American Journal of Hematology

doi: 10.1002/ajh.2830360301pmid: N/A

Lopez‐Fernandez, M. F.; Gonzalez‐Boullosa, R.; Blanco‐Lopez, M. J.; Perez, M.; Batlle, J.

doi: 10.1002/ajh.2830360302pmid: 1996556

We describe two members of a single family, father and son, with mild factor XII deficiency associated to von Willebrand disease (vWD) with aberrant structure in whom distinct multimeric abnormalities and an abnormal proteolytic processing of von Willebrand factor (vWF) after desmopressin (DDAVP) administration were present. They had a mild bleeding history, low levels of vWF‐related activities, and a prolonged bleeding time. Low‐resolution agarose‐ gel electrophoresis showed a vWF with all size multimers in plasma and platelets. Higher‐resolution agarose gels demonstrated that the main band was present, but the relative proportion of the satellite bands was markedly reduced. The smallest oligomer was not increased. After the infusion of DDAVP to the father, a transient increase in the relative proportion of the satellite bands was seen, as described in normal individuals. No difference in the structure of vWF was observed when blood was collected with proteinase inhibitors. The analysis of native subunits of vWF and their proteolytic derived fragments, after DDAVP administration, showed a temporary augmentation of the 176 kDa fragment, as seen in normal subjects, as well as an increase of the 189 kDa fragment. This finding had not been reported previously either in normal individuals or in patients with vWD.

Friedenberg, William R.; Kyle, Robert A.; Knospe, William H.; Bennett, John M.; Tsiatis, Anastasios A.; Oken, Martin M.

doi: 10.1002/ajh.2830360303pmid: 1996557

In order to assess the efficacy and toxicity of dexamethasone as a single agent without the concomitant infusion of Adriamycin and vincristine (VAD), an ECOG pilot study was initiated using 40 mg by mouth daily for 4 days every week for 8 weeks. Patients who responded were then maintained on the same treatment, but at 2 week intervals. Of the 32 patients evaluable for response, three were completely refractory to all prior therapy. All patients had advanced disease and 26 had received multiple prior treatments. There were 13/32 (40%) objective responses by ECOG criteria. Of the 28 patients evaluable for subjective response, i.e., significant decrease in performance status and/or bone pain, eight (28.5%) responded. Of the 34 patients evaluable for toxicity, 19 patients (55%) had moderate to severe side effects, including nine who had central nervous system effects, three who had gastrointestinal bleeding, two who had pulmonary emboli, one with psychosis, and four who had serious infections with one death. Median survival for the entire group was 19 weeks, with 31 weeks in the responders and 9 weeks in the non‐responders. Although high‐dose dexamethasone is capable of producing a significant number of partial responses (40%), it is associated with excessive toxicity. Less frequent administration of the dexamethasone at 2 week intervals was well tolerated in the maintenance of partial response, but has not been studied for efficacy in induction of remission.

Asakura, Hidesaku; Jokaji, Hiroshi; Saito, Masanori; Uotani, Chika; Kumabashiri, Ichiro; Morishita, Eriko; Yamazaki, Masahide; Matsuda, Tamotsu

doi: 10.1002/ajh.2830360304pmid: 1899963

Plasma levels of tissue‐plasminogen activator · plasminogen activator inhibitor (t‐PA · PAI) complex and active PAI were assayed in 58 cases of disseminated intravas‐cular coagulation (DIC). A significant elevation of both parameters was observed in most cases of DIC, especially in patients with non‐Hodgkin lymphoma, sepsis, or some patients with acute leukemia, but no such elevation was observed in patients with acute promyelocytic leukemia (APL). The levels of both parameters were higher in cases of DIC with multiple organ failure (MOF) than in those without MOF. Since no elevation of t‐PA · PAI complex was observed in most cases of APL, t‐PA did not seem to play an important role in the activation of fibrinolytic system in APL. Active PAI, which reflects the inhibitory regulation in fibrinolytic system, was considered to play a role in the progression of MOF. Plasma levels of active PAI were low in the cases of APL, which had no complication of MOF.

Rieder, R. F.; Safaya, S.; Gillette, P.; Fryd, S.; Hsu, H.; Adams, J. G.; Steinberg, M. H.

doi: 10.1002/ajh.2830360305pmid: 1996558

In 113 black American adults with sickle cell anemia (HbSS), we examined nine polymorphic restriction sites, including the Xmnl site 5' to the Gγ gene, to see whether haplotype is related to the level of HbF and the proportion of Gγ chains or if it influences the hematological and clinical features of the disease. Seventy‐five percent of the patients were homozygous or heterozygous for the Benin (no. 19) or Central African Republic (Bantu, no.20) haplotypes; 13.3% were homozygous fo heterozygous for the Senegal (no.3) haplotype, while 11.5% had other genotypes. Of the subjects, 14.2% were either homozygous or heteroxygous for the Xmnl restriction site 5' to the Gγ gene. We found no effect of haplotype on HbF levels. The level of Gγ chains was 60.5% ± 17.0% in individuals with other haplotypes. Subjects with the Xmnl site 5' to the Gγ gene had Gγ globin levels of 59.5% ± 16.7% while those lacking that site had an average of 47.2% ± 12.1%. There were no significant differences among these groups in hemoglobin concentration, packed cell volume, mean cell volume, or haplotype 3 and the 5' G γ Xmnl site were associated with increased Gγ chains, there was no effect on HbF level or other hematological and clinical features that might reflect disease severity. It is likelu that determinants unrelated to haplotype, linked or unlinked to the β‐globin gene cluster, are the major effectors of differences in the levels of HbF in American patients with sickle cell anemia.

Weber, Jed P.; Walsh, Patrick C.; Peters, Craig A.; Spivak, Jerry L.

doi: 10.1002/ajh.2830360306pmid: 1705094

To examine the role of testosterone in the maintenance of hemoglobin levels, we studied the effect of reversible androgen deprivation on hemoglobin, serum immunoreactive erythropoietin, and serum testosterone in seven men treated with a luteinizing hormone‐releasing factor (LHRH) agonist for 6 months and then followed for an additional 6 months. The mean serum testosterone level was 4.35 ± 1.05 ng/ml initially and it decreased to castrate levels in all patients by 6 months. After stopping therapy, there was a rapid increase in serum testosterone such that by 12 months the mean concentration was normal. The pretreatment hemoglobin was 15.2 ± 0.9 g/dl (mean ± SD); after 6 months of androgen deprivation it had fallen to 14.1 ± 0.4 g/dl (P < 0.05). Six months after stopping therapy, the hemoglobin rose to pre‐treatment levels. Before treatment, serum immunoreactive erythropoietin was 9.5 ± 4.6 mu/ml (mean ± SD) and did not change significantly during or after the 6 month period of androgen deprivation. No significant inhibition of burst‐forming unit‐erythroid (BFU‐E) or colony‐forming unit‐granulocyte macrophage (CFU‐GM) was observed at the serum levels of nafarelin acetate obtainable in vivo. These data suggest that, within the normal range of hemoglobin in men, androgens are a determinant of the red cell mass.

Berkman, Neville; Michaeli, Yossef; Or, Reuven; Eldor, Amiram

doi: 10.1002/ajh.2830360307pmid: 1899964

EDTA‐dependent pseudothrombocytopenia (EDTA‐PTCP) is the phenomenon of a spurious low platelet count due to the appearance of antibodies that cause platelet agglutination in blood anticoagulated with EDTA. We review here the clinical features of 18 patients with EDTA‐PTCP treated in our hospital from 1984 to 1987 as well as those of 34 patients reported in the literature. This phenomenon appears more frequently in severely ill patients, in association with autoimmune, neoplastic, atherosclerosis‐related, and liver diseases. In the majority of our patients, EDTA‐PTCP appeared during hospitalization, indicating that the antibody is an acquired one. Neither splenomegaly nor the presence of autoimmune markers were features of this entity. Unlike true thrombocytopenias, EDTA‐PTCP is associated with a normal mean platelet volume. Awareness of this entity is essential since EDTA‐PTCP is frequently misdiagnosed and therefore incorrectly treated.

Sinzinger, Helmut; Kaliman, Josef; O'Grady, John

doi: 10.1002/ajh.2830360308pmid: 1899965

In 2 male patients (35 and 38 years) presenting with myocardial infarction an abnormal conversion of exogenous 14C‐arachidonic acid by the patients' platelets, incubated in vitro, was observed. Neither patient's platelets showed evidence of a lipoxygenase pathway. Platelet thromboxane formation from exogenous and endogenous substrate was high, while the platelet aggregation responses were normal. A myeloproliferative syndrome was excluded by bone marrow puncture. Similar defects have only been described so far in patients with myeloproliferative syndrome. This defect may be causative for the onset of clinical thrombotic events. It is speculative whether in vivo therapy with r‐IFNα1c might be able to eradicate the pathological platelet clone.

Sthoeger, Z. M.; Sthoeger, D.; Mellnick, S. D.; Steen, D.; Berrebi, A.

doi: 10.1002/ajh.2830360309pmid: 1825446

A 30‐year‐old man presented with an episode of deep vein thrombosis. He was found to have primary antiphospholipid syndrome with anticardiolipin antibodies and protein S deficiency. All other investigations were negative. Three months later, anticardiolipin antibodies were negative and protein S levels were normal. The transient presence of anticardiolipin antibodies and functional protein S deficiency in this patient suggests a new mechanism for the association between anticardiolipin antibodies and venous thrombosis.

Adler, Mark J.; Hershberg, Robert; Yu, Alice

doi: 10.1002/ajh.2830360310pmid: 1825447

Presented is an unusual case of chronic T‐cell leukemia. Immunophenotypic profile revealed the leukemia cells to express T4 and T8 surface markers simultaneously. The patient was treated with low‐dose deoxycoformycin and control of symptoms and lymphocyte levels shown to correlate with ADA and dATP/ATP levels.