The empty sack syndrome: a platelet storage pool deficiency associated with empty dense granules

Summary. Two sisters with lifelong bleeding tendencies were examined to determine whether their condition was associated with a platelet defect. Their platelet aggregation in response to epinephrine and collagen was abnormal, and the secretion of serotonin and ATP was markedly reduced. The platelet contents of serotonin, ADP, and ATP were all diminished and the ATP:ADP ratio was increased. Direct enumeration by whole-mount and quinacrine-fluorescence techniques demonstrated that the platelets from both sisters had significantly fewer dense granules than controls. These characteristics are similar to an individual with Hermansky-Pudlak syndrome and are consistent with a platelet dense granule deficiency. In contrast, immunofluorescence studies using an antibody against the dense granule membrane protein granulophysin suggested that both sisters had numbers of granules within the normal range. Evaluation by immunoblotting and ELISA indicated the presence of normal levels of granulophysin in the platelets from both sisters: FACS analysis demonstrated the surface expression of granulophysin under conditions of selective dense granule release. These results are consistent with these sisters having a form of dense granule storage pool deficiency where the granular membranes are present but the granules have reduced contents. This observation represents a novel form of storage pool disease which we have termed the empty sack syndrome.     

Tumour cell-antibody interactions. II. In vitro studies.

The interaction of L5178Y thymic lymphoma cells syngeneic to DBA/2 mice and of normal thymocytes with goat IgG antibodies was studied in vitro. Viable tumour and normal cells exerted a rapid, continuous and temperature-dependent destruction of antibody activity. Fractionation studies of culture supernatants from antibody-coated cells revealed that a significant portion of the antibody was completely degraded to amino acids. Tumour cells digested antibody more effectively than did normal lymphocytes. This observed degradation of antibody was most extensive at 37 degrees, significantly less at room temperature (23 degrees) and not detectable at 0 degrees. Undegraded antibody released from antibody-coated cells had also lost its antibody activity to a considerable extent. This was due to the formation of soluble antigen-antibody complexes, which was observed even at 0 degrees. Cells fixed with 10% formalin bound maximum amounts of antibody were incapable of digesting antibody even at 37 degrees and did not release immune complexes. These findings are of relevance to cancer immunodiagnosis and immunotherapy.     

Partial thromboplastin time in the presence of heparin: a rapid polybrene neutralization method

The detection of heparin in plasma and its neutralization to permit assessment of the prolonged partial thromboplastin time is a constant need in the clinical laboratory. A rapid, simple method which utilizes Polybrene after the initial contact activation step is described and compared to the standard neutralization procedures. The present method has the advantage of not requiring Polybrene titration and of requiring only small volumes of plasma making it particularly valuable in pediatric patients.     

The efficacy and toxicity of SIOP preoperative chemotherapy in Malawian children with a Wilms tumour

Background

In Malawi, preoperative chemotherapy for Wilms tumour is a logical strategy, but detailed information on toxicity and efficacy in such a resource limited setting has been unavailable.

Procedure

Patients diagnosed with a unilateral Wilms tumour received preoperative chemotherapy—a two‐drug 4‐week regimen for localized disease and 6 weeks of a three‐drug regimen for metastatic disease. Estimated maximum tumour diameter, decrease in tumour size, resectability, stage distribution and haematological toxicity during therapy were documented.

Results

At diagnosis, 28% of 72 patients had an estimated maximum tumour diameter of more than 25 cm; 29% of patients had metastases. Eight children (11%) died during preoperative chemotherapy. More than half (59%) of the patients developed moderate neutropenia (neutrophils <1.0 × 10⁹/L; CTC grade 3) and 27% severe neutropenia (CTC grade 4 neutrophils <0.5 × 10.9/L). Grade 4 neutropenia occurred significantly more frequently in children receiving the three‐drug regimen compared to the two‐drug regimen; 50% (10/20) versus 15% (6/40) (P = 0.004). Fifty‐seven percent of all patients had CTC grade 4 anaemia (Hb < 6.5 g/dL) during treatment. Most tumours (92%, 56/61) showed a response to chemotherapy but 14% (8/58) remained unresectable.

Conclusion

Preoperative chemotherapy for Wilms tumour causes considerable haematological toxicity and treatment‐related mortality in malnourished Malawian children. A significant number of children have unresectable disease despite preoperative chemotherapy. To reduce treatment related mortality, consideration should be given to starting treatment with reduced doses in acutely malnourished patients. Pediatr Blood Cancer 2012;59:636–641. © 2012 Wiley Periodicals, Inc.     

Bleeding disorders: characterization, dental considerations and management

Hemostasis is a finely balanced process in which an insult to a blood vessel wall, either by injury or surgical intervention, stimulates a pair of parallel, yet associated, pathways that lead to the termination of blood loss. The coagulation cascade is initiated by the interaction between exposed subendothelial tissue factor and circulating blood and includes a series of amplification steps that result in thrombin generation. Concurrently, exposed subendothelial collagen stimulates platelets, which, in the presence of thrombin, are consolidated by fibrin to form a blood clot, thus terminating blood loss. Multiple inherited and acquired abnormalities in these pathways can seriously compromise hemostasis. Furthermore, several drugs, including over-the-counter preparations, also adversely affect hemostasis. These present significant concerns to the dentist conducting invasive procedures as they can prolong postoperative bleeding, impair wound healing and increase risk of infection. In this article, we review the current knowledge of bleeding abnormalities and discuss preoperative systemic precautions and intraoperative hemostatic measures.     

Evaluation of families wherein a single male manifests a phenotype of X-linked lymphoproliferative disease (XLP)

The Epstein-Barr virus (EBV)-induced diseases of males with X-linked lymphoproliferative disease (XLP) include fatal infectious mononucleosis (IM), non-Hodgkin lymphoma (ML), agammaglobulinemia, and aplastic anemia. These phenotypes also occur as sporadic cases in families, and EBV seronegative males in these families must be considered at risk for XLP until they seroconvert normally to EBV. Given that 50% of males inheriting the defective XLP gene die following primary EBV infection, it is vital that they be identified pre-EBV infection. Here we report result using molecular genetic techniques to provide information as to the relative risks of EBV negative males and potential carrier females in ten families wherein a single male had died of IM. © 1993 Wiley-Liss, Inc.