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Pulmonary embolism is a common complication after intracranial hemorrhage. As thrombolysis is contraindicated in this situation, surgical pulmonary embolectomy may be indicated in case of high-risk pulmonary embolism but requires transient anticoagulation with heparin during cardiopulmonary bypass. We report the case of a patient with a history of heparin-induced thrombocytopenia who presented with a high-risk pulmonary embolism 10 days after the spontaneous onset of a voluminous intracerebral hematoma. Despite high doses of heparin required to run the cardiopulmonary bypass and subsequent anticoagulation by danaparoid sodium, the brain hematoma remained stable and the patient was discharged without complications 30 days after surgery., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 International Anesthesia Research Society.)

Xenotransplantation using pigs' liver offers a potentially alternative method to overcome worldwide donor shortage, or more importantly as a bridge to allotransplantation. However, it has been challenged by profound thrombocytopenia and fatal coagulopathy in non-human primate models. Here we suggest that a left auxiliary technique can be a useful method to achieve extended survival of the xenograft. Fifteen consecutive liver xenotransplants were carried out in a pig-to-cynomolgus model. Right auxiliary technique was implemented in two cases, orthotopic in eight cases, and left auxiliary in five cases. None of the right auxiliary recipients survived after surgery due to hemorrhage during complex dissection between the primate's right lobe and inferior vena cava. Orthotopic recipients survived less than 7 days secondary to profound thrombocytopenia and coagulopathy. Two out of five left auxiliary xenotransplants survived more than 3 weeks without uncontrolled thrombocytopenia or anemia, with one of them surviving 34 days, the longest graft survival reported to date. Left auxiliary xenotransplant is a feasible approach in non-human primate experiments, and the feared risk of thrombocytopenia and coagulopathy can be minimized. This may allow for longer evaluation of the xenograft and help better understand histopathological and immunological changes that occur following liver xenotransplantation., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Purpose: Cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) is an adverse drug reaction occurring after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. CVST-VITT patients often present with large intracerebral haemorrhages and a high proportion undergoes decompressive surgery. Clinical characteristics, therapeutic management and outcomes of CVST-VITT patients who underwent decompressive surgery are described and predictors of in-hospital mortality in these patients are explored., Methods: Data from an ongoing international registry of patients who developed CVST within 28 days of SARS-CoV-2 vaccination, reported between 29 March 2021 and 10 May 2022, were used. Definite, probable and possible VITT cases, as defined by Pavord et al. (N Engl J Med 2021; 385: 1680-1689), were included., Results: Decompressive surgery was performed in 34/128 (27%) patients with CVST-VITT. In-hospital mortality was 22/34 (65%) in the surgical and 27/94 (29%) in the non-surgical group (p < 0.001). In all surgical cases, the cause of death was brain herniation. The highest mortality rates were found amongst patients with preoperative coma (17/18, 94% vs. 4/14, 29% in the non-comatose; p < 0.001) and bilaterally absent pupillary reflexes (7/7, 100% vs. 6/9, 67% with unilaterally reactive pupil, and 4/11, 36% with bilaterally reactive pupils; p = 0.023). Postoperative imaging revealed worsening of index haemorrhagic lesion in 19 (70%) patients and new haemorrhagic lesions in 16 (59%) patients. At a median follow-up of 6 months, 8/10 of surgical CVST-VITT who survived admission were functionally independent., Conclusions: Almost two-thirds of surgical CVST-VITT patients died during hospital admission. Preoperative coma and bilateral absence of pupillary responses were associated with higher mortality rates. Survivors often achieved functional independence., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Splenectomy is an effective intervention in primary immune thrombocytopenia (ITP). Attempts to define pre-clinical predictors of platelet response to splenectomy are inconsistent. Based on international studies defining the likelihood of platelet response using platelet sequestration, patients with relapsed/refractory ITP being considered for splenectomy at a regional Australian hospital were assessed with 111 indium-labelled autologous platelet sequestration (ILAPS) studies., Aims: To audit the use of ILAPS in an Australian setting and define its role in predicting response to splenectomy., Methods: A retrospective review of all patients referred for an ILAPS study at a regional hospital was performed. Results for each patient were expressed as an 'R' value (spleen/ liver uptake ratio) to quantify the platelet sequestration pattern and outcome post-splenectomy, based on platelet counts., Results: A total of 45 patients was identified: 13 underwent splenectomy and 32 were medically managed. Patients with favourable ILAPS scans (pure or predominant splenic sequestration) demonstrated a superior response post-splenectomy (100% overall response rate (ORR); 83.5% complete remission (CR)) compared with those with unfavourable ILAPS scans (mixed or pure hepatic sequestration) (71.4% ORR; 57.1% CR) over 12 months., Conclusions: The use of ILAPS in the Australian setting is feasible and this experience confirms larger international studies demonstrating its utility as a predictor of response to splenectomy in ITP. An unfavourable ILAPS scan could be considered a negative predictor of response prompting consideration for other emerging ITP treatments such as thrombopoietin-receptor agonists or B-cell depleting therapy such as Rituximab., (© 2021 Royal Australasian College of Physicians.)

The multilocular thymic cyst (MTC) is a rare, acquired disease caused by inflammatory changes in the thymus, and is associated with autoimmune diseases. We report a case of MTC with thrombocytopaenia, which improved following surgical resection. A 45-year-old man developed thrombocytopaenia with an anterior mediastinal tumour. Thrombocytopaenia due to an autoimmune mechanism, associated with thymoma or thymus-related disease, was suspected. Pathologic analysis following thoracoscopic thymectomy confirmed MTC. The platelet level recovered postoperatively. Our findings suggested a relationship between the acquired formation of MTC and the development of autoimmune antibodies. However, further investigation is needed to obtain more information., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Wound infection is frequently reported following snakebite (SB). This study is retrospective. It was conducted in the emergency department and the Intensive Care Unit (ICU) of Cayenne General Hospital between 1 January 2016 and 31 July 2021. We included 172 consecutive patients hospitalized for SB envenoming. All patients were monitored for wound infection. Sixty-three patients received antibiotics at admission (36.6%). The main antibiotic used was amoxicillin-clavulanate (92.1%). Wound infection was recorded in 55 cases (32%). It was 19% in grade 1, 35% in grade 2, and 53% in grade 3. It included abscess (69.1%), necrotizing fasciitis (16.4%), and cellulitis (21.8%). The time from SB to wound infection was 6 days (IQR: 3-8). The main isolated microorganisms were A. hydrophila and M. morganii (37.5% and 18.8% of isolated organisms). Surgery was required in 48 patients (28.1%), and a necrosectomy was performed on 16 of them (33.3%). The independent factors associated with snakebite-associated infection were necrosis ( p < 0.001, OR 13.15, 95% CI: 4.04-42.84), thrombocytopenia ( p = 0.002, OR: 3.37, 95% CI: 1.59-7.16), and rhabdomyolysis ( p = 0.046, OR: 2.29, 95% CI: 1.02-5.19). In conclusion, wound infection following SB is frequent, mainly in grade 2 and 3 envenomed patients, especially those with necrosis, thrombocytopenia, and rhabdomyolysis. The main involved bacteria are A. hydrophila and M. morganii .

The epidural blood patch is the gold-standard therapy to treat postdural puncture headaches from dural puncture when conservative therapies fail. However, an epidural blood patch is contraindicated in patients with coagulopathy and thrombocytopenia (platelet count of 60,000/µL) due to concerns of an epidural hematoma. We present a case of an adolescent with acute lymphocytic leukemia, thrombocytopenia, and persistent postdural puncture headaches. The patient was successfully treated with a sphenopalatine ganglion nerve block at the bedside without any side effects and complications., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Evans syndrome is a rare haematological disease that may cause several complications during heart surgery. Herein we documented heart valve surgery in a patient with Evans syndrome who was receiving monoclonal antibody therapy, and valve replacement was successfully performed via prophylactic measures against haemolysis., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Evans syndrome is defined by bilineal autoimmune cytopenia, typically coombs positive hemolytic anemia and thrombocytopenia. Corticosteroids are the mainstay of treatment, with rituximab and/or mycophenolate mofetil often used in steroid-refractory cases. However, no treatment methodology has ever evaluated by a randomized clinical trial. We present a 15-year-old boy with Evans syndrome and common variable immunodeficiency who experienced a severe, refractory flare 16 months postsplenectomy. After failing to respond to multiple other agents, he achieved a durable response to a bortezomib-based regimen. Bortezomib may be a reasonable second or third line option, especially before high-morbidity therapies such as splenectomy or stem cell transplantation.

Objective: Evans syndrome, the combination of immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA) or autoimmune neutropenia, is associated with a high rate of relapsed/refractory disease. There are limited data on the efficacy of splenectomy for this condition. We reviewed patient outcomes after splenectomy for Evans syndrome compared to ITP at our institution., Methods: We performed a retrospective analysis of patients who underwent splenectomy for autoimmune cytopenias over a 23-year period with the intention of comparing disease relapse rates after splenectomy in patients with Evans syndrome and in those with ITP., Results: During the study period, 77 patients underwent splenectomy for ITP and seven underwent splenectomy for Evans syndrome. In the Evans cohort, splenectomy led to an 85.7% initial response rate with a 42.8% rate of relapse within one year and a long-term (one-year) response rate of 42.8%. In the ITP cohort, the initial response rate was 90.9% with a long-term response rate of 70.1%., Conclusion: Our data suggest that long-term remission rates after splenectomy are lower in adults with Evans syndrome compared to those with ITP, although splenectomy may still be an acceptable treatment for certain patients with Evans syndrome. Our findings underscore the need for further research and development of additional therapeutic strategies for this patient population., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Spinal drain placement to prevent spinal cord ischemia during thoracic aorta surgery is a necessary yet complex undertaking in patients with coagulopathies. Thromboelastography (TEG) can be used as a point-of-care management tool to monitor coagulation status before drain placement and removal. We present 2 cases: a case of a patient with factor VII deficiency and a case of a patient with thrombocytopenia for whom TEG was an important procedural adjunct during coagulopathy reversal. TEG parameters are also discussed to encourage more frequent TEG use as an adjunct during these complex cases.

Background: Patients with thrombocytopenia associated with chronic liver disease (CLD) are at greater risk of bleeding during invasive procedures. This study characterized the pharmacokinetic/pharmacodynamic (PK/PD) profile of lusutrombopag, a novel thrombopoietin-receptor agonist, using modelling and simulation, and evaluated the appropriate dose regimen for treatment of thrombocytopenia in CLD patients undergoing invasive procedures., Methods: A population PK/PD model was developed using plasma lusutrombopag concentrations from 78 healthy subjects and 349 CLD patients, as well as platelet counts from 347 of these 349 patients. Covariates were explored from subject characteristics. Monte-Carlo simulations were performed to assess a dose response for efficacy (platelet counts ≥ 50,000/μL) and a risk for platelet overshooting (platelet counts > 200,000/μL)., Results: Visual predictive checks indicated the developed models described the PK/PD profile of lusutrombopag well. In the simulations, without stopping criteria, lusutrombopag 3 mg once daily for 7 days before scheduled invasive procedures provided effective platelet response (85.2% probability for efficacy). The probability of platelet overshooting was 1.2%, indicating that platelet monitoring is not necessary. Although body weight was an influential covariate on the pharmacokinetics of lusutrombopag, individually estimated peak platelet counts overlapped among the body weight groups, suggesting no clinically significant effect on body weight., Conclusion: The modelling and simulation support lusutrombopag 3 mg once daily for 7 days without platelet monitoring.

Background and Purpose: Acute ischemic stroke (AIS) has well-known risk factors. The role of platelets in patients treated using mechanical thrombectomy (MT) has not been studied. The aim of this study was to study if there is an association of initial thrombocytopenia (TP) and a decline of platelets counts (DPC) with the clinical outcomes, mortality and intracranial hemorrhage (ICH) rates in AIS patients treated with MT., Materials and Methods: In a case-control study consecutive MT-stroke patients were analyzed. A multivariate logistic regression model was used to test for good clinical outcome (mRS 90 days <= 2) and mortality adjusting for age, initial NIHSS, pretreatment with tPA, statins and platelet inhibitors, occlusion site, time from symptom onset to recanalization, initial TP (< 150 × 10 9 /L) and DPC (> 26%). Additionally, rates of ICH were compared., Results: Of 294 patients included, 9.6% had an initial TP and 23.8% a DPC > 26%. The mortality rate in patients with normal platelet counts was 26.1% vs. 48.3% (p = 0.002) in patients with initial TP with an aOR of 3.47 (CI 1.28-9.4, p = 0.005). No difference regarding the rate of good clinical outcome (p = 0.204) and ICH (p = 0.18) was observed. A DPC of more than 26% during the first 5 days of hospitalization predicted the rate of mortality (aOR 2.4 CI 1.14-5.04, p = 0.021) and the chances of a good clinical outcome (aOR 0.291 CI 0.128-0.666, p = 0.003) without significant differences of ICH rates (p = 0.735)., Conclusion: In AIS patients treated with MT an initial TP was independently associated with higher mortality rates and a marked DPC with higher mortality rates as well as poorer clinical outcomes.

Competing Interests: Competing interests: None declared.

Background: It is a novel idea that platelet counts may be associated with postoperative outcome following liver surgery. This may help in planning an extended hepatectomy (EH), which is a surgical procedure with high morbidity and mortality., Aim: The aim of this study was to evaluate the predictive potential of platelet counts on the outcome of EH in patients without portal hypertension, splenomegaly, or cirrhosis., Methods: A series of 213 consecutive patients underwent EH (resection of ≥ five liver segments) between 2001 and 2016. The association of preoperative platelet counts with posthepatectomy liver failure (PHLF), morbidity (based on Clavien-Dindo classification), and 30-day mortality was evaluated using multivariate analysis., Results: PHLF was detected in 26.3% of patients, major complications in 26.8%, and 30-day mortality in 11.3% of patients. Multivariate analysis revealed that the preoperative platelet count is an independent predictor of PHLF (odds ratio [OR] 4.4, 95% confidence interval [CI] 1.3-15.0, p =0.020) and 30-day mortality (OR 4.4, 95% CI 1.1-18.8, p =0.043)., Conclusions: Preoperative platelet count is associated with PHLF and mortality following extended liver resection. This association was independent of other related parameters. Prospective studies are needed to evaluate the predictive role and to determine the impact of preoperative correction of platelet count on postoperative outcomes after EH.

May-Hegglin anomaly (MHA) is an inherited autosomal dominant disorder characterized by giant platelets and inclusion bodies in granulocytes, and thrombocytopenia. There is no consensus on the perioperative management of this disorder. We report a case involving a patient with MHA who was perioperatively managed without platelet transfusion for cervical laminectomy and laminoplasty. In our case, the platelet count was measured to be 0.6 × 10 4 /µL using an automatic blood cell counter. Peripheral blood smear and genetic test analyses were performed, leading to a definitive diagnosis of MHA. However, clot retraction, serotonin release, and platelet aggregation were normal. Total intravenous anesthesia with propofol and remifentanil, in combination with intermittent injection of fentanyl, was administered. The total blood loss volume was 300 mL, and perioperative course was uneventful. Visual platelet count and platelet function were preserved in this case, although platelet or red blood cell transfusion was not performed. No bleeding tendency was observed during perioperative management.

Epstein syndrome is an extremely rare genetic disorder characterized by the association of nephritis, deafness and megathrombocytopenia. We present the case of a 21-year-old patient diagnosed with Epstein syndrome and hyperparathyroidism secondary to chronic kidney disease. The main particularity of this case resides in the association between megathrombocytopenia and secondary hyperparathyroidism requiring surgery, which could lead to a series of concerns regarding the intra- and postoperative hemorrhagic risk of the procedure. Nevertheless, both the surgical procedure and the postoperative recovery were uneventful, suggesting that the lower threshold for preoperative thrombocyte count in megathrombocytopenia should be specifically considered on an individual case analysis.

Introduction: The absence of evidence-based guidelines for platelet transfusion surrounding invasive neurosurgical procedures leads to uncertainty in management. Multiple studies have illuminated this lack of high quality data, and subsequent reliance on expert opinion. The generally accepted threshold for platelet transfusion has hovered around 100,000/μL., Methods: We have conducted a review of available clinical literature to identify any evidence that may support or refute these general guidelines, in an attempt to clarify the need for platelet transfusion in the patient requiring neurosurgical intervention., Results: The available evidence is sparse and of low quality, but suggests that a platelet count <100,000/μL is associated with increased risk of hemorrhagic complications. In addition, the acuity of thrombocytopenia, magnitude of decrease in platelet count, and responsiveness to platelet transfusions impact the risk of neurosurgical intervention, and should be taken into account when evaluating a patient's surgical candidacy. Higher quality, prospective studies on the subject are unlikely, given a general lack of clinical equipoise on the subject, and the ethical concerns such a study would present., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Rationale: Intravascular large B-cell lymphoma (IVLBCL) is an extremely rare subtype of large B-cell lymphoma characterized by the presence of lymphoma cells within the lumen of small blood vessels. IVLBCL presents with nonspecific symptoms such as fever, weight loss, and bleeding. Because of its rarity and unremarkable clinical presentation, a timely diagnosis is very challenging., Patient Concerns: A 71-year-old Korean man complained of fever, but apart from pretibial pitting edema and mild thrombocytopenia, the physical examination and laboratory test findings were unremarkable., Diagnoses: A bone marrow biopsy was also nonspecific. The fever persisted and his thrombocytopenia became more pronounced, prompting further laboratory tests that indicated infiltrative liver disease., Interventions: Because of coagulopathy, a liver biopsy was performed using a transjugular instead of apercutaneous approach., Outcomes: The procedure was performed without complications, and the pathologic examination findings were consistent with IVLBCL. Unfortunately, the patient died because of disease progression before treatment could be administered., Lessons: Given that an early diagnosis can affect the prognosis of IVLBCL, quickly and safely obtaining a biopsy specimen is very important. The case presented here shows that a liver biopsy obtained via a transjugular approach is safe and could be preferentially considered when there is a high risk for bleeding complications.

Splenic macrophages play a key role in immune thrombocytopenia (ITP) pathogenesis by clearing opsonized platelets. Fcγ receptors (FcγR) participate in this phenomenon, but their expression on splenic macrophages and their modulation by treatment have scarcely been studied in human ITP. We aimed to compare the phenotype and function of splenic macrophages between six controls and 24 ITP patients and between ITP patients according to the treatments they received prior to splenectomy. CD86, human leucocyte antigen D-related (HLA-DR) and FcγR expression were measured by flow cytometry on splenic macrophages. The major FcγR polymorphisms were determined and splenic macrophage function was assessed by a phagocytosis assay. The expression of the activation markers CD86 and HLA-DR was higher on splenic macrophages during ITP compared to controls. While the expression of FcγR was not different between ITP and controls, the phagocytic function of splenic macrophages was reduced in ITP patients treated with intravenous immunoglobulin (IVIg) within the 2 weeks prior to splenectomy. The FCGR3A (158V/F) polymorphism, known to increase the affinity of FcγRIII to IgG, was over-represented in ITP patients. Thus, these are the first results arguing for the fact that the therapeutic use of IVIg during human chronic ITP does not modulate FcγR expression on splenic macrophages but decreases their phagocytic capabilities., (© 2017 British Society for Immunology.)

Background: Carotid endarterectomy (CEA) is infrequently performed in patients with mild to moderate thrombocytopenia., Objective: To determine whether preoperative thrombocytopenia is associated with a higher rate of complications after CEA., Methods: We analyzed patient characteristics, comorbid conditions, operative details, and 30-day postoperative outcomes for patients who underwent CEA in the CEA-targeted American College of Surgeons National Surgical Quality Improvement Program Registry. Thrombocytopenia was defined based on the preprocedure platelet count of ≤150  000 platelets/μL. The odds ratios (ORs) for selected outcomes were calculated using logistic regression with stepwise forward selection with age, sex, symptomatic status, and high-risk individuals as potential confounders., Results: Thrombocytopenia was present in 896 of 8658 patients (10.3%) who underwent CEA: mild (100 000-149 000 platelets/μL) and moderate (50 000-99 000 platelets/μL) in 805 patients (89.8%) and 91 patients (10.2%), respectively. The adjusted rates of myocardial infarction/arrhythmia (3.7% vs 1.8%; OR: 1.9; 95% confidence interval [CI]: 1.3-2.8; P = .001), unplanned intubations (2.6% vs 1.2%; OR: 2.2; 95% CI: 1.4-3.5; P = .001), ventilator requirement >48 hours (1.5% vs 0.7%; OR: 2.1; 95% CI: 1.1-3.8; P = .02), deep venous thrombosis/thrombophlebitis (0.7% vs 0.2%; OR: 3.7; 95% CI: 1.4-9.7; P = .01), and surgical deep incisional infections (0.3% vs 0.1%; OR: 4.3; 95% CI: 1.1-17.4; P = .04) post-CEA were higher among patients with thrombocytopenia compared with those without thrombocytopenia. Thrombocytopenia did not significantly contribute to 1-month mortality or stroke., Conclusion: The higher rate of postprocedure complications in patients with preoperative thrombocytopenia needs to be recognized for adequate risk stratification before CEA., (Copyright © 2016 by the Congress of Neurological Surgeons)

Thrombocytopenia as well as anti-platelet factor 4/heparin (PF4/H) antibodies are common in cardiac surgery patients and those treated in the intensive care unit. In contrast, heparin-induced thrombocytopenia (HIT) is uncommon in these populations (~1 % and ~0.5 %, respectively). A stepwise approach where testing for anti-PF4/H antibodies is performed only in patients with typical clinical symptoms of HIT improves diagnostic specificity of the laboratory assays without losing sensitivity, thereby helping to avoid overdiagnosis and resulting HIT overtreatment. Short-term re-exposure to heparin, especially given intraoperatively for cardiovascular surgery, is a reasonable therapeutic option in patients with a history of HIT who subsequently test negative for HIT antibodies. Organ failure(s), enhanced bleeding risks, and other characteristics require special considerations regarding non-heparin anticoagulation: Argatroban is the alternative anticoagulant with pharmacokinetics independent of renal function, but it has a prolonged half-life in case of impaired liver function. For bivalirudin, protocols during cardiopulmonary bypass surgery are established, and it is suitable for patients with liver insufficiency. A major issue of direct thrombin inhibitors are false high activated partial thromboplastin time values in patients with comorbidities affecting prothrombin, which can result in systematic underdosing of the drugs. This is not the case for danaparoid and fondaparinux, which can be monitored by anti-factor Xa assays, but have long half-lives and no suitable antidote. This review includes also information on management of on- and off-pump cardiac surgery, ventricular assist devices, percutaneous interventions, continuous renal replacement therapy, and extracorporeal membrane oxygenation in patients with HIT.

Introduction: In patients with transient thrombocytopenia being treated with high-dose chemotherapy followed by stem cell rescue-haematopoietic stem cell transplantation (HSCT), prophylactic transfusions are standard therapy to prevent bleeding. However, a recent multicentre trial suggests that prophylactic platelet transfusions in HSCT may not be necessary. Additionally, the potential overuse of platelet products places a burden on a scarce healthcare resource. Moreover, the benefit of prophylactic platelet transfusions to prevent clinically relevant haemorrhage is debatable. Current randomised data compare different thresholds for administering prophylactic platelets or prophylactic versus therapeutic platelet transfusions. An alternative strategy involves prescribing prophylactic antifibrinolytic agents such as tranexamic acid to prevent bleeding., Methods and Analysis: This report describes the design of an open-labelled randomised pilot study comparing the prophylactic use of oral tranexamic acid with platelet transfusions in the setting of autologous HSCT. In 3-5 centres, 100 patients undergoing autologous HSCT will be randomly assigned to either a prophylactic tranexamic acid or prophylactic platelets bleeding prevention strategy-based daily platelet values up to 30 days post-transplant. The study will be stratified by centre and type of transplant. The primary goal is to demonstrate study feasibility while collecting clinical outcomes on (1) WHO and Bleeding Severity Measurement Scale (BSMS), (2) transplant-related mortality, (3) quality of life, (4) length of hospital stay, (5) intensive care unit admission rates, (6) Bearman toxicity scores, (7) incidence of infections, (8) transfusion requirements, (9) adverse reactions and (10) economic analyses., Ethics and Dissemination: This study is funded by a peer-reviewed grant from the Canadian Institutes of Health Research (201 503) and is registered on Clinicaltrials.gov NCT02650791. It has been approved by the Ottawa Health Science Network Research Ethics Board. Study results will presented at national and international conferences. Importantly, the results of this trial will inform the feasibility and conduct of a larger study., Trial Registration Number: NCT02650791; Pre-results., Competing Interests: Conflicts of Interest: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: Splenectomy and partial splenic embolization as the surgical approach in the treatment of hypersplenism and thrombocytopenia have been reported. However, there are still some disadvantages in the application of these techniques. In this article, we propose a new technique for the treatment of hypersplenism and thrombocytopenia in children and report our preliminary experience., Methods: From Aug 2014 to Dec 2014, four children with hypersplenism and three children with idiopathic thrombocytopenic purpura were treated in our hospital. Laparoscopic splenic vessels ligation was performed in all patients. The gastric wall was suspended to expose the pancreatic tail and spleen, and the splenic artery was ligated at the superior border of the pancreas. The splenic venous branches were dissected and ligated at the splenic hilum using the Hem-o-lok., Results: The laparoscopic splenic vessels ligation was successfully performed in all patients. The average operative time was 126 min (range 120-150 min). No patient required transfusion, and the length of hospital stay varied from 4 to 11 days (mean 6.6 days). The patients were followed up for 6-10 months (mean 8.5 months). The complete blood counts were within normal range. The size of spleen decreased postoperatively. The partial splenic infarction and the reduction in splenic blood flow were confirmed in all patients by postoperative ultrasound and CT., Conclusions: The laparoscopic splenic vessels ligation is a feasible option for treating hypersplenism and thrombocytopenia in children.

Background: Blood salvage systems help to minimize intraoperative transfusion of allogenic blood. So far no data is available on the use of argatroban for anticoagulation of such systems. We conducted an ex-vivo trial to evaluate the effectiveness of three different argatroban doses as compared to heparin and to assess potential residual anticoagulant in the red cell concentrates., Methods: With ethical approval and individual informed consent, blood of 23 patients with contraindications for use of blood salvage systems during surgery was processed by the Continuous-Auto-Transfusion-System (C.A.T.S. ® Cell Saver System, Fresenius Kabi, Bad Homburg, Germany) using 5,50 or 250 mg of argatroban or 25.000 U of heparin in 1000 ml saline for anticoagulation of the system. Emergency and high-quality washing modes were applied in random order. Patency of the system and residual amount of anticoagulants in the re-transfusion bag were measured. The collected blood was not re-infused, but only used for analysis of hematocrit, heparin and argatroban concentrations., Results: Patency of the system was provided by all anticoagulants except for 3/8 cases with 5 mg of argatroban. Residual anticoagulant was found in 2/10 (20 %) heparin samples in two different patients (1 emergency and 1 high-quality washing) and in all argatroban samples. High quality washing eliminated 89-95 % and emergency washing 60-90 % of the initial argatroban concentration. Residual argatroban concentrations ranged from 55 ng ml(-1) to 6810 ng ml(-1), with initial argatroban concentrations of 5 and 250 mg, respectively., Conclusion: The C.A.T.S. does not reliably remove heparin and should therefore not be used in HIT patients. Anticoagulation with 50 and 250 mg argatroban, maintains the systems patency and is significantly removed during washing. In this ex-vivo study a concentration of 50 μg ml(-1) argatroban provided the best ratio of system patency and residual argatroban concentration. Additional dose-finding studies with different blood salvage systems are needed to evaluate the optimal argatroban concentration.

An eight-yr-old female with a history of multifocal lymphangioendotheliomatosis and thrombocytopenia presented for MVT. The patient had multiple vascular lesions in the skin and stomach in infancy. Although her cutaneous lesions resolved with vincristine and methylprednisolone, her gastric lesions persisted. Eight yr later, she was diagnosed with portal hypertension and decompensating liver function despite therapy with bevacizumab, propranolol, furosemide, and spironolactone. Upon presentation, she was found to have a Kasabach-Merritt-like coagulopathy in association with multiple lesions in her GI tract and persistent gastric lesions. Although treatment with methylprednisolone and sirolimus normalized her coagulation factors and d-dimer levels, she never developed sustained improvement in her thrombocytopenia. Her liver function continued to deteriorate and she developed hepatorenal syndrome. Given better outcomes after OLT in comparison with MVT, she underwent OLT, with the plan to manage her GI lesions with APC post-transplant. Post-transplant, her liver function and coagulopathy normalized, and GI tract lesions disappeared upon screening with capsule endoscopy. The patient is doing well, without recurrence of either GI lesions or thrombocytopenia, at 18 months after transplantation., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The direct thrombin inhibitor bivalirudin is an option for anticoagulation in patients with heparin induced thrombocytopenia (HIT) requiring cardiopulmonary bypass (CPB). There are a limited number of reports of pediatric patients in which bivalirudin has been used for anticoagulation for CPB. We present the case of an 11 year old male with acute onset heart failure secondary to idiopathic dilated cardiomyopathy that developed heparin induced thrombocytopenia with thrombosis (HITT). The patient was anticoagulated in the operating room with bivalirudin and placed on CPB for insertion of a HeartWare(®) Ventricular Assist Device (Heartware(®)). Modified techniques were utilized. This included use of the Terumo CDI 500 (Terumo Cardiovascular Systems, Inc.) in-line blood gas monitor which contains a heparin coated arterial shunt sensor. We flushed this sensor with buffered saline preoperatively and noted no significant decrease in platelet count postoperatively. The patient was successfully placed on the ventricular assist device and was subsequently listed for heart transplantation.

Background: Perioperative hemorrhage impacts patient outcomes and health care resource utilization, yet the risks of transfusion therapies are significant. In patients with preoperative thrombocytopenia, the effects of prophylactic preoperative platelet (PLT) transfusion on perioperative bleeding complications remain uncertain., Study Design and Methods: This is a retrospective cohort study of noncardiac surgical patients between January 1, 2008, and December 31, 2011. Propensity-adjusted analyses were used to evaluate associations between preoperative thrombocytopenia, preoperative PLT transfusion, and the outcomes of interest, with a primary outcome of perioperative red blood cell (RBC) transfusion., Results: A total of 13,978 study participants were included; 860 (6.2%) had a PLT count of not more than 100 × 10(9) /L with 71 (8.3%) receiving PLTs preoperatively. Administration of PLTs was associated with higher rates of perioperative RBC transfusion (66.2% vs. 49.1%, p = 0.0065); however, in propensity-adjusted analysis there was no significant difference between groups (odds ratio [OR] [95% confidence interval {95% CI}], 1.68 [0.95-2.99]; p = 0.0764]. Patients receiving PLTs had higher rates of intensive care unit (ICU) admission (OR [95% CI], 1.95 [1.10-3.46]; p = 0.0224) and longer hospital lengths of stay (estimate [95% bootstrap CI], 7.2 [0.8-13.9] days; p = 0.0006) in propensity-adjusted analyses., Conclusion: Preoperative PLT transfusion did not attenuate RBC requirements in patients with thrombocytopenia undergoing noncardiac surgery. Moreover, preoperative PLT transfusion was associated with increased ICU admission rates and hospital duration. These findings suggest that more conservative management of preoperative thrombocytopenia may be warranted., (© 2015 AABB.)

Background: Prophylactic platelet (PLT) transfusions are often administered to patients before bronchoscopy or bronchoalveolar lavage (BAL) to prevent bleeding. There is a paucity of data to validate this approach, with a commonly suggested PLT transfusion threshold of fewer than 50 × 10(9) /L, largely based on expert opinion. We conducted a retrospective study on the incidence of bleeding complications in patients with thrombocytopenia undergoing bronchoscopy., Study Design and Methods: We identified 150 consecutive patients with PLT counts of not more than 100 × 10(9) /L who underwent bronchoscopy and/or BAL from January 2009 to May 2014 at our institution. The British Thoracic Society (BTS) guidelines were used to categorize bleeding associated with bronchoscopy., Results: Infection (40%) was the primary indication for bronchoscopy with BAL. Fifty-eight of 89 (65%) patients with baseline PLT counts of not more than 50 × 10(9) /L received prophylactic transfusions compared to 8% of those with PLT counts of more than 50 × 10(9) /L. The PLT count did not increase to more than 50 × 10(9) /L in many patients who received transfusions. Seventy-two patients had counts of less than 50 × 10(9) /L at the time of bronchoscopy, with 15 patients having counts of less than 20 × 10(9) /L. Only one patient with a PLT count of 61 × 10(9) /L had bleeding that required continuous suctioning but then resolved spontaneously (termed "mild bleeding" by BTS criteria). Bloody lavage that resolved spontaneously without continuous suctioning (termed "no bleeding" by the BTS criteria) was observed in nine (6%) patients., Conclusion: The very low incidence of bleeding complications from bronchoscopy with or without BAL even in patients with PLT counts of not more than 30 × 10(9) /L (no episodes of clinically significant bleeding in 35 patients) demonstrates that bronchoscopy can be done safely in patients with severe thrombocytopenia., (© 2015 AABB.)

Background: Mutations of nonmuscle myosin heavy chain 9 (MYH9) gene are an autosomal dominant cause of inherited thrombocytopenia in children. MYH9 spectrum disorders include May-Hegglin anomaly and Sebastian, Fechtner, and Epstein syndromes. Patients with these disorders often present with macroplatelets and thrombocytopenia and have a mild bleeding tendency; extrahematologic manifestations (nephropathy, deafness, and cataracts) correlate with specific mutations. No definitive guidelines exist for preoperative prophylactic platelet (PLT) transfusion in these patients., Study Design and Methods: This was a case study and literature review., Results: A 6-year-old male presented with appendicitis. Review of records revealed that he and his siblings had thrombocytopenia; polymerase chain reaction amplification with DNA sequence analysis showed a variation in the MYH9 gene previously reported as a known cause of MYH9-related disorders. Involvement of other organ systems was not found on initial work-up. The patient's PLT count on admission was 20 × 10(9) /L. The degree of thrombocytopenia prompted transfusion of apheresis PLTs and he had good response (73 × 10(9) /L). After infusion he developed hives, rash, itching, and nausea, which resolved after administration of epinephrine and hydrocortisone. Transfusion reaction work-up was negative and symptoms were interpreted as an allergic reaction. The appendectomy was uneventful., Conclusion: This patient's PLT count was within guidelines to warrant transfusion; however, some patients with MYH9 mutations have counts above the transfusion threshold. To the authors' knowledge, there are no set guidelines for preoperative prophylaxis in a patient with an MYH9 deficiency. The management of the bleeding diathesis in these patients, especially in the setting of invasive procedures, is uncertain., (© 2015 AABB.)

Heparin-induced thrombocytopenia (HIT) is a rare but life-threatening side effect of heparin therapy. It is a demanding therapeutic challenge in patients undergoing left ventricular assist device (LVAD) implantation. We present our experience with LVAD implantation under extracorporeal life support (ECLS) in patients suffering from HIT. Seven patients (mean age 54.0 ± 16.7 years, 1 female, 6 male patients) suffering from acute heart failure were stabilized with ECLS. Under heparin therapy, they all showed a sudden decrease of mean platelet count (maximum 212.6 ± 41.5 tsd/μl; minimum 30.7 ± 13.1 tsd/μl). Due to the clinical suspicion of HIT anticoagulation was switched from heparin to argatroban (aPTT 70-80 s.). No improvement of cardiac function could be detected under ECLS, so LVAD implantation was indicated. We performed LVAD implantation under ECLS. During LVAD implantation under argatroban (aPTT of 50-60 s.) one patient developed massive intraventricular thrombus formations, so the device had to be removed. In 6 cases, we could successfully perform LVAD implantation under argatroban with a higher aPTT of 70-80 s and modified operative strategy. Four patients needed postoperative re-exploration because of bleeding complications. Perioperative management of LVAD patients under argatroban anticoagulation is very difficult. We were able to minimize the perioperative risk for thrombosis with a target aPTT of 70-80 s. To keep the phase of stasis within the device as short as possible we anastomosed the VAD outflow graft to the ascending aorta first before connecting the device to the apex. However, postoperative bleeding complications are frequent.

An autosomal dominant hereditary disease, Epstein syndrome (ES) is characterized by sensorineural hearing impairment, macrothrombocytopenia, and hereditary nephritis, and can progress to end-stage kidney disease after puberty. Generally, kidney transplantation is difficult to perform in Epstein syndrome owing to the high risk of perioperative bleeding. Additionally, due to previous platelet transfusions, ES patients sometimes have antihuman leukocyte antigen (HLA) antibodies, including antiplatelet antibodies and donor-specific anti-HLA antibodies (DSA), which may result in refractoriness to platelet transfusion and antibody-mediated rejection (AMR). We report a case of successful kidney transplantation in a patient with ES who had DSA and antiplatelet antibodies. To prevent AMR, we used a desensitization protocol (a combination of plasmapheresis, rituximab, and basiliximab induction). Surveillance biopsy performed at 4 months and 1 year after transplantation showed no pathological findings suggesting AMR. To prevent perioperative bleeding complications, we infused the patient with HLA-matched platelets, thereby maintaining the platelet count at >10.0 × 10(4)/μL, and no postoperative episodes of bleeding occurred., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Budd-Chiari syndrome is a rare condition caused by interrupted hepatic venous outflow in the hepatic veins, inferior vena cava, or right atrium. Reports from the literature have delineated on focal nodular hyperplasia (FNH)-like lesions in association with Budd-Chiari Syndrome. To our knowledge, there are no reports about true FNH lesions in patients with Budd-Chiari Syndrome. Focal nodular hyperplasia develops in disorders with aberrant circulation and vasculature. We report a case of Budd-Chiari syndrome in association with large solitary FNH in a 22-year-old man who was referred to our institution with sudden intermittent right upper quadrant abdominal pain, vomiting, diarrhea with pale stool, decreased appetite, dark urine, and abdominal distention for 15 days. Laboratory investigations revealed anemia, thrombocytosis, and abnormal liver function tests and coagulation profile. Imaging revealed hepatic vein thrombosis, confirming Budd-Chiari syndrome, and a 6.2 × 6.1 × 6.8 cm lesion in segment 8 of the liver. Primary cause of Budd-Chiari syndrome was essential thrombocythemia according to bone marrow biopsy and molecular testing results. The patient was treated medically and underwent transjugular intrahepatic portosystemic shunt insertion. The lesion in segment 8 continued to enlarge. Cadaveric liver transplantation was carried out. On gross and histologic examination of the explanted liver, the lesion was found to be a true FNH., (Copyright © 2015 Elsevier Inc. All rights reserved.)

We present a case of a patient with hypersplenism secondary to portal hypertension due to hepato-splenic schistosomiasis, which was accompanied by severe and refractory thrombocytopenia. We performed spleen ablation and measured the total spleen and ablated volumes with contrast-enhanced computed tomography and volumetry. No major complications occurred, thrombocytopenia was resolved, and platelet levels remained stable, which allowed for early treatment of the patient's underlying disease. Previous work has shown that splenic radiofrequency ablation is an attractive alternative treatment for hypersplenism induced by liver cirrhosis. We aimed to contribute to the currently sparse literature evaluating the role of radiofrequency ablation (RFA) in the management of hypersplenism. We conclude that splenic RFA appears to be a viable and promising option for the treatment of hypersplenism.

The small GTPase RAP1 is critical for platelet activation and thrombus formation. RAP1 activity in platelets is controlled by the GEF CalDAG-GEFI and an unknown regulator that operates downstream of the adenosine diphosphate (ADP) receptor, P2Y12, a target of antithrombotic therapy. Here, we provide evidence that the GAP, RASA3, inhibits platelet activation and provides a link between P2Y12 and activation of the RAP1 signaling pathway. In mice, reduced expression of RASA3 led to premature platelet activation and markedly reduced the life span of circulating platelets. The increased platelet turnover and the resulting thrombocytopenia were reversed by concomitant deletion of the gene encoding CalDAG-GEFI. Rasa3 mutant platelets were hyperresponsive to agonist stimulation, both in vitro and in vivo. Moreover, activation of Rasa3 mutant platelets occurred independently of ADP feedback signaling and was insensitive to inhibitors of P2Y12 or PI3 kinase. Together, our results indicate that RASA3 ensures that circulating platelets remain quiescent by restraining CalDAG-GEFI/RAP1 signaling and suggest that P2Y12 signaling is required to inhibit RASA3 and enable sustained RAP1-dependent platelet activation and thrombus formation at sites of vascular injury. These findings provide insight into the antithrombotic effect of P2Y12 inhibitors and may lead to improved diagnosis and treatment of platelet-related disorders.

Background: Evans syndrome (ES) is characterized by the simultaneous or sequential presence of multiple autoimmune cytopenias. It is often secondary to rheumatologic disorders or lymphoid malignancies, but has not previously been associated with babesiosis. Here we present two cases of severe cytopenias in asplenic patients precipitated by active babesiosis., Case Report: The first patient had a history of Hodgkin's lymphoma in remission and autoimmune hemolytic anemia (AIHA) treated by splenectomy 12 years prior who presented with severe AIHA and thrombocytopenia after Babesia infection. The second patient had a history of ES requiring splenectomy, which relapsed after Babesia infection., Results: The complex presentation and medical histories of both patients made the diagnosis challenging. Both patients' cytopenias responded to therapy, although the use of immunosuppressive agents in patients with active hematologic infections was challenging and required a multidisciplinary approach., Conclusion: These two cases illustrate the possibility of babesiosis to not only reactivate ES in asplenic patients, but also precipitate increased levels of immune deregulation, potentially provoking ES, a phenomenon not previously reported., (© 2014 AABB.)

Objective: Developmental abnormalities of the appendicular skeleton are among the most common and easily identified birth defects. The aim of this report was to describe the phenotypic characterization of several patients with thrombocytopenia-absent radius (TAR) syndrome and the orthopaedic interventions performed on them. TAR syndrome is inherited in an autosomal recessive manner and results from compound heterozygosity of RBM8A mutations., Methods: Reconstructions were designed and performed in five patients with TAR syndrome, mainly comprising orthopaedic interventions to correct their upper limb defects. Additional lower limb deformities (severe internal rotation of the tibiae) was been encountered in one patient., Results: The affected patients' wrists were re-aligned and stabilized and the musculotendinous forces around the wrist rebalanced to reverse the ulnar forearm bow., Conclusion: Patients with TAR syndrome who receive optimal treatment can expect to return to most activities of daily living with some limitation of wrist extension and ulnar deviation and, of course, with a reduced total active range of digital motion., (© 2015 Chinese Orthopaedic Association and Wiley Publishing Asia Pty Ltd.)

Unlabelled: Silicone oil is used for complicated retinal detachment, but it can be associated with relevant side effects. We report a 6-year-old South American female admitted to our hospital with steroid-resistant Fisher-Evans syndrome. She also had developed a retinal detachment, managed with intravitreal oil injection. During treatment for Fisher-Evans syndrome, she progressively developed recurrent and refractory bronchospasm, peaks of hypereosinophilia and orbital soft-tissue swelling. Despite the persistent negativity of all microbiologic tests, she was treated empirically with antibiotics. Failure of the treatment led to the execution of a biopsy of the periocular tissue that revealed an intense polymorphous infiltrate constituted by numerous monoclonal population (FR2 monoclonality) of plasma-cells. A diagnosis of lymphoma with plasmacytoid differentiation was suspected and cytotoxic treatment was started without response. For the appearance of swelling in left parotid and laterocervical region, an excisional biopsy was performed and a diagnosis of granulomatous reaction to ocular implant of silicone oil was made. In consideration of the clinical evolution, enucleation was considered, but parents did not consent to the procedure until the child developed cerebral lesions suspected to be silicone localizations. After enucleation, eosinophilic count normalized and the child no longer presented any new episode of fever or swelling., Conclusions: In this patient a granulomatous reaction is present at distance from the site of oil injection. This case suggests caution in using this substance even in ocular diseases, especially in immunocompromised patients.