BACKGROUND: Preeclampsia (PE), an obstetric disorder, remains one of the leading causes of maternal and infant mortality worldwide. In individuals with PE, the coagulation-fibrinolytic system is believed to be among the most significantly impacted systems due to maternal inflammatory responses and immune dysfunction. Therefore, this systematic review and meta-analysis aimed to assess the association of prothrombin time (PT), thrombin time (TT) and activated partial thromboplastin time (APTT) levels with preeclampsia.
METHODS: This systematic review and meta-analysis was conducted in accordance with the PRISMA guidelines. Articles relevant to the study, published from July 26, 2013, to July 26, 2023, were systematically searched across various databases including PubMed, Scopus, Embase, and Hinari. The methodological quality of the articles was evaluated using the Joanna Briggs Institute critical appraisal checklist. Utilizing Stata version 14.0, a random-effects model was employed to estimate the pooled standardized mean difference (SMD) along with the respective 95% CIs. The I2 statistics and Cochrane Q test were utilized to assess heterogeneity, while subgroup analyses were performed to explore its sources. Furthermore, Egger\'s regression test and funnel plot were employed to assess publication bias among the included studies.
RESULTS: A total of 30 articles, involving 5,964 individuals (2,883 with PE and 3,081 as normotensive pregnant mothers), were included in this study. The overall pooled SMD for PT, APTT, and TT between PE and normotensive pregnant mothers were 0.97 (95% CI: 0.65-1.29, p < 0.001), 1.05 (95% CI: 0.74-1.36, p < 0.001), and 0.30 (95% CI: -0.08-0.69, p = 0.11), respectively. The pooled SMD indicates a significant increase in PT and APTT levels among PE patients compared to normotensive pregnant mothers, while the increase in TT levels among PE patients was not statistically significant.
CONCLUSIONS: The meta-analysis underscores the association between PE and prolonged PT and APTT. This suggests that evaluating coagulation parameters like PT, APTT, and TT in pregnant women could offer easily accessible and cost-effective clinical indicators for assessing PE. However, multicenter longitudinal studies are needed to evaluate their effectiveness across various gestational weeks of pregnancy.

Whereas lupus anticoagulant (LA) and anti-factor VIII (anti-VIII) antibody are both acquired autoimmune coagulation inhibitors, they exhibit different pathophysiologic mechanisms and opposite clinical manifestations. Distinguishing between these two inhibitors is therefore essential for optimizing appropriate management. Harboring both antibodies, which is a rare condition, is of a challenging and confounding laboratory work-up.
We illustrate a case report of a 39-year-old man admitted for the management of recurrent deep-vein thrombosis. Curiously, the initial physical examination revealed several hematoma and bruises of varying sizes. Biologically, a prolonged activated partial thromboplastin time (APTT) was objectified and was not corrected by the mixing study. The following detection of synchronous LA and anti-VIII was made using specific assays.
Through this case, we illustrate the complexity of diagnosing coexistent LA and FVIII inhibitors. In fact, the biological hallmark of both inhibitors is an isolated prolonged APTT that does not correct by the mixing study. Despite the progress in LA and anti-VIII assays and the ongoing updating of standardized recommendations, the lack of specific tests for LA and the limited availability of VIII quantification tests other than the clot-based assays make it difficult to distinguish adequately between the two inhibitors. Therefore, it is crucial to correlate test results with clinical features and patient evaluation.

The aim of this article is to describe a case in which protamine was used for a low-molecular-weight heparin (LMWH) overdose and present an up-to-date review of the literature on the management of LMWH overdose in adults.
An unintentional administration of enoxaparin 900 mg occurred in a 73-year-old man with coronavirus disease 2019-related pulmonary embolism. Management of the overdose included a protamine bolus followed by an infusion. Anti-factor Xa levels and activated partial thromboplastin time were monitored. Anti-factor Xa levels declined in a linear fashion irrespective of protamine administration. No bleeding or further thrombotic complications occurred in the patient. A review of the literature revealed that the optimal strategy to treat an LMWH overdose is unknown, with treatment of overdoses ranging from clinical observation to aggressive protamine dosing in reported cases. Although protamine effectively neutralizes unfractionated heparin, it is unable to completely reverse LMWH activity and has variable effects on laboratory measures of LMWH anticoagulant activity.
The current case report provides additional data to previous literature suggesting that protamine may have a limited effect in decreasing anti-factor Xa levels in LMWH overdose. Continued reporting on the management of LMWH overdoses is warranted to clarify the optimal treatment strategy.

The initiation of the extracorporeal membrane oxygenation (ECMO) is associated with complex coagulatory and inflammatory processes and consequently needed anticoagulation. Systemic anticoagulation bears an additional risk of serious bleeding, and its monitoring is of immense importance. Therefore, our work aims to analyze the association of anticoagulation monitoring with bleeding during ECMO support.
Systematic literature review and meta-analysis, complying with the PRISMA guidelines (PROSPERO-CRD42022359465).
Seventeen studies comprising 3249 patients were included in the final analysis. Patients experiencing hemorrhage had a longer activated partial thromboplastin time (aPTT), a longer ECMO duration, and higher mortality. We could not find strong evidence of any aPTT threshold association with the bleeding occurrence, as less than half of authors reported a potential relationship. Finally, we identified the acute kidney injury (66%, 233/356) and hemorrhage (46%, 469/1046) to be the most frequent adverse events, while almost one-half of patients did not survive to discharge (47%, 1192/2490).
The aPTT-guided anticoagulation is still the standard of care in ECMO patients. We did not find strong evidence supporting the aPTT-guided monitoring during ECMO. Based on the weight of the available evidence, further randomized trials are crucial to clarify the best monitoring strategy.

Anticoagulation is critical in patients supported on extracorporeal membrane oxygenation (ECMO). The appropriate monitoring strategies for heparin remain unclear.
This systematic review aimed to compare the accuracy and safety of various monitoring strategies for patients supported on ECMO.
The PubMed and Web of Science databases were searched for articles in March 2023 without restrictions on publication date. Anticoagulation monitoring strategies for adults supported on ECMO were compared across all included studies. The incidence of bleeding, thrombosis, mortality, blood transfusion, correlation between tests and heparin dose, and the discordance between different tests were discussed in the included studies. The risk of bias was assessed using the Newcastle-Ottawa Scale and Cochrane Collaboration\'s tool.
Twenty-six studies, including a total of 1,684 patients, met the inclusion criteria. The monitoring of anticoagulation by activated partial thromboplastin time (aPTT) resulted in less blood product transfusion than that by activated clotting time (ACT). Moreover, the monitoring of anticoagulation by anti-factor Xa (Anti-Xa) resulted in a more stable anticoagulation than that by aPTT. Anti-Xa and aPTT correlated with heparin dose better than ACT, and the discordance between different monitoring tests was common. Finally, combined monitoring showed some advantages in reducing mortality and blood product transfusion.
Anti-Xa and aPTT are more suitable for anticoagulation monitoring for patients supported on ECMO than ACT. Thromboelastography and combination strategies are less applied. Most of the studies were retrospective, and their sample sizes were relatively small; thus, more appropriate monitoring strategies and higher quality research are needed.

BACKGROUND: There are no randomized controlled trials comparing low and high activated partial thromboplastin time (aPTT) targets in heparinized adult veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) patients. Our systematic review and meta-analysis summarized complication rates in adult VA ECMO patients treated with low and high aPTT targets.
METHODS: Studies published from January 2000 to May 2022 were identified using Pubmed, Embase, Cochrane Library, and LILACS (Latin American and Caribbean Health Sciences Literature). Studies were included if aPTT was primarily used to guide heparin anticoagulation. For the low aPTT group, we included studies where aPTT goal was ≤60 seconds and for the high aPTT group, we included studies where aPTT goal was ≥60 seconds. Proportional meta-analysis with a random effects model was used to calculate pooled complication rates for patients in the two aPTT groups.
RESULTS: Twelve studies met inclusion criteria (5 in the low aPTT group and 7 in the high aPTT group). The pooled bleeding complication incidence for low aPTT studies was 53.6% (95% CI = 37.4%-69.4%, I2 = 60.8%) and for high aPTT studies was 43.8% (95% CI = 21.7%-67.1%, I2 = 91.8%). No studies in the low aPTT group reported overall thrombosis incidence, while three studies in the high aPTT group reported overall thrombosis incidence. The pooled thrombosis incidence for high aPTT studies was 16.1% (95% CI = 9.0%-24.5%, I2 = 13.1%).
CONCLUSIONS: Adult ECMO patients managed with low and high aPTT goals appeared to have similar bleeding and other complication rates further highlighting the need for a randomized controlled trial.

BACKGROUND: Hereditary factor XI (FXI) deficiency is a rare coagulation disorder that may result in excessive bleeding requiring intervention to restore haemostasis.
OBJECTIVE: The aim of this review was to report the current knowledge of the worldwide incidence and prevalence of FXI deficiency.
METHODS: A targeted PubMed search using terms related to FXI deficiency was conducted to identify studies published from April 2002 through April 2022. A manual search supplemented the electronic search. Studies were eligible for data abstraction if they reported population-based incidence proportions/rates or prevalence proportions for FXI deficiency.
RESULTS: The electronic and manual searches returned 253 publications. After applying exclusion criteria, seven publications were included in the analysis, including a global report from the World Federation of Haemophilia (WFH). Six publications provided information on the prevalence of FXI deficiency that included 74 countries and regions. The estimated prevalence of FXI in the WFH report ranged from 0/100,000 in several countries to 55.85/100,000 individuals in the United Kingdom. Prevalence estimates in the PubMed findings ranged from .1 to 246.2/1,000,000 inhabitants with varying methods of case identification and time periods of analysis. One study estimated the incidence of FXI deficiency in Yecla, Spain at 2% of blood donors and .09% of hospital inpatients/outpatients with activated partial thromboplastin time (aPTT) tests.
CONCLUSIONS: FXI deficiency is rare across the world, but additional steps could be taken to improve incidence and prevalence estimation, for example, development of a consistent FXI deficiency definition and incorporating genetic testing into a clinical routine to better identify and characterise cases.

Acute compartment syndrome (ACS) with acquired hemophilia A (AHA) is rare and has no established treatment strategy. A 64-year-old woman presented with a giant hematoma in the rectus abdominis. Laboratory findings included decreased hemoglobin and increased activated partial thromboplastin time. Arterial embolization was performed for hemostasis. After catheter removal, she developed severe arm pain and numbness with blistering. Fasciotomy was performed to decrease intracompartmental pressure. Laboratory investigations revealed decreased factor VIII (FVIII) activity and increased FVIII inhibitor. AHA was diagnosed and treated with immunosuppressive and FVIII inhibitor-bypassing agents.
Fasciotomy should be performed promptly if ACS with AHA is suspected.

Coagulation mechanisms are reported to be affected in dengue illness and evidenced by prolonged activated partial thromboplastin time (APTT) and prothrombin time (PT). The main aim of this systematic review and meta-analysis is to determine the magnitude of coagulation abnormalities among patients with dengue fever infection.
This systematic review and meta-analysis were conducted per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The Joana Brigg\'s Institute (JBI) critical appraisal checklist was used for quality appraisal. STATA version 11 software was used for meta-analysis. The magnitude of coagulation abnormalities among dengue fever patients was determined by using a random-effects model. Subgroup and sensitivity analysis were performed to investigate the possible source of heterogeneity. Egger weighted regression tests were used to check the presence of publication bias among the included articles.
Forty-two studies with a total of 12,221 dengue fever patients were eligible for meta-analysis in this study. Of which 22, 15, and 26 studies were used to determine the magnitude of prolonged APTT, PT, and thrombocytopenia, respectively. The magnitude of prolonged APTT and PT among patients with dengue fever infection were 42.91% (95% CI: 30.95, 54.87) I2 = 99.1% and 16.48% (95% CI: 10.95, 22.01) I2 = 97.0%, respectively. Besides, the magnitude of thrombocytopenia among dengue fever patients was 70.29% (95% CI: 62.69, 77.89) I2 = 99.3%. The magnitude of prolonged APTT in children and adults was 51.21% (95% CI: 24.54, 77.89) and 44.89% (95% CI: 28.32, 61.45), respectively. Similarly, the overall magnitude of prolonged PT in children and adults were 13.40% (95% CI: 6.09, 20.71) and 18.73% (95% CI: 7.49, 29.96), respectively.
The result of this study showed that there is a high magnitude of prolonged APTT and PT in dengue fever patients. Therefore, screening and early correction of coagulation abnormalities may be helpful to reduce further complications in those patients.

There are many preanalytical variables (PAV) that are known to affect coagulation testing. The more commonly acknowledged PAV addressed by the clinical laboratory tend to start with their influence on blood collection, but realistically coagulation PAV starts with the patient, where the laboratory has less influence or control. Patient selection and appropriate timing for blood collection may be integral for assuring proper diagnosis and management. Laboratory control and assurance for ideal phlebotomy practice would mitigate most PAVs related to blood collection to minimize suboptimal sample collection. Laboratory oversight of sample transportation, processing and storage will assure sample integrity until testing can be facilitated. The purpose of this document is to review common PAV that should be taken into consideration when ordering, performing and interpreting a coagulation test result, with additional attention to the effect of direct oral anticoagulants (DOACs).