Plasma rich in growth factors (PRGF) in non-surgical periodontal therapy: a randomized clinical trial
Braz Oral Res. 2020;34:e034
The aim of this split mouth, double blinded, randomized clinical trial was to evaluate the clinical efficacy of use of Plasma rich in growth factors (PRGF) as an adjunct to scaling and root planing (SRP) in the treatment of periodontal pockets. Twenty six patients (15 males, 11 females) diagnosed with generalized periodontitis with Pocket Depth > 5mm and plaque index score < 1.5, were randomly allocated by using computer generated random sequence, into two groups, one treated with intra-pocket application of PRGF adjunct to SRP and other with SRP alone. The clinical outcomes like pocket depth (PD), relative attachment level (RAL) and sulcus bleeding index (SBI) were assessed at baseline, 3 months and 6 months. Twenty two patients (44 sites) were analyzed at the end of 6 month follow-up, using SPSS 20.0v software. There was a significant statistical difference observed between both the groups favouring SRP +PRGF group in terms of PD (p = 0.007) and RAL (p = 0.021) at the end of 6 month follow-up. Also there was a statistical significant difference (< 0.001) at all time points compared to baseline, for all parameters in intra-group comparison. Moreover, the sites with PD>4mm necessitating further treatment after 6-month follow-up were significantly lesser for SRP+PRGF group. The use of PRGF technology in non-surgical periodontal therapy, by single intra-pocket application in to periodontal pockets as an adjunct to SRP, in chronic periodontitis patients, was found to be effective in reduction of pocket depth and gain in clinical attachment level.
Prothrombin complex concentrate vs. fresh frozen plasma in adult patients undergoing heart surgery - a pilot randomised controlled trial (PROPHESY trial)
There is equipoise regarding the use of prothrombin complex concentrate vs. fresh frozen plasma in bleeding patients undergoing cardiac surgery. We performed a pilot randomised controlled trial to determine the recruitment rate for a large trial, comparing the impact of prothrombin complex concentrate vs. fresh frozen plasma on haemostasis (1 h and 24 h post-intervention), and assessing safety. Adult patients who developed bleeding within 24 h of cardiac surgery that required coagulation factor replacement were randomly allocated to receive prothrombin complex concentrate (15 IU.kg(-1) based on factor IX) or fresh frozen plasma (15 ml.kg(-1) ). If bleeding continued after the first administration of prothrombin complex concentrate or fresh frozen plasma administration, standard care was administered. From February 2019 to October 2019, 180 patients were screened, of which 134 (74.4% (95%CI 67-81%)) consented, 59 bled excessively and 50 were randomly allocated; 25 in each arm, recruitment rate 35% (95%CI 27-44%). There were 23 trial protocol deviations, 137 adverse events (75 prothrombin complex concentrate vs. 62 fresh frozen plasma) and 18 serious adverse events (5 prothrombin complex concentrate vs. 13 fresh frozen plasma). There was no increase in thromboembolic events with prothrombin complex concentrate. No patient withdrew from the study, four were lost to follow-up and two died. At 1 h after administration of the intervention there was a significant increase in fibrinogen, Factor V, Factor XII, Factor XIII, α(2) -antiplasmin and antithrombin levels in the fresh frozen plasma arm, while Factor II and Factor X were significantly higher in the prothrombin complex concentrate group. At 24 h, there were no significant differences in clotting factor levels. We conclude that recruitment to a larger study is feasible. Haemostatic tests have provided useful insight into the haemostatic changes following prothrombin complex concentrate or fresh frozen plasma administration. A definitive trial is needed to ascertain the benefits and safety for each.
Cardiac surgery patients who developed bleeding within 24 hours of surgery (n= 50).
Prothrombin complex concentrate (n= 25).
Fresh frozen plasma (n= 25).
There were 137 adverse events (75 prothrombin complex concentrate vs. 62 fresh frozen plasma) and 18 serious adverse events (5 prothrombin complex concentrate vs. 13 fresh frozen plasma). There was no increase in thromboembolic events with prothrombin complex concentrate. At 1 h after administration of the intervention there was a significant increase in fibrinogen, Factor V, Factor XII, Factor XIII, α(2) -antiplasmin and antithrombin levels in the fresh frozen plasma arm, while Factor II and Factor X were significantly higher in the prothrombin complex concentrate group. At 24 h, there were no significant differences in clotting factor levels.
Coagulation ability when separating from cardiopulmonary bypass with and without fresh frozen plasma: a pilot study
Gen Thorac Cardiovasc Surg. 2020
OBJECTIVE Several strategies are employed for administering fresh frozen plasma (FFP) during weaning from cardiopulmonary bypass (CPB). This study evaluated by coagulation function aimed to compare two strategies of administering FFP in cardiovascular surgery: administering 4 units of FFP before separating from CPB or administering it after weaning from CPB. METHODS Thirty patients who underwent CPB and were expected to receive 8 units of FFP and 20 units of platelet concentrate were randomly allocated into group A (8 units of FFP and 20 units of platelet concentrate administered after separating from CPB) and group B (4 units of FFP administered before separation, and 4 units of FFP and 20 units of platelet concentrate administered after separating from CPB). Thromboelastography (TEG6s((R)), HAEMONETICS Japan GK, Tokyo, Japan) was conducted at four time points before and after separation. Blood test results, blood loss, and required amounts of blood transfusion were compared. The primary outcome was the difference in coagulation function evaluated by TEG6s 90 min after protamine administration. RESULTS Twenty-eight patients were enrolled in the study. Coagulation function after separating from CPB was not significantly different between the groups. Additionally, no significant differences were found in intensive care unit outcomes, such as 24-h transfusion requirements. CONCLUSIONS Coagulation function 90 min after separating from CPB was not significantly different between the groups. Prior FFP administration before separation did not provide significant improvement in coagulation function.
Efficacy of Application of Plasma Rich in Growth Factors Along with the Tunnel Technique for Treatment of Gingival Recession: a Clinical Trial
Journal of dentistry (Shiraz, Iran). 2020;21(4):275-283
STATEMENT OF THE PROBLEM The tunnel technique has shown promising results in treatment of gingival recession. Plasma rich in growth factors (PRGF) is considered effective for soft tissue regeneration since it is a rich source of growth factors. PURPOSE This clinical trial aimed to assess the efficacy of PRGF along with the tunnel technique and connective tissue graft for treatment of gingival recession. MATERIALS AND METHOD In this controlled clinical trial, 20 areas around anterior and posterior teeth in 3 patients with gingival recession were bilaterally selected. The tunnel technique was used with and without PRGF in the test and control groups, respectively (10 areas in each group). The keratinized gingival width (KGW), clinical attachment level (CAL), clinical probing depth (PD), cementoenamel junction (CEJ) to mucogingival junction (MGJ) distance, and the esthetic visual analog scale (EVAS) score were evaluated preoperatively and at 6 weeks and 3 months, postoperatively. The gingival recession width (RW) and vertical recession depth (VRD) were assessed preoperatively and at 2 weeks and 3 months, postoperatively. The pain visual analog scale (PVAS) score was measured at 1, 3 and 7 days, post-treatment and the healing index (HI) was measured at 1, 3 and 7 days and 1 month, postoperatively. The root coverage percentage was assessed during 3 months. Paired t-test and repeated measures ANOVA were used for statistical analyses. p Value< 0.05 was considered statistically significant. RESULTS Significant improvements were noted in all tested parameters in both groups (p< 0.05). The mean root coverage percentage after 6 months was 88.68%±20.69% and 78.77%±24.94% in the test and control groups, respectively. None of the tested parameters were significantly different between two groups (p> 0.05). CONCLUSION Treatment of gingival recession with the tunnel technique can yield favorable clinical outcome, irrespective of the employment of PRGF.
Fresh frozen plasma prime and the level of gammaglobulin after pediatric cardiopulmonary bypass
American journal of clinical and experimental immunology. 2020;9(5):91-100
Different organ perturbation and multiple complications might occur after cardiopulmonary bypass (CPB). A variety of solutions might be used for pump priming with different advantages and disadvantages. The advantage of fresh frozen plasma (FFP) inclusion in pump prime has been shown in post-CPB coagulation management. Acquired hypogammaglobulinemia is the disadvantage of albumin (ALB) pump prime. Our aim was to assess the impact of FFP prime on the post-pump serum level of immunoglobulin G (IgG) and its subclasses. Fifty-six patients under the age of 5 years old who were scheduled for cardiac surgery on CPB were randomly primed with FFP or ALB. Any innate or acquired immune deficiency was considered as exclusion criteria. The pre-CPB and 24-hour post-CPB collected blood samples were analyzed by the nephelometric method for the plasma level of IgG and its four subclasses. Twenty-two patients (mean age and weight of 13 months and 6.8 kilograms) in the ALB prime group and 26 patients (mean age and weight of 15 months and 8.1 kilograms) in the FFP prime group completed the study. Using paired t-test and repeated measures ANOVA test, patients in the ALB prime group had a significant drop in the post-CPB serum level of total IgG (597±138 mg/dL to 379±179 mg/dL, P value <0.001) and its two subclasses of IgG1 and IgG3. In contrast, there was a slight elevation in the serum level of total IgG (549±207 mg/dL to 630±180 mg/dL, P value =0.008) and its two subclasses of IgG2 and IgG4 in patients who had FFP prime solution. In conclusion, compared to the ALB prime solution, FFP inclusion in prime could hamper the pediatric post-CPB induced hypogammaglobulinemia.
Resuscitation of endotheliopathy and bleeding in thoracic aortic dissections: the VIPER-OCTA randomized clinical pilot trial
Anesthesia and Analgesia. 2018;127((4):):920-927
BACKGROUND Thoracic aorta dissection is an acute critical condition associated with shock-induced endotheliopathy, coagulopathy, massive bleeding, and significant morbidity and mortality. Our aim was to compare the effect of coagulation support with solvent/detergent-treated pooled plasma (OctaplasLG) versus standard fresh frozen plasma (FFP) on glycocalyx and endothelial injury, bleeding, and transfusion requirements. METHODS Investigator-initiated, single-center, blinded, randomized clinical pilot trial of adult patients undergoing emergency surgery for thoracic aorta dissection. Patients were randomized to receive OctaplasLG or standard FFP as coagulation factor replacement related to bleeding. The primary outcome was glycocalyx and endothelial injury. Other outcomes included bleeding, transfusions and prohemostatics at 24 hours, organ failure, length of stay in the intensive care unit and in the hospital, safety, and mortality at 30 and 90 days. RESULTS Fifty-seven patients were included to obtain 44 evaluable on the primary outcome. The OctaplasLG group displayed significantly reduced damage to the endothelial glycocalyx (syndecan-1) and reduced endothelial tight junction injury (sVE-cadherin) compared to standard FFP. In the OctaplasLG group compared to the standard FFP, days on ventilator (1 day [interquartile range, 0-1] vs 2 days [1-3]; P = .013), bleeding during surgery (2150 [1600-3087] vs 2750 [2130-6875]; P = .046), 24-hour total transfusion and platelet transfusion volume (3975 mL [2640-6828 mL] vs 6220 mL [4210-10,245 mL]; P = .040, and 1400 mL [1050-2625 mL] vs 2450 mL [1400-3500 mL]; P = .027), and goal-directed use of prohemostatics (7/23 [30.4%] vs 13/21 [61.9%]; P = .036) were all significantly lower. Among the 57 patients randomized, 30-day mortality was 20.7% (6/29) in the OctaplasLG group and 25% (7/28) in the standard FFP group (P = .760). No safety concern was raised. CONCLUSIONS In this randomized, clinical pilot trial of patients undergoing emergency surgery for thoracic aorta dissections, we found that OctaplasLG reduced glycocalyx and endothelial injury, reduced bleeding, transfusions, use of prohemostatics, and time on ventilator after surgery compared to standard FFP. An adequately powered multicenter trial is warranted to confirm the clinical importance of the findings.
Early or late fresh frozen plasma administration in newborns and small infants undergoing cardiac surgery: the APPEAR randomized trial
British Journal of Anaesthesia. 2017;118((5)):788-796.
Background: In newborns and small infants undergoing cardiac surgery with cardiopulmonary bypass (CPB) and blood priming, it is unclear whether there is reduced blood loss if fresh frozen plasma (FFP) is added to the CPB priming volume. This single-centre, randomized trial tested the hypothesis that the administration of FFP after CPB (late FFP group) is superior to FFP priming (early FFP group) in terms of postoperative bleeding and overall red blood cell (RBC) transfusion. Methods: Seventy-three infants weighing <10 kg were randomly allocated to receive FFP to supplement RBCs in the CPB priming solution ( n =36) or immediately after CPB ( n =37). The primary endpoint was a difference in postoperative blood loss; secondary endpoints included the amount of RBCs and FFP transfused through the first 48 postoperative hours. Results: All patients were included in the analysis. Patients in the late FFP arm had greater postoperative mean blood loss than patients in the early FFP arm [33.1 ( sd 20.6) vs 24.1 (12.9) ml kg -1 ; P =0.028], but no differences in transfusions were found. The subgroup of cyanotic heart disease patients had comparable results, but with greater use of RBCs in the late FFP group. Conclusions: In infants undergoing cardiac surgery, FFP in the priming solution appears slightly superior to late administration in terms of postoperative bleeding. Clinical trial registration: www.ClinicalTrials.gov , NCT02738190.
Fresh frozen plasma for cardiovascular surgery
Cochrane Database of Systematic Reviews.. 2015;((7)):CD007614.
BACKGROUND Fresh frozen plasma (FFP) is a blood component containing procoagulant factors, which is sometimes used in cardiovascular surgery with the aim of reducing the risk of bleeding. The purpose of this review is to assess the risk of mortality for patients undergoing cardiovascular surgery who receive FFP. OBJECTIVES To evaluate the risk to benefit ratio of FFP transfusion in cardiovascular surgery for the treatment of bleeding patients or for prophylaxis against bleeding. SEARCH METHODS We searched 11 bibliographic databases and four ongoing trials databases including the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3, 2015), MEDLINE (OvidSP, 1946 to 21 April 2015), EMBASE (OvidSP, 1974 to 21 April 2015), PubMed (e-publications only: searched 21 April 2015), ClinicalTrials.gov, World Health Organization (WHO) ICTRP and the ISRCTN Register (searched 21 April 2015). We also searched the references of all identified trials and relevant review articles. We did not limit the searches by language or publication status. SELECTION CRITERIA We included randomised controlled trials in patients undergoing major cardiac or vascular surgery who were allocated to a FFP group or a comparator (no plasma or an active comparator, either clinical plasma (any type) or a plasma-derived blood product). We included participants of any age (neonates, children and adults). We excluded studies of plasmapheresis and plasma exchange. DATA COLLECTION AND ANALYSIS Two authors screened all electronically derived citations and abstracts of papers identified by the review search strategy. Two authors assessed risk of bias in the included studies and extracted data independently. We took care to note whether FFP was used therapeutically or prophylactically within each trial. MAIN RESULTS We included 15 trials, with a total of 755 participants for analysis in the review. Fourteen trials compared prophylactic use of FFP against no FFP. One study compared therapeutic use of two types of plasma. The timing of intervention varied, including FFP transfusion at the time of heparin neutralisation and stopping cardiopulmonary bypass (CPB) (seven trials), with CPB priming (four trials), after anaesthesia induction (one trial) and postoperatively (two trials). Twelve trials excluded patients having emergency surgery and nine excluded patients with coagulopathies.Overall the trials were small, with only four reporting an a priori sample size calculation. No trial was powered to determine changes in mortality as a primary outcome. There was either high risk of bias, or unclear risk, in the majority of trials included in this review.There was no difference in the number of deaths between the intervention arms in the six trials (with 287 patients) reporting mortality (very low quality evidence). There was also no difference in blood loss in the first 24 hours for neonatal/paediatric patients (four trials with 138 patients; low quality evidence): mean difference (MD) -1.46 ml/kg (95% confidence interval (CI) -4.7 to 1.78 ml/kg); or adult patients (one trial with 120 patients): MD -12.00 ml (95% CI -101.16 to 77.16 ml).Transfusion with FFP was inferior to control for preventing patients receiving any red cell transfusion: Peto odds ratio (OR) 2.57 (95% CI 1.30 to 5.08; moderate quality evidence). There was a difference in prothrombin time within two hours of FFP transfusion in eight trials (with 210 patients; moderate quality evidence) favouring the FFP arm: MD -0.71 seconds (95% CI -1.28 to -0.13 seconds). There was no difference in the risk of returning to theatre for reoperation (eight trials with 398 patients; moderate quality evidence): Peto OR 0.81 (95% CI 0.26 to 2.57). Only one included study reported adverse events as an outcome and reported no significant adverse events following FFP transfusion. AUTHORS' CONCLUSIONS This review has found no evidence to support the prophylactic administration of FFP to patients without coagulopathy undergoing elective cardiac surgery. There was insufficient evidence about treatment of p
Prophylactic versus reactive transfusion of thawed plasma in patients undergoing surgical repair of craniosynostosis: a randomized clinical trial
Paediatric Anaesthesia. 2015;25((3):):279-87.
BACKGROUND Surgical repair of craniosynostosis in young children is associated with copious bleeding and often coagulopathy. Typically, a reactive transfusion strategy is used to treat coagulopathy whereby fresh frozen plasma (FFP) is given only after clinical manifestation of clotting abnormality. This prospective, randomized clinical trial was designed to test the hypothesis that prophylactic FFP during craniofacial surgery reduces blood loss and blood transfusion requirements compared to a reactive FFP transfusion strategy. METHODS Eighty-one patients less than 2 years of age requiring primary repair of craniosynostosis were randomized to receive FFP using either a prophylactic or reactive strategy. Laboratory values were measured at four standardized time points. The volume of blood products transfused, length of stay in the pediatric intensive care unit (PICU), hospital length of stay, and number of donor exposures were recorded for each patient. RESULTS The prophylactic FFP group received a significantly greater average volume of FFP compared to the reactive group (29.7 mlkg(-1) vs 16.1 mlkg(-1) ; P < 0.001), which was associated with improvement in coagulation values at multiple time points. However, there was no difference in blood transfusion requirements or blood loss between the two groups. The two transfusion strategies resulted in similar median donor exposures. There was no difference in PICU or hospital length of stay. CONCLUSION A reactive FFP transfusion strategy required less plasma transfusion and was associated with similar rates of blood loss and PRBC transfusion as prophylactic FFP despite improvement in coagulation values in the prophylactic FFP group.Copyright 2014 John Wiley & Sons Ltd.
Evidence-based use of FFP: the influence of a priming strategy without FFP during CPB on postoperative coagulation and recovery in pediatric patients
OBJECTIVE Although fresh frozen plasma (FFP) is one of the most commonly used hemostatic agents in clinical specialties today, there is little evidence available supporting its administration. Our present study observed the effects of a priming strategy without FFP during cardiopulmonary bypass (CPB) on postoperative coagulation and clinical recovery in pediatric patients, aiming to supply new evidence for evidence-based use of FFP. METHOD Eighty pediatric patients with congenital heart disease undergoing cardiac surgery with CPB were randomized to receive either 10-20 ml/kg 4% succinylated gelatin (Gelofusine, GEL group, n = 40) or 1-2 units FFP (FFP group, n = 40) in the pump prime. Rapid-thromboelastography (r-TEG) and functional fibrinogen level were measured before skin incision and 15 minutes after heparin reversal. We recorded the volume of chest tube drainage, transfusion requirements and the dosage of pharmacological agents. The ventilation time, ICU length of stay and hospitalization time after surgery were also collected. RESULTS After heparin neutralization, there were significantly elevated levels of fibrinogen in the FFP group, which were manifested by r-TEG parameters MAf and FLEV. No significant differences were observed between the two groups in postoperative bleeding, transfusion requirements and the usage of pharmacological agents. Recovery time was also comparable between the two groups. CONCLUSION In conclusion, prophylactic use of FFP in the priming solution does not provide clinical benefits as presumed. Artificial colloids, such as Gelofusine, can be used safely and effectively as a substitute for FFP in the pump prime. TEG is an effective assessment tool to evaluate postoperative coagulation function in pediatric patients.Copyright © The Author(s) 2014.