Israel Medical Association Journal

Background: Unfractionated heparin is the preferred anticoagulant used during open heart surgeries, including left ventricular assist device (LVAD) implantation. In cases in which patients are heparin-induced thrombocytopenia positive (HIT+), the accepted practice has been to substitute heparin with bivalirudin. This practice may be associated with significant bleeding and adverse outcomes.

Objectives: To review our experience with HIT+ patients who were heparin-induced thrombocytopenia with thrombosis negative (HITT-) and who underwent HeartMate 3 LVAD implantation using heparin intraoperatively rather than bivalirudin.

Methods: From 2016 to 2022, 144 adult patients were implanted with HeartMate 3 LVAD at our center. Among them, 7 were detected as HIT+ but HITT- and therefore were prescribed intraoperatively with heparin and treated pre- and postoperatively with bivalirudin. We reviewed the preoperative, intraoperative, and postoperative characteristics as well as short-term mortality and the complication rates of these HIT+ patients.

Results: The median age of our cohort was 56 years (51–60), 71% were male (n=5), all were INTERMACS Level 1, and most were bridged to transplant (n=6, 86%). The 30-day mortality rate post-implantation was 0%. The average 24-hour chest drain postoperative output was 1502.86 ± 931.34 ml. There were no intraoperative pump thromboses, perioperative thromboses, cerebrovascular accidents, or gastrointestinal bleeding within the first 24 hours postoperative. One patient required a revision due to bleeding.

Conclusions: Intraoperative unfractionated heparin may be administered to patients who are HIT+ and HITT- while undergoing LVAD implantation. However, further investigation is required.

Background: Among the most frequent complications following transcatheter aortic valve replacement (TAVR) is hemostasis imbalance that presents either as thromboembolic or bleeding. Deviations in platelet count (PC) and mean platelet volume (MPV) are markers of hemostasis imbalance.

Objectives: To determine the predictive value of pre- and post-procedural PC and MPV fL 1-year all-cause mortality in patients who underwent TAVR.

Methods: In this population-based study, we included 236 TAVR patients treated at the Tzafon Medical Center between 1 June 2015 and 31 August 2018. Routine blood samples for serum PC levels and MPV fL were taken just before the TAVR and 24-hour post-TAVR. We used backward regression models to evaluate the predictive value of PC and MPV in all-cause mortality in TAVR patients.

Results: In this study cohort, MPV levels 24-hour post-TAVR that were greater than the cohort median of 9 fL (interquartile range 8.5–9.8) were the strongest predictor of 1-year mortality (hazard ratio 1.343, 95% confidence interval 1.059–1.703, P-value 0.015). A statistically significant relationship was seen in the unadjusted regression model as well as after the adjustment for clinical variables.

Conclusions: Serum MPV levels fL 24-hour post-procedure were found to be meaningful markers in predicting 1-year all-cause mortality in patients after TAVR.

Background: The CHA₂DS₂-VASc score has been shown to predict systemic thromboembolism and mortality in certain groups in sinus rhythm (SR), similar to its predictive value with atrial fibrillation (AF).

Objectives: To compare factors of inflammation, thrombosis, platelet reactivity, and turnover in patients with high versus low CHA₂DS₂-VASc score in SR.

Methods: We enrolled consecutive patients in SR and no history of AF. Blood samples were collected for neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), immature platelet fraction (IPF%) and count (IPC), CD40 ligand, soluble P-selectin (sP-selectin) and E-selectin. IPF was measured by autoanalyzer and the other factors by ELISA.

Results: The study comprised 108 patients (age 58 ± 18 years, 63 women (58%), 28 (26%) with diabetes), In addition, 52 had high CHA₂DS₂-VASc score (³ 2 for male and ³ 3 for female) and 56 had low score. Patients with low scores were younger, with fewer co-morbidities, and smaller left atrial size. sP-selectin was higher in the high CHA₂DS₂-VASc group (45, interquartile ratio [IQR] 36–49) vs. 37 (IQR 28–46) ng/ml, P = 0.041]. Inflammatory markers were also elevated, CRP 3.1 mg/L (IQR 1.7–9.3) vs. 1.6 (IQR 0.78–5.4), P < 0.001; NLR 2.7 (IQR 2.1–3.8) vs. 2.1 (IQR 1.6–2.5), P = 0.001, respectively. There was no difference in E-selectin, CD40 ligand, IPC, or IPF% between the groups.

Conclusions: Patients in SR with high CHA₂DS₂-VASc score have higher inflammatory markers and sP-selectin. These findings may explain the higher rate of adverse cardiovascular events associated with elevated CHA₂DS₂-VASc score.

Background: Fibromyalgia syndrome (FMS) is a chronic disorder characterized by widespread musculoskeletal pain accompanied by various additional symptoms. The prevalence of FMS ranges between 2–8% of the population. The exact pathophysiology of the disease remains unknown, and under certain circumstances it is difficult for the physician to diagnose. Previous studies have shown a correlation between inflammatory biomarkers such as C-reactive protein (CRP) and FMS activity, suggesting that an inflammatory component may play a role in this disease pathogenesis.

Objectives: To investigate the role of certain new inflammatory biomarkers in the diagnosis of patients with FMS.

Methods: In this study data were collected from FMS patients who were admitted to Ziv Medical Center during the period 2013 to 2019 in an attempt to find a connection between inflammatory markers detectable by a traditional complete blood count (CBC) tests such as neutrophil-lymphocytes ratio (NLR), platelet-lymphocyte ratio (PLR), mean platelet value (MPV), red cell distribution width (RDW), and C-reactive protein (CRP) and FMS.

Results: We found significantly higher CRP levels, MPV, and PLR and lower lymphocyte count in the FMS group compared to the control group.

Conclusions: FMS has certain inflammatory components that may be useful in disease diagnosis

Background: Mean platelet volume (MPV), an essential component of the complete blood count (CBC) indices, is underutilized in common practice. In recent years, MPV has drawn strong interest, especially in clinical research. During inflammation, the MPV has a higher value because of platelet activation.

Objectives: To verify whether high MPV values discovered incidentally in healthy naïve patients indicates the development or the presence of cardiovascular risk factors, particularly metabolic syndrome and pre-diabetes.

Methods: A cohort study was used to assess the diagnostic value of high MPV discovered incidentally, in naïve patients (without any known cause of an abnormal high MPV, greater than  upper limit of the normal range, such as active cardiovascular diseases and metabolic syndrome).

Results: The mean MPV value in the patient group was 12.3 femtoliter. There was a higher incidence of metabolic syndrome in our research group than in the general population and a non-significant tendency of pre-diabetes. Family doctors more frequently meet naïve patients with high MPV than a hospital doctor. The results of our study are more relevant for him, who should know the relevance of such a finding and search for a hidden pre-diabetes or metabolic syndrome.

Conclusions: High MPV values discovered incidentally in healthy naïve subjects suggest the development or the presence of cardiovascular risk factors, particularly metabolic syndrome and pre-diabetes. No statistically significant association was found between MPV and the presence of cardiovascular disease

Background: Venous thromboembolism (VTE) is a serious disease, which demands a fast accurate diagnosis to begin suitable treatment. It presents a major problem in the emergency department (ED), and its confirmation requires adequate evaluation.

Objectives: To evaluate a potential role of mean platelet volume (MPV) in differentiating VTE from other potential diagnosis in patients with suspected VTE.

Methods: We conducted a retrospective case-controlled study of 440 consecutive patients who presented to the ED of our hospital with clinical VTE, but only 316 with proven VTE. A control group was composed of patients (124) who presented with clinical VTE but without proven VTE. We checked the MPV value in all 440 patients and the correlation with VTE occurrence in the study group vs. control group.

Results: Statistical analysis of the acquired results indicated that MPV value could not aid in determining the difference of real VTE vs. patients with VTE-like clinical picture presenting to the ED. We found an inverse correlation between MPV value and proven VTE, in contrast to most researchers who have studied the same issue.

Conclusions: Although MPV can be a useful diagnostic marker in many diseases, we found no definite association between low MPV and VTE

Background: An association was shown between thrombocytosis and future development of several cancers.

Objectives: To investigate whether pre-treatment platelet counts correlated with clinical outcomes of patients with breast cancer.

Methods: This retrospective study included 22 patients who had been diagnosed with stage I breast cancer and were 66.8 ± 13.2 years of age. Of these, 22 with stage II were 61.6 ± 12.3 years old and 9 with stage III and IV were 64.4 ± 15.3 years old. Clinical and hematological data from the first visit to the oncology clinic were collected. The follow-up period was 12 months to 5 years.

Results: A significant difference in platelet counts was found between patients who died (187,000 ± 4000 µ/L) and those who were disease free for 5 years (248,000 ± 83,000 µ/L, P = 0.0001). A significant difference in platelet-to-lymphocyte ratio was found between patients who died and those with recurrence (192 ± 81 vs. 124 ± 71, P = 0.01). A negative correlation was found between age and lymph nodes (Ps = -0.305, P = 0.02) and staging and white blood cells count (Ps = -0.280, P = 0.04). A positive correlation was found between clinical staging and lymph nodes (Ps = 0.443, P = 0.001) and clinical staging and metastases (P = 0.308, P = 0.02).

Conclusions: Platelet counts may be a prognostic marker for breast cancer. Patients who died within 1 year had lower pre-treatment platelet count, which could represent an insidious disseminated intravascular coagulopathy cancer related consumption process.

Background: The incidence of Clostridium difficile-associated diarrhea (CDAD) is increasing and is associated with significant morbidity and mortality. Therefore, there is a need to find new tools to determine the severity of the disease.

Objectives: To investigate the prognostic values of inflammatory markers such as mean platelet volume (MPV), neutrophil-lymphocyte ratio (NLR), and C-reactive protein (CRP) in patients with CDAD.

Methods: The study comprised of 100 patients diagnosed with CDAD. The study included an additional control group of 69 patients with diarrhea who were negative for C. difficile toxin. The control group was age- and sex-matched and hospitalized at the same time period. NLR and MPV were obtained from complete blood count results. Serum CRP levels were measured by the latex particle enhanced immunoturbidimetric assay. Blood samples for all inflammatory markers were collected at time of diagnosis and prior to initiating the antibiotic therapy. Demographic, clinical, laboratory, and prognostic data were collected from medical records for a period of 90 days from the initial diagnosis of CDAD.

Results: The mean age of the CDAD group was 68.6 ± 21.5 years compared to 65.6 ± 24.5 in the control group (P = 0.29). Our findings show that patients with CDAD had significantly higher NLR, MPV and serum CRP levels compared to the control group (P < 0.001)). Moreover, significantly higher levels were observed when CDAD was fatal (P < 0.001).

Conclusions: Elevated NLR, MPV, and serum CRP levels may serve as biomarkers for prediction of recurrence and mortality in patients with CDAD.

Platelets have the ability to influence the immune system and the inflammatory process and may be strongly involved in the whole pathogenic process of chronic inflammatory joint diseases, such as rheumatoid arthritis. They may play a significant role even before the clinical onset of the disease, contributing to the loss of tolerance of the immune system and the induction of autoimmunity. Subsequently, they can interact with the most important cellular players involved in autoimmunity and inflammation, namely innate immunity cells and T cells and eventually contribute to the building of inflammation in the synovium, thus inducing the activation, migration, and proliferation of fibroblasts that eventually lead to joint damage. Due to their peculiar features, studying the behavior of platelets is a challenging task; however, platelets may prove to be valuable therapeutic targets in the future.

Objective: To study the mechanism of platelet function inhibition in a patient with acquired thrombasthenia.

Methods: Aggregation assays of platelets from the patient and healthy controls were performed. In addition, anti-glycoprotein (GP) IIbIIIa antibodies binding to normal platelets in the presence or absence of the patient’s serum was studied by flow cytometry.

Results: Aggregation of normal platelets in the presence of patient's plasma was inhibited four- and 2.5-fold in the presence of ADP and arachidonic acid respectively, while collagen-induced aggregation was completely abolished. Ristocetin-induced aggregation was normal. The patient's serum inhibited binding of commercial anti-glycoprotein IIbIIIa antibodies to normal platelets twofold by flow cytometry. Treatment with anti-CD20 monoclonal antibody (rituximab) normalized the patient's platelet aggregation.

Conclusions: These results suggest that the patient developed inhibitory anti-GPIIbIIIa autoantibodies that caused acquired thrombasthenia. 

Background: The effect of anti-platelet drugs on surgical blood loss and perioperative complications has not been studied in depth and the management of surgical patients taking anti-platelet medications is controversial.

Objective: To assess the effect of anti-platelet therapy on perioperative blood loss in patients undergoing appendectomy either laparoscopically or via open surgery.

Methods: We reviewed the files of all patients > 40 years old who underwent open or laparoscopic appendectomies from 2007 to 2010. Excluded were patients with short hospitalization and no follow-up of hemoglobin level, patients on warfarin treatment and patients who underwent additional procedures. Estimation of blood loss was based on decrease in hemoglobin level from admission to discharge. Risk factors for blood loss, such as anti-platelet therapy, age, gender, surgical approach, surgical time, surgical findings and complications, were analyzed.

Results: The final cohort included 179 patients (mean age 61 ± 14 years, range 40–93) of whom 65 were males. The mean perioperative hemoglobin decrease was 1.59 ± 1.07 mg/dl (range 0–5 mg/dl). Thirty-nine patients received anti-platelet therapy prior to surgery and 140 did not. No significant differences in decrease of hemoglobin level were found between patients receiving anti-platelet therapy and those who were not (1.73 ± 1.21 vs. 1.55 ± 1.02 mg/dl, P = 0.3). In addition, no difference was found between patients on anti-platelet therapy operated laparoscopically and those operated in an open fashion (1.59 ± 1.18 vs. 2.04 ± 1.28 mg/dl, P = 0.29). Five patients required blood transfusions, two of whom were on anti-platelet therapy. Blood loss was significantly greater in patients with a perforated appendicitis and in those with an operative time of more than one hour.

Conclusions: Anti-platelet therapy does not pose a risk for increased blood loss following emergent appendectomy performed either laparoscopically or in an open fashion.
 

Background: Several murine models are susceptible to atherosclerosis, such as low density-lipoprotein receptor-deficient (LDLR^-/-) and apolipoprotein E-deficient (apoE^-/-) mice, and are used for studying pathophysiological mechanisms. Atherosclerotic lesions in the aortic valve and thoracic/abdominal aorta are commonly associated with hyperlipidemia. We recently demonstrated the development of large atherosclerotic plaques in Helicobacter pylori-infected heterozygous LDLR^+/- apoE^+/- mice.

Objectives: To measure novel biomarkers related to atherosclerosis, blood coagulation, and oxidative stress in order to investigate their possible pathogenic roles in atherosclerosis-prone mice.

Methods: Mice were fed with a normal chow diet or high-fat diet and sacrificed at different age intervals to measure aortic plaque size. Plasma cholesterol was enzymatically measured. Enzyme-linked immunosorbent assay was used to measure oxidized LDL (oxLDL)/beta-2-glycoprotein I (β2GPI) complexes, immunoglobulin M (IgM) antibodies against native LDL, oxLDL, or oxLDL/β2GPI, and urine 11-dehydro-thromboxane B₂ (11-dhTxB₂) or 8-hydroxy-deoxyguanosine.

Results: There was a parallel increase in plaque size, plasma cholesterol, and urinary 11-dhTxB₂ in atherosclerosis-prone mice. In contrast to atherosclerosis-prone strains, an elevation of urinary 11-dhTxB₂ with no significant plaque generation was observed in LDLR^+/- apoE^+/- mice. The atherogenic autoantigen oxLDL/β2GPI complex was detected only in LDLR^-/- mice. These levels seem to depend on plaque size. IgM antibodies against oxLDL in apoE^-/- mice were found, accompanied by atherosclerotic progression.

Conclusions: Progression of atherosclerotic lesions was associated not only with cholesterolemia but also with platelet activation and natural autoimmune-mediated regulatory mechanism(s) in murine models.