Applying a direct aPTT ratio (PlatelinLS/ActinFS) permits to identify rapidly and reliably a bleeding-related factor deficiency or a lupus anticoagulant sequential to an isolated prolongation of aPTT in paediatric pre-operative screening.

OBJECTIVES: An isolated prolongation of activated partial thromboplastin time (aPTT) found in paediatric pre-operative screening could be due to bleeding or non-bleeding aetiologies. The aim of our study was to evaluate clinical benefits of an additional ActinFS and/or a mixing aPTT study to identify a bleeding-related factor deficiency (BRFD). METHODS: Over a 4-yr period, isolated prolongation of aPTT with PlatelinLS was detected in 308 paediatric patients and confirmed in 161 cases by a 2nd sample. ActinFS, a mixing study, FVIII, FIX, FXI, FXII and lupus anticoagulant (LA) were performed. Three different aPTT ratios between PlatelinLS and ActinFS were analysed. RESULTS: We found 17 BRFD, 31 FXII deficiencies and 64 positive LA. A prolonged ActinFS had a significant association with BRFD (P < 0.0001) while a corrected mixing study did not. The direct aPTT ratio had a significant relationship with positive LA (P < 0.05), and with BRFD (P < 0.0001). Using this ratio, the sensitivity of BRFD's and LA's detection could be increased, respectively, to 82% from 59% using ActinFS alone, and to 86% from 55% using mixing study. CONCLUSIONS: Applying this direct aPTT ratio allows to quickly and reliably identify both BRFD and LA sequential to an isolated prolongation of aPTT.

Surgical interventions in childhood rare factor deficiencies: a single-center experience from Turkey.

Congenital rare factor deficiencies may present in infancy by life-threatening bleedings or may not show any symptoms until adulthood. It is reported more commonly in countries having consanguineous marriages. Data regarding surgical interventions of rare congenital factor deficiencies are based on case reports and records of guidelines. There are no well documented and separately prepared directories related to pre-surgical and prophylactic approaches of surgical interventions of these deficiencies. Our retrospective study consisted of 171 rare factor deficiencies that were followed up in our clinic, and of whom 61 had 88 surgical interventions between 1990 and 2012. Of these patients, 45 were having factor VII deficiency, and factor V, X, XI, XIII and fibrinogen deficiencies were present in five, four, three, two and two patients, respectively. In 23 patients, factor coagulant activities were under 5% (37.7%), in 15 it was between 5 and 30% (24.6%), and in 23 between 30 and 50% (37.7%). Twenty-eight were symptomatic and 33 were asymptomatic. Information of 51 (83.6%) male and 10 (16.4%) female patients with an age range of 5-25 years (13 ±â€Š5.27), whose age at presentation ranged between 3 weeks and 18 years (7 ±â€Š4.66), were retrieved from patient records and from the records contained in the data-processing environment introduced in 2005. The rate of familial consanguinity was 49.2%. Of the surgical interventions, 24 (27.3%) were major, 24 (27.3%) were minor and 40 (45.4%) were circumcision. We used fresh frozen plasma in 32, recombinant factor (rF)VIIa in 20, prothrombin complex concentrate in five and fibrinogen in three patients during surgical interventions. In 18 patients, antifibrinolytic agents were also used. In 27 patients, surgical interventions were applied without any replacement therapy. No additional doses were required after surgical prophylaxis doses. Thrombotic events were not observed. Antibody occurrence was not detected in these patients. In our study, we evaluated preparation for surgical procedures, factor replacement therapy before surgical intervention and postoperative follow-up in patients with rare coagulation factor deficiency.

Hematoma after augmentation mammaplasty in a patient with von Willebrand's disease / Hematoma após mamaplastia de aumento em paciente portadora de doença de von Willebrand

We present the case of a patient submitted to augmentation mammaplasty who developed 2 hematoma episodes as a result of von Willebrand's disease, which was not previously diagnosed. As a routine part of preoperative evaluation, the patient should always be tested for von Willebrand's disease. This disease affects 1-3 percent of the population and occurs twice as often as hemophilia. In our case, the patient recovered quite satisfactorily. Preventive and therapeutic approaches are discussed in this paper.

Os autores relatam o caso de uma paciente submetida a mamaplastia de aumento, não diagnosticada previamente como portadora de doença de von Willebrand, que teve dois episódios de hematoma no pós-operatório. Entre os distúrbios de coagulação, a doença de von Willebrand deve ser considerada na avaliação pré-operatória, pois afeta cerca de 1 por cento a 3 por cento da população, não é diagnosticada na maioria das pessoas, além de ser duas vezes mais frequente que a hemofilia. A paciente evoluiu bem no pós-operatório e medidas preventivas e terapêuticas são discutidas neste artigo.

Long-term production of major coagulation factors and inhibitors by primary human hepatocytes in vitro: perspectives for clinical application.

BACKGROUND/AIMS: Patients with coagulation factor disorders require lifelong symptomatic treatment. This is associated with limited efficacy and transmission risks. From a clinical point of view, hepatocyte transplantation offers a rational alternative but is currently being hampered by lack of functional stability of engrafted cells. It was the aim of our study to devise culture conditions providing stable cell polarity, attachment and growth factor stimulation to improve longevity and coagulation factor production. METHODS: Human hepatocytes (HC) were plated on different extracellular matrices, inside collagen gel or Matrigel. HC were grown inside growth factor-enriched serum-free medium (SFM) or exposed to media switching from differentiation (DM) to dedifferentiation (DeDM). RESULTS: Over more than 30 days in vitro human HC synthesized coagulation factors (factors VII, VIII, IX, fibrinogen) and coagulation inhibitors (antithrombin III, protein C). Protein synthesis was augmented when HC were grown inside a 3D collagen type I matrix, while Matrigel showed no additional benefit. Soluble growth factors improved coagulation factor production when applied in SFM or in sequential DM/DeDM. Coagulation factor levels ranged from 3% to 12% in the first week to 2.5-5% after 4 weeks, reaching biologically relevant levels. CONCLUSION: Preserved synthesis and secretion of coagulation factors in balanced proportion by human HC in this model may offer new perspectives for HC transplantation in coagulation defects of patients.

The use of recombinant factor VIIa in children with inherited platelet function disorders.

Inherited deficiencies of platelet surface glycoproteins such as Glanzmann's thrombasthenia (GT) or Bernard-Soulier syndrome (BSS) can lead to a severe bleeding diathesis. In the past, bleeding episodes in these patients have often required platelet transfusion to secure haemostasis but recently a number of patient reports have suggested that recombinant factor VIIa (rVIIa) may also be effective. We have used rVIIa on 33 occasions in seven children with inherited platelet function disorders over a 2-year period: five had GT, one had BSS and one had storage pool disease with a severe phenotype. Bleeding ceased with rVIIa alone in 10 of 28 acute bleeding episodes, but recurred in two of these. The two features that predicted response to rVIIa were the severity of the bleeding and the delay from the onset of bleeding to treatment. Five episodes of planned surgical intervention were treated successfully with rVIIa. Eighteen out of the 28 acute episodes and none of the planned surgical episodes required blood product support. We have found variable efficacy of rVIIa for acute bleeding episodes in this small series of children with inherited platelet function defects but larger studies are warranted, particularly as rVIIa is a relatively low-risk treatment approach for these disorders.

Restrictive interatrial communication with protein-losing enteropathy and coagulopathy in hypoplastic left heart syndrome after Norwood palliation.

The Norwood procedure is one option for neonates born with hypoplastic left heart syndrome. We describe a case of an infant with hypoplastic left heart syndrome, palliatively repaired with the Norwood procedure. The infant developed restriction of the interatrial communication, despite atrioseptectomy at the first stage of palliation. Consequently, a protein-losing enteropathy with severe coagulopathy developed which resolved after a repeat atrioseptectomy.