Sclerotherapy of esophageal varices in hemophilia patients with liver cirrhosis - a prospective, controlled clinical study.

INTRODUCTION: Bleeding from esophageal varices is a serious clinical condition in hemophilia patients due to congenital deficiency or lack of clotting factors VIII (in hemophilia A) and IX (in hemophilia B), decreased clotting factor II, VII, IX, X synthesis in the course of chronic liver disease and hipersplenic thrombocytopenia. The aim of this study was to assess the efficacy and safety of endoscopic sclerotherapy in acute esophageal variceal bleeding and in secondary prophylaxis of hemorrhage. The aim was also to investigate the optimal activity of deficiency factors VIII or IX and duration of replacement therapy required to ensure proper hemostasis after sclerotherapy procedures. MATERIAL AND METHODS: 22 hemophilia patients (A-19, B-4) with coexistent liver cirrhosis and active esophageal variceal bleeding treated with endoscopic sclerotherapy were subjected to prospective analysis. The patients who survived were qualified to repeated sclerotherapy procedures every 3 weeks within secondary prophylaxis of bleeding (investigated group). A 3-day substitution therapy enhanced the infusion of the deficient or lacking factor in doses allowing to reach 80-100% of normal value activity of factor VIII on the 1st day and 60-80% in the next two days. The desired activity of factor IX was 60- 80% and 40-60% respectively. The control group consisted of 20 non-hemophiliac patients with liver cirrhosis comparable in terms of age, sex, stage of advancement of liver cirrhosis, who underwent the same medical proceedings as the investigated group. RESULTS: Active esophageal bleeding was stopped in 21 of 22 (95%) hemophilia patients. Complications were observed in 3 patients; 2 patients died. The rate of hemostasis, complications and deaths in the control group were comparable and no statistical differences were found. In hemophilia patients subjected to secondary prophylaxis of hemorrhage, in 18 of 20 (80%), complete eradication of esophageal varices was achieved after 4 to 7 sclerotherapy procedures in 1 patient (average 5.4). Recurrent bleeding was observed in 15% of patients, complication in 20%; 1 patient died. Time lapse from bleeding to eradication was 12-21 weeks (average 15.2). In the control group the rate of variceal eradication, complication and deaths was comparable and no statistical differences were found. The usage of factor VIII concentrates was as follows: in hemophilia A, in a severe form - 80.9 U/kg b.w./day, in hemophilia A in a severe form with an inhibitor <5 BU - 95.2 U/kg b.w./day, in mild form - 64.2 U/kg b.w./day and in severe hemophilia B - 91.6 U/kg b.w./day. CONCLUSIONS: Sclerotherapy is an effective method in the management of esophageal variceal bleeding in hemophilia patients. It is also effective for total eradication of varices when applied as a secondary prophylaxis of hemorrhage. In our opinion, a 3-day replacement therapy at the applied doses is sufficient to ensure hemostasis and avoid bleeding complications.

[Strategy for secure hemostasis in hemophilia patients undergoing surgery for malignant neoplasms]. / Strategia zapewnienia bezpiecznej hemostazy u chorych na hemofilie operowanych z powodu nowotworów zlosliwych.

UNLABELLED: Surgery for malignant neoplasms in hemophilia patients is no different from standard procedures in the general population on condition that the normal hemostatic activity of deficient factors: VIII in hemophilia A and IX in hemophilia B in perioperative period is ensured. The aim of the study was to determine the type and frequency of malignant neoplasms in hemophilia patients as well as to provide a strategy for establishing safe hemostatic activity in surgically treated hemophilia patients. MATERIAL AND METHODS: In the period 2003-2008, surgical procedures were performed on 19 hemophilia A and B patients with diagnosed malignant neoplasms of various location. The following cases were diagnosed: 9 colorectal neoplasms, 2 pancreatic carcinomas, 2 larynx carcinomas, 1 stomach carcinoma, 1 liver, 1 nasopharyngeal, 1 testicle, 1 prostate and 1 skin. Seventeen patients were hemophilia A (6 severe, 4 severe with inhibitor, including 2 high titre and 2 low titre, 1 moderate and 6 mild) and 2 were hemophilia B (1 severe, 1 moderate). Patients mean age was 55.8 years (22-82). In factor-replacement therapy for patients with no inhibitor the strategy was to maintain the activity of the deficient clotting factor VIII before the operation at 80-100% of normal value, within the 80-100% range on the 1-3 day following surgery, at 60-80% on days 4-6, at 30-60% on days 7-10 day and at 20-40% on all subsequent days until the surgical wound healed. In hemophilia B patients the levels were about 20% lower. Deficient factor was injected every 8 or 12 hours or administered in continuous intravenous infusion. In hemophilia A patients with high titre inhibitors to factor VIII (above 5 Bethesda units/ml) activated prothrombin complex concentrates (aPCC)-FEIBA (Baxter AG) were used at 50-100 U/kg b.m., every 8-12 hours. RESULTS: The nineteen patients with diagnosed malignant neoplasms (in the period 2003-2008) constituted 0.77% of the overall 2475 hemophilia patients entered into the National Registry Congenital of Hemorrhagic Diathesis. An overall number of 26 surgical procedures were performed in this group of 19 hemophilia patients including 20 procedures for malignant neoplasms and 6 for postoperative complications. All patients survived surgery. Two patients with pancreatic carcinoma died in the postoperative period due to multi-organ failure. Complications occured in 7 (37%) patients including 6 (32%) with bleeding complications: haemopneumothorax (n=1), intraperitoneal bleeding (n=2), abdominal parietal hematoma (n=1), hematuria (n=1), bleeding from esophago-pharyngo-cutaneous fistula following total laryngectomy (n=1). Other complications included: ileus (n=1), leakage of pancreato-jejunal anastomosis (n=1), dehiscence of abdominal wound (n=1) and bleeding from duodenal ulcer (n=1). These complications were successfully treated with surgery or endoscopy. CONCLUSIONS: Surgery of malignant neoplasms in hemophilia patients is burdened with a high risk of complications which include bleedings despite adequate replacement therapy and administration of factor eight by-passing concentrates in patients with high titre inhibitor. Therefore surgical procedures involving these patients should be performed in specialized centers with experienced team (surgeon, anaesthesiologist, haematologist) and supported by a laboratory for coagulation disorders.

Acquired hemophilia: a case report.

Acquired hemophilia is a severe bleeding diathesis that affects both males and females. It is caused by suddenly appearing autoantibodies that interfere with coagulation factor VIII activity. This disorder is characterized by spontaneous and post-traumatic subcutaneous bleeds and massive mucosal hemorrhages. We report in the current article a case of acute renal failure and bleeding from the urinary tract caused by idiopathic acquired hemophilia in a 54-year-old woman. Hemostatic tests indicated prolonged activated partial thromboplastin time (APTT) to 107.8 sec (norm 26-36 sec), normal value of the prothrombin index which was 82% (norm 70-130%), increased fibrinogen concentration to 583 mg/dl (normal value 200-400 mg/dl), the bleeding time was 5 min and 20 s (norm < 10 min) and the platelet count was 366 x 10(9)/l (norm 130-400 x10(9)/l). The autoantibody against factor VIII in a titer of 121 Bethesda Units/ml (BU/ml) and decreased factor VIII activity to 2% (norm 50-150%) with normal plasma concentration of factor IX. Activated (FEIBA, Baxter) and nonactivated prothrombin complex concentrates (factor IX concentrate) have been used in the treatment of bleeding episode. Immunosuppressive treatment with the combination of oral prednisone 60 mg/24h and cyclophosphamide 150 mg/24h was administered in order to remove the factor VIII inhibitor. Reduction of the factor VIII inhibitor titer to 38 BU/ml and increase of factor VIII activity to 4% was initially achieved. This treatment has been continued for two years and led to normalization of hemostatic parameters (APTT 26 sec, factor VIII activity 108%) which means a total removal of factor VIII inhibitor.

Portal venous system after endoscopic sclerotherapy of esophageal varices in patients with liver cirrhosis--prospective study with Doppler sonography.

BACKGROUND/AIMS: The aim of this prospective, clinical study was an ultrasonographic color Doppler evaluation of morphological and hemodynamic changes in the portal system prior to and after repeated, endoscopic injection sclerotherapy in patients with liver cirrhosis and hemorrhage from esophageal varices. METHODOLOGY: Twenty-six patients before and after complete eradication of esophageal varices by repeated sclerotherapy with 5% ethanolamine oleate as obliterating agent were examined. The diameter of the portal and splenic veins, the patency of the veins, the direction of the blood flow, the mean and maximal velocity of blood flow, spleen size and presence and number of collateral circulation pathways were determined. Hemodynamic examinations of the portal system were performed with duplex Doppler method with color imaging of blood flow. RESULTS: The study revealed no statistically significant differences between diameters of the portal and the splenic vein or between the size of the spleen prior to and after sclerotherapy. The blood flow was intrahepatic and portal vein thrombosis was not detected in any of the patients. The mean velocity blood flow in the portal vein prior to and after sclerotherapy did not reveal any changes. The maximal velocity of blood flow in the portal vein increased from 23.7 +/- 2.5 cm/s to 27.2 +/- 2.8 cm/s, but it was not statistically significant. Prior to the commencement of sclerotherapy collateral portal-systemic circulation was detected in 17 out of 26 patients (65%), with a total of 25 collateral circulation pathways. After completion of sclerotherapy collaterals were detected in 19 out of 26 patients (73%) and number of pathways was increased by 7. CONCLUSIONS: Endoscopic sclerotherapy of esophageal varices does not affect the direction of blood flow in the portal vein and causes no thrombosis of the portal system. Effective sclerotherapy and complete eradication of esophageal varices results in closure of collateral circulation pathways through submucosal esophageal varices as well as development of new pathways of collateral circulation.