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Objective To investigate the causes of abnormal decrease in maximum amplitude(MA) of thromboelastography(TEG) and its effect on prognosis by monitoring the changes of coagulation-related indexes in emergency trauma patients. Methods A total of 319 cases of trauma patients admitted to our hospital from September 2020 to September 2023 were retrospectively analyzed, and the coagulation-related indexes of 0 h and 24 h after admission were observed. According to the MA results, they were divided into normal MA group(>50 mm) and reduced MA group(≤50 mm) to compare the hemoglobin(Hb), platelets count(Plt), activated partial thromboplastin time(APTT), prothrombin time(PT), fibrinogen(Fib), thrombin time(TT), D-dimer(D-D), coagulation reaction time(R), clot formation kinetics(Angle), 30 min clot dissolution rate(Ly30), MA, thrombine-antithrombin complex(TAT) and plasminase-α2 plasminase inhibitor complex(PIC). The correlation between MA and fibrinolysis indexes in 319 trauma patients was analyzed. According to whether tranexamic acid(TXA) was used, the reduced MA group was divided into a TXA group and a non-drug group. The differences in the change of the above coagulation-related indexes, mortality rate and changes in blood product dosage were compared between the two groups. Results Compared with the normal MA group, Hb, Plt, Fib, diastolic blood pressure and GCS scores decreased, while heart rate, ISS score and mortality increased significantly in the reduced MA group(P0.05). The mortality rate in the TXA group was reduced significantly(P

Background: von Willebrand factor (vWF) plays a crucial role in physiological hemostasis through platelet and subendothelial collagen adhesion. However, its role in shear‐induced platelet activation and functional alteration under non‐physiological conditions common to blood‐contacting medical devices (BCMDs) is not well investigated. Methods: Fresh healthy human blood was treated with an anti‐vWF antibody to block vWF–GPIbα interaction. Untreated blood was used as a control. They were exposed to three levels of non‐physiological shear stress (NPSS) (75, 125, and 175 Pa) through a shearing device with an exposure time of 0.5 s to mimic typical shear conditions in BCMDs. Flow cytometric assays were used to measure the expression levels of PAC‐1 and P‐Selectin and platelet aggregates for platelet activation and the expression levels of GPIbα, GPIIb/IIIa, and GPVI for receptor shedding. Collagen/ristocetin‐induced platelet aggregation capacity was characterized by aggregometry. Results: The levels of platelet activation and aggregates increased with increasing NPSS in the untreated blood. More receptors were lost with increasing NPSS, resulting in a decreased capacity of collagen/ristocetin‐induced platelet aggregation. In contrast, the increase in platelet activation and aggregates after exposure to NPSS, even at the highest level of NPSS, was significantly lower in treated blood. Nevertheless, there was no notable difference in receptor shedding, especially for GPIIb/IIIa and GPVI, between the two blood groups at the same level of NPSS. The block of vWF exacerbated the decreased capacity of collagen/ristocetin‐induced platelet aggregation. Conclusions: High NPSS activates platelets mainly by enhancing the vWF–GPIbα interaction. Platelet activation and receptor shedding induced by high NPSS likely occur through different pathways. [ABSTRACT FROM AUTHOR]

Schistosomiasis is a neglected tropical disease referring to the infection with blood parasitic trematodes of the genus Schistosoma. It impacts millions of people worldwide, primarily in low-to-middle-income countries. Patients infected with schistosomiasis often exhibit a distinct hematological profile, including anemia, eosinophilia, thrombocytopenia, and coagulopathy. Platelets, essential components of the hemostatic system, play a crucial role in the pathogenesis of schistosomiasis. Schistosomes secrete serine proteases and express ectoenzymes, such as calpain protease, alkaline phosphatase (SmAP), phosphodiesterase (SmNPP5), ATP diphosphohydrolase (SmATPDase1), serine protease Sk1, SmSP2, and Sm22.6, which can interfere with platelet normal functioning. This report provides comprehensive, up-to-date information on platelet abnormalities observed in patients with schistosomiasis, highlighting their importance in the disease progression and complications. It delves into the interactions between platelets and schistosomes, including the impact of platelet dysfunction on hemostasis and immune responses, immune-mediated platelet destruction, and the potential mechanisms by which schistosome tegumental ectoenzymes affect platelets. Furthermore, the report clarifies the relationship between platelet abnormalities and clinical manifestations such as thrombocytopenia, coagulation disorders, and the emergence of portal hypertension and gastrointestinal bleeding. Understanding the complex interplay between platelets and schistosomes is crucial for improving patient management and outcomes in schistosomiasis, particularly for those with platelet alterations. This knowledge contributes to improved diagnostic methods, innovative treatment strategies, and global efforts to control and eliminate schistosomiasis. [ABSTRACT FROM AUTHOR]

Background: Antithrombotic therapy, such as acetylsalicylic acid (ASA) and clopidogrel, may interfere with platelet aggregation in thrombotic strokes. Therefore, a platelet aggregation test is essential for monitoring therapy. A previous study observed a decrease in platelet aggregation using antithrombotics with a manual LTA analyzer. Further research is required to compare this with an automatic tool to determine whether both instruments have similar detection capabilities. Methods: PPP and PRP samples were collected from 30 thrombotic stroke outpatients and 30 healthy controls. Platelet aggregation tests were performed using ADP 5μM and Collagen 2μg/mL on both instruments, Chronolog® Model 490, and Sysmex® CS-2500. The tests were then analyzed using the Wilcoxon test for differences, the Spearman test for correlation, and the Bland-Altman analysis for agreement. Results: No differences were observed in MA values and numerical alignment between the two instruments for ADP and Collagen. If the MA result for the platelet aggregation test on Chrono-log® Model 490 was high, it was likewise high on Sysmex CS-2500 and vice versa. Although the values of LP and Vel differed, the numbers for ADP and Collagen in both instruments were consistent. Conclusion: The comparison between both instruments indicates good agreement. Automated LTA demonstrates the same suitability as manual LTA and can be applied in clinical routines to assess platelet aggregation function. Due to many variations in the pre-analytics stage that might affect the results, it is vital to standardize both the pre-analytics, analytics, and post-analytics stages to compare platelet aggregation tests on the two instruments. [ABSTRACT FROM AUTHOR]

Thrombocytopenia is a cardinal symptom of hantavirus-induced diseases including Puumala virus (PUUV)-induced hemorrhagic fever with renal syndrome (HFRS), which is associated with impaired platelet function, bleeding manifestations and augmented thrombotic risk. However, the underlying mechanisms causing thrombocytopenia and platelet hypo-responsiveness are unknown. Thus, we investigated the direct and indirect impact of PUUV on platelet production, function and degradation. Analysis of PUUV-HFRS patient blood revealed that platelet hypo-responsiveness in PUUV infection was cell-intrinsic and accompanied by reduced platelet-leukocyte aggregates (PLAs) and upregulation of monocyte tissue factor (TF), whereas platelet vasodilator-stimulated phosphoprotein (VASP) phosphorylation was comparable to healthy controls. Plasma CXCL4 levels followed platelet count dynamics throughout disease course. PUUV activated both neutrophils and monocytes in vitro , but platelet desialylation, degranulation and GPIIb/IIIa activation as well as PLA formation and endothelial adhesion under flow remained unaltered in the presence of PUUV. Further, MEG-01 megakaryocytes infected with PUUV displayed unaltered polyploidization, expression of surface receptors and platelet production. However, infection of endothelial cells with PUUV significantly increased platelet sequestration. Our data thus demonstrate that although platelet production, activation or degradation are not directly modulated, PUUV indirectly fosters thrombocytopenia by sequestration of platelets to infected endothelium. Upregulation of immunothrombotic processes in PUUV-HFRS may further contribute to platelet dysfunction and consumption. Given the pathophysiologic similarities of hantavirus infections, our findings thus provide important insights into the mechanisms underlying thrombocytopenia and highlight immune-mediated coagulopathy as potential therapeutic target. [Display omitted] • Thrombocytopenia in PUUV-HFRS is not associated with latent platelet activation. • Platelet-intrinsic hypo-responsiveness in PUUV infection is cAMP-independent. • Platelet production, activation or desialylation are not directly modulated by PUUV. • PUUV fosters thrombocytopenia via platelet sequestration to infected endothelium. • Immunothrombotic processes may contribute to platelet dysfunction and consumption. [ABSTRACT FROM AUTHOR]

Objectives: To determine platelet function and assess fibrinolysis in dogs following trauma using multiple electrical impedance aggregometry and a modified thromboelastographic (TEG) technique. To determine if the severity of trauma, as assessed by the Animal Trauma Triage (ATT) score and clinicopathological markers of shock, is associated with a greater degree of platelet dysfunction and fibrinolysis. Setting: University teaching hospital. Animals: Twenty client‐owned dogs with trauma (occurring <24 h prior to admission and blood sampling) and ATT score of >4 were prospectively recruited. A control group of 10 healthy dogs was included. Interventions: None. Measurements and Main Results: Platelet function was measured using multiple electrode platelet aggregometry (MEPA) utilizing arachidonic acid, ADP, and collagen agonists. Fibrinolysis was assessed in citrated whole blood with the addition of tissue plasminogen activator (tPA; 50 U/mL) using kaolin‐activated TEG. Conventional statistical analysis was performed to compare coagulation parameters between the groups and assess linear correlations. Median (interquartile range) ATT score was 5 (5–7), and 65% (n = 13) of dogs suffered polytrauma. Mean (± SD) time from trauma to blood sampling was 9 hours (± 6). Median (interquartile range) shock index and plasma lactate concentration were 1.1 (0.7–2.0, n = 16) and 2.9 mmol/L (0.9–16.0, n = 18), respectively. Four dogs did not survive to discharge (20%). There were no differences between the trauma and control group coagulation variables. A moderate negative correlation between ATT score and area under the curve for ADP was found (P = 0.043, r2 = −0.496). Conclusions: Preliminary evaluation of platelet function measured by MEPA, and fibrinolysis measured by tPA‐modified TEG, is not significantly different in this population of dogs with traumatic injury compared to healthy dogs. [ABSTRACT FROM AUTHOR]

The bleeding risk in immune thrombocytopenia (ITP) is related not only to low platelet count but also to the presence of platelet dysfunction. However, diagnosing a concomitant platelet dysfunction is challenging as most of the available platelet function assays (PFAs) require a platelet count of greater than 100,000/μL. Sonoclot coagulation and platelet function analyzer works on the principle of viscoelastometry, and results remain unaffected by the platelet counts. To assess the platelet function in adult acute ITP patients with the help of sonoclot coagulation and platelet function analyzer and correlate it with the risk of bleeding. Newly diagnosed acute ITP patients with a platelet count less than 20,000/μL were divided into two groups based on WHO bleeding grade: ITP non-bleeder (ITP-NB) group (WHO bleeding grade ≤1) and ITP bleeder (ITP-B) group (WHO bleeding grade ≥2). Platelet function was assessed by sonoclot in both groups. The patients without significant bleeding (ITP-NB) were followed up monthly for six months with the assessment of platelet function during each contact. Eighty patients (30 ITP-B and 50 ITP-NB) were prospectively included in this study. The median age of patients in the two groups was 37 years and 30 years, respectively. The female-to-male ratio was 4:1 and 1:1 in ITP-B and ITP-NB groups. The median platelet count in ITP-B and ITP-NB was 12000/μL (range 1000–19000/μL) and 8000/μL (range 1000–19000/μL), respectively. Mean platelet functions by sonoclot in both groups were lower than the normal cut-off (>1.6). However, the mean platelet function in the ITP-B group (0.2 + 0.17) was significantly lower than the ITP-NB group (1.2 ± 0.52) (p = 0.01). During the follow-up period of 6 months, patients in ITP-NB with a normal platelet function (>1.6) on sonoclot had lesser episodes (one episode) of clinically significant bleeding than patients with a low platelet function (4 episodes). Patients with acute severe thrombocytopenia and bleeding phenotype have a greater abnormality on platelet function by sonoclot than patients with non-bleeding phenotype. This information may help in taking therapeutic decisions in patients with acute ITP. [ABSTRACT FROM AUTHOR]

Abstract Background Platelet-type bleeding disorder 20 (BDPLT20), as known as SLFN14-related thrombocytopenia, is a rare inherited thrombocytopenia (IT). Previously, only 5 heterozygous missense mutations in the SLFN14 gene have been reported. Methods A comprehensive clinical and laboratory examination of a 17-year-old female patient with macrothrombocytopenia and severe mucocutaneous bleeding was performed. Examination was carried out using standardized questionnaires to assess bleeding, high-throughput sequencing (Next Generation Sequencing), optical and fluorescence microscopy, flow cytometry with activation and analysis of intracellular calcium signaling of platelets, light transmission aggregometry and thrombus growth in the flow chamber. Results Analysis of the patient’s genotype revealed a previously undescribed c.655 A > G (p.K219E) variant in the hotspot of the SLFN14 gene. Immunofluorescence and brightfield examination of platelets in the smear showed heterogeneity in cells size, including giant forms over 10 μm (normal size 1–5) in diameter, with vacuolization and diffuse distribution of β1-tubulin and CD63. Activated platelets showed impaired contraction and shedding/internalization of GPIb. GP IIb/IIIa clustering was increased at rest and attenuated upon activation. Intracellular signalling study revealed impaired calcium mobilization upon TRAP 35.97 nM (reference range 180 ± 44) and CRP-XL 10.08 nM (56 ± 30) stimulation. Aggregation with ADP, collagen, TRAP, arachidonic acid and epinephrine was impaired in light transmission aggregometry; agglutination with ristocetin persisted. In the flow chamber with a shear rate of 400 s-1 platelet adhesion to collagen and clot growth were impaired. Conclusion The revealed disorders of phenotype, cytoskeleton and intracellular signaling explain the nature of SLFN14 platelet dysfunction and the patient’s severe hemorrhagic syndrome.

Major cardiac surgery related blood loss is associated with increased postoperative morbidity and mortality. Platelet dysfunction is believed to contribute to post-cardiopulmonary bypass (CPB)-induced microvascular bleeding. We hypothesised that moderately hypothermic CPB induces platelet dysfunction and that supplemental fibrinogen can restore in vitro thrombus formation. Blood from 18 patients, undergoing first-time elective isolated aortic valve surgery was drawn before CPB, 30 min after initiation of CPB, and after CPB and protamine administration, respectively. Platelet aggregation was quantified by optical aggregometry, platelet activation by flow-cytometric detection of platelet surface expression of P-selectin, annexin V, and activated glycoprotein IIb/IIIa, thrombus formation under flow and effect of supplemental fibrinogen (4 mg ml−1) on in vitro thrombogenesis. Post-CPB adenosine–diphosphate and TRAP-6-induced aggregation decreased by 40% and 10% of pre-CPB levels, respectively (P <0.0001). Although CPB did not change glycoprotein IIb/IIIa receptor expression, it increased the percentage of unstimulated P-selectin (1.2% vs 7%, P <0.01) positive cells and annexin V mean fluorescence intensity (15.5 vs 17.2, P <0.05), but decreased percentage of stimulated P-selectin (52% vs 26%, P <0.01) positive cells and annexin V mean fluorescence intensity (508 vs 325, P <0.05). Thrombus area decreased from 6820 before CPB to 5230 after CPB (P <0.05, arbitrary units [a.u.]). Supplemental fibrinogen increased thrombus formation to 20 324 and 11 367 a.u. before CPB and after CPB, respectively (P <0.001), thereby restoring post-CPB thrombus area to levels comparable with or higher than pre-CPB baseline. Single valve surgery using moderately hypothermic CPB induces partial platelet dysfunction. Thrombus formation was restored in an experimental study design by ex vivo supplementation of fibrinogen. [ABSTRACT FROM AUTHOR]

Depression and macrovascular diseases are globally recognized as significant disorders that pose a substantial socioeconomic burden because of their associated disability and mortality. In addition, comorbidities between depression and macrovascular diseases have been widely reported in clinical settings. Patients afflicted with coronary artery disease, cerebrovascular disease or peripheral artery disease exhibit an elevated propensity for depressive symptoms. These symptoms, in turn, augment the risk of macrovascular diseases, thereby reflecting a bidirectional relationship. This review examines the physiological and pathological mechanisms behind comorbidity while also examining the intricate connection between depression and macrovascular diseases. The present mechanisms are significantly impacted by atypical activity in the hypothalamic-pituitary-adrenal axis. Elevated levels of cortisol and other hormones may disrupt normal endothelial cell function, resulting in vascular narrowing. At the same time, proinflammatory cytokines like interleukin-1 and C-reactive protein have been shown to disrupt the normal function of neurons and microglia by affecting blood-brain barrier permeability in the brain, exacerbating depressive symptoms. In addition, platelet hyperactivation or aggregation, endothelial dysfunction, and autonomic nervous system dysfunction are important comorbidity mechanisms. Collectively, these mechanisms provide a plausible physiological basis for the interplay between these two diseases. Interdisciplinary collaboration is crucial for future research aiming to reveal the pathogenesis of comorbidity and develop customised prevention and treatment strategies. [ABSTRACT FROM AUTHOR]

Rectus sheath hematoma (RSH) is an uncommon cause of acute abdominal pain that may mimic other intra-abdominal pathologies. It is caused by the rupture of the superior or inferior epigastric artery or vein in the rectus abdominis muscle. Clinical features include sudden-onset abdominal pain and a palpable mass, and common risk factors include anti-coagulants, platelet dysfunction, and cough. Workup includes a physical exam, complete blood count, coagulation profile, ultrasound, and computed tomography. While most cases are treated conservatively, uncontrolled hemorrhage may be lethal and requires prompt recognition. We discuss a case of RSH which developed in the setting of paroxysmal coughing and platelet dysfunction. The purpose is to highlight the diagnosis and treatment of RSH and emphasize the importance of its inclusion in the differential for acute abdominal pain. [ABSTRACT FROM AUTHOR]

Background: Platelet-type bleeding disorder 20 (BDPLT20), as known as SLFN14-related thrombocytopenia, is a rare inherited thrombocytopenia (IT). Previously, only 5 heterozygous missense mutations in the SLFN14 gene have been reported. Methods: A comprehensive clinical and laboratory examination of a 17-year-old female patient with macrothrombocytopenia and severe mucocutaneous bleeding was performed. Examination was carried out using standardized questionnaires to assess bleeding, high-throughput sequencing (Next Generation Sequencing), optical and fluorescence microscopy, flow cytometry with activation and analysis of intracellular calcium signaling of platelets, light transmission aggregometry and thrombus growth in the flow chamber. Results: Analysis of the patient's genotype revealed a previously undescribed c.655 A > G (p.K219E) variant in the hotspot of the SLFN14 gene. Immunofluorescence and brightfield examination of platelets in the smear showed heterogeneity in cells size, including giant forms over 10 μm (normal size 1–5) in diameter, with vacuolization and diffuse distribution of β1-tubulin and CD63. Activated platelets showed impaired contraction and shedding/internalization of GPIb. GP IIb/IIIa clustering was increased at rest and attenuated upon activation. Intracellular signalling study revealed impaired calcium mobilization upon TRAP 35.97 nM (reference range 180 ± 44) and CRP-XL 10.08 nM (56 ± 30) stimulation. Aggregation with ADP, collagen, TRAP, arachidonic acid and epinephrine was impaired in light transmission aggregometry; agglutination with ristocetin persisted. In the flow chamber with a shear rate of 400 s-1 platelet adhesion to collagen and clot growth were impaired. Conclusion: The revealed disorders of phenotype, cytoskeleton and intracellular signaling explain the nature of SLFN14 platelet dysfunction and the patient's severe hemorrhagic syndrome. [ABSTRACT FROM AUTHOR]

Qualitative platelet disorders remain rare and varied. We describe here 2 additional patients with giant platelets, thrombocytopenia, deficiency in alpha granules and the presence of membranous inclusions within the cytoplasm. Collectively known as Medich syndrome, we further elucidated structural and clinical features of this rare syndrome. Platelets obtained from 2 patients with macro-thrombocytopenia were evaluated by electron microscopy. Structural findings were correlated with clinical characteristics. The defining morphologic feature found in the platelets of these patients is the presence of long, tubular inclusions consisting of several layers of membrane wrapped around a core of cytoplasm. These inclusions may deform the discoid shape of the platelet. In addition, abnormal giant alpha granules are present. Clinically all patients in the current report and review of the literature had mucosal bleeding and were often misdiagnosed as having immune related thrombocytopenia. To date five cases of Medich giant platelet syndrome have been reported. The cases are unified by the ultrastructural findings of abnormal alpha granules and unusual cytoplasmic scrolls. All patients experienced mucosal bleeding, however many clinical, biologic and genetic characteristics of this rare disorder remain to be determined.

Abstract Background Autologous platelet-rich plasma (PRP) has been shown to alleviate the symptoms of patients suffering from knee osteoarthritis (KOA), but for certain patients with hematologic diseases with platelet dysfunction and patients receiving anti-platelet medications, autologous PRP is not an optimum solution. Allogeneic PRP has been proven to be safe and effective in the treatment of osteoarthritis, rotator cuff disease, refractory wounds and other medical fields. However, a well-designed and long-term follow-up prospective randomized controlled trial (RCT) to evaluate the effect of allogeneic PRP intra-articular injections for KOA combined with hematologic blood dyscrasias has not yet been performed. Methods/ design We will conduct an allogeneic PRP injection for KOA combined with hematologic blood dyscrasias with platelet dysfunction study: a prospective, randomized, double-blind, placebo-controlled trial. One hundred participants with KOA combined with hematologic blood dyscrasias with platelet dysfunction will be randomly allocated to receive either one allogeneic PRP injection or one saline injection into the knee joint. The primary outcome will be a 12-month change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score. Secondary outcomes will be the 36-Item Short-Form General Health Survey (SF-36) score, Lysholm score, overall knee pain score and MRI assessment at 1-, 3-, 6- and 12-month. Discussion The results of this study will help determine whether allogeneic PRP could be used as a non-surgical intervention to treat patients with knee OA combined with hematologic blood dyscrasias with platelet dysfunction. Trial registration Chinese Clinical Trials Registry reference: ChiCTR2100048624. Prospectively registered 11th of July 2021.

Rectus sheath hematoma (RSH) is an uncommon cause of acute abdominal pain that may mimic other intra-abdominal pathologies. It is caused by the rupture of the superior or inferior epigastric artery or vein in the rectus abdominis muscle. Clinical features include sudden-onset abdominal pain and a palpable mass, and common risk factors include anti-coagulants, platelet dysfunction, and cough. Workup includes a physical exam, complete blood count, coagulation profile, ultrasound, and computed tomography. While most cases are treated conservatively, uncontrolled hemorrhage may be lethal and requires prompt recognition. We discuss a case of RSH which developed in the setting of paroxysmal coughing and platelet dysfunction. The purpose is to highlight the diagnosis and treatment of RSH and emphasize the importance of its inclusion in the differential for acute abdominal pain.

Platelet dysfunction has been demonstrated after traumatic brain injury (TBI) regardless of the use of platelet inhibitors. The purpose of this study was to determine the efficacy of a platelet-mapping thromboelastography (PM-TEG) in predicting TBI patients who would benefit from platelet transfusion. We hypothesized that adenosine diphosphate (ADP) and arachadonic acid (AA) inhibition in patients with TBI is associated with increased mortality and can be corrected with platelet transfusion. This is a retrospective review of patients admitted to a level 1 trauma center from January 2016 through September 2017 with moderate to severe blunt TBI (msTBI), defined by an initial Glasgow Coma Scale (GCS) ?12 with intracranial hemorrhage. Patients received PM-TEG. Those with platelet dysfunction (ADP or AA inhibition ?60%) received one unit of platelets followed by repeat PM-TEG, until inhibition 55 years of age or with GCS

Immune thrombocytopenia (ITP) is an autoimmune disease which is characterized by antibody-mediated destruction of platelets by the reticuloendothelial system. The rate of ITP is 3.3 per 100,000 adults per year with a prevalence of 9.5 per 100,000 adults. Pregnancy does not increase the frequency or severity of ITP, but ITP can significantly affect pregnancy and cause bleeding in women. Pregnancy requires regular control of the number of platelets: monthly in the I and II trimesters, every 2 weeks – in the III trimester, and weekly control near the delivery date. Indications for treatment are determined by the pregnant woman condition, not the fetus, since it has not been proven that the treatment reduces the risks of thrombocytopenia in newborns with the development of cerebral hemorrhage. The drug of the first line of treatment of such pathology is prednisolone at a dose of 1 mg/kg orally once a day. An increase in the number of platelets is usually observed within 3-7 days, the maximum response is determined after 2-3 weeks. If necessary, the dose can be increased. When the required level of platelets is reached, the dose can be gradually reduced by 10-20 % to the minimum dose necessary to maintain the number of platelets at an acceptable level. Thrombocytopathy can be the cause of primary hemostasis disorders, even if the number of platelets in the blood is normal. For diagnosis, tests are carried out to detect the aggregation ability of platelets. In addition, flow cytometry can be used, which makes it possible to detect the defects of surface membrane receptors, as well as defects of the end point of secretion. ITP is a common cause of thrombocytopenia after viral infections. The onset of this pathology is more often detected in the second and third weeks after the onset of COVID-19. The treatment aim is to prevent the significant bleeding in patients with COVID-19. The article presents a clinical case of a pregnant woman with ITP and thrombocytopathy, whose pregnancy was complicated by COVID-19. The patient complained on bleeding gums, the appearance of hematomas on the skin. Medical treatment of the main disease included prednisolone, eltrombopag, intravenous human immunoglobulin, transfusion of platelet concentrate. At 34–35 weeks of pregnancy alive boy was born with a body weight of 2800 g, length of 49 cm, 7–8 points on the Apgar scale. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the effect of metformin in improving platelet dysfu nction in women with gestational diabetes mellitus (GDM). Patients and methods: A randomized controlled trial was conducted on pregnant women diagnosed with GDM. Singleton low-risk pregnancies meeting the inclusion criteria were randomly allocated at 27–31 weeks to receive metformin and placebo through the rest of pregnancy. Thirty-seven and 39 cases were recruited into the metformin group and the placebo group, respectively. MPVs, P-selectin, and 8-isoprostane levels were determined at the time of allocation and 6 weeks after treatment. Obstetric and neonatal outcomes were also assessed. Results: Most baseline characteristics of the two groups were comparable. The levels of P-selectin after 6 weeks of treatment were significantly higher in the metformin group (68.9 ± 14.4 vs 60.6 ± 11.3; P-value = 0.006), indicating more platelet activation. All of the obstetric and neonatal outcomes were comparable except that birth weight was significantly lower in the metformin group (3018 ± 364 g vs 3204 ± 393 g; P-value = 0.037). Conclusion: Metformin, in addition to diet and lifestyle modifications, doe s not improve or worsen oxidative stress and platelet dysfunction in women with GDM. Nevertheless, metformin significantly reduces fetal weight in women with GDM, theoretically preventing macrosomia.

Platelet dysfunction is one of the serious and common complications associated with pregnancy-induced hypertension (PIH). Nevertheless, the role of platelet dysfunction in the newborns of PIH mothers is unclear. This study aimed to study platelet problems in infants and women affected by PIH. A prospective cohort study was conducted on singleton pregnancies who delivered at a gestation age of 32 weeks or more. The women were divided into the PIH group and the normal control group. The blood tests for maternal and neonatal platelet evaluation such as platelet concentration, mean platelet volume (MPV), and clotting time were performed for comparisons between both groups. A total of 106 cases were recruited for the study (55 cases in the PIH group and 51 cases in the control group). Hematologic studies showed a significant increase in the incidence of thrombocytopenia and platelet dysfunction (increased MPV) in women affected with PIH when compared with those in the control group (p =.028 and p =.001). However, the platelet study in newborns was not significantly different between both groups (p =.680 and p =.265). This study supports the theory that endothelial cell damage and platelet aggregation as indicated by thrombocytopenia together with increased MPV levels in maternal affected with PIH. Importantly, this study provides new insight into that these problems in mothers with PIH do not occur in their neonatal vessels, as indicated by normal platelet counts and MPV levels. [ABSTRACT FROM AUTHOR]

Qualitative platelet disorders remain rare and varied. We describe here 2 additional patients with giant platelets, thrombocytopenia, deficiency in alpha granules and the presence of membranous inclusions within the cytoplasm. Collectively known as Medich syndrome, we further elucidated structural and clinical features of this rare syndrome. Platelets obtained from 2 patients with macrothrombocytopenia were evaluated by electron microscopy. Structural findings were correlated with clinical characteristics. The defining morphologic feature found in the platelets of these patients is the presence of long, tubular inclusions consisting of several layers of membrane wrapped around a core of cytoplasm. These inclusions may deform the discoid shape of the platelet. In addition, abnormal giant alpha granules are present. Clinically all patients in the current report and review of the literature had mucosal bleeding and were often misdiagnosed as having immune related thrombocytopenia. To date five cases of Medich giant platelet syndrome have been reported. The cases are unified by the ultrastructural findings of abnormal alpha granules and unusual cytoplasmic scrolls. All patients experienced mucosal bleeding, however many clinical, biologic and genetic characteristics of this rare disorder remain to be determined. [ABSTRACT FROM AUTHOR]

Non-physiological shear stress (NPSS) and thrombin have two distinct mechanisms for activating platelets. NPSS in mechanically assisted circulation (MAC) devices can cause platelet dysfunction, e.g., by shedding its key receptors. In addition, patients with heart failure have increased levels of thrombin generation, which may further affect the NPSS-induced platelet dysfunction, resulting in device-associated complications. This study aimed to assess the combined effect of NPSS and thrombin in platelet activation, expression of adhesion receptors on the platelet surface, and alterations of platelet aggregation. Fresh human blood from healthy donors was divided into two groups; one group was treated by adding 0.01 U/mL thrombin, and another group not treated with thrombin served as a control comparison. They were then pumped through a novel blood shearing device which produces similar shear stress conditions to those in the MAC devices. Three levels of NPSS (i.e., 75, 125, and 175 Pa) with a 1.0 s exposure time were selected for the shearing conditions. Expression of platelet activation markers (PAC-1, activated GPIIb/IIIa and CD62P, platelet surface P-selectin) were investigated along with the shedding of platelet receptors (GPIb, GPIIb/IIIa, and GPVI), generation of platelet microparticles, and Phosphatidylserine (PS)-positive platelets detected by flow cytometry. Platelet aggregation (induced by collagen/ristocetin) was measured by Lumi-aggregometry. Platelet receptors were shed after exposure to NPSS showing a positive correlation with the level of shear stress. The generation of platelet microparticles and PS-positive platelets also increased with greater NPSS. Elevated NPSS decreased the platelet aggregation capacity. Platelet activation level increased with greater NPSS. Being treated by thrombin can further exacerbate these characteristics under same level of NPSS, except that platelet activation level drastically dropped after the exposure to 175 Pa NPSS in the thrombin-treated blood. After being treated by thrombin, platelets became more susceptible to NPSS, resulting in more receptor shedding, platelet microparticles, and PS-positive platelets, thus limiting platelet aggregation capacity after exposure to NPSS. Platelet activation, in terms of PAC-1 and P-selectin, is an interim status competing between the expression and shedding of these makers/receptors. When platelets have reached a saturation level of activation, exposure to excessive NPSS can potentially impair activation. [ABSTRACT FROM AUTHOR]

Blood flow through left ventricular assist devices (LVAD) may induce activation and dysfunction of platelets. Dysfunctional platelets cause coagulation disturbances and form platelet-neutrophil conjugates (PNC), which contribute to inflammatory tissue damage. This prospective observational cohort study investigated patients, who underwent implantation of a LVAD (either HeartMate II (HM II) (n = 7) or HeartMate 3 (HM 3) (n = 6)) and as control patients undergoing coronary artery bypass grafting (CABG) and/or aortic valve replacement (AVR) (n = 10). We performed platelet and leukocyte flow cytometry, analysis of platelet activation markers, and platelet aggregometry. Platelet CD42b expression was reduced at baseline and perioperatively in HM II/3 compared to CABG/AVR patients. After surgery the platelet activation marker β-thromboglobulin and platelet microparticles increased in all groups while platelet aggregation decreased. Platelet aggregation was more significantly impaired in LVAD compared to CABG/AVR patients. PNC were higher in HM II compared to HM 3 patients. We conclude that LVAD implantation is associated with platelet dysfunction and proinflammatory platelet-leukocyte binding. These changes are less pronounced in patients treated with the newer generation LVAD HM 3. Future research should identify device-specific LVAD features, which are associated with the least amount of platelet activation to further improve LVAD therapy.

Heatstroke is a critical heat-related condition characterized by coagulopathy and multiple organ dysfunction. One of the most severe complications of heatstroke is disseminated intravascular coagulation. This condition manifests as excessive clot formation and bleeding that are primarily due to platelet depletion and dysfunction. Fibrinogen plays a crucial role in hemostasis because it links integrin αIIbβ3 on adjacent platelets, thereby promoting the platelet activation and aggregation necessary for clot formation. However, reduced fibrinogen levels may impair the formation of the initial platelet plug and increase the risk of bleeding. The current study explored the effect of fibrinogen on platelet dysfunction in a heatstroke model. Male Wistar rats were subjected to heat stress, and subsequent changes in hemodynamic, biochemical, and coagulation parameters were analyzed. Platelet viability, aggregation, adhesion, spreading and fibrin clot retraction were assessed. The rats with heatstroke exhibited a variety of clinical symptoms, including hypotension, tachycardia, multiple organ dysfunction, and coagulopathy. Platelet viability in the heatstroke group was comparable to that in the healthy control group. However, the heatstroke group exhibited significant reductions in plasma fibrinogen levels and platelet aggregation, adhesion, spreading, and fibrin clot retraction. Notably, fibrinogen supplementation markedly augmented the aggregation responses of platelets in the heatstroke group. The impairment of platelet adhesion, spreading, and fibrin clot retraction in the rats with heatstroke was partially ameliorated by fibrinogen supplementation. An early use of fibrinogen replacement may serve as a therapeutic intervention to alleviate platelet hyporeactivity and prevent the complications in patients with heatstroke. [Display omitted] • The rats with heatstroke exhibited significant reductions in plasma fibrinogen levels and platelet functions. • Fibrinogen improved the impairment of platelet aggregation, adhesion, spreading, and clot retraction in heatstroke rats. • Fibrinogen supplementation is a promising therapeutic approach to managing platelet hyporeactivity in heatstroke patients. [ABSTRACT FROM AUTHOR]

Non-surgical bleeding (NSB) is one of the major clinical complications in patients under continuous-flow left ventricular assist device (LVAD) support. The increased shear stress leads to an altered platelet receptor composition. Whether these changes increase the risk for NSB is unclear. Thus, we compared the platelet receptor composition of patients with (bleeder group, n = 18) and without NSB (non-bleeder group, n = 18) prior to LVAD implantation. Blood samples were obtained prior to LVAD implantation and after bleeding complications in the post-implant period. Platelet receptor expression of GPIbα, GPIIb/IIIa, P-selectin and CD63 as well as intra-platelet oxidative stress levels were quantified by flow cytometry. Bleeders and non-bleeders were comparable regarding clinical characteristics, von Willebrand factor diagnostics and the aggregation capacity before and after LVAD implantation (p > 0.05). LVAD patients in the bleeder group suffered from gastrointestinal bleeding (33%; n = 6), epistaxis (22%; n = 4), hematuria or hematoma (17%; n = 3, respectively) and cerebral bleeding (11%; n = 2). Prior to LVAD implantation, a restricted surface expression of the platelet receptors P-selectin and GPIIb/IIIa was observed in the bleeder group (P-selectin: 7.2 ± 2.6%; GPIIb/IIIa: 26,900 ± 13,608 U) compared to non-bleeders (P-selectin: 12.4 ± 8.1%, p = 0.02; GPIIb/IIIa: 36,259 ± 9914 U; p = 0.02). We hypothesized that the reduced platelet receptor expression of P-selectin and GPIIb/IIIa prior to LVAD implantation may be linked to LVAD-related NSB. [ABSTRACT FROM AUTHOR]

Trauma is a prevalent cause of coagulopathy, with traumatic brain injury (TBI) accompanied by coagulation disorders particularly linked to adverse outcomes. TBI is distinguished by minimal bleeding volume and unique injury sites, which precipitate complex coagulation disturbances. Historically, research into trauma-induced coagulopathy has primarily concentrated on the molecular biology and pathophysiology of endogenous anticoagulation and inflammation. Nonetheless, recognizing that cells are the fundamental units of structure and function in all living organisms, the present review aimed to distill our understanding of coagulopathy post-TBI by elucidating the intricate cellular mechanisms involving endothelial cells, neutrophils and platelets. Additionally, this study evaluates the strengths and weaknesses of various diagnostic tools and discusses the characteristics of pharmacological treatments and potential therapies for patients with TBI and coagulation disorders. The aim of this review is to amalgamate recent updates in mechanistic research and innovative diagnostic and therapeutic methodologies, thereby fostering the progression of precision medicine within this specialized domain., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Hou et al.)