Plasma trial: Pilot randomized clinical trial to determine safety and efficacy of plasma transfusions
BACKGROUND Plasma is frequently administered to patients with prolonged INR prior to invasive procedures. However, there is limited evidence evaluating efficacy and safety. STUDY DESIGN AND METHODS We performed a pilot trial in hospitalized patients with INR between 1.5 and 2.5 undergoing procedures conducted outside the operating room. We excluded patients undergoing procedures proximal to the central nervous system, platelet counts <40,000/μl, or congenital or acquired coagulation disorders unresponsive to plasma. We randomly allocated patients stratified by hospital and history of cirrhosis to receive plasma transfusion (10-15 cc/kg) or no transfusion. The primary outcome was change in hemoglobin concentration within 2 days of procedure. RESULTS We enrolled 57 patients, mean age 56.0, 34 (59.6%) with cirrhosis, and mean INR 1.92 (SD = 0.27). In the intention to treat analysis, there were 10 of 27 (38.5%) participants in the plasma arm with a post procedure INR <1.5 and one of 30 (3.6%) in the no treatment arm (p < .01). The mean INR after receiving plasma transfusion was -0.24 (SD 0.26) lower than baseline. The change from pre-procedure hemoglobin level to lowest level within 2 days was -0.6 (SD = 1.0) in the plasma transfusion arm and -0.4 (SD = 0.6) in the no transfusion arm (p = .29). Adverse outcomes were uncommon. DISCUSSION We found no differences in change in hemoglobin concentration in those treated with plasma compared to no treatment. The change in INR was small and corrected to less than 1.5 in minority of patients. Large trials are required to establish if plasma is safe and efficacious.
Photochemically treated fresh frozen plasma for transfusion of patients with acquired coagulopathy of liver disease
Patients with cirrhosis (n= 57).
Plasma transfusion (n= 27).
No transfusion (n= 30).
In the intention to treat analysis, there were 10 of 27 (38.5%) participants in the plasma arm with a post procedure INR <1.5 and one of 30 (3.6%) in the no treatment arm. The mean INR after receiving plasma transfusion was -0.24 (SD 0.26) lower than baseline. The change from pre-procedure haemoglobin level to lowest level within 2 days was -0.6 (SD = 1.0) in the plasma transfusion arm and -0.4 (SD = 0.6) in the no transfusion arm. Adverse outcomes were uncommon.
An ex vivo photochemical treatment (PCT) process was developed to inactivate pathogens in fresh frozen plasma (PCT-FFP). A prospective, controlled, double-blinded, randomized study was conducted to evaluate the efficacy and safety of PCT-FFP compared with conventional FFP (C-FFP). Patients (n = 121) with acquired coagulopathy, largely due to liver disease, including hepatic transplantation, were transfused with either PCT-FFP or C-FFP for up to 7 days. Primary end points were changes in the prothrombin time (PT) and the partial thromboplastin time (PTT) in response to the first FFP transfusion. Secondary analyses compared changes in the PT and the PTT, factor VII levels, clinical hemostasis, blood component usage, and safety following FFP transfusions for up to 7 days. Following the first transfusion, correction in the PT and PTT adjusted for FFP dose and patient weight was not different. Changes in the PT were equivalent between treatment groups (P = . 002 by noninferiority). Equivalence was not demonstrated for changes in the PTT. Following multiple transfusions, correction of the PT and the PTT was similar between groups. No differences were observed in use of blood components, clinical hemostasis, or safety. These results suggest PCT-FFP supported hemostasis in the treatment of acquired coagulopathy similarly to conventional FFP.
Cryoprecipitate for the correction of coagulopathy associated with liver disease
Anaesthesia and Intensive Care. 2003;31((4):):357-61.
In patients with liver disease at risk of pulmonary oedema, cryoprecipitate (small volume) might be a viable alternative to fresh frozen plasma (FFP, large volume) in the correction of coagulopathy. However, the efficacy of cryoprecipitate in these patients has not been tested. We evaluated the role of cryoprecipitate in the correction of the coagulopathy of liver disease. To establish initial evidence of efficacy, six consecutive patients with hepatic failure and coagulopathy received five units of cryoprecipitate. Then, using a crossover design, 11 consecutive patients were randomized to receive either four units of FFP or five units of cryoprecipitate. Pre and post infusion International Normalized Ratio (INR), activated Partial Thromboplastin Time (aPTT), fibrinogen D-dimers, Factors V and IX, and reptilase time were measured. In the first six patients, cryoprecipitate improved the INR, aPTT and fibrinogen concentration (P = 0. 03). In the crossover study, FFP administration produced a greater improvement in INR (P = 0. 007) and aPTT (P = 0. 005) than cryoprecipitate. However, there were no differences in any of the other measured variables. One patient developed acute pulmonary oedema while receiving FFP. Cryoprecipitate improves the coagulopathy of liver disease. Four units of FFP are more efficacious than five units of cryoprecipitate. Cryoprecipitate may have a role in correction of the coagulopathy associated with liver disease where concerns about pulmonary oedema exist.
Effects of increasing blood hemoglobin levels on systemic hemodynamics of acutely anemic cirrhotic patients
Journal of Hepatology. 1998;29((5):):789-95.
BACKGROUND/AIMS: In experimental portal hypertension, blood hemoglobin levels have been shown to influence the hyperdynamic circulatory state. The aim of this study was to assess the hemodynamic effects of increasing hemoglobin concentration in human portal hypertension. METHODS Sixteen cirrhotic patients recovering from a variceal bleeding episode were randomly assigned to receive two units of packed red cells or 500 ml of a protein solution. Systemic and portal hemodynamics, and rheological and hormonal parameters were measured at baseline and after expansion. RESULTS Both groups were similar with respect to the degree of liver failure, severity of the bleeding episode, activation of the endogenous vasopressor systems, and hemodynamic parameters. The administration of either erythrocytes or a protein solution prompted a similar increase in total blood volume and suppression of vasopressor systems. Both groups of patients experienced similar increases in wedged hepatic venous pressure. Hepatic venous pressure gradient was not significantly modified but tended to increase in erythrocyte-transfused patients. Cardiopulmonary pressures increased, but this increment was significant in the non-blood-transfused patients only. Cardiac output decreased in erythrocyte-transfused patients, while it increased in the group receiving a protein solution. Red blood cell transfusion resulted in an increase in systemic vascular hindrance (resistance/blood viscosity), whereas the administration of a protein solution prompted a decrease in this parameter, thus reflecting true vasoconstriction and vasodilation, respectively. CONCLUSIONS An increase in blood hemoglobin in acutely anemic cirrhotic patients attenuates their hyperdynamic circulation beyond viscosity-dependent changes, an effect which might be counteracted by the effects on portal venous pressure gradient.
Virally inactivated fresh frozen plasma in the coagulopathy of liver disease/transplantation
British Journal of Haematology. 1997;97((Suppl 1):):85. Abstract No. 311.
Multicentre clinical trial of low volume fresh frozen plasma therapy in acute pancreatitis
British Journal of Surgery. 1987;74((10):):907-11.
Fresh frozen plasma (FFP) has been proposed as a specific therapy for acute pancreatitis. Reduced mortality encountered in an uncontrolled clinical study and a controlled experimental study may be attributable to replenishment by FFP of the naturally occurring antiprotease system. To investigate this potential therapy further, 202 patients presenting with acute pancreatitis were randomized to receive FFP (2 units daily for 3 days) or a similar volume of colloid control as part of their intravenous fluid therapy. Clinical progress was monitored and the major serum antiproteases (alpha 1-antiprotease and alpha 2-macroglobulin) were measured on days 1, 3 and 7. There was no significant difference between the two groups in terms of clinical outcome. alpha 1-Antiprotease levels rose significantly from day 1 to day 3 in both groups (P less than 0.0001) and remained elevated at day 7. alpha 1-Antiprotease is an acute phase protein in man and raised serum levels would be anticipated. FFP appears to have no effect on the magnitude of this rise. Serum alpha 2-macroglobulin levels were reduced in both groups on day 1 and continued to fall significantly from day 1 to day 3 in the colloid control group (P less than 0.005) whilst remaining substantially unaltered in patients receiving FFP (P = 0.6527). alpha 2-Macroglobulin plays a central role in the elimination of proteases during acute pancreatitis and the ability of relatively low volumes of FFP to reduce the fall in serum alpha 2-macroglobulin levels seen during the early stages of this disease may have therapeutic implications.