Coagulation Screening Tests Research Articles

Ramadan intermittent fasting is associated with improved anticoagulant activity among healthy people: a case–control study

Data on the pathophysiological mechanisms of hemostatic alterations in the thrombotic events that occur during Ramadan intermittent fasting (RIF), particularly in the natural coagulation inhibitors, are very limited. Thus, our objective was to evaluate the effect of RIF on the natural anticoagulants level, antithrombin, protein C, and total and free protein S (PS) in healthy participants. Participants were divided into two groups. Group I consisted of 29 healthy fasting participants whose blood samples were taken after 20 days of fasting. Group II included 40 healthy non-fasting participants whose blood samples were taken 2–4 weeks before the month of Ramadan. Coagulation screening tests including prothrombin time (PT), activated partial thromboplastin time (APTT) and plasma fibrinogen level, natural anticoagulants; antithrombin, protein C, free and total PS and C4 binding protein (C4BP) levels were evaluated in the two groups. High levels of total and free PS without change in antithrombin, protein C, and C4BP levels were noted in the fasting group as compared with non-fasting ones (p < 0.05). PT and APTT showed no difference between the two groups. However, the fibrinogen level was higher in the fasting group. In conclusion, RIF was found to be associated with improved anticoagulant activity in healthy participants, which may provide temporal physiological protection against the development of thrombosis in healthy fasting people.

HEART FAILURE WITH RELAPSING ATRIAL FIBRILLATION: BELOW THE SURFACE

Abstract Advances in pharmacologic and device therapy have greatly improved prognosis of patients with HFrEF. However, the typical clinical course is still characterized by recurring symptoms, worsening functional status and risk of frequent hospitalizations. A 72–years–old male patient with arterial hypertension, poorly controlled T2DM, TIA and chronic kidney disease presented to Cardiology service in 2018 with dyspnoea on effort and first evidence of EF 35% at echocardiography. He was admitted for elective coronary angiography, which demonstrated limited coronary heart disease of circumflex artery and its first marginal branch, treated by PTCA and stenting. CMR confirmed severe LV dysfunction, but also revealed extensive fibrotic areas with ischaemic and non–ischaemic patterns beyond revascularized regions. With such evidences, HF treatments were intensified, with titration of disease– modifying therapies and DOAC was added for asymptomatic paroxysmal AF. CRT–D was implanted for QRS of 160 msec, which was narrowed to 130 msec. Nevertheless, in one–year time the patient presented worsening of symptoms with several hospital admissions for acute HF and AF with fast rate. A switch to rhythm–control strategy was hence chosen. DCCV was performed, after an initial deferral for thrombosis of LAA due to poor adherence to DOAC. However, three–days after DCCV, the patient presented again to emergency services for dyspnoea, left upper flank pain and AF with fast rate. He was admitted to Acute Medicine Unit and treated with high flow O2, iv Furosemide and Digoxin, analgesics. CT chest and abdomen with contrast was performed in the suspicion of systemic venous thromboembolism for persistent type 1 respiratory failure, raised D–dimer and elevated liver function tests, despite appropriate anticoagulation. CT revealed an unexpected left superior pulmonary vein thrombosis, splenic and small left renal infarcts. The patient was discharged after recovery on subcutaneous heparin. At 15–day review, the patient was in stable conditions and awaiting completion of coagulation screening tests. This case study addresses some important aspects in the care of HF. An accurate assessment of HF aetiology and recurrent triggers, a timely planning of pharmacologic and device treatments, alongside with management of co–morbidities, therapeutic adherence and appropriate anticoagulation, can provide the clinician powerful tools to accomplish the difficult task of managing HF below the surface.

Factor XIII deficiency, a rare coagulopathy: case reports

Introduction: Hereditary Factor XIII (FXIII) deficiency is a rare autosomal recessive hemostatic disorder with an estimated incidence of one case per two million individuals and a higher prevalence in descendants of consanguineous relationships. Possible clinical manifestations include intracranial hemorrhage, umbilical cord bleeding at birth, hematoma, spontaneous abortions, and menometrorrhagia. Objective: To highlight the peculiarities of this hemostatic disorder, as well as the recommended management. Case Report: The authors describe two cases of FXIII deficiency with different hemorrhagic manifestations. Case 1 presented extensive spontaneous hematoma in the right thigh, while Case 2 had umbilical cord bleeding at birth and intracranial hemorrhage, requiring hemotherapy support. Both patients had normal results in screening laboratory tests for coagulation disorders. Coagulation factor serum levels and diagnostic assessments identified mild Factor XIII deficiency in Case 1 and severe deficiency in Case 2. The patient in Case 1 is under regular control and follow-up, while the patient in Case 2 is on a monthly prophylactic regimen with FXIII infusion. Conclusion: The diagnosis of FXIII deficiency in patients with significant bleeding should be considered if screening coagulation tests are normal. The Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis has established an algorithm for laboratory diagnosis and identification of different forms of FXIII deficiency. Quantitative determination of FXIII activity, antigenic assays, and molecular studies are necessary.

Utilization of International Normalized Ratio-Derived Formula to Predict Plasma Rivaroxaban Level - Validation Study and Real-World Experience

Introduction: Specific assay of plasma rivaroxaban level are not always readily available with short turn-around-time which hampered the management of urgent clinical situations. The response of routine coagulation screening tests show huge lot-to-lot differences with the plasma rivaroxaban level. International normalized ratio (INR) is a standardized measurement taking into account of lot-to-lot variations of PT reagents. In this study, we aimed to build a predictive formula of plasma rivaroxaban levels from INR value and validated in real world clinical situations. Method: The study period was 1 st January 2018 to 31 st December 2021. Ninety-four patients who taking rivaroxaban participated in the study. Patients were randomized into testing cohort and validation cohorts. The prediction formula was built from the testing cohort and then validated in validation cohort. The predictive performance was further validated on real-world clinical requests. Results: The baseline characteristics of both cohorts were well-balance. There was significant correlation between the plasma rivaroxaban level and PT in both the testing and validation cohorts (Testing cohort: R square 0.838, p &amp;lt; 0.01; Validation cohort: R square 0.836, p &amp;lt; 0.01). The plasma rivaroxaban level showed significant correlation with APTT in both the testing and validation cohorts (Testing cohort: R square 0.744, p &amp;lt; 0.01; Validation cohort: R square 0.654, p &amp;lt; 0.01). There was also significant correlation between INR and plasma rivaroxaban levels in both the testing and validation cohorts (Testing cohort: R square 0.819, p &amp;lt;0.01; Validation cohort: R square 0.816, p &amp;lt; 0.01). Both INR and plasma rivaroxaban levels were undergone natural logarithmic transformation. We choose the quadratic model to determine the relationship between the natural log of plasma rivaroxaban level and the natural log of INR as it had highest R square value (R square 0.850, p&amp;lt;0.01). The formula is: ln (plasma rivaroxaban level) = 2.96+7.87 X ln (INR) - 5.04X (ln (INR))^2. The root mean square error (RMSE) of the predictive formula for the testing and validation cohorts were 61.81 ng/ml and 69.32 ng/ml, respectively. We received a total of 43 requests for plasma rivaroxaban assay involved 29 patients during the study period (Table 1). Three patients had multiple requests for plasma DOAC level assays during this period. The cut-off INR value was 1.3 for administration of antidote for rivaroxaban, which corresponded to a rivaroxaban level of 75 ng/ml. The sensitivity and specificity for using this INR cut-off value to determine the threshold plasma rivaroxaban level (75 ng/ml) for administration of reversal agents were 95% (95%CI: 85.4 -100%) and 87.5% (95%CI:71.3-100%) respectively in real world clinical situations (Table 2). Conclusion: Plasma rivaroxaban level can be calculated from prediction formula by INR value with satisfactory accuracy and the INR cut-off value derived from it can be used to guide the decision for administration of reversal agents with excellent sensitivity and specificity.

Rotational Thromboelastometry Reduces Fresh Frozen Plasma Requirement in Patients without Liver Disease Undergoing Therapeutic Endoscopic Procedures with Deranged Screening Coagulation Tests—A Pilot Study

Abstract Background/Aims Rotational thromboelastometry (ROTEM) is a viscoelastic test that is used in patients with liver disease for guiding blood component use. This study is aimed at comparing the amount of blood products transfused and bleeding rates in patients without liver disease, who underwent therapeutic endoscopic procedures with deranged screening coagulation tests (prothrombin time [PT]; activated partial thromboplastin time [aPTT]), with and without hypocoagulable ROTEM. Methods Patients with deranged PT and aPTT without liver disease who underwent therapeutic endoscopic interventions during the period 2020 to 2022 were retrospectively analyzed. Baseline parameters, amount of blood products transfused, and outcomes such as 30-day bleeding and mortality rates were recorded in those with and without hypocoagulable ROTEM. Results Of the 204 patients with deranged PT/aPTT who underwent therapeutic endoscopy during the study period, 180 of those with liver disease were excluded. Six patients (M:F = 5:1; median age: 37, 20–54 years) had hypocoagulable ROTEM and 18 patients (M:F = 11:7; median age: 56, 20–71 years) had normo-/hypercoagulable ROTEM. There were significant differences in the total amount of fresh frozen plasma (FFP) transfused and FFP transfused per patient between the two groups (9,000 vs. 4,500 mL and 2,000 vs. 1,000 mL; p = 0.04, respectively). Two patients with hypocoagulable ROTEM bled within 30 days, while none did in the comparator group (p = 0.03). One patient in the hypocoagulable group died within 30 days and none in the normo-/hypercoagulable group. Conclusion The use of ROTEM reduces FFP requirement in patients without liver disease with deranged PT/aPTT undergoing therapeutic endoscopic procedures without any increased risk of early or late rebleeding, and 30-day mortality.

Poor Correlation of Rivaroxaban Concentration with the Routine Coagulation Screening Test in Chinese Patients with Atrial Fibrillation

Aims. The aim of this study is to assess the relationship between rivaroxaban plasma concentration quantified by the gold standard and anticoagulant activities measured by routine coagulation assays in Chinese atrial fibrillation (AF) patients. Whether the normal results of these tests were reliable to rule out clinically relevant rivaroxaban levels at various thresholds was also explored. The effect of clinical drug-drug interactions (DDIs) on the exposure and anticoagulant effect of rivaroxaban were further evaluated. Methods. 116 patients receiving rivaroxaban for the management of nonvalvular AF were recruited. Rivaroxaban concentrations and coagulation tests were measured by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and a blood coagulation analyzer, respectively. Results. The correlation of trough concentration (Ctrough) and prothrombin time (PT) or international normalized ratio (INR) was moderate with Spearman’s correlation coefficient of 0.495 and 0.506, respectively. A normal PT/INR was unable to rule out Ctrough levels of &gt;30 ng/mL and &gt;50 ng/mL, but the negative predictive value reached 100% to exclude Ctrough of &gt;100 ng/mL. Ctrough showed a small correlation with activated partial thromboplastin time (aPTT) (Spearman’s correlation coefficient: 0.241) and no correlation with thrombin time (TT) (Spearman’s correlation coefficient: 0.074). Neither aPTT nor TT accurately predicted Ctrough at any concentration. Peak concentration (Cpeak) did not correlate with any coagulation parameters. The presence of digoxin and febuxostat significantly increased rivaroxaban Ctrough by 2.18 fold and prolonged PT and INR by 44.16% and 43.60%, respectively. Conclusions. Normal routine coagulation assays were insufficient to monitor therapy with rivaroxaban. Poor correlations between rivaroxaban concentration and routine coagulation assays were observed in Chinese AF patients. The use of digoxin/febuxostat alone had no effect on rivaroxaban concentrations; however, combined strong breast cancer resistance protein inhibitor (febuxostat) and P-glycoprotein probe (digoxin) in patients with renal impairment is likely to cause clinically significant DDI with rivaroxaban. More studies are needed to establish routine therapeutic drug monitoring of rivaroxaban in clinical practice.

Viscoelastometry to Manage Bleeding in Liver Disease.

A state of "re-balanced haemostasis" describes complex coagulation changes that arise in patients with liver disease. Changes include alterations in procoagulant and anticoagulant proteins, platelets and von Willebrand factor, as well as the fibrinolytic system. Various circumstances including infection, trauma, or surgery may disrupt this balance and predispose an individual to bleeding or thrombosis. The prothrombin time, international normalised ratio, and activated partial thromboplastin time are conventional coagulation screening tests that are routinely employed by clinicians to investigate unexplained bleeding, monitor anticoagulation, and inform preoperative assessments of bleeding risk. These standard coagulation tests assess quantitative defects in procoagulant clotting factors and are insensitive to levels of natural anticoagulants, which together with procoagulant factors, are often perturbed in liver disease. Therefore, the prolongation of clotting times measured by these tests often does not reflect the multifaceted alterations of haemostasis in these patients. Viscoelastic testing (VET) provides a more encompassing assessment of clotting function by recording real-time viscoelastic changes in whole blood and includes parameters that provide information on coagulation factor function, platelet contribution to clot formation, as well as fibrinolysis. To date, VET has been employed to predict and inform transfusion support in obstetric, trauma, and cardiac surgical fields, and its use in patients undergoing liver transplantation is well established. The ability of VET to accurately predict bleeding risk and precisely guide transfusion algorithms for patients with liver disease undergoing other invasive procedures or experiencing bleeding complications has been the topic of research over the last decade. This review is a critical summary of this data and provides a detailed snapshot of the position of VET as a clinical tool in patients with liver disease.

Direct oral anticoagulant adsorption and laboratory detection of lupus anticoagulant.

In this study, the effect of activated charcoal (DOAC-Stop, DS) as a DOAC-adsorbent was investigated on samples from DOACs treated and untreated patients. 165 plasma samples with a LA request were collected in three laboratories: 105 were from patients receiving DOACs and 60 were from nonanticoagulated patients with 30 LA negative and 30 LA positive. All coagulation screening assays and LA assays were evaluated before and after DS treatment. The adsorption technique reduced DOACs concentration below the Lower Limit of Quantification. For nonanticoagulated patients: no significant difference in ratio results of coagulation screening (prothrombin time, activated partial thromboplastin time and thrombin time) and LA tests were observed before and after addition of DS in LA positive and negative patients. Every LA was correctly classified. For anticoagulated patients: a statistically significant difference was found for coagulation screening assays and LA assays. Final LA conclusions changed after DS addition from positive to negative in 58.9% of patients (more frequently with Rivaroxaban) and from negative to positive in 8% of patients (more frequently with Apixaban). Our study suggests that DOAC-Stop can be used in daily laboratory practice to remove DOACs interference for a more accurate assessment of LA that is essential for diagnosis and management of APS patients.

Preoperative coagulation screening tests in pediatric patients: Clinical relevance and hemorrhagic outcomes of abnormal results.

Coagulation screening tests in children are still frequently performed in many countries to evaluate bleeding risk. The aim of this study was to assess the management of unexpected prolongations of the activated partial thromboplastin time (APTT) and prothrombine time (PT) in children prior to elective surgery, and the perioperative hemorrhagic outcomes. Children with prolonged APTT and/or PT who attended a preoperative anesthesia consultation from January 2013 to December 2018 were included. Patients were grouped according to whether they were referred to a Hematologist or were scheduled to undergo surgery without further investigation. The primary endpoint was to compare perioperative bleeding complications. 1835 children were screened for eligibility. 102 presented abnormal results (5.6%). Of them, 45% were referred to a Hematologist. Significant bleeding disorders were associated with a positive bleeding history, odds ratio of 51 (95% CI 4.8 to 538.5, P = 0.0011). No difference in perioperative hemorrhagic outcomes were found between the groups. An additional cost of 181 euros per patient and a preoperative median delay of 43 days was observed in patients referred to Hematology. Our results suggest that hematology referral has limited value in asymptomatic children with a prolonged APTT and/or PT. Hemorrhagic complications were similar among patients referred and not referred to Hematology. A positive personal or family bleeding history can help identify patients with a higher bleeding risk, thus it should guide the need for coagulation testing and hematology referral. Further efforts should be made to standardize preoperative bleeding assessments tools in children.

Comparing modified Lee and White method against 20-minute whole blood clotting test as bedside coagulation screening test in snake envenomation victims.

Twenty-minute whole blood clotting test (20WBCT) and Modified Lee and White (MLW) method are the most routinely employed bedside tests for detecting coagulopathic snake envenomation. Our study compared the diagnostic utility of MLW and 20WBCT for snakebite victims at a tertiary care hospital in Central Kerala, South India. This single-center study recruited 267 patients admitted with snake bites. 20WBCT and MLW were performed simultaneously at admission along with the measurement of Prothrombin Time (PT). The diagnostic utility of 20WBCT and MLW was determined by comparing the sensitivity (Sn), specificity (Sp), positive and negative predictive values, likelihood ratios, and accuracy at admission with an INR value > 1.4. Out of 267 patients, 20 (7.5%) patients had VICC. Amongst those who had venom-induced consumption coagulopathy (VICC), MLW was prolonged for 17 patients, (Sn 85% 95% confidence interval [CI]: 61.1-96.0) whereas 20WBCT was abnormal for 11 patients (Sn 55%, 95% CI: 32.04-76.17). MLW and 20WBCT were falsely positive for the same patient (Sp 99.6%, 95% CI: 97.4-99.9%). MLW is more sensitive than 20WBCT to detect coagulopathy at the bedside amongst snakebite victims. However, further studies are necessary for standardizing bedside coagulation tests in snakebite cases.

COMPARING THE EFFECTIVENESS OF CONCENTRATE OF ALL PROTHROMBIN COMPLEX FACTORS WITH RECOMBINANT HUMAN COAGULATION FACTOR VIIa IN THE TREATMENT OF BLEEDING AFTER CARDIAC SURGERY

Aim: The authors evaluated the effectiveness of treatment with recombinant human coagulation factor VIIa and concentrate of all prothrombin complex factors in patients with massive postoperative bleeding that could not be controlled with traditional therapy. Materials and Methods: In the period from 2020 to 2021, recombinant human coagulation factor VIIa was administered to 18 patients after cardiac surgery (group I), while the concentrate of all prothrombin complex factors was administered to 16 patients postoperatively (group II). During this period, 647 patients were operated on. The patients had normal coagulation screening tests (APTT, INR, TT, fibrinogen level, and PLT level) before surgery. Mean blood loss before and after administration of eptacog alfa and the total prothrombin complex concentrate was assessed. The mean dose of eptacog alfa was 30.95 mcg/kg b.w., and the total prothrombin complex factor concentrate dose was 14.17 mcg/kg b.w. After transfusion with red blood cell concentrate, fresh frozen plasma, and platelet concentrate, in the absence of improvement in the dynamics of postoperative drainage, it was decided to include recombinant human coagulation factor VIIa or a concentrate of all prothrombin complex factors in the treatment. Results: After administration of recombinant human coagulation factor VIIa at a dose of 30.95 mcg/kg b.w., bleeding stopped in 12 patients, but the remaining 6 patients required reoperation due to persistently high drainage. The decision to perform a rethoracotomy was made by a team of cardiothoracic surgeons and anesthesiologists, taking into account the dynamics of drainage (bleeding) and the hemodynamic stability of the patient. After the administration of concentrate of all prothrombin complex factors at a dose of 14.17 U/kg b.w., bleeding stopped in 12 patients. Four patients required reoperation due to persistent bleeding. Conclusions: Treatment with recombinant human coagulation factor VIIa and concentrate of all prothrombin complex factors is effective and safe for cardiac surgery patients.

The diagnosis and Management of HIV Associated Acquired Hemophilia A: A Case Series From Durban, South Africa.

In acquired hemophilia A (AHA), the body produces auto-antibodies against Factor VIII. Although AHA is rare, with an incidence of 1.5 patients/1 million population/year, there is a strong association with human immunodeficiency virus (HIV) infection. The accurate interpretation of screening coagulation tests is critical to identify patients with AHA, as the mortality rate secondary to bleeding is high. This was a retrospective case series which included all newly diagnosed AHA patients that were referred to Hemophilia care unit at King Edward VIII Hospital, Durban, South Africa from January 2011 to December 2021. The clinical presentation and laboratory results were documented. Five patients were included in this case series. All patients were females aged between 28 and 64 years of age and they were HIV seropositive. They presented with spontaneous cutaneous and intramuscular bleeding. Four patients were virologically suppressed on anti-retroviral therapy, and no patient had a family history of congenital bleeding diathesis. Laboratory investigations confirmed AHA with high Factor VIII inhibitor titers, which ranged from 41 to 900 Bethesda Units (BU). All patients were managed with bypassing agents and oral corticosteroids. The monitoring of patients after the initiation of treatment was difficult as they all defaulted treatment. In view of the prevalence of HIV in sub-Saharan Africa, there is a possibility that AHA is under-diagnosed in our setting. The clinician and the laboratory have a combined critical role in identifying patients with AHA as the investigation of a prolonged APTT is mandatory. There are challenges in managing AHA patients in a resource-constrained setting.

Platelet function testing: Current practice among clinical centres in Northern Europe.

IntroductionPlatelet function tests are used to screen and diagnose patients with possible inherited platelet function defects (IPFD). Some acquired platelet dysfunction may be caused by certain drugs or comorbidities, which need to be excluded before testing.AimsTo identify current practice among centres performing platelet function tests in Northern Europe.MethodsA total of 14 clinical centres from Sweden (six), Finland (two), Denmark (two), Norway (one), Estonia (two) and Iceland (one) completed the survey questionnaire, the population capture area of about 29.5 million.ResultsSix of the 14 (42.8%) centres providing platelet function assessment represent comprehensive treatment centres (EUHANET status). A Bleeding score (BS) or ISTH bleeding assessment tool (ISTH BAT score) is evaluated in 11/14 (78.6%) centres and family history in all. Five/14 centres (35.7%) use structured preanalytical patient instructions, and 10/14 (71.4%) recorded questionnaire on the preassessment of avoidance of any drugs or natural products affecting platelet functions. Preliminary investigations of screening tests of coagulation are performed in 10/14 (71.4%), while in 4/14 (28.6%), the diagnostic work‐up of IPFD and von Willebrand disease (VWD) is performed simultaneously. The work‐up of IPFD includes peripheral blood smear in 10/14 (71.4%), platelet aggregometry in all, flow cytometry in 10/14 (71.4%) and Platelet Function Analysis (PFA) in 3/11 (28.6%). Molecular genetic diagnosis is available in 7/14 (50%) centres.ConclusionsThe considerable variability in the current practice illustrates the need for harmonization between the Northern European centres according to the international registers (i.e. EUHASS) and IPFD guidelines (ISTH, EHA).

Laboratory work-up/diagnostics of acquired factor XI inhibitor

Acquired coagulation factor deficiencies are caused by inhibitory autoantibodies which are usually directed against clotting factor VIII (FVIII), causing acquired hemophilia A (AHA). Clotting factor inhibitors usually cause abnormalities in screening coagulation tests (activated partial thromboplastin time [aPTT] and/or prothrombin time [PT]). Other coagulation factor inhibitors are much rarer, particularly inhibitors to factor XI (FXI). We present the case of an 82-year-old woman referred to a hematological center for isolated aPTT prolongation in pre-surgery screening tests. No bleeding symptoms were reported either at admission or in the patient’s medical history. One stage coagulation factor assays revealed lower factor VIII, IX, XI, XII levels. The Nijmegen modification of the Bethesda assay showed the presence of an inhibitor to factor XI (22.1 BU/mL). No autoantibodies to coagulation factors VIII, IX and XII were found: inhibitor titers were all below 0.6 BU/mL. Acquired hemophilia C was diagnosed (the presence of autoantibodies to clotting factor XI).

Uncontrollable bleeding after tooth extraction from asymptomatic mild hemophilia patients: two case reports

BackgroundUncontrollable bleeding after tooth extraction usually occurs in patients with coagulation diseases, including hemophilia, von Willebrand’s disease, vitamin K deficiency, platelet deficiency, and taking anticoagulant drugs. Hemophilia A is an X-linked recessive disorder caused by insufficiency of coagulation factor VIII. Mild hemophilia, defined by factor level between 0.05 and 0.40 IU/mL, is characterized by uncontrollable hemorrhage after trauma or invasive operations. Some mild hemophiliacs may remain undiagnosed until late adulthood. Therefore, surgical management of these patients may be relatively neglected. These case reports describe two uncontrollable bleeding patients with unknown mild hemophilia A after tooth extraction.Case presentationThis paper reports 2 cases of persistent bleeding after tooth extraction under local anesthesia which could not be completely stopped by routine treatments. Both of them denied prior illness and injury, allergies, anticoagulant medication history, systemic and family illness. The APTT and other coagulation screening tests of the two patients before surgery were normal. Finally, they were diagnosed with mild hemophilia A via coagulation factor assays. The patients acquired complete hemostasis by receiving coagulation factor supplement therapy in hematologic department.ConclusionMild hemophilia is marked by subclinical, asymptomatic and even normal coagulation test results. The purpose of these case reports is to bring dental professionals’ attention that APTT test alone cannot be used to exclude mild hemophilia, and provide reasonable evaluation and treatment procedures of bleeding patients after tooth extraction.

Markers of activation of coagulation in cancer patients.

Prothrombotic tendency is characteristic of tumors. The aim of the study is to investigate the changes in the laboratory parameters for coagulation and fibrinolysis, namely in fibrinogen, thrombin-antithrombin complex (ТАТ), tissue factor (ТF), prothrombin fragment (F1+2), antithrombin III (AT III), D-dimer and screening coagulation tests in cancer patients before initiation of chemotherapy. Levels of F1+2, fibrinogen, ТАТ, AT III, TF, D-dimer, PT, aPTT and TT were measured baseline in 80 patients with breast and lung cancer before systemic treatment. The same parameters were investigated in 65 healthy volunteers. TF, ТАТ, F1+2 were measured by ELISA; AT III, D-dimer, fibrinogen and screening coagulation tests were measured by automated coagulation system Sysmex CS 2000i. RESULTS: Levels of F1+2, fibrinogen, ТАТ, TF, and D-dimer in cancer patients were significantly higher than those in the control group, while the levels of ATIII activity were significantly lower (p < 0.001). The highest area under the ROC curve was for D-dimer, which made it a good marker for the risk of thrombosis. Higher levels of TF, ТАТ, F1+2, fibrinogen and D-dimer and lower activity of АТ III in cancer patients support our hypothesis of an association between malignant disease and coagulation disorders. Cancer patients are at an increased risk of thrombosis wherefore antithrombotic prophylaxis may be considered (Tab. 6, Fig. 2, Ref. 34). Text in PDF www.elis.sk Keywords: coagulation, fibrinolysis, cancer.

Hemostasis testing in patients with liver dysfunction: Advantages and caveats.

Due to concomitant changes in pro- and anti-coagulant mechanisms, patients with liver dysfunction have a “rebalanced hemostasis”, which can easily be tipped toward either a hypo- or a hypercoagulable phenotype. Clinicians are often faced with the question whether patients with chronic liver disease undergoing invasive procedures or surgery and those having active bleeding require correction of the hemostasis abnormalities. Conventional coagulation screening tests, such as the prothrombin time/international normalized ratio and the activated partial thromboplastin time have been demonstrated to have numerous limitations in these patients and do not predict the risk of bleeding prior to high-risk procedures. The introduction of global coagulation assays, such as viscoelastic testing (VET), has been an important step forward in the assessment of the overall hemostasis profile. A growing body of evidence now suggests that the use of VET might be of significant clinical utility to prevent unnecessary infusion of blood products and to improve outcomes in numerous settings. The present review discusses the advantages and caveats of both conventional and global coagulation assays to assess the risk of bleeding in patients with chronic liver disease as well as the current role of transfusion and hemostatic agents to prevent or manage bleeding.

Relative Interfering Effects of In Vivo Direct Oral Anticoagulants on Routine Coagulation Tests

Background:The interfering effects of DOACs on the screening coagulation tests, such as prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen assay, have been shown mainly by in vitro spiking experiments. However, the effects of DOACs on coagulation tests in real-world samples from anticoagulated patients are unknown because of the difficulty in selectively eliminating DOAC from blood samples already containing DOACs.Method:Citrated blood samples were drawn from patients on anticoagulation therapy (rivaroxaban and edoxaban). In addition, blood samples from patients not on anticoagulation were collected. PT INR and APTT were measured from those samples by coagulometers from two manufacturers (Roche t711, Swiss and ACL-TOP, USA). We also measured DOAC levels from the same samples by anti-FXa activity (Hyphen Biomed, France). Then, we compared the test results in relation to the DOAC levels.Results:The PT INR, APTT, and fibrinogen assay results from non-anticoagulated patients measured by the two coagulometers were comparable (PT INR: y = -3.353 + 1.029 x; APTT: y = -6.276 + 1.101x; fibrinogen: y = -3.353 + 1.029 x; Passing Bablok). We included blood samples from 61 patients on rivaroxaban and 75 patients on edoxaban. From the rivaroxaban samples we observed the regression line change for PT INR (y = 0.6303 + 0.3712x) and for APTT (y = -10.71+1.358x). The comparability of fibrinogen assay was not affected significantly (y = -17.39+1.01x). From the edoxaban samples we also observed the similar change of the regression line (PT INR: y = 0.4728 + 0.5661x; APTT: y = -133.07+2.014x). Fibrinogen levels were comparable (y = -28.95+1.082x).Conclusion:The susceptibility of screening coagulation tests to the interfering effects of in vivo DOAC is dependent on the reagents and coagulometers. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

A CASE REPORT WITH SEVERE CONGENITAL FACTOR XIII DEFICIENCY AND AN UNCOMPLICATED PREGNANCY AND BIRTH PROCESS

Factor XIII deficiency is an extremely rare type among bleeding diathesis. In factor XIII deficiency, normal results of coagulation screening tests are expected. It usually does not cause spontaneous bleeding. Apart from bleeding diathesis, it may cause delayed wound healing and recurrent spontaneous abortions in women. Here, we present a 32-year-old case with severe congenital factor XIII deficiency who had an uncomplicated pregnancy and birth with regular replacement therapies. A 32-year-old patient with severe congenital factor XIII deficiency, who had a history of spontaneous abortion at the 11th week of her first pregnancy, applied to our center with a request for childbirth. It was learned that the factor XIII levels of the patient could not be measured, that she was using plasma-derived FXIII concentrate at a dose of 25 units/kg every time once a month, and in cases where this could not be obtained, 5 units/kg cryoprecipitate was given instead. After the completion of the pre-pregnancy assessments, starting 3 months before the planned pregnancy and continuing for the whole pregnancy and for 3 months after birth, 25 units/kg plasma-derived concentrate at a dose of 25 units/kg was applied each time and every two weeks, and in cases where this could not be provided, the follow-up was continued by applying cryoprecipitate at a dose of 5 units / kg instead. During this whole process, FXIII levels ranged between 70% and 100%. The patient, who developed an abortion risk due to decidual bleeding in the first trimester, was hospitalized and an additional 25 units / kg plasma-derived FXIII concentrate was administered and a parenteral dose of 30 mg / kg tranexamic acid was applied until the signs of decidual bleeding disappeared. An additional 50 units/kg dose of plasma-derived FXIII concentrate was administered to the patient 30 minutes before birth who had a planned delivery by cesarean section at 38 weeks of gestation, and 30 mg/kg parenteral tranexamic acid was administered for 7 days following the delivery. FXIII level was detected 50% in the child of a healthy, 3500-g born boy. The patient and her baby, who are in the first year after birth, are followed up without any complications, and prophylactic plasma-derived FXIII concentrate or cryoprecipitate is administered to the patient once a month. Inherited bleeding diathesis lead to an increased risk of bleeding and abortion in obstetric patients. Factor XIII deficiency is an extremely rare type among them. FXIII has a role in angiogenesis as well as hemostasis. Therefore, wound healing and tissue repair are impaired in Factor XIII deficiency. The risk of premature separation of the placenta, miscarriage especially in the first trimester, and postpartum uterine bleeding are increased in FXIII deficiency. Tranexamic acid can be used safely in obstetric patients with bleeding diathesis. It may be possible to ensure that patients with factor XIII deficiency have an uncomplicated pregnancy and delivery with regular follow-ups, regular prophylactic factor preparations, plasma replacements if they are not found, and in cases of bleeding, with additional doses of factor preparations or plasma replacement applications with tranexamic acid.

Preoperative unexpected prolongation of the activated partial thromboplastin time and prothrombin time in adults. Do we need to pursue abnormal results? A retrospective analysis

BackgroundPreoperative coagulation screening tests are still performed often to assess bleeding risk; however, the effectiveness of this practice is a matter of debate and no longer recommended by some professional societies. We aimed to assess the management of unexpected prolonged activated partial thromboplastin time (APTT) and/or prothrombin time (PT) prior to elective surgery, and the perioperative hemorrhagic outcomes. MethodsThis was a retrospective cohort study conducted at a tertiary care hospital in Madrid, Spain. Patients who attended a preoperative anesthesia consultation between January 2013 and December 2018 were selected. 45,223 patients were screened for eligibility. After excluding children and patients with a preexisting cause for abnormal coagulation or who were receiving anticoagulation therapy, 722 adults with prolonged APTT and/or prolonged PT in coagulation screening tests were included in the study. Patients were grouped according to whether they were referred for a Hematology consultation or were scheduled to undergo surgery without further investigation. The primary endpoint was to compare perioperative bleeding complications. Results271 patients (38.5%, 95% CI 34.9 to 65.1) were referred to a Hematologist while 433 (61.5%, 95% CI 57.9 to 65.1) did not undergo further investigation. In 95% of the patients referred for a Hematology consultation, no significant hemostatic disorders were detected. No difference in perioperative hemorrhagic outcomes were found between the two groups. Additional studies were associated with a follow up pre-anesthetic evaluation median delay of 36,5 days (IQR 28 to 49) and a total referral cost of 45 596 euros ($ 54,100). ConclusionsFurther investigations of APTT and PT prolongations did not have any benefit in terms of hemorrhagic complications, and were associated with a significant preoperative delay and increase of healthcare costs. We recommend the more beneficial and cost-effective approach of selective preoperative coagulation testing based on bleeding history.