Temporal Platelet Aggregatory Function in Hypoxic Newborn Piglets Reoxygenated With 18%, 21%, and 100% Oxygen

Abstract

Thromboembolic and bleeding complications are common after asphyxia. We studied the temporal effects of different oxygen concentrations used in resuscitating hypoxic newborn piglets on platelet aggregatory function. Alveolar normocapnic hypoxia (fractional inspired oxygen concentration = 0.15) was induced in piglets (1-4 d, 1.7-2.5 kg) for 2 h, followed by reoxygenation with 18%, 21%, or 100% oxygen for 1 h and then 21% for 2 h (n = 8-9 per group). Control piglets underwent surgery with no hypoxia-reoxygenation (n = 5). Platelet counts and collagen-stimulated (2-10 microg/mL) whole blood aggregation were studied at normoxic baseline and at 3 h, 2 d, and 4 d of recovery. Platelet activation markers including plasma thromboxane B2 and matrix metalloproteinase 2 and 9 levels were measured. At 2 h hypoxia (mean PaO2 30-35 mmHg), all piglets were hypotensive and acidotic (mean pH 7.19-7.24). In 100% reoxygenation piglets, the concentration-response curves of collagen-stimulated platelet aggregation were significantly shifted upward at 3 h and 2 d of recovery with no differences in the collagen concentration required to induce 50% of maximum aggregation, and this normalized to baseline on 4 d. In the 18% and 21% reoxygenated groups, there were no changes in platelet aggregation during the experiment. Platelet counts were not different between groups and over time. Hypoxic-reoxygenated piglets had increased plasma thromboxane B2 (100% group) and matrix metalloproteinase-2 levels (21% and 100% groups) (versus respective baseline, P < 0.05), with no difference between experimental groups. These findings suggest transient platelet activation in hypoxic newborn piglets resuscitated with 100% but not with 18% and 21% oxygen, of which the clinical significance requires further investigation.

Delayed Inhibition of Agonist-Induced Granulocyte-Platelet Aggregation After Low-Dose Sevoflurane Inhalation in Humans

“…The reason for this hypercoagulable state is not clear, but may have been related to the reported procoagulant effects of oxygen on platelets. 39,40 Irrespectively, sevoflurane completely abolished this untoward effect and reestablished normal coagulation. Since maximal clot strength was reported to correlate with postoperative thrombotic complications, this finding may be of clinical significance.…”

Thrombotic Alterations under Perinatal Hypoxic Conditions: HIF and Other Hypoxic Markers

“…Unfortunately, a common complication of these treatments is an increased risk of thrombosis, which is solved by anticoagulant administration [57]. For instance, a swine model of asphyxia revealed that therapeutic re-oxygenation triggers unwanted transient platelet activation, eliciting deranged coagulation [58]. The decreased temperature during therapeutic hypothermia slows the hemostatic system down even further, increasing the risk of uncontrolled bleeding and hemorrhage [59].…”

Platelets in the Newborn

“…It was reported that mechanical ventilation led to reduced platelet counts in newborns with respiratory distress, or in rabbit models, regardless of the oxygen concentration used [121]. However, using newborn piglet models of hypoxia, it was found that various platelet indices were affected particularly by high oxygen level used [122]. Resuscitation with 100% oxygen led to enhanced collagen-stimulated platelet aggregation, while using 18-21% oxygen did not do so [122].…”

“…However, using newborn piglet models of hypoxia, it was found that various platelet indices were affected particularly by high oxygen level used [122]. Resuscitation with 100% oxygen led to enhanced collagen-stimulated platelet aggregation, while using 18-21% oxygen did not do so [122].…”