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Fibrinolytic Disorders. ARUP Consult®. Retrieved February 15, 2026, https://arupconsult.com/content/fibrinolytic-disorders

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Fibrinolytic Disorders

Last Literature Review: November 2025 Last Update:

Medical Experts

Contributor

Smock

Kristi J. Smock, MD
Kristi J. Smock, MD
Professor of Pathology (Clinical), University of Utah
Vice President, ARUP Institute for Clinical and Experimental Pathology® (Research and Development)
Medical Director, Hemostasis/Thrombosis Laboratory, ARUP Laboratories
Contributor

Moser

Karen A. Moser, MD
Karen A. Moser, MD
Associate Professor of Pathology (Clinical), University of Utah
Medical Director, Hematopathology and Hemostasis/Thrombosis Laboratory, ARUP Laboratories

Fibrinolytic disorders are caused by absent or dysfunctional components of the fibrinolytic pathway. This pathway enzymatically degrades blood clots by breaking down fibrin networks once clots are no longer needed, playing a critical role in maintaining hemostatic balance. This process, known as fibrinolysis, is mediated by plasmin and tightly regulated by multiple activators and inhibitors. ,  Abnormalities in this pathway can lead to excessive thrombotic or bleeding risks, although the severity and type of clinical manifestation depend on the underlying cause.  These disorders may be congenital or acquired. Congenital forms include alpha 2-antiplasmin (α2-AP) deficiency, plasminogen activator inhibitor type I (PAI-1) deficiency, and Quebec platelet disorder. Acquired abnormalities of fibrinolysis typically occur secondary to conditions such as disseminated intravascular coagulation (DIC), trauma, malignancy, and sepsis.  Acquired causes should be considered before evaluating for rare congenital disorders. Although global fibrinolytic assays are under investigation, there is currently no single definitive laboratory test for diagnosing fibrinolytic disorders. Diagnosis relies on a comprehensive approach that integrates clinical context and family history with multiple laboratory assays. These tests are used to exclude more common bleeding disorders and infer fibrinolytic function. , 

Quick Answers for Clinicians

Which tests should be ordered before ordering specific tests for fibrinolytic disorders?

In the absence of a positive family history, fibrinolytic disorders are generally considered a diagnosis of exclusion. Initial laboratory evaluation should focus on ruling out more common bleeding disorders (such as hemophilia, von Willebrand disease [VWD], and functional platelet disorders) before proceeding to specialized fibrinolytic assays. The recommended workup for more common bleeding disorders includes :

  • Platelet count and peripheral blood smear to assess platelet number and morphology
  • Prothrombin time (PT) and activated partial thromboplastin time (aPTT) to assess intrinsic, extrinsic, and common pathways of coagulation
  • Fibrinogen activity to evaluate for fibrinogen disorders
  • Von Willebrand factor antigen and activity assays to evaluate for VWD
  • Factor VIII and IX activities to assess for hemophilia A and B or test for other factor activities if PT and aPTT results indicate other possible factor deficiencies
  • Platelet aggregation
  • Factor XIII activity and/or antigen testing

Indications for Testing

Fibrinolytic disorders lack a single pathognomonic clinical feature. Affected individuals may present with variable bleeding tendencies, and less commonly, with thrombotic events. Clinical suspicion typically arises after more common causes of abnormal bleeding have been excluded or when there is a known family history of a fibrinolytic disorder.

Symptoms associated with fibrinolytic disorders include:

  • Delayed bleeding following trauma or invasive procedures such as surgeries or dental extractions , 
  • Excessive or severe bleeding after procedures or injuries , 
  • Mucosal bleeding, such as heavy menstrual bleeding, epistaxis, and hematuria , 
  • Obstetric complications, including postpartum hemorrhage, miscarriage, or preterm birth , 
  • Mild or moderate bleeding symptoms not explained by platelet or coagulation defects 

Standard laboratory measurements of hemostasis (e.g., prothrombin time [PT], activated partial thromboplastin time [aPTT], fibrinogen, and platelet count) are typically normal. Specific testing to evaluate fibrinolytic function is required. 

Laboratory Testing

Laboratory evaluation of fibrinolysis includes global screening assays to assess overall fibrinolytic function, specific assays to measure individual components of the pathway, and, in some cases, genetic testing.

Global Screening Assays

Functional tests such as euglobulin clot lysis time (ECLT) and thromboelastography/rotational thromboelastometry (ROTEM) provide a global assessment of fibrinolytic activity. They are best used as an initial screening tool to determine if fibrinolytic activity is abnormal.  However, viscoelastic tests such as thromboelastography/ROTEM are not sensitive to milder disorders and typically only identify abnormally increased fibrinolysis in severe acquired disorders such as with extensive traumatic injuries or major cardiac or hepatic surgery. ,  

Specific Assays

Specific assays measure individual components of the fibrinolytic pathway. They are particularly useful in diagnosing congenital fibrinolytic disorders and determining the underlying defect.  Components include plasminogen, α2-AP, tissue plasminogen activator (t-PA), and PAI-1. The availability of certain tests, such as thrombin activatable fibrinolysis inhibitor (TAFI), is predominantly limited to research settings. Furthermore, these tests often have technical limitations that create interpretation challenges. For instance, available clinical laboratory assays for PAI-1 were developed to identify increased PAI-1 associated with thrombotic disorders rather than PAI-1 deficiency; as such, results from patients with PAI-1 deficiency may overlap with normal values. Interpretation is facilitated by ordering the tests together on the same specimen. 

Genetic Testing

Genetic testing may be considered when there is a strong suspicion of an inherited fibrinolytic disorder and conventional assays are inconclusive. Genetic testing usually consists of a bleeding disorder panel containing multiple genes relevant to hemostasis.

ARUP Laboratory Tests

References