Prehospital plasma is associated with survival principally in patients transferred from the scene of injury: A secondary analysis of the PAMPer trial
BACKGROUND We sought to characterize if prehospital transfer origin from the scene of injury (SCENE) or from a referral emergency department (REF) alters the survival benefit attributable to prehospital plasma resuscitation in patients at risk of hemorrhagic shock. METHODS We performed a secondary analysis of data from a recently completed prehospital plasma clinical trial. All of the enrolled patients from either the SCENE or REF groups were included. The demographics, injury characteristics, shock severity and resuscitation needs were compared. The primary outcome was a 30-day mortality. Kaplan-Meier analysis and Cox-hazard regression were used to characterize the independent survival benefits of prehospital plasma for transport origin groups. RESULTS Of the 501 enrolled patients, the REF group patients (n = 111) accounted for 22% with the remaining (n = 390) originating from the scene. The SCENE group patients had higher injury severity and were more likely intubated prehospital. The REF group patients had longer prehospital times and received greater prehospital crystalloid and blood products. Kaplan-Meier analysis revealed a significant 30-day survival benefit associated with prehospital plasma in the SCENE group (P < .01) with no difference found in the REF group patients (P = .36). The Cox-regression verified after controlling for relevant confounders that prehospital plasma was independently associated with a 30-day survival in the SCENE group patients (hazard ratio 0.59; 95% confidence interval 0.39-0.89; P = .01) with no significant relationship found in the REF group patients (hazard ratio 1.03, 95% confidence interval 0.4-3.0). CONCLUSION Important differences across the SCENE and REF cohorts exist that are essential to understand when planning prehospital studies. Prehospital plasma is associated with a survival benefit primarily in SCENE group patients. The results are exploratory but suggest transfer origin may be an important determinant of prehospital plasma benefit.
Clinical and Radiographic Evaluation of Applying Atorvastatin 1.2% Bio Adhesive with Plasma Rich in Growth Factor (PRGF) for Treatment of Mandibular Class II Furcation Defects: a Randomized Clinical Trial
Journal of dentistry (Shiraz, Iran). 2022;23(2):86-94
STATEMENT OF THE PROBLEM Molar teeth with furcation involvement are one of the most common problems in patients with periodontal disease. Regeneration methods are of the most controversial treatment strategies for these lesions. PURPOSE The purpose of this study was to determine the effect of plasma rich in growth factors (PRGF) with 1.2% Atorvastatin (ATV) in the treatment of furcation involvement of mandibular molars. MATERIALS AND METHOD The present randomized clinical trial was conducted on 15 patients with moderate periodontitis and class II furcation involvements; 24 defects were located in four groups of six, including debridement, ATV1.2%, PRGF, PRGF with ATV1.2%. The parameters of vertical probing depth (VPD), vertical clinical attachment level (VCAL), gingival index (GI), horizontal probing depth (HPD) and gingival recession (GR) were measured at baseline (T0), immediately before surgery (T1), 3 (T2), and 6 (T3) months after surgery. Moreover, the bone conditions were evaluated by digital subtraction radiography before and six months after surgery. Data were analyzed using SPSS23 software. RESULTS No significant difference in radiographic parameters was observed among the groups (p= 0.08). There was no significant difference in the mean levels of VPD, VCAL and HPD among the groups at different times (p<0.05). Comparison of clinical parameters of VPD, VCAL and GI in the treatment groups compared to the baseline showed a significant improvement in each group (p< 0.05) but there was no significant difference among different groups (p< 0.05). CONCLUSION The use of PRGF with ATV 1.2% in grade II furcation involvement in mandi-bular molars was effective in the improvement of clinical and radiographic parameters six months after treatment, but this effect revealed no difference in comparison with the other groups.
Post-injury Complement C4 Activation is Associated with Adverse Outcomes and is Potentially Influenced by Plasma Resuscitation
The journal of trauma and acute care surgery. 2022
BACKGROUND Complement activation after trauma promotes hemostasis but is associated with increased morbidity and mortality. However, the specific pathways and downstream mediators remain unclear. Recently the anaphylatoxin C4a has been shown to bind to thrombin receptors. While plasma-based resuscitation has been shown to modify the endotheliopathy of trauma, it may provide complement zymogens that fuel ongoing inflammatory cascades. We sought to characterize the activation of complement after injury and the effect of fresh frozen plasma (FFP) on this inflammatory response. We hypothesized that trauma induces C4 activation, which is associated with worse outcomes and influenced by FFP resuscitation. METHODS Blood was collected from injured patients at a single Level I Trauma Center enrolled in the COMBAT randomized clinical trial. Proteomic analyses were performed through targeted liquid chromatography coupled with mass spectrometry. For the present observational study, concentrations of complement proteins were analyzed at multiple time points, compared between treatment groups, and correlated with outcomes. RESULTS C4 activation occurred over the first six hours post-injury with peak activation 6-24 hours. Tissue hypoperfusion, defined as base deficit >10 mEq/L, and requirement for massive transfusion were associated with greater C4 activation. C4 activation was associated with mortality, multiple organ failure, and longer ventilator requirement. Additionally, temporal trends of C1q, factor B, and C3 by outcome groups support the prevailing theory of primary classical pathway activation with alternative pathway amplification. Resuscitation with FFP over the first six hours was associated with increased C4 activation at 12 and 24 hours. CONCLUSIONS C4 activation has an important inflammatory role post-injury, and FFP has the potential to augment this complement activation during resuscitation. EVIDENCE Level III, Prognostic/Epidemiological.
Effect of plasma rich in growth factors on quality of life following mandibular third molar removal: a double-blind randomized controlled trial
International journal of oral and maxillofacial surgery. 2022
The objective of this study was to investigate the effect of plasma rich in growth factors (PRGF) on patient- and clinician-reported outcomes following mandibular third molar removal. Seventy-four patients requiring surgical removal of a unilateral impacted mandibular third molar under local anaesthesia were recruited into the study. PRGF was prepared for all patients irrespective of study arm allocation. Reviews were conducted 3 days (T1) and 7 days (T2) postoperatively. Primary outcome measures were pain (numerical rating scale, NRS), OHIP-14 (Oral Health Impact Profile-14), and postoperative symptom severity scale (PoSSe) data. Secondary outcome measures including mouth opening, dry socket, socket healing, and analgesic consumption were also explored. The statistical analysis was performed using analysis of covariance and the χ(2) test. NRS pain scores were higher in the PRGF group at T1, demonstrating borderline significance (mean difference 1.0; P = 0.06), with no difference at T2. PoSSe scores did not differ between the groups, with the exception of the 'interference with daily activities' subscale at T1, where PRGF group patients scored 1.2 units higher (P = 0.02). OHIP-14 scores demonstrated a 25% increased likelihood of PRGF patients reporting discomfort on eating at T1 (P = 0.02), with no statistical significance at T2. Secondary outcomes did not differ between the groups. No difference in clinical or quality of life outcomes was observed for patients receiving adjunctive PRGF in third molar sockets.
Prothrombin Complex Concentrate for Trauma Induced Coagulopathy: A Systematic Review and Meta-Analysis
Journal of acute medicine. 2021;11(3):81-89
BACKGROUND Optimal management for trauma-induced coagulopathy (TIC) is a clinical conundrum. In conjunction with the transfusion of fresh-frozen plasma (FFP), additional administration of prothrombin complex concentrate (PCC) was proposed to bring about further coagulative benefit. However, investigations evaluating the efficacy as well as corresponding side effects were scarce and inconsistent. The aim of this study was to systematically review current literature and to perform a meta-analysis comparing FFP+PCC with FFP alone. METHODS Web search followed by manual interrogation was performed to identify relevant literatures fulfilling the following criteria, subjects as TIC patients taking no baseline anticoagulants, without underlying coagulative disorders, and reported clinical consequences. Those comparing FFP alone with PCC alone were excluded. Comprehensive Meta-analysis software was utilized, and statistical results were delineated with odd ratio (OR), mean difference (MD), and 95% confidence interval (CI). I(2) was calculated to determine heterogeneity. The primary endpoint was set as all-cause mortality, while the secondary endpoint consisted of international normalized ratio (INR) correction, transfusion of blood product, and thrombosis rate. RESULTS One hundred and sixty-four articles were included for preliminary evaluation, 3 of which were qualified for meta-analysis. A total of 840 subjects were pooled for assessment. Minimal heterogeneity was present in the comparisons (I(2) < 25%). In the PCC + FFP cohort, reduced mortality rate was observed (OR: 0.631; 95% CI: 0.450-0.884, p = 0.007) after pooling. Meanwhile, INR correction time was shorter under PCC + FFP (MD: -608.300 mins, p < 0.001), whilst the rate showed no difference (p = 0.230). The PCC + FFP group is less likely to mandate transfusion of packed red blood cells (p < 0.001) and plasma (p < 0.001), but not platelet (p = 0.615). The incidence of deep vein thrombosis was comparable in the two groups (p = 0.460). CONCLUSIONS Compared with FFP only, PCC + FFP demonstrated better survival rate, favorable clinical recovery and no elevation of thromboembolism events after TIC.
Patients with trauma induced coagulopathy (3 studies, n= 840).
Prothrombin complex concentrate and fresh-frozen plasma (PCC + FFP).
Fresh-frozen plasma (FFP).
In the PCC + FFP cohort, reduced mortality rate was observed (OR: 0.631) after pooling. Meanwhile, international normalized ratio correction time was shorter under PCC + FFP (MD: -608.300 mins), whilst the rate showed no difference. The PCC + FFP group was less likely to mandate transfusion of packed red blood cells and plasma, but not platelet. The incidence of deep vein thrombosis was comparable in the two groups.
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.
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.
Platelet-rich plasma: a narrative review
EFORT open reviews. 2021;6(4):225-235
The aim of this article was to synopsize platelet-rich plasma (PRP) use in musculoskeletal pathologies through evidence-based assessment of the preparation, classification, mechanism of action and applications of PRP, thereby answering which PRP type is best for each clinical indication.The literature search was performed using Medline, EMBASE and Cochrane Reviews databases for papers containing the key terms "platelet-rich plasma" AND "orthopaedics" AND ("classification" OR "mechanism of action" OR "preparation" OR "clinical application"). Generated papers were evaluated for pertinence in following areas: preparation, classification, mechanism of action, clinical application within orthopaedics. Non-English papers were excluded. Included studies were evaluated for quality.Sixty studies were included in our review. There are many commercial PRP preparation kits with differing component concentrations. There is no consensus on optimal component concentrations. Multiple PRP classifications exist but none have been validated. Platelet-rich plasma acts via growth factors (GFs) released from α-granules within platelets. Growth factors have been shown to be beneficial in healing. Grossly elevated concentrations of GFs may have inhibitory effects on healing. Multiple systematic reviews show efficacy of PRP in tendinopathies, early osteoarthritis, acute muscle injuries and in combination with rotator cuff repair and anterior cruciate ligament reconstruction.The literature suggests leukocyte-rich PRP (L-PRP) is more beneficial in tendinopathies and pure PRP (P-PRP) is more beneficial in cartilage pathology. However, different PRP preparations have not been directly compared in any pathology. Classification of PRP type is frequently not stated in research. Standardization of PRP research parameters is needed to streamline findings and generate clear indications for PRP types to yield maximum clinical benefit. Cite this article: EFORT Open Rev 2021;6:225-235. DOI: 10.1302/2058-5241.6.200017.
Treatment of Atrophic Acne Scars: Topical or intralesional plasma gel?
Photodermatology, photoimmunology & photomedicine. 2021
BACKGROUND Atrophic post acne scarring is considered to be a therapeutic challenge. OBJECTIVES The aim was to compare the safety and efficacy of A) FCL combined with intradermal injection of plasma gel, B) FCL combined with topical application of plasma gel, and C) FCL monotherapy in the treatment of atrophic postacne scars. METHODS Thirty patients with facial atrophic post-acne scars were enrolled in this study and randomly assigned into one of three groups. All of them underwent 4 treatment sessions at 4-weeks intervals. They were assessed objectively by the quantitative global scarring grading system (GSGS). This system was applied at baseline, and after 1- and 6-month follow-up (FU). Subjective assessments were performed through the global aesthetic improvement scale (GAIS) and level of patient satisfaction. The DLQI questionnaire was employed at the baseline and 6-month FU. RESULTS According to the quantitative GSGS scores, the reductions in group A (68.4%) and group B (63%) scores were comparable and both were significantly higher than that in group C (41.2%) in all steps of evaluation. At 6-month FU, both groups A and B showed further significant improvement while group C did not. Based on the GAIS and patients' satisfaction, there were no significant differences between all groups. The reductions in DLQI scores in groups A and B were comparable, however both were significantly higher than group C (p<0.001). CONCLUSIONS The combination of plasma gel and FCL resurfacing was noticeably outstanding in their efficacy and impact on the patients' quality of life.
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.
Forgot calcium? Admission ionized-calcium in two civilian randomized controlled trials of pre-hospital plasma for traumatic hemorrhagic shock
The journal of trauma and acute care surgery. 2020
BACKGROUND Randomized clinical trials(RCTs) support the use of pre-hospital plasma in traumatic hemorrhagic shock, especially in long transports. The citrate added to plasma binds with calcium, yet most pre-hospital trauma protocols have no guidelines for calcium replacement. We reviewed the experience of two recent pre-hospital plasma RCTs regarding admission ionized-calcium (i-Ca) blood levels and its impact on survival. We hypothesized that pre-hospital plasma is associated with hypocalcemia, which in turn is associated with lower survival. METHODS We studied patients enrolled in two institutions participating in pre-hospital plasma RCTs (Control=Standard-of-care; Experimental=Plasma), with i-Ca collected prior to calcium supplementation. Adults with traumatic hemorrhagic shock(SBP≤70 mmHg or 71-90mmHg+HR≥108bpm) were eligible. We use generalized linear mixed models with random intercepts and Cox proportional hazards models with robust standard errors to account for clustered data by institution. Hypocalcemia was defined as i-Ca<1.0mmol/L. RESULTS Of 160 subjects(76% men), 48% received pre-hospital plasma, median age 40years(IQR:28-53), 71% suffered blunt trauma, median ISS=22(IQR:17-34). Pre-hospital plasma and control patients were similar regarding age, sex, ISS, blunt mechanism, and brain injury. Pre-hospital plasma recipients had significantly higher rates of hypocalcemia compared to controls (53% vs 36%, Adjusted Relative Risk, aRR=1.48; 95%CI: 1.03-2.12, p=0.03). Severe hypocalcemia was significantly associated with decreased survival(Adjusted Hazard Ratio:1.07;95%CI:1.02-1.13, p=0.01) and massive transfusion(aRR= 2.70;95%CI:1.13-6.46, p=0.03), after adjustment for confounders(randomization group, age, ISS, and shock index). CONCLUSION Pre-hospital plasma in civilian trauma is associated with hypocalcemia, which in turn predicts lower survival and massive transfusion. These data underscore the need for explicit calcium supplementation guidelines in pre-hospital hemotherapy. LEVEL OF EVIDENCE