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F W Leebeek

Publications and source records attributed to F W Leebeek.

24 records · Page 2Linked to original sources
PubMed1991

A shift in balance between profibrinolytic and antifibrinolytic factors causes enhanced fibrinolysis in cirrhosis.

The aim of this study was to assess the cause of enhanced fibrinolysis in cirrhosis by studying the balance between profibrinolytic and antifibrinolytic proteins in 24 patients with mild or severe cirrhosis. Antigen levels of both tissue-type plasminogen activator and plasminogen-activator inhibitor 1 were increased in mild and severe cirrhosis. Activity levels showed a very wide variability, but median activity levels of both proteins were normal. In most patients, the increase in tissue-type plasminogen activator was counterbalanced by the increased levels of plasminogen-activator inhibitor 1, but in a subgroup of patients the change in balance resulted in extremely high tissue-type plasminogen-activator levels. The specific activity of both proteins (activity/antigen quotient) was reduced in either mild or severe cirrhosis. This finding indicates either that more enzyme-inhibitor complexes circulate in the blood of patients with cirrhosis than in normal individuals or that dysfunctional molecules circulate. Plasminogen and alpha 2-antiplasmin antigen and activity levels were decreased in both mild and severe cirrhosis. The binding of alpha 2-antiplasmin to fibrin was decreased in severe cirrhosis, making fibrin clots more susceptible to lysis. Clot lysis experiments were performed to see if equal decreases in plasminogen and alpha 2-antiplasmin levels, as found in cirrhosis, result in a change in the rate of fibrinolysis. It was found that the proportionate decreases led to enhancement of fibrinolysis, indicating that the inhibitor depletion is more important than the proenzyme depletion. The authors conclude that enhanced fibrinolysis frequently found in cirrhosis may be attributed to an increased tissue-type plasminogen-activator activity relative to plasminogen-activator-inhibitor activity and decreased levels of alpha 2-antiplasmin, resulting in a reduced binding of alpha 2-antiplasmin to fibrin.

Fibrin↗
PubMed1990

Plasmin inhibitors in the prevention of systemic effects during thrombolytic therapy: specific role of the plasminogen-binding form of alpha 2-antiplasmin.

To delineate the role of plasmin inhibitors, especially the two molecular forms of alpha 2-antiplasmin (that is, the plasminogen-binding and the nonplasminogen-binding forms), in the control of systemic effects during thrombolytic therapy, the consumption of plasmin inhibitors and the degree of fibrinogen breakdown were studied in 35 patients with acute myocardial infarction treated with recombinant tissue-type plasminogen activator (rt-PA) or streptokinase. At a low degree of plasminogen activation (in six patients treated with rt-PA), plasminogen-binding alpha 2-antiplasmin was consumed first. At a higher degree of plasminogen activation (in 20 patients), plasminogen-binding alpha 2-antiplasmin became exhausted (less than 20%) and other plasmin inhibitors (that is, nonplasminogen-binding alpha 2-antiplasmin and alpha 2-macroglobulin) were consumed. After extensive plasminogen activation (in nine patients treated with streptokinase), plasminogen-binding alpha 2-antiplasmin consumption was complete and nonplasminogen-binding alpha 2-antiplasmin and alpha 2-macroglobulin were consumed to about 30% to 50% of the pretreatment level. No significant C1-inactivator consumption occurred, even at extreme degrees of plasminogen activation. Fibrinogen breakdown as a marker for systemic effects correlated strongly with consumption of plasminogen-binding alpha 2-antiplasmin. Fibrinogen breakdown did occur, but only when the amount of plasminogen-binding alpha 2-antiplasmin was decreased to less than 20% of the pretreatment level. The other plasmin inhibitors could not prevent fibrinogen breakdown. These results were confirmed by in vitro studies. It is concluded that plasminogen-binding alpha 2-antiplasmin is the most important inhibitor of plasmin in the circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Complement C1 Inactivator Proteins↗
PubMed1989

Severe thrombotic tendency associated with a type I plasminogen deficiency.

We report a 45-year-old female patient with recurrent spontaneous deep vein thrombosis associated with an isolated hypoplasminogenemia (plasminogen activity and antigen level of 42% and 37%, respectively). The plasminogen molecule was normal as demonstrated by a normal activation by tissue plasminogen activator, electrophoretic mobility on crossed immunoelectrophoresis, molecular weight, and binding to lysine sepharose. All other hemostatic parameters predisposing to recurrent thrombosis were normal. A stimulation test with desmopressin acetate (DDAVP) showed a normal plasma rise of both tissue plasminogen activator and factor VIIIR:WF. This isolated plasminogen deficiency apparently is due to a decreased synthesis of a normal plasminogen molecule and is associated with a severe thrombotic tendency.

Deamino Arginine Vasopressin↗
PubMed1989

Histidine-rich glycoprotein is elevated in mild liver cirrhosis and decreased in moderate and severe liver cirrhosis.

Histidine-rich glycoprotein (HRG) reduces by complex formation with plasminogen the amount of "free" plasminogen in circulation and is therefore considered an inhibitor of fibrinolysis. We studied the levels of both HRG and plasminogen in patients with different degrees of liver cirrhosis to assess the role of HRG in enhanced fibrinolysis in these patients. In mild (Child A) cirrhosis, HRG levels unexpectedly were significantly increased. The total plasminogen level and the calculated amount of free plasminogen were decreased. In moderate (Child B) cirrhosis, both HRG levels and total plasminogen levels were reduced, resulting in a normal amount of free plasminogen in circulation. In severe (Child C) cirrhosis, HRG level, total plasminogen level, and free plasminogen level were all decreased. Because the HRG level is increased in Child A liver cirrhosis, we suggest that other mechanisms, other than simply a decreased synthetic capacity of the liver, contribute to the changes in HRG levels in patients with liver disease. Because of the reduction of free plasminogen levels in severe liver cirrhosis, we propose that the decrease in HRG levels in liver cirrhosis plays no role in enhanced fibrinolysis in these patients. The increase in the HRG level in Child A liver cirrhosis may be of importance in future studies on familial thrombosis associated with elevated levels of HRG, where mild liver dysfunction should at least be excluded.

Adult↗
PubMed1988

Mild haemostatic problems associated with congenital heterozygous alpha 2-antiplasmin deficiency.

A Dutch family, of which 13 members are heterozygotes, deficient for alpha 2-antiplasmin (alpha 2-AP) is reported. Clinical studies showed that 2 heterozygotes had a mild bleeding tendency, which presented as bleeding episodes after tooth extraction and after surgery and, in one patient, also as excessive menstruation. Laboratory investigations revealed an alpha 2-AP activity of 62% (51-71) (median and range) and an antigen level of 60% (60-66). The plasminogen binding as well as the fibrin binding properties of alpha 2-AP were normal. Plasminogen concentrations were significantly higher in the heterozygotes compared to the other family members. However, free plasminogen not bound to histidine-rich glycoprotein was not significantly different between these two groups. We propose that in this family the deficiency of alpha 2-AP is due to a decreased synthesis of a normal alpha 2-AP molecule. This present study brings the frequency of heterozygous alpha 2-AP deficient patients with a bleeding tendency to 13 out of 59 heterozygotes reported in the literature.

Adult↗