in vitro impairment of the PC/PS pathway is less pronounced particularly for PS defects (sensitivity for PC and PS defect, 85-100 and 30-90%, respectively). In this study, we hypothesized that the lower sensitivity described for PS defect, compared with those of PC and FV Leiden defects, could also be related to the clinical condition of the subject investigated (symptomatic/asymptomatic) rather than solely to the PS plasma activity/level. Therefore, we analyzed 126 subjects with single congenital defects in the PC/PS pathway: 46 subjects with PS deficiency (26 thrombotic cases and 20 asymptomatic relatives), 40 subjects with PC deficiency (25 thrombotic cases and 15 asymptomatic relatives), and 40 heterozygous FV Leiden subjects (25 thrombotic cases and 15 asymptomatic relatives). By a cut-off of normalized Agkistrodon contortix snake venom ratio of 0.84, the sensitivity in the whole group of cases (sensitivity a) was 76.1, 95.0 and 100%, respectively, for PS, PC and FV Leiden defects. The test failed to detect 11 (23.9%) among the 46 PS-deficient subjects, and all these cases except two belonged to the asymptomatic subgroup (9/20; 45%). Excluding the 20 asymptomatic relatives, the new sensitivity (sensitivity b) for the PS defect was 92.3%. The comparison of the sensitivity in the symptomatic PS cases and in the asymptomatic ones was significantly different (P = 0.010). Among the 40 PC-deficient subjects, only two (5.0%) were not detected by the test and they belonged indifferently to the two subgroups. Finally, none of the 40 FV Leiden heterozygotes were misdiagnosed by the test. These results suggest that in symptomatic PS-deficient cases the test could reflect a post-thrombotic effect and/or reveal potential unidentified prothrombotic influences assessing a prothrombotic risk condition.

Publication Type: Journal Article.

<16>

Unique Identifier [PMID]: 10364776

Authors: Baron RM. Goldhaber SZ.

Institution: Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.

Title: Deep venous thrombosis: early discharge strategies and outpatient management.

Source: Journal of Thrombosis & Thrombolysis. 7(2):113-22, 1999 Apr.

Abstract: Conventional management of acute deep venous thrombosis (DVT) consists of initiating continuous infusion intravenous unfractionated heparin (UFH) for 5 days in the hospital as well as warfarin. Low-molecular-weight heparins (LMWHs) appear to confer similar protection against recurrent DVT compared with UFH but exhibit prolonged bioavailability; increased ease of dosing, and fewer side effects. The advent of LMWH has resulted in increased numbers of patients undergoing initial management of acute DVT with only several days of hospitalization. While 3-month follow-up studies with LMWH demonstrate similar efficacy and safety to UFH, longer term experience with these new agents is necessary to determine their optimal use and safety. We suggest a system for triage in the initial management of DVT patients for: (1) complete outpatient management with LMWH, or (2) short-term hospitalization for initiation of LMWH, or (3) 5-day hospitalization for treatment with UFH. A review of DVT management with LMWH and algorithms for each of these pathways are provided.

Publication Type: Journal Article.

<17>

Unique Identifier [PMID]: 7740528

Authors: D'Angelo SV. Mazzola G. Della Valle P. Testa S. Pattarini E. D'Angelo A.

Institution: Servizio di Coagulazione, IRCCS H.S. Raffaele, Milan, Italy.

Title: Variable interference of activated protein C resistance in the measurement of protein S activity by commercial assays.

Source: Thrombosis Research. 77(4):375-8, 1995 Feb 15.

Publication Type: Journal Article.

<18>

Unique Identifier [PMID]: 7878649

Authors: Faioni EM. Boyer-Neumann C. Franchi F. Wolf M. Meyer D. Mannucci PM.

Title: Another protein S functional assay is sensitive to resistance to activated protein C.

Source: Thrombosis & Haemostasis. 72(4):648, 1994 Oct.

Publication Type: Letter.

<19>

Unique Identifier [PMID]: 7803245

Authors: Cooper PC. Hampton KK. Makris M. Abuzenadah A. Paul B. Preston FE.

Institution: Department of Haematology, Royal Hallamshire Hospital, Sheffield.

Title: Further evidence that activated protein C resistance can be misdiagnosed as inherited functional protein S deficiency.

Source: British Journal of Haematology. 88(1):201-3, 1994 Sep.

Abstract: A recent report that activated protein C (APC) resistance interferes with functional protein S (PS) assays prompted us to re-investigate two pedigrees previously diagnosed as having functional PS deficiency. APC resistance was demonstrated in all individuals with apparent functional PS deficiency. The latter diagnosis was shown to be due to the assay being non-linear, functional protein S becoming normal at higher dilutions. This observation, taken in conjunction with results of in vitro recovery studies with purified PS, leads us to conclude that APC resistance was the primary disorder in both pedigrees. The misdiagnosis of APC resistance as functional PS deficiency can be prevented by performing the PS assay at several dilutions, including concentrations lower than those recommended by PS assay manufacturers. Subjects previously diagnosed as having functional PS deficiency should be re-investigated for APC resistance.

Publication Type: Journal Article.