Christine A. Johnson

Molecular cytogenetic analysis of a familial 8p23.1 deletion associated with minimal dysmorphic features, seizures, and mild mental retardation

SummaryWe report a family in which three members presented with minimal phenotypic abnormalities, normal intelligence to mild mental retardation, and a cytogenetically terminal chromosome deletion at band 8p23.1 Whole chromosomal painting with a chromosome 8-specific DNA library confirmed this familial chromosome abnormality as a deletion, while fluorescence in situ hybridization with telomeric probes demonstrated the presence of telomeres at the deletion site. Coagulation studies were additionally performed to evaluate the purported location of the coagulation factor VII regulator gene at 8p23.1. A review of the clinical findings of seven cases of del(8)(p23.1) is presented.

Acquired von Willebrand disease associated with an inhibitor to factor VIII antigen and gastrointestinal telangiectasia

A patient with acquired von Willebrand disease and gastrointestinal telangiectasia is described. He presented with the recent onset of spontaneous hemorrhage and demonstrated a prolonged bleeding time, reduced factor VIII coagulant (FVIII:C), and undetectable factor VIII-related antigen (FVIIIR:AG) and ristocetin cofactor (FVIIIR:WF). Following transfusion of cryoprecipitate, there was a smaller than expected immediate increase in FVIII:C, FVIIIR:WF and FVIIIR:AG, with a rapid return to baseline levels and no secondary increase in FVIII:C. An inhibitor could be demonstrated in the patients plasma which markedly decreased the level of FVIIIR:AG in normal plasma whereas it only weakly decreased the activity of FVIIIR:WF and FVIII:C. The inhibitor was contained in the immunoglobulin G(IgG) fraction of plasma and lacked precipitating properties. This inhibitor demonstrates a specificity not previously seen in spontaneous antifactor VIII antibodies. Our report also demonstrates that ristocetin-induced agglutination of platelets is not always the most sensitive method for detecting an inhibitor in acquired von Willebrand disease.

Coagulation studies in children with isolated recurrent epistaxis

IN 1 9 5 9, Schulman I reported on 34 children with recurrent epistaxis. Seventeen of these children had no personal or family history suggestive of a bleeding disorder. No coagulation abnormalities were found in this group. The other 17 children had multisymptomatic bleeding histories, or positive family history for a coagulation disorder, and all but one were shown to have hemorrhagic disorders. Schulman concluded that isolated, recurrent epistaxis was unlikely to be associated with coagulation disorders. In the past 20 years, advances in understanding and technology have increased our ability to identify mild bleeding disorders. We elected to re-evaluate prospectively a gr6up of children specifically referred for evaluation of isolated, recurrent epistaxis, to determine whether or not a significant number of youngsters with this problem have a mild bleeding disorder.

Prevalence of Hepatitis A Antibodies in Hemophiliacs: Preliminary Results from the Southeastern Delta Hepatitis Study

The University of North Carolina at Chapel Hill. N.C., Vanderbilt University, Nashville, Tenn., University of Tennessee at Knoxville, Tenn., Medical College of Georgia, Augusta, Ga., Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, N.C., and Tulane University of Louisiana, New Orleans, La., USA: University of Calgary, Aka., Canada Prevalence of Hepatitis A Antibodies in Hemophiliacs: Preliminary Results from the

Treatment of idiopathic autoimmune hemolytic anemia in children. Review and report of two fatal cases in infancy.

Abstract. Report of two cases of severe idiopathic autoimmune hemolytic anemia (AIHA) in infants who underwent splenectomy and received corticosteroids and cyclophosphamide without benefit. One infant, additionally, was treated with thymectomy and azathioprine without influencing his disease. Experience of therapy for childhood AIHA is reviewed. Four children with AIHA have been thymectomized. Two of these failed to benefit from surgery. There have been fifteen previous trials with immunosuppressive agents in childhood AIHA. About 60% of the children so treated (9 of 15) have shown improvement. Additional clinical trials with this agent are warranted.

EFFECTS OF FRESH FROZEN PLASMA INFUSIONS ON COAGULATION SCREENING TESTS IN SICK NEONATES

It is commonly stated that transfusion of fresh frozen plasma (FFP) in a volume of 10-20 cc/Kg. will correct non-platelet related coagulation defects in sick neonates. We studied 23 neonates in our Intensive Care Nursery who received 10-15 cc/Kg. of FFP for treatment of hypotension associated with respiratory distress syndrome. Gestational ages of infants studied ranged from 27-37 weeks. Prothrombin time (PT), partial thromboplastin time (PTT), and fibrinogen were performed prior to plasma infusion, and again 15-30 minutes, following infusion. Three infants were felt to have disseminated intravascular coagulation and were excluded. Eleven of the 20 remaining infants had pre-infusion PTs>16 seconds (sec.). Of these 11, 4 infants corrected to 16 sec. or less, while 7 showed almost no change in PT values. Eighteen of the 20 infants studied had initial PTT values >70 sec. Of these 18, only 5 infants corrected PTT values to<70 sec. after infusions. Post-infusion, 4 infants (22%) still had PTTs>90 sec. Our preliminary data would suggest that, at least in sick infants with hypotension, FFP infusion may not result in dramatic improvement in coagulation parameters. Sick infants who receive FFP for bleeding problems should have careful monitoring of coagulation parameters, since therapy more aggressive than FFP infusion may be required.

Functional Studies of Toung Versus Old Platelets in a Patient with Chronic Thrombocytopenia

The reprdoucible platelet production cycle following infusion of fresh frozen plasma (FFP) in a girl with chronic thrombocytopenia [Blood 16: 943, 1960] provided a unique opportunity to study the functional capacity of young and old platelets. Study cycles were initiated by infusing FFP when the patients platelet count was less than 20,000/mm3. ‘Young’ platelet studies were done 4 days after FFP when the patients platelet count was less than 20,000/mm3); ‘old’ platelet studies were done 21 days after FFP (average platelet count, 200,000/mm3). All studies were repeated during several such cycles. In association with a young platelet population, were normal Ivy bleeding times, normal or increased platelet adhesiveness, normal aggregation to ADP and collagen, and normal platelet factor 3 availability (PF-3a). By contrast, when the patients circulating platelets were old, she was found to have long bleeding times, abnormally low adhesiveness in vivo and in vitro, and decreased PF-3a. Aggregation to ADP and collgen was slightly decreased but remained within normal limits. No abnormalities were seen by electron microscopy on platelet samples obtained throughout the cycle. (Performed by Dr. JAMES WHITE, Univ. of Minn.) It is of interest that on several occasions the patient experienced mild bleeding manifestations at the end of a cycle but while her platelet count was still normal. These episodes correlated with the findings of long bleeding time and decreased adhesiveness.