Recombinant factor VIIa as last-resort treatment of desperate haemorrhage.

INTRODUCTION: Studies are inconclusive regarding clinical outcomes after administration of recombinant activated coagulation factor VII (rFVIIa) during severe haemorrhage. The circumstances encountered during desperate haemorrhage make it difficult to include the most critically ill patients that could possibly benefit the most from such treatment into randomized controlled trials. We report our experience with rFVIIa as last-resort treatment of desperate haemorrhage when all standard treatment has failed. MATERIALS AND METHODS: Hospital charts of all consecutive patients treated with rFVIIa for desperate non-haemophilic bleeding over a 10-year period at the single institution administering rFVIIa were surveyed for treatment indications, clinical outcome, transfusion need and coagulation profiles. RESULTS: Fifty-five rFVIIa treatment occasions of desperate bleeding were identified in 54 patients (median age 54 years). A single rFVIIa dose was used in 86%, and haemorrhage was considered effectively contained by immediate clinical response on 81% of occasions. Overall, 38 patients (71%) survived for over 30 days. Two thromboembolic events occurred (3.6%). The 24-h mortality in 45 rFVIIa immediate clinical responders and 10 non-responders was 2% and 50%, respectively (P = 0.0004), and the 30-day mortality was 25% and 60%, respectively (P = 0.05). Blood product use decreased with rFVIIa (P < 0.01) as did the prothrombin time (20.0-13.3 s, P < 0.0001). CONCLUSIONS: The majority of unselected consecutive patients receiving rFVIIa as last-resort treatment for desperate haemorrhage were considered to have immediate clinical response as well as reduced transfusion requirements and correction of coagulation parameters. An immediate clinical response to rFVIIa may possibly be predictive of survival.

Fludarabine and cytarabine as a sequential infusion regimen for treatment of adults with recurrent, refractory or poor prognosis acute leukemia.

We did a retrospective analysis on the safety and efficacy of sequential infusion fludarabine and cytosine arabinoside (ara-C) in treating refractory, recurrent or poor prognosis acute leukemia in adult patients. Forty-five adult patients with acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL) received a total of 68 courses of sequential continuous infusion of fludarabine for 2 days (total dose 71.5 mg/m(2) ) followed by 3 days of ara-C (total dose 7590 mg/m(2) ). Thirty-nine patients had refractory or recurrent disease, and six had other adverse prognostic features. Thirty-six patients had AML, seven had ALL, and two had CML in blastic phase. Complete remission was seen in 20 patients (44%), and partial remission in 5 patients (11%), giving a total response rate of 56%, similar for both AML and ALL. Duration of response to prior therapy did not affect the response rate. All 3 patients with Philadelphia chromosome positive ALL obtained complete remission. Median remission duration was 4.7 months (range 0.6-36.6), and median overall survival was 5.0 months (0.7-40+). Median overall survival was 10.1 months in responders. Pulmonary toxicity was seen in 8 patients, of whom 2 died from adult respiratory distress syndrome. No cardiac toxicity was observed, but 3 patients had transient cerebellar toxicity. Profound myelosuppression was seen in all patients. We conclude that the sequential infusion of fludarabine and ara-C is an effective non-cardiotoxic regimen for adults with refractory, recurrent or poor prognosis acute leukemia, may be particularly useful for resistant Philadelphia chromosome positive ALL, and may warrant further investigation in this subset. Pulmonary rather than neurological toxicity may be a unique side effect of the regimen.

Transient effusive-constrictive pericarditis due to chemotherapy.

Commonly used chemotherapeutic agents, specifically cytarabine and daunorubicin, can cause effusive-constrictive pericarditis. We describe a case of transient effusive-constrictive pericarditis in a patient with acute myelogenous leukemia. This is the first case report of a patient with transient effusive-constrictive pericarditis due to chemotherapy.

Activated and total coagulation factor VII, and fibrinogen in coronary artery disease.

Fibrinogen (FBG) and total coagulation factor VII (FVIIc) concentrations are higher in those patients with coronary artery disease who are at increased future risk of acute ischemic events. The relationship between activated factor VII (FVIIa) and cardiovascular events, however, has not been intensively studied. Data were collected from 401 consecutive patients who underwent coronary angiography because of suspected coronary artery disease. Conventional risk factors FVIIc, FVIIa and FBG were assessed in relation to the severity of coronary artery disease, left ventricular ejection fraction, and previous clinical events. A strong positive correlation was found between FVIIa and FVIIc (p < 0.001), but neither FVIIa nor FVIIc correlated with FBG. No correlation was found between FVIIa, FVIIc or FBG levels and stenosis score for the severity of coronary artery disease, and all were similar in patients with stable or unstable angina pectoris. Multivariate regression analysis showed FVIIc to be higher in women (p = 0.004), and positively related to triglycerides (p = 0.001) and HDL cholesterol (p = 0.006), but not to a previous myocardial infarction or total cholesterol. FVIIa, on the other hand, was lower in patients with a previous myocardial infarction (p = 0.004), higher in women (p = 0.001) and those that previously had undergone percutaneous transluminal coronary angioplasty (p = 0.039), and positively related to total cholesterol (p = 0.011), duration of coronary artery disease (p = 0.032), and smoking (p = 0.008). FBG was positively associated with a previous myocardial infarction (p = 0.013), hypertension (p = 0.016), smoking (p = 0.005), and the thrombocyte count (p < 0.001). Finally, stepwise logistic regression analysis verified a previous myocardial infarction to be negatively associated with FVIIa (p = 0.03), and positively with FBG (p = 0.03), total cholesterol (p = 0.02), and the severity of coronary artery disease (p < 0.001). In conclusion, in patients suspected of coronary artery disease undergoing cardiac catheterization, FVIIa was decreased and FBG increased in those who had a previous myocardial infarction. FVIIa, FVIIc, or FBG levels were not, however, related to the severity of coronary artery disease, and they were similar in patients with stable or unstable angina pectoris.