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Journal of Chest Surgery Jan 2024Prothrombin complex concentrate (PCC) and fresh frozen plasma (FFP) are commonly used to manage bleeding in patients during cardiac surgery. However, the relative... (Review)
Review
BACKGROUND
Prothrombin complex concentrate (PCC) and fresh frozen plasma (FFP) are commonly used to manage bleeding in patients during cardiac surgery. However, the relative efficacy and safety of these 2 strategies remain uncertain.
METHODS
MEDLINE, Embase, and Cochrane were searched for studies comparing PCC and FFP in patients who underwent cardiac surgery complicated by bleeding. Review Manager (RevMan) ver. 5.4 (Nordic Cochrane Centre, The Cochrane Collaboration) was used for statistical analysis. Binary and continuous outcomes were compared using pooled risk ratios and mean differences, respectively. The meta-analysis protocol was registered in the International Prospective Register of Systematic Reviews under protocol number CRD42022379144.
RESULTS
We included 8 studies with 1,500 patients, of whom 613 (40.9%) received PCC. The mean follow-up period ranged from 28 to 90 days. The PCC group had significantly lower chest tube drainage at 24 hours (mean difference [MD], -148.50 mL; 95% CI, -253.02 to -43.99 mL; p=0.005; I=42%). Fewer units of red blood cells (RBCs) were transfused within the first 24 hours (MD, -1.02 units; 95% CI, -1.81 to -0.24 units; p=0.01; I=56%), and fewer patients required RBC transfusion within the first 24 hours (risk ratio, 0.85; 95% CI, 0.78-0.93; p<0.007; I=45%) in the PCC group. There were no statistically significant differences in secondary outcomes. Nonetheless, a subgroup analysis of randomized controlled trials failed to corroborate the results obtained from the main analysis.
CONCLUSION
Our findings suggest that PCC can be effective, without increased adverse events, when compared with FFP in patients undergoing cardiac surgery complicated by bleeding.
PubMed: 37994088
DOI: 10.5090/jcs.23.081 -
Critical Care (London, England) Nov 2023Trauma-induced coagulopathy (TIC) is common in trauma patients with major hemorrhage. Prothrombin complex concentrate (PCC) is used as a potential treatment for the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Trauma-induced coagulopathy (TIC) is common in trauma patients with major hemorrhage. Prothrombin complex concentrate (PCC) is used as a potential treatment for the correction of TIC, but the efficacy, timing, and evidence to support its use in injured patients with hemorrhage are unclear.
METHODS
A systematic search of published studies was performed on MEDLINE and EMBASE databases using standardized search equations. Ongoing studies were identified using clinicaltrials.gov. Studies investigating the use of PCC to treat TIC (on its own or in combination with other treatments) in adult major trauma patients were included. Studies involving pediatric patients, studies of only traumatic brain injury (TBI), and studies involving only anticoagulated patients were excluded. Primary outcomes were in-hospital mortality and venous thromboembolism (VTE). Pooled effects of PCC use were reported using random-effects model meta-analyses. Risk of bias was assessed for each study, and we used the Grading of Recommendations Assessment, Development, and Evaluation to assess the quality of evidence.
RESULTS
After removing duplicates, 1745 reports were screened and nine observational studies and one randomized controlled trial (RCT) were included, with a total of 1150 patients receiving PCC. Most studies used 4-factor-PCC with a dose of 20-30U/Kg. Among observational studies, co-interventions included whole blood (n = 1), fibrinogen concentrate (n = 2), or fresh frozen plasma (n = 4). Outcomes were inconsistently reported across studies with wide variation in both measurements and time points. The eight observational studies included reported mortality with a pooled odds ratio of 0.97 [95% CI 0.56-1.69], and five reported deep venous thrombosis (DVT) with a pooled OR of 0.83 [95% CI 0.44-1.57]. When pooling the observational studies and the RCT, the OR for mortality and DVT was 0.94 [95% CI 0.60-1.45] and 1.00 [95% CI 0.64-1.55] respectively.
CONCLUSIONS
Among published studies of TIC, PCCs did not significantly reduce mortality, nor did they increase the risk of VTE. However, the potential thrombotic risk remains a concern that should be addressed in future studies. Several RCTs are currently ongoing to further explore the efficacy and safety of PCC.
Topics: Adult; Humans; Child; Venous Thromboembolism; Blood Coagulation Factors; Blood Coagulation Disorders; Hemorrhage; Randomized Controlled Trials as Topic
PubMed: 37919775
DOI: 10.1186/s13054-023-04688-z -
Cureus Sep 2023The coronavirus disease 2019 (COVID-19) is associated with prolonged prothrombin time (PT), active partial thromboplastin time (aPTT), and increased D-dimer levels.... (Review)
Review
The coronavirus disease 2019 (COVID-19) is associated with prolonged prothrombin time (PT), active partial thromboplastin time (aPTT), and increased D-dimer levels. Therefore, we aim to investigate if anticoagulants (AC) and antiplatelet (AP) therapy play a role in mitigating COVID-19 and its associated thrombosis along with its effect on the mortality rate, the need for mechanical ventilation, and the risk of hospital admission. Electronic databases were searched from their inception to July 19, 2022. The studies were divided into two groups: Group A (any dose of AC/AP versus no AC/AP) and Group B (therapeutic dose of AC (tAC)/AP versus prophylactic dose of AC (pAC)/AP). Review Manager (RevMan) version 5.4.1 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark) was used for all statistical analyses. Adjusted data ratios were extracted from all included studies and pooled using the random effects model. A total of 33 studies were taken for the analysis of two groups (Group A: 285,065 COVID-19-positive patients, Group B: 2,421 COVID-19-positive patients). Overall analysis in Group A showed that the AC/AP group had a low risk of mortality in COVID-19 patients compared to the control group (risk ratio (RR): 0.77, 95% confidence interval (CI): 0.69-0.86). There was no significant difference in the need for mechanical ventilation (RR: 0.80, 95% CI: 0.60-1.08) and hospital admission (RR: 1.12, 95% CI: 0.78-1.59) between the AC/AP and no AC/AP group. Alongside, in Group B, tAC/AP did not demonstrate a significant decrease in mortality as compared to pAC/AP (RR: 0.62, 95% CI: 0.37-1.06). Treatment with AC and AP drugs can significantly decrease the mortality rate in COVID-19-infected patients, while AC also significantly reduces the need for mechanical ventilation.
PubMed: 37872904
DOI: 10.7759/cureus.45749 -
The Cochrane Database of Systematic... Oct 2023Outcome after acute spontaneous (non-traumatic) intracerebral haemorrhage (ICH) is influenced by haematoma volume. ICH expansion occurs in about 20% of people with acute... (Review)
Review
BACKGROUND
Outcome after acute spontaneous (non-traumatic) intracerebral haemorrhage (ICH) is influenced by haematoma volume. ICH expansion occurs in about 20% of people with acute ICH. Early haemostatic therapy might improve outcome by limiting ICH expansion. This is an update of a Cochrane Review first published in 2006, and last updated in 2018.
OBJECTIVES
To examine 1. the effects of individual classes of haemostatic therapies, compared with placebo or open control, in adults with acute spontaneous ICH, and 2. the effects of each class of haemostatic therapy according to the use and type of antithrombotic drug before ICH onset.
SEARCH METHODS
We searched the Cochrane Stroke Trials Register, CENTRAL (2022, Issue 8), MEDLINE Ovid, and Embase Ovid on 12 September 2022. To identify further published, ongoing, and unpublished randomised controlled trials (RCTs), we scanned bibliographies of relevant articles and searched international registers of RCTs in September 2022.
SELECTION CRITERIA
We included RCTs of any haemostatic intervention (i.e. procoagulant treatments such as clotting factor concentrates, antifibrinolytic drugs, platelet transfusion, or agents to reverse the action of antithrombotic drugs) for acute spontaneous ICH, compared with placebo, open control, or an active comparator.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcome was death/dependence (modified Rankin Scale (mRS) 4 to 6) by day 90. Secondary outcomes were ICH expansion on brain imaging after 24 hours, all serious adverse events, thromboembolic adverse events, death from any cause, quality of life, mood, cognitive function, Barthel Index score, and death or dependence measured on the Extended Glasgow Outcome Scale by day 90.
MAIN RESULTS
We included 20 RCTs involving 4652 participants: nine RCTs of recombinant activated factor VII (rFVIIa) versus placebo/open control (1549 participants), eight RCTs of antifibrinolytic drugs versus placebo/open control (2866 participants), one RCT of platelet transfusion versus open control (190 participants), and two RCTs of prothrombin complex concentrates (PCC) versus fresh frozen plasma (FFP) (47 participants). Four (20%) RCTs were at low risk of bias in all criteria. For rFVIIa versus placebo/open control for spontaneous ICH with or without surgery there was little to no difference in death/dependence by day 90 (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.74 to 1.05; 7 RCTs, 1454 participants; low-certainty evidence). We found little to no difference in ICH expansion between groups (RR 0.81, 95% CI 0.56 to 1.16; 4 RCTs, 220 participants; low-certainty evidence). There was little to no difference in all serious adverse events and death from any cause between groups (all serious adverse events: RR 0.81, 95% CI 0.30 to 2.22; 2 RCTs, 87 participants; very low-certainty evidence; death from any cause: RR 0.78, 95% CI 0.56 to 1.08; 8 RCTs, 1544 participants; moderate-certainty evidence). For antifibrinolytic drugs versus placebo/open control for spontaneous ICH, there was no difference in death/dependence by day 90 (RR 1.00, 95% CI 0.93 to 1.07; 5 RCTs, 2683 participants; high-certainty evidence). We found a slight reduction in ICH expansion with antifibrinolytic drugs for spontaneous ICH compared to placebo/open control (RR 0.86, 95% CI 0.76 to 0.96; 8 RCTs, 2866 participants; high-certainty evidence). There was little to no difference in all serious adverse events and death from any cause between groups (all serious adverse events: RR 1.02, 95% CI 0.75 to 1.39; 4 RCTs, 2599 participants; high-certainty evidence; death from any cause: RR 1.02, 95% CI 0.89 to 1.18; 8 RCTs, 2866 participants; high-certainty evidence). There was little to no difference in quality of life, mood, or cognitive function (quality of life: mean difference (MD) 0, 95% CI -0.03 to 0.03; 2 RCTs, 2349 participants; mood: MD 0.30, 95% CI -1.98 to 2.57; 2 RCTs, 2349 participants; cognitive function: MD -0.37, 95% CI -1.40 to 0.66; 1 RCTs, 2325 participants; all high-certainty evidence). Platelet transfusion likely increases death/dependence by day 90 compared to open control for antiplatelet-associated ICH (RR 1.29, 95% CI 1.04 to 1.61; 1 RCT, 190 participants; moderate-certainty evidence). We found little to no difference in ICH expansion between groups (RR 1.32, 95% CI 0.91 to 1.92; 1 RCT, 153 participants; moderate-certainty evidence). There was little to no difference in all serious adverse events and death from any cause between groups (all serious adverse events: RR 1.46, 95% CI 0.98 to 2.16; 1 RCT, 190 participants; death from any cause: RR 1.42, 95% CI 0.88 to 2.28; 1 RCT, 190 participants; both moderate-certainty evidence). For PCC versus FFP for anticoagulant-associated ICH, the evidence was very uncertain about the effect on death/dependence by day 90, ICH expansion, all serious adverse events, and death from any cause between groups (death/dependence by day 90: RR 1.21, 95% CI 0.76 to 1.90; 1 RCT, 37 participants; ICH expansion: RR 0.54, 95% CI 0.23 to 1.22; 1 RCT, 36 participants; all serious adverse events: RR 0.27, 95% CI 0.02 to 3.74; 1 RCT, 5 participants; death from any cause: RR 0.49, 95% CI 0.16 to 1.56; 2 RCTs, 42 participants; all very low-certainty evidence).
AUTHORS' CONCLUSIONS
In this updated Cochrane Review including 20 RCTs involving 4652 participants, rFVIIa likely results in little to no difference in reducing death or dependence after spontaneous ICH with or without surgery; antifibrinolytic drugs result in little to no difference in reducing death or dependence after spontaneous ICH, but result in a slight reduction in ICH expansion within 24 hours; platelet transfusion likely increases death or dependence after antiplatelet-associated ICH; and the evidence is very uncertain about the effect of PCC compared to FFP on death or dependence after anticoagulant-associated ICH. Thirteen RCTs are ongoing and are likely to increase the certainty of the estimates of treatment effect.
Topics: Adult; Humans; Hemostatics; Antifibrinolytic Agents; Fibrinolytic Agents; Cerebral Hemorrhage; Stroke; Anticoagulants
PubMed: 37870112
DOI: 10.1002/14651858.CD005951.pub5 -
Seminars in Thrombosis and Hemostasis Apr 2024Venous thromboembolism (VTE) is a main contributor to morbidity and mortality in cancer patients. Biomarkers with the potential to predict cancer-associated VTE are...
Venous thromboembolism (VTE) is a main contributor to morbidity and mortality in cancer patients. Biomarkers with the potential to predict cancer-associated VTE are continually sought. Of these, markers of thrombin generation present a likely option. The present systematic review examines the ability of three widely used biomarkers of thrombin generation: prothrombin fragment 1.2 (F1.2), thrombin-antithrombin complex (TAT), and ex vivo thrombin generation, to predict VTE in both solid and hematologic adult cancer patients. Relevant studies were identified in the PubMed and Embase databases, and the review conformed to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Each study was evaluated using the quality assessment tool from the National Heart, Lung, and Blood Institute. The review protocol was published on PROSPERO with identifier CRD42022362339. In total, 24 papers were included in the review: 11 reporting data on F1.2, 9 on TAT, and 12 on ex vivo thrombin generation. The quality ratings of the included studies varied from good ( = 13), fair ( = 8), to poor ( = 3) with a high heterogenicity. However, F1.2, TAT complex, and ex vivo thrombin generation were all found to be associated with the development of VTE. This association was most pronounced for F1.2. Furthermore, the determination of F1.2 was able to improve the precision of several established risk assessment scores. In conclusion, markers of thrombin generation were found to be elevated in cancer patients with VTE, and particularly, F1.2 was found to be a promising predictor of cancer-associated VTE.
Topics: Adult; Humans; Thrombin; Venous Thromboembolism; Biomarkers; Risk Factors; Neoplasms
PubMed: 37813372
DOI: 10.1055/s-0043-1775856 -
European Journal of Cardio-thoracic... Oct 2023Literature is scarce on the management of patients using direct oral anticoagulants (DOACs) undergoing elective, urgent and emergency surgery. Therefore, we summarize... (Review)
Review
OBJECTIVES
Literature is scarce on the management of patients using direct oral anticoagulants (DOACs) undergoing elective, urgent and emergency surgery. Therefore, we summarize the current evidence and provide literature-based recommendations for the management of patients on DOACs in the perioperative phase.
METHODS
A general literature review was conducted on the pharmacology of DOACs and for recommendations on the management of cardiac surgical patients on DOACs. Additionally, we performed a systematic review for studies on the use of direct DOAC reversal agents in the emergency cardiac surgical setting.
RESULTS
When surgery is elective, the DOAC cessation strategy is relatively straightforward and should be adapted to the renal function. The same approach applies to urgent cases, but additional DOAC activity drug level monitoring tests may be useful. In emergency cases, idarucizumab can be safely administered to patients on dabigatran in any of the perioperative phases. However, andexanet alfa, which is not registered for perioperative use, should not be administered in the preoperative phase to reverse the effect of factor Xa inhibitors, as it may induce temporary heparin resistance. Finally, the administration of (activated) prothrombin complex concentrate may be considered in all patients on DOACs, and such concentrates are generally readily available.
CONCLUSIONS
DOACs offer several advantages over vitamin K antagonists, but care must be taken in patients undergoing cardiac surgery. Although elective and urgent cases can be managed relatively straightforwardly, the management of emergency cases requires particular attention.
Topics: Humans; Administration, Oral; Anticoagulants; Cardiac Surgical Procedures; Dabigatran; Hemorrhage; Heparin
PubMed: 37812245
DOI: 10.1093/ejcts/ezad340 -
International Journal of Surgery... Jan 2024Liver transplantation (LT) is the gold standard for end-stage liver disease, yet postoperative complications challenge patients and physicians. Indocyanine green (ICG)...
BACKGROUND
Liver transplantation (LT) is the gold standard for end-stage liver disease, yet postoperative complications challenge patients and physicians. Indocyanine green (ICG) clearance, a quantitative dynamic test of liver function, is a rapid, reproducible, and reliable test of liver function. This study aimed to systematically review and summarize current literature analyzing the association between ICG tests and post-LT outcomes.
METHODS
This systematic review was conducted according to PRISMA guidelines. MEDLINE and Cochrane Library, as main databases, and other sources were searched until August 2022 to identify articles reporting the prognostic value of postoperative ICG tests associated with outcomes of adult LT recipients.Risk of bias of included articles was assessed using Quality In Prognosis Studies tool. Methodological quality varied from low to high across risk of bias domains.
RESULTS
Six studies conducted between 1994 and 2018 in Europe, America, and Asia were included. The study population ranged from 50 to 332 participants. ICG clearance on the first postoperative day was associated with early allograft dysfunction, graft loss, 1-month and 3-month patient survival probability, prolonged ICU, and hospital stay. The dichotomized ICG plasma disappearance rate (PDR) provided a strong association with medium-term and long-term outcomes: PDR less than 10%/min with 1-month mortality or re-transplantation (odds ratio: 7.89, 95% CI 3.59-17.34, P <0.001) and PDR less than 16.0%/min with 3-month patient survival probability (hazard ratio: 13.90, 95% CI 4.67-41.35, P <0.01). The preoperative model for end-stage liver disease and body mass index were independent prognostic factors for early allograft dysfunction, early complications, and prolonged ICU stay; post-LT prothrombin time and INR were independently associated with graft loss and bilirubin with a prolonged hospital stay.
CONCLUSION
This review shows that ICG clearance tests are associated with graft function recovery, suggesting that a potential prognostic role of ICG test, as an aid in predicting the post-LT course, could be considered.
Topics: Adult; Humans; Indocyanine Green; Liver Transplantation; End Stage Liver Disease; Severity of Illness Index; Prognosis; Coloring Agents
PubMed: 37800567
DOI: 10.1097/JS9.0000000000000779 -
Pediatric and Developmental Pathology :... 2024Lymphoma is the fourth most common tumor to display placental metastasis. This study aimed to report a case of high-grade lymphoma involving the placenta and review the...
Lymphoma is the fourth most common tumor to display placental metastasis. This study aimed to report a case of high-grade lymphoma involving the placenta and review the literature on lymphomas metastatic to the placenta. A systematic review was performed following the PRISMA guidelines, using the keywords "lymphoma" AND "placenta." All case reports and case series on lymphoma infiltrating the placenta were collected. Eight cases from 7 studies, including the present case, were synthesized. The mean patient age is 29.5 years. The clinical presentation is non-specific. Hematologic derangements included cytopenias or cytoses, and elevated prothrombin time. The mean gestational age (GA) when a diagnosis of lymphoma was rendered is 27 weeks. Five cases presented with either lymphadenopathy or visceral masses on imaging. Four of these cases eventually led to maternal demise. The mean GA when the fetus was delivered is 31 3/4 weeks. Grossly, most placentas had non-specific findings. Leukemic infiltrates were mostly seen within intervillous spaces. Intravillous infiltrates were associated with high-grade lymphomas, resulting in either maternal demise or stillborn fetuses. This study suggests that the placenta has mechanisms to guard against malignancies; however, these defense mechanisms are not foolproof and may be breached by tumor cells.
Topics: Pregnancy; Female; Humans; Adult; Infant; Placenta; Placenta Diseases; Neoplasms; Fetus; Lymphoma
PubMed: 37771167
DOI: 10.1177/10935266231200114 -
Research and Practice in Thrombosis and... Aug 2023Various inherited traits contribute to the overall risk of venous thromboembolism (VTE). In addition, the epidemiology of thrombophilia in the East-Asian VTE population...
BACKGROUND
Various inherited traits contribute to the overall risk of venous thromboembolism (VTE). In addition, the epidemiology of thrombophilia in the East-Asian VTE population remains unclear; thus, we aimed to assess the proportion of hereditary thrombophilia via a meta-analysis.
METHODS
Publications from PubMed, EMBASE, web of science, and Cochrane before December 30, 2022, were searched. Studies from Japan, Korea, China, Hong Kong, Taiwan, Singapore, Thailand, Vietnam, Myanmar, and Cambodia were included. Congenital thrombophilia was described as diseases including protein C (PC) deficiency, protein S (PS) deficiency, antithrombin (AT) deficiency, factor (F)V Leiden (FVL), and prothrombin G20210A mutations. Studies were selected by 2 reviewers for methodological quality analysis. A random-effects model was used for the meta-analysis, assuming that estimated effects in the different studies are not identical.
RESULTS
Forty-four studies involving 6453 patients from 7 counties/regions were included in the meta-analysis. The prevalence of PC, PS, and AT deficiencies were 7.1%, 8.3%, and 3.8%, respectively. Among 2924 patients from 22 studies, 5 patients were carriers of FVL mutation. Among 2196 patients from 10 studies, 2 patients were carriers of prothrombin G20210A mutation in a Thailand study.
CONCLUSION
The prevalence of PC, PS, and AT deficiencies was relatively high, while a much lower prevalence of FVL and prothrombin G20210A mutations were identified in East-Asian patients with VTE. Our data stress the relative higher prevalence of PC, PS, and AT deficiencies for thrombophilia in the East-Asian VTE population.
PubMed: 37674867
DOI: 10.1016/j.rpth.2023.102157 -
Thrombosis Research Oct 2023The role of inherited thrombophilia in arterial disease is uncertain. We performed a systematic-review and meta-analysis of inherited thrombophilia in cerebrovascular...
INTRODUCTION
The role of inherited thrombophilia in arterial disease is uncertain. We performed a systematic-review and meta-analysis of inherited thrombophilia in cerebrovascular (CVD), coronary heart (CHD), and peripheral artery disease (PAD) patients.
MATERIALS AND METHODS
MEDLINE and EMBASE were searched up to February 2022. Pooled prevalences (PPs) and odds ratios (ORs) with 95 % confidence intervals (95%CI) were calculated in a random-effects model. Factor V Leiden (G1691A), prothrombin (G20210A), MTHFR C677T/A1298C and PAI-1 4G/5G were evaluated.
RESULTS
377 studies for 98,186 patients (32,791 CVD, 62,266 CHD, 3129 PAD) and 108,569 controls were included. Overall, 37,249 patients had G1691A, 32,254 G20210A, 42,546 MTHFR C677T, 8889 MTHFR A1298C, and 19,861 PAI-1 4G/5G gene polymorphisms. In CVD patients, PPs were 6.5 % for G1691A, 3.9 % for G20210A, 56.4 % for MTHFR C677T, 51.9 % for MTHFR A1298C, and 77.6 % for PAI-1. In CHD, corresponding PPs were 7.2 %, 3.8 %, 52.3 %, 53.9 %, and 76.4 %. In PAD, PPs were 6.9 %, 4.7 %, 55.1 %, 52.1 %, and 75.0 %, respectively. Strongest ORs in CVD were for homozygous G1691A (2.76; 95 %CI, 1.83-4.18) and for homozygous G20210A (3.96; 95 %CI, 2.05-7.64). Strongest ORs in CHD were for homozygous G1691A (OR 1.68; 95%CI, 1.02-2.77) and G20210A (heterozygous 1.49 95%CI, 1.22-1.82; homozygous 1.54 95%CI, 0.79-2.99). The OR for PAI-1 4G/4G in PAD was 5.44 (95%CI, 1.80-16.43). Specific subgroups with higher PPs and ORs were identified according to age and region.
CONCLUSIONS
Patients with arterial disease have an increased prevalence and odds of having some inherited thrombophilia. Some thrombophilia testing may be considered in specific subgroups of patients.
PubMed: 37643522
DOI: 10.1016/j.thromres.2023.08.006