Journal of thrombosis and haemostasis : JTH
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J. Thromb. Haemost. · Aug 2004
Haplotypes of the EPCR gene, plasma sEPCR levels and the risk of deep venous thrombosis.
Binding of protein C (PC) to the endothelial cell PC receptor (EPCR) stimulates PC activation by increasing the affinity of PC for the thrombin-thrombomodulin complex. A soluble form of this receptor (sEPCR) circulates in plasma and inhibits both PC activation and APC anticoagulant activity. ⋯ Our data do not suggest a strong association between EPCR haplotypes and thrombosis risk, but low sEPCR levels appear to reduce the risk of DVT.
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J. Thromb. Haemost. · Aug 2004
Use of different D-dimer levels to exclude venous thromboembolism depending on clinical pretest probability.
Currently, the same D-dimer cut-off point is used to define a positive result for all patients with suspected venous thromboembolism, regardless of their pretest probability. However, use of a relatively high D-dimer cut-off point (lower sensitivity) for those with a low clinical pretest probability, and a low D-dimer cut-off point (higher sensitivity) for those with a high clinical pretest probability, may be preferable. To determine if using three different D-dimer cut-off points according to low, moderate or high clinical pretest probability has greater utility for exclusion of venous thromboembolism than using the same single D-dimer cut-off point in all patients. ⋯ When three pretest probability-specific cut-off points were used instead of the previously determined single D-dimer cut-off point (0.5 FEU microgram mL(-1)), sensitivity and negative predictive value were unchanged (95 and 98%, respectively), but specificity increased from 44.7 to 60.4% (P < 0.001). This resulted in exclusion of venous thromboembolism in 80 additional patients. Use of three pretest probability-specific D-dimer cut-off points rather than a single D-dimer cut-off point for all patients, has the potential to increase the utility of D-dimer testing for the diagnosis of venous thromboembolism.
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J. Thromb. Haemost. · Aug 2004
Effects of all-trans retinoic acid or chemotherapy on the molecular regulation of systemic blood coagulation and fibrinolysis in patients with acute promyelocytic leukemia.
We studied the pathogenesis of the bleeding disorder in acute promyelocytic leukemia by measuring procoagulant, profibrinolytic, and proinflammatory mediators in peripheral blood and bone marrow cells from 25 previously untreated patients. Patients were induced with either all-trans retinoic acid (ATRA) or chemotherapy. Plasma levels of fibrinopeptide A (FPA), fibrin d-dimer, thrombin antithrombin (TAT) complex, prothrombin fragment 1.2 (F1.2), urokinase-type plasminogen activator (uPA), tissue-type plasminogen activator (t-PA) and plasminogen activator-inhibitor 1 (PAI-1) were measured before and after therapy, as was the cellular expression of the genes for tissue factor (TF) and interleukin-1 beta (IL-1 beta). ⋯ Our data confirms and extends earlier observations by others that ATRA is more effective than chemotherapy alone in rapidly reducing the procoagulant burden of APL tumor cells. However, our data also suggests that cytokine expression in some patients may be accelerated by either chemotherapy or ATRA. The implications of this observation for understanding the retinoic acid syndrome will require further studies.
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J. Thromb. Haemost. · Aug 2004
Clinical criteria to prevent unnecessary diagnostic testing in emergency department patients with suspected pulmonary embolism.
Overuse of the d-dimer to screen for possible pulmonary embolism (PE) can have negative consequences. This study derives and tests clinical criteria to justify not ordering a d-dimer. The test threshold was estimated at 1.8% using the method of Pauker and Kassirer. ⋯ Application of the rule in the low-risk and very low-risk populations yielded sensitivities of 96% and 100% and specificities of 27% and 15%, respectively. The prevalence of PE in those who met the rule criteria was 1.4% (0.5-3.0%) and 0% (0-6.2%), respectively. The derived eight-factor block rule reduced the pretest probability below the test threshold for d-dimer in two validation populations, but the rule's utility was limited by low specificity.