Improvement of fibrin clot structure after factor VIII injection in haemophilia A patients treated on demand

Aleksandra Antovic; Danijela Mikovic; Ivo Elezovic; Michael Zabczyk; Kjell Hutenby; Jovan P. Antovic

doi:10.1160/TH13-06-0479

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2014; 111(04): 656-661
DOI: 10.1160/TH13-06-0479

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Improvement of fibrin clot structure after factor VIII injection in haemophilia A patients treated on demand

Aleksandra Antovic

¹Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital, Division of Cardiovascular Medicine, Stockholm, Sweden

,

Danijela Mikovic

²Haemostasis Department and Haemophilia Centre, Blood Transfusion Institute of Serbia, Belgrade, Serbia

,

Ivo Elezovic

³Clinic of Haematology, Clinical Centre of Serbia & Faculty of Medicine, University of Belgrade, Serbia

,

Michael Zabczyk

⁴Department of Molecular Medicine and Surgery/Clinical Chemistry/Coagulation Research, Karolinska Institute, Stockholm, Sweden

⁵Institute of Cardiology, Medical College, Jagiellonian University, Krakow, Poland

,

Kjell Hutenby

⁶Division of Clinical Research, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden

,

Jovan P. Antovic

⁷Department of Coagulation Research, Institute for Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

⁸Department of Clinical Chemistry, Karolinska University Hospital, Stockholm, Sweden

› Author Affiliations

Abstract

Summary

Patients with haemophilia A have seriously impaired thrombin generation due to an inherited deficiency of factor (F)VIII, making them form unstable fibrin clots that are unable to maintain haemostasis. Data on fibrin structure in haemophilia patients remain limited. Fibrin permeability, assessed by a flow measurement technique, was investigated in plasma from 20 patients with severe haemophilia A treated on demand, before and 30 minutes after FVIII injection. The results were correlated with concentrations of fibrinogen, FVIII and thrombin-activatable fibrinolysis inhibitor (TAFI), and global haemostatic markers: endogenous thrombin potential (ETP) and overall haemostatic potential (OHP). Fibrin structure was visualised using scanning electron microscopy (SEM). The permeability coefficient Ks decreased significantly after FVIII treatment. Ks correlated significantly with FVIII levels and dosage, and with ETP, OHP and levels of TAFI. SEM images revealed irregular, porous fibrin clots composed of thick and short fibers before FVIII treatment. The clots had recovered after FVIII replacement almost to levels in control samples, revealing compact fibrin with smaller intrinsic pores. To the best of our knowledge, this is the first description of fibrin porosity and structure before and after FVIII treatment of selected haemophilia patients. It seems that thrombin generation is the main determinant of fibrin structure in haemophilic plasma.

Keywords

Fibrin clot structure - scanning electron microscopy - FVIII - haemophilia A

Full Text

References

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