Zoonotic Bacterial Infections Triggering Cytokine Storm Syndrome.

Zoonotic infections can result in life-threatening complications that can manifest with hemophagocytic lymphohistiocytosis (HLH)/cytokine storm syndrome (CSS). Bacteria constitute the largest group of zoonotic infection-related HLH cases. The growing list of zoonotic bacterial infections associated with HLH/CSS include Brucella spp., Rickettsia spp., Ehrlichia, Coxiella burnetii, Mycobacterium spp., and Bartonella spp. Patients most commonly present with fever, cytopenias, hepatosplenomegaly, myalgias, and less frequently with rash, jaundice, and lymphadenopathy.

Predictors of intraoperative massive transfusion in orthotopic liver transplantation.

BACKGROUND: Although transfusion management has improved during the last decade, orthotopic liver transplantation (OLT) has been associated with considerable blood transfusion requirements which poses some challenges in securing blood bank inventories. Defining the predictors of massive blood transfusion before surgery will allow the blood bank to better manage patients' needs without delays. We evaluated the predictors of intraoperative massive transfusion in OLT. STUDY DESIGN AND METHODS: Data were collected on patients who underwent OLT between 2007 and 2017. Repeat OLTs were excluded. Analyzed variables included recipients' demographic and pretransplant laboratory variables, donors' data, and intraoperative variables. Massive transfusion was defined as intraoperative transfusion of ≥10 units of packed red blood cells (RBCs). Statistical analysis was performed using SPSS version 17.0. RESULTS: The study included 970 OLT patients. The median age of patients was 57 (range: 16-74) years; 609 (62.7%) were male. RBCs, thawed plasma, and platelets were transfused intraoperatively to 782 (80.6%) patients, 831 (85.7%) patients, and 422 (43.5%) patients, respectively. Massive transfusion was documented in 119 (12.3%) patients. In multivariate analysis, previous right abdominal surgery, the recipient's hemoglobin, Model for End Stage Liver Disease (MELD) score, cold ischemia time, warm ischemia time, and operation time were predictive of massive transfusion. There was a direct significant correlation between the number of RBC units transfused and plasma (Pearson correlation coefficient r = .794) and platelets (r = .65). DISCUSSION: Previous abdominal surgery, the recipient's hemoglobin, MELD score, cold ischemia time, warm ischemia time, and operation time were predictive of intraoperative massive transfusion in OLT.

Clinical and laboratory characteristics of patients with cold agglutinin disease: A retrospective analysis at a tertiary medical center.

BACKGROUND: Cold agglutinin disease (CAD) is relatively rare and has primarily been reported as retrospective case series. AIM: We reviewed our experience with CAD to shed light on this disease. STUDY SETTINGS AND DESIGN: This was a retrospective review of all patients with CAD managed at our institution between 2007 and 2018. MATERIALS AND METHODS: The study was approved by our institutional review board. We extracted patients' demographic, clinical, and laboratory data, blood transfusions, and outcomes from their electronic medical records. STATISTICAL ANALYSIS USED: Statistical analysis was performed using SPSS version 17. The method of Kaplan-Meier was used to plot survival curves. RESULTS: Forty-eight patients fulfilled the inclusion criteria for CAD. The median age of patients was 73.1 (range, 43-99) years; 36 (75%) were female. The majority (n = 38; 79.2%) of patients were Caucasians. Most patients (n = 25, 52.1%) presented with symptomatic anemia. Eight patients were asymptomatic. The median hemoglobin level was 8.6 g/dL (range, 3-12 g/dL); 7 (14.6%) patients had concurrent thrombocytopenia. Lactate dehydrogenase was elevated in 40/47 (85.1%) patients and haptoglobin was below normal in 35/46 (76.1%) patients. Coagulopathy was observed in 19 (52.8%) of 36 patients. Sixteen (33.3%) patients required blood transfusion during admission at the time of diagnosis with a median number of 3.5 red blood cell units. Twenty-five (52.1%) patients were alive after a median follow-up of 50.1 months. The 5-year and 10-year survival was estimated at 58.2% and 30.8%, respectively. CONCLUSION: CAD poses considerable burden on patients and health-care systems. Patients vary widely in their disease severity and course.

Complete Neurologic Recovery of Cerebral Fat Embolism Syndrome in Sickle Cell Disease.

Sickle cell disease is one of the most common inherited hemoglobinopathies diagnosed in the United States. Patients often present with severe anemia, pain crises, infections, and vaso-occlusive phenomena. Complications of these disorders can lead to significant debilitating morbidity and mortality. Fat embolism syndrome (FES) is a rare and devastating complication of sickle cell disease. It usually presents with a rapidly deteriorating clinical course, and the prognosis is dismal. We report a case of FES in a 19-year-old African American male with a history of sickle cell disease who presented with tonic-clonic seizures and was found to have multi-organ failure. FES was diagnosed 20 days from a presentation based on blood cytopenias and magnetic resonance imaging findings that were obscured at the initial presentation. We describe in this report, the patient's course from presentation until diagnosis and resolution. Our case is peculiar as the patient had a very good outcome without the need for red blood cell (RBC) exchange; instead, supportive treatment and simple RBC transfusions were enough to change the clinical course of this almost fatal syndrome.

Extracorporeal photopheresis: A case of graft-versus-host-disease and hemophagocytic lymphohistiocytosis following liver transplantation.

BACKGROUND: Graft-versus-host-disease (GVHD) is one of the rare complications following liver transplantation. We report on the efficacy and safety of extracorporeal photopheresis (ECP) in managing GVHD and hemophagocytic lymphohistiocytosis (HLH) after liver transplantation. CASE REPORT: The patient is a 63-year-old male with hepatitis B cirrhosis who underwent liver transplantation. Three weeks after transplant, he presented with fever, diarrhea, and poor appetite. The patient also had bilateral blanchable erythematous patches on his palms, biopsy of which was suggestive of GVHD. The patient continued to have high-grade fever with altered mental status. CBC showed pancytopenia. Liver function examination was normal. Patient was started on methylprednisolone. Additional laboratory analysis showed high ferritin (>15000 ug/L), triglycerides (280 mg/dl), and low fibrinogen (80 mg/dl). Chimerism analysis using short tandem repeat (STR) PCR confirmed the diagnosis of GVHD. Marrow biopsy showed hemophagocytosis. The patient fulfilled the HLH-2004 diagnostic criteria. He was kept on tacrolimus and steroids and was started on etanercept and ECP. After the first two cycles of ECP (one cycle defined as the weekly two procedures of ECP), the patient reported improvement of symptoms. He tolerated ECP well. His labs improved during the course of treatment, until his peripheral blood STR showed 100% recipient DNA. He was discharged after the fourth cycle of ECP to receive the remaining treatments as outpatient. At one year follow-up, the patient is asymptomatic with no evidence of GVHD or HLH. DISCUSSION: ECP in combination with immunosuppressive therapy and etanercept was safe and efficient in managing GVHD and HLH following liver transplantation.

Hemophagocytosis on ascitic fluid cytology: Diagnosis of HLH.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome of pathologic immune response characterized by excessive activation of macrophages. Hemophagocytosis is one of the diagnostic criteria for HLH, and it usually involves the bone marrow, spleen, lymph nodes, or any part of the reticuloendothelial system. Hemophagocytosis in the ascitic fluid has rarely been reported in HLH. Here, we report the case of a patient who presented with fever and abdominal distention and ascites. Ascitic fluid cytology showed hemophagocytosis which was the clue for HLH diagnosis. We also review the literature for this rare cytological occurrence.

Lack of alloimmunization to the D antigen in D-negative orthotopic liver transplant recipients receiving D-positive red blood cells perioperatively.

BACKGROUND AND OBJECTIVES: D-negative patients undergoing orthotopic liver transplantation (OLT) might require a large number of red blood cell (RBC) units, which can impact the inventory of D-negative blood. The blood bank might need to supply these patients with D-positive RBCs because of inventory constraints. This study evaluates the prevalence of anti-D formation in D-negative OLT patients who received D-positive RBCs perioperatively, as this will assist in successful patient blood management. MATERIALS AND METHODS: This was a retrospective study performed at a single academic medical centre. Electronic medical records for all 1052 consecutive patients who underwent OLT from January 2007 through December 2017 were reviewed. D-negative patients who were transfused perioperatively with D-positive RBCs and had antibody screening at least 30 days after transfusion were included. RESULTS: Of a total of 155 D-negative patients, 23 (14.8%) received D-positive RBCs perioperatively. Seventeen patients were included in the study. The median age was 54 years (range 36-67 years); 13 (76.5%) were male. The median number of D-positive RBC units transfused perioperatively was 7 (range 1-66 units). There was no evidence of D alloimmunization in any patient after a median serologic follow-up of 49.5 months (range 31 days to 127.7 months). The average number of antibody screening post OLT was 7.29. CONCLUSION: Our study showed that transfusion of D-positive RBCs in D-negative OLT recipients is a safe and acceptable practice in the setting of immunosuppression. This practice allows the conservation of D-negative RBC inventory.

Transfusion requirements and alloimmunization to red blood cell antigens in orthotopic liver transplantation.

BACKGROUND AND OBJECTIVES: Orthotopic liver transplantation (OLT) has been associated with high blood transfusion requirements. We evaluated the transfusion needs and frequency of alloimmunization to RBC antigens among OLT recipients pre- and post-transplantation. MATERIALS AND METHODS: We reviewed the medical records of patients who underwent a first OLT between January 2007 and June 2017. Transfusions given only during the perioperative period, defined by 1 week before OLT until 2 weeks following OLT, were included in this study. Records were reviewed in June 2019 for updated antibody testing results. RESULTS: A total of 970 patients underwent OLT during the study period. The median age of patients was 57 years; 608(62.7%) were male. During the perioperative period, transfused patients received an average of 10.7 (±10.7) RBC units, 15.6 (±16.2) thawed plasma units and 4.1 (±4.3) platelet units. At the time of OLT, a total of 101 clinically significant RBC alloantibodies were documented in 58(5.98%) patients. Fifty-three of these antibodies were directed against Rh blood group antigens. Twenty-two (37.9%) patients had more than one alloantibody. Patients with alloimmunization before OLT (N = 58) received perioperatively comparable number of RBCs to non-alloimmunized patients (10.5 ± 10.6 vs. 9.6 ± 10.7; p = 0.52). There was no significant difference in perioperative or intraoperative RBC transfusion between patients with one alloantibody and those with multiple alloantibodies. Only 16 patients (16/737; 2.17%) developed new alloantibodies at a median of 61 days after OLT. The overall alloimmunization rate was 9.8% (72/737), and female patients were more likely to be alloimmunized. CONCLUSION: Blood transfusion requirements in OLT remain high. However, the rate of RBC alloimmunization was not higher than the general patient population.

Platelet Transfusion: An Update on Indications and Guidelines.

Platelets are commonly transfused either therapeutically or prophylactically to maintain hemostasis. Most platelet transfusions are used to manage patients with hematologic malignancies. Although platelet transfusion guidelines have been published, platelet transfusion practices are still heterogeneous. Platelet transfusion guidelines partly lack recommendations or differ in the platelet threshold recommendations in some clinical situations. This article reviews platelet transfusions focusing on transfusion guidelines and platelet thresholds in different clinical settings.

Thrombocytapheresis for acquired von Willebrand syndrome in a patient with essential thrombocythemia and recent multivisceral transplantation.

BACKGROUND: Essential thrombocythemia (ET) is associated with increased risk of bleeding secondary to acquired von Willebrand syndrome (AVWS). Bleeding in ET requires urgent platelet reduction by cytoreductive therapy such as hydroxyurea or thrombocytapheresis. We report on the efficacy and safety of thrombocytapheresis in managing AVWS in a patient with ET and multivisceral transplantation. CASE REPORT: The patient was a 51-year-old female who underwent multivisceral transplantation. Her postoperative course was complicated by bleeding from oral cavity, IV lines, gastrointestinal and upper respiratory tracts as well as vaginal bleeding, which coincided with ET flare with a platelet count of 1512 × 109 /L. Coagulation studies including von Willebrand factor (vWF) antigen and activity, vWF propeptide antigen, and vWF multimer analysis were consistent with AVWS. Hydroxyurea was initiated. However, due to major bleeding, rapidly increasing platelet count, and uncertainty of response to hydroxyurea being given through the enteral tube, thrombocytapheresis was initiated for rapid platelet reduction. The patient tolerated the procedure well. Platelet count was reduced from 1636 × 109 /L to 275 × 109 /L with rapid cessation of bleeding. The patient's condition stabilized over the next few days; however, bleeding recurred with increasing platelet count, which required a second thrombocytapheresis 8 days after the first one. The patient was maintained on hydroxyurea 500 mg twice/day. At 11-month follow-up, she had a normal platelet count and no recurrence of bleeding. DISCUSSION: Thrombocytapheresis is safe and efficient in managing postoperative bleeding due to ET/AVWS in solid organ transplant patients. The procedure can be an adjunct to bridging therapy before response to hydroxyurea is achieved.

P-selectin expression assay in a repeatedly serotonin-release assay-negative patient with heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is an immune complication of heparin therapy caused by antibodies to complexes of platelet factor 4 (PF4) and heparin. Pathogenic antibodies to PF4/heparin bind and activate platelets to propagate a hypercoagulable state culminating in life-threatening thrombosis. The serotonin-release assay (SRA) is considered the gold-standard test to diagnose HIT. However, the sensitivity of the SRA was questioned with reported cases of clinical diagnosis of HIT and negative SRA. Herein, we present the utility of platelet factor 4-dependent P-selectin expression assay (PEA) in diagnosing HIT in a patient with thrombocytopenia and recurrent thrombosis who repeatedly tested negative with SRA.

Increasing ferritin predicts early death in adult hemophagocytic lymphohistiocytosis.

INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome of pathologic immune activation. Most studies on adult HLH have evaluated prognostic factors for overall survival; factors predicting early mortality have not been sufficiently investigated. METHODS: This was a collaborative study between Henry Ford Hospital and Barnes-Jewish Hospital. We identified all adult HLH patients with at least 2 ferritin levels within 30 days from admission. RESULTS: One-hundred twenty-four patients were identified. There were 77 males and 47 females; the median age at diagnosis was 48 years. Multivariate analysis showed that age (OR = 11.41; 95% CI:2.71-48.04; P = .001), hepatomegaly (OR = 15.68; 95% CI:3.24-75.96; P = .001), hyponatremia (OR = 5.94; 95% CI:1.76-20.1; P = .004), hypoalbuminemia (OR = 7.47; 95% CI:2.08-26.85; P = .002), and increasing ferritin levels (OR = 19.46; 95% CI:4.69-80.71; P < .001) were significant predictors of 30-day mortality. Patients with declining ferritin by more than 35% from the ferritin peak were more likely to survive the first 30 days of admission (OR = 4.33; 95% CI:1.04-18.1; P = .033). By risk stratifying our cohort, we identified changes in ferritin levels to be the most significant prognostic factor of 30-day mortality among other risk factors. Further investigating the prognostic utility of ferritin showed that increasing ferritin during the 1st week of admission (data available for 44 patients) was the only significant predictor of 30-day mortality. CONCLUSIONS: To the best of our knowledge, this is the first study reporting changes in ferritin to be a predictor for early death in adult HLH. Changes in ferritin might be a useful indicator of adult HLH disease activity and early prognosis.

Paradoxical embolic strokes in a liver transplant recipient with atrial septal defect undergoing therapeutic plasma exchange.

Therapeutic plasma exchange (TPE) is a technique used to separate blood components into layers based on their density difference, thus removing plasma and exchanging it with replacement fluids. A variety of adverse reactions has been described during TPE. Thrombotic events, especially strokes, are extremely rare complications of TPE. Our patient was a 55-year-old female with history of decompensated nonalcoholic steatohepatitis (NASH) liver cirrhosis. She underwent an orthotopic liver transplant (OLT) that was complicated with asystole during reperfusion. Cardiac workup revealed a new atrial septal defect (ASD) with left to right flow. Within the first 5 days after surgery, she developed refractory and persistent hyperbilirubinemia, with total bilirubin levels as high as 42 mg/dL. Our plasmapheresis service was consulted to initiate TPE. Towards the end of the first and only session of TPE, the patient developed hypoxia and left-sided hemiplegia. Stroke response was initiated, and the patient was intubated. MRI done 24 hours after the incident showed multiple acute small embolic infarcts scattered within the bilateral cerebral and cerebellar hemispheres. Bilateral lower and upper extremities venous duplex studies were positive for acute left internal jugular (IJ) vein thrombosis. Patient was treated with anticoagulation and the IJ catheter was removed. Patient also had closure of her ASD. On last follow up, she was doing well with complete reversal of neurologic deficits and stable liver function. Our patient had an uncommon complication of TPE. Her thrombosis manifested with multiple embolic strokes that would not have happened without an ASD with left to right flow.

Pharmacologic Therapies to Prevent Relapse of Acute Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation.

Relapse is the main cause of mortality in patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Adverse cytogenetic or molecular risk factors, as well as refractory disease or persistent measurable residual disease (MRD) at the time of transplantation are associated with an increased risk of recurrence. Salvage therapy for AML relapse after allo-HSCT is often limited to chemotherapy, donor lymphocyte infusions and/or second transplants and is rarely successful. Effective post-transplant preventive intervention in high risk AML may be crucial. The most frequent and promising approach is the use of post-transplant maintenance with hypomethylating agents or with FLT3 tyrosine kinase inhibitors when the target is present. Moreover, IDH1/IDH2 inhibitors and BCL-2 inhibitors in combination with other strategies are promising approaches in the maintenance setting. Here we summarize the current knowledge about the preemptive and prophylactic use of pharmacologic agents after allo-HSCT to prevent relapse of AML.

FLT3 inhibitors in acute myeloid leukemia: ten frequently asked questions.

The FMS-like tyrosine kinase 3 (FLT3) gene is mutated in approximately one third of patients with acute myeloid leukemia (AML), either by internal tandem duplications (FLT3-ITD), or by a point mutation mainly involving the tyrosine kinase domain (FLT3-TKD). Patients with FLT3-ITD have a high risk of relapse and low cure rates. Several FLT3 tyrosine kinase inhibitors have been developed in the last few years with variable kinase inhibitory properties, pharmacokinetics, and toxicity profiles. FLT3 inhibitors are divided into first generation multi-kinase inhibitors (such as sorafenib, lestaurtinib, midostaurin) and next generation inhibitors (such as quizartinib, crenolanib, gilteritinib) based on their potency and specificity of FLT3 inhibition. These diverse FLT3 inhibitors have been evaluated in myriad clinical trials as monotherapy or in combination with conventional chemotherapy or hypomethylating agents and in various settings, including front-line, relapsed or refractory disease, and maintenance therapy after consolidation chemotherapy or allogeneic stem cell transplantation. In this practical question-and-answer-based review, the main issues faced by the leukemia specialists on the use of FLT3 inhibitors in AML are addressed.

Acute Splenic Sequestration Crisis in Hemoglobin SC Disease: Efficiency of Red Cell Exchange.

Acute splenic sequestration crisis (ASSC) is recognized as a serious complication of sickle cell disease in children. ASSC presents with progressive splenic enlargement, transfusion-dependent anemia, and, eventually, circulatory compromise. ASSC is rare in adult patients, thus making its management and outcome in adults not well-defined. The purpose of this article is to describe our experience in managing ASSC in an adult female with hemoglobin (Hb) SC disease. The patient underwent an automated red blood cell (RBC) exchange, thus avoiding a planned splenectomy. To the best of our knowledge, our case is the third report in the literature on the use of RBC exchange in adults with HbSC disease and ASSC. RBC exchange should be considered in adults with HbSC disease with ASSC not responding to simple transfusion; a treatment that could alleviate patients' symptoms and avoid splenectomy complications, especially in young patients.

Human ehrlichiosis at a tertiary-care academic medical center: Clinical associations and outcomes of transplant patients and patients with hemophagocytic lymphohistiocytosis.

BACKGROUND: Ehrlichiosis is an acute febrile tick-borne disease which can rarely be a trigger for secondary hemophagocytic lymphohistiocytosis (HLH). METHODS: We reviewed our experience with Ehrlichia infections at a tertiary-care academic medical center. RESULTS: Over 10 years, 157 cases of ehrlichiosis were identified. Ten patients (6.4%) had infection with E. ewingii, 7(4.5%) of whom were transplant patients as compared to 3(1.9%) non-transplant patients (p = .035). Transplant patients were more likely to have leukopenia and elevated creatinine compared to immunocompetent patients; length of hospital stay and early mortality were not different between the two groups. Ten patients met the HLH-2004 diagnosis criteria, which could be an underestimation of HLH occurrence as most patients were not completely evaluated for these criteria. We calculated the H-Score to find the probability of HLH; 25 patients scored high making the occurrence rate of HLH at least 16%. Ehrlichia-induced HLH patients (N = 25) had more anemia, thrombocytopenia, elevated creatinine and AST. Moreover, they had a significantly longer hospital stay (median 9 days) compared to patients without HLH (median 4 days) (p = .006). CONCLUSIONS: Ehrlichia-induced HLH is a potential serious complication with relatively high occurrence rate; patients manifest severe disease with end-organ damage requiring longer hospital stay.

Transfusion requirements and 30-day mortality predictors for adult hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a rare clinical syndrome characterized by an uncontrolled hyper-inflammatory response. We assessed the transfusion requirements and predictors of 30-day mortality for adult HLH patients. We identified all adult patients with a diagnosis of HLH at a large academic hospital from October 2003 through February 2017. We extracted patients' clinical and laboratory data, including transfusion requirements, from their medical records. One-hundred sixteen patients were identified. Their median age was 48 years (range 18-82); 72(62%) were male. Median duration of hospital stay was 19 days (range 1-89 days). At 30 days from admission, 81(70%) patients were alive. Death was attributed to sepsis in 21 patients, lymphoma in six, bleeding in four, GVHD in one, liver failure in one, metastatic solid tumor in one, and unknown in one. Transfusion requirements at 30 days from admission were as follows: RBC, 86% of patients, median 6 units (range 1-58); platelets, 74% of patients, median 6 units (1-67); plasma, 40% of patients, median 4 units (1-56). Renal failure (OR = 4.39; P = 0.008) and hypofibrinogenemia (OR = 4.07; P = 0.009) correlated with 30-day mortality. The transfusion requirements for adult HLH patients were high. Our study indicated that renal insufficiency and hypofibrinogenemia are predictors of early death in adult HLH.

Vascular access for red blood cell exchange.

Red blood cell exchange is the process of removing red blood cells from a patient and replacing them with donated blood using either automated or manual techniques. Red blood cell exchange is a well-recognized and effective therapy for many red blood cell-related diseases, especially sickle cell disease. However, decisions regarding the best methods for vascular access are not intuitive and must account for the patient's clinical condition, complication risks, and lifestyle, especially in the context of long-term vascular access. In this review, we discuss the recognized indications for red blood cell exchange, considerations for the selection of exchange modality and vascular access, and recommendations for the appropriate care and prevention of risks associated with vascular access.