Figure 1.
Overview of the fibrinolytic process. α2-AP, α2-antiplasmin; F, coagulation factor; PAI, plasminogen activator inhibitor; PL, phospholipids; TAFI, thrombin-activatable fibrinolysis inhibitor; TF, tissue factor; tPA, tissue plasminogen activator.
Figure 1.
Overview of the fibrinolytic process. α2-AP, α2-antiplasmin; F, coagulation factor; PAI, plasminogen activator inhibitor; PL, phospholipids; TAFI, thrombin-activatable fibrinolysis inhibitor; TF, tissue factor; tPA, tissue plasminogen activator.
Figure 2.
The clot-lysis curve and derived parameters.
Figure 3.
Top: Example of lysis resistance: only partial lysis is obtained. Bottom: Example of flat curve showing no net fibrin formation. Note the baseline correction.
Table 1.
Interpretation of clot-lysis results.
Parameter | Reference Interval [15] | Represents | Interpretation |
---|
Peak absorbance (AU) | 0.18–0.74 | Maximum fibrin concentration reached in well | ↑: Increased procoagulant activity; high plasma fibrinogen ↓: Decreased procoagulant activity, may be due to low plasma levels of coagulation factors or fibrinogen |
Integral (AU * s) | 219–1051 | Net fibrin formation Balance between fibrin formation and breakdown | ↑: Increased procoagulant activity; decreased endogenous anticoagulant activity; decreased fibrinolytic capacity ↓: Decreased procoagulant activity or clot stability, may be due to low circulating coagulation factors, fibrinogen or factor XIII; increased fibrinolytic activity |
50% lysis time (s) | 309–1565 | Time from maximum fibrin concentration is reached until 50% of the clot is lysed 1 | ↑: Decreased fibrinolytic capacity, may be due to low circulating plasminogen, high PAI-1 and/or TAFI [16] or anti-fibrinolytic treatment ↓: Increased fibrinolytic activity may be due to high plasma levels of tPA or uPA |
Table 2.
Clot-lysis parameters with tissue factor vs. thrombin.
Parameter | Thrombin 0.03 U/mL | Tissue Factor 1:5000 |
---|
Peak absorbance (AU) | 0.32 (0.26–0.40) | 0.68 (0.59–0.75) |
Integral (AU × s) | 408 (289–585) | 1381 (1083–1733) |
50% lysis time (s) | 726 (570–912) | 1483 (1154–1828) |
Table 3.
Clot-lysis parameters with tissue plasminogen activator (tPA) 83 ng/mL vs. 116 ng/mL.
Parameter | tPA 83 ng/mL | tPA 116 ng/mL |
---|
Peak absorbance (AU) | 0.69 (0.61–0.76) | 0.68 (0.58–0.75) |
Integral (AU × s) | 1410 (1111–1748) | 826 (665–1025) |
50% lysis time (s) | 1509 (1166–1830) | 802 (653–1027) |
Table 4.
The clot-lysis assay in clinical conditions.
Condition | Findings |
---|
Cardiovascular disease | ACS: ↑ lysis time ACS patients vs. healthy controls [20]; ↑ lysis time at ACS associated with ↑ 1-year mortality [21] Stable CAD: ↑ lysis time in CAD patients with previous MI [22]; ↑ integral but not lysis time associated with subsequent poor cardiovascular outcome [23] |
Ischaemic stroke | ↑ lysis time in stroke patients at onset vs. healthy controls [24]; ↑ lysis time at onset associated with poor 3-month neurological function [25] |
Venous thrombosis | ↑ lysis time in DVT and PE patients compared with healthy controls [26,27]; in PE, ↑ lysis time associated with ↑ 12-month mortality [28] ↓ lysis time in patients with PE vs. patients with DVT alone [29] ↑ lysis time may predict VTE recurrence [30], though other studies found no association [16,31] |
Diabetes mellitus | ↑ integral and lysis time in CAD patients with type 2 diabetes vs. non-diabetic patients [32] |
Hepatic dysfunction | Stable cirrhosis: uncertain; may vary according to etiology. ASH: ↓ lysis time; NASH: ↑ lysis time [33,34] ACLF: variable lysis times, influenced by concurrent factors [35] ALF: ↑↑ lysis time/lysis resistance |
Sepsis | ↑ lysis time in sepsis vs. healthy controls [36] and in septic vs. non-septic ACLF patients [35]; ↑ lysis time associated with lower platelet count but not survival [36] ↑ integral in sepsis vs. healthy controls; flat or lysis resistant clot-lysis curves associated with ↑ DIC and SOFA score * |