More on Shortened PTTs

More on Shortened PTTs
Feb 14, 2010 5:30pm

Here is a reference Dr. Larry Smith found describing the relationship of a short PTT with other coagulation parameters followed by three references found by Dr. Elaine Keohane on the same topic.

Blood Coagul Fibrinolysis. 2010 Mar;21(2):152-7.
A laboratory evaluation into the short activated partial thromboplastin time.
Mina AFavaloro EJMohammed SKoutts J.
Department of Endocrinology, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, NSW 1245, Australia.
Although short activated partial thromboplastin times (APTTs) are generally considered to be laboratory artefacts of problematic blood collections, there is mounting evidence that in some cases a short APTT may reflect a hypercoagulable state, potentially associated with increased thrombotic risk and adverse cardiovascular events. We prospectively evaluated the phenomenon of short APTTs in 113 consecutive samples compared with an equal number of age and sex-matched normal APTT samples. We found a significant difference in various test parameters including prothrombin time (PT ), Factor (F) V, FVIII , FXI, FXII, von Willebrand factor (VWF ) antigen and collagen-binding activity, and in the level of procoagulant phospholipids, as assessed using a novel assay procedure (XACT). Interestingly, there was a significant negative association for fibrinogen, and although elevated, there was no significant association for FIX. On the basis of identified consecutive samples having multiple low APTTs on several sequential days, a proportion of laboratory-defined short APTTs appear to represent in-vivo hypercoagulability. In conclusion, plasma from patients presenting with short APTTs is reflective of a complex hypercoagulant milieu that could feasibly contribute to thrombotic risk, and 20% or more of laboratory definable short APTTs appear to reflect in-vivo phenomenon.

Pathophysiol Haemost Thromb. 2002 May-Jun;32(3):137-42.
Abnormally short activated partial thromboplastin times are related to elevated plasma levels of TAT , F1+2, D-dimer and FVIII :C.
Laboratory for Clinical Chemistry, Hematology and Immunology, Medical Center of Alkmaar, Alkmaar, The Netherlands. E.ten.Boekel@mca.nl
Abnormally short activated partial thromboplastin times (APTTs) are associated with an increased risk of thrombotic disorders. We have examined the status of coagulation activity in subjects with short APTTs. In addition, the presence of the thrombotic risk factors G1691A-factor V, G20210A-prothrombin gene mutation and factor VIII coagulant activity (FVIII :C) was determined. Plasma levels of TAT , F1+2, D-dimer and FVIII :C were markedly higher in subjects with short APTTs compared with subjects with normal APTTs. APTTs were inversely related to TAT , F1+2, D-dimer and FVIII :C levels. The prevalence of G1691A-factor V and G20210A-prothrombin gene mutation between the group with short APTTs and the control group was not significantly different. Hence, these gene polymorphisms do not contribute to the increased risk of thrombosis associated with short APTTs. In conclusion, short APTTs are indicative of marked coagulation activity and elevated FVIII :C levels. Elevated FVIII :C levels may play a pathogenic role in the increased risk of thrombosis associated with abnormally short APTTs
Thromb Res. 2007;121(3):361-7. Epub 2007 Jun 12.
Detection of shortened activated partial thromboplastin times: an evaluation of different commercial reagents.
Department of Clinical laboratory, Sint Lucas Andreas Hospital Amsterdam, The Netherlands. e.tenboekel@slaz.nl
INTRODUCTION: Abnormally shortened activated partial thromboplastin times (aPTT ) are associated with significantly increased risk of thrombotic disorders and in-hospital mortality. Shortened aPTTs have been related to increased levels of factor (F) VIII and thrombin-antithrombin complex (TAT ). In the current study, four different commercial aPTT reagents were evaluated for their performance to detect shortened aPTTs. MATERIALS AND METHODS: aPTT of 400 patients was determined using Actin-FS (Dade Behring), APTT-SP (Instrumentation Laboratory), Automated-APTT (bioMerieux) and Platelin-LS (bioMerieux) reagents. FVIII , FIX, FXI and TAT levels were measured in shortened and normal aPTT samples. RESULTS: An association between shortened aPTTs and elevated levels of coagulation factors (FVIII , FIX and FXI) and thrombin generation (TAT ) was found with all tested aPTT reagents. Method-comparison studies demonstrated good agreement between Instrumentation Laboratory and bioMerieux reagents. However, 53 to 59% of the patients with a shortened aPTT measured with Actin-FS reagent was determined as a normal aPTT with APTT-SP, Automated-APTT and Platelin-LS reagents. These patients had increased levels of FVIII , FIX and FXI and moderately increased levels of TAT. CONCLUSION: Overall, an acceptable agreement between the different commercial reagents was found with respect to detection of short aPTTs. However, a disparity between some of reagents existed. Actin-FS reagent appeared to be more sensitive in inducing shortened aPTT reactions than APTT-SP, Automated-APTT and Platelin-LS reagents.
Semin Thromb Hemost. 2008 Oct;34(7):604-11. Epub 2008 Dec 15.
Activated partial thromboplastin time: new tricks for an old dogma.
Sezione di Chimica Clinica, Università di Verona, Verona, Italy. giuseppe.lippi@univr.it
The activated partial thromboplastin time (APTT ) is the most common coagulation test procedure performed in routine laboratories, apart from the prothrombin time. The test is traditionally used for identifying quantitative and qualitative abnormalities in the intrinsic and common pathways of coagulation, monitoring anticoagulant therapy with unfractionated heparin, and detecting inhibitors of blood coagulation, the most common of which is the lupus anticoagulant. Whereas short APTT values have been mostly overlooked in the past, recent evidence suggests that these might be associated with hypercoagulability. Although clinical relevance is yet to be clearly defined, hypercoagulability detected by a shortened APTT appears to be significantly associated with a major risk of venous thromboembolism independently from other variables such as blood group, the presence of inherited thrombophilia, and factor VIII levels. This novel finding suggests that this traditional, simple, and inexpensive test might have renewed utility along with traditional thrombophilic tests in the evaluation of venous thromboembolic risk. In addition, APTT waveform analysis is also providing mounting evidence of added utility, in particular for identifying sepsis and disseminated intravascular coagulation in critically ill patients (particularly where this might worsen the prognosis), for monitoring therapy in patients with inhibitors, and as a diagnostic aid to identify patients with antiphospholipid antibodies. In total, such emerging evidence suggests that the APTT is either an old dogma displaying new tricks or else might describe a new dogma for an old laboratory trick.
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Here is a reference Dr. Larry Smith found describing the relationship of a short PTT with other coagulation parameters followed by three references found by Dr. Elaine Keohane on the same topic.

Blood Coagul Fibrinolysis. 2010 Mar;21(2):152-7.
A laboratory evaluation into the short activated partial thromboplastin time.
Mina AFavaloro EJMohammed SKoutts J.
Department of Endocrinology, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, NSW 1245, Australia.
Although short activated partial thromboplastin times (APTTs) are generally considered to be laboratory artefacts of problematic blood collections, there is mounting evidence that in some cases a short APTT may reflect a hypercoagulable state, potentially associated with increased thrombotic risk and adverse cardiovascular events. We prospectively evaluated the phenomenon of short APTTs in 113 consecutive samples compared with an equal number of age and sex-matched normal APTT samples. We found a significant difference in various test parameters including prothrombin time (PT ), Factor (F) V, FVIII , FXI, FXII, von Willebrand factor (VWF ) antigen and collagen-binding activity, and in the level of procoagulant phospholipids, as assessed using a novel assay procedure (XACT). Interestingly, there was a significant negative association for fibrinogen, and although elevated, there was no significant association for FIX. On the basis of identified consecutive samples having multiple low APTTs on several sequential days, a proportion of laboratory-defined short APTTs appear to represent in-vivo hypercoagulability. In conclusion, plasma from patients presenting with short APTTs is reflective of a complex hypercoagulant milieu that could feasibly contribute to thrombotic risk, and 20% or more of laboratory definable short APTTs appear to reflect in-vivo phenomenon.

Pathophysiol Haemost Thromb. 2002 May-Jun;32(3):137-42.
Abnormally short activated partial thromboplastin times are related to elevated plasma levels of TAT , F1+2, D-dimer and FVIII :C.
Laboratory for Clinical Chemistry, Hematology and Immunology, Medical Center of Alkmaar, Alkmaar, The Netherlands. E.ten.Boekel@mca.nl
Abnormally short activated partial thromboplastin times (APTTs) are associated with an increased risk of thrombotic disorders. We have examined the status of coagulation activity in subjects with short APTTs. In addition, the presence of the thrombotic risk factors G1691A-factor V, G20210A-prothrombin gene mutation and factor VIII coagulant activity (FVIII :C) was determined. Plasma levels of TAT , F1+2, D-dimer and FVIII :C were markedly higher in subjects with short APTTs compared with subjects with normal APTTs. APTTs were inversely related to TAT , F1+2, D-dimer and FVIII :C levels. The prevalence of G1691A-factor V and G20210A-prothrombin gene mutation between the group with short APTTs and the control group was not significantly different. Hence, these gene polymorphisms do not contribute to the increased risk of thrombosis associated with short APTTs. In conclusion, short APTTs are indicative of marked coagulation activity and elevated FVIII :C levels. Elevated FVIII :C levels may play a pathogenic role in the increased risk of thrombosis associated with abnormally short APTTs
Thromb Res. 2007;121(3):361-7. Epub 2007 Jun 12.
Detection of shortened activated partial thromboplastin times: an evaluation of different commercial reagents.
Department of Clinical laboratory, Sint Lucas Andreas Hospital Amsterdam, The Netherlands. e.tenboekel@slaz.nl
INTRODUCTION: Abnormally shortened activated partial thromboplastin times (aPTT ) are associated with significantly increased risk of thrombotic disorders and in-hospital mortality. Shortened aPTTs have been related to increased levels of factor (F) VIII and thrombin-antithrombin complex (TAT ). In the current study, four different commercial aPTT reagents were evaluated for their performance to detect shortened aPTTs. MATERIALS AND METHODS: aPTT of 400 patients was determined using Actin-FS (Dade Behring), APTT-SP (Instrumentation Laboratory), Automated-APTT (bioMerieux) and Platelin-LS (bioMerieux) reagents. FVIII , FIX, FXI and TAT levels were measured in shortened and normal aPTT samples. RESULTS: An association between shortened aPTTs and elevated levels of coagulation factors (FVIII , FIX and FXI) and thrombin generation (TAT ) was found with all tested aPTT reagents. Method-comparison studies demonstrated good agreement between Instrumentation Laboratory and bioMerieux reagents. However, 53 to 59% of the patients with a shortened aPTT measured with Actin-FS reagent was determined as a normal aPTT with APTT-SP, Automated-APTT and Platelin-LS reagents. These patients had increased levels of FVIII , FIX and FXI and moderately increased levels of TAT. CONCLUSION: Overall, an acceptable agreement between the different commercial reagents was found with respect to detection of short aPTTs. However, a disparity between some of reagents existed. Actin-FS reagent appeared to be more sensitive in inducing shortened aPTT reactions than APTT-SP, Automated-APTT and Platelin-LS reagents.
Semin Thromb Hemost. 2008 Oct;34(7):604-11. Epub 2008 Dec 15.
Activated partial thromboplastin time: new tricks for an old dogma.
Sezione di Chimica Clinica, Università di Verona, Verona, Italy. giuseppe.lippi@univr.it
The activated partial thromboplastin time (APTT ) is the most common coagulation test procedure performed in routine laboratories, apart from the prothrombin time. The test is traditionally used for identifying quantitative and qualitative abnormalities in the intrinsic and common pathways of coagulation, monitoring anticoagulant therapy with unfractionated heparin, and detecting inhibitors of blood coagulation, the most common of which is the lupus anticoagulant. Whereas short APTT values have been mostly overlooked in the past, recent evidence suggests that these might be associated with hypercoagulability. Although clinical relevance is yet to be clearly defined, hypercoagulability detected by a shortened APTT appears to be significantly associated with a major risk of venous thromboembolism independently from other variables such as blood group, the presence of inherited thrombophilia, and factor VIII levels. This novel finding suggests that this traditional, simple, and inexpensive test might have renewed utility along with traditional thrombophilic tests in the evaluation of venous thromboembolic risk. In addition, APTT waveform analysis is also providing mounting evidence of added utility, in particular for identifying sepsis and disseminated intravascular coagulation in critically ill patients (particularly where this might worsen the prognosis), for monitoring therapy in patients with inhibitors, and as a diagnostic aid to identify patients with antiphospholipid antibodies. In total, such emerging evidence suggests that the APTT is either an old dogma displaying new tricks or else might describe a new dogma for an old laboratory trick.

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