Document Detail

Paradoxical hyperfibrinolysis is associated with a more intensely haemorrhagic phenotype in severe congenital haemophilia.
MedLine Citation:
PMID:  12410645     Owner:  NLM     Status:  MEDLINE    
To elucidate potential causes for differing bleeding phenotypes of haemophilic patients of identical degree of coagulation factor deficiency, we investigated 21 male patients with severe haemophilia. Median annual coagulation factor demand and the extent of haemophilic arthropathy were used to discriminate between intensely and less intensely haemorrhagic phenotypes. Haemophiliacs with a median annual coagulation factor demand of 800 IU per kg bodyweight or more and with three or more joints affected by haemophilic arthropathy represented the intensely haemorrhagic phenotype group; all other patients comprised the less intense group. The discriminator values represent the respective medians of the overall group. The results of activated partial thromboplastin time, endogenous thrombin potential, pro- and anticoagulant factor analysis did not differ between the two groups. Median tissue-type plasminogen activator concentration (TPA) was elevated significantly in haemophiliacs with an intensely haemorrhagic phenotype, as was the activity of the thrombin-activatable fibrinolysis inhibitor. Median activity of the plasminogen activator inhibitor 1 (PAI 1) and the concentration of TPA-PAI 1 complexes were increased to approximately double those in nonsevere haemophiliacs. Coexistent congenital thrombophilia was found significantly more often in the less intensely haemorrhagic group. Thus, increased stimulation of the fibrinolytic system was associated with a more intensely haemorrhagic phenotype in our patients. We hypothesize that ineffective haemophilic haemostasis in response to trauma evokes a protracted stimulation of the entire haemostatic system, including costimulation of fibrinolysis. The absence of coexistent congenital thrombophilia predisposes to excess stimulation of fibrinolysis, which cannot be downregulated effectively due to the dysfunctional intrinsic pathway. The association of a more intensely haemorrhagic phenotype with a paradoxical hyperstimulation of the fibrinolytic system resembles a vicious circle, where bleeding seems to cause predisposition to more bleeding.
M Grünewald; A Siegemund; A Grünewald; A Konegan; M Koksch; M Griesshammer
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Haemophilia : the official journal of the World Federation of Hemophilia     Volume:  8     ISSN:  1351-8216     ISO Abbreviation:  Haemophilia     Publication Date:  2002 Nov 
Date Detail:
Created Date:  2002-11-04     Completed Date:  2003-04-14     Revised Date:  2009-10-21    
Medline Journal Info:
Nlm Unique ID:  9442916     Medline TA:  Haemophilia     Country:  England    
Other Details:
Languages:  eng     Pagination:  768-75     Citation Subset:  IM    
Department of Haematology, Haemostaseology Division, University of Ulm, Germany.
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MeSH Terms
Blood Coagulation Factors / analysis
Drug Administration Schedule
Factor IX / administration & dosage
Factor VIII / administration & dosage
Hemarthrosis / blood
Hemophilia A / blood*,  complications
Hemophilia B / blood*,  complications
Hemorrhage / blood*,  etiology
Middle Aged
Thrombophilia / complications
Tissue Plasminogen Activator / analysis
Reg. No./Substance:
0/Blood Coagulation Factors; 9001-27-8/Factor VIII; 9001-28-9/Factor IX; EC Plasminogen Activator

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