Jonathan C. Goldsmith

Hickman catheter-induced thoracic vein thrombosis. Frequency and long-term sequelae in patients receiving high-dose chemotherapy and marrow transplantation

One hundred sixty‐eight bone marrow transplant recipients and 49 patients who received high‐dose chemotherapy were evaluated for symptomatic thrombosis after Hickman catheter placement. The timing of thrombotic complications was different between these two groups, with the transplant group having a significantly lower thrombus‐free survival by 28 days after catheter placement. By 100 days after placement the thrombus‐free survival rates of the two groups were similar. The platelet count at time of catheter placement was significantly lower in the nontransplant group, and the thrombus‐free survival was longer in patients whose catheter was placed when their platelet count was less than 150,000, suggesting that thrombocytopenia delays thrombotic complications. Placement of two Hickman catheters resulted in a 12.9% thrombosis rate (21 of 162 patients) and was significantly more likely to be associated with thrombosis than placement of one catheter. Long‐term follow‐up evaluation of patients treated without successful fibrinolytic therapy showed no residual symptoms of venous obstruction. In those patients presenting with concomitant catheter obstruction resulting from thrombosis, low‐dose fibrinolytic therapy was successful in restoring catheter function 70% of the time. Placement of two Hickman catheters is associated with an inordinate incidence of thrombosis. Thrombocytopenia at the time of catheter placement may delay this complication. Thrombotic catheter obstruction can be treated successfully with low‐dose fibrinolytic therapy. Even without fibrinolytic therapy, catheter‐induced subclavian vein thrombosis rarely causes long‐term disability.

T-Lymphocyte Subpopulation Abnormalities in Apparently Healthy Patients with Hemophilia

T-lymphocyte populations in 12 apparently healthy heterosexual adult patients with hemophilia have been examined to ascertain if these patients have abnormalities in their lymphocyte subpopulations similar to those in homosexual men, Haitian refugees, and narcotic addicts. A striking reduction in the helper to suppressor cell ratio ([0.86 +/- 0.14]:1) was found in 9 of the 12 patients. These abnormalities were similar to those previously described in two patients with hemophilia critically ill with Pneumocystis carinii pneumonia, and in homosexual men. The abnormality in the ratio of helper to suppressor T cells may be related to the continual exposure of patients with hemophilia to commercial clotting factor concentrates. However, these patients with abnormal T-lymphocyte subpopulations remain healthy. At present there is insufficient evidence to advocate a change in therapeutic practices in patients with hemophilia.

Prevention of conversion to abnormal transcranial Doppler with hydroxyurea in sickle cell anemia: A Phase III international randomized clinical trial

Children with sickle cell anemia (SCA) and conditional transcranial Doppler (TCD) ultrasound velocities (170–199 cm/sec) may develop stroke. However, with limited available clinical data, the current standard of care for conditional TCD velocities is observation. The efficacy of hydroxyurea in preventing conversion from conditional to abnormal TCD (≥200 cm/sec), which confers a higher stroke risk, has not been studied prospectively in a randomized trial. Sparing Conversion to Abnormal TCD Elevation (SCATE #NCT01531387) was a National Heart, Lung, and Blood Institute‐funded Phase III multicenter international clinical trial comparing alternative therapy (hydroxyurea) to standard care (observation) to prevent conversion from conditional to abnormal TCD velocity in children with SCA. SCATE enrolled 38 children from the United States, Jamaica, and Brazil [HbSS (36), HbSβ0‐thalassemia (1), and HbSD (1), median age = 5.4 years (range, 2.7–9.8)]. Because of the slow patient accrual and administrative delays, SCATE was terminated early. In an intention‐to‐treat analysis, the cumulative incidence of abnormal conversion was 9% (95% CI = 0–35%) in the hydroxyurea arm and 47% (95% CI = 6–81%) in observation arm at 15 months (P = 0.16). In post hoc analysis according to treatment received, significantly fewer children on hydroxyurea converted to abnormal TCD velocities when compared with observation (0% vs. 50%, P = 0.02). After a mean of 10.1 months, a significant change in mean TCD velocity was observed with hydroxyurea treatment (−15.5 vs. +10.2 cm/sec, P = 0.02). No stroke events occurred in either arm. Hydroxyurea reduces TCD velocities in children with SCA and conditional velocities. Am. J. Hematol. 90:1099–1105, 2015.

Aerosolized Pentamidine and Pregnancy

Excerpt Pentamidine isethionate is an aromatic diamidine-derivative antiprotazoal agent now being used in treatingPneumocystis cariniipneumonia in patients with immunodeficient disease states (1). ...

Augmentation of natural cytotoxicity by leucine enkephalin in cultured peripheral blood mononuclear cells from patients infected with human immunodeficiency virus

Natural Killer (NK) activity of lymphocytes from acquired immunodeficiency syndrome (AIDS) patients is frequently below normal and declines as disease progresses. We studied the potential of leucine enkephalin (leu-enkephalin) to restore this immune parameter by incubating nylon wool nonadherent mononuclear cells from 14 patients in the presence or absence of leu-enkephalin, and measuring NK cytolysis in a standard 51Cr release assay. The NK activity of human immunodeficiency virus antibody positive (HIV+) individuals with some remaining NK lytic ability was significantly augmented by leu-enkephalin concentrations of 10(-10) and 10(-8) M (n = 7). HIV+ patients with no measurable basal level of NK activity (n = 3) were not responsive to stimulation with leu-enkephalin. Human immunodeficiency virus antibody negative (HIV-) individuals (n = 4) responded in a pattern similar to normals. In addition, naloxone, an antagonist of alkaloid and peptide opiates including leu-enkephalin, displayed the properties of an antagonist/agonist, reflecting the immunoregulatory capacities of the endogenous opiate system.

False-positive enzyme-linked immunosorbent assay reactions for antibody to human immunodeficiency virus in a population of midwestern patients with congenital bleeding disorders.

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High prevalence and high titers of LAV/HTLV-III in antibodies in healthy hemophiliacs in the Midwestern United States☆

Twenty-eight patients from the Nebraska Regional Hemophilia Center were studied for the prevalence and titers of antibodies to lymphadenopathy-associated virus/human T cell lymphotropic virus type III (LAV/HTLV-III) and for clinical symptoms of possible progression to the acquired immune deficiency syndrome (AIDS). Ten of 18 (56 percent) patients with hemophilia A who were frequently treated with commercial factor VIII concentrate were seropositive for LAV/HTLV-III antibodies as determined by immunofluorescent study and Western blot testing. Of the four factor VIII-deficient patients who were seronegative, one had received only heat-treated factor VIII concentrates, two had received only cryoprecipitate, and one had received no transfusions since 1983. None of the patients treated only with factor IX concentrate, volunteer donor plasma, or cryoprecipitate had LAV/HTLV-III antibodies. In nine of 10 seropositive hemophiliacs, titers of serum antibodies to LAV/HTLV-III ranged from 1:1,280 to 1:10,240, indicating a strong immune response against LAV/HTLV-III antigens and/or persistent infection with the virus. Serum from seropositive hemophiliacs interacted on Western blot testing with all the major LAV/HTLV-III polypeptides, including envelope proteins gp 42 and gp 120. Despite the possible exposure to LAV/HTLV-III during the past four years, none of the patients in this group had symptoms suggestive of progression towards AIDS. Whether or not immunity to the AIDS retrovirus developed in this group of patients remains to be determined.