Thromboelastography in children with coagulation factor deficiencies.

Hemophilia is traditionally classified according to the levels of the deficient coagulation factor as Severe (<1%), Moderate (1-5%) or Mild (>5%). However, it is well known that the factor activity does not necessarily correspond to the clinical bleeding manifestations. As prophylactic therapy is the best method of prevention of serious complications such as hemophilic arthropathy, a test that may predict the bleeding pattern would be extremely beneficial. Thromboelastography (TEG) uses whole blood to determine clot formation characteristics, such as initiation, propagation as well as strength of the clot, and is now being extensively studied in bleeding and thrombophilia. This study attempted to determine the TEG characteristics in 47 children with moderate hemophilia (MH) and severe hemophilia with (SHI) and without inhibitors (SH) and tried to retrospectively correlate them to the clinical bleeding patterns. TEG showed evidence of faster and better clot formation, as evidenced by a higher maximum thrombin/fibrin generation, in those with mild bleeding manifestations compared to those with severe bleeding tendency, in addition to the expected prolongation in time to formation of clot related to factor deficiency. This may be a potentially useful tool to evaluate the bleeding tendency and determine need for prophylaxis in children with hemophilia.

Ceftriaxone induced hemolysis complicated by acute renal failure.

Over the last decade, second and third generation cephalosporins have been the most common drugs causing hemolytic anemia (HA). Of these cases, 20% have been attributed to ceftriaxone. The clinical presentation of ceftriaxone-induced HA is usually abrupt with sudden onset of pallor, tachypnea, cardio-respiratory arrest and shock. Acute renal failure (ARF) has been reported in 41% of such cases with a high fatality rate. We report a pediatric patient with ARF complicating ceftriaxone-induced HA who survived. Ceftriaxone is a commonly used drug, and early recognition of HA and institution of supportive care, including dialysis is likely to improve the outcome.

Pulmonary embolism-experience at a single children's hospital.

INTRODUCTION: Pulmonary embolism in children is a rare, potentially life threatening condition. The clinical characteristics of pediatric pulmonary embolism have not been well studied and the exact incidence in children is not known. We report a case series of fourteen patients with pulmonary embolism and describe their clinical characteristics. MATERIALS AND METHODS: Inpatient and outpatient clinic charts of patients with proven pulmonary embolism (PE) followed at the Hemostasis and Thrombosis Center at Children's Hospital of Michigan were reviewed for relevant clinical and laboratory information. RESULTS: All patients with PE were symptomatic but accurate diagnosis of PE was often delayed in the outpatient setting. Screening testing with D-dimer was normal in 40% of patients. Acquired risk factors and lower extremity clots were more common in patients analyzed. Treatment regimens differed but most patients had resolution of pulmonary emboli on follow-up. CONCLUSIONS: A high index of suspicion is needed for the diagnosis of pediatric PE. D-Dimer may be normal in some children with PE. Pediatric multicenter trials are needed to evaluate clinical characteristics, risk factors, long-term outcome and effects of PE on pulmonary and cardiac function.

Bleeding and coagulation changes during spinal fusion surgery: a comparison of neuromuscular and idiopathic scoliosis patients.

OBJECTIVE: Major blood loss is common during spinal fusion surgery. We have previously demonstrated that patients with neuromuscular scoliosis have more blood loss and greater transfusion requirement than those with idiopathic scoliosis. Our objective is to study the relationships between etiology of scoliosis, blood loss, and coagulation changes in children and adolescents undergoing spinal fusion surgery. DESIGN: Prospective, observational study. SETTING: University teaching hospital. PATIENTS: A total of 25 patients, 11 with neuromuscular and 14 with idiopathic scoliosis, undergoing spinal fusion surgery. INTERVENTIONS: Blood was obtained preoperatively, 2 and 4 hrs intraoperatively, and 2 and 24 hrs postoperatively for prothrombin time, partial thromboplastin time, thrombin time, platelet count, D-dimer, factor VII and VIII activity, thrombin-antithrombin III complex, and protein induced by vitamin K absence. Changes in coagulation over time were analyzed by repeated-measures analysis of variance. Comparisons between groups were made using independent t-tests. RESULTS: Neuromuscular scoliosis patients had significantly greater blood loss than idiopathic scoliosis patients (median blood loss, 78% of total blood volume; range, 25-127% vs. 20%, 2-82%; p < .001). Prothrombin time increased over time in both groups and was higher in the neuromuscular than the idiopathic group both preoperatively and postoperatively (p < .05). Factor VII activity decreased over time in both groups (p < .001) and was lower in the neuromuscular than the idiopathic group during surgery (p < .05). No changes in partial thromboplastin time, thrombin time, or factor VIII activity were observed. D-dimers were present in both groups by 4 hrs intraoperatively. Protein induced by vitamin K absence was not detected in any patient. CONCLUSIONS: Neuromuscular scoliosis patients have more blood loss during spinal fusion surgery than idiopathic scoliosis patients. The prolongation of prothrombin time and decrease in Factor VII activity suggest activation of the extrinsic coagulation pathway. Depletion of clotting factors during scoliosis surgery occurs to a greater extent in patients with underlying neuromuscular disease.

Tissue plasminogen activator induced fibrinolysis: standardization of method using thromboelastography.

Fibrinolysis is a complex physiological process that involves the interaction of several anticoagulant proteins. Defects of the fibrinolytic system are extremely difficult to diagnose and study because there are no standardized tests available. Thromboelastography is a novel method that allows the study of both coagulation and fibrinolysis using one sample of whole blood, thereby allowing a more physiologic assessment of the coagulation process. Several in-vitro studies have been attempted to determine whether thromboelastography would be a useful assay for the study of fibrinolysis but have reported problems with reproducibility and reliability. Here we report the process involved in developing a thromboelastographic assay in which tissue plasminogen activator (t-PA) is used to induce fibrinolysis. The assay was standardized to ensure that the concentration of the coagulation inducer (tissue factor) and fibrinolytic agent (t-PA) was adequate to induce a clot with lysis parameters that were reproducible and reliable. This method can be used to rapidly assess the intrinsic fibrinolytic potential of whole blood. Our assay showed that it could rapidly predict high levels of plasminogen activator inhibitor, and this information would be beneficial in patients with acute stroke or myocardial infarction.

Fibrinolytic parameters in children with noncatheter thrombosis: a pilot study.

Although the incidence of pediatric thrombosis has increased over the last decade, noncatheter-related deep venous thrombosis (nCDVT) is rare in children. Congenital and acquired hypercoagulable states may play an important role in the pathogenesis of nCDVT. In this study, we evaluated fibrinolytic parameters by measuring individual concentrations of fibrinolytic proteins and by tissue factor initiated whole blood thromboelastography (TEG), in which a fibrin clot was lyzed by exogenously added tissue plasminogen activator (tPA). Children with nCDVT were compared with age and sex-matched controls. TAFI concentrations were significantly higher in the patient group but there was no difference in the PAI-1, tPA and lipoprotein (a) concentrations. Significantly decreased fibrinolysis was found on TEG in the patient group suggesting that hypofibrinolysis may play an important role in the pathogenesis of nCDVT in children. To our knowledge, this is the first pediatric study that has systematically evaluated the role of fibrinolysis in the pathogenesis of DVT. Given our results, the role of fibrinolysis in the pathogenesis of nCDVT in children should be further evaluated in larger studies.

Increased lymphocyte Fas expression and high incidence of common variable immunodeficiency disorder in childhood Evans' syndrome.

Evans' syndrome (ES) is characterized by autoimmune hemolytic anemia and thrombocytopenia and has been associated with immune deficiency and lymphoproliferation in some cases. Abnormalities of Fas-mediated apoptosis have been reported in various immune dysregulation disorders associated with autoimmunity and lymphoproliferation. We measured lymphocyte Fas expression and Fas-mediated T lymphocyte apoptosis in 7 children with ES, 7 with acute idiopathic thrombocytopenic purpura (ITP) and 9 with non-immune-mediated disorders. Patients with ES had higher Fas expression on peripheral blood T and B lymphocytes (P<0.001 and P=0.046, respectively) and increased Fas-mediated elimination of activated T lymphocytes compared with the control groups. While two ES patients had panhypogammaglobulinemia at testing, three more developed it later, reaching a frequency of 83%. Some children with ES have increased lymphocyte Fas expression and Fas-mediated T lymphocyte apoptosis and these may be early signs of common variable immunodeficiency disorder in ES.

Sirolimus rescue for tacrolimus-associated post-transplant autoimmune hemolytic anemia.

Autoimmune hemolytic anemia (AIHA) has been reported to occur after renal transplantation, and typically does so in the first few weeks post-transplant. We report on a 3-yr-old child who developed cold AIHA nearly 1 yr after an ABO identical, living donor renal transplant from his mother. Numerous transfusions, pulse steroids, repeat plasma exchange treatments, and IVIG were unsuccessful. Nearly 3 wk into his illness, tacrolimus was changed to cyclosporine, and then to sirolimus, and resulted in a prompt response. He currently has a normal renal function and a normal hemoglobin level on sirolimus monotherapy.

Primitive neuroectodermal tumor (PNET) of the uterus in a renal allograft patient: a case report.

The incidence of malignancy after renal transplant has been reported to range from 4% to 18%. Tumors of the skin and lip tend to be the most common with non-Hodgkin lymphoma comprising 20% of all neoplasms. Primitive neuroectodermal tumors (PNET) are collectively described as being a part of the Ewing sarcoma family of tumors. PNET occur more commonly in the second decade of life, predominantly affecting Whites and Hispanics, and rarely occur in individuals of African or Asian descent. The most common primary site of involvement is along the central axis, particularly the chest (Askin tumor), but it can arise in any soft tissue. PNET also occur in the head and neck. PNET involving the cervix, urinary bladder, uterus, and vagina have been reported. We describe a case of a 15-year-old female who, 9 years after receiving a living related renal transplant, developed a post-transplant PNET of the uterus.