Platelet Consumption Research Articles

Epic Fail? Try Again

We read with interest the manuscript titled “Failure of Crotalidae Immune F(ab’)2 Equine Antivenom to Achieve Control in a Southern Pacific Rattlesnake Envenomation” by Levine et al. The authors indicate that their patient “failed to respond adequately to F(ab’)2AV” because his initially unmeasurable platelet count reached a maximum of 102,000/μL at 56 hours after envenomation. We have several concerns with this conclusion. Adequate platelet response in the setting of venom-induced hemotoxicity is not universally defined. Although some patients may have complete reversal of thrombocytopenia after a single antivenom dose, others may have increasing platelet numbers but never achieve a platelet count of >150,000/μL. A 2011 study by Yin et al1Yin S. Kokko J. Lavonas E. et al.Factors associated with difficulty achieving initial control with crotalidae polyvalent immune fab antivenom in snakebite patients.Acad Emerg Med. 2011; 18: 46-52Crossref PubMed Scopus (21) Google Scholar suggested that it “may not be reasonable to attempt to completely control” thrombocytopenia. Antivenom may have been underdosed initially. F(ab’)2AV is dosed at 10 vials over 1 hour and repeated hourly until initial control is obtained, as evidenced by the halt of proximal swelling and improvement in laboratory markers. However, as above, there is no consensus on specific numeric goals.2Anavip [Package Insert]. Franklin, TN: Rare Disease Therapeutics, Inc.Google Scholar Although the patient received 10 vials initially, his next dose approximately 1 to 2 hours later was only 4 vials. He received the remaining 6 vials after approximately 9 hours. His platelet count continued to increase. The trend suggests that earlier administration may have prevented persistent thrombocytopenia. After viper envenomation, platelets may be sequestered, pro- and anti-aggregated, and destroyed through multiple mechanisms, leading to recurrent or refractory thrombocytopenia, which is difficult to predict in the absence of routine venomic studies on individual patients. This inability to reliably predict the mechanism of thrombocytopenia results in the inability to predict platelet response to antivenom.3Shen C. Liu M. Mackeigan D.T. et al.Viper venoms drive the macrophages and hepatocytes to sequester and clear platelets: novel mechanism and therapeutic strategy for venom-induced thrombocytopenia.Arch Toxicol. 2021; 95: 3589-3599Crossref PubMed Scopus (4) Google Scholar,4De Queiroz M.R. de Sousa B.B. da Cunha Pereira D.F. et al.The role of platelets in hemostasis and the effects of snake venom toxins on platelet function.Toxicon. 2017; 133: 33-47Crossref PubMed Scopus (45) Google Scholar Owing to platelet sequestration and aggregation, antivenom should quickly reverse thrombocytopenia. However, with platelet destruction or consumption, levels would not increase until the patient could synthesize more platelets de novo. This patient may have had ongoing platelet consumption to repair venom-induced tissue damage, yet the authors did not describe the progression of cytotoxicity. The lack of fibrinogen trend also makes the inference of ongoing venom effect problematic. Rattlesnake antivenom is best suited not to resolve thrombocytopenia but to reverse defibrination, so the significance of persistent thrombocytopenia in the absence of fibrinogen levels is unclear.5Dudley S. Smelski G. Massey D.J. et al.Fashionably late: A characterization of late coagulopathies in rattlesnake envenomations between Fab and F (ab’) 2 antivenoms.Toxicon. 2022; 212: 49-54Crossref Scopus (0) Google Scholar Twenty-three years of unpublished data from the Arizona Poison and Drug Information Center shows that persistent thrombocytopenia after antivenom is common regardless of which of the two commercially available antivenoms is used (FabAV or F[ab’]2AV). Considering cases with thrombocytopenia during initial hospital stay, 197 of 556 (35.43%) FabAV patients and 39 of 107 (36.45%) F(ab’)2AV patients were discharged with a platelet count of < 150,000/μL. Some patients did not develop thrombocytopenia until after discharge. Among FabAV patients, 106 of 472 (22.46%) developed delayed thrombocytopenia compared with only 7 of 130 (5.38%) F(ab’)2AV patients. Similar rates of persistent thrombocytopenia in the inpatient setting suggest that destruction of platelets occurs in some patients regardless of antivenom manufacturer. The difference in delayed thrombocytopenia suggests that the longer half-life of F(ab’)2AV continues to protect against thrombocytopenia compared with FabAV. Finally, the authors did not provide an illustration of the patient’s overall clinical picture throughout his hospital stay, including progression of edema, pain, and coagulation factors. Isolated thrombocytopenia is not an indication to provide more antivenom as bleeding due to thrombocytopenia is unlikely if there is no defibrination. A patient with stabilization of other indicators, despite persistent thrombocytopenia, has had an adequate response to antivenom. As always in medicine, treat the patient, not the number.

Clinical Manifestations, Current and Future Therapy, and Long-Term Outcomes in Congenital Thrombotic Thrombocytopenic Purpura.

Congenital thrombotic thrombocytopenic purpura (cTTP) is an extremely rare disease characterized by the severe deficiency of a disintegrin and metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13), caused by ADAMTS13 mutations. While ADAMTS13 supplementation by fresh frozen plasma (FFP) infusion immediately corrects platelet consumption and resolves thrombotic symptoms in acute episodes, FFP treatment can lead to intolerant allergic reactions and frequent hospital visits. Up to 70% of patients depend on regular FFP infusions to normalize their platelet counts and avoid systemic symptoms, including headache, fatigue, and weakness. The remaining patients do not receive regular FFP infusions, mainly because their platelet counts are maintained within the normal range or because they are symptom-free without FFP infusions. However, the target peak and trough levels of ADAMTS13 to prevent long-term comorbidity with prophylactic FFP and the necessity of treating FFP-independent patients in terms of long-term clinical outcomes are yet to be determined. Our recent study suggests that the current volumes of FFP infusions are insufficient to prevent frequent thrombotic events and long-term ischemic organ damage. This review focuses on the current management of cTTP and its associated issues, followed by the importance of upcoming recombinant ADAMTS13 therapy.

Expert Consensus on the Use of Human Serum Albumin in Adult Cardiac Surgery.

Expert Consensus on the Use of Human Serum Albumin in Adult Cardiac Surgery.

Platelet Indices: Is it a Reliable Biomarker in Viral Infections?

Platelets are non-nucleated blood cells that are essential for maintaining hemostasis. While platelet activation and increased platelet numbers (thrombocytosis) are associated with a higher risk of thrombotic events, low platelet counts (thrombocytopenia) and a variety of platelet function abnormalities are associated with a higher risk of bleeding. Platelets and their activation state have been proven in recent years to influence innate and adaptive immune responses, and low platelet counts have been identified as a surrogate indicator for poor prognosis in septic patients. Platelet activation frequently occurs in conjunction with viral infections. Viruses, on the other hand, can interact directly with platelets and megakaryocytes, modulating their function. All these factors contribute to platelet activation, which leads to increased platelet consumption and elimination, as well as thrombocytopenia, which is common during viral infection Platelets and their secreted products have been demonstrated to suppress infection and aid virus persistence in the presence of certain viruses, making platelets a double-edged sword during viral infections. In this review we have highlighted about what is currently known about platelet interactions with various types of viruses, virus effects on platelet activation, as well as platelet-mediated regulation of innate and adaptive immune responses.

Optimising platelet usage during the induction therapy of acute myeloid leukaemia: Impact of physician education.

Platelet products are scarce and expensive resources to be used judiciously. However, inappropriate usage is common. Lack of physician awareness is an important issue. We implemented a physician education program (PEP) along with repeated WhatsApp reminders at our centre. We audited the platelet usage practise before and after the intervention. Charts of patients with acute myeloid leukaemia (AML) treated between January 2020 and August 2020 was reviewed, and the mean platelet usage per patient per day was calculated. Physician education was implemented between September 2020 and December 2020 (2 PowerPoint lectures of 20 min each and weekly WhatsApp messages containing the guidelines). Data of patientstreated between Jan 2021 and August 2021 was prospectively audited to understand platelet usage and the indications for transfusions. The British Committee for the Standards in Haematology (BCSH) platelet transfusion guidelines were used as the adjudication tool to evaluate compliance. The mean platelet usage per day per kg body weight of a patient before and after the PEP was compared using the t-test. Group A (before physician education) consisted of 22 patients, and group B (after physician education) consisted of 23 patients. The mean number of platelet transfusions for each patient in a day per kg body weight was 125.7 × 108 in group A whereas, after the PEP, it had reduced to 73.9 × 108 amounting to an absolute reduction of 51 × 108 (58.8%) from the baseline with a statistical significance of P=0.001. After implementing the PEP, the mean number of random donor platelets used reduced by 10.25 units (34% reduction), and the mean single donor platelets used reduced by 0.83 units (19% reduction). The 190 requests for platelet transfusion received during this period were classified as appropriate (157/190), which constituted 82.63% of the requests, or inappropriate (33/190), which accounted for 17.36%. A short-duration education programme supplemented with weekly WhatsApp messages and an active feedback mechanism on the rationale of platelet transfusion by the treating physician and transfusion specialist could significantly reduce platelet consumption during the therapy of acute myeloid leukaemia patients. This is a measure that can be considered by all high-volume haematology centres, which can improve patient safety and reduce costs.

Biogenesis aberration: One of the mechanisms of thrombocytopenia in COVID-19.

Background: The pathogenesis of COVID-19, including thrombocytopenia, has not been fully clarified. The lungs are a major organ of platelet production and thrombocytopenia induced by severe COVID-19 was proposed. Methods: the change of platelet level was analysed with clinical parameters in 95 hospitalized COVID-19 patients in Wuhan Third Hospital. The production of platelets in the lungs was explored in an ARDS rat model. Results: The level of platelets was negatively correlated with disease severity and was recovered with disease improvement. The non-survivors were accompanied by lower levels of platelet. The odds ratio (OR) of the valley level of the platelet count (PLTlow) was greater than 1, suggesting that PLTlow could be a death exposure factor. The platelet/lymphocyte ratio (PLR) was positively associated with severity of COVID-19, and the platelet/lymphocyte ratio threshold of 248.5 was best correlated with death risk (sensitivity 0.641 and specificity 0.815). To demonstrate the possible biogenesis aberration of platelet in lungs, an LPS-induced ARDS rat model was applied. Lower level of platelet in peripheral and less production of platelet from lungs in ARDS were demonstrated. Though megakaryocyte (MK) number in ARDS lungs is higher than controls, the immature platelet fraction (IPF) in postpulmonary blood is still at the same level as prepulmonary in ARDS rat, indicating that ARDS rats generated fewer platelets in lungs. Conclusion: Our data suggested that COVID-19-induced severe lung inflammation may impair platelet production in the lung. Thrombocytopenia may be mainly caused by platelet consumption for multiorgan thrombosis; however, biogenesis aberration of platelet in the lung induced by diffuse interstitial pulmonary damage cannot be ruled out.

Mutations in the alternative complement pathway in multiple myeloma patients with carfilzomib-induced thrombotic microangiopathy

Thrombotic microangiopathy (TMA) has been reported to occur in multiple myeloma (MM) patients in association with treatment with carfilzomib, an irreversible proteasome inhibitor (PI). The hallmark of TMA is vascular endothelial damage leading to microangiopathic hemolytic anemia, platelet consumption, fibrin deposition and small-vessel thrombosis with resultant tissue ischemia. The molecular mechanisms underlying carfilzomib-associated TMA are not known. Germline mutations in the complement alternative pathway have been recently shown to portend increased risk for the development of atypical hemolytic uremic syndrome (aHUS) and TMA in the setting of allogeneic stem cell transplant in pediatric patients. We hypothesized that germline mutations in the complement alternative pathway may similarly predispose MM patients to carfilzomib-associated TMA. We identified 10 MM patients with a clinical diagnosis of TMA in the context of carfilzomib treatment and assessed for the presence of germline mutations in the complement alternative pathway. Ten, matched MM patients exposed to carfilzomib but without clinical TMA were used as negative controls. We identified a frequency of deletions in the complement Factor H genes 3 and 1 (delCFHR3-CFHR1) and genes 1 and 4 (delCFHR1-CFHR4) in MM patients with carfilzomib-associated TMA that was higher as compared to the general population and matched controls. Our data suggest that complement alternative pathway dysregulation may confer susceptibility to vascular endothelial injury in MM patients and predispose to development of carfilzomib-associated TMA. Larger, retrospective studies are needed to evaluate whether screening for complement mutations may be indicated to properly counsel patients about TMA risk with carfilzomib use.

The History of Extracorporeal Membrane Oxygenation and the Development of Extracorporeal Membrane Oxygenation Anticoagulation.

Extracorporeal membrane oxygenation (ECMO) was first started for humans in early 1970s by Robert Bartlett. Since its inception, there have been numerous challenges with extracorporeal circulation, such as coagulation and platelet activation, followed by consumption of coagulation factors and platelets, and biocompatibility of tubing, pump, and oxygenator. Unfractionated heparin (heparin hereafter) has historically been the defacto anticoagulant until recently. Also, coagulation monitoring was mainly based on bedside activated clotting time and activated partial thromboplastin time. In the past 50 years, the technology of ECMO has advanced tremendously, and thus, the survival rate has improved significantly. The indication for ECMO has also expanded. Among these are clinical conditions such as postcardiopulmonary bypass, sepsis, ECMO cardiopulmonary resuscitation, and even severe coronavirus disease 2019 (COVID-19). Not surprisingly, the number of ECMO cases has increased according to the Extracorporeal Life Support Organization Registry and prolonged ECMO support has become more prevalent. It is not uncommon for patients with COVID-19 to be on ECMO support for more than 1 year until recovery or lung transplant. With that being said, complications of bleeding, thrombosis, clot formation in the circuit, and intravascular hemolysis still remain and continue to be major challenges. Here, several clinical ECMO experts, including the "Father of ECMO"-Dr. Robert Bartlett, describe the history and advances of ECMO.

Fatal cerebral venous sinus thrombosis with preceding thrombocytopenia in a patient with new-onset eosinophilic granulomatosis with polyangiitis.

A previously healthy, 44-year-old, female patient was hospitalised for acute abdominal pain and bilateral pneumonia. Eosinophilic granulomatosis with polyangiitis (EGPA) was diagnosed on the basis of eosinophilia, eosinophilic tissue inflammation, polyneuropathy, and bilateral pneumonia. She had a fatal cerebral venous sinus thrombosis following thrombocytopenia, which was apparently caused by platelet consumption. It may have been possible to prevent the deterioration of the venous thrombosis by starting immunosuppressive or anticoagulant therapy earlier. If a patient with EGPA presents with unexplained thrombocytopenia, the physician should assess for physical findings or laboratory abnormalities suggestive of thrombosis. Additionally, if the patient complains of headache or nausea with normal head computed tomography findings, magnetic resonance imaging or magnetic resonance venography should be performed to assess for cerebral venous sinus thrombosis.

Double Filtration Plasmapheresis with Polyvinyl Alcohol-Based Membrane Lowers Serum Inflammation and Toxins in Patients with Hyperlipidemia.

Hyperlipidemia is increasing in prevalence and is highly correlated with cardiovascular disease (CVD). Lipid-lowering medications prevent CVD but may not be suitable when the side effects are intolerable or hypercholesterolemia is too severe. Double-filtration plasmapheresis (DF) has shown its therapeutic effect on hyperlipidemia, but its side effects are not yet known. We enrolled 45 adults with hyperlipidemia in our study. The sera before and two weeks after DF were evaluated, and we also analyzed perfluorochemicals to see if DF could remove these lipophilic toxins. After DF, all lipid profile components (total cholesterol, triglycerides, high-density lipoprotein [HDL], and low-density lipoprotein [LDL]) had significantly decreased. Leukocyte counts increased while platelet levels decreased, which may have been caused by the puncture wound from DF and consumption of platelets during the process. As for uremic toxins and inflammation, levels of C-reactive protein, uric acid, and alanine transaminase (ALT) all decreased, which may be related to the removal of serum perfluorooctane sulfonate (PFOS) and improvement of renal function. The total cholesterol/HDL ratio and triglycerides were significantly higher in the diabetes mellitus (DM) group at baseline but did not significantly differ after DF. In conclusion, DF showed potential for improving inflammation and removing serum lipids and PFOS in adults with hyperlipidemia.

Perbandingan Jumlah Trombosit pada Pasien COVID-19 dengan Kadar Glukosa yang Berbeda

Hyperglycemia has increased arachidonic acid thromboxane which is an effective ingredient in platelet activation. Thrombocytopenia in COVID-19 patients occurs through a variety of mechanisms, such as uncontrolled production of cytokines destroying bone marrow progenitor cells, direct inhibition of hematopoiesis viral infection of the bone marrow, increase in autoantibodies and immune complexes that cause platelet destruction, and lung injury that causes platelet aggregation and consumption of platelets so that platelets in the circulation are reduced. Objectives: To analyzed the ratio of platelet counts in COVID-19-positive patients who had different blood glucose levels. Methods: This research used secondary data, with types of analytical observational research as well as comparative study approaches. Statistical tests were conducted using an independent samples t-test with a confidence level of 95%. Results: The average platelet count was normal, but a low platelet count of 3.30% was obtained with normal blood glucose levels and a high platelet count of 2.20% with normal blood glucose levels, with a significance value of platelet count with normal blood glucose levels of 0.790 and platelet counts with blood glucose levels above normal which is 0.791 with a confidence level of 95%. Conclusion: There was no significant difference between the platelet count in COVID-19 patients with normal and above normal blood glucose levelsKeywords: blood glucose, platelets, COVID-19

Use of PLT-F channel and immature platelet fraction parameters in differential diagnosis of thrombocytopenia

Establishing the true causes of thrombocytopenia is of paramount importance, since the tactics of managing patients depend on it. Obtaining information about the activity of thrombocytopoiesis until recently was possible only after examining the bone marrow, but modern laboratory diagnostic capabilities make it possible to evaluate thrombocytopoiesis by a comprehensive clinical blood test performed on a hematological analyzer using a fluorescent optical method (PLT-F). At the same time, in addition to the number of platelets in peripheral blood, information is available on the number of immature platelets (IPF) in absolute and relative terms. Objective: to evaluate the possibility of using the PLT-F channel and IPF parameters in the differential diagnosis of thrombocytopenia. We reviewed three clinical cases with different pathogenetic variants of thrombocytopenia (immune thrombocytopenia, thrombocytopenia in DIC and thrombocytopenia associated with bone marrow damage). In all cases, a clinical blood test was performed on a Sysmex XN 1000 hematological analyzer using the PLT-F channel. When using the PLT-F channel, parameters are available to differentiate thrombocytopenia according to the mechanism of pathogenesis. The absolute value of IPF is a criterion for the activity of thrombocytopoiesis in the bone marrow, while the relative value of IPF, namely the increase in this parameter, is a criterion for the loss of platelets in the peripheral bloodstream (destruction or increased consumption of platelets). The availability of obtaining diagnostic information about the activity of thrombocytopoiesis and loss of platelets in the peripheral bloodstream using a clinical blood test using the PLT-F channel on Sysmex XN hematological analyzers is of great clinical importance, since a clinical blood test, being a routine study, does not require special conditions for sampling biomaterial, and can be performed not only at the stage of diagnosis, but also during therapy monitoring.

Thrombocytopenia following implantation of different types of bioprosthetic aortic valves in severe aortic valve stenosis replacement

Abstract Aim The use of bioprosthetic valves in the surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI) of severe aortic stenosis has been associated with post-implantation thrombocytopenia, usually reversible and rarely combined with severe bleeding events. The purpose of this study was to compare the grade of thrombocytopenia and the presence of bleeding events following the implantation of bioprosthetic valves, where either surgery (Solo, Perceval, Trifecta) or transcatheter method (self-expandable TAVI) was followed. Methods 89 patients with severe aortic stenosis were included in the study. All patients underwent either SAVR or TAVI. In each group 3 different types of bioprosthetic valves were used [59 patients in SAVR group: Solo (14), Perceval (27), Trifecta (18), 30 patients in TAVI group: Evolut R (10), Portico (15), Acurate (5)]. All patients had normal or slightly reduced platelet count at baseline. Patients previously receiving anticoagulants, patients with a primary blood disorder affecting the number of platelets, as well as patients with a post-surgery complication that could affect the number of platelets (e.g., HIT syndrome, etc.) were excluded from the study. Blood samples were taken in the morning before intervention and every morning during the first week of follow-up. Platelet count values before and after implantation were compared with paired t-test (SPSS V21.0, Inc., Chicago, IL, USA), while the reduction of platelets was compared between the 4 different valves with independent t-test. P-values of &amp;lt;0.05 were considered significant. Results Mean age was 76.8±5.1 years. There was no statistically significant difference between the 2 groups of patients concerning the baseline characteristics and the administered anticoagulants. Statistically significant reduction of the blood count was observed in all groups [Solo: 136±80x103/μl (p=0.009), Perceval: 129±75x103/μl (p&amp;lt;0.001), Trifecta: 74±32x103/μl (p&amp;lt;0.001, TAVI: 60±103μl)]. There was no observed statistically significant difference between Solo and Perceval group (p=0.85) or Solo and Trifecta group (p=0.053), but in the case of Perceval and Trifecta group, a statistically significant difference was noted (p=0.047). A statistically significant difference in both SAVR and TAVI groups was demonstrated (p=0.040) regarding blood count reduction. There was no occurrence of any major bleeding events. 3 patients (3.3%) presented mild bleeding disorders (1 patient epistaxis and 2 patients mild hematuria). Conclusion Both methods, surgical and transcatheter severe aortic stenosis replacement and all the different bioprosthetic valves that were implanted, were associated with statistically significant reduction of platelet count post-implantation. This reduction was linked to the procedure due to endothelial damage, shear stress injury, inflammation-related platelet consumption, and was not associated with clinically significant bleeding events. Funding Acknowledgement Type of funding sources: None.

COCAINE INTOXICATION LEADING TO HYPERTHERMIA, DISSEMINATED INTRAVASCULAR COAGULATION, AND ACUTE RENAL FAILURE

COCAINE INTOXICATION LEADING TO HYPERTHERMIA, DISSEMINATED INTRAVASCULAR COAGULATION, AND ACUTE RENAL FAILURE

Ensemble approach on predicting blood platelets using supervised approach via computational bio informatics

Platelets are little leukocytes that are essential for such blood coagulation. When an individual does not generate sufficient platelets they won't function effectively, then they will likely to have frequent haemorrhage and bruising since normal deterioration towards the exterior of blood vessels can go inoperable. This may be prescribed to accommodate patients using platelet transfusions via blood donors to halt such haemorrhage. Unfortunately, such medication is not optimal since patients develop antigens against given blood platelets, preventing them from being managed with platelets of similar blood groups in the future. As a result, blood centres are looking towards finding alternatives to donor platelets. Platelet transplants are commonly utilised to reduce or eliminate haemorrhage in a range of patient groups, including those that are currently haemorrhage and those who have malfunctioning or inadequate platelets. Because of the unpredictability of demands, commodity highly perishable, and cost, all institutions and health centres must prioritise estimating hospital-wide platelet consumption. Also, with fast advancement of ML technology, now it is extensively applied in the treatment of a variety of disorders. The benefit of machine learning methods is how they can interpret high-order range of predictor correlations and produce more solid predictions.

344.7: Early Post-operative Thrombotic Microangiopathy in Deceased Donor Kidney Transplant: Case Series

Background: Transplant associated thrombotic microangiopathy (TA-TMA) is well recognized as a serious complication of renal transplantation. TA-TMA is characterized by injury of arterioles and capillaries and encompasses syndromes of thrombocytopenia, microangiopathic hemolytic anemia(MAHA) and variable degrees of kidney graft dysfunction. TA-TMA can be classified into recurrent TMA (from underlying complement mutations) and de novo TMA. The incidence of de novo TMA ranges from 3-14%. Causes of de novo TMA include immunosuppressive drugs (tacrolimus, mTOR inhibitors, valgancyclovir), ischemia reperfusion injury, viral infections (CMV, Parvovirus B19, HIV, HHV-6) and antibody-mediated rejection. We have found that many of these cases also have very low levels of ADAMTS13 but do not meeting clinical criteria for TTP. If the latter is secondary to endothelial damage vs consumption process is still unknown. Objective: The purpose of this study was to identify if any specific risk factors or variables are associated with TA-TMA in the setting of deceased donor kidney transplantation (DDKT). Methods: We retrospectively collected data on 11 patients who were diagnosed with TA-TMA in the immediate post operative period (defined as less than 2 weeks from transplant date) since January, 2017. We analyzed donor characteristics including age, type of deceased donor, last known platelet count, biopsy features, pump parameters, cold ischemia time (CIT), warm ischemia time (WIT), reperfusion injury (RI) described at transplant surgery. Recipient variables included baseline platelet count on admission, the post-op day of diagnosis and at resolution (defined as platelet count > 100K and no need for additional transfusion), the use of thymoglobulin, ADAMS13 activity, changes in maintenance immunosuppression, evidence of post op bleeding, delayed graft function (DGF) and its recovery, and renal function at 1 and 3 months post transplant (Table). Results: 72% of the kidneys were from donation after cardiac death donors (DCD). The mean arterial pressure on the perfusion pump was 39 ± 7 mmHg and the flow was 148 ± 35 ml/sec. 81 % of the donor biopsies showed mild ATN, 72% had evidence of atherosclerosis and 54% of fibrosis and only one showed fibrin thrombi in the glomerulus. The mean CIT and WIT were 1913 ± 423 and 27 ± 32 min, respectively. The mean donor platelet count and baseline recipient’s platelet count were 209 ± 210 and 166 ± 71 x 10(3)/mcl, respectively. The TA-TMA event occurred on post op day 3± 1.3 with a mean platelet count of 45 ± 19 x 10(3)/mcl. ADAMTS 13 level was <10% in 54% of the cases and LDH level 2880 ± 55 U/L. 3 patients received FFP infusions, 5 received plasmapheresis and 3 received conservative treatment. The microangiopathic hemolytic anemia recovered in 10 ± 2.4 days to a platelet count of 130 ± 67 x 10(3)/mcl. There were 6 cases of post op bleeding (55%) with 4 requiring surgical intervention and 4 cases of RI (36%). Of the 8 patients that sustained DGF, 6 recovered at one month, one recovered at 3 months post transplant (having history of low C3 and late biopsy proven TMA) and one died. The mean SCr and eGFR at 1 and 3 months were 2± 1.1, 51 ± 34 and 1 ± 0.5 mg/dl and 66± 30 ml/min, respectively.There were no statistical differences on the above parameters when the patients were grouped by the presence of post operatory bleeding. However, when we added the reperfusion injury factor, we found a lower ADAMTS 13 levels of 17 ±7 UI/dl in the non bleeding group who sustained RI (60%) vs 21± 37 UI/dl in the bleeding group who had only one patient with RI (17%) (p=0.24). Conclusions: TA-TMA in the immediate postoperative period can be difficult to diagnose and treat. Our findings demonstrated that 55% of the cases were associated with post operatory bleeding leading to the reduction of ADAMTS 13 levels, most likely by platelet consumption. 36% were related to reperfusion injury where the consumption of ADAMTS 13 could be explained by direct endothelial damage. None of the patients needed other than conservative therapy. This data needs to be correlated in a larger cohort. In this context we are planning to prospectively study ADAMTS 13 activity in the immediate post kidney transplant period.

Markable coagulopathy in the patient with severe COVID-19

The variative coagulation abnormalities with thrombotic and microvascular complications are distinguishing feature of the severe new coronavirus infection (COVID-19) pathogenesis. Abnormal coagulopathy is directly related to the risk of death in COVID-19 patients. In many patients with COVID-19, hemostasis disorders have been observed, which increase the risk of developing DIC (disseminated intravascular coagulation), thrombotic microangiopathy or antiphospholipid syndrome as a result of the pathogenetic factors combination: inflammatory response, endothelial dysfunction, increased platelet consumption, microvascular thrombosis. The mechanism of coagulopathy associated with COVID is still being found, COVID-associated coagulopathy exemplifies the potentiating multi-factor interactions between the immune system and the coagulation. We’re reporting a fatal case of 51-year-old male with COVID-19, complicated by severe acute respiratory syndrome (SARS) and severe thrombocytopenia, markedly enhanced fibrinolytic activity with skin-hemorrhagic syndrome, thrombotic complication (myocardial infarction), probably related to the DIC. This case demonstrates the need more basic and clinical research is warranted to further our understanding of the role of coagulation disorders mechanism in COVID-19 to prevent severe outcomes and mortality.

In vitro thrombogenicity evaluation of rotary blood pumps by thromboelastometry.

In vitro thrombogenicity tests for rotary blood pumps (RBPs) could benefit from assessing coagulation kinematics, as RBP design improves. In this feasibility study, we investigated if the method of thromboelastometry (TEM) is able to assess coagulation kinematics under the in vitro conditions of RBP tests. We conducted in vitro thrombogenicity tests (n=4) by placing Deltastream® DP3 pumps into test loops that were filled with 150mL of slightly anti-coagulated porcine blood, adjusted to an activated clotting time (ACT) well below clinically recommended levels. Blood samples were taken at certain time points during the experiment until a continuous decrease in pump flow indicated major thrombus formation. Blood samples were analyzed for ACT, platelet count (PLT), and several TEM parameters. While visible thrombus formation was observed in three pumps, ACT indicated an ongoing activation of coagulation, PLT might have indicated platelet consumption. Unexpectedly, most TEM results gave no clear indications. Nonetheless, TEM clotting time obtained by non-anticoagulated and chemically non-activated whole blood (HEPNATEM-CT) appeared to be more sensitive for the activation of coagulation in vitro than ACT, which might be of interest for future pump tests. However, more research regarding standardization of thrombogenicity pump tests is urgently required.

A mean platelet volume in inflammatory bowel disease: A systematic review and meta-analysis.

BackgroundInflammatory bowel disease (IBD) is a chronic gastrointestinal tract inflammatory state, which is affecting millions of individuals in the world. It can affect alimentary canals such as colon, rectum, ileum and other parts. In IBD, platelet parameters underwent several changes. Therefore, the aim of this review was determining the estimated pooled mean platelet volume and mean difference in inflammatory bowel disease to elucidate its potential diagnostic value.MethodsArticles were extensively searched in bibliographic databases using Medical Subject Heading and entry phrases or terms. In addition, articles were directly searched in Google Scholar to account for the studies omission in searching bibliographic databases. Observational (cohort, cross-sectional and case-control) studies, published in English language and conducted on IBD were included. For studies meeting the eligibility criteria, the first author’s name, publication year, population, study design, study area, sample size, mean platelet volume and standard deviation were extracted and entered in to Microsoft-excel. The analysis was done by Stata version 11. In order to estimate the pooled mean platelet volume and mean difference, random effect model was done. The heterogeneity was quantified using Higgin’s I2 statistics. Publication bias was determined using Egger’s test statistics and funnel plot. Sub-group analysis based on population carried to reduce heterogeneity.ResultsA total of 17 relevant articles with 2957 participants (1823 IBD cases and 1134 healthy controls) were included to this study. The pooled estimated MPV was 9.29fl; 95% CI: 9.01–9.57 and 9.50fl; 95% CI: 8.81–10.20 in IBD and control groups, respectively. The standardized pooled estimate of mean difference in mean platelet volume was -0.83fl; 95% CI: -1.15, -0.51; I2: 93.1%; P-value < 0.001. In subgroup analysis based on population, the highest estimated mean difference in MPV was observed among patients of CD; -2.30; 95% CI: -3.46, -1.14; I2: 97.8%; P-value < 0.001.ConclusionAccording to the current systematic review and meta-analysis, mean platelet volume was lower in IBD compared to control. The decreased mean platelet volume could be attributed to platelet consumption or sequestration associated with the progression of IBD. As a result, in IBD, mean platelet volume can provide diagnostic and prognostic information.

Simultaneous C5 and CD14 inhibition limits inflammation and organ dysfunction in pig polytrauma.

Dysfunctional complement activation and Toll-like receptor signaling immediately after trauma are associated with development of trauma-induced coagulopathy and multiple organ dysfunction syndrome. We assessed the efficacy of the combined inhibition therapy of complement factor C5 and the TLR co-receptor CD14 on thrombo-inflammation and organ damage in an exploratory 72-h polytrauma porcine model, conducted under standard surgical and intensive care management procedures. Twelve male pigs were subjected to polytrauma, followed by resuscitation (ATLS® guidelines) and operation of the femur fracture (intramedullary nailing technique). The pigs were allocated to combined C5 and CD14 inhibition therapy group (n=4) and control group (n=8). The therapy group received intravenously C5 inhibitor (RA101295) and anti-CD14 antibody (rMil2) 30 min post-trauma. Controls received saline. Combined C5 and CD14 inhibition reduced the blood levels of the terminal complement complex (TCC) by 70% (p=0.004), CRP by 28% (p=0.004), and IL-6 by 52% (p=0.048). The inhibition therapy prevented the platelet consumption by 18% and TAT formation by 77% (p=0.008). Moreover, the norepinephrine requirements in the treated group were reduced by 88%. The inhibition therapy limited the organ damage, thereby reducing the blood lipase values by 50% (p=0.028), LDH by 30% (p=0.004), AST by 33%, and NGAL by 30%. Immunofluorescent analysis of the lung tissue revealed C5b-9 deposition on blood vessels in five from the untreated, and in none of the treated animals. In kidney and liver, the C5b-9 deposition was similarly detected mainly the untreated as compared to the treated animals. Combined C5 and CD14 inhibition limited the inflammatory response, the organ damage, and reduced the catecholamine requirements after experimental polytrauma and might be a promising therapeutic approach.