PMID- 20075386 OWN - NLM STAT- MEDLINE DCOM- 20100514 LR - 20140730 IS - 1535-4970 (Electronic) IS - 1073-449X (Linking) VI - 181 IP - 9 DP - 2010 May 1 TI - Fibrin resistance to lysis in patients with pulmonary hypertension other than thromboembolic. PG - 992-6 LID - 10.1164/rccm.200907-1135OC [doi] AB - RATIONALE: Reportedly, fibrin isolated from patients with chronic thromboembolic pulmonary hypertension (CTEPH) is resistant to lysis. Persistence of regions within the fibrin beta chain, which mediate cell signaling and migration, could trigger the organization of pulmonary thromboemboli into chronic intravascular scars. OBJECTIVES: Ascertain whether fibrin resistance to lysis occurs in patients with pulmonary hypertension (PAH) other than CTEPH, and in those with prior pulmonary embolism (PE) and no pulmonary hypertension. METHODS: Fibrinogen was purified from 96 subjects (17 with CTEPH, 14 with PAH, 39 with prior PE, and 26 healthy control subjects) and exposed to thrombin to obtain fibrin clots. Plasmin-mediated cleavage of fibrin beta chain was assessed hourly over a 6-hour period by polyacrylamide gel electrophoresis. Fibrin band intensity was measured by densitometry of stained gels. Data were normalized to the band intensity of the undigested protein. MEASUREMENTS AND MAIN RESULTS: By 1 hour of digestion, fibrin band intensity had decreased by a median of 25% (interquartile range [IQR], 20 to 27%) in control subjects, and by 15% (IQR, 11 to 18%) in patients with prior PE (P < 0.0001). The 1-hour median reduction in band intensity was 2% (IQR, 1 to 3%) in CTEPH, and 4% (IQR, 2 to 7%) in PAH (P < 0.0001 vs. control subjects and PE). The decline in fibrin band intensity remained significantly different among the four groups up to 6 hours (P < 0.0001). CONCLUSIONS: Fibrin resistance to lysis occurs in pulmonary hypertension other than CTEPH and, to a smaller extent, in patients with prior PE and no pulmonary hypertension. FAU - Miniati, Massimo AU - Miniati M AD - Dipartimento di Area Critica Medico Chirugica, Universita di Firenze, Viale Morgagni 85, 50134 Florence, Italy. massimo.miniati@unifi.it FAU - Fiorillo, Claudia AU - Fiorillo C FAU - Becatti, Matteo AU - Becatti M FAU - Monti, Simonetta AU - Monti S FAU - Bottai, Matteo AU - Bottai M FAU - Marini, Carlo AU - Marini C FAU - Grifoni, Elisa AU - Grifoni E FAU - Formichi, Bruno AU - Formichi B FAU - Bauleo, Carolina AU - Bauleo C FAU - Arcangeli, Chiara AU - Arcangeli C FAU - Poli, Daniela AU - Poli D FAU - Nassi, Paolo Antonio AU - Nassi PA FAU - Abbate, Rosanna AU - Abbate R FAU - Prisco, Domenico AU - Prisco D LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100114 PL - United States TA - Am J Respir Crit Care Med JT - American journal of respiratory and critical care medicine JID - 9421642 RN - 9001-31-4 (Fibrin) SB - IM MH - Adult MH - Blood Protein Electrophoresis MH - Echocardiography MH - Electrophoresis, Polyacrylamide Gel MH - Female MH - Fibrin/*physiology MH - Fibrinolysis MH - Hemodynamics MH - Humans MH - Hypertension, Pulmonary/*blood/physiopathology MH - Male MH - Middle Aged MH - Pulmonary Embolism/blood EDAT- 2010/01/16 06:00 MHDA- 2010/05/15 06:00 CRDT- 2010/01/16 06:00 PHST- 2010/01/16 06:00 [entrez] PHST- 2010/01/16 06:00 [pubmed] PHST- 2010/05/15 06:00 [medline] AID - 200907-1135OC [pii] AID - 10.1164/rccm.200907-1135OC [doi] PST - ppublish SO - Am J Respir Crit Care Med. 2010 May 1;181(9):992-6. doi: 10.1164/rccm.200907-1135OC. Epub 2010 Jan 14.