Controversies and challenges in elective orthopedic surgery in patients with hemophilia and inhibitors.

Until recently, orthopedic surgery was strongly contraindicated in patients with hemophilia and inhibitors. However, recent advances in our knowledge of bypassing agents (particularly recombinant activated factor VII [rFVIIa]) that provide effective surgical hemostasis have allowed us to successfully perform major orthopedic procedures in these patients. Adequate hemostasis during surgery and postoperative rehabilitation is crucial, as development of a wound hematoma may jeopardize long-term outcomes. It also should be noted that success depends not only on appropriate drug therapy but also on preoperative preparations and adequate perioperative surveillance. Preoperative assessment of vascular status is very important, and strong motivation--on the part of the patient, the surgeon, and the hematologist--is needed to ensure a satisfactory result. Although inhibitor patients undergoing surgery face a higher risk of bleeding and other complications than their non-inhibitor counterparts, outcomes are generally good if a multidisciplinary team approach is applied.

Late reactivation of resolved hepatitis B virus infection: an increasing complication post rituximab-based regimens treatment?

Reactivation of hepatitis B infection is an increasing problem for patients with lymphoma, even in resolved infections, who were treated with rituximab-based regimens. Our cases point out the need of prolonged prophylaxis in HBsAg-negative patients due to the high risk of developing fatal reactivation.

"Primary prophylaxis" with rFVIIa in a patient with severe haemophilia A and inhibitor.

The development of antibodies that inhibit or neutralize replacement therapy with factor VIII or factor IX is today the most serious complication of haemophilia and its treatment. Inhibitor patients have more severe joint morbidity than patients without inhibitors, and older adults experience significant orthopaedic disabilities. Because of the serious and disabling consequences of persistent inhibitors, there is considerable clinical and research interest in establishing effective bypassing agent regimens to prevent bleeding in inhibitor patients in much the same way as prophylaxis procedure works in noninhibitor patients. In the majority of these patients, the bypass agent was used as a secondary prophylactic. In this report, the use of recombinant factor VIIa prior to any clinically evident joint bleed in a patient with haemophilia A and high-titre inhibitor is described.

Nutritional recommendations in hematopoietic stem cell transplantation.

Hematopoietic stem cell transplantation is a procedure necessitating the administration of high-dose chemoradiotherapy. This therapy may induce aggressive disruptions that can lead to special nutritional and metabolic conditions. These patients are at an increased risk for malnutrition in the phase before transplantation and afterward. Artificial nutrition, total parenteral nutrition in particular, is provided to patients undergoing hematopoietic stem cell transplantation to help minimize adverse nutritional consequences.

Are activation markers (CD25, CD38 and CD103) predictive of sensitivity to purine analogues in patients with T-cell prolymphocytic leukemia and other lymphoproliferative disorders?

T-cell prolymphocytic leukemia (T-PLL) is a rare lymphoproliferative disorder with distinctive clinical and laboratory features. It is often resistant to conventional chemotherapy, but complete or partial responses have been documented with the use of purine analogues. We report on two cases of T-PLL with a slightly different immunophenotype but a remarkably different response to pentostatin. We discuss the possible therapeutic implications of this finding and establish a comparison between immunophenotype and sensitivity to purine analogues in patients with T-PLL and other chronic lymphoproliferative disorders.

Otolaryngologic surgery in children with von Willebrand disease.

OBJECTIVE: To assess the efficacy, safety, and complications of otolaryngologic surgery in children with von Willebrand disease (vWD) undergoing surgery. DESIGN: A prospective, controlled study of 41 children with vWD who underwent surgery between June 1, 1999, and January 31, 2001. SETTING: A tertiary care, university-based children's hospital. INTERVENTIONS: All children had a preoperative diagnosis of vWD. The patients were treated with either a protocol that includes the use of desmopressin acetate and tranexamic acid (37 children) or factor VIII concentrate in children with a positive history of seizures (4 children). MAIN OUTCOME MEASURES: Immediate and delayed postoperative bleeding, hyponatremia, seizures, and urine output. RESULTS: Two adenotonsillectomy patients (5%) had an immediate postoperative hemorrhage. Delayed postoperative bleeding was not detected in our patients. Severe hyponatremia occurred in 2 patients (1 of them with clinical manifestations). CONCLUSIONS: Our management of children with vWD was efficacious in otolaryngologic surgery. One child had important adverse effects with the use of desmopressin (seizure). Thus, the use of desmopressin should be weighed and closely monitored.

Review: Factor XI deficiency: review and management in pregnant women.

Factor XI deficiency is a rare disease found predominantly in Ashkenazi Jews. There is a poor correlation between factor XI level and bleeding in patients with factor XI deficiency. Individuals with severe factor XI deficiency are usually at risk of excessive bleeding after surgery and injury, particularly when trauma involves tissues rich in fibrinolytic activity. Women with partial or severe deficiency are at risk of excessive uterine bleeding during labor. The unpredictable nature of factor XI deficiency complicates management during pregnancy and delivery. This review gives an overview of the management of pregnant women with factor XI deficiency.

Positron emission tomography/computed tomography: diagnostic accuracy in lymphoma.

An accurate initial staging of patients with non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) is critical for the selection of an appropriate treatment. Computed tomography (CT) remains the standard imaging technique, although it is based on anatomic criteria. Positron emission tomography (PET) with 2-deoxy-2-[fluorine-18]fluoro-d-glucose (FDG) provides useful functional information but requires anatomical correlation to localise lesions accurately. We have prospectively compared the accuracy of combined PET/CT with that of CT and PET alone at initial staging in lymphoma patients. Forty-seven newly diagnosed patients were evaluated. PET/CT was superior compared with CT and PET in nodal evaluation and detection of extranodal disease. Using a staging algorithm with PET/CT resulted in the disease stage being increased in 11 of 47 patients (10 NHL and 1 HL) (McNemar test P = 0.012). Therefore, a different treatment strategy based on PET/CT findings was suggested for seven patients (14.8%). PET/CT markedly improves accuracy in the diagnostic work-up of patients with lymphoma.

Acquired hemophilia: a single-center survey with emphasis on immunotherapy and treatment-related side-effects.

OBJECTIVES: Acquired hemophilia is a rare disease caused by the development of autoantibodies against factor VIII. Since 1981 we have observed 17 patients with this disorder in our institution. The objective of this survey was to assess the epidemiological features, clinical course, and mortality rate of these patients, with special emphasis on therapy-related side-effects. Also, we present our results with an immunosuppressive approach based on the severity of bleeding episodes. METHODS: Clinical records of all patients with acquired hemophilia due to factor VIII inhibitor admitted or referred to our hospital between 1981 and 2001 were reviewed retrospectively. We collected each patient's sex, age, medical history, presenting symptoms, activated partial thromboplastin time, factor VIII activity, and inhibitor titre. Patient's clinical courses, including their bleeding episodes, response to therapy, and therapy-related side-effects, were also recorded. RESULTS: Complete and partial responses were achieved in 14 and one patient, respectively (overall response rate 88%) after a median time to complete response of 3.5 months (range 30 d - 25 months). The inhibitor-related and overall mortality rates were 12% and 29%, respectively. Side-effects were frequent: two patients had blood-borne infections, three patients had thrombotic complications, and nine patients had immunosuppressive therapy-related side-effects. In five patients, discontinuation of cyclophosphamide or prednisone was required. CONCLUSIONS: Although our response rates were remarkable, this survey showed that treatment-related morbidity could also be very important. Therefore, it is pertinent to bear in mind these potential side-effects in order to decide the most appropriate therapy for each particular patient.

Anti-CD20 monoclonal antibody therapy in refractory immune thrombocytopenic purpura.

Multiple agents have been tried in patients with refractory immune thrombocytopenic purpura (ITP); however, none of these stands as a clear first choice. We administered rituximab, 375 mg/m2 weekly x 4, to four patients with refractory ITP. With a median follow-up of 7 months, one patient has achieved a complete response, proving the possible efficacy of such a therapeutic modality in this context.

CD56 expression in myeloperoxidase-negative FAB M5 acute myeloid leukemia.

CD56 is a natural killer (NK) cell marker that has been identified in approximately 15-20% of acute myeloid leukemia (AML) cases, where it has been associated with monocytic morphology and chromosomal abnormalities such as trisomy 8, t(8;21), t(15;17), and 11q23 rearrangements. The clinical presentation, chromosomal abnormalities as detected by fluorescent in-situ hybridization (FISH), and clinical outcomes of 7 patients with AML are presented. These cases were characterized by French-American-British (FAB) M5 morphology, myeloperoxidase (MPO) negativity, and co-expression of myelomonocytic and NK cell-associated antigens (CD11c(+), CD13(+), CD15(+), CD33(+), HLA-DR(+), and CD56(+)). All patients presented lymph node, hepatic, or splenic involvement at diagnosis. Despite the homogeneous morphologic and immunophenotypic characteristics the outcomes varied considerably. Two patients died during induction therapy, but the other five patients attained complete remission (CR). Of these five patients, 4 have received a bone marrow transplantation (autologous or allogeneic) and 3 of them are in CR (median follow-up: 45 months). The three patients with 11q23 rearrangements had a poor outcome and died of their disease within 1 year of diagnosis. Further studies with a larger group of patients would help establish the actual prognostic value of these morphologic, immunophenotypic and cytogenetic features.

Radiation therapy and combination of cladribine, cyclophosphamide, and prednisone as treatment of Bing-Neel syndrome: Case report and review of the literature.

Waldenström's macroglobulinemia is a low-grade lymphoma that produces monoclonal IgM. Central nervous system symptoms are frequent in Waldenström's macroglobulinemia, mostly associated with blood hyperviscosity. Nevertheless, central nervous system infiltration by malignant cells (Bing-Neel syndrome) has rarely been reported. We describe the case of a 72-year-old man with Waldenstrom's macroglobulinemia and central nervous system infiltration by malignant cells with tumor formation. All similar cases reported in the literature are reviewed and the different therapeutic approaches discussed.

Induction of a hypercoagulability state and endothelial cell activation by granulocyte colony-stimulating factor in peripheral blood stem cell donors.

In June, 1997, we initiated a prospective study to analyze the effect of granulocyte colony-stimulating factor (G-CSF) on coagulation system in peripheral blood stem cells (PBSC) donors following G-CSF administration. Since, 25 consecutively healthy donors received G-CSF (filgrastim) to mobilize and collect PBSC and 20 donors were finally included in the study. Blood samples were collected immediately before starting G-CSF and prior to PBSC collection to analyze the following parameters: prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, hypercoagulability markers (D-dimer, TAT complex, F1 + 2), natural anticoagulants (antithrombin, protein C, protein S), endothelial activation markers [von Willebrand factor antigen (vWF:Ag) and angiotensin converting enzyme (ACE)], and resistance to activated protein C. We found a significant increase in F1 + 2 and D-dimer while a significant decrease of antithrombin and protein C activity was evidenced. Regarding endothelial cell activation markers, a significant increase of vWF:Ag with a slightly significant decrease of ACE were also observed. Therefore, in PBSC donors receiving G-CSF our results reveal activation of both coagulation and endothelial cells that could favor the developing of thrombotic events. In consequence, a careful monitoring should be considered in those cases with risk factors for thrombosis.