Cause Of Thrombocytopenia Research Articles

Identification of subphenotypes in critically ill thrombocytopenic patients with different responses to therapeutic interventions: a retrospective study.

The causes of thrombocytopenia (TP) in critically ill patients are numerous and heterogeneous. Currently, subphenotype identification is a popular approach to address this problem. Therefore, this study aimed to identify subphenotypes that respond differently to therapeutic interventions in patients with TP using routine clinical data and to improve individualized management of TP. This retrospective study included patients with TP admitted to the intensive care unit (ICU) of Dongyang People's Hospital during 2010-2020. Subphenotypes were identified using latent profile analysis of 15 clinical variables. The Kaplan-Meier method was used to assess the risk of 30-day mortality for different subphenotypes. Multifactorial Cox regression analysis was used to analyze the relationship between therapeutic interventions and in-hospital mortality for different subphenotypes. This study included a total of 1,666 participants. Four subphenotypes were identified by latent profile analysis, with subphenotype 1 being the most abundant and having a low mortality rate. Subphenotype 2 was characterized by respiratory dysfunction, subphenotype 3 by renal insufficiency, and subphenotype 4 by shock-like features. Kaplan-Meier analysis revealed that the four subphenotypes had different in-30-day mortality rates. The multivariate Cox regression analysis indicated a significant interaction between platelet transfusion and subphenotype, with more platelet transfusion associated with a decreased risk of in-hospital mortality in subphenotype 3 [hazard ratio (HR): 0.66, 95% confidence interval (CI): 0.46-0.94]. In addition, there was a significant interaction between fluid intake and subphenotype, with a higher fluid intake being associated with a decreased risk of in-hospital mortality for subphenotype 3 (HR: 0.94, 95% CI: 0.89-0.99 per 1 l increase in fluid intake) and an increased risk of in-hospital mortality for high fluid intake in subphenotypes 1 (HR: 1.10, 95% CI: 1.03-1.18 per 1 l increase in fluid intake) and 2 (HR: 1.19, 95% CI: 1.08-1.32 per 1 l increase in fluid intake). Four subphenotypes of TP in critically ill patients with different clinical characteristics and outcomes and differential responses to therapeutic interventions were identified using routine clinical data. These findings can help improve the identification of different subphenotypes in patients with TP for better individualized treatment of patients in the ICU.

Adjudicating the Diagnosis of Immune Thrombocytopenia in a Clinical Research Study

Background: Establishing the diagnosis of immune thrombocytopenia (ITP) is challenging in clinical practice and research settings even for experienced hematologists because it is a diagnosis of exclusion. Methods: We developed criteria to adjudicate the diagnosis of ITP using patients enrolled in the McMaster ITP Registry. At each patient visit, the cause of the thrombocytopenia was determined by the treating physician according to published criteria using all available information. We adjudicated the cause of the thrombocytopenia for any patient whose diagnosis was uncertain, if the diagnosis changed from one follow-up visit to another, or if the thrombocytopenia occurred in the context of pregnancy. Adjudication was done independently by one of the principal investigators, an external hematologist and a research associate using predefined criteria. Results: The etiology of the thrombocytopenia was adjudicated for 130 patients (n= 195 clinic visits). Reasons for adjudication were: a change in diagnosis from one visit to the next (n= 77; 59.2%), no clear cause of the thrombocytopenia was identified (n=46; 35.4%), and pregnancy-related thrombocytopenia (n=7; 5.4%). After adjudication, the most common changes in diagnosis were from primary ITP to secondary ITP (n=10), from “unknown” diagnosis to either primary ITP (n=15) or non-immune thrombocytopenia (n=10), or a change in the cause of non-immune thrombocytopenia (n=10). The diagnosis did not change for 38 patients (29.7%) after adjudication. Conclusions: Adjudication led to a more accurate diagnosis for 92 of 130 (70.8%) patients enrolled in the registry who presented with thrombocytopenia. This process can improve the clinical diagnosis of ITP.

Immune Thrombocytopenia Relapse in Patients Who Received mRNA COVID-19 Vaccines.

Immune thrombocytopenia (ITP) is a blood disorder in which antibodies coating platelets cause platelet destruction in the spleen with a resultant low platelet count and an increased tendency for bleeding. Coronavirus disease 2019 (COVID-19) is an illness caused by SARS-CoV-2. Though pneumonia and respiratory failure are major causes of morbidity and mortality, multisystemic complications were identified, including hematological ones. Several ITP relapse cases post-mRNA SARS-CoV-2 vaccines have been reported, and different pathophysiological theories have been proposed. The objective of this study is to identify the causal relationship between mRNA COVID-19 vaccines and ITP relapse, to highlight the longer-term effect of these vaccines on the platelet count more than 6 months after receiving the vaccine, and to identify if there is a statistical difference between Comirnaty and Spikevax vaccines on ITP relapse rate. In this retrospective study, 67 patients with known ITP were followed before and after receiving the mRNA COVID-19 vaccine. The follow-up parameters included platelet counts when available and bleeding symptoms. All patients were adults over 18 years old, with no other identified causes of thrombocytopenia. Forty-seven patients received the Comirnaty vaccine, and 20 patients received the Spikevax vaccine. Data analysis showed 6% ITP relapse in the first 3 months, and a 10% relapse rate 3-6 months after receiving one of the mRNA COVID-19 vaccines, with no statically significant difference between the two vaccines. mRNA COVID-19 vaccines increase the risk of ITP relapse and can lead to a prolonged reduction in platelet count in a proportion of ITP patients, with no statistically significant difference between Comirnaty and Spikevax vaccines.

Thrombocytopenia and Retina

Platelets play a role in blood coagulation and wound healing. Thrombocytopenia is defined as a platelet count of less than 150000/mm3 in the peripheral blood. The most common cause of thrombocytopenia is increased destruction. Ocular involvement is rare in thrombocytopenia, and bleeding is the most common complication. The increased tendency to thrombosis observed in some types of thrombocytopenia causes occlusion in retinal arterioles, and this results in retinal ischemia. Combined systemic and ocular interventions are used in the treatment.

Recent Advances in SARS-CoV-2-Induced Immune Thrombocytopenia --Review

SARS-CoV-2-induced immune thrombocytopenia (SARS-CoV-2-induced ITP) is an autoimmune disease secondary to virus infections. Its diagnosis is often based on exclusion of other possible causes of thrombocytopenia in COVID-19 patients. Common laboratory examinations include coagulation function, thrombopoietin and drug-dependent antibodies. Since both bleeding and thrombosis risks are seen in SARS-CoV-2-induced ITP patients, individual remedy is essential for the treatment of this disease. Because thrombopoietin receptor agonist(TPO-RA) has the side effect of accelerating thrombosis and may aggravate the pulmonary embolism symptoms of patients, it should be used for refractory SARS-CoV-2-induced ITP patients only. This review briefly summarizes the recent research progress in the pathogenesis, diagnosis and treatment of SARS-CoV-2-induced ITP.

The Cause and Effect of Immune Thrombocytopenia (ITP) on Individuals

Immune thrombocytopenia is a rare blood disorder in which an individual has a decreased level of platelets due to the immune system destroying the blood-clotting platelets. Platelets function in the body to help clot the blood, but in people with ITP, the body produces antibodies that disrupt and attack the creation, leading to lower levels. The average platelet count ranges from 150,000-400,000 per microliter of blood, but in individuals with ITP, the platelet count is less than 100,000 [1]. This significant decrease in platelet count can cause easy bruising, bleeding, and fatigue, among various symptoms that can disrupt an individual's life. The current diagnosis of ITP is centered on presumptions and excludes other causes of thrombocytopenia due to a variety of acquired and inherited that can present similar symptoms. In some cases, ITP may not cause symptoms, and for most children and adults, ITP is not severe. Acute ITP will typically go away on its own without the need for extensive therapy. In individuals with more advanced cases, or chronic ITP, one may receive a wide range of treatments. The stage of the disorder, current medical history, and genetics all have significant roles in determining the treatment an individual will receive.

A rare combination of immune thrombocytopenia and disaggregation thrombocytopathy: course and termination of pregnancy complicated by COVID-19 (Clinical case)

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.

DIAGNOSTIC ROLE OF PLATELET INDICES IN PATIENTS WITH THROMBOCYTOPENIA

Introduction: Thrombocytopenia is the most common cause of abnormal bleeding and can result from Hyper destruction of platelets, Hypoproduction of platelets and Abnormal platelet pooling. The aim of this study was to evaluate role of platelet indices (MPV, PDW, PCT) in diagnosing various causes of thrombocytopenia. In this observational analytic study 600 st Methodology: udy samples were divided into two groups: 300 cases diagnosed as thrombocytopenia (1.5 lakhs /microliter) and 300 healthy control. Cases of thrombocytopenia were further classied in 3 categories depending upon the predominant mechanism of thrombocytopenia. Statistical Analysis: Mean and SD of platelet count, mean platelet volume (MPV), platelet distribution width (PDW) and plateletcrit (PCT) in each group was calculated and compared among groups using unpaired T- test. Out of 300 cases of Thrombocytopenia, Group A constituted 224 cas Results: es (75%) due to hyper destruction of platelets, Group B constituted 72 cases (24%) due to hypoproduction of platelets and Group C constituted 4 cases (1%) of Thrombocytopenia due to abnormal pooling of platelets. On comparing mean MPV and PDW values among groups, the MPV and PDW of hyper destructive thrombocytopenia was found to be higher than mean MPV and PDW of hypo productive thrombocytopenia as well as control group. The mean PCT of hyper destructive group was higher than that of hypo productive group. Combined interpretati Conclusion: on of platelet count and platelet indices are of signicant discriminating value in differentiating various causes of thrombocytopenia thus their standardized measures can signicantly increase its utility in diagnosis and understanding mechanism of various clinical condition

Novel Biomarkers for Diagnosis and Monitoring of Immune Thrombocytopenia

Lower-than-normal platelet counts are a hallmark of the acquired autoimmune illness known as immune thrombocytopenia, which can affect both adults and children. Immune thrombocytopenia patients' care has evolved significantly in recent years, but the disease's diagnosis has not, and it is still only clinically achievable with the elimination of other causes of thrombocytopenia. The lack of a valid biomarker or gold-standard diagnostic test, despite ongoing efforts to find one, adds to the high rate of disease misdiagnosis. However, in recent years, several studies have helped to elucidate a number of features of the disease's etiology, highlighting how the platelet loss is not only caused by an increase in peripheral platelet destruction but also involves a number of humoral and cellular immune system effectors. This made it possible to identify the role of immune-activating substances such cytokines and chemokines, complement, non-coding genetic material, the microbiome, and gene mutations. Furthermore, platelet and megakaryocyte immaturity indices have been emphasized as new disease markers, and prognostic signs and responses to particular types of therapy have been suggested. Our review's goal was to compile information from the literature on novel immune thrombocytopenia biomarkers, markers that will help us improve the management of these patients.

Concurrence of immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura: a case report and review of the literature

BackgroundImmune thrombocytopenic purpura and thrombotic thrombocytopenic purpura are both causes of thrombocytopenia. Recognizing thrombotic thrombocytopenic purpura is crucial for subsequent treatment and prognosis. In clinical practice, corticosteroids and rituximab can be used to treat both immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura; plasma exchange therapy is the first-line treatment in thrombotic thrombocytopenic purpura, while corticosteroids are strongly recommended as first-line treatment in immune thrombocytopenic purpura. The differential diagnosis of immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura is essential in clinical practice. However, case reports have suggested that immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura can occur concurrently.Case presentationWe report the case of a 32-year-old Asian female without previous disease who presented with pancytopenia, concurrent with immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura. The morphology of the megakaryocytes in the bone marrow indicated immune-mediated thrombocytopenia. The patient received glucocorticoid treatment, and her platelet count increased; however, schistocytes remained high during the course of the therapy. Further investigations revealed ADAMTS13 activity deficiency and positive ADAMTS13 antibodies. The high titer of antinuclear antibody and positive anti-U1-ribonucleoprotein/Smith antibody indicated a potential autoimmune disease. However, the patient did not fulfill the current criteria for systemic lupus erythematosus or mixed connective tissue disease. The patient responded well to plasma exchange therapy, and her platelet count remained normal on further follow-up.ConclusionsConcurrence of immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura is rare, but clinicians should be aware of this entity to ensure prompt medical intervention. Most of the reported cases involve young women. Human immunodeficiency virus infection, pregnancy, and autoimmune disease are the most common underlying conditions.

A case of Tocilizumab-induced thrombocytopenia in steroid-resistant Graves orbitopathy

Abstract Introduction Graves’ orbitopathy (GO) is the main extrathyroidal manifestation of Graves’ disease (GD). It is more common in women, but men have more severe evolution of the disease. GO appears in 25–70% of patients with GD and can have a severe evolution in 5% cases and even lead to sight loss. In mild forms local treatment is often sufficient to alleviate eye symptoms. However, in moderate-to-severe cases systemic glucocorticoids are used, combined or not with immunosuppressive drugs. In moderate-to-severe glucocorticoid-refractory cases, conventional and biological immunosuppressive drugs have been used, among which is treatment with Tocilizumab (TCZ) – a monoclonal antibody targeting the interleukin-6 receptor, involved in GO's pathogenesis. Clinical Case A 49 years old former smoking Caucasian man was admitted to the endocrinology unit with asymmetrical bilateral exophthalmos, spontaneous and movement induced retrobulbar pain, hyperlacrimation. He has been diagnosed with Graves disease 9 months prior to the admission to our clinic. At that time the patient was treated with antithyroid drugs and oral prednisolone. The clinical activity score – CAS 7/7 points confirmed an active form of GO. Laboratory findings revealed a suppressed TSH 0.01 UI/ml, increased freeT4 40,1 pmol/l, positive TR-Ab (30,04 IU/L). Treatment with high-dose regimen of i.v. methylprednisolone (Mt), cumulative dose 5.75 g in 12 weeks was applied. The patient was soon thereafter admitted repeatedly for evaluation: a non-response to Mt has been established, occurrence of diplopia, convergent strabismus, therefore a second-line treatment with tocilizumab (TCZ) was considered. His blood platelet count before TCZ was 158×10*9. The patient received the first 8 mg/kg dose of i.v. TCZ and showed an improvement in the CAS score (5/7 points), however 1 month later, the platelet count had decreased to 48×10*3 and further treatment with TCZ has been postponed until thrombocyte count increases above 100×10*9. His oral medicines were thiamazole and levothyroxine. Other causes of thrombocytopenia (HIV, Hepatitis C, Ebstein-Barr virus, Helicobacter pylori, liver disease) have been excluded. 7 weeks later thrombocyte count increased spontaneously to 102×10*3 and TCZ treatment has been resumed. Discussion. The mechanism of thrombocytopenia induced by TCZ is dependent on its effect on IL-6 receptor, which stimulates thrombopoiesis through thrombopoietin induction. Clinical studies prove the effectiveness of TCZ in the treatment of GO, but side effects limit its use. Older age and low platelet count before TCZ treatment were associated with the development of thrombocytopenia after treatment. Conclusion Thrombocytopenia induced by tocilizumab is tolerable. However, in patients with known risk factors, close monitoring of platelet counts is recommended. An individual approach is appropriate, considering the high cost of the drug, side effects and comorbidities.

Apoptosis is one cause of thrombocytopenia in patients with high-altitude polycythemia

High-altitude polycythemia (HAPC) can occur in individuals who are intolerant to high-altitude hypoxia. In patients with HAPC, erythrocytosis is often accompanied by a decrease in platelet count. Chronic hypoxia can increase the incidence of arteriovenous thrombosis and the risk of bleeding during antithrombotic treatment due to thrombocytopenia; therefore, understanding the cause of thrombocytopenia can reduce the risk of treatment-related bleeding. In this study, we examined platelet production and apoptosis to understand the cause of thrombocytopenia in patients with HAPC. The classification of myeloid-derived megakaryocytes (MKs) in HAPC patients was mainly granular MKs rather than mature MKs, suggesting impaired differentiation and maturation. However, the total number of MKs and newly generated reticulated platelets in the peripheral blood increased, indicating sufficient platelet generation in HAPC thrombocytopenia. Increased platelet apoptosis may be one of the causes of thrombocytopenia. Platelet activation and GP1bα pathway activation induced by thrombin and von Willebrand factor can lead to platelet apoptosis. Platelet production was not reduced in patients with HAPC, whereas platelet apoptosis was associated with thrombocytopenia. These findings provide a rationale for considering the bleeding risk in HAPC patient while treating thrombotic diseases.

Recent progress in immune thrombocytopenia pathophysiology and treatment

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by increased platelet destruction and impaired platelet production from bone marrow megakaryocytes. The details of different platelet destruction mechanisms resulting from differences in autoantibodies and autoantibody-independent direct platelet destruction remain unclear although antiplatelet autoantibodies directed against platelet glycoproteins, such as GPIIb/IIIa and GPIb, play a central role in ITP pathogenesis. ITP is diagnosed by excluding other causes of thrombocytopenia due to the lack of standard tests or biomarkers for its confirmation. Plasma thrombopoietin level measurement and reticulated platelet ratio are useful in distinguishing the cause of thrombocytopenia and will be included in the new "Diagnostic reference guide of adult immune thrombocytopenia." Currently, the treatment of refractory chronic ITP is mainly based on thrombopoietin receptor agonists, but ITP drugs with novel mechanisms of action are actively developed. New therapeutic agents are expected to be selected based on an accurate diagnosis and tailored to the pathophysiology of each case in ITP treatment.

Immature Platelet Fraction as a Predictor of Recovery of Platelets in Febrile Thrombocytopenia Patients

Abstract Introduction: Infection is the most common cause of thrombocytopenia. Thrombocytopenia is a common hematological abnormality in infections such as viral (dengue), malaria, rickettsial infections, and leptospirosis which demands platelet transfusion in many severe cases. Although platelet transfusion is lifesaving, it has its own hazards. Hence, we used new parameters such as immature platelet fraction (IPF), which is a measure of reticulated platelets that reflects the rate of thrombopoiesis. This study was performed to assess the role of IPF in predicting platelet recovery in febrile thrombocytopenia patients. Materials and Methods: Blood samples from 50 patients were collected for IPF on day 2 of admission with 5 days of platelet count (day 1 through day 5 of admission). IPF is analyzed by Sysmex XE-2100 hematology analyzer in the platelet channel with fluorescent dye and carefully designed gating system and counted with a special software IPF master 7. IPF values against platelet count were assessed separately from day 1 to day 5. Results: The reference intervals of IPF >8% and IPF <8% were assessed against platelet count. An increase in IPF favored an increase in platelet count on day 4 and day 5. It was found that IPF has a strong correlation with the recovery of platelet counts. In patients with febrile thrombocytopenia, 82.4% of patients showed recovery within 24 h after attaining the peak IPF. One hundred percent of patients showed recovery within 24–48 h of the rise of the IPF. Conclusion: A rapid and inexpensive automated measurement of IPF can be integrated as a standard parameter to evaluate the thrombopoietic state of the bone marrow. From the study, we concluded that IPF is an important predictor of increase in platelet count. Increase in IPF >8% suggests that platelet count will be increased in the next 48 h indicating that further platelet transfusion will not be required.

Older Adults and Immune Thrombocytopenia: Considerations for the Clinician

Many epidemiological studies have shown that the incidence of immune thrombocytopenia (ITP) increases after age 60 years and peaks in patients over age 80 years. Therefore, ITP is a concern for physicians taking care of older patients, especially regarding its diagnosis and management. The diagnostic work-up should exclude other causes of thrombocytopenia and secondary ITP, including myelodysplastic syndrome and drug-induced ITP. The treatment decision is influenced by an increased risk of bleeding, infectious diseases and thrombosis in this population and should take into account comorbidities and concomitant medications such as anticoagulant drugs. First-line treatment is based on short corticosteroids courses and intravenous immunoglobulin, which should be reserved for patients with more severe bleeding complications, with their higher risk of toxic effects as compared with younger patients. Second-line treatment should be tailored to the patient's history, comorbidities and preferences. Preferred second-line treatments are thrombopoietin receptor agonists for most groups and guidelines given their good efficacy/tolerance ratio, but the thrombotic risk is increased in older people. Other second-line options that can be good alternatives depending on the clinical context include rituximab, dapsone, fostamatinib or immunosuppressive drugs. Splenectomy is less often performed but remains an option for fit patients with chronic refractory disease. Emerging treatments such as Syk or Bruton tyrosine kinase inhibitors and FcRn antagonists are becoming available for ITP and may modify the treatment algorithm in the near future. The aim of this review is to describe the particularities of the diagnosis and treatment of ITP in older people, including the response and tolerance to the currently available drugs. We also discuss some situations related to co-morbidities that can frequently lead to adapt the management strategy in older patients.

A machine-learning model for reducing misdiagnosis in heparin-induced thrombocytopenia: A prospective, multicenter, observational study.

Diagnosing heparin-induced thrombocytopenia (HIT) at the bedside remains challenging, exposing a significant number of patients at risk of delayed diagnosis or overtreatment. We hypothesized that machine-learning algorithms could be utilized to develop a more accurate and user-friendly diagnostic tool that integrates diverse clinical and laboratory information and accounts for complex interactions. We conducted a prospective cohort study including 1393 patients with suspected HIT between 2018 and 2021 from 10 study centers. Detailed clinical information and laboratory data were collected, and various immunoassays were conducted. The washed platelet heparin-induced platelet activation assay (HIPA) served as the reference standard. HIPA diagnosed HIT in 119 patients (prevalence 8.5%). The feature selection process in the training dataset (75% of patients) yielded the following predictor variables: (1) immunoassay test result, (2) platelet nadir, (3) unfractionated heparin use, (4) CRP, (5) timing of thrombocytopenia, and (6) other causes of thrombocytopenia. The best performing models were a support vector machine in case of the chemiluminescent immunoassay (CLIA) and the ELISA, as well as a gradient boosting machine in particle-gel immunoassay (PaGIA). In the validation dataset (25% of patients), the AUROC of all models was 0.99 (95% CI: 0.97, 1.00). Compared to the currently recommended diagnostic algorithm (4Ts score, immunoassay), the numbers of false-negative patients were reduced from 12 to 6 (-50.0%; ELISA), 9 to 3 (-66.7%, PaGIA) and 14 to 5 (-64.3%; CLIA). The numbers of false-positive individuals were reduced from 87 to 61 (-29.8%; ELISA), 200 to 63 (-68.5%; PaGIA) and increased from 50 to 63 (+29.0%) for the CLIA. Our user-friendly machine-learning algorithm for the diagnosis of HIT (https://toradi-hit.org) was substantially more accurate than the currently recommended diagnostic algorithm. It has the potential to reduce delayed diagnosis and overtreatment in clinical practice. Future studies shall validate this model in wider settings. Swiss National Science Foundation (SNSF), and International Society on Thrombosis and Haemostasis (ISTH).

Primary immune thrombocytopenia and cytomegalovirus infection About a case

Primary Immune Thrombocytopenia (ITP) is an acquired coagulation disease characterized by a decrease in platelets below 100 x 109/L in the absence of other causes of thrombocytopenia and that may be preceded by viral processes or vaccination. A 16-year-old male adolescent who presented a febrile syndrome was diagnosed as part of the studies as an infection by cytomegalovirus, later he began to present purpuric hemorrhagic manifestations on the skin and mucous membranes, for which a medulogram was performed and the diagnosis of Primary ITP was made. Conclusions: an adolescent who developed a TIP after cytomegalovirus infection, requiring treatment with steroids and valganciclovir for its management.

Incidence and severity of thrombocytopenia associated with use of intravascular microaxial ventricular assist devices for treatment of cardiogenic shock.

The use of temporary mechanical circulatory support (MCS) for patients with refractory cardiogenic shock has increased over the past decade. Impella devices (intravascular microaxial ventricular assist devices [VADs]) have become common MCS options but reportedly cause thrombocytopenia. Limited published data regarding the incidence or severity of microaxial VAD-associated thrombocytopenia exists. The goal of this study was to determine the incidence, timing, and severity of thrombocytopenia in a microaxial VAD population. A retrospective multicenter review of electronic medical records identified all patients implanted with microaxial VAD at three US academic teaching hospitals between June 2015 and August 2017. Patients were excluded for short-term procedural microaxial VAD use during percutaneous coronary intervention. Sixty-four patients underwent microaxial VAD insertion (95% for left-sided support) during the observed time period. Support was in place for a median duration of 5.2 (interquartile range [IQR]: 2.4-10.0) days. Within 7 days postinsertion, 98.5% of patients developed thrombocytopenia (platelet count <150,000/μl) and 81.3% of patients experienced a>50% platelet decrease. Average platelet count nadir was 68,200/μl or 63.9% from baseline occurring on median day 3.8 (IQR: 2.4-5.4). Twenty-four patients (38.1%) were tested for heparin-induced thrombocytopeniaby the heparin-dependent antibody (HDA) test. All HDAs were either negative or had serotonin release assay negative confirmation. Postdevice removal, platelet counts returned to baseline or >150,000/μl in 63% of patients by Day 5. Microaxial VAD-associatedthrombocytopenia is common. Practitioners should consider this when evaluating supported patients for other causes of thrombocytopenia. Platelet counts return to preimplantation levels within days of device removal.

Thrombotic Thrombocytopenic Purpura in a Parturient Leading to Life-Threatening Thrombocytopenia and Neonatal Demise—A Case Report

Abstract Thrombocytopenia is common (up to 12%) in pregnancy; thrombotic thrombocytopenia is a rare cause of thrombocytopenia; however, it is immediately life-threatening to both mother and fetus and requires immediate intervention. This is compounded by the need to act on a presumptive diagnosis with high level of suspicion given the relatively long laboratory confirmation time. A 31-year-old gravida 3, para 1 parturient at 26 weeks of gestation presented to outside hospital with recent onset of easy bruising and blurry vision. A blood count was drawn and showed a platelet count of 19,000/μL. She was transferred to our institution for management where an initial diagnosis of preeclampsia with severe features was made based on thrombocytopenia and fetal growth restriction (&lt;1%). Platelet count nadired at 14,000/μL and a blood smear showed schistocytes, suggesting microangiopathic hemolysis, prompting discussion of urgent cesarean delivery and anesthesia consult. An urgent hematology consult led to presumptively diagnosing thrombotic thrombocytopenic purpura and cesarean delivery was deferred after discussion with the patient and team. Plasma exchange and steroid therapy were started promptly, and her platelet count improved within 12 hours. Unfortunately, the patient experienced neonatal demise. Undetectable ADAMTS13 levels confirmed diagnosis of thrombotic thrombocytopenia. She was transitioned to rituximab, platelets recovered to baseline, and she continues to do well. Thrombotic thrombocytopenia is a rare, life-threatening cause of thrombocytopenia in pregnancy. Despite grim fetal prognosis, especially in early pregnancy, low threshold of suspicion, early anesthesia involvement, and multidisciplinary approach can facilitate diagnosis and timely intervention. In our case, it was likely lifesaving.

Predicting Platelet Age Using Artificial Intelligence Techniques

Background: Platelets are small, enucleated cells with their primary physiological role to repair vascular damage (hemostasis) and initiate thrombus formation in response to vascular injury. Low platelet count (thrombocytopenia) is associated with increased bleeding risk and is caused by decreased platelet production and/or increased platelet clearance. Platelet transfusion is a routinely used lifesaving procedure to control or prevent bleeding in patients with thrombocytopenia or platelet dysfunction. During storage platelet function deteriorates significantly over time and regulation of platelet granular content is essential in maintaining a healthy platelet function. Currently no in vitro tests are available to predict platelet age, which may be used to diagnose the underlying cause of thrombocytopenia, or to determine storage time of platelet concentrates (PC). Using confocal and super-resolution microscopy we could quantify loss of platelet granule content during aging. In this study we used Artificial intelligence techniques (AIT) to derive exact platelet age from imaging data. Aim: To develop AIT-based algorithms that can determine platelet age from images of platelets stored in plasma-rich-plasma (PRP) and in platelets concentrates (PC) measured by confocal microscopy. Methods: Platelets were stored in PRP for 8 hours at room temperature. Platelets were isolated and stained with antibodies for alpha-tubulin, von Willebrand Factor (VWF), SPARC or alpha-tubulin and imaged at T=0, 4 and 8 hours using confocal microscopy. Additionally 3 single donor PC in plasma were stored for 10 days at standard blood bank conditions. Platelet samples were pooled and analyzed at day 1,2,3,6,7,8,9 and 10. We trained a neural network consisting of multiple convolutional layers to classify age (time after donation) of platelets that were stored in either PRP or PC. Results: During storage in PRP as well as of PC we used for each time point 1334 62µm x 62µm x 4µm 3D images, containing 50 to 150 platelets per image, for training. When staining with markers VWF, SPARC or alpha-tubulin alone as training set we could already classify mean platelet age up to 78%, 85%, 88% respectively. When combining all three markers a maximum accuracy of 95% for platelets stored in PRP up to 8 hours was reached (Figure 1). The additional effect of combining these three markers highlights that the model used information in the images synergistically. For PC, an accuracy of 90% was reached for classifying mean platelet age of platelets stored up to 8 days. The model could not be trained to discriminate between days 9 and 10 resulting in an overfitted model. However the model was able to distinguish day between day 1, 3, 6 and 10 (Figure 2). As negative control a model trained on a randomized sample was made. This control model was not able to assign a category correctly, indicating an actual difference in platelet characteristics during storage was detected. By using visualization of the weight-gradient (e.g. where in the images the model assigns the most weight) we additionally confirmed that the model used separate individual platelets to characterize the age of the complete platelet sample. Conclusion: Combining confocal platelet images with a convolutional neural network, we trained a model that could synergistically integrate different stainings and information of individual platelets to predict with >95% accuracy platelet age in vitro as well as in PC up to 10 days of storage. Additionally our model could distinguish "young" platelets (stored 1, 3 or 6 days) from "old" platelets (stored 10 days). Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal