Plasmin-α2-plasmin inhibitor complex in plasma of patients with disseminated intravascular coagulation

Abstract Background The functional dynamics of coagulation and fibrinolysis in patients with disseminated intravascular coagulation (DIC) vary due to the pathology and severity of various underlying diseases. Conventional measurements of hemostasis such as thrombin–antithrombin complex, plasmin-α2-plasmin-inhibitor complex, and fibrinogen-fibrin degradation products may not always reflect critical pathophysiologic mechanisms in DIC. This article aims to clarify the pathology of sepsis-associated DIC using assessment of comprehensive coagulation and fibrinolysis. Methods Plasma samples were obtained from 57 patients with sepsis-associated DIC at the time of initial diagnosis. Hemostasis parameters were quantified by clot-fibrinolysis waveform analysis (CFWA) and thrombin/plasmin generation assays (T/P-GA). The results were expressed as ratios relative to normal plasma. Results CFWA demonstrated that the maximum coagulation velocity (|min1|) ratio modestly increased to median 1.40 (min − max: 0.10 − 2.60) but the maximum fibrinolytic velocity (|FL-min1|) ratio decreased to 0.61 (0 − 1.19). T/P-GA indicated that the peak thrombin (Th-Peak) ratio moderately decreased to 0.71 (0.22 − 1.20), whereas the peak plasmin (Plm-Peak) ratio substantially decreased to 0.35 (0.02 − 1.43). Statistical comparisons identified a correlation between |min1| and Th-Peak ratios (ρ = 0.55, p < 0.001), together with a strong correlation between |FL-min1| and Plm-Peak ratios (ρ = 0.71, p < 0.001), suggesting that CFWA reflected the balance between thrombin and plasmin generation. With |min1| and |FL-min1| ratios, DIC was classified as follows: coagulation-predominant, coagulation/fibrinolysis-balanced, fibrinolysis-predominant, and consumption-impaired coagulation. The majority of patients in our cohort (80.7%) were coagulation-predominant. Conclusion A pathological clarification of sepsis-associated DIC based on the assessment of coagulation and fibrinolysis dynamics may be useful for the hemostatic monitoring and management of optimal treatment in these individuals.

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Depressed plasma activity of plasminogen or α2 plasmin inhibitor is not due to consumption coagulopathy in septic patients with disseminated intravascular coagulation

Blood Coagulation & Fibrinolysis ◽

10.1097/00001721-200106000-00008 ◽

2001 ◽

Vol 12 (4) ◽

pp. 275-281 ◽

Cited By ~ 13

Author(s):

H. Asakura ◽

Y. Ontachi ◽

T. Mizutani ◽

M. Kato ◽

T. Ito ◽

...

Keyword(s):

Disseminated Intravascular Coagulation ◽

Consumption Coagulopathy ◽

Intravascular Coagulation ◽

Plasmin Inhibitor ◽

Plasma Activity

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Clinical Features of Disseminated Intravascular Coagulation According to the French-American-British Classification in Patients With Acute Leukemia and Thrombomodulin Alfa Treatment—A Cohort Study Using a Postmarketing Surveillance Database

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/10760296211054094 ◽

2021 ◽

Vol 27 ◽

pp. 107602962110540

Author(s):

Seki Yoshinobu ◽

Goichi Honda ◽

Noriaki Kawano ◽

Toshimasa Uchiyama ◽

Kazuo Kawasugi ◽

...

Keyword(s):

Acute Leukemia ◽

Clinical Features ◽

Disseminated Intravascular Coagulation ◽

Lymphoblastic Leukemia ◽

Postmarketing Surveillance ◽

Intravascular Coagulation ◽

Plasmin Inhibitor ◽

Surveillance Database ◽

French American British

The aims of this study were to analyze the clinical features of a large number of cases with disseminated intravascular coagulation (DIC) associated with acute leukemia and to assess the safety and efficacy of thrombomodulin alfa (TM-α) using the French-American-British (FAB) classification of hematological malignancies. We retrospectively examined 644 patients with acute leukemia in postmarketing surveillance for TM-α. M3, M2, M4, M1, and M5 subtypes of acute myeloid leukemia (AML) and L2 and L1 subtypes of acute lymphoblastic leukemia (ALL) have been found more frequently among patients with DIC. Bleeding symptoms at baseline were more frequent in M3 and M7 subtypes. Fibrinogen concentrations were lower, and plasmin-plasmin inhibitor complex values were higher in M3 and Philadelphia-positive (Ph+) ALL. Overall DIC resolution rate was 60.2%, higher in L1 and Ph+ ALL, lower in M1, and generally higher in ALL than in AML. Overall survival rate was generally high, at 79.8%, with higher rates in L3, Ph+ ALL, and M3. Regardless of FAB subgroup, TM-α showed improved bleeding symptoms and DIC scores in clinical practice for DIC patients with acute leukemia.

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Increased Soluble Fibrin in Plasma of Patients with Disseminated Intravascular Coagulation

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/107602960300900308 ◽

2003 ◽

Vol 9 (3) ◽

pp. 233-240 ◽

Cited By ~ 27

Author(s):

Hideo Wada ◽

Tomohiro Sase ◽

Takeshi Matsumoto ◽

Fumihiko Kushiya ◽

Miho Sakakura ◽

...

Keyword(s):

Disseminated Intravascular Coagulation ◽

Plasma Levels ◽

Operating Characteristic ◽

Degradation Products ◽

Characteristic Analysis ◽

Soluble Fibrin ◽

Intravascular Coagulation ◽

Hemostatic Markers ◽

Plasmin Inhibitor

Plasma levels of soluble fibrin (SF) were measured in 1184 patients with disseminated intravascular coagulation (DIC) according to Japanese Ministry of Health and Welfare (JMHW) criteria. The usefulness of SF for the diagnosis of DIC was compared with other hemostatic molecular markers. Most hemostatic markers were significantly increased in patients with DIC than in those without DIC. Plasma levels of fibrin and fibrinogen degradation products, thrombin-antihtrombin complex, plasmin-plasmin inhibitor complex, D-dimer, thrombomodulin, and SF levels were also significantly higher in those with pre-DIC than in those without DIC. In classification of overt DIC by International Society of Thrombosis and Haemostasis (ISTH) criteria, most hemostatic markers were significantly increased in patients with overt DIC than in those without overt DIC. Plasma levels of SF 'in patients with DIC were significantly higher than those in patients with pre-DIC, which were significantly higher than in those without DIC. Plasma levels of SF were also significantly higher in patients with overt DIC than in those with non-overt DIC. The correlation between plasma SF levels and DIC score according to JMHW criteria or ISTH criteria was good. Receiver operating characteristic analysis shows that SF was the best marker for the diagnosis of DIC or overt DIC. These findings suggest that plasma SF might be useful marker for the diagnosis of DIC or overt DIC.

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Outcome of Disseminated Intravascular Coagulation in Relation to the Score when Treatment was Begun

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649835 ◽

1995 ◽

Vol 74 (03) ◽

pp. 848-852 ◽

Cited By ~ 130

Author(s):

Hideo Wada ◽

Yoshihiro Wakita ◽

Tutomu Nakase ◽

Minori Shimura ◽

Katsuyo Hiyoyama ◽

...

Keyword(s):

Disseminated Intravascular Coagulation ◽

Plasma Levels ◽

Early Stage ◽

Coagulation Factors ◽

Underlying Disease ◽

Blood Coagulation Factors ◽

Intravascular Coagulation ◽

The Relationship ◽

Plasmin Inhibitor ◽

D Dimer

SummaryWe examined 395 patients with disseminated intravascular coagulation (DIC) divided into two groups: non-leukemic and leukemic. In 58% of the patients as a whole, treatment of DIC resulted in complete or partial remission, while exacerbation and death occurred in 31%. The efficacy of DIC treatment in the non-leukemic group was less than that in the leukemic group, indicating that the outcome of DIC depended, in part, on the underlying disease. We examined hemostatic indicators in relation to DIC score: prothrombin time (PT) ratio, FDP, platelet count, and fibrinogen levels were found to be important indicators for the diagnosis of DIC, but not for Pre-DIC. Plasma levels of fibrin-D-dimer, thrombin-antithrombin complex (TAT), and plasmin- plasmin inhibitor complex (PPIC) were significantly increased in pre-DIC. The efficacy of treatment in relation to the DIC score when the treatment was begun showed that greater efficacy was achieved in pre-DIC than in DIC patients. The outcome was poorer with increasing DIC score, suggesting that early diagnosis and early treatment are important. On examining the relationship between outcome and hemostatic indicators, we found that the PT ratio and the levels of antithrombin, plasminogen, PPIC, the PPIC/TAT ratio, and thrombomodulin were related to outcome, suggesting that very high consumption of blood coagulation factors, liver dysfunction, hypofibrinolysis, or organ failure caused a poor outcome. Although the outcome in DIC patients may not depend substantially on plasma levels of TAT and fibrin-D- dimer, we can use these indicators to treat DIC patients at an early stage.

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