von Willebrand disease in children and adolescents.

The term von Willebrand disease includes many bleeding disorders caused by abnormalities of vWF. Frequent or severe bleeding may be indicative of vWD or other bleeding conditions. Primary care practitioners need to be familiar with vWD and evaluate possibly affected individuals with appropriate laboratory studies. Patients with vWD should be educated about their disorder and preventive measures to limit its effect. Medications are available that can treat or prevent bleeding complications for most patients with vWD. Intervention with blood products is occasionally necessary.

Neonatal polycythemia and hyperviscosity.

The neonatal polycythemia/hyperviscosity syndrome continues to perplex the pediatrician. Although it is reasonably common, with an incidence of 1% to 5%, significant symptoms are less frequent and may be more due to predisposing factors such as perinatal asphyxia, intrauterine hypoxia, or hypoglycemia. Infants who are small for gestational age or affected by maternal gestational diabetes are at high risk for the disorder. Partial exchange transfusion used to lower hematocrit will decrease viscosity, reverse many of the physiologic abnormalities, and ameliorate most symptoms, but has not been shown to significantly impact the long-term outcomes of these children.

Prevalence of von Willebrand disease in children: a multiethnic study.

OBJECTIVE: Von Willebrand disease (vWD) was thought to be a rare disorder until a recent survey reported a prevalence of 0.8% in an ethnically homogenous community in northern Italy. The purpose of this study was to determine the prevalence of vWD in an ethnically heterogenous population. METHODS: Von Willebrand factor (vWF) was measured by the ristocetin cofactor method in 600 healthy children, aged 2 to 18 years, seen for routine school physical examinations in a three-state region. Personal and family bleeding symptoms were determined by questionnaire. The diagnosis of vWD required a personal history of bleeding symptoms, an abnormal vWF activity concentration, and a family history of at least one immediate family member with bleeding symptoms. RESULTS: A total of 315 subjects were white, 212 were black, 16 were Hispanic, 10 were from other groups, and 47 were biracial. Eight subjects (four black, four white) met the criteria for vWD, for a prevalence of 1.3%. Seven subjects with vWD had blood group O (mean vWF = 32 U/dl; range, 10 to 42 U/dl), and one had blood group A (vWF = 41 U/dl). Children who had blood group O had significantly (p < 0.001) lower vWF activities (median, 83 U/dl, range, 43 to 162 U/dl) than those from non-O blood groups (median, 98 U/dl; range, 51 to 190 U/dl). There were no significant differences in vWF activity by ethnicity. The vWF activity was significantly (p < 0.02) greater for boys than girls in both blood groups. CONCLUSION: Von Willebrand disease is the most common congenital hemostatic disorder; its high prevalence is not limited to one ethnic group.

Relative value of diagnostic studies for von Willebrand disease.

Laboratory tests recommended to screen patients with mucosal bleeding for hemostatic disorders generally include determinations of prothrombin time, partial thromboplastin time, platelet count, and bleeding time. To determine the best tests to identify patients with von Willebrand disease (vWD), we reviewed the laboratory studies of 24 children with vWD and performed receiver operating characteristic analysis on the diagnostic studies. The vWD disease diagnostic tests included determinations of vWF activity (ristocetin cofactor activity), vWF factor antigen, and factor VIII procoagulant (VIII:c). The diagnosis of vWD required the presence of a personal and family history of bleeding symptoms and a documented abnormality of vWF activity or vWF antigen. vWF activity, vWF antigen, factor VIII:c and blood type were determined in 104 symptom-free children. There were no differences between patients and normal subjects for age, gender, or blood type. The bleeding time was abnormal in 43%, the partial thromboplastin time was abnormal in 25%, and either one or both were abnormal in 58% of the patients. The vWF activity, vWF antigen, and factor VIII:c were abnormal in 79%, 58%, and 33%, respectively. Receiver-operated-characteristic analysis showed the vWF activity to be superior to either the vWF antigen or factor VIII:c in establishing the diagnosis of vWD. The combination of the activity, bleeding time, and partial thromboplastin time successfully identified 92% of the patients as abnormal. Determination of vWF activity should be included routinely in the evaluation of hemostasis in children with symptomatic disease.

Osteoporosis as the presenting sign of leukemic relapse in an adolescent: case report and literature review.

Osteoporosis in adolescence is rare and usually secondary to an underlying disease process whose diagnosis may be difficult to detect. Osteoporotic vertebral collapse is an uncommon presenting sign of acute lymphoblastic leukemia (ALL). We describe a 13-year-old boy with osteoporotic vertebral collapse secondary to relapse of ALL whose blood count and blood morphology were normal but whose 1,25 = (OH2) = vitamin D level was deficient. A combination of chemotherapy, calcitriol and calcitonin therapy was successful in reversing the process. His case is presented to describe the diagnostic and therapeutic issues involved.

Immunosuppressive therapy versus bone marrow transplantation for children with aplastic anemia.

A total of 15 patients 1 to 16 years of age were treated for aplastic anemia (13 of a severe degree) and followed-up for a mean of 24 months (range 2 to 64 months). Six patients had an HLA-matched sibling and underwent allogeneic bone marrow transplantation. Nine patients who lacked a suitable donor were given immunosuppressive therapy. Antithymocyte globulin was the initial treatment for eight of these nine patients. Two patients who failed to respond to antithymocyte globulin were then treated with cyclosporine A. Pretreatment age, hematologic measurements, duration of follow-up, and interval prior to therapy were similar between the two groups. All of the patients receiving bone marrow transplants had a complete response and now have normal blood cell counts. Six of nine patients (67%) responded to antithymocyte globulin and are now transfusion free, although three have mild thrombocytopenia. Both patients given cyclosporine A had a good response and are also transfusion free. Patients who underwent marrow transplantation had a significantly shorter period of transfusion dependence for RBCs (9 v 4 weeks, P less than .005) and platelets (5 v 21 weeks, P less than .05). The patients given immunosuppressive therapy have significantly lesser platelet counts in follow-up but have similar values for both hemoglobin and absolute granulocyte counts. Although HLA-matched bone marrow transplantation leads to a faster and more complete recovery for children with aplastic anemia, immunosuppressive therapy can provide a good outcome for children with this disorder.

Inhibition of human malignant neuroblastoma cell DNA synthesis by lipoxygenase metabolites of arachidonic acid.

In vivo studies have shown that inhibitors of cyclooxygenase metabolism of arachidonic acid may diminish growth and metastasis of certain tumors. Because cyclooxygenase inhibition may increase the production of lipoxygenase products of arachidonic acid metabolism, we have investigated the effect of two such products, 12-hydroxyeicosatetraenoic acid (12-HETE) and 15-hydroxyeicosatetraenoic acid (15-HETE) on tumor cell proliferation in vitro. When neuroblastoma cells (SK-N-SH) in culture were treated with 12-HETE for 18 hr, incorporation of [3H]thymidine was inhibited up to 64% at concentrations from 20 to 50 microM. Under the same conditions, 15-HETE resulted in inhibition of up to 46%, while arachidonic acid had no apparent effect. When evaluated in the presence of serum, 12-HETE at a concentration of 120 microM produced a 20.6 +/- 2.8% (S.E.) inhibition of the increase in total DNA content over 48 hr, while 15-HETE at this concentration produced a 16.5 +/- 5.3% inhibition. We conclude that 12-HETE, the product of platelet lipoxygenase, and 15-HETE, a product of neutrophil and lymphocyte lipoxygenases, can inhibit human neuroblastoma cell growth in vitro and may play a role in the effect of cyclooxygenase inhibitors on tumor growth in vivo.