Conventional sunscreen application does not lead to sufficient body coverage.

OBJECTIVE: This study aimed to assess sunscreen application habits and relative body coverage after single whole body application. METHODS: Fifty-two healthy volunteers were asked to use the test product once, following their usual sunscreen application routine. Standardized UV photographs, which were evaluated by Image Analysis, were conducted before and immediately after product application to evaluate relative body coverage. In addition to these procedures, the volunteers completed an online self-assessment questionnaire to assess sunscreen usage habits. RESULTS: After product application, the front side showed significantly less non-covered skin (4.35%) than the backside (17.27%) (P = 0.0000). Females showed overall significantly less non-covered skin (8.98%) than males (13.16%) (P = 0.0381). On the backside, females showed significantly less non-covered skin (13.57%) (P = 0.0045) than males (21.94%), while on the front side, this difference between females (4.14%) and males (4.53%) was not significant. CONCLUSION: In most cases, the usual sunscreen application routine does not provide complete body coverage even though an extra light sunscreen with good absorption properties was used. On average, 11% of the body surface was not covered by sunscreen at all. Therefore, appropriate consumer education is required to improve sunscreen application and to warrant effective sun protection.

Pipette aspiration applied to the characterization of nonhomogeneous, transversely isotropic materials used for vocal fold modeling.

The etiology and treatment of voice disorders are still not completely understood. Since the vibratory characteristics of vocal folds are strongly influenced by both anatomy and mechanical material properties, measurement methods to analyze the material behavior of vocal fold tissue are required. Due to the limited life time of real tissue in the laboratory, synthetic models are often used to study vocal fold vibrations. In this paper we focus on two topics related to synthetic and real vocal fold materials. First, because certain tissues within the human vocal folds are transversely isotropic, a fabrication process for introducing this characteristic in commonly used vocal fold modeling materials is presented. Second, the pipette aspiration technique is applied to the characterization of these materials. By measuring the displacement profiles of stretched specimens that exhibit varying degrees of transverse isotropy, it is shown that local anisotropy can be quantified using a parameter describing the deviation from an axisymmetric profile. The potential for this technique to characterize homogeneous, anisotropic materials, including soft biological tissues such as those found in the human vocal folds, is supplemented by a computational study.

Toxoplasma gondii in foxes and rodents from the German Federal States of Brandenburg and Saxony-Anhalt: seroprevalence and genotypes.

Data on the genotypes of Toxoplasma gondii circulating in wildlife are scarce. In the present study, foxes and rodents from two Federal States in Central or Eastern Germany were examined for T. gondii infections. Body fluids were collected at necropsy or fluids were obtained from frozen tissues of naturally exposed red foxes (Vulpes vulpes), voles (Microtus arvalis), shrews (Neomys anomalus) and a striped field mouse (Apodemus agrarius) and tested for T. gondii by serology. DNA isolated from tissues of seropositive foxes and all the rodents was examined by PCR. In the German Federal States of Brandenburg and Saxony-Anhalt 152/204 (74.5%) and 149/176 (84.7%) of foxes, respectively, but none of the rodents (0/72) had antibodies to T. gondii. Only 28/152 (18.4%) and 20/149 (13.4%) of seropositive foxes from Brandenburg and Saxony-Anhalt, respectively, but none of the rodents tested PCR-positive for T. gondii. The complete T. gondii genotype could be determined for twelve samples using nine PCR-restriction fragment length polymorphism (PCR-RFLP) markers (newSAG2, SAG3, BTUB, GRA6, c22-8, c29-2, PK1, L358 and Apico). In addition to T. gondii clonal type II (Apico II) and type II (Apico I), type III and T. gondii genotypes showing non-canonical allele patterns were observed in foxes. This suggests that, while T. gondii type II prevails in foxes, other genotypes circulate in wildlife. The population structure of T. gondii in Germany may be more diverse than previously thought.

Measurement of the elasticity modulus of soft tissues.

A measurement setup combined with a Finite Element (FE) simulation is presented to determine the elasticity modulus of soft materials as a function of frequency. The longterm goal of this work is to measure in vitro the elasticity modulus of human vocal folds over a frequency range that coincides with the range of human phonation. The results will assist numerical simulations modeling the phonation process by providing correct material parameters. Furthermore, the measurements are locally applied, enabling to determine spatial differences along the surface of the material. In this work the method will be presented and validated by applying it to silicones with similar characteristics as human vocal folds. Three silicone samples with different consistency were tested over a frequency range of 20-250 Hz. The results of the pipette aspiration method revealed a strong frequency dependency of the elasticity modulus, especially below 100 Hz. In this frequency range the elasticity moduli of the samples varied between 5 and 27 kPa.

Pro- and anticoagulatory factors under sodium valproate-therapy in children.

OBJECTIVE: To evaluate sodium valproate-induced hemostatic side effects in children. METHODS: A variety of both pro- and anticoagulatory parameters were longitudinally investigated in 80 children before therapy and up to 720 days after initiation of sodium valproate (VPA) therapy. RESULTS: VPA caused a significant reduction in platelet count (309,000/ micro l +/- 122,000 before treatment to 261,000/ micro l +/- 150,000 under VPA therapy, p = 0.007). However platelet function was not impaired. While vWF antigen was reduced during VPA therapy (1.05 U/ml +/- 0.4 U/ml before therapy, 0.95 +/- 0.4 U/ml under VPA therapy), the in vivo activity of vWF (ratio between function and antigen concentration) increased significantly (1.06 +/- 0.2 before therapy, 1.36 +/- 0.3 under VPA therapy, p = 0.01). Both procoagulatory and anticoagulatory factors were significantly reduced (fibrinogen: 264.5 +/- 64.5 mg/dl before therapy, 221.4 +/- 47.5 mg/dl under therapy, p = 0.001; protein C: 81.3 % +/- 18 before therapy, 65.6 % +/- 21.4 under VPA therapy, p = 0.005, antithrombin: 122.7 % +/- 23.7 before therapy, 101.7 % +/- 18 under VPA therapy, p = 0.04). With the exception of fibrinogen, these effects were identical in children treated either with monotherapy or with polytherapy. CONCLUSIONS: Besides already known alterations of a variety of procoagulatory parameters, a relevant influence of VPA on the anticoagulatory system is demonstrated. We hypothesize that this additional alteration of anticoagulatory parameters might reduce the absolute bleeding risk of children treated with VPA.

[Catheter-related thrombosis and its prevention in infancy]. / Katheterthrombosen im Kindesalter und ihre Prävention.

Vascular catheters are the most important cause of thromboembolism in neonates. Additionally, a concomittant genetic predisposition with the well-known mutations is often present. In order to understand the pathology, knowledge about the specific condition of the newborn is important, especially concerning the altered hemostatic balance. For indications the specific situation of the very small infant is to be considered, e. g. the increased risk of cerebral bleeding in the first days of life of prematures. Therefore, careful consideration of indication and contraindications is mandatory. To avoid catheter-related thrombosis different schedules of prophylaxis are well-tried, especially low dose heparinization (sometimes as continuous infusion) is recommended for different types of vascular access. In neonates specific organ-related complications of umbilical catheters are to be considered. For the early diagnosis of catheter-related thrombosis, attention should be given to its first signs. Thrombolytic therapy is worth to be considered. However, the state of the patient and the dynamic of thrombus growth must be taken into account.

Problems with platelet counting in thrombocytopenia. A rapid manual method to measure low platelet counts.

Because most automated platelet counters cannot be relied on in thrombocytopenia, clinicians face a problem when decision making is based on platelet counts. Therefore we evaluated a visual platelet counting method from a blood smear with white blood cells (WBCs) as reference (PCW = platelet count based on WBC). Platelet counting for 74 thrombocytopenic (<120 x 10(9)/L) children was performed with PCW and with an automated counter (impedance principle); both methods were compared with evaluation by phase-contrast microscopy as the standard method. The PCW correlated well with the phase-contrast microscopy evaluation (y = -0.38 + 1.01x, r2 = 0.99). For platelet counts <20 x 10(9)/L the maximal deviation was 2 x 10(9)/L. The correlation between automated counts and the standard method was poor. The regression was y = 9.63 + 0.94x, r2 = 0.86. For platelet counts <20 x 10(9)/L the maximal deviation was 37 x 10(9)/L; on average, 7 x 10(9)/L platelets were counted in excess when compared with the standard method. PCW, in contrast to the automated impedance method, discriminated platelets from nonplatelet particles such as debris, fragments of red blood cells (hemolytic-uremic syndrome [HUS]) and of blast cells, and identified platelets of abnormal size. In addition, the appearance ofplatelets, WBCs, and RBCs gave clues to the etiology of thrombocytopenia, such as leukemia, infection, HUS, familial macrothrombocytopenia, and immune thrombocytopenia. PCW is a fast, reliable platelet counting method requiring less experience than the phase-contrast method. Visual evaluation from a stained smear clearly differentiates platelets and nonplatelet particles in contrast to most automated counters. In addition, the original smear can be preserved and reevaluated.

Acute immune thrombocytopenia (ITP) in childhood: retrospective and prospective survey in Germany.

Treatment of acute childhood immune thrombocytopenia (ITP) is controversial. For information on the present situation in Germany, a retrospective and a prospective survey were carried out. In the retrospective survey, questionnaires were sent to all German pediatric hospitals asking about local policies for handling ITP and whether in the preceding year (starting on October 1995) death or ICH had occurred; 86% answered. In the prospective survey, 94% responded to the mailings ("have you seen a case of ITP?") sent in monthly intervals between October 1, 1996 and September 30, 1997; 89% of the questionnaires were retrieved. In the retrospective survey, no deaths and no ICH were reported. If only mild bleedings, such as skin bleeds alone (or additional mild mucous membrane bleeding) were present, 20.5% (26.4%) preferred the "watchful waiting" regimen (supportive care), irrespective of the platelet count; 79.5% (73.6%) would treat if the platelet counts were <5 x 10(9)/L, 73.5% (67.9%) if < 10, 35.9% (33.6%) if < 20, and 4.2% (2.6%) if <30. Of the treaters, 50.5% would prefer immunoglobulins (Ig), 24.4% glucocorticosteroids (GC), and 20.5% GC and/or Ig. Generally, a rise in platelets, most frequently >50 x 10(9)/L was considered as therapeutic success. In the prospective survey, from the reported 323 children an annual incidence of 2.16 per 100,000 children was calculated. The incidence depended on age and gender, being highest for boys younger than 2 years with 5.8 (girls 3.42) and low with 0.44 for boys (girls 0.89) older than l4 years. About 60% of the patients had a preceding infection. Although 83% had a platelet count <20 x 10(9)/L (56% <10 x 10(9)/L), almost all (97.5%) had only mild bleeding symptoms; 2.5% had serious bleeding symptoms requiring blood transfusion or nasal packing, none had ICH, and no death was reported. The mean platelet count on admission was 11.348 (lowest count 8.253) x 10(9)/L. Sixty-one percent received Ig, 19% GC (both either alone or as first choice), 6% Ig plus GC, and 14% no treatment. Side effects were reported in 22% of the children treated with Ig. The retrospective survey mirrored the uncertainty in regard to treatment. The prospective survey provided new aspects on incidence, age, and gender distribution. Although almost all patients had only mild bleeding symptoms, most received Ig and/or GC. The decision to treat depended mainly on the platelet count. From these surveys, conclusions about the effectiveness of treatment cannot be drawn. Recommendations based primarily on platelet counts must be reconsidered.

Function of von Willebrand factor in children with diarrhea-associated hemolytic-uremic syndrome (D+ HUS).

Reports on von Willebrand factor (vWF) in hemolytic-uremic syndrome (HUS) are not unequivocal. Because of potential pathogenic implications, we examined the ability of vWF to bind to collagen in vitro, which reflects its function. Plasma vWF antigen (vWF:Ag) and collagen-binding activity (vWF:CBA) were measured by enzyme-linked immunosorbent assay in children with (1) diarrhea-associated (D+) HUS (n = 27), (2) chronic renal insufficiency (CRI) (n = 8), (3) gastroenteritis (GE) not associated with HUS (n = 15), (4) immune thrombocytopenia (ITP) (n = 40) and from controls (n = 35). Structural vWF was evaluated by multimer analysis. Children with D+ HUS had vWF:Ag of 2.53 and vWF:CBA of 1.98 U/mL. The corresponding values for patients with ITP were 1.35 and 1.82 U/mL, with CRI 1.55 and 1.55 U/mL, and with GE 1.68 and 2.10 U/mL; all values were higher than in controls (1.04 and 1.16 U/mL). The mean ratio of vWF:CBA to vWF:Ag ratio in controls was 1.13; only children with HUS had a dysfunctional vWF, as indicated by a low ratio of 0.78; the ratio was elevated in children with ITP (1.36) and GE (1.27) and was normal in those with CRI (1.06). No ultralarge molecular multimers of vWF were detected in any group, including HUS. The very high concentration of plasma vWF:Ag in HUS probably reflects endothelial cell damage or irritation. In contrast to all other groups, only children with HUS had a dysfunctional vWF, caused either by a primary (due to enterohemorrhagic Escherichia coli) or secondary (due to consumption of functionally active vWF) process. This abnormality was not obvious as structural anomaly by multimer analysis.

Heparin-induced thrombocytopenia in pediatrics.

As in adult patients, heparin is used for prophylaxis and treatment of thromboembolism in newborns, children, and adolescents. Patients receiving heparin are potentially at risk to develop heparin-induced thrombocytopenia (HIT). HIT type II has been extensively described in the adult population; only a few reports address HIT type II in pediatric patients (total of 15 neonates, 4 young children, 12 older children and adolescents). The available data are discussed, and the case of a patient with recurrent thrombosis and HIT type II without thrombocytopenia is presented. The review of the literature reveals that HIT type II occurs especially in neonates and adolescents, corresponding to the two age peaks of thrombosis in pediatric patients. Risk factors for thrombosis include hereditary factors, immobilization, and surgery. HIT complications are severe and partly lead to life-threatening thromboembolism. In three patients, an increasing heparin demand was found. In five cases, thrombocytopenia was absent. Heparin was replaced mostly by danaparoid sodium; in three patients hirudin was used as an alternative anticoagulant. HIT type II represents a potentially dangerous complication of heparin therapy in pediatric patients and should be taken into consideration whenever heparin is given for prophylactic or therapeutic use in newborns, children, or adolescents.

Vitamin K deficiency during the perinatal and infantile period.

Coagulation-related plasma proteins develop slowly during the gestational period and are still markedly lower than normal at birth. Great interest exists in the status of the vitamin K-dependent procoagulant factors (factors II, VII, IX and X) because a number of healthy newborns develop postpartum a bleeding tendency that is due to vitamin K deficiency. The most serious cases involve intracranial bleeding with convulsions, coma and potential death. Typically, these infants have markedly prolonged prothrombin times that shorten following the administration of vitamin K. A common feature of these infants is that they are breast-fed, although other factors, especially hepatobiliary diseases, contribute to this disorder. Vitamin K deficiency bleeding can develop as early as in the first 24 hours after birth, but most infants are diagnosed between days 2 and 7 postpartum. Late forms (> 1 week and up to 6 months) are also noted. This deficiency can be compensated for by prophylactically administering vitamin K to the newborns or by bottle-feeding. Although vitamin K2 may pass in small quantities through the placenta, it is insufficient to make up for the deficit. The first dose of vitamin K can also be given orally to the newborn after one or two regular feedings, and the second dose can be administered upon discharge from the hospital. A problem that remains to be solved is the late development of vitamin K deficiency in spite of prophylaxis at birth.

Molecular biology and clinical manifestation of hereditary factor VII deficiency.

Inherited factor VII (FVII) deficiency is a rare autosomal recessive disorder. Mutations and polymorphisms of the FVII gene were characterized in more than 40 unrelated patients with FVII deficiency. Among the 29 different mutations, the most frequent were Ala294 Val, Ala294Val;404delC, IVS7+7, and Val281 Phe. Four novel mutations (IVS2+1G>C, Arg247 Cys, Glu265 Lys, Asp343 His) were detected. The relationships between genotypes of mutations and polymorphisms of the FVII gene, FVII deficiency, and clinical phenotype were investigated. Homozygosity of the Phe4 Leu, IVS4+1G>A, Cys135 Arg, Ala244 Val, and Ala294 Val;404delC and the double heterozygosity of Tyr68 Cys / IVS3-1G>A, Val252 Met / IVS2+5G>T, Val281 Phe / Cys135 Arg, Ala294 Val / Val281 Phe, Ala294 Val;404delC / Val281Phe, Ala294 Val;404delC / Arg152 stop, Ala294Val;404delC / Gln(-35) stop, Ala294 Val / Val252 Met, Ala294 Val / Gly156 Asp, and Thr359 Met / Asp242 His were related to clinical symptoms. Double heterozygotes for Arg247 Cys / IVS2+1G>C, Ala206 Thr / Pro303 Arg, Leu(-20) Pro / Val252 Met as well as IVS7+7 /Ala294 Val, IVS7+7 /Ala206 Thr, and IVS7+7 / Met298 Ile were asymptomatic. The clinical symptomatology is rather poor in correlation with the FVII activity. Concerning the clinical phanotype, a correlation seems to exist between specific mutations and clinical symptoms.

DDAVP (desmopressin; 1-deamino-cys-8-D-arginine-vasopressin) treatment in children with haemophilia B.

We tested the response to desmopressin (1-deamino-cys-8-D-arginine-vasopressin; DDAVP) in four patients with haemophilia B [factor IX (F IX) at diagnosis 1.4-5%]. The activated partial thromboplastin time (aPTT) was significantly shortened in all patients. Although there was an up to 1.4-fold increase in F IX levels in three patients, maximal F IX activity remained below 10%. Much more prominent were the increases in F VIII (three- to fourfold), in von Willebrand factor antigen (VWF:Ag; 2.5-fold) and particularly in VWF collagen-binding activity (VWF:CBA; fivefold). These changes were reflected by the prophylactic efficacy of DDAVP for dental surgery. After pretesting, DDAVP could be a useful drug for reducing the need for plasma products for prevention of minor surgical bleeding in patients with mild to moderate haemophilia B.

Bleeding and thrombosis in children with acute lymphoblastic leukaemia, treated according to the ALL-BFM-90 protocol.

A multi-center retrospective survey was conducted to evaluate the incidence and types of hemostatic complications occurring in children with acute lymphoblastic leukemia (ALL) during treatment according to the ALL-BFM-90 treatment protocol. All of the BFM-treatment centers (n = 77) were approached and a 95% response rate with information on 1100 patients was obtained. Thrombotic or bleeding episodes occurred in 31 patients (2.8%), 19 of whom had thrombosis and 12 bleeding complications, involving the central nervous system (42%), the subclavian vein (29%), the gastro-intestinal tract, skin, lower extremities or pelvis (29%). Recovery was noted in 28 of 31 patients, while 3 died as a result of hemostatic complications. Bleeding or thrombosis occurred in patients receiving prophylactic substitution with plasma or plasma-derived concentrates (n = 16) as well as in those without substitution (n = 13). The majority of hemostatic complications (90%) occurred during the induction therapy of the treatment protocol, in particular during the period which included simultaneous administration of glucocorticoids and E. coli L-asparaginase. The concurrent administration of E. coli L-asparaginase and glucocorticoids may be an additional risk factor for thromboembolic events during therapy according to the ALL-BFM-90 protocol.

Effect of glucocorticoids, E. coli- and Erwinia L-asparaginase on hemostatic proteins in children with acute lymphoblastic leukemia.

BACKGROUND: The concentrations of plasma hemostatic proteins were analyzed prospectively in 42 children with acute lymphoblastic leukemia (ALL), treated according to the protocol ALL-BFM-90. PROCEDURE: Treatment included glucocorticosteroids (GC), E. coli L-asparaginase (Asparaginase, Medac) or Erwinia L-asparaginase (Erwinase, Speywood), vincristine, anthracyclines and intrathecal methotrexate. The analysis of hemostatic proteins was performed during induction and re-induction therapy. RESULTS: At diagnosis, the plasma concentrations of fibrinogen, antithrombin III (AT), plasminogen and protein C were within normal limits, whereas the von Willebrand factor antigen (vWF:Ag) was elevated. After eight days of mono-therapy with GC the concentration of fibrinogen decreased to 59%, vWF:Ag decreased to 67%, AT increased to 124%, protein C increased to 201% of the initial value (mean all p < or = 0.01), while the concentration of plasminogen remained unchanged. During the re-induction phase, the concentrations of the hemostatic proteins, with exception of vWF:Ag, altered in a similar way in response to GC as observed during the induction phase. Administration of two doses of E. coli L-asparaginase (10,000 U/m2) during the induction therapy led to a significant decrease of AT (123 +/- 24 to 63 +/- 15%/mL), protein C (168 +/- 34 to 87 +/- 19%/mL), plasminogen (94 +/- 21 to 41 +/- 12%/mL) and fibrinogen (148 +/- 59 to 79 +/- 30 mg/dL, p < or = 0.01 for all parameters). In contrast, administration of two doses of Erwinia L-asparaginase (10,000 U/m2) during re-induction therapy did not lead to change in the concentration of AT, protein C or plasminogen, and the decrease in fibrinogen (162 +/- 17 to 121 +/- 24 mg/dL) was less pronounced. CONCLUSIONS: Our results indicate that GC and E. coli L-asparaginase, in particular, induce hemostatic alterations which have implications on our understanding of thrombotic and hemorrhagic events during the treatment of ALL in children.

Vitamin K deficiency bleeding (VKDB) in infancy. ISTH Pediatric/Perinatal Subcommittee. International Society on Thrombosis and Haemostasis.

TERMINOLOGY: Replace the term "Hemorrhagic Disease of the Newborn" (HDN) by "Vitamin K Deficiency Bleeding" (VKDB), as neonatal bleeding is often not due to VK-deficiency and VKDB may occur after the 4-week neonatal period. DEFINITION: VKDB is bleeding due to inadequate activity of VK-dependent coagulation factors (II, VII, IX, X), correctable by VK replacement. DIAGNOSIS: In a bleeding infant a prolonged PT together with a normal fibrinogen level and platelet count is almost diagnostic of VKDB; rapid correction of the PT and/or cessation of bleeding after VK administration are confirmative. WARNING SIGNS: The incidence of intracranial VKDB can be reduced by early recognition of the signs of predisposing conditions (prolonged jaundice, failure to thrive) and by prompt investigation of "warning bleeds". CLASSIFICATION: VKDB can be classified by age of onset into early (<24 h), classical (days 1-7) and late (>1 week <6 months), and by etiology into idiopathic and secondary. In secondary VKDB, in addition to breast feeding, other predisposing factors are apparent, such as poor intake or absorption of VK. VK-PROPHYLAXIS: BENEFITS: Oral and intramuscular VK (one dose of 1 mg) protect equally well against classical VKDB but intramuscular VK is more effective in preventing late VKDB. The efficacy of oral prophylaxis is increased with a triple rather than single dose and by using doses of 2 mg vitamin K rather than 1 mg. Protection from oral doses repeated daily or weekly may be as high as from i.m. VK. VK-PROPHYLAXIS: RISKS: VK is involved in carboxylation of both the coagulation proteins and a variety of other proteins. Because of potential risks associated with extremely high levels of VK and the possibility of injection injury, intramuscular VK has been questioned as the routine prophylaxis of choice. Protection against bleeding should be achievable with lower peak VK levels by using repeated (daily or weekly) small oral doses rather than by using one i.m. dose. BREAST FEEDING MOTHERS TAKING COUMARINS: Breast feeding should not be denied. Supervision by pediatrician is prudent. Weekly oral supplement of 1 mg VK to the infant and occasional monitoring of PT are advisable. CONCLUSION: VKDB as defined is a rare but serious bleeding disorder (high incidence of intracranial bleeding) which can be prevented by either one i.m. or multiple oral VK doses.

Acute bilateral renal vein thrombosis complicating Netherton syndrome.

UNLABELLED: A 1-year old male infant suffering from Netherton syndrome with severe generalized erythroderma presented with acute renal failure due to bilateral renal vein thrombosis (RVT) after a short episode of enteritis. The imperceptible fluid loss through the skin and the additional enteric water loss had led to decompensation of the delicate fluid balance and had resulted in RVT as a sequel of haemoconcentration. Reperfusion of the left kidney could be achieved by treatment with urokinase and heparin. Prophylactic oral anticoagulation was instituted for several weeks. CONCLUSION: In severe Netherton disease meticulous surveillance of the fluid balance is important and aggressive treatment is indicated in case of additional fluid loss.

Bilateral renal vein thrombosis and venous sinus thrombosis in a neonate with factor V mutation (FV Leiden).

Bilateral renal vein thrombosis and venous sinus thrombosis were diagnosed within 3 weeks of birth in a full-term neonate. Heterozygosity for a factor V mutation leading to resistance against the anticoagulatory properties of activated protein C was found. Heparin therapy led to resolution of the thrombotic manifestations. With long-term oral anticoagulation, no relapse or other thrombotic event occurred during infancy.