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Fibrinolytic and hemostatic abnormalities in gastro-esophageal variceal bleeding in cirrhotic patients
April 2000
myeloproliferative disorders in 18 -essential thrombocytemia in 15 and polycytemia vera in 3- (of these 1 also had hyperhomocysteinemia and 1 prothrombin mutation), antiphospholipid antibodies in 7, surgery or abdominal trauma in 2, inflammatory bowel diseases in 2, hyperhomocysteinemia + antiphospholipid antibodies in I patient. 5 patients are under investigation. Clinical presentation: the clinical presentation was abdominal pain z fever in 25 patients, splenomegaly in 12, GI bleeding in 11 and ascites in 1; 11 patients were asymptomatic. Esophageal varices were present in 43 out of 60 patients (71.6%). Conclusion: a comprehensive thrombophylic screening in adult noncirrhotic patients with portal vein thrombosis reveals a congenital or acquired thrombophylic state in about 75% of patients. This figure is much higer than previously reported. Since the majority of these conditions need to be treated, thrombophylic screening in these patients is warranted.
AASLDA967
prophylactic treatment bled. 30/60 patients were treated with oral anticoagulants for their thrombophylic state: 21 of these had varices (small 9, large 12).Of the 12 patients with large varices 0/8 receiving prophylactic therapy with f3-blockers bled, while 4/4 untreated patients bled. 30 patients did not receive anticoagulant therapy. 22 of these had varices (9 small, 13 large). Of the 13 patients with large varices,0/6 receiving prophylactic treatment (f3-blockers 4, banding 2) bled, while 4/7 (57.1%) untreated patients bled. Patients with small varices never bled, regardless of anticoagulant treatment and of prophylactic treatment for bleeding. Mortality: 2 patients (3%) died after 192 and 39 months of follow-up, for lung cancer and unknown cause respectively. Conclusion: patients with EHPVO and large varices are at high risk of variceal bleeding. Pharmacological and endoscopic treatment are effective in preventing both first bleeding and rebleeding. Treating the thrombophylic state and preventing portal hypertension-related bleeding is likely to improve the prognosis of these patients.
1036 FIBRINOLYTIC AND HEMOSTATIC ABNORMALITIES IN GASTRO-ESOPHAGEAL VARICEAL BLEEDING IN CIRRHOTIC PATIENTS. Massimo Primignani, Alessandra Dell'Era, Paolo Carnevale, Paoletta Preatoni, Marco Cattaneo, Bianca M. Bottasso, Maria T. Bajetta, Paolo Bucciarelli, Gianlorenzo Scacchi, Luigi Tognini, Elia Martino, Roberto de Franchis, Service di Gastroenterologia-Ospedale Policlinico, Milano, Italy; Ctr A Bianchi Bonomi-Ospedale Policlinico, Milano, Italy; Inst di Chirurgia d'Urgenza-Ospedale Policlinico, Milano, Italy. Introduction: bleeding from gastro-esophageal (GE) varices in cirrhotic patients has a high mortality rate (30% within six weeks). It is likely that fibrinolytic and hemostatic abnormalities playa relevant role in defining the prognosis. Aim: to evaluate the correlation between hemostatic (PT, aPTT, prothrombin fragment FI +2, thrombin-antithrombin complexes, fibrinogen) and fibrinolytic (t-PA, plasminogen activator inhibitor, DDimer, plasmin-antiplasmin complexes) parameters and mortality in cirrhotic patients with acute GE variceal hemorrage. Methods: we enrolled cirrhotic patients at their first episode of bleeding from GE varices. Blood was drawn at bleeding, hemodynamic stabilization, after 3, 8, 15 days and 6 weeks. The control group was composed of cirrhotic patients comparable for sex, age and Child class, with stable hemodynamic conditions and GE varices. Data were analyzed by means of analysis of variance and, if statistically different, Student's t-test, Death risk was expressed by Odds Ratio (OR). Such risk was adjusted for Child-Pugh class by means of multivariate logistic regression. Results: 25 patients (6 Child A, 8 B, 11 C) were included in the study from March 1997 to June 1999. Control of bleeding was achieved in 23 patients (92%) by sclerotherapy, banding, balloon tamponade or vasoactive drugs. 3 patients (12%) rebled. 13 patients (52%) died in the course of follow-up (1 Child A, 2 B, 11 C); of these, 11 (44%) died within 6 weeks (bleeding- related deaths). The control group consisted of 23 patients. Plasma values of t-PA and D-Dimer in bleeding patients were significantly higher than in the control group at bleeding time and hemodinamic stabilization, due to the higher values in patients destined to death vs surviving patients. Multivariate analysis showed that poor prognosis can be predicted by high plasma values of t-PA (OR 7.4, 95% CI 0.7- 80) and D-Dimer (OR 15.6, 95% CI 1.5- 164). Further data are needed to assess whether such parameters have independent prognostic value vs Child-Pugh class. No relationship could be found between the other evaluated parameters and severity of liver disease and prognosis. Conclusions: a hyperfibrinolytic condition is present in patients with acute GE variceal bleeding and poor prognosis. Anti-fibrinolytic agents, effective in other bleeding events, could be useful in opposing such a condition. These evidences support the execution of a controlled clinical study with antifibrinolytic agents as adjuvant therapy for variceal bleeding.
1037 NATURAL HISTORY OF EXTRA-HEPATIC PORTAL VEIN OBSTRUCTION (EHPVO) IN WESTERN COUNTRIES. Massimo Primignani, Nicola De Bortoli, Marco Moia, Paolo Bucciarelli, Paolo Carnevale, Paoletta Preattoni, Roberto de Franchis, IRCCS Hosp Maggiore -Servizio di Gastroenterologia-, Milano, Italy; IRCCS Hosp Maggiore -Centro A Bianchi Bonomi-, Milano, Italy. Introduction: in western countries, extra-hepatic portal vein obstruction in the absence of previous liver disease (EHPVO) accounts for less than 10% of cases of portal hypertension. In most cases, EHPVO is due to congenital or acquired thrombophylic disorders. Object: we retrospectively evaluated the natural history of consecutive patients with EHPVO seen at our Hospital between 1987 and 1999. Patients and methods: 60 patients (35f, 25m; mean age 45.5 yrs, range 16-76) underwent a thrombophylic screening. Results: EHPVO was idiopathic in 10 patients (16.7%), related to a thrombophylic state in 45 (75%)-congenital in 15 (25%),acquired in 30 (50%)-, while 5 patients are under investigation. Median follow-up is 115 months (range 2-228) Natural history: clinical presentation was: abdominal pain ::': fever in 25 patients, splenomegaly in 12, GI bleeding in 11 and ascites in 1; 11 were asymptomatic. Large (25) or small (18) esophageal varices were present in 43 patients (71.6%); 7 of 11 patients (63.6%) who bled at clinical outset rebled before prophylaxis of rebleeding was started. After prophylaxis was started (porto-systemic shunt in I, endoscopic therapy in 6, f3-blockers in 4), only 1 patient rebled from a sclerotherapyinduced esophageal ulcer. 14/32 patients with no previous bleeds underwent primary prophylaxis with f3-blockers (12) or banding (2); none of these bled. 4 of the remaining 18 patients (22%) who did not receive
1038 DIAGNOSIS OF PORTAL HYPERTENSIVE GASTROPATHY BY CONTRAST (SHU 508A) ENHANCED COLOR DOPPLER. Michael 1. Gebel, Martin Caselitz, Katbrin Strerath, Peter N. Meier, Joerg S. Bleck, Bita Boozari, Michael P. Manns, Med Hochschule Hannover, Div Gastroenterol and Hepatol, Hannover, Germany; Med Hochschule Hannover, Hannover, Germany; Medicine Hochschule Hannover, Hannover, Germany. Portal hypertensive gastropathy (PHG) is a complication of portal hypertension and a distinct clinical entity different from various types of gastritis. There is histological evidence that this type of gastrits is the consequence of small submucosal arterio-venous shunts developing during the course of portal hypertension. PHG is the a leading bleeding cause in patients with portal hypertension, second only to variceal bleeding. Enhancement of the ultrasound color doppler signal (CD) by echo contrast agent should show increased vascular blood flow of the gastric mucosa if PHG is present. Method:This study comprised 44 patients: 33 with portal hypertension, 11 without portal hypertension; 15 female, 19 male patients, age 53 years (range 36-76 years); 31 patients with liver cirrhosis: toxic 12, viral 15, PBC I, PSC I, cryptogenic 2; 2 patients without liver cirrhosis but with portal vein thrombosis. The patients received a bolus injection of 2.5 g (300 mg/ml) microbubble based echo contrast agent SHU 508A (Levovist®, Schering Inc.Berlin, Germany, written consent according GMP and Helsinki declaration) during examination of the stomach wall by CD (Toshiba 270, 3.75 MHz). Enhancement of the CD signal was graded (no, positive, strong positive) and compared to endoscopic findings (PHG grading according to McCormack 1985, examiners unaware of CD findings). Results: Signal enhancement of the gastric mucosa if present started 19 s after start of injection, reached maximum after 36 s and lasted for 160 s. Spectral doppler showed predominantly strong arterial signals with low resistive index followed by faint venous signals. Compared to gastroscopy (GS) 29/31 showed marked increase in CD mucosal signals (29 right pos., I false pos.,2 false neg., 12 right neg.; sensitivity 94%, specificity 92%).There was a good agreement of PHG grading (CD/GS neg. 14/13; pos. 18/25, strong pos. 12/6). Conclusion:Echocontrast (SHU 508A) enhanced CD seems to be a sensitive noninvasive new method for the detection of PHG. Equivocal endoscopic findings could be clarified by echocontrast enhanced CD. Furthermore the results of this study support the hypothesis of small arterio-venous shunts as underlying pathophyiology of PHG and suggest that PHG and pure congestion should be separated by means of echocontrast enhanced CD.
1039 IS THERE ANY HEMODYNAMIC CHARACTERISTIC OF DOPPLER ULTRASONOGRAPHY PREDICTIVE OF ESOPHAGEAL VARICEAL BLEEDING IN PATIENTS WITH LIVER CIRRHOSIS? Soon Koo Baik, Seong Jin Park, Hyun Soo Kim, Dong Ki Lee, Sang Ok Kwon, Wonju Coll of Medicine, Wonju, South Korea. Background!Aims: Prediction of esophageal variceal bleeding has been based on the endoscopic findings of large variceal size and the red color sign. This study was designed in order to discover any characteristic hemodynamic feature in patients with liver cirrhosis with variceal bleeding, compared with those without bleeding, by using Doppler ultrasonography. Methods: The subjects were a total 100 patients with liver cirrhosis. The diameter, mean velocity, and blood flow volume of the portal vein and splenic vein were measured in patients with and without variceal bleeding. Also, the resistive index and pulsatility index of splenic artery, which have been known to reflect portal hypertension, were measured in both groups. The above measured data were statistically compared between the groups with and without variceal bleeding. Results: In univariate analysis, we found that the values of the diameter and blood flow volume of the portal vein, and the diameter, mean velocity and blood flow volume of the splenic vein, and the size of spleen were significantly increased in the group with variceal bleeding, compared with those of the group without variceal bleeding. However multivariate analysis(multiple logistic regression analysis) showed no significant independent multivariate value for the group with variceal bleeding. Conclusions: These results suggest that variceal bleeding is affected not by a single hemodynamic factor but by a composite of complex hemodynamic features of the portal system. There is no single hemodynamic characteristic on Doppler ultrasonography which can predict esophageal variceal bleeding in patients with liver cirrhosis.
myeloproliferative disorders in 18 -essential thrombocytemia in 15 and polycytemia vera in 3- (of these 1 also had hyperhomocysteinemia and 1 prothrombin mutation), antiphospholipid antibodies in 7, surgery or abdominal trauma in 2, inflammatory bowel diseases in 2, hyperhomocysteinemia + antiphospholipid antibodies in I patient. 5 patients are under investigation. Clinical presentation: the clinical presentation was abdominal pain z fever in 25 patients, splenomegaly in 12, GI bleeding in 11 and ascites in 1; 11 patients were asymptomatic. Esophageal varices were present in 43 out of 60 patients (71.6%). Conclusion: a comprehensive thrombophylic screening in adult noncirrhotic patients with portal vein thrombosis reveals a congenital or acquired thrombophylic state in about 75% of patients. This figure is much higer than previously reported. Since the majority of these conditions need to be treated, thrombophylic screening in these patients is warranted.
AASLDA967
prophylactic treatment bled. 30/60 patients were treated with oral anticoagulants for their thrombophylic state: 21 of these had varices (small 9, large 12).Of the 12 patients with large varices 0/8 receiving prophylactic therapy with f3-blockers bled, while 4/4 untreated patients bled. 30 patients did not receive anticoagulant therapy. 22 of these had varices (9 small, 13 large). Of the 13 patients with large varices,0/6 receiving prophylactic treatment (f3-blockers 4, banding 2) bled, while 4/7 (57.1%) untreated patients bled. Patients with small varices never bled, regardless of anticoagulant treatment and of prophylactic treatment for bleeding. Mortality: 2 patients (3%) died after 192 and 39 months of follow-up, for lung cancer and unknown cause respectively. Conclusion: patients with EHPVO and large varices are at high risk of variceal bleeding. Pharmacological and endoscopic treatment are effective in preventing both first bleeding and rebleeding. Treating the thrombophylic state and preventing portal hypertension-related bleeding is likely to improve the prognosis of these patients.
1036 FIBRINOLYTIC AND HEMOSTATIC ABNORMALITIES IN GASTRO-ESOPHAGEAL VARICEAL BLEEDING IN CIRRHOTIC PATIENTS. Massimo Primignani, Alessandra Dell'Era, Paolo Carnevale, Paoletta Preatoni, Marco Cattaneo, Bianca M. Bottasso, Maria T. Bajetta, Paolo Bucciarelli, Gianlorenzo Scacchi, Luigi Tognini, Elia Martino, Roberto de Franchis, Service di Gastroenterologia-Ospedale Policlinico, Milano, Italy; Ctr A Bianchi Bonomi-Ospedale Policlinico, Milano, Italy; Inst di Chirurgia d'Urgenza-Ospedale Policlinico, Milano, Italy. Introduction: bleeding from gastro-esophageal (GE) varices in cirrhotic patients has a high mortality rate (30% within six weeks). It is likely that fibrinolytic and hemostatic abnormalities playa relevant role in defining the prognosis. Aim: to evaluate the correlation between hemostatic (PT, aPTT, prothrombin fragment FI +2, thrombin-antithrombin complexes, fibrinogen) and fibrinolytic (t-PA, plasminogen activator inhibitor, DDimer, plasmin-antiplasmin complexes) parameters and mortality in cirrhotic patients with acute GE variceal hemorrage. Methods: we enrolled cirrhotic patients at their first episode of bleeding from GE varices. Blood was drawn at bleeding, hemodynamic stabilization, after 3, 8, 15 days and 6 weeks. The control group was composed of cirrhotic patients comparable for sex, age and Child class, with stable hemodynamic conditions and GE varices. Data were analyzed by means of analysis of variance and, if statistically different, Student's t-test, Death risk was expressed by Odds Ratio (OR). Such risk was adjusted for Child-Pugh class by means of multivariate logistic regression. Results: 25 patients (6 Child A, 8 B, 11 C) were included in the study from March 1997 to June 1999. Control of bleeding was achieved in 23 patients (92%) by sclerotherapy, banding, balloon tamponade or vasoactive drugs. 3 patients (12%) rebled. 13 patients (52%) died in the course of follow-up (1 Child A, 2 B, 11 C); of these, 11 (44%) died within 6 weeks (bleeding- related deaths). The control group consisted of 23 patients. Plasma values of t-PA and D-Dimer in bleeding patients were significantly higher than in the control group at bleeding time and hemodinamic stabilization, due to the higher values in patients destined to death vs surviving patients. Multivariate analysis showed that poor prognosis can be predicted by high plasma values of t-PA (OR 7.4, 95% CI 0.7- 80) and D-Dimer (OR 15.6, 95% CI 1.5- 164). Further data are needed to assess whether such parameters have independent prognostic value vs Child-Pugh class. No relationship could be found between the other evaluated parameters and severity of liver disease and prognosis. Conclusions: a hyperfibrinolytic condition is present in patients with acute GE variceal bleeding and poor prognosis. Anti-fibrinolytic agents, effective in other bleeding events, could be useful in opposing such a condition. These evidences support the execution of a controlled clinical study with antifibrinolytic agents as adjuvant therapy for variceal bleeding.
1037 NATURAL HISTORY OF EXTRA-HEPATIC PORTAL VEIN OBSTRUCTION (EHPVO) IN WESTERN COUNTRIES. Massimo Primignani, Nicola De Bortoli, Marco Moia, Paolo Bucciarelli, Paolo Carnevale, Paoletta Preattoni, Roberto de Franchis, IRCCS Hosp Maggiore -Servizio di Gastroenterologia-, Milano, Italy; IRCCS Hosp Maggiore -Centro A Bianchi Bonomi-, Milano, Italy. Introduction: in western countries, extra-hepatic portal vein obstruction in the absence of previous liver disease (EHPVO) accounts for less than 10% of cases of portal hypertension. In most cases, EHPVO is due to congenital or acquired thrombophylic disorders. Object: we retrospectively evaluated the natural history of consecutive patients with EHPVO seen at our Hospital between 1987 and 1999. Patients and methods: 60 patients (35f, 25m; mean age 45.5 yrs, range 16-76) underwent a thrombophylic screening. Results: EHPVO was idiopathic in 10 patients (16.7%), related to a thrombophylic state in 45 (75%)-congenital in 15 (25%),acquired in 30 (50%)-, while 5 patients are under investigation. Median follow-up is 115 months (range 2-228) Natural history: clinical presentation was: abdominal pain ::': fever in 25 patients, splenomegaly in 12, GI bleeding in 11 and ascites in 1; 11 were asymptomatic. Large (25) or small (18) esophageal varices were present in 43 patients (71.6%); 7 of 11 patients (63.6%) who bled at clinical outset rebled before prophylaxis of rebleeding was started. After prophylaxis was started (porto-systemic shunt in I, endoscopic therapy in 6, f3-blockers in 4), only 1 patient rebled from a sclerotherapyinduced esophageal ulcer. 14/32 patients with no previous bleeds underwent primary prophylaxis with f3-blockers (12) or banding (2); none of these bled. 4 of the remaining 18 patients (22%) who did not receive
1038 DIAGNOSIS OF PORTAL HYPERTENSIVE GASTROPATHY BY CONTRAST (SHU 508A) ENHANCED COLOR DOPPLER. Michael 1. Gebel, Martin Caselitz, Katbrin Strerath, Peter N. Meier, Joerg S. Bleck, Bita Boozari, Michael P. Manns, Med Hochschule Hannover, Div Gastroenterol and Hepatol, Hannover, Germany; Med Hochschule Hannover, Hannover, Germany; Medicine Hochschule Hannover, Hannover, Germany. Portal hypertensive gastropathy (PHG) is a complication of portal hypertension and a distinct clinical entity different from various types of gastritis. There is histological evidence that this type of gastrits is the consequence of small submucosal arterio-venous shunts developing during the course of portal hypertension. PHG is the a leading bleeding cause in patients with portal hypertension, second only to variceal bleeding. Enhancement of the ultrasound color doppler signal (CD) by echo contrast agent should show increased vascular blood flow of the gastric mucosa if PHG is present. Method:This study comprised 44 patients: 33 with portal hypertension, 11 without portal hypertension; 15 female, 19 male patients, age 53 years (range 36-76 years); 31 patients with liver cirrhosis: toxic 12, viral 15, PBC I, PSC I, cryptogenic 2; 2 patients without liver cirrhosis but with portal vein thrombosis. The patients received a bolus injection of 2.5 g (300 mg/ml) microbubble based echo contrast agent SHU 508A (Levovist®, Schering Inc.Berlin, Germany, written consent according GMP and Helsinki declaration) during examination of the stomach wall by CD (Toshiba 270, 3.75 MHz). Enhancement of the CD signal was graded (no, positive, strong positive) and compared to endoscopic findings (PHG grading according to McCormack 1985, examiners unaware of CD findings). Results: Signal enhancement of the gastric mucosa if present started 19 s after start of injection, reached maximum after 36 s and lasted for 160 s. Spectral doppler showed predominantly strong arterial signals with low resistive index followed by faint venous signals. Compared to gastroscopy (GS) 29/31 showed marked increase in CD mucosal signals (29 right pos., I false pos.,2 false neg., 12 right neg.; sensitivity 94%, specificity 92%).There was a good agreement of PHG grading (CD/GS neg. 14/13; pos. 18/25, strong pos. 12/6). Conclusion:Echocontrast (SHU 508A) enhanced CD seems to be a sensitive noninvasive new method for the detection of PHG. Equivocal endoscopic findings could be clarified by echocontrast enhanced CD. Furthermore the results of this study support the hypothesis of small arterio-venous shunts as underlying pathophyiology of PHG and suggest that PHG and pure congestion should be separated by means of echocontrast enhanced CD.
1039 IS THERE ANY HEMODYNAMIC CHARACTERISTIC OF DOPPLER ULTRASONOGRAPHY PREDICTIVE OF ESOPHAGEAL VARICEAL BLEEDING IN PATIENTS WITH LIVER CIRRHOSIS? Soon Koo Baik, Seong Jin Park, Hyun Soo Kim, Dong Ki Lee, Sang Ok Kwon, Wonju Coll of Medicine, Wonju, South Korea. Background!Aims: Prediction of esophageal variceal bleeding has been based on the endoscopic findings of large variceal size and the red color sign. This study was designed in order to discover any characteristic hemodynamic feature in patients with liver cirrhosis with variceal bleeding, compared with those without bleeding, by using Doppler ultrasonography. Methods: The subjects were a total 100 patients with liver cirrhosis. The diameter, mean velocity, and blood flow volume of the portal vein and splenic vein were measured in patients with and without variceal bleeding. Also, the resistive index and pulsatility index of splenic artery, which have been known to reflect portal hypertension, were measured in both groups. The above measured data were statistically compared between the groups with and without variceal bleeding. Results: In univariate analysis, we found that the values of the diameter and blood flow volume of the portal vein, and the diameter, mean velocity and blood flow volume of the splenic vein, and the size of spleen were significantly increased in the group with variceal bleeding, compared with those of the group without variceal bleeding. However multivariate analysis(multiple logistic regression analysis) showed no significant independent multivariate value for the group with variceal bleeding. Conclusions: These results suggest that variceal bleeding is affected not by a single hemodynamic factor but by a composite of complex hemodynamic features of the portal system. There is no single hemodynamic characteristic on Doppler ultrasonography which can predict esophageal variceal bleeding in patients with liver cirrhosis.