Introducing Noninvasive and Continuous Real-time Hemoglobin Monitoring with Masimo Rainbow Set

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<lb>Introduction: Renal vein thrombosis, although rare in adults, is<lb>well recognized in neonates and is one of the most common<lb>manifestations of neonatal thromboembolic events. The etiology<lb>of renal vein thrombosis remains unidentified in the majority of<lb>cases. We report a case of renal vein thrombosis in a neonate<lb>associated with elevated maternal lipoprotein (a). Case presentation: A full-term female infant, appropriate for<lb>gestational age, was born via spontaneous vaginal delivery to an<lb>18-year-old primigravida. The infant’s birth weight was 3680g<lb>and the Apgar scores were eight and nine at 1 and 5 minutes<lb>respectively. Evaluation of the infant in the newborn nursery<lb>revealed a palpable mass in the right lumbar area. Tests<lb>revealed hematuria and a high serum creatinine level of 1.5<lb>mg/dl. An abdominal ultrasound Doppler flow study<lb>demonstrated an enlarged right kidney, right renal vein<lb>thrombosis, and progression of the thrombosis to the inferior<lb>vena cava. There was no evidence of saggital sinus thrombosis.<lb>An extensive work-up of parents for hypercoagulable conditions<lb>was remarkable for a higher plasma lipoprotein (a) level of 73<lb>mg/dl and an elevated fibrinogen level of 512 mg/dl in the<lb>mother. All paternal levels were normal. The plasma lipoprotein<lb>(a) level in the neonate was also normal. The neonate was<lb>treated with low molecular weight heparin (enoxaparin) at 1.5<lb>mg/kg/day every 12 hours for 2 months, at which time a follow-<lb>up ultrasound Doppler flow study showed resolution of the<lb>thrombosis in both the renal vein and the inferior vena cava. Conclusion: There have been no studies to date that have<lb>explored the effect of abnormal maternal risk factors on fetal<lb>hemostatsis. A case-control study is required to investigate<lb>whether elevated levels of maternal lipoprotein (a) may be a<lb>risk factor for neonatal thrombotic processes. Although infants<lb>with this presentation are typically treated with anticoagulation,<lb>there is a lack of evidence-based guidelines. Treatment<lb>modalities vary between study and treatment centers which<lb>warrants the establishment of a national registry. Introduction<lb>Renal vein thrombosis (RVT), although rare in adults, is well<lb>recognized in neonates and is one of the most common<lb>manifestations of neonatal thromboembolic events.1 The clinical<lb>signs of neonatal RVT (NRVT) include an enlarged kidney,<lb>hematruia, proteinuria, renal failure, hypertension and/or<lb>thrombocytopenia. Long-term consequences of NRVT include<lb>hypoplastic kidney, tubular defects, hypertension and renal<lb>insufficiency.2 We report a case of NRVT associated with<lb>elevated maternal lipoprotein (a) [Lp (a)]. Case presentation<lb>A full-term female infant, appropriate for gestational age, was<lb>born via spontaneous vaginal delivery, weighing 3680g, to an 18-<lb>year-old primigravid Hispanic mother and a 21-year-old African<lb>American father. The neonate adapted well to extra-uterine life<lb>as evidenced by Apgar scores of eight and nine at 1 and 5<lb>minutes, respectively. The pregnancy had been uneventful, and<lb>the maternal screens were all negative. There was no evidence<lb>of diabetes or pre-eclampsia during pregnancy. The neonate was<lb>transferred to the newborn nursery for routine newborn care.<lb>Physical examination in the newborn nursery revealed a<lb>palpable mass in the right lumbar area. Significant laboratory<lb>findings in the neonate included hematuria, and an elevated<lb>serum creatinine level of 1.5 mg/dl prompting transfer to the<lb>neonatal intensive care unit. A renal ultrasound evaluation<lb>showed an enlarged right kidney (5.56 cm) with loss of<lb>coricomedullary distinction. A renal Doppler flow study<lb>demonstrated an increased resistive index of the right renal<lb>artery with suboptimal wave forms of the right renal vein and a<lb>clot in the right renal vein (Figure 1). A Doppler flow study of<lb>the left renal artery and vein was normal. The neonate had<lb>normal blood pressures throughout the hospital stay. The neonate and her parents were evaluated for prothrombotic<lb>risk factors. The mother’s laboratory parameters were<lb>remarkable for an elevated level of Lp (a) of 73 mg/dl (normal 0<lb>to 40 mg/dl), and fibrinogen of 512 mg/dl (156 to 400 mg/dl). The<lb>Vivek Subbiah is with the Department of Internal Medicine/Pediatrics, Case Western Reserve University School of Medicine, MetroHealth Medical Center, Cleveland, OH; Prabhu Parimi is with the Division of Neonatology, Department of Pediatrics, University of Kansas, KU Medical Center, Kansas City. Reprinted from BioMed Central, © 2008, the Journal of Medical Case Reports. This is an open access article distributed under the terms of the Creative Commons Attribution License. 34<lb>neonatal INTENSIVE CARE Vol. 21 No. 4 !<lb>July-August 2008 Figure 1<lb>Figure 2 plasma Lp (a) concentration was measured by the enzyme-<lb>linked immunosorbent assay (ELISA) technique using mouse<lb>monoclonal anti-apo (a) capture antibody and sheep polyclonal<lb>anti-apoB detection antibody (COALIZA Lp (a), Chromogenix).<lb>The other laboratory tests on the mother were normal: plasma<lb>homocysteine 5.3 μmol/l; protein C activity greater than 125%;<lb>protein S activity greater than 125%; anticardiolipin antibody<lb>IgG 6.21gG phospholipid binding units; anticardiolipin IgM<lb>6.41gM phospholipids binding units; beta 2 glycoprotein IgG less<lb>than 9 standard IgG antibeta 2 glycoprotein units; beta 2<lb>glycoprotein IGM less than 9 standard IgM antibeta 2<lb>glycoprotein units; lupus anticoagulant negative; Factor VIII A<lb>assay 108%; antinuclear antibody (ANA) screening negative;<lb>antithrombin III 94%; prothrombin time (PT), partial<lb>thromboplastin time (PTT), international normalized ratio (INR)<lb>normal. DNA analysis showed no point mutation (G20210A) in<lb>the 3’ untranslated region of the prothrombin gene, no genetic<lb>polymorphism (ARG 506/Glu 206) for Factor V Leiden, and no<lb>gene mutation (C677T) for 5’ 10 methylenetetrahydrofolate<lb>reductase (MTHFR). The paternal screens were all normal. The plasma Lp (a) level in the neonate was 11 mg/dl (0 to 40<lb>mg/dl). This was measured when the maternal Lp (a) results<lb>became available, that is, 4 days after the diagnosis of RVT. The<lb>plasma homocysteine level was 4.6 μmol/l (4 to 13.7 μmol/l). A<lb>computed tomography (CT) scan of the head of the neonate was<lb>negative for saggital sinus thrombosis. The neonate was started<lb>on low molecular weight heparin (enoxaparin) at 1.5 mg/kg/day<lb>every 12 hours, with antifactor Xa monitoring. The antifactor Xa<lb>activity measured was 0.741U/ml (less than 0.10IU/ml). The<lb>serum creatinine level decreased to 0.5 mg/dl 9 days after<lb>initiation of treatment, and urinalysis showed no evidence of<lb>hematuria. Renal ultrasound Doppler flow studies were<lb>repeated at weekly intervals during the hospital stay. One week<lb>after initiation of treatment, an ultrasound demonstrated<lb>persistence of RVT and development of a new thrombosis in the<lb>inferior vena cava. The neonate was discharged home on<lb>enoxaparin and followed by a hematologist, a nephrologists and<lb>a primary care physician. A follow-up ultrasound Doppler flow<lb>study at 2 months of age showed a normal flow pattern in the<lb>aorta, inferior vena cava, right and left renal arteries and veins<lb>indicating resolution of the thrombosis (Fig. 2). Enoxaparin was<lb>discontinued at 2 months of age. The baby continued to do well<lb>with no evidence of residual renal dysfunction or hypertension<lb>of 18 months of age. Discussion<lb>The etiology of NRVT remains unidentified in the majority of<lb>cases. The existence of underlying predisposing factors, such as<lb>asphyxia, sepsis, diabetic fetopathy or indwelling intravascular<lb>catheters, in combination with inherited prothrombotic risk<lb>factors, play a major role in the pathogenesis of NRVT,1-4 however their role is not well defined. The association between<lb>maternal thrombophilia and thrombotic complications in the<lb>neonate is unknown.5 Lp (a) consists of phospholipids, cholesterol and apolipoprotein<lb>B-100 (low-density lipoprotein), with apolipoprotein (a)<lb>attached to the latter at a single point. Recent studies have<lb>demonstrated the significance of prothrombotic risk factors,<lb>especially the elevation of Lp (a) in the etiology of NRVT. It has<lb>been shown that Lp (a) competes with plasminogen for the<lb>plasminogen receptor on endothelial cells and initiates<lb>thrombosis. It has also been demonstrated that Lp (a)<lb>inactivates the ‘tissue factor (TF) pathway inhibitor,’ which is a<lb>major endogenous regulator of TF-mediated coagulation.6 Elevated plasma concentration of Lp (a) has been consistently<lb>shown to be a risk factor for the development of a variety of<lb>thrombotic and atherosclerotic disorders in humans. Lp (a) has<lb>been implicated in NRVT1 as well as in cerebral venous<lb>thrombosis.5 Lp (a) greater than 30 mg/dl has been shown to be<lb>a risk factor for the development of venous thromboembolism<lb>in children.7 There is a paucity of data exploring prothrombotic risk factors<lb>in the development of NRVT in neonates. None of the studies<lb>reported to date have explored the effect of abnormal maternal<lb>risk factors on fetal hemostasis. The mechanism by which an<lb>elevated maternal Lp (a) with a normal level in the neonate<lb>contributes to the formation of a thrombus was unclear in this<lb>case. There is no evidence that Lp (a) crosses the placenta given<lb>the large size of this molecule. A higher level of maternal Lp (a)<lb>crosses the placenta given the large size of this molecule. A<lb>higher level of maternal Lp (a) could be an independent risk<lb>factor in neonatal thromboembolic events. A case-control study<lb>is required to investigate whether elevated levels of maternal Lp neonatal INTENSIVE CARE Vol. 21 No. 4 !<lb>July-August 2008<lb>35 (a) are a risk factor for neonatal thrombotic processes. In<lb>addition to measuring plasma levels of Lp (a) by standardized<lb>methods, genetic polymorphisms of Lp (a) should also be explored to identify secretor haplotypes.


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