Acute Polycythemia Increases the Disappearance Rate of Clottable Fibrinogen in the Newborn Dog

Abstract

ABSTRACT. To explore the pathophysiology of the necrotizing enterocolitis caused by polycythemia in the newborn dog, the effect of acute polycythemia on fibrinogen disappearance rate was studied in 3 8 puppies (3-14 days). All pups received an exchange transfusion removing 6 5 ml/ kg of blood and transfusing 8 5 ml/kg of either whole blood (control, resulting hematocrit = 37), or packed red blood cells (polycythemia, resulting hematocrit = 68). Necrotizing enterocolitis was found in 1 5 of 19 polycythemic and four of 1 9 control pups ( p < 0.01). Iz5I fibrinogen and Evan's blue (an albumin marker) were injected 2 h after transfusion and the concentration of clottable labeled fibrinogen and albumin tracer were measured a t % and 2 h after injection. The fraction of the tracer that disappeared over the 1%-h period was calculated. In the polycythemic group 45 2 18 SD% of the clottable fibrinogen disappeared versus only 28 f 15% in the control group ( p < 0.01). In the polycythemic group 36 2 21% of the albumin tracer disappeared versus 31 f 12% in the control group (NS). Thus polycythemia in the newborn dog is associated with an increased disappearance rate of clottable fibrinogen not associated with a general increase in protein disappearance rate. Thus an intravascular coagulopathy is evident in the polycythemic animals. Whether this coagulopathy is the cause of the necrotizing enterocolitis or is secondary to the necrotizing enterocolitis seen in this animal model cannot be determined from this experiment. (Pediatr Res 20: 151-154,1986) Abbreviation pH,, arterial p H Polycythemia is a common condition in human newborns (1) that is thought to cause significant acute disease and possibly long-term neurologic sequelae (2-9). Hakanson and Oh (10) describe an association between polycythemic hyperviscosity and necrotizing enterocolitis in small for gestation age infants. We have demonstrated that polycythemia will cause necrotizing enterocolitis in the newborn dog (1 1). This article, as far as we are aware, was the only description of a disease seen in human infants with polycythemia, caused by polycythemia in an animal model. Since coagulation abnormalities have been associated with polycythemia in vitro (12-16) we sought to determine if coagulation abnormalities could be demonstrated in our model. Attempts to demonstrate coagulopathy in human infants with

Large Animal Models for Simulating Physiology of Transfusion of Red Cell Concentrates—A Scoping Review of The Literature

“…However, the study by Muenster et al exposed erythrocyte concentrates to oxygen or nitric oxide prior to transfusion [21]. (C) In 13 out of the 36 included studies, a total of 440 dogs were included, with only three studies describing a repeated use of the same animals [14,[42][43][44][45][46][47][48][49][50][51][52][53]. Study populations showed similar ranges compared to the other two species, with studies using six to 76 dogs per study [14,[42][43][44][45][46][47][48][49][50][51][52][53].…”

“…(C) In 13 out of the 36 included studies, a total of 440 dogs were included, with only three studies describing a repeated use of the same animals [14,[42][43][44][45][46][47][48][49][50][51][52][53]. Study populations showed similar ranges compared to the other two species, with studies using six to 76 dogs per study [14,[42][43][44][45][46][47][48][49][50][51][52][53]. In three out of 13 publications, male and female dogs were included in the same study [42,50,53].…”

“…Study populations showed similar ranges compared to the other two species, with studies using six to 76 dogs per study [14,[42][43][44][45][46][47][48][49][50][51][52][53]. In three out of 13 publications, male and female dogs were included in the same study [42,50,53]. For all studies in pigs and sheep, animals of only one sex were used for each study.…”

“…For all studies in pigs and sheep, animals of only one sex were used for each study. However, the studies utilizing canine models were markedly dominated by male dogs [42,[50][51][52][53]. Beagles were preferably chosen as a breed, with seven publications providing data in this regard [14,[43][44][45][46][47][48].…”

Resistance to activated protein C in newborns with necrotizing enterocolitis

“…Large studies have failed to de®ne any consistent risk factors in premature infants, except for prematurity itself. Ischaemic necrosis is one of the hallmarks in the pathology of NEC and animal studies in a dog model suggest that NEC is associated with intravascular coagulopathy [4]. Thrombosis of mesenteric vessels is a frequent ®nding at autopsy of infants who died because of NEC [5].…”