RESUMEN
BACKGROUND: Hyperhemolysis syndrome (HHS) is an uncommon transfusion reaction described in several hematologic disorders, including sickle cell disease (SCD). HHS is characterized by a decline in hemoglobin (Hb) values below pre-transfusion levels following transfusion of red blood cells (RBCs), coupled with laboratory markers consistent with hemolysis. The proposed pathophysiologic mechanisms underlying HHS include increased phosphatidylserine expression, macrophage activation, and complement dysregulation. Many pathophysiologic mechanisms thought to contribute to HHS have been similarly described in cases of severe COVID-19. CASE REPORT: A 28-year-old male with a history of HbSS presented with shortness of breath, right-sided chest pain, and a two-day history of fever. Polymerase chain reaction (PCR) detected SARS-CoV-2 infection with the omicron variant. The patient required an RBC transfusion (pre-transfusion hemoglobin [Hb]5.8 g/dL) with an immediate post-transfusion Hb of 6.3 g/dL. However, Hb rapidly declined to 1.7 g/dL, and lactate dehydrogenase (LDH) rose to 8701 u/L. The absolute reticulocyte count of 538 × 109/L correspondingly fell to 29 × 109/L. Despite additional RBC transfusions and initiation of immunosuppressive therapy, he expired on Day 9(D9). CONCLUSION: Given the similarities in their proposed pathophysiology, patients with SCD and concomitant SARS-CoV-2 infection may be predisposed to developing HHS.
Asunto(s)
Anemia de Células Falciformes , COVID-19 , Masculino , Humanos , Adulto , COVID-19/complicaciones , SARS-CoV-2 , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/terapia , Hemólisis , Síndrome , HemoglobinasRESUMEN
This study aimed to characterize the utilization of four-factor prothrombin complex concentrate (4F-PCC) at a tertiary academic medical center and evaluate the incidence of thromboembolic events (TEs) and mortality when used in an on-label versus off-label context. All medical records for consecutive patients having received 4F-PCC over 61-months were retrospectively evaluated. On-label indications for 4F-PCC were defined per FDA guidance, with the remaining indications considered off-label. Three hundred sixty-nine 4F-PCC doses were administered to 355 patients, with 46.6% of administrations classified as off-label. On-label and off-label groups demonstrated similar rates of TEs (16.2% vs. 14%). On-label patients receiving repeated administrations of 4F-PCC or with a post-administration INR ≤ 1.5 had a significantly higher incidence of TE. Off-label patients with a prior history of TE were more likely to develop a TE following 4F-PCC administration. Off-label patients also had a significantly higher 30-day mortality relative to on-label patients (29.1% versus 18.3%). In conclusion, in a large cohort of patients, observed rates of off-label 4F-PCC use were high. Underlying prothrombotic risk factors were predictive of TEs in off-label patients. Moreover, patients receiving off-label 4F-PCC demonstrated higher transfusion rates. Overall, our study findings suggest that the utilization of 4F-PCC in an off-label context may convey a significant risk to patients with uncertain clinical benefits.
Asunto(s)
Uso Fuera de lo Indicado , Tromboembolia , Humanos , Estudios Retrospectivos , Factores de Coagulación Sanguínea/efectos adversos , Factor IX , Tromboembolia/inducido químicamente , Anticoagulantes/efectos adversos , Relación Normalizada InternacionalAsunto(s)
Reversión de la Anticoagulación , Hemorragia Cerebral , Inhibidores del Factor Xa , Factor Xa , Proteínas Recombinantes , Humanos , Hemorragia Cerebral/inducido químicamente , Hemorragia Cerebral/tratamiento farmacológico , Factor Xa/administración & dosificación , Factor Xa/efectos adversos , Inhibidores del Factor Xa/efectos adversos , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Rivaroxabán/efectos adversos , Estudios Multicéntricos como Asunto , Reversión de la Anticoagulación/efectos adversos , Reversión de la Anticoagulación/métodos , Ensayos Clínicos Fase IV como Asunto , Proyectos de Investigación , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Acquired von Willebrand syndrome (AVWS) is a rare hematologic disorder characterized by quantitative or qualitative defects of von Willebrand factor (vWF), a protein crucial for normal hemostasis. AVWS has been described in association with several pathologic entities with varied mechanisms. Among these, lymphoproliferative disorders are the most common, with monoclonal gammopathy of undetermined significance (MGUS) being the most frequently reported. AVWS in this setting is commonly associated with the development of bleeding that is clinically challenging to manage due to accelerated clearance of vWF, limiting the utility of many conventional treatment modalities such as DDAVP or vWF/FVIII. We report a case of a 43-year-old male who was sent to our institution for new-onset easy bruising and laboratories concerning for von Willebrand disease (vWD). Further diagnostic workup revealed evidence of an IgG monoclonal gammopathy and findings suggestive of vWF inhibition. Ultimately, he was found to have monoclonal gammopathy of clinical significance (MGCS)-associated AVWS refractory to conventional treatment but responsive to lenalidomide and dexamethasone. This case suggests that lenalidomide may be suitable for patients with AVWS secondary to MGCS.
Asunto(s)
Gammopatía Monoclonal de Relevancia Indeterminada , Paraproteinemias , Enfermedades de von Willebrand , Masculino , Humanos , Adulto , Enfermedades de von Willebrand/complicaciones , Enfermedades de von Willebrand/tratamiento farmacológico , Gammopatía Monoclonal de Relevancia Indeterminada/complicaciones , Gammopatía Monoclonal de Relevancia Indeterminada/tratamiento farmacológico , Factor de von Willebrand/metabolismo , Lenalidomida/uso terapéutico , Paraproteinemias/complicaciones , Paraproteinemias/tratamiento farmacológico , Paraproteinemias/diagnósticoRESUMEN
BACKGROUND: Acquired Hemophilia A (AHA) is a rare autoimmune disorder associated with the development of autoantibodies against factor VIII (FVIII). Although obtaining hemostatic control through the use of recombinant factor VIIa, activated prothrombin complex concentrate and recombinant porcine FVIII are cornerstones in the clinical management of AHA, these therapies have several disadvantages, including a higher risk for the development of thromboembolic events, unpredictable efficacy and short half-lives. While emicizumab has been FDA licensed for use in bleeding prophylaxis for patients with Congenital Hemophilia A (CHA) with and without inhibitors, it has not been approved for use in AHA, with only a few reports describing its use in this context. CASE REPORT: We report our experience with the use of emicizumab in an 83-year old male with AHA, complicated by the onset of atrial fibrillation following admission, drug-induced thrombocytopenia, infectious complications, and the identification of a low-grade lymphoproliferative disorder, in which emicizumab prophylaxis was used for bleeding prophylaxis in the context of persistently elevated inhibitor titers without evidence of thrombotic events or thrombotic microangiopathy.
Asunto(s)
Anticuerpos Biespecíficos , Hemofilia A , Hemostáticos , Masculino , Porcinos , Animales , Hemofilia A/tratamiento farmacológico , Factor VIII/uso terapéutico , Anticuerpos Biespecíficos/farmacología , Anticuerpos Biespecíficos/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Hemorragia/tratamiento farmacológico , Hemorragia/prevención & control , Hemostáticos/uso terapéuticoRESUMEN
Hyperviscosity syndrome (HVS) is a life-threatening syndrome caused by high concentrations of large plasma proteins like IgM, rheumatoid factor, and other immune complexes, leading to increased blood viscosity and symptoms such as visual abnormalities, neurological impairment, bleeding diathesis, and thrombosis. While Waldenström's macroglobulinemia accounts for 80% to 90% of cases, HVS may develop in other clinical settings characterized by elevations in plasma proteins. Limited evidence currently exists describing the safety and efficacy of therapeutic plasma exchange (TPE) for the management of HVS secondary to non-neoplastic conditions. We report a case of recurrent HVS associated with juvenile rheumatoid arthritis and Felty syndrome that demonstrated improvement in clinical symptoms following initiation of TPE. These findings suggest that TPE may be utilized as an adjunct treatment option in patients with HVS secondary to autoimmune disorders.
Asunto(s)
Artritis Juvenil/terapia , Intercambio Plasmático/métodos , Viscosidad , Adulto , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/terapia , Síndrome de Felty/inmunología , Síndrome de Felty/terapia , Femenino , Hemorragia/terapia , Humanos , Leucopenia/complicaciones , Esplenomegalia/complicacionesRESUMEN
OBJECTIVES: Use of viscoelastic testing, such as thromboelastography (TEG), is recommended in cardiac surgery to monitor coagulation and to guide the transfusion of blood products. The Quantra QPlus System is a novel point-of-care platform that uses ultrasonic pulses to characterize dynamic changes in viscoelastic properties of a blood sample during coagulation. Despite the ability to assess similar aspects of clot formation, limited studies addressing the interchangeability of viscoelastic testing parameters exist. The primary aim of the present study was to assess the correlation and agreement between Quantra and TEG5000 results using blood samples from cardiac surgery patients. DESIGN: Tertiary care, academic medical center. SETTING: Prospective observational study. PARTICIPANTS: Twenty-eight patients undergoing elective cardiac surgery undergoing cardiopulmonary bypass were evaluated. MEASUREMENTS AND MAIN RESULTS: Perioperative blood samples were collected and assessed using Quantra, and results were compared with TEG and conventional coagulation testing. Method comparison analysis demonstrated that Quantra parameters (Quantra clot time, clot stiffness, and fibrinogen contribution to clot stiffness) significantly correlated with TEG R and TEG G after induction of anesthesia, during cardiopulmonary bypass, and after rewarming (rsâ¯=â¯0.83, rsâ¯=â¯0.84, and rsâ¯=â¯0.73, respectively). However, Quantra parameters demonstrated poor agreement compared with equivalent TEG5000 parameters. CONCLUSIONS: The Quantra QPlus System significantly correlated with TEG5000, suggesting that this test may be used in a similar clinical context. Despite the strength of correlation between Quantra and TEG parameters, measurements are not interchangeable.
Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Tromboelastografía , Coagulación Sanguínea , Pruebas de Coagulación Sanguínea , Puente Cardiopulmonar , Humanos , Estudios ProspectivosRESUMEN
Desialylation of platelets results in platelet clearance by the Ashwell-Morrell Receptors (AMR) found on hepatocytes. Studies suggest that oseltamivir phosphate inhibits human sialidases, enzymes responsible for desialylation, extending the lifespan of circulating platelets. We thus evaluated, the effects of oseltamivir on platelet count (PC) following treatment. Of the 385 patients evaluated for influenza, 283 (73.5%) were influenza-infected. Of the 283 infected patients, 241 (85.2%) received oseltamivir (I + O+) while 42 patients did not (I + O-). One hundred two non-infected patients received oseltamivir (I-O+). The two groups receiving oseltamivir (I + O+, I-O+), demonstrated a statistically greater increase in the PC (57.53 ± 93.81, p = .013 and 50.79 ± 70.59, p = .023, respectively) relative to the group that did not (18.45 ± 89.33 × 109/L). The observed increase in PC was statistically similar (p = .61) in both groups receiving oseltamivir (I + O+, I-O+), suggesting that this effect is independent of influenza. Comparing clinical characteristics between responders and non-responders to oseltamivir treatment showed that only duration of oseltamivir treatment (AOR = 1.30, 95% CI 1.05-1.61, p = .015) was associated with a positive PC response. Our findings suggest a correlation between oseltamivir treatment and an increase in PCs. Future studies assessing the possible uses of oseltamivir in medical conditions characterized by diminished or defective thrombopoiesis are warranted.
Asunto(s)
Oseltamivir/sangre , Recuento de Plaquetas/métodos , Anciano , Humanos , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: Familial chylomicronemia syndrome (FCS) is caused by a genetic defect in triglyceride (TG) metabolism that leads to severe hypertriglyceridemia, which in turn is associated with multiple morbidities and may cause severe pancreatitis that is both recurrent and progressive. Management of hypertriglyceridemia in FCS is challenging, as both dietary and medical interventions are often ineffective. Therapeutic plasma exchange (TPE) has been shown to rapidly decrease circulating levels of chylomicrons and TGs in patients presenting with acute hypertriglyceridemic-associated pancreatitis. Conversely, limited evidence exists to suggest that prophylactic use of TPE is effective at preventing recurrence of acute pancreatitis. CASE REPORT: Herein, we report our experience with the use of chronic, prophylactic TPE to reduce the incidence of recurrent acute pancreatitis in a patient with FCS.
Asunto(s)
Hiperlipoproteinemia Tipo I/complicaciones , Hipertrigliceridemia/terapia , Pancreatitis/prevención & control , Intercambio Plasmático , Adolescente , Ácidos Grasos no Esterificados/sangre , Humanos , Hipertrigliceridemia/complicaciones , Masculino , RecurrenciaRESUMEN
Routine mixing studies are frequently used to evaluate patients presenting with prolonged partial thromboplastin times (PTT) and/or prothrombin times (PT). Unfortunately, mixing studies have a number of inherent limitations including lack of standardization in terms of what defines normal pooled plasma (NPP), the processing of a patient's plasma for platelet removal (platelet poor plasma versus platelet-free plasma), performance of appropriate controls, conducting an incubation step to evaluate for a time and temperature dependent inhibitor, and finally interpretation of test results. Moreover, misinterpretation of study results can lead to a delayed or incorrect diagnosis or worse, inappropriate treatment. Within this manuscript, we present four cases illustrating the shortcomings associated with inappropriate utilization and interpretation of routine mixing studies; and present practical steps for managing abnormal PT or PTT results.
Asunto(s)
Tiempo de Tromboplastina Parcial/métodos , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: Stiff person syndrome (SPS) is commonly associated with antibodies directed against 65-kDa glutamic acid decarboxylase (GAD65). Therapeutic Plasma Exchange (TPE) has been used as an adjunct therapy in patients who do not respond well to conventional treatment, which includes immunosuppression therapies, anti-anxiety medications, muscle relaxants, anticonvulsants, and pain relievers. METHODS: We retrospectively analyzed the clinical data and outcomes of ten patients with the clinical diagnosis of anti-GAD65 positive SPS in which TPE was employed to improve symptoms refractory to conventional treatment during an eight-year period. RESULTS: TPE was initiated as complementary therapy in patients with worsening of symptoms characteristic of SPS. Six patients underwent chronic treatment with TPE following an initial course, of which the frequency of TPE was guided by the clinical response. Two patients only had transient improvements with further disease progression. Four patients developed a relapse of symptoms when the interval between procedures was increased. One of the four patients dependent on TPE had worsening of symptoms following complete cessation of TPE due to lack of insurance coverage. Four patients underwent only an acute hospitalized course of treatment with TPE; one demonstrated complete resolution of symptoms; one had a partial response; and two experienced no improvement. CONCLUSION: Our study supports previous reports that TPE may be beneficial for the management of patients with anti-GAD65 positive SPS, both for acute exacerbations and long-term maintenance, either as an adjunct therapy, or in lieu of treatment with disease modifying agents.
Asunto(s)
Intercambio Plasmático , Síndrome de la Persona Rígida/terapia , Adulto , Anciano , Autoanticuerpos/sangre , Femenino , Glutamato Descarboxilasa/sangre , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Síndrome de la Persona Rígida/sangreRESUMEN
Thyroid storm is a severe manifestation of thyrotoxicosis characterized by systemic organ dysfunction secondary to a hypermetabolic state. Although antithyroid drugs, steroids, beta-blockers, antipyretics, and cholestyramine are the standard of care, some patients inadequately respond to these conventional therapies. Therapeutic plasma exchange has been previously utilized as a treatment modality in patients with a poor response to routine therapies or with contraindications to them. Herein, we report our experience with the management of a case of thyroid storm refractory to conventional treatment but responsive to therapeutic plasma exchange.
Asunto(s)
Intercambio Plasmático/métodos , Crisis Tiroidea/terapia , Manejo de la Enfermedad , Humanos , Terapia Recuperativa/métodos , Resultado del TratamientoRESUMEN
The liver plays a pivotal role in hemostasis. Consequently, patients with cirrhosis frequently demonstrate abnormal coagulation profiles on routine laboratory tests. These tests mainly reflect decreased procoagulant proteins. However, in cirrhosis, complex changes also occur in anticoagulant and fibrinolytic pathways. Recent evidence demonstrates that patients with cirrhosis exist in a state of hemostatic rebalance. Accordingly, routine tests inadequately represent hemostatic alterations in these patients. Unfortunately, these tests are regularly used to guide the transfusion of blood components with the assumption that they will correct laboratory abnormalities and improve hemostasis in a bleeding patient or prevent excessive bleeding following a procedure. With an absence of both accurate laboratory testing to assess hemostasis and evidence-based guidelines to direct the transfusion of blood components, management of patients with cirrhosis poses a significant challenge to clinicians. Therefore, we developed multidisciplinary guidelines for the periprocedural transfusion of blood components in patients with cirrhosis based on concurrent evidence and personal experience at our medical center.
Asunto(s)
Transfusión de Componentes Sanguíneos/estadística & datos numéricos , Procedimientos Quirúrgicos del Sistema Digestivo , Cirrosis Hepática/cirugía , Anticoagulantes/uso terapéutico , Trastornos de la Coagulación Sanguínea/complicaciones , Trastornos de la Coagulación Sanguínea/terapia , Pérdida de Sangre Quirúrgica , Transfusión Sanguínea/normas , Transfusión Sanguínea/estadística & datos numéricos , Procedimientos Quirúrgicos del Sistema Digestivo/efectos adversos , Hemostasis/fisiología , Hemostasis Quirúrgica/métodos , Hemostasis Quirúrgica/normas , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/fisiopatología , Grupo de Atención al Paciente/organización & administración , Grupo de Atención al Paciente/normas , Transfusión de Plaquetas/normas , Transfusión de Plaquetas/estadística & datos numéricos , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina/normas , Pautas de la Práctica en Medicina/estadística & datos numéricosRESUMEN
BACKGROUND: Factor V (FV) deficiency may be inherited as an autosomal recessive disease or acquired as a result of autoantibody formation, either spontaneously or secondary to exposure to bovine thrombin or medications. Congenital FV deficiency has traditionally been treated with plasma transfusions. However, recent evidence has suggested that platelet (PLT) transfusions may be a better alternative as FV stored within PLT alpha granules has greater procoagulant potential and is released locally at sites of vascular injury. We report three cases of FV deficiency, one congenital and two acquired, and emphasize the different management approaches. CASE REPORTS: Patient 1 was a 30-year-old man with congenital FV deficiency who presented with a trauma-induced hematoma of his lower extremity. He was treated with 5 PLT units over 48 hours. Patient 2 was a 64-year-old woman who presented with an upper-extremity thrombus and was discovered to have a FV inhibitor, likely secondary to antibiotics. Patient 3 was a 75-year-old woman with hepatitis C virus (HCV) who presented with minor ecchymosis and was found to have a FV inhibitor secondary to either HCV or antibiotic exposure. Corticosteroids alone were able to eradicate the inhibitors in both patients with acquired inhibitors. CONCLUSIONS: FV deficiency can present with a diverse range of symptoms. For bleeding patients, PLT transfusions should be the initial therapy. In patients with thrombosis, the risks and benefits of anticoagulation must be carefully assessed before treatment. For patients with minor bleeds, transfusions may be withheld, and elimination of the inhibitor should be the primary objective.
Asunto(s)
Deficiencia del Factor V/terapia , Corticoesteroides/uso terapéutico , Adulto , Anciano , Autoanticuerpos/sangre , Manejo de la Enfermedad , Factor V/antagonistas & inhibidores , Factor V/uso terapéutico , Deficiencia del Factor V/complicaciones , Deficiencia del Factor V/etiología , Femenino , Hemorragia/etiología , Hemorragia/terapia , Humanos , Masculino , Persona de Mediana Edad , Transfusión de Plaquetas , Trombosis/tratamiento farmacológico , Trombosis/etiologíaRESUMEN
BACKGROUND: Due to the convenience afforded by the lack of required laboratory monitoring, direct oral anticoagulants (DOACs) are increasingly used as alternatives to Vitamin-K antagonists for certain medical conditions. However, there are circumstances in which assessment of DOAC plasma concentrations may be helpful in guiding clinical decisions, including patients presenting with either bleeding or thrombosis, or patients requiring urgent invasive procedures. Evaluating the anticoagulant effects of DOACs is often difficult because of the limited availability of DOAC-specific assays in most laboratories. OBJECTIVE: To evaluate the correlation between ex vivo plasma concentrations of rivaroxaban and a chromogenic anti-Xa assay for low-molecular-weight heparin (LMWH) routinely used in our coagulation laboratory. MATERIALS AND METHODS: Twenty-nine blood samples from 20 patients anticoagulated with rivaroxaban (dose; 10-20 mg/day) were evaluated using an anti-Xa assay for LMWH and results were correlated with rivaroxaban plasma concentrations using a rivaroxaban specific assay. RESULTS: A linear dose-dependent relationship was demonstrated between plasma concentrations of rivaroxaban and the chromogenic anti-Xa assay for LMWH (R2 = 0.92). PT and PTT demonstrated poor correlations (R2 = 0.03; and R2 = 0.01, respectively) with rivaroxaban plasma concentrations. CONCLUSION: Findings from this study suggest that if specific assays for rivaroxaban are unavailable, then the chromogenic anti-Xa assay for LMWH may be useful for assessing the anticoagulant effects of rivaroxaban.