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Background Thrombotic microangiopathy encompasses a wide range of conditions, of which thrombotic thrombocytopenic purpura being a medical emergency requires prompt intervention, with schistocytes being a reliable morphological indicator of microvascular injury. However, there are conditions other than thrombotic microangiopathic anemia where schistocytes can be seen in large numbers. These nonthrombotic microangiopathic conditions are broadly grouped under cytoskeletal abnormalities, mechanical damage, and thermal injuries. Automated methods in schistocyte evaluation have shown varied reproducibility requiring manual identification. International Council for Standardization in Hematology (ICSH) recommends standardized morphological criteria and quantitative assessment as a percentage after counting at least 1,000 red blood cells in optimal areas of smear to reduce interobserver variability.

Background: The PLASMIC score was developed for distinguishing thrombotic thrombocytopenic purpura (TTP) from other types of thrombotic microangiopathy. However, two components of the PLASMIC score, mean corpuscular volume (MCV) and international normalized ratio (INR), showed non‐significant differences between TTP and non‐TTP patients in previous validations. Here, we validate the PLASMIC score and aim to modify it by adjusting the criteria of MCV and INR. Materials and Methods: A retrospective validation of suspected TTP patients was performed by reviewing electronic medical records from two medical centers in Taiwan. The performance of different modified types of the PLASMIC score was carried out. Results: Among 50 patients included in the final analysis, 12 were diagnosed with TTP based on deficiency of ADAMTS13 activity and clinical judgement. When stratified by high (score ≥ 6) and low‐intermediate risk (score < 6), the positive predictive value (PPV) of the PLASMIC score to predict TTP was 0.45 (95% confidence interval [CI]: 0.29‐0.61). The area under curve (AUC) was 0.70 (95% CI: 0.56‐0.82). When adjusting the criteria of the PLASMIC score from MCV < 90 fL to MCV ≥ 90 fL, the PPV increased to 0.57 (95% CI: 0.37‐0.75). The AUC was 0.75 (95% CI: 0.61‐0.87). When adjusting the INR from >1.5 to >1.1, the PPV increased to 0.56 (95% CI: 0.39‐0.71). The AUC was 0.81 (95% CI: 0.68‐0.90). Conclusion: MCV ≥ 90 fL and/or INR > 1.1 might be suitable modifications for PLASMIC score but should be validated in a larger sample size. [ABSTRACT FROM AUTHOR]

Background Thrombotic microangiopathy encompasses a wide range of conditions, of which thrombotic thrombocytopenic purpura being a medical emergency requires prompt intervention, with schistocytes being a reliable morphological indicator of microvascular injury. However, there are conditions other than thrombotic microangiopathic anemia where schistocytes can be seen in large numbers. These nonthrombotic microangiopathic conditions are broadly grouped under cytoskeletal abnormalities, mechanical damage, and thermal injuries. Automated methods in schistocyte evaluation have shown varied reproducibility requiring manual identification. International Council for Standardization in Hematology (ICSH) recommends standardized morphological criteria and quantitative assessment as a percentage after counting at least 1,000 red blood cells in optimal areas of smear to reduce interobserver variability. Objectives The aim of this study was to evaluate and quantitate schistocytes in thrombotic microangiopathic and nonthrombotic microangiopathic groups using ICSH guidelines and to evaluate interobserver reproducibility of manual schistocyte count. Materials and Methods Overall, 157 peripheral blood smears showing schistocytes were studied by two independent observers using ICSH recommendations on light microscopy. The hematological findings were correlated with clinical diagnosis and other relevant investigations. Results Schistocytes were observed in five cases of thrombotic microangiopathic anemia and 152 cases of nonthrombotic microangiopathic anemia. Schistocyte count in thrombotic microangiopathic anemia and nonthrombotic microangiopathic anemia groups with mean (±standard deviation) value was 2.28 ± 2.65% and 0.76 ± 0.67%, respectively (p < 0.001). The correlation coefficient between the two observers was 0.59 (confidence interval = 0.966–1.346) showing an excellent agreement on the reproducibility of schistocytes by application of ICSH guidelines. Conclusion Percentage of schistocytes more than 1% is a robust morphological indicator for diagnosis of thrombotic microangiopathic anemia in adults. Strict application of ICSH guidelines reduces interobserver bias. [ABSTRACT FROM AUTHOR]

Summary: Many medications have been reported to be associated with thrombotic thrombocytopenic purpura (TTP) through pharmacovigilance data and published case reports. Whilst there are existing data available regarding drug‐induced thrombotic microangiopathy, there is no available synthesis of evidence to assess drug‐induced TTP (DI‐TTP). Despite this lack of evidence, patients with TTP are often advised against using many medications due to the theoretical risk of DI‐TTP. This systematic review evaluated the evidence for an association of medications reported as potential triggers for TTP. Of 5098 records available 261 articles were assessed further for eligibility. Fifty‐seven reports, totalling 90 patients, were included in the final analysis. There were no cases where the level of association was rated as definite or probable, demonstrating a lack of evidence of any drug causing DI‐TTP. This paucity of evidence was also demonstrated in the pharmacovigilance data, where 613 drugs were reported as potential causes of TTP without assessment of the strength of association. This systematic review demonstrates the need for standardised reporting of potential drugs causing TTP. Many reports omit basic information and, therefore, hinder the chance of finding a causative link if one exists. [ABSTRACT FROM AUTHOR]

A 40-year-old male patient with a history of dental disease was sent to the emergency room mainly for fever, unclear consciousness, and purpura. Computed tomography reveals subarachnoid hemorrhage and blood analysis reveals platelet reduction. The patient was started daily intravenous piperacillin tazobactam glucocorticoid and gamma globulin. Two weeks later, symptoms improved but still had severe complications such as fever, platelet reduction, hepatosplenic abscess, and severe myocardial injury. Subsequently, Rothia dentocariosa was cultured from the blood samples of patient's limb. The patient was started on daily injections of tigecycline and penicillin. Ten days later, symptoms improved and amikacin was tried, which was later confirmed to be ineffective in this patient. Cardiac ultrasound revealed aortic valve vegetations and magnetic resonance imaging revealed brain abscess formation. Then, antibiotics were adjusted to vancomycin and meropenem. Finally, the patient underwent valve replacement. Infectious endocarditis – after surgery, vancomycin and meropenem were utilized for a week leading to symptom resolution. The patient was transferred to rehabilitation hospital. This case will provide clinical experience for the treatment of R. dentocariosa.

A 40-year-old male patient with a history of dental disease was sent to the emergency room mainly for fever, unclear consciousness, and purpura. Computed tomography reveals subarachnoid hemorrhage and blood analysis reveals platelet reduction. The patient was started daily intravenous piperacillin tazobactam glucocorticoid and gamma globulin. Two weeks later, symptoms improved but still had severe complications such as fever, platelet reduction, hepatosplenic abscess, and severe myocardial injury. Subsequently, Rothia dentocariosa was cultured from the blood samples of patient's limb. The patient was started on daily injections of tigecycline and penicillin. Ten days later, symptoms improved and amikacin was tried, which was later confirmed to be ineffective in this patient. Cardiac ultrasound revealed aortic valve vegetations and magnetic resonance imaging revealed brain abscess formation. Then, antibiotics were adjusted to vancomycin and meropenem. Finally, the patient underwent valve replacement. Infectious endocarditis – after surgery, vancomycin and meropenem were utilized for a week leading to symptom resolution. The patient was transferred to rehabilitation hospital. This case will provide clinical experience for the treatment of R. dentocariosa. [ABSTRACT FROM AUTHOR]

Abstract Immune‐mediated thrombotic thrombocytopenic purpura (iTTP) is an ultra‐rare, blood‐clotting disorder. Management historically relies on plasma exchange and immunosuppression; however, a 10%–20% mortality rate is still observed. Caplacizumab binds to von Willebrand factor and directly inhibits platelet aggregation; addition of caplacizumab to historical treatment induced faster resolution of platelet count in clinical trials. In 2019, a modified‐Delphi study was conducted with UK experts, to develop consensus statements on management of acute TTP and the potential role of caplacizumab. An unmet need was acknowledged, and areas requiring improvement included: time to diagnosis and treatment initiation; time to platelet normalisation (TTPN) during which patients remain at risk of persistent microvascular thrombosis and organ damage; and incidence of subsequent exacerbations and relapses. Caplacizumab addition to historical treatment within 24 h (after confirmatory ADAMTS13 [a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13] assay) would significantly reduce TTPN, which directly influences acute outcomes, with manageable bleeding risk and reduced burden on healthcare systems. Expert panellists agree that poor outcomes in iTTP largely result from failure to rapidly control microvascular thrombosis. Use of caplacizumab during a confirmed iTTP episode could offer better control and may plausibly improve long‐term outcomes. However, this consensus must be validated with further clinical trials and robust real‐world evidence.

Background: Different preparations for therapeutic plasma are available on the market. The German hemotherapy guideline has been completely updated in 2020 and, for this purpose, has reviewed the evidence for the most frequent clinical indications for the use of therapeutic plasma in adult patients. Summary: The German hemotherapy guideline has reviewed the evidence for the following indications for the use of therapeutic plasma in the adult patient: massive transfusion and bleeding, severe chronic liver disease, disseminated intravascular coagulation, plasma exchange for TTP, and the rare hereditary FV and FXI deficiencies. The updated recommendations for each indication are discussed on the background of existing guidelines and new evidence. For most indications, the quality of evidence is low due to missing prospective randomized trials or rare diseases. However, due to the "balanced" content of coagulation factors and inhibitors therapeutic plasma remains an important pharmacological treatment option in clinical situations with an already activated coagulation system. Unfortunately, the "physiological" content of coagulation factors and inhibitors limits the efficacy in clinical scenarios with high blood losses. Key Messages: The evidence for the use of therapeutic plasma for the replacement of coagulation factors due to massive bleeding is poor. Coagulation factor concentrates seem to be more appropriate for this indication, although the quality of evidence is also low. However, for diseases with an activated coagulation or endothelial system (e.g., disseminated intravascular coagulation, TTP) the balanced replacement of coagulation factors, inhibitors, and proteases may be of advantage. [ABSTRACT FROM AUTHOR]

Helicobacter pylori is considered to be one of the significant reasons of formation of gastroduodenal pathology. Data on the role of H. pylori in the development of extragastric diseases are confirmed by a positive effect of eradication on peripheral blood changes. In spite of this fact both aspects are still not revealed. However, undoubtedly that H. pylori persistence on gastric epithelium creates conditions for chronic local and systematic inflammation. The aim of the sur- vey was the analysis of literary data about bacterial factors in the development of iron-, vitamin B12-deficiency anaemia and thrombocytopenic purpura included by the international consensus into the circle of evedences for diagnosis and treatment of H. pylori. Material and methods. There was accomplished search of literature sources with the help of data bases PubMed, CyberLeninka, eLibrary, Google Scholar. The results of our analysis specify mechanisms of cer- tain blood diseases pathogenesis in association with H. pylori. Multiple roles of virulent strains of pathogen in anaemia and thrombocytopenic purpura include: development of erosive and ulcerative lesions of mucosa, hypoacidity, chron- ic inflammation and autoimmune response. Data about these changes in haematological syndromes and independent eradication effects on blood parameters normalisation, are controversial. Н. pylori host iron competition theory has not been found convincing confirmation. Conclusions. It is necessary to study more deeply the connection of H. pylori and haematological diseases. The dietary research and application to maintain the mucous integrity and bacterial adhesion prevention are perspective.

All variants of thrombotic microangiopathy (TMA) in obstetric practice develop in an avalanche-like manner and require a rapid decision on the choice of treatment tactics. Although all these diseases have similar features, typical of the TMA syndrome as a whole, they are separate diseases with differing etiology and pathogenesis. Because the manifestations of TMA are almost identical in the different diseases, they may all imitate pre-eclampsia and the therapeutic approaches differ, a differential diagnosis is essential and often determines the prognosis.The differential diagnostic search between the different TMA variants that can develop in pregnancy is described, as the prognosis of life often depends on the correct diagnosis. The main differences between pre-eclampsia/HELLP syndrome and life-threatening conditions such as atypical hemolytic-uremic syndrome, thrombotic thrombocytopenic purpura and catastrophic antiphospholipid syndrome are considered. Algorithms of diagnostic search are proposed. Attention is drawn to the fact that existing algorithms for the diagnosis of severe TMA prior to ADAMTS 13 results, based on the severity of thrombocytopenia and azotemia as well as scoring during pregnancy can serve as a guide, but not as a defining feature of the diagnosis.The key to the differential diagnosis is the effect of delivery on the regression of TMA: if hemolysis and thrombocytopenia decrease after delivery, one can speak of ‘pure’ pre-eclampsia (PE) or HELLP-syndrome. If persistent or increasing, thrombotic thrombocytopenic purpura (TTP) and aHUS should be considered. With an ADAMTS 13 level of less than 10%, a diagnosis of TTP is made. With ADAMTS 13 over 10-20%, the patient falls into the «grey zone» and a repeat enzyme test is required. If there are signs of fulminant multiple organ failure, especially in a patient with initial suspicion of APS, CAPS can be suspected. To confirm it, high titres of APA are required. In addition, TMA may cause: sepsis and various urgent obstetric conditions complicated by the development of DIC.

Therapeutic plasma exchange in children is increasingly recognized as a life-saving treatment and is challenged by some technical considerations. As extracorporeal membrane oxygenation has been used for nearly half a century for refractory reversible respiratory and/or cardiac failure in both pediatric and adult populations, it may serve as an extracorporeal platform for therapeutic plasma exchange. It is most commonly described in patients with sepsis with multiple organ failure or thrombocytopenia associated multi organ failure. Additional pathophysiological processes of inflammatory and immunological storms might benefit from the combination of extracorporeal membrane oxygenation and plasma exchange. This is a nonmethodological review of English-language reports of therapeutic plasma exchange performed in patients supported by extracorporeal membrane oxygenation, both pediatric and adult, searching six databases, MEDLINE, Clinical Key, GOOGLE SCHOLAR, CINAHL, Cochrane library, and EMBASE. [ABSTRACT FROM AUTHOR]

Acquired thrombocytopenic thrombotic purpura (aTTP) is an autoantibody-mediated disease against the enzyme A Disintegrin and Metalloprotease domain with ThromboSpondin-1 type motif 13, which until now has been treated with plasma exchange (PEX) and corticosteroids. A 29-year-old female patient, who presented with aTTP in the context of pregnancy, has developed multiple relapses after treatment with PEX, corticosteroids, and rituximab. Recently, caplacizumab, a nanobody against von Willebrand factor, has been approved for the treatment of aTTP. In our patient, caplacizumab achieved better disease control, with a lower platelet count restoration time, days of PEX and hospitalization duration, as compared to standard therapy, reproducing the results of clinical trials. Caplacizumab represents a significant advance in the treatment of aTTP, especially in cases of recurrent relapses. [ABSTRACT FROM AUTHOR]