From an estimated population of 2500 hemophiliacs seen between 1965 and 1976, 71 with documented central nervous system (CNS) bleeding were studied retrospectively: 56 had factor VIII deficiency and ...15 had factor IX deficiency. More than two-thirds were less than 18 yr old, and one-third were age 3 yr or less when CNS bleeding occurred. Thirty-eight (54%) had a history of recent trauma; one-half of these had a long symptom-free interval of 4 ± 2.2 days (1 SD). Four had hypertension and three had underlying congenital anomalies. No etiology was apparent in 38%. Sixty-five patients had intracranial bleeding. Those with intracerebral bleeding had a poorer prognosis than did those with subarachnoid or subdural bleeding. Intraspinal bleeding occurred in six patients. The combined mortality rate was 34%. Of 47 survivors, 12 (26%) had recurrent bleeding in the absence of known trauma. Recurrent bleeding 1 yr or more after the initial episodes seemed to be more common in factor IX-deficient than in factor VIII-deficient patients. Clotting factor concentrates to maintain minimum blood levels at 30%-50% of normal were usually given for at least 10-14 days in those who survived. Forty-seven percent (22 of 47 survivors) had neurologic sequellae, such as mental retardation, seizure disorders, or motor impairment. From these observations we conclude that the evaluation and treatment of intracranial bleeding in hemophiliacs should include (1) prompt replacement therapy with factor VIII or IX for either cranial-spinal axis trauma or CNS signs and symptoms in the absence of a history of trauma, (2) documentation of bleeding by computerized tomography scanning or other diagnostic techniques, and (3) prolonged replacement therapy in patients with documented CNS bleeding.
Twenty-three patients with thalassemia contracted to improve their adherence with subcutaneous desferrioxamine by increasing their number of days of use. Adherence, as measured by empty vial counts, ...was positively reinforced by careful monitoring and behavioral reward system. Contingency contracting was successful in 76% of patients over a 6-month period, with 69% maintaining improvement in adherence 2 months after the program. Findings supported the efficacy of behavioral intervention strategies in the care of patients with chronic illness.
Intravenous immunoglobulin is not only a dramatic clinical therapy, but it is also extremely interesting in regard to mechanism of action. The high cost of therapy limits its application, yet it ...appears to be equal to or perhaps slightly more effective than corticosteroids as a treatment of ITP and is far less toxic with prolonged use. The appropriate place for its exact use remains to be determined but probably includes patients urgently requiring rapid platelet increases (in conjunction with steroids), treatment of immunocompromised patients, and treatment of chronic patients, either children to avoid splenectomy or adults with severe disease after splenectomy. Controlled trials to resolve these clinical questions are urgently needed. Existing studies on its mechanisms of actions are very interesting and have furthered our understanding of the pathophysiology of ITP. Although future work may lead to further applications, initial enthusiasm for the use of IVGG in the treatment of other autoimmune diseases with the exception of myasthenia gravis has been limited by subsequent clinical experience.
Solid-phase enzyme immunoassays using recombinant gag and env proteins were developed to study humoral immune responses to HIV infection in a cohort of 105 hemophiliac patients. Thirteen patients ...with ARC or AIDS and 92 asymptomatic patients were studied. A cross-sectional study showed a wide range of antibody responses to gag and env proteins; however, the differences between the ARC/AIDS and asymptomatic patients were statistically significant for both antigens (P less than .0004). In a longitudinal study, antibody levels in sera from 11 asymptomatic patients with gag antibody log units less than or equal to 1.5 were compared to levels in sera from 10 ARC/AIDS patients and 8 asymptomatic patients with gag antibody greater than 1.5. These patient groups were followed for comparable periods of time (67.1-71.7 mo). The asymptomatic patients with low gag antibody and the ARC/AIDS patients showed a similar pattern of antibody response to gag protein overtime. In hemophiliac patients with HIV-1 infection a low titer of antibody to gag protein is not invariably associated with clinical deterioration and is not a useful serologic marker of impending progression to AIDS.
Six haemophilia B patients were studied while undergoing infusion with factor IX concentrate. All were negative for factor IX antigen (IX:AG) and inhibitor to factor IX coagulant activity (IX:C). One ...patient showed an atypical response pattern, with prolonged survival of IX:C and IX:Ag. This patient remained under prophylactic treatment and more than 1 year later developed an inhibitor to IX:C of clinical significance. Retrospective study revealed that this patient had significantly higher levels of circulating immune complexes than other haemophilia B patients and in vivo formation of immune complexes containing IX:Ag prior to detection of his inhibitor in conventional clotting assays, suggesting long-term persistence of an occult inhibitor. The inhibitor was shown to be an IgG antibody with both kappa and lambda light chains.
We have found bioassayable somatomedin activity to be subnormal in 20 of 32 children and adults with beta-thalassemia. The levels were comparable to values reported in growth hormone-deficient ...subjects. Since patients with thalassemia are not growth hormone deficient, the data suggest the possibility of defective hepatic biosynthesis of somatomedin. Increased iron stores in these patients, who have secondary hemosiderosis of many organs, including the liver, may depress somatomedin activity. Therapy for one year with daily subcutaneous infusions of the iron-chelating agent deferoxamine had no effect on mean bioassayable serum somatomedin activity.
An 8-month-old male with acute monoblastic leukemia died during induction chemotherapy of severe bleeding refractory to repeated infusions of platelets and clotting factors. A heparin effect was ...suggested by prothrombin time (PT) of 26 seconds, partial thromboplastin time (PTT) of 94 seconds, thrombin time 240 seconds, and reptilase time 18.4 seconds, with a fibrinogen of 88 mg/dl. Both plasma mixed with the patient's urine and the patient's plasma had their thrombin times corrected toward normal by both PF4 and protamine. Synergism of the anticoagulant with antithrombin III was demonstrated not only by enhanced inhibition of thrombin but also by an increased rate of formation of thrombin--antithrombin III complexes in the presence of the anticoagulant, which was eliminated by preincubation with heparinase. Since the anticoagulant activity was not found in the blasts themselves, it is presumed that the anticoagulant is heparin/heparan liberated from the endothelial lining by products of the cell destruction secondary to chemotherapy.
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