Blood Coagulation Changes Following Hypoxemia in the Near-Term Fetal Lamb

C Thomas Kisker; Jean E Robillard; William R Clarke

doi:10.1203/00006450-198209000-00006

Summary: The effects of severe hypoxemia on blood coagulation factor activities and other physiologic parameters were examined in ten near-term chronically catheterized fetal lambs (135–140 days gestation). Six lambs were subjected to a mean Po2 of 13.8 ± 1.4 mmHg for 60 min. The other four served as controls. Before, during and after hypoxemia, the white blood cell count, hemoglobin, hematocrit, platelet count, pH, Pco2, Po2, mean arterial pressure, heart rate, norepinephrine and epinephrine were measured. Measures of coagulation factor activities including platelet counts, partial thromboplastin times, prothrombin times and quantitation of plasma activities for factors I, II, V, VII, VIII, IX, X, XI, XII, fibrin degradation products (FDP), antithrombin III, fibrin monomer and ristocetin cofactor activity were also done. An increase in mean arterial pressure from 48 ± 2 mmHg to 56 ± 2 mmHg, and an increase in epinephrine from 22 ± 9 pg/dl to 419 ± 199 pg/dl, and norepinephrine from 431 ± 98 pg/dl to 2408 ± 868 pg/dl occurred in the hypoxemic animals. There was also a slight decrease in the pH from 7.37 ± 0.01 to 7.32 ± 0.03 in the hypoxemic animals. The only significant change in blood coagulation factors during hypoxemia was a slight increase in fibrin monomer from 5.6 ± 0.8 ±g/ml to 12.6 ± 2.0 μg/ml. After the experiment, the animals were allowed to go to term and deliver spontaneously. Delivery occurred from 2–12 days after the experiment (mean 6 days). Blood coagulation factor activities I, II, V, VII, VIII, IX, X, XI, XII, antithrombin III, fibrin monomer, and fibrin degradation products were measured after delivery in the hypoxemic and control animals. Except for factor XII, values obtained from ten previously catheterized control fetal lambs after spontaneous delivery did not differ from the current control animals after delivery. Values on postdelivery samples for the two control groups were therefore pooled for analysis. Factors VIII, and IX were found to show increased activity during the 2 wk after delivery in hypoxemic animals when compared with controls. In contrast, the values for factors II, V, VII, X and fibrinogen showed lower activity in hypoxemic as compared to control animals during the early neonatal period. The study demonstrates that though there are no severe acute effects on blood coagulation during severe hypoxemia in the near-term fetus except perhaps transient low-grade disseminated intravascular coagulation, the episode of hypoxemia appears to alter the future development of blood coagulation factor activities during the early neonatal period. Speculation: Hypoxemia in the near-term fetus delays the normal development of prothrombin, factors V, VII, X, and fibrinogen during the early neonatal period and accelerates the development of factors VIII and IX. The differences in factor responses may help explain the variable results reported in human infants. The results also suggest that both thrombotic and hemorrhagic tendencies might be a consequence of prenatal hypoxemia.

Blood Coagulation Changes Following Hypoxemia in the Near-Term Fetal Lamb

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