J Korean Med Sci.  2011 Apr;26(4):474-481. 10.3346/jkms.2011.26.4.474.

Tissue Plasminogen Activator and Plasminogen Activator Inhibitor-1 Levels in Patients with Acute Paraquat Intoxication

• Seok SJ
• Kim SJ
• Gil HW
• Yang JO
• Lee EY
• Hong SY

• KMID: 1777876
• DOI: http://doi.org/10.3346/jkms.2011.26.4.474

Abstract

To investigate the effects of reactive oxygen species (ROS) on tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) plasma levels, and their possible implications on clinical outcome, we measured tPA and PAI-1 levels in 101 patients with acute paraquat (PQ) intoxication. The control group consisted of patients who ingested non-PQ pesticides during the same period. tPA and PAI-1 levels were higher in the PQ group than in the controls. PQ levels were significantly correlated with ingested amount, timelag to hospital, tPA level, and hospitalization duration. tPA levels were correlated with PAI-1, fibrin degradation product (FDP), and D-dimer. D-dimer levels were lower in the PQ group than in the controls. Univariate analysis indicated the following significant determinants of death: age, ingested amount, PQ level, timelag to hospital, serum creatinine, lipase, pH, pCO2, HCO3-, WBC, FDP, PAI-1, and tPA. However, multivariate analysis indicated that only PQ level was significant independent factor predicting death. In conclusion, tPA and PAI-1 levels were higher, while D-dimer levels were lower in the PQ group than in the controls, implying that ROS stimulate tPA and PAI-1, but PAI-1 activity overrides tPA activity in this setting. Decreased fibrinolytic activity appears to be one of the clinical characteristics of acute PQ intoxication.

Keyword

Tissue Plasminogen Activator; Plasminogen Activator Inhibitor 1; Paraquat; Reactive Oxygen Species

MeSH Terms

Acute Disease
Adult
Aged
Female
Fibrin Fibrinogen Degradation Products/analysis
Herbicides/blood/*poisoning
Humans
Male
Middle Aged
Paraquat/blood/*poisoning
Plasminogen Activator Inhibitor 1/*blood
Reactive Oxygen Species/metabolism
Risk Factors
Tissue Plasminogen Activator/*blood
Tomography, X-Ray Computed

Figure

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  Fig. 1 Comparison of the tPA and PAI-1 levels between the control and PQ intoxication groups. Note that tPA and PAI-1 levels are significantly higher in the PQ group than in the control group.

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  Fig. 2 Comparison of the levels of D-dimer and fibvin degradation product (FDP) between the control and PQ intoxication groups. Note that the D-dimer levels are significantly lower in the PQ group than in the control group.

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  Fig. 3 Relationship between PQ levels and the levels of tPA and PAI-1 in PQ-intoxicated patients. PQ-intoxicated patients were divided into 2 subgroups according to their PQ level: ≥ 10 µg/mL vs < 10 µg/mL.

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  Fig. 4 Relationship between the amount of PQ ingested and the levels of tPA (A) and PAI-1 (B) in PQ-intoxicated patients. Note that there is a positive correlation between the amount of PQ ingested and the levels of tPA and PAI-1.

• 

  Fig. 5 Pulmonary artery computerized tomography angiogram from a PQ-intoxicated patient who suffered pulmonary artery thrombosis. A 64-yr-old woman swallowed a mouthful of a 24.5% PQ solution. Her plasma PQ level was 0.08 µg/mL at 15 hr after PQ ingestion. On day 9 of admission, the patient complained of right sided chest pain and dyspnea. Arterial blood gas analysis indicated: pH, 7.459; PaO2, 46.3 mmHg; and PaCO2, 37.9 mmHg. D-dimer was elevated at 2.9 (0-0.5) µg/mL. A chest X-ray showed an increased density along the apex of the right lung. (A) obtained at 9 days after PQ ingestion. Note the thrombus in the pulmonary artery and interlobar pulmonary artery (arrow a, b). A subcutaneous injection of low molecular weight heparin was started on the 9th day and warfarin was started on the 10th day. (B) obtained at 20 days after PQ ingestion. The thrombus was completely resolved (arrow c, d). The patient made a full recovery from this condition.

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  Fig. 6 Low extremity venogram computerized tomography from a PQ-intoxicated patient who suffered deep vein thrombosis in the leg. A 50-yr-old woman swallowed 2 mouthfuls of a 24.5% PQ solution. (A) On day 21 after admission, the patient complained of left leg swelling and pain, and a deep vein thrombosis was suspected. D-dimer was elevated at 25.6 µg/mL. (B) Deep vein thrombosis was noted in the left deep venous system (arrow a, b). (C, D) Obtained at 63-days after PQ ingestion. The extent of the thrombus was significantly reduced (arrow c, d).

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