Plasma procoagulant phospholipid clotting time and venous thromboembolism risk

Cathrine Ramberg; Line Wilsgård; Nadezhda Latysheva; Sigrid K. Brækkan; Kristian Hindberg; Timofey Sovershaev; Omri Snir; John‐Bjarne Hansen

doi:10.1002/rth2.12640

Coagulation Profile Changes Due to Thromboprophylaxis and Platelets in Trauma Patients at High-Risk for Venous Thromboembolism

The American Surgeon ◽

10.1177/000313481508100713 ◽

2015 ◽

Vol 81 (7) ◽

pp. 663-668 ◽

Cited By ~ 14

Author(s):

Casey J. Allen ◽

Clark R. Murray ◽

Jonathan P. Meizoso ◽

Juliet J. Ray ◽

Laura F. Teisch ◽

...

Keyword(s):

Risk Assessment ◽

Venous Thromboembolism ◽

High Risk ◽

Trauma Patients ◽

Clotting Time ◽

Coagulation Profile ◽

Profile Score ◽

Risk Patients ◽

Profile Changes

We hypothesize there are coagulation profile changes associated both with initiation of thromboporphylaxis (TPX) and with change in platelet levels in trauma patients at high-risk for venous thromboembolism (VTE). A total of 1203 trauma intensive care unit patients were screened with a VTE risk assessment profile. In all, 302 high-risk patients (risk assessment profile score ≥ 10) were consented for weekly thromboelastography. TPX was initiated between initial and follow-up thromboelastography. Seventy-four patients were analyzed. Upon admission, 87 per cent were hypercoagulable, and 81 per cent remained hypercoagulable by Day 7 ( P = 0.504). TPX was initiated 3.4 ± 1.4 days after admission; 68 per cent received unfractionated heparin and 32 per cent received low-molecular-weight heparin. The VTE rate was 18 per cent, length of stay 38 (25–37) days, and mortality of 17.6 per cent. In all, 76 per cent had a rapid clotting time at admission versus 39 per cent at Day 7 ( P < 0.001); correcting from 7.75 (6.45–8.90) minutes to 10.45 (7.90–15.25) minutes ( P < 0.001). At admission, 41 per cent had an elevated maximum clot formation (MCF) and 85 per cent had at Day 7 ( P < 0.001); increasing from 61(55–65) mm to 75(69–80) mm ( P < 0.001). Platelets positively correlated with MCF at admission (r = 0.308, R2 = 0.095, P = 0.008) and at Day 7 (r = 0.516, R2 = 0.266, P < 0.001). Change in platelet levels correlated with change in MCF (r = 0.332, R2 = 0.110, P = 0.005). In conclusion, hypercoagulability persists despite the use of TPX. Although clotting time normalizes, MCF increases in correlation with platelet levels. As platelet function is a dominant contributor to sustained trauma-evoked hypercoagulability, antiplatelet therapy may be indicated in the management of severely injured trauma patients.

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The effect of routine preoperative interruption of dabigatran therapy on coagulation parameters and dabigatran plasma levels in a mixed surgical population

Anaesthesia and Intensive Care ◽

10.1177/0310057x19841009 ◽

2019 ◽

Vol 47 (2) ◽

pp. 183-188 ◽

Cited By ~ 2

Author(s):

Oliver F Brett ◽

Christian N Brett ◽

Paul KL Chin

Keyword(s):

Atrial Fibrillation ◽

Venous Thromboembolism ◽

Elective Surgery ◽

Potential Utility ◽

Preoperative Period ◽

Clotting Time ◽

Preoperative Management ◽

Reversal Agent ◽

Coagulation Tests ◽

Dabigatran Therapy

Summary Dabigatran is an oral anticoagulant used for atrial fibrillation and venous thromboembolism. While an effective antibody reversal agent is available, its cost precludes routine use and the mainstay of preoperative management is timely dabigatran interruption. Unlike warfarin, there are no universally accepted protocols for interruption of dabigatran in the preoperative period and there is uncertainty around the interpretation of standard coagulation tests in the presence of dabigatran. We performed a prospective, observational pilot study in patients presenting for elective surgery to examine: 1) the preoperative plasma dabigatran concentrations on day of surgery associated with the local dabigatran interruption protocol, 2) the potential utility of dabigatran concentrations on day of surgery, and 3) the utility of standard coagulation tests in determining whether dabigatran concentrations were below a ‘safe’ threshold for surgery. We recruited patients presenting to pre-admission clinics for elective surgery. Dabigatran concentrations below 30 µg/L were considered adequate for proceeding with surgery. Data were obtained and analysed from 21 patients with a median (range) age of 70 (20–86) years. Median (range) dabigatran concentrations on the day of surgery were 5 (0–59) µg/L. Two patients had day of surgery concentrations exceeding 30 µg/L. Of the standard coagulation tests examined, only the thrombin clotting time (TCT) was abnormal for these two patients. Our interruption protocol was associated with safe dabigatran concentrations in most patients on the day of surgery. A minority of patients had dabigatran concentrations above the safe threshold, which were detectable by abnormal TCT results.

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The effect of DOAC-Stop on lupus anticoagulant testing in plasma samples of venous thromboembolism patients receiving direct oral anticoagulants

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2018-1197 ◽

2019 ◽

Vol 57 (9) ◽

pp. 1374-1381 ◽

Cited By ~ 17

Author(s):

Michał Ząbczyk ◽

Magdalena Kopytek ◽

Joanna Natorska ◽

Anetta Undas

Keyword(s):

Venous Thromboembolism ◽

Screening Test ◽

Lupus Anticoagulant ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Activated Partial Thromboplastin Time ◽

Clotting Time ◽

The Impact ◽

Anticoagulated Patients

Abstract Background Direct oral anticoagulants (DOACs) cause false positive lupus anticoagulant (LA) results. We assessed the impact of DOAC-Stop, reversing in vitro effects of DOACs, on LA testing in anticoagulated patients. Methods We assessed 75 venous thromboembolism patients aged 44.5±14.6 years. Blood samples were collected 2–28 h since intake of DOACs, including 50 patients on rivaroxaban, 20 on dabigatran and five on apixaban. LA testing was performed at baseline and after DOAC-Stop treatment. Positive LA was defined as the normalized (patient/standard plasma clotting time) LA screening and screening (LA1)/confirmation (LA2) ratios exceeding 1.2. Results LA diluted Russell’s viper venom time (dRVVT) normalized screening test revealed abnormal results in 73 (97.3%) and activated partial thromboplastin time (APTT)-LA in 49 (65.3%) patients. In six (8%) patients, antiphospholipid syndrome (APS) was diagnosed. dRVVT LA1/LA2 was abnormal in 35 (50.7%) patients taking DOACs. The APTT ratio was normal in all studied subjects. DOAC-Stop completely removed dabigatran and reduced by 98% rivaroxaban and by 92.3% apixaban concentrations (all p<0.05). After DOAC-Stop screening dRVVT remained prolonged in 34 (49.3%) patients (p<0.001), while dRVVT LA1/LA2 was abnormal in six (8.7%) subjects, with no association with DOAC concentrations at baseline and after DOAC-Stop. The APTT-LA screening test remained prolonged in five (7.2%) patients, while the APTT LA1/LA2 ratio was normal in those subjects. DOAC-Stop did not influence LA testing in APS patients. Conclusions Application of DOAC-Stop effectively reduced plasma DOAC concentrations leading to appropriate dRVVT results in up to 97% of VTE patients.

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Comparison of aPTT (Platelin LS®) and Dilute Russell’s Viper Venom (Viperquik LA Test®) for the Screening of Lupus Anticoagulant in Patients with Venous Thromboembolism.

Blood ◽

10.1182/blood.v106.11.4122.4122 ◽

2005 ◽

Vol 106 (11) ◽

pp. 4122-4122

Author(s):

Celso A. Roprigues ◽

Aline A. Martinez ◽

Vania M. Morelli ◽

Raniely C. Silveira ◽

Maria Aparecida E. Noguti ◽

...

Keyword(s):

Venous Thromboembolism ◽

Partial Thromboplastin Time ◽

Lupus Anticoagulant ◽

Activated Partial Thromboplastin Time ◽

Screening Tests ◽

Clotting Time ◽

Substantial Agreement ◽

Confirmatory Tests ◽

Russell’S Viper ◽

Rule Out

Abstract INTRODUCTION: To rule out the presence of LA antibodies, two or more assays that are sensitive to these antibodies must be negative. The dilute Russell’s Viper Venom Time (dRVVT) and the activated partial thromboplastin time (aPTT) using sensitive reagents have been employed to detect LA. The aim of this study was to assess the concordance level of aPTT using Platelin LS and dRVVT as screening tests to identify LA in patients with venous thromboembolism (VTE). METHODS: 94 patients (58 women, 62%) with VTE were evaluated. The detection of circulating inhibitor with Platelin LS and dRVVT was based on a prolonged clotting time and a prolonged 1:1 mixture of sample plasma and normal pooled plasma. The confirmation of the phospholipid dependency was performed only with dRVVT. RESULTS: Among the 94 patients, an abnormal test was found in 24 patients (26%) with aPTT and in 61 patients (65%) using dRVVT. After mixing tests, aPTT ratio remained long in 25% of patients with abnormal aPTT, and in 9.8% with long dRVVT. Five patients had a prolonged mixing study identified by both tests, which resulted in a substantial agreement between the two tests (Kappa= 0.78). Confirmatory tests for LA were positive in 5 out of the 6 patients with long dRVVT mixture, resulting in a prevalence of LA detected by dRVVT of 5.3%. The 5 patients with LA detected by dRVVT also had prolonged mixture with aPTT. CONCLUSION: Our results indicate that aPTT with Platelin LS is highly associated with the presence of LA detected by dRVVT and may be suitable as a screening test for LA in patients with VTE.

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Biomarkers for the diagnosis of venous thromboembolism: D-dimer, thrombin generation, procoagulant phospholipid and soluble P-selectin

Journal of Clinical Pathology ◽

10.1136/jclinpath-2018-205293 ◽

2018 ◽

Vol 71 (11) ◽

pp. 1015-1022 ◽

Cited By ~ 8

Author(s):

Nicoletta Riva ◽

Kevin Vella ◽

Kieron Hickey ◽

Lorenza Bertù ◽

Daniel Zammit ◽

...

Keyword(s):

Venous Thromboembolism ◽

Thrombin Generation ◽

Diagnostic Algorithm ◽

Pulmonary Angiography ◽

Forest Plot ◽

Clotting Time ◽

Lung Scan ◽

Soluble P ◽

The Impact ◽

D Dimer

BackgroundThe diagnostic algorithm for venous thromboembolism (VTE) currently involves a composite of pre-test probability, D-dimer and imaging. Other laboratory tests, however, may assist in the identification of patients with VTE.AimTo assess the accuracy of different coagulation tests (D-dimer, thrombin generation, phospholipid-dependent (PPL) clotting time, soluble P-selectin (sP-selectin)) as biomarkers of acute VTE.MethodsRandom samples arriving at the Coagulation Laboratory at Mater Dei Hospital (Msida, Malta) from the Accident and Emergency Department with a request for D-dimer measurement were collected between August 2015 and February 2016. The following tests were performed: Innovance D-dimer (Siemens Healthcare Diagnostics), HemosIL D-dimer HS (Instrumentation Laboratory), thrombin generation (using the calibrated automated thrombogram), STA Procoag PPL (Diagnostica Stago) and sP-selectin (Affymetrix; eBioscience). VTE was objectively confirmed by compression ultrasonography, CT pulmonary angiography or ventilation/perfusion lung scan.Results100 samples were collected (33 with VTE). A strong positive linear correlation was found between the two D-dimer tests (r=0.97, p<0.001). Patients with VTE showed significantly higher sP-selectin concentrations compared with patients without VTE (75.7 ng/mL vs 53.0 ng/mL, p<0.001). In the random forest plot, the two D-dimer assays showed the highest variable importance, followed by sP-selectin. A sP-selectin cut-off of 74.8 ng/mL was associated with 72.7% sensitivity and 78.2% specificity for acute VTE in our cohort.ConclusionOur results confirmed D-dimer as the main biomarker of VTE and speculated a role for sP-selectin. The impact of thrombin generation was limited and no role emerged for the PPL clotting time. These observations need to be confirmed in large management studies.

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