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Blood Advances Jan 2022Idiopathic purpura fulminans (IPF) is a rare but severe prothrombotic coagulation disorder that can occur after chickenpox or human herpesvirus 6 (HHV-6) infection. IPF...
Idiopathic purpura fulminans (IPF) is a rare but severe prothrombotic coagulation disorder that can occur after chickenpox or human herpesvirus 6 (HHV-6) infection. IPF leads to an autoantibody-mediated decrease in the plasma concentration of protein S. We conducted a retrospective multicenter study involving patients with IPF from 13 French pediatric centers and a systematic review of cases in published literature. Eighteen patients were included in our case series, and 34 patients were included as literature review cases. The median age was 4.9 years, and the diagnostic delay after the first signs of viral infection was 7 days. The lower limbs were involved in 49 patients (94%) with typical lesions. In all, 41 patients (78%) had a recent history of varicella-zoster virus infection, and 7 patients (14%) had been infected by HHV-6. Most of the patients received heparin (n = 51; 98%) and fresh frozen plasma transfusions (n = 41; 79%); other treatment options were immunoglobulin infusion, platelet transfusion, corticosteroid therapy, plasmapheresis, and coagulation regulator concentrate infusion. The antithrombin level and platelet count at diagnosis seemed to be associated with severe complications. Given the rarity of this disease, the creation of a prospective international registry is required to consolidate these findings.
Topics: Child; Child, Preschool; Humans; Chickenpox; Delayed Diagnosis; Prospective Studies; Protein S; Purpura Fulminans; Retrospective Studies
PubMed: 34788405
DOI: 10.1182/bloodadvances.2021005126 -
The Cochrane Database of Systematic... Nov 2021Acute limb ischaemia usually is caused by a blood clot blocking an artery or a bypass graft. Severe acute ischaemia will lead to irreversible damage to muscles and... (Review)
Review
BACKGROUND
Acute limb ischaemia usually is caused by a blood clot blocking an artery or a bypass graft. Severe acute ischaemia will lead to irreversible damage to muscles and nerves if blood flow is not restored in a few hours. Once irreversible damage occurs, amputation will be necessary and the condition can be life-threatening. Infusion of clot-busting drugs (thrombolysis) is a useful tool in the management of acute limb ischaemia. Fibrinolytic drugs are used to disperse blood clots (thrombi) to clear arterial occlusion and restore blood flow. Thrombolysis is less invasive than surgery. A variety of techniques are used to deliver fibrinolytic agents. This is an update of a review first published in 2004.
OBJECTIVES
To compare the effects of infusion techniques during peripheral arterial thrombolysis for treatment of patients with acute limb ischaemia.
SEARCH METHODS
The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registries to 20 October 2020. We undertook reference checking to identify additional studies.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) comparing infusion techniques for fibrinolytic agents in the treatment of acute limb ischaemia.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures as recommended by Cochrane. We assessed the risk of bias in included trials using the Cochrane 'Risk of bias' tool. We evaluated certainty of evidence using GRADE. For dichotomous outcomes, we calculated the odds ratio (OR) with the corresponding 95% confidence interval (CI). We were not able to carry out meta-analyses due to clinical heterogeneity, so we have reported the results and performed the comparisons narratively. The main outcomes of interest were amputation-free survival or limb salvage, amputation, mortality, vessel patency, duration of thrombolysis, and complications such as cerebrovascular accident and major and minor bleeding.
MAIN RESULTS
Nine studies with a total of 671 participants are included in this update. Trials covered a variety of infusion techniques, dosage regimens, and adjunctive agents. We grouped trials according to types of techniques assessed (e.g. intravenous and intra-arterial delivery of the agent, 'high-' and 'low-dose' regimens of the agent, continuous infusion and 'forced infusion' of the agent, use of adjunctive antiplatelet agents). We assessed the certainty of evidence as very low to low due to the limited power of individual studies to deliver clinically relevant results, small and heterogeneous study populations, use of different inclusion criteria by each study in terms of severity and duration of ischaemia, considerably different outcome measures between trials, and use of different fibrinolytic agents. This heterogeneity prevented pooling of data in meta-analyses. No regimen has been shown to confer benefit in terms of amputation-free survival (at 30 days), amputation, or death. For vessel patency, complete success was more likely with intra-arterial (IA) than with intravenous (IV) infusion (odds ratio (OR) 13.22, 95% confidence interval (CI) 2.79 to 62.67; 1 study, 40 participants; low-certainty evidence); radiological failure may be more likely with IV infusion (OR 0.02, 95% CI 0.00 to 0.38; 1 study, 40 participants; low-certainty evidence). Due to the small numbers involved in each arm and design differences between arms, it is not possible to conclude whether any technique offered any advantage over another. None of the treatment strategies clearly affected complications such as cerebrovascular accident or major bleeding requiring surgery or blood transfusion. Minor bleeding complications were more frequent in systemic (intravenous) therapy compared to intra-arterial infusion (OR 0.03, 95% CI 0.00 to 0.56; 1 study, 40 participants), and in high-dose compared to low-dose therapy (OR 0.11, 95% CI 0.01 to 0.96; 1 study, 63 participants). Limited evidence from individual trials appears to indicate that high-dose and forced-infusion regimens reduce the duration of thrombolysis. In one trial, the median duration of infusion was 4 hours (range 0.25 to 46) for the high-dose group and 20 hours (range 2 to 46) for the low-dose group. In a second trial, treatment using pulse spray was continued for a median of 120 minutes (range 40 to 310) compared with low-dose infusion for a median of 25 hours (range 2 to 60). In a third trial, the median duration of therapy was reduced with pulse spray at 195 minutes (range 90 to 1260 minutes) compared to continuous infusion at 1390 minutes (range 300 to 2400 minutes). However, none of the studies individually showed improvement in limb salvage at 30 days nor benefit for the amputation rate related to the technique of drug delivery. Similarly, no studies reported a clear difference in occurrence of cerebrovascular accident or major bleeding. Although 'high-dose' and 'forced-infusion' techniques achieved vessel patency in less time than 'low-dose' infusion, more minor bleeding complications may be associated (OR 0.11, 95% CI 0.01 to 0.96; 1 study, 72 participants; and OR 0.48, 95% CI 0.17 to 1.32; 1 study, 121 participants, respectively). Use of adjunctive platelet glycoprotein IIb/IIIa antagonists did not improve outcomes, and results were limited by inclusion of participants with non-limb-threatening ischaemia.
AUTHORS' CONCLUSIONS
There is insufficient evidence to show that any thrombolytic regimen provides a benefit over any other in terms of amputation-free survival, amputation, or 30-day mortality. The rate of CVA or major bleeding requiring surgery or blood transfusion did not clearly differ between regimens but may occur more frequently in high dose and IV regimens. This evidence was limited and of very low certainty. Minor bleeding may be more common with high-dose and IV regimens. In this context, thrombolysis may be an acceptable therapy for patients with marginally threatened limbs (Rutherford grade IIa) compared with surgery. Caution is advised for patients who do not have limb-threatening ischaemia (Rutherford grade I) because of risks of major haemorrhage, cerebrovascular accident, and death from thrombolysis.
Topics: Amputation, Surgical; Arteries; Fibrinolytic Agents; Humans; Ischemia; Thrombolytic Therapy
PubMed: 34786692
DOI: 10.1002/14651858.CD000985.pub3 -
Annals of Palliative Medicine Oct 2021To investigate the prevention of platelet transfusion refractoriness (PTR) by platelet antigen gene matching using literature search and meta-analysis. (Meta-Analysis)
Meta-Analysis
BACKGROUND
To investigate the prevention of platelet transfusion refractoriness (PTR) by platelet antigen gene matching using literature search and meta-analysis.
METHODS
PubMed (2000.1-2021.8), Embase (2000.1-2021.8), Cochrane (2010.1-2021.8), and the Chinese Biomedical Literature Database CBM (2010.1-2021.8) were selected as the search database platform. The keywords (HLA/Human leukocyte antigen), (HPA/Human platelet alloantigens), (genotyping/cross-match), platelet transfusion (PLT), and (CCI/Corrected Count Increment) were used for the joint search. After the literature was screened for inclusion and exclusion criteria, the Cochrane intervention handbook was used for bias risk assessment, and Revman 5.3.5 software was used for analysis to obtain the statistical forest plot and funnel plot.
RESULTS
The preliminary results revealed 255 publications, and seven (297 patients in total) were finally included in the quantitative analysis. A total of five publications reported comparison of the 1 h CCI index of HLA or HPA gene matching and PLT after random selection, and the heterogeneity test showed statistical difference (I2=49%, P=0.10). The combined statistical analysis results were: (MD =8.57, 95% CI: 7.30-9.80, Z=13.30, P<0.00001), and while six publications reported the effective rate index of PLT, and the heterogeneity test showed no statistical difference (I2=43%, P=0.12). The fixed effect mode was used to compare the effective rate of the two intervention methods (OR =4.90, 95% CI: 3.50-6.86, Z=9.23, P<0.00001).
DISCUSSION
HLA or HPA gene matching can improve the increment after PLT and reduce the incidence of ineffective PLT.
Topics: Antigens, Human Platelet; Blood Platelets; HLA Antigens; Humans; Platelet Transfusion; Thrombocytopenia
PubMed: 34763457
DOI: 10.21037/apm-21-2603 -
Oral Surgery, Oral Medicine, Oral... Apr 2022The objective of this study was to determine bleeding control interventions (BCIs) that were reported to be effective in controlling postoperative bleeding in patients... (Review)
Review
World Workshop on Oral Medicine VII: Bleeding control interventions for invasive dental procedures in patients with inherited functional platelet disorders: A systematic review.
OBJECTIVES
The objective of this study was to determine bleeding control interventions (BCIs) that were reported to be effective in controlling postoperative bleeding in patients with inherited functional platelet disorders (IFPDs) undergoing invasive dental procedures.
STUDY DESIGN
We searched MEDLINE/PubMed, Embase, Cochrane Library (Wiley), and Scopus from 1960 through April 2020 for studies on patients with IFPD undergoing invasive dental procedures. Two reviewers conducted assessments independently.
RESULTS
We found a total of 620 nonduplicate published articles, of which 32 studies met our inclusion criteria. Management with BCI in patients with IFPD included in this systematic review was effective in 80.7% of treatment sessions. Local measures used intraoperatively were found to be effective. Three different protocols of BCI were noted; the most effective protocol consisted of antifibrinolytics, scaffold/matrix agents, and sutures (P < .01). An adjunct protocol consisting of a tissue sealant was also effective (P < .01). A third protocol of platelet transfusion and antifibrinolytics was ineffective in controlling postoperative bleeding in 4 of 6 dental sessions.
CONCLUSIONS
This systematic review supports the use of local measures intraoperatively and antifibrinolytics postoperatively. It also supports making decision regarding platelet transfusion based on the clinician's clinical judgment and medical history of the individual patient.
Topics: Antifibrinolytic Agents; Dentistry; Humans; Platelet Transfusion; Postoperative Hemorrhage
PubMed: 34758941
DOI: 10.1016/j.oooo.2021.08.003 -
Journal of Acute Medicine Sep 2021Optimal management for trauma-induced coagulopathy (TIC) is a clinical conundrum. In conjunction with the transfusion of fresh-frozen plasma (FFP), additional...
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 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 < 25%). In the PCC + FFP cohort, reduced mortality rate was observed (OR: 0.631; 95% CI: 0.450-0.884, = 0.007) after pooling. Meanwhile, INR correction time was shorter under PCC + FFP (MD: -608.300 mins, < 0.001), whilst the rate showed no difference ( = 0.230). The PCC + FFP group is less likely to mandate transfusion of packed red blood cells ( < 0.001) and plasma ( < 0.001), but not platelet ( = 0.615). The incidence of deep vein thrombosis was comparable in the two groups ( = 0.460).
CONCLUSIONS
Compared with FFP only, PCC + FFP demonstrated better survival rate, favorable clinical recovery and no elevation of thromboembolism events after TIC.
PubMed: 34595091
DOI: 10.6705/j.jacme.202109_11(3).0001 -
Digestive and Liver Disease : Official... Nov 2021Severe thrombocytopenia in cirrhosis can preclude invasive procedures. Platelet transfusion is recommended if platelet count pre-procedure is potential alternative to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Severe thrombocytopenia in cirrhosis can preclude invasive procedures. Platelet transfusion is recommended if platelet count pre-procedure is potential alternative to platelet transfusion is thrombopoietin-receptor (TPO) agonists.
AIM
Evaluate TPO-agonist efficacy and safety in cirrhotic patients with severe thrombocytopenia undergoing invasive procedures.
METHODS
Randomized control trials (RCT) from electronic reference databases were searched from inception till December 2019. PRISMA guidelines were followed. Primary outcome was platelet transfusion avoidance. Secondary outcomes were weighted mean difference (WMD) in platelet count from baseline to pre-procedure and rates of major adverse events (AE). Pooled Odds Ratio (OR) were estimated using a random-effects model.
RESULTS
Six RCTs with 1,229 patients were included. All studies had low risk of bias. Compared with placebo, those treated with TPO-agonists had a pooled OR of 0.12(0.08-0.17), P<0.01 for platelet transfusion avoidance, and WMD in platelet count (x10 3 /µL) of 35.6(28.6-42.7), P<0.01. Major AE did not differ between groups [Pooled OR: 0.87(0.47-1.62), P=0.66].
CONCLUSION
Compared to placebo, TPO-agonists used in cirrhotic patients with severe thrombocytopenia prior to elective invasive procedures had 88% reduced odds of requiring peri-procedural platelet transfusion and increased platelet count pre-procedure, with no difference in AE rates.
Topics: Elective Surgical Procedures; Humans; Liver Cirrhosis; Platelet Count; Preoperative Care; Randomized Controlled Trials as Topic; Receptors, Thrombopoietin; Thrombocytopenia
PubMed: 34373229
DOI: 10.1016/j.dld.2021.07.015 -
Blood Transfusion = Trasfusione Del... Sep 2022Acquired platelet function disorders (PFD) are rare bleeding diseases that should be suspected in all patients with unexplained mucocutaneous bleedings of recent onset,... (Review)
Review
Acquired platelet function disorders (PFD) are rare bleeding diseases that should be suspected in all patients with unexplained mucocutaneous bleedings of recent onset, with no previous history of haemorrhages, and with normal coagulation test and platelet count. Drug-induced platelet function bleeding disorders are the most frequent PFDs and can easily be identified on the basis of recent administration of platelet-inhibiting drugs. Apart from these, the most challenging acquired PFDs are those caused by autoimmune mechanisms. In fact, demonstration of autoantibodies inhibiting platelet function may be difficult in most non-specialised centres. Among autoimmune PFDs (aPFDs), acquired Glanzmann thrombasthenia (aGT), which is caused by autoantibodies that bind to platelet αIIbβ3 integrin, inhibiting its function, is the most frequent. aGT can be associated with underlying haematological malignancies or autoimmune diseases but can also be idiopathic. More rarely, other immune-mediated PFDs can occur, such as acquired delta storage pool disease (aδSPD). Treatment of aPFDs must rely on the control of acute and chronic bleedings, treatment of the underlying disease in secondary forms, and immunosuppressive treatment for autoantibody reduction or eradication. aPFDs may completely resolve upon treatment of any underlying disease that may be present. In primary aPFDs, and in the majority of secondary forms, treatment relies on immunosuppressive therapies.Here we present a systematic review of previously described immune-mediated aGT and aδSPD cases. Clinical and laboratory characteristics, treatments for the control of bleedings and for the eradication of autoantibodies, and responses to treatments are also discussed. Although no guidelines are available for the management of these very rare conditions, presentation of all cases reported so far can help clinicians in the diagnosis and treatment of these life-threatening diseases.
Topics: Albinism; Autoantibodies; Autoimmune Diseases; Hemorrhagic Disorders; Hermanski-Pudlak Syndrome; Humans; Platelet Glycoprotein GPIIb-IIIa Complex; Thrombasthenia
PubMed: 34369869
DOI: 10.2450/2021.0119-21 -
Transfusion Jul 2021In traumatic bleeding, transfusion practice has shifted toward higher doses of platelets and plasma transfusion. The aim of this systematic review was to investigate... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In traumatic bleeding, transfusion practice has shifted toward higher doses of platelets and plasma transfusion. The aim of this systematic review was to investigate whether a higher platelet-to-red blood cell (RBC) transfusion ratio improves mortality without worsening organ failure when compared with a lower ratio of platelet-to-RBC.
METHODS
Pubmed, Medline, and Embase were screened for randomized controlled trials (RCTs) in bleeding trauma patients (age ≥16 years) receiving platelet transfusion between 1946 until October 2020. High platelet:RBC ratio was defined as being the highest ratio within an included study. Primary outcome was 24 hour mortality. Secondary outcomes were 30-day mortality, thromboembolic events, organ failure, and correction of coagulopathy.
RESULTS
In total five RCTs (n = 1757 patients) were included. A high platelet:RBC compared with a low platelet:RBC ratio significantly improved 24 hour mortality (odds ratio [OR] 0.69 [0.53-0.89]) and 30- day mortality (OR 0.78 [0.63-0.98]). There was no difference between platelet:RBC ratio groups in thromboembolic events and organ failure. Correction of coagulopathy was reported in five studies, in which platelet dose had no impact on trauma-induced coagulopathy.
CONCLUSIONS
In traumatic bleeding, a high platelet:RBC improves mortality as compared to low platelet:RBC ratio. The high platelet:RBC ratio does not influence thromboembolic or organ failure event rates.
Topics: Blood Platelets; Erythrocyte Count; Erythrocytes; Hemorrhage; Humans; Platelet Count; Wounds and Injuries
PubMed: 34269443
DOI: 10.1111/trf.16455 -
Mayo Clinic Proceedings Sep 2021To evaluate the effectiveness and adverse events of autologous platelet-rich plasma (PRP) in individuals with lower-extremity diabetic ulcers, lower-extremity venous... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the effectiveness and adverse events of autologous platelet-rich plasma (PRP) in individuals with lower-extremity diabetic ulcers, lower-extremity venous ulcers, and pressure ulcers.
PATIENTS AND METHODS
We searched multiple databases from database inception to June 11, 2020, for randomized controlled trials and observational studies that compared PRP to any other wound care without PRP in adults with lower-extremity diabetic ulcers, lower-extremity venous ulcers, and pressure ulcers.
RESULTS
We included 20 randomized controlled trials and five observational studies. Compared with management without PRP, PRP therapy significantly increased complete wound closure in lower-extremity diabetic ulcers (relative risk, 1.20; 95% CI, 1.09 to 1.32, moderate strength of evidence [SOE]), shortened time to complete wound closure, and reduced wound area and depth (low SOE). No significant changes were found in terms of wound infection, amputation, wound recurrence, or hospitalization. In patients with lower-extremity venous ulcers or pressure ulcers, the SOE was insufficient to estimate an effect on critical outcomes, such as complete wound closure or time to complete wound closure. There was no statistically significant difference in adverse events.
CONCLUSION
Autologous PRP may increase complete wound closure, shorten healing time, and reduce wound size in individuals with lower-extremity diabetic ulcers. The evidence is insufficient to estimate an effect on wound healing in individuals with lower-extremity venous ulcers or pressure ulcers.
TRIAL REGISTRATION
PROSPERO Identifier: CRD42020172817.
Topics: Blood Transfusion, Autologous; Chronic Disease; Diabetic Foot; Female; Humans; Male; Observational Studies as Topic; Platelet Transfusion; Platelet-Rich Plasma; Pressure Ulcer; Randomized Controlled Trials as Topic; Varicose Ulcer; Wound Healing
PubMed: 34226023
DOI: 10.1016/j.mayocp.2021.01.030 -
The Journal of Trauma and Acute Care... Oct 2021Platelet transfusion during major hemorrhage is important and often embedded in massive transfusion protocols. However, the optimal ratio of platelets to erythrocytes... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Platelet transfusion during major hemorrhage is important and often embedded in massive transfusion protocols. However, the optimal ratio of platelets to erythrocytes (platelet-rich plasma [PLT]/red blood cell [RBC] ratio) remains unclear. We hypothesized that high PLT/RBC ratios, as compared with low PLT/RBC ratios, are associated with improved survival in patients requiring massive transfusion.
METHODS
Four databases (Pubmed, CINAHL, EMBASE, and Cochrane) were systematically screened for literatures published until January 21, 2021, to determine the effect of PLT/RBC ratio on the primary outcome measure mortality at 1 hour to 6 hours and 24 hours and at 28 days to 30 days. Studies comparing various PLT/RBC ratios were included in the meta-analysis. Secondary outcomes included intensive care unit length of stay and in-hospital length of stay and total blood component use. The study protocol was registered in PROSPERO under number CRD42020165648.
RESULTS
The search identified a total of 8903 records. After removing the duplicates and second screening of title, abstract, and full text, a total of 59 articles were included in the analysis. Of these articles, 12 were included in the meta-analysis. Mortality at 1 hour to 6 hours, 24 hours, and 28 days to 30 days was significantly lower for high PLT/RBC ratios as compared with low PLT/RBC ratios.
CONCLUSION
Higher PLT/RBC ratios are associated with significantly lower 1-hour to 6-hour, 24-hour, 28-day to 30-day mortalities as compared with lower PLT/RBC ratios. The optimal PLT/RBC ratio for massive transfusion in trauma patients is approximately 1:1.
LEVEL OF EVIDENCE
Systematic review and meta-analysis, therapeutic Level III.
Topics: Erythrocyte Transfusion; Hemorrhage; Hospital Mortality; Humans; Length of Stay; Platelet Transfusion; Platelet-Rich Plasma; Trauma Severity Indices; Treatment Outcome; Wounds and Injuries
PubMed: 34225351
DOI: 10.1097/TA.0000000000003323