Clinical spectrum of viral infections in hemophilic patients.

Although both hemophilia A and B do not impair immunity, the use of human blood products to treat bleeding has resulted in a potential exposure to numerous viral agents. The course of infections with HIV, hepatitis B, and hepatitis C are described in this article, with comments on the interaction of these viruses in the hemophilic host. The impact of these infections on the family and community is also described.

Hb Warsaw (beta 42 Phe----Val): an unstable hemoglobin with decreased oxygen affinity. I. Hematologic and clinical expression.

Four members in two generations of a Polish-American family exhibited findings of congenital Heinz-body hemolytic anemia accompanied by cyanosis. Two of the affected family members have also developed severe pulmonary hypertension, with a fatal outcome in one of them. Blood from the affected individuals showed decreased oxygen affinity and contained elevated levels of methemoglobin. An unstable hemoglobin fraction underwent rapid precipitation following exposure of the red cell lysates to isopropyl alcohol or heat. This hemoglobin contained a newly identified abnormal beta chain with an amino acid substitution at the same position as that of Hb Hammersmith and Hb Bucuresti-Louisville.

Further evidence of von Willebrand factor involvement in thrombotic thrombocytopenia purpura.

Fourteen patients diagnosed as having thrombotic thrombocytopenia purpura (TTP) were studied. Those who survived have been followed during a 1 to 7 year period. The clinical diagnosis was based on changing neurological findings, thrombocytopenia and evidence of microangiopathic hemolytic anemia. Laboratory tests included the determination of von Willebrand factor antigen (VWF:Ag), ristocetin cofactor (RiCof) and the electrophoretic mobility of von Willebrand factor (CIE VWF:Ag). The ratio of RiCof to VWF:Ag was then calculated. Control individuals included healthy subjects and patients with thrombocytopenia of several etiologies. Statistical differences between the values of RiCof, the ratio of RiCof:VWF:Ag and the CIE of VWF:Ag were found for samples comparing active disease and remission phase. The recovery from thrombocytopenia paralleled the correction of abnormal parameters. Similarly, significant differences were found when above parameters were compared between thrombocytopenia of TTP with other thrombocytopenic states. We suggest that these abnormal tests could be useful in distinguishing TTP from other disorders, and may have prognostic significance in patients already diagnosed as having TTP.

Pulmonary function in hemophiliac patients treated with commercial factor VIII concentrates.

Pulmonary function was tested before and after the administration of a commercial preparation of factor VIII concentrate in 20 patients with hemophilia A. The material was infused through the filter provided by the manufacturer, which is supposed to remove particles larger than 170 mu. Baseline information showed that patients who smoke had a lower pulmonary diffusing capacity for carbon monoxide than nonsmokers (22.9 +/- 4.2 ml/minute/mm Hg, p less than 0.01). The administration of factor VIII was not associated with clinical abnormalities. There was a small reduction in carbon monoxide diffusing capacity (27 +/- 5.8 to 26.2 +/- 5.9 ml/minute/mm Hg, p = 0.03), which was no longer significant after carbon monoxide diffusing capacity was corrected for lung volume (5.66 +/- 1.32 to 5.54 +/- 1.34, p greater than 0.06). This study does not support the need for 40 mu filtration of factor VIII concentrate.

Pregnancy complicated by thrombotic thrombocytopenic purpura with fetal sparing.

Thrombotic thrombocytopenic purpura (TTP) occurred in a young woman during the ninth month of an uneventful pregnancy. At birth, the infant was asymptomatic, with a platelet count of 160,000/cu mm. Repeated examinations of the infant's peripheral blood film have shown normal platelet estimates and no fragmented erythrocytes. These findings support the conclusion that the placenta serves as an effective barrier to plasmatic changes presumed to be of importance in the pathogenesis of TTP.

Cycles of agglutination-disagglutination induced by ristocetin in thrombasthenic platelets.

An oscillatory pattern of platelet agglutination-disagglutination in response to Ristocetin (R) at narrow concentration ranges was observed in citrated platelet rich plasma (PRP) of 10 patients with Glanzmann's thrombasthenia. The cyclic pattern decreased in intensity over time, was reproducible, and was not pH dependent. Formalin-fixed thrombasthenic platelets agglutinated with R but did not show a cyclic pattern. Incubation with 2.5 microM ADP inhibited R oscillation response, but small increases in R dose overcame this inhibition. The addition of ATP or creatine phosphate/creatine phosphokinase to thrombasthenic platelets inhibited by ADP restored the R oscillation response. In the platelets of a single patient, intracellular levels of ADP and ATP were shown to diminish during an oscillation response to R. There was an increase in AMP levels during the same period of time. The changes in these three intracellular nucleotides were gradual over time and did not vary with phases of the oscillation. Acetyl salicylic acid (ASA), at concentrations shown to block cyclooxygenase activity in control platelets, enabled thrombasthenic platelets to respond to R with full agglutination without oscillations. Lower concentrations of ASA in the PRP gave a return of the oscillation response. Our data suggest that the disagglutination phase of the R response of thrombasthenic platelets is not a function of the known glycoprotein membrane defect, but depends on materials originating in the platelet whose release is blocked by ASA.

Platelet function and immunologic parameters in von Willebrand's disease following cryoprecipitate and factor VIII concentrate infusion.

Results of functional and immunologic tests of factor VIII and of platelet function were followed in two patients with severe von Willebrand's disease who were given cryoprecipitate during preparation for surgery. Initial correction of factor VIII coagulant activity was found to persist from 48 to 72 hours. Correction of immunologically measured factor VIII persisted for 48 hours and correlated with the patients' platelet response to ristocetin aggregation. Bleeding times were corrected for only 6 to 8 hours and showed fairly good correlation with the ristocetin aggregation factor, as suggested by Weiss. The administration of commercial factor VIII concentrate corrected all parameters except the bleeding time and the ristocetin aggregation factor measurement.

Surgery in hemophilic patients.

Surgery in hemophilic patients was performed under proper factor-replacement therapy, and a wide variety of orthopaedic procedures (twenty-six in seventeen patients) were done with good results. There were no complications in any of the patients since the advent of concentrates in 1966. Multiple procedures under one anesthetic are recommended because the complications associated with repeated administration of blood substitutes are minimized.