Peripheral microthrombotic purpura associated with acute promyelocytic leukemia in pregnancy

Summary A case is presented of a pregnant patient in the 28th week of gestation with promyelocytic leukemia and an unusual thrombohemorrhagic skin lesion. Ultrastructural examination revealed a microthrombotic purpura. Reduced coagulation factors increased during heparin treatment. The exacerbation of disseminated intravascular coagulation is explained by a hypercoagulable state in pregnancy in association with the as yet unknown etiology of promyelocytic fibrinopathic leukemia.Presented in part at the 21st Jahrestagung der Deutschen Arbeitsgemeinschaft für Blutgerinnungsforschung Essen, 24.-27.2.1977     

Low antithrombin III: accurate predictor of idiopathic respiratory distress syndrome in premature neonates

A prospective study was performed in premature neonates to determine the predictive values of antithrombin III (AT III) deficiency immediately after birth, for the subsequent development of idiopathic respiratory distress syndrome (IRDS), intraventricular haemorrhage (IVH) and death. Of the 81 premature infants studied, 24 developed IRDS (30%). Of these 24 premature infants, 8 also developed IVH and 9 infants died within the follow-up period of 7 days. The mean plasma AT III level was significantly lower in the infants developing IRDS (0.23 U/ml vs 0.35 U/ml,P<0.0005). Within this study group 33 neonates of less than 30 weeks' gestation showed a prevalence for IRDS of 48%. In this group, AT III activity levels below 0.30 U/ml were 8.5 times as likely to result from infants with IRDS than from infants without IRDS. The diagnostic accuracy indices of criteria for the development of IRDS were: a sensitivity of 100%, a specificity of 88%, a positive predictive value of 89% and a negative predictive value of 100%. The predictive values for the development of IVH and occurrence of death were insignificant. Therefore, in premature neonates the combination of less than 30 weeks' gestation and an AT III below 0.30 U/ml is highly suggestive of IRDS and may facilitate the evaluation of early treatment.Abbreviations AT III antithrombin III - DIC disseminated intravascular coagulation - IRDS idiopathic respiratory distress syndrome - IVH intraventricular haemorrhage - NPV negative predictive value - PPV positive predictive value     

Clinical and anatomo-histopathological features of experimental infection by DF-2 in rabbits

Clinical and anatomo-histopathological features of experimental infection by DF-2 in rabbits are described. Hyperthermy, sensory reduction, diarrhoea, weight loss and catarrhal nasal discharge are reported. PTT and PT are shown to increase and number of platelets diminish markedly. Considerable haemorrhagic diathesis is reported for several organs. Several clots (especially in pulmonary vessels), serious alterations in kidney glomeruli, degeneration of hepatocytes and disseminated necrosis foci are also reported. Lesions are stated as being very similar to those observed in man.     

Intraocular microsporidiosis due to Encephalitozoon cuniculi in a patient with idiopathic CD4+ T-lymphocytopenia

Encephalitozoon cuniculi was documented to cause disseminated microsporidial infection including an iris tumor and endophthalmitis in an adolescent with idiopathic CD4+ T-lymphocytopenia. The diagnosis was established by microscopic, serologic and molecular methods. E. cuniculi (rabbit strain) was identified from the iris tumor, as well as from urine, conjunctival, corneal, and nasal swabs. Treatment with oral albendazole led to rapid improvement. This case raises the possibility of disseminated microsporidial infection in the context of idiopathic CD4+ T-lymphocytopenia and possibly advanced human immunodeficiency virus (HIV) infection, and above all the possibility of intraocular infection with E. cuniculi in humans.     

Neutrophil and monocyte activation markers have prognostic impact in disseminated intravascular coagulation: in vitro effect of thrombin on monocyte CD163 shedding

Monocyte and neutrophil activation occur during microvascular disturbance of disseminated intravascular coagulation (DIC). This study investigated the diagnostic and prognostic value of circulating neutrophil elastase (NE) and neutrophil volume distribution width (NDW) as neutrophil activation markers and circulating soluble CD163 (sCD163) and monocyte volume distribution width (MDW) as monocyte activation markers in 168 patients suspected of having DIC. The sCD163 provided significant diagnostic value. The prognostic value of sCD163 was comparable to that of D-dimer, but was dependent on other coagulation markers. In vitro, thrombin significantly induced sCD163 from monocytes upregulated with IL-10 or dexamethasone. NDW was an independent and powerful prognostic marker. MDW and NE did not provide diagnostic and prognostic power. Excessive thrombin during ongoing DIC induces florid secretion of CD163; sCD163 might therefore be a potential diagnostic and prognostic marker for DIC. NDW, a convenient parameter measured by an automated hematology analyzer, may be an independent prognostic parameter for DIC.     

Animal models of DIC and their relevance to human DIC: a systematic review

Disseminated intravascular coagulation (DIC) is a severe clinical condition with activation of coagulation and fibrinolysis. Its diagnosis is based on the International Society of Thrombosis and Haemostasis (ISTH) scoring system of DIC. Animal models of DIC, used to investigate pathophysiology and evaluate treatments, have not been developed in a standardized way, which impedes comparison between models and translation to the human setting.In the current review of animal models of DIC an overview of species, inducers, and dosing regimens is provided. Diagnostic approaches are compared in the light of the ISTH score and treatments tested in animal models of DIC are summarized.Systematic analysis revealed that the rat is by far the preferred species amongst animal models of DIC and lipopolysaccharides (LPS) the preferred inducer of DIC. An overview of the reporting of ISTH DIC score parameters elucidated that only about 25% of the studies measure all of the four parameters necessary for the implementation the ISTH scoring system. Furthermore, most therapeutic interventions tested in animal models of DIC are administered prophylactically, which may be irrelevant to the clinical setting and could explain why compounds effective in preclinical animal models often fail in clinical trials.It is concluded that Implementation of a scoring system in animal models of DIC may increase the ability to compare DIC amongst animal models and improve the translational aspect of treatment effect.     

Perinatal asphyxia may present with features of neonatal atypical hemolytic uremic syndrome

Hemolytic uremic syndrome (HUS) is the consequence of platelet consumption at sites of endothelial injury. Perinatal asphyxia (PA) may cause renal failure after birth and can be associated with disseminated intravascular coagulopathy (DIC) with platelet consumption. No biological investigation permits us to distinguish clearly between neonatal HUS and DIC. We report on three neonates with renal failure due to different degrees of PA. They presented biological features compatible with HUS, such as fragmentocytes (∼2%), thrombopenia (<50,000/mm³), and anemia (<8 g/dl). One patient required peritoneal dialysis. Haptoglobin was undetectable for all three patients. Factor H and factor I, as well as components of the complement system (C3 and C4) and ADAMTS13 activity, were decreased. Two patients received daily fresh frozen plasma infusions over the first 4 weeks. Renal function improved in two patients; one patient had chronic renal failure. No neurological sequelae were noted. All blood parameters suggestive of thrombotic microangiopathy (TMA) were normal on days 12, 30, and 60. We hypothesize that endothelial cell damage concomitant with PA may lead to a vicious circle that results in consumption of platelets and plasma factors involved in hemostasis and/or fibrinolysis. In conclusion, PA, DIC and HUS are difficult to distinguish, and endothelial cell damage may be their common pathophysiological pathway.     

Successful treatment of disseminated Fusariosis after allogeneic hematopoietic stem cell transplantation with the combination of voriconazole and liposomal amphotericin B

Fusarium is an opportunistic fungal pathogen which is emerging as a significant cause of morbidity and mortality in the immunocompromised host [Fleming RV, Walsh TJ, Anaissie EJ. Emerging and less common fungal pathogens. Infect Dis Clin North Am 2002;16:915–34]. This disease can be localized, focally invasive or disseminated, when two or more noncontiguous sites are involved. Therapeutic options are scarce and mortality reaches 80–90% in patients subjected to allogeneic hematopoietic stem cell transplant (allo-SCT) [Nucci M, Marr KA, Queiroz-Telles F, Martins CA, Trabasso P, Costa S, et al. Fusarium infection in hematopoietic stem cell transplant recipient. Clin Infect Dis 2004;1237–42]. We report a case of disseminated Fusariosis in a severe immunocompromised patient after allo-SCT that responded to treatment with the early combination of intravenous voriconazole and liposomal amphotericin B.     

低分子肝素超早期干预对DIC发生率的影响

目的研究对有DIC(disseminated intravascular coagulation,弥散性血管内凝血)高发因素的重症患者超早期应用低分子肝素(Low-Molecular-Weight Heparins Calcium Injection,LMWH)能否减少DIC的发生率。方法选择有DIC高发因素的重症患者46例随机分为2组,对照组按相应疾病诊疗常规治疗,LMWH超早期干预组在对照组方法治疗的基础上,在出凝血机制无明显障碍的前提下,入院即给予低分子肝素皮下注射2次/日。观察两组患者10天内DIC发生情况的差异。结果 LMWH超早期干预组发生DIC 1例(4.4%),对照组6例(26.1%)。对照组DIC发生率明显高于LMWH组,组间差异有显著性(P<0.05)。结论对有DIC高发因素的重症患者超早期应用低分子肝素治疗,能有效减少DIC的发生率,提高重症患者的存活率。