Prevalence of Clinical and Laboratory Markers of Hypofibrinolysis in Psychotic Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01487291
Recruitment Status : Completed
First Posted : December 7, 2011
Last Update Posted : December 16, 2014
Rio de Janeiro State Research Supporting Foundation (FAPERJ)
Information provided by (Responsible Party):
Silvia Hoirisch Clapauch, Universidade Federal do Rio de Janeiro

Brief Summary:
At the Thrombophilia Clinic of the Hospital Federal dos Servidores do Estado do Rio de Janeiro there is a high prevalence of acute psychotic episodes, which allows the investigators to raise the suspicion that the thrombotic tendency or hypofibrinolysis play a role in the onset of the disease. It is striking that most of these patients, after some time on anticoagulants, no longer need to take psychiatric medication.

Condition or disease
Insulin Resistance Thrombophilia Psychosis

Detailed Description:

If the thrombotic tendency plays a significant role in the etiology of psychosis, one would expect to find ischemic brain injuries in neuroimaging studies, but it does not happen. Therefore, if there is a correlation between thrombotic tendency-hypofibrinolysis and psychosis it is likely to occur at the biochemical level, such as in neuronal transmission.

The investigators hypothesis is that mechanisms that inhibit tissue plasminogen activator (t-PA) and therefore promote hypofibrinolysis, are directly or indirectly involved in the genesis of psychosis, because t-PA participates in neuronal plasticity and low t-PA levels are related to dementia.

Hypofibrinolysis due to t-PA inhibition can be seen in:

  • Insulin resistance, when the pancreas must produce large amounts of insulin and proinsulin by feedback. If pancreatic reserve is inadequate, the result is diabetes mellitus. If the response is adequate, proinsulin stimulates the production of PAI-1 (plasminogen activator inhibitor 1. PAI-1 inhibits the formation of plasmin, whose function is to dissolve fibrin which makes up the clot. Obesity, certain infections and inflammations potentiate insulin resistance.
  • Antiphospholipid antibody syndrome.
  • PAI-1 4G/5G or 4G/4G polymorphism.

Some hypofibrinolysis indicators are:

  • severe dysmenorrhea, because strong uterine contractions are necessary to expel undissolved clots.
  • PCOS because plasmin is required to activate some metalloproteinases involved in ovary remodelling.
  • early pregnancy losses, as some metalloproteinases involved in placental angiogenesis are activated by plasmin,
  • preeclampsia and eclampsia, as metalloproteinases that dissolve elastic fibers of the placental vessels, to create a low flow resistance, are activated by plasmin. Vascular endothelial growth factor (VEGF), a protein that restricts glomerular porosity, is also activated by plasmin,
  • sudden death and heart attack before age 50 in first degree relatives.

On physical exam, acanthosis, high body mass index, and in women, hirsutism and acne are indirect indicators of insulin resistance. Livedo suggest antiphospholipid antibody syndrome.

This study intents to investigate the prevalence of hypofibrinolysis markers, such as PAI-1 4G/5G and 4G/4G, protein S deficiency, antiphospholipid antibodies and prothrombin G20210A, in psychotic patients.

Study Type : Observational
Actual Enrollment : 176 participants
Observational Model: Case Control
Time Perspective: Cross-Sectional
Official Title: Prevalence of Clinical and Laboratory Markers of Hypofibrinolysis in Psychotic Patients
Study Start Date : January 2013
Actual Primary Completion Date : May 2013
Actual Study Completion Date : May 2013

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Psychotic patients
Inpatients and outpatients followed at Instituto de Psiquiatria da Universidade Federal do Rio de Janeiro, Brazil

Primary Outcome Measures :
  1. Prevalence of hypofibrinolysis markers in psychotic patients [ Time Frame: One year ]
    The investigators' hypothesis is that a high prevalence of hypofibrinolysis markers will be probably found in psychotic patients.

Secondary Outcome Measures :
  1. Prevalence of Clinical and Laboratory Markers of Hypofibrinolysis in Patients who Need Electroconvulsive Therapy [ Time Frame: 2013-2014 ]
    The investigators are assessing clinical and laboratory markers of plasminogen activator imbalance in psychiatric patients who require electroconvulsive therapy, specifically patients with major depressive disorders and schizophrenia.

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Psychotic patients treated at IPUB-UFRJ, comprising patients with schizophrenia, schizoaffective disorders, bipolar disorders (mania or depressive episodes, provided that the patient has shown an acute psychotic episode in the last two years.

Age-matched control group


Inclusion Criteria:

  • Diagnosis of schizophrenia or schizoaffective disorder by the Semi-structured Interview MINI 5.0.

Exclusion Criteria:

  • Inability to provide information.
  • Use of illicit drugs.
  • Infections such as cerebral toxoplasmosis in HIV seropositive or tertiary syphilis. Patients with "recurrent syphilis" will not be excluded, because false positive tests are common in antiphospholipid antibody syndrome.

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01487291

Institudo de Psiquiatria da UFRJ
Rio de Janeiro, Brazil, 22290-140
Sponsors and Collaborators
Universidade Federal do Rio de Janeiro
Rio de Janeiro State Research Supporting Foundation (FAPERJ)
Study Chair: Antonio E Nardi, MD, PhD Universidade Federal do Rio de Janeiro, Brazil

Publications of Results:
Other Publications:
Responsible Party: Silvia Hoirisch Clapauch, MD, Responsible for the HFSE Thrombophilia Clinic, Universidade Federal do Rio de Janeiro Identifier: NCT01487291     History of Changes
Other Study ID Numbers: UFRiodJaneiro
First Posted: December 7, 2011    Key Record Dates
Last Update Posted: December 16, 2014
Last Verified: December 2014

Keywords provided by Silvia Hoirisch Clapauch, Universidade Federal do Rio de Janeiro:
Thrombophilia tests

Additional relevant MeSH terms:
Insulin Resistance
Glucose Metabolism Disorders
Metabolic Diseases
Hematologic Diseases