Year: 2014
Type: dissertation
Study design: Observational Study
Abstract: A complex interaction prevails between coagulation and inflammation. The coagulation system is adapted to thrombotic challenges during and after birth, leading to specific features in the coagulation system of the newborn. Inflammation and intra-alveolar fibrin formation characterize respiratory distress syndrome (RDS). Tissue factor (TF) is a link between inflammation and coagulation pathways. In the very low birth weight (VLBW) infant, birth and intensive care present major immunological challenges, and the developmental immaturity of the immune system adds to the risks of intensive care. A protective response to a strong inflammatory stimulus downregulates the antigen-presenting molecules (Human leukocyte antigen (HLA)-DR) on monocytes. If severe, however, the response may lead to immunodepression or immunoparalysis, which in adults is associated with increased morbidity and death. Antenatal betamethasone treatment for mothers at risk for premature delivery effectively reduces neonatal morbidity and mortality. This thesis evaluates the bidirectional interaction between inflammation and coagulation and combines the findings in VLBW infants with clinical morbidity. Patients were 56 VLBW infants, with a gestational age (GA) of less than 32 weeks and a birth weight of less than 1500 g. A control population comprised 25 healthy infants with a GA of more than 34 weeks. VLBW infants showed low monocyte HLA-DR expression. On day 3, 45% of infants presented with immunodepression. VLBW infants showed high plasma TF in circulation, but which did not lead to coagulation. In VLBW infants, tissue factor pathway inhibitor (TFPI) was the main anticoagulant in the first days; on day 3, however, the TF surge exceeded the TFPI capacity, leaving the VLBW infant with a pool of plasma TF. In VLBW infants, antenatal betamethasone associated with immunodepression and suppressed both proinflammatory IL-6 and anti-inflammatory IL-10. VLBW infants are postnatally in a state of immunodepression, which associated with RDS, low GA, and subsequent infections. Immunodepression may represent a link between low GA and risk for infections. TF is expressed in the lungs of a VLBW infant and leaks into circulation. TFPI could not control the TF surge on day 3. Plasma TF does not lead to thrombin formation, thereby making it available for inflammatory pathways (e.g. protease-activated receptors (PARs)). VLBW infants showed an inflammatory profile similar to adult sepsis or acute respiratory distress syndrome, with additional VLBW-specific features: a lower net anti-inflammatory cytokine effect without TF-induced activation of coagulation. Antenatal betamethasone (BM) was associated in a time-dependent manner to immunodepression, those infants with BM less than 24 hours before birth showing the deepest nadir in HLA-DR expression.
Source: Työväentutkimus Vuosikirja
Author: Anniina Palojärvi
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W1496915735