Background
Pulmonary embolism (PE) is a serious complication of acute lymphoblastic leukemia (ALL). We examined the cumulative incidence and clinical presentation of PE in a well‐defined cohort of patients with ALL aged 1‐45 years treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol.
Methods
As part of the mandatory toxicity reporting of NOPHO ALL2008, thromboembolism including PE was reported consecutively. The cumulative incidence of first‐time PE was calculated using the Aalen‐Johansen estimator during a 2.5‐year period from ALL diagnosis. We used Fisher’s exact test to examine categorical variables and Cox logistic regression to estimate hazard ratios (HRs) for PE.
Results
PE was diagnosed in 32 of 1685 patients. The 2.5‐year cumulative incidence of first‐time PE increased with age: 0.43% (95% CI, 0.18‐1.03) in children aged 1‐9 years, 3.28% (95% CI, 1.72‐6.22) in children aged 10‐17 years, and 7.22% (95% CI, 4.61‐11.21) in adults aged 18‐45 years. The majority of PEs, 78% (25/32), occurred during asparaginase treatment. HRs adjusted for age and sex were associated with male sex (HR, 2.4; 95% CI, 1.0‐5.6) and older age (10‐17 years: HR 7.5; 95% CI, 2.5‐22.2), 18‐45 years: HR, 16.5; 95% CI, 6.1‐44.5). In two‐thirds of the patients (63%; 17/27), PE and its treatment had no impact on the administered doses of asparaginase. PE‐associated 30‐day mortality was 9.4% (95% CI, 1.9‐25.0).
Conclusions
Awareness of PE is warranted during ALL treatment. Larger multicenter studies are needed to examine predictors of PE in ALL.
Introduction: Venous malformations (VMs) are congenital low-flow lesions with a wide spectrum of clinical manifestations. An increasing number of studies link VMs to coagulation abnormalities, especially to elevated D-dimer and decreased fibrinogen. This condition, termed localized intravascular coagulopathy (LIC), may pose a risk for hemostatic complications. However, detailed data on the laboratory variables for coagulation and fibrinolytic activity in VM patients are limited. We addressed this question by systematically analyzing the coagulation parameters in pediatric VM patients. Methods: We included 62 patients (median age 11.9 years) with detailed laboratory tests for coagulation and fibrinolytic activity at a clinically steady phase. We assessed clinical and imaging features of VMs and their correlations with coagulation and fibrinolysis variables using patient records and MRI. Results: D-dimer was elevated in 39% and FXIII decreased in 20% of the patients, as a sign of LIC. Elevated D-dimer and decreased FXIII were associated with large size, deep location, and diffuse and multifocal VMs. FVIII was elevated in 17% of the patients and was associated with small VM size, superficial and confined location, discrete morphology, and less pain. Surprisingly, antithrombin was elevated in 55% of the patients but without associations with clinical or other laboratory variables. Conclusions: LIC was common in pediatric patients with VMs. Our results provide a basis for when evaluating the risks of hemostatic complications in children with VMs. Further research is warranted to explore the mechanisms behind coagulation disturbances and their relation to clinical complications.
Children with community-acquired bacterial-type pneumonia show distinctive changes in their coagulation system. The finding of coagulation system activation and depressed function of natural anticoagulants in uncomplicated pneumonia helps to understand the rapid and unpredictable changes observed in the coagulation status in patients with more severe forms of disease.
Thrombin generation was enhanced in patients who did not receive UFH, which may increase the risk of thrombotic complications. In group A, routine heparinization seemed excessive by all monitoring methods. UFH prevented an increase in prothrombin to thrombin conversion, resulting in unaltered fibrin formation. The current UFH protocol seemed to have no effect on postprocedural activation of coagulation. Further studies are needed to clarify adequate heparin dosing for children during cardiac catheterization to prevent thrombotic complications without predisposing the patient to bleeding complications.
Coagulation system is disturbed by several mechanisms after allogeneic haematopoietic stem cell transplantation (HSCT). We evaluated the effect of HSCT on coagulation system by various conventional and investigational methods in 30 children and adolescents who received HSCT due to haematological malignancies. Pro-thrombin fragment 1 + 2, a specific measure of thrombin generation, and von Willebrand factor, a measure of endothelial activation, increased after conditioning treatment, and remained elevated until 3 months after HSCT ( < 0.05 for all comparisons to pre-conditioning treatment). D-dimer, a measure of fibrin turnover, was elevated from the second week onwards until 4 weeks after HSCT ( < 0.05). Endogenous thrombin potential was increased after conditioning, and at 2 weeks after HSCT ( < 0.05). Furthermore, the activities of acute phase reactants fibrinogen and coagulation factor VIII were increased ( < 0.05 for all comparisons to pre-conditioning treatment) from the first week onwards up to 3 weeks and 3 months after HSCT, respectively. Taken together, paediatric patients receiving HSCT demonstrate distinct and prolonged variations in the coagulation system towards a pro-coagulant state. This shift is of importance when estimating the risk of haemostatic and thrombotic complications in these children.
In VLBW infants plasma TF fails to associate with thrombin formation. This is partly explained by release of TFPI. Despite TFPI, the newborn VLBW infant is subjected to a substantial circulating pool of TF with potential proinflammatory effects.
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