High Levels IPF as Possible Predictor Heparin-Induced Thrombocytopenia

Background: Heparin-Induced Thrombocytopenia (HIT) represents a serious complication of heparin treatment. IgG antibodies binding Platelet Factor 4 (PF4) and heparin trigger the clinical manifestations of HIT. A 4T score is used to stratify the selection of patients suitable for examination. However, the selection of suitable patients remains at the discretion of the clinician, who is confronted with determining the cause of thrombocytopenia. The inclusion of the evaluation of the Immature platelet fraction result seems to be a suitable complement to the stratification of patients because we do not climb elevated IPF values when consuming platelets due to their immunization. Materials and Methods: In a group of 432 thrombocytopenic samples IPF was detected and analyzed in 45 patients with suspected HIT, a 4T score was determined; IPF and HIT functional tests were examined. IPF was determined by oxazine fluorescent dyeing structures of nucleic acid-containing platelets and fluorescence detection on a Sysmex XN 1000 analyser. To determine HIT, impedance aggregometry using the Multiplate® analyser (MEA) as heparin-induced aggregation techniques. The MEA method uses sensitization of donor platelets with patient plasma in the presence of heparin at a concentration of 0.5IU/mL. Results: From the results of the test, it is evident that 10 patients from our group of 45 examined showed positivity of HIT, which is a significant number due to the proven occurrence of HIT in patients treated with LMWH and showing thrombocytopenia. If we evaluate these 10 patients in terms of IPF value, it is evident that 6 of them have an increased value of IPF >10%, which is a 33% positive predictive value and 4 have IPF >30%, when the positive predictive value is even 100%. Conclusions: Diagnosis of HIT remains a complicated clinical laboratory issue. However, new diagnostic options provide considerable potential for solving this problem. The implementation of IPF assays helps us in the diagnosis of HIT on two levels. On the one hand, it provides us with information on platelet consumption in hospitalized patients and thus draws our attention to HIT as one of the options for congestive thrombocytopenia, unless, of course, disseminated intravascular coagulation or thrombotic microangiopathy. Secondly, its implementation will increase the predictive value of the 4T score in patients at medium risk, which is, however, the vast majority indicated for HIT examination.

Safety and Efficacy of Recombinant Factor VIIa (NovoSeven) Use during ECMO Support in Patients after Cardiac Surgery

Background: Acute postoperative bleeding in cardiac surgical patients is a major cause of morbidity and mortality. Substitution of coagulatory factors may not always provide optimal hemostasis and off label, use of recombinant FVIIa has been proposed. When on ECMO, extra care must be taken during coagulatory substitution as clotting of the system may cause cardiovascular complications and possible ECMO failure, leading to death. In this paper, we examined the safety and efficacy of rFVIIa during ECMO support in postoperative cardio-surgical patients. Methods: We retrospectively examined all patients receiving rFVIIa postoperatively from December 2005 and January 2020. Clinical characteristics, demographics, bleeding, thrombotic complications, mortality, and rFVIIa administration were analyzed. Results: A total of 74 patients received rFVIIa postoperatively due to uncontrollable bleeding after cardiac surgery on our ICU. Of these patients, 23 patients were on ECMO treatment. Twelve patients received rFVIIa during, but not prior to the initiation of ECMO therapy. Six patients (50%) were male; mean age was 46 years (30-72 years). Eleven patients (91.7%) were on venoarterial ECMO, one patient was on central ECMO (8.3%). Dose of administered rFVIIa was corrected for body weight; mean dosage was 82μg/kg. We saw a significant reduction in need for red packed cells, fresh frozen plasma and thrombocyte transfusion after rFVIIa administration. There was no impact on the functionality of the ECMO system, especially regarding the oxygenator after rFVIIa administration. One patient suffered a stroke due thromboembolism (8.3%). One patient developed late thromboembolism in the leg (8.3%), and two cases of pulmonary embolism (16.7%) were recorded. Overall survival was 25% and there was no significant difference in survival between ECMO and non-ECMO patients. Weaning from ECMO could be achieved successfully in 41.7% of our patients. Conclusion: Recombinant Factor VIIa is an effective agent in reducing blood loss during ongoing ECMO therapy in patients with refractory bleeding. Although no direct relation between rFVIIa application and thromboembolic events could be established, its use should be done with the utmost care and in selected patients. However, rFVIIa therapy did not impact ECMO function in our cohort.

Nutraceuticals and Atherothrombosis: A Glance to Human Trials

The leading causes of death worldwide are ischaemic heart disease and stroke. These Cardiovascular Diseases (CVDs) are two of the main clinical manifestations of atherothrombosis. Above all, the major causes of this complex condition include genetic susceptibility along with lifestyle habits or behavioral risk factors such as smoking, physical inactivity, alcohol abuse, and unhealthy diets. The most important way to prevent atherothrombotic events is through lifestyle optimization. In particular, nutritional intervention plays a key role in the treatment and prevention of atherothrombosis, with specific dietary patterns as potential modulators of cardiovascular health. Nutraceuticals are substances derived from food and offer health benefits along with their nutritional value and could become promising agents in the prevention and treatment of CVDs, particularly for individuals or populations with low adherence to certain dietary patterns. However, for most nutraceuticals, the evidence for their use in cardiovascular health is limited and requires further attention. This review will summarize some nutraceuticals with strong evidence from large sample size randomized controlled trials for the primary or secondary prevention of CVDs.

Combination of Topical Use of a Thrombin-Based Hemostatic Matrix and Tranexamic Acid does not have a Synergic Effect on Reducing Postoperative Blood Loss in Minimally Invasive Total Knee Arthroplasty. A Prospective Randomized Controlled Study

Background: There is limited information regarding the blood-conservation effect of combined topical Tranexamic Acid (TXA) and Thrombin-Based Hemostatic Matrix (TBHM) in Total Knee Arthroplasty (TKA). This study is to evaluate whether there is synergic effect of combined use of TXA and TBHM to reduce blood loss during TKA. Materials and Methods: Sixty-nine patients (69 knees) who underwent primary TKA were randomly assigned into a TXA group (n=34), who received intra-articular administration of 3g of TXA in 60mL saline, and a TXA + TBHM group (n=35), who received intra-articular TBHM and TXA (3g) in 60mL saline after TKA. The primary outcomes were Total Blood Loss (TBL) and postoperative Hemoglobin (Hb) level. Secondary outcomes included the transfusion rate and the incidence of Venous Thromboembolism (VTE). Results: The mean TBL in the TXA + TBHM group was 678 ± 203 mL , which was similar to that in the TXA only group at 733 ± 217 mL (p=0.276). There were no differences in the postoperative Hb level between the two groups. The transfusion rate was similar in the TXA + TBHM group and the TXA only group (2.9% versus 0%, p=0.242). No patients in either group developed VTE within 3 months. Conclusions: Our prospective randomized controlled study did not show a synergic blood-conservation effect of combined use of topical TBHM and TXA in patients undergoing TKA. Further investigation with a larger sample size may be required.

Risk of Thromboembolic Disease and Hemorrhage in Patients with Multiform Glioblastoma

Introduction: Glioblastoma Multiforme (GBM) is the most frequent malignant brain tumor, with an aggressive course and a short life expectancy despite standard treatment (chemotherapy and radiotherapy). The possibility of the development of Thrombotic Events (VTE) with this type of cancer is frequent. We designed this study to determine the risk of presenting VTE and hemorrhagic events in patients affected by GBM. Methods: Observational retrospective study of patients with GBM diagnosis at the General University Hospital of Ciudad Real between 2012 and 2015. The demographic characteristics of patients were studied, predictive models were compared, and a survival analysis was performed. Results: 77 patients were studied, 42 (55.3%)/34 (44.7%), men and women respectively, with an average age of 66.42 years. 13 (16.9%) presented VTE; of which 10 (61.54%) in the form of Deep Venous Thrombosis (DVT), 3 (23.08%) Pulmonary Embolism (PE) and 2 (15.38%) mixed events. The quality of life according to the performance status ECOG scale at the moment of diagnosis was 1 in 42 (15.38%) patients, and at the time of VTE, 5 (41.7%) had a value of 2, and 4 (33.3.3 %) registered 3. In the group that developed VTE according to the predictive model of risk for thrombosis in Khorana 5 (38.5%) had low risk and 8 (61.5%) intermediate; on the ASCO 2013 modified scale 5 (38.5%) had an Intermediate risk and 8 (61.5%) high. With a median, 1 year follow-up, 64 (84.2%) patients died, with an average time after the diagnosis of 279.09 days (216.6-341.6) (SE 31,8). 2 (2.6%) of the patients presented a greater haemorrhagic event and 7 (7.9%) cerebral haemorrhage, of which 4 (44.4%) had prophylactic Low Molecular Weight Heparins (LMWHs). In the survival analysis of Kaplan Meyer, patients who received prophylactic treatment with LMWHs had a higher survival rate with an average of 298.5 days compared to 239.3 of those who did not (p >0.05). There were no significant variables in the multivariate analysis for thrombotic or haemorrhagic events. Conclusion and Discussion: The demographic and clinical characteristics of our patients were similar to those reported in other international publications. The predictive scale of Khorana was not validated in our study, in contrast, the modified ASCO 2013 scale was closer to our results. The creation of a precise predictive model would help to delineate the benefit of prophylactic anticoagulation in high-risk patients. Long-term prophylaxis with LMWHs has demonstrated a reduction of thrombotic events without significantly increasing the fatal haemorrhagic episodes, also demonstrating greater long-term survival, independent of thrombotic events. Randomized prospective studies are needed to demonstrate its benefits.

Measurement of Bivalirudin Thrombin Inhibition Activity in Plasma with Clotting or Chromogenic Assays and Dedicated Calibrators and Controls

Bivalirudin is a parenteral direct thrombin inhibitor anticoagulant and does not induce any impairment of the Protein C pathway, which function remains preserved. This drug meets increasing applications for cardiac surgery and heart diseases, especially when heparin is contra-indicated in presence of heparin-induced thrombocytopenia. Major indications concern Extra Corporeal Circulation, PCI/PTCA, and myocardial infarction. Drug clearance occurs partly through kidney. Patients with moderate or severe renal dysfunctions are exposed to drug accumulation and subsequent bleeding, the major adverse effect reported. This study presents 2 automated assays, a clotting method, and a kinetics chromogenic technique, proposed for the quantitative measurement of bivalirudin in citrated plasma. Both assays need a specific bivalirudin calibration, are fully automatable on coagulation instruments, and can be available at any time in specialized clinical laboratories for an on time monitoring of treated patients. Assay ranges are from 0.3 to 5.0 μg/ml (clotting assay) or to 6.0μg/ml (chromogenic assay), and up to 20.0μg/ml with an additional automatic plasma dilution. These methods offer excellent performances, with good reproducibility and repeatability. This study reports the results obtained with both assays on bivalirudin measurements in 26 treated patients collected at 4 timings. Both methods are fully consistent and contribute to facilitate and secure the use of this anticoagulant when it is indicated.

Effects of Long-term Direct Thrombin Inhibition by Dabigatran Etexilate on Progression of Atherosclerosis in ApoE-/- and LDLR-/- Double-knockout Mice

Background: Atherosclerosis is characterized by a hypercoagulable state, during which coagulation and fibrinolytic factors are simultaneously activated. However, details regarding the progression of atherosclerosis remain unknown. Here, we investigated the effects of direct long-term inhibition of thrombin by dabigatran etexilate on atherosclerotic progression in apolipoprotein E–/– and low-density lipoprotein receptor–/– double-knockout mice. Methods: Mice received either standard chow (placebo group) or dabigatran-supplemented chow for 22 weeks. The amount of atherosclerosis was estimated as the ratio of the atherosclerotic area to the total aortic intimal area. Immunohistochemistry was used to examine the expression of Matrix Metalloproteinase-9 (MMP-9), Vascular Endothelial Growth Factor (VEGF), Tissue-Type Plasminogen Activator (t-PA), and Endothelial Nitric Oxide Synthase (eNOS) in atherosclerotic regions. Results: The atherosclerotic area was smaller in the dabigatran group than in the placebo group. Immunohistochemistry revealed decreased expression of MMP-9 and VEGF, but increased expression of eNOS, in the dabigatran group compared with the placebo group. t-PA expression did not differ between the groups. Conclusion: Direct long-term inhibition of thrombin by dabigatran in mice led to a decrease in atherosclerosis progression via decreased expression of MMP-9 and VEGF.

Anticoagulation Clinical Pharmacist: Anticoagulation Care between the Headset and the Dial Pad

Anticoagulant is a class of medication that saves lives while carries an intrinsic risk of harm. The American College of Chest Physicians Consensus Conference on Antithrombotic Therapy for the first time in 1995 endorsed the setting of specialized anticoagulation clinics instead of usual medical care. Recently telemedicine is not a brand-new method of patient care, yet, telemedicine utilization has increased dramatically during the last year to comply with the curfew that most cities of the world had to apply to reduce the spread of COVID-19. Telemedicine and especially anticoagulation care need careful systems, the minimum infrastructure of patient records including telephone contact number, facility telephone, and clinic appointment system. The top three challenges when applying telehealth are payment, confidentiality, and un-updated patients’ information.

Acquired Hemophilia a Secondary to Autoimmune Pancreatitis with Elevated IG4

Acquired Hemophilia A (AHA) is a rare disease resulting from autoantibodies against Factor VIII (FVIII) that leads to bleeding. AHA associated with IgG4 related diseases is even rarer. The patient was diagnosed with IgG4 associated autoimmune pancreatitis in January 2019, and the condition improved after two hospitalizations. However, 22 months later, the patient was admitted to hospital due to generalized bleeding points. He was diagnosed with AHA and improved after hormone therapy and plasma exchange. Although IgG4 is associated with IgG4-related disease and AHA, its relevance to the etiology of both diseases is not well understood.

Performance Metrics of the AGGRESTAR PL-12® Platelet Function Analyser in Patients with TIA or Ischaemic Stroke on Commonly-Prescribed Antiplatelet Regimens

Introduction: The optimal time interval after venepuncture to perform platelet function/reactivity testing at low shear stress on the novel AGGRESTAR PL-12® platelet function analyser in non-Chinese Cerebrovascular Disease (CVD) patients is unknown. Methods: Twelve TIA/ischaemic stroke patients were recruited to this cross-sectional, methodological study: 3 on aspirin monotherapy, aspirindipyridamole combination therapy, clopidogrel monotherapy and aspirinclopidogrel combination therapy, respectively. The PL-12 (‘mode 2’) was used to calculate the % maximum aggregation rate to fixed doses of arachidonic acid (%MARAA) and adenosine diphosphate (%MARADP). Samples were analysed every 15 minutes from 30-135 minutes, and every 30 minutes between 165-225 minutes after venepuncture to calculate the time interval providing optimal interassay Coefficients of Variation (CVs). Results: Mean CVs were ≤ 7.37% for the %MARAA assay in patients on aspirin monotherapy or combination therapy, and ≤ 10.24% for the %MARADP assay in patients on clopidogrel monotherapy or combination therapy if assays were performed between 90-120 minutes post-venepuncture. CVs ≤ 10% were also obtained from assays performed between 90-165 minutes postvenepuncture on aspirin monotherapy or combination therapy. Discussion: Reliable and reproducible platelet function/reactivity data can be obtained with the AGGRESTAR PL-12 analyser in non-Chinese CVD patients on commonly-prescribed antiplatelet monotherapy or combination therapy regimens between 90-120 minutes post-venepuncture.