Microvascular injury, thrombosis, inflammation, and apoptosis in the pathogenesis of heatstroke: a study in baboon model.

OBJECTIVE: Severe heatstroke is a leading cause of morbidity and mortality during heat waves. The pathogenesis of tissue injury, organ failure, and death in heatstroke is not well understood. METHODS AND RESULT: We investigated the pathways of heatstroke-induced tissue injury and cell death in anesthetized baboons (Papio hamadyras) subjected to environmental heat stress until core temperature attained 42.5 degrees C (moderate heatstroke; n = 3) or onset of severe heatstroke (n = 4) signaled by a fall in systolic blood pressure to < 90 mm Hg and rise in core temperature to 43.1+/-0.1 degrees C. Three sham-heated animals served as controls. Light and electron microscopy revealed widespread hemorrhage and thrombosis, transmural migration of leukocytes, and microvascular endothelium injury in severe heatstroke. Immunohistology and ultrastructural analysis demonstrated increased staining of endothelial von Willebrand factor (vWF), tissue factor (TF), and endothelial leukocyte-platelet interaction. Extensive apoptosis was noted in spleen, gut, and lung, and in hematopoeitic cells populating these organs. Double-labeling studies colocalized active caspase-3 and TF with apoptotic cells. Findings in sham-heated animals were unremarkable. CONCLUSIONS: These data suggested that microvascular injury, thrombosis, inflammation, and apoptosis may play an important role in the pathogenesis of heatstroke injury.

Intra-leukocytic hemosiderin inclusions detected as pseudoeosinophils by automated depolarization analysis in a patient with beta-thalassaemia major and immune hemolysis.

This report describes a patient with intra-leukocytic hemosiderin inclusions associated with iron overload and acute infection. These inclusions resulted in a false identification of eosinophils rather than neutrophils using an automated analyzer. The analyzer interpreted the aberrant increased depolarization as a reflection of eosinophils. No eosinophils were found by examination of the blood smear. The implications for the hematology morphologist is that visual inspection of a blood smear is nearly always indicated whenever any departure from strict normality is noted in the output from an automated blood cell counter.

Single center review of clinicopathological characterization in 77 patients with positive lupus anticoagulant antibodies.

BACKGROUND: The antiphospholipid syndrome (APS) is a thrombophillic disorder characterized by the presence of antiphospholipid antibodies (APA). It often occurs in patients with systemic lupus erythematosus (SLE) and may be associated with recurrent abortions and thrombocytopenia and, occasionally, catastrophic thrombotic events. OBJECTIVES: To examine, retrospectively, the clinico-pathological features of patients with APS detected by the presence of the lupus anticoagulant (LAC). METHODS: Patients were selected for study on the basis of a positive LAC test on review of the laboratory computer records of the King Faisal Specialist Hospital and Research Center. Following this, a clinical chart review was conducted in order to determine the clinical presentations, treatment and the course of patients identified. The information obtained was entered into an electronic database and subsequently analyzed. RESULTS: Seventy-seven patients were identified and reviewed. Fifty-six (73%) were female and 16 (21%) were children less than 15-years-old. Thirty-two patients (42%) had no clinical events (incidental APS). The syndrome was classified as primary in 40 (52%) patients and secondary in 37 (48%). Out of the 45 (58%) patients who presented with symptoms related to APA 22 (49%) had thrombosis, 24 (53%) had pregnancy failure, and 4 (9%) presented with catastrophic APS. The activated partial thromboplastin time (aPTT) was elevated and not corrected by mixing with normal plasma in 47 (61%). On the other hand, the prothrombin time (PT) was normal in 66 (90%). There is a significant difference between aPTT and PT as a screening test with P value of < 0.0001. Tests for anticardiolipin antibodies (ACA) were positive in 39 patients (70%). Only 13 (17%) patients had thrombocytopenia. All patients who presented with thrombosis were treated with warfarin but only 5 (23%) had received aspirin. Out of the 22 patients presenting with thrombosis, 12 (55%) had one or more recurrent thrombotic events while only 6 (25%) out of the 24 patients who presented with pregnancy failure had events other than pregnancy failure. Fifty-two patients were followed up regularly and were alive. CONCLUSIONS: We find that thrombosis, venous or arterial, and obstetric complications are the most frequent clinical findings in our patients with circulating LAC. Incidental APS is not an uncommon finding in patients screened for APS. There is a clear association between the presence of LAC and an abnormal aPTT, which is much less obvious with the PT.

Patterns of presentation of malaria in a tertiary care institute in Saudi Arabia.

OBJECTIVE: The occurrence of malaria in a non-endemic area is an exceptional event. Review of clinical experience at the King Faisal Specialist Hospital & Research Centre (a tertiary medical centre located in a non-endemic area) demonstrated a relatively frequent infection rate among patients. We therefore examined circumstances that could contribute to the high rate of occurrence observed. METHODS: We retrieved archived blood smears of patients diagnosed with malaria from the records of the Hematology Section of King Faisal Specialist Hospital & Research Centre, Riyadh, Kingdom of Saudi Arabia, followed by a review of the clinical records to extract demographic data, clinical presentations including history of proximate blood transfusion, and travel to, or residence in, areas endemic for malaria. RESULTS: There were 217 patients diagnosed with malaria between 1978 and 1999, (1398 to 1419 Hejira calendar) resulting in an average yearly frequency of 9.86 cases. Males were 2.6 times more frequently affected than females (p<0.001). The majority of patients were infected through natural means, either by residence in endemic areas (N=83) or by travel to one (N=90). A significant minority, 44 (20.3%), became infected through blood transfusion. The majority of blood transfusion-induced malaria occurred in patients who were immunocompromised for various reasons, mostly related to dysfunction of the hematopoietic system or to major surgical insult. The most frequently implicated organism was Plasmodium falciparum, accounting for 74.2% of cases, whilst Plasmodium vivax accounted for 25.4%. CONCLUSION: We demonstrate that patients presenting with malaria are more likely to be males who have been exposed during travel to endemic areas or through blood transfusion. In all cases, Plasmodium falciparum is the most likely organism to be implicated.