Peter A. Lane

Vitamin K in infancy.

Vitamin K is required for carboxylation of a number of calcium-binding proteins including the coagulation factors II, VII, IX and X; the anticoagulant proteins C and S; other proteins in kidney, dentin and lung and osteocalcin in bone. When there is deficiency of vitamin K, inactive, uncarboxylated forms of the clotting proteins (descarboxy-proteins or PIVKAs Proteins formed In Vitamin K Absence) circulate and are a much more sensitive measure of deficiency than the prothrombin time. There are two natural sources of vitamin K, plants and bacteria. Plants produce phylloquinone, also called vitamin K1. Bacteria produce a range of related compounds, the menaquinones or vitamins K2. The naturally occurring K vitamins are fat soluble and absorption from the small intestine is dependant on the presence of bile salts and pancreatic lipases. Dietary vitamin K~ is certainly the main, if not the only, source in human infants; contrary to what is commonly taught, colonic absorption of bacterially-produced menaquinones is unproven. The maternal:fetal gradient for vitamin K1 across the placenta may be as high as 40: 1, which explains the very low cord blood concentrations. The infant who is formula fed from birth is at an immediate advantage regarding vitamin K (though perhaps in no other way) because he can drink until satisfied and the milk contains a high concentration of the vitamin (about 50 gg/1 in most formulae); by contrast, the breast fed baby has a meagre supply of milk in the early days and the vitamin K content is only about 2 ~tg/1. Delay in establishing feeding, especially by breast, may precipitate vitamin K deficiency in the early days of life and it is the breast

Acute multiorgan failure syndrome: A potentially catastrophic complication of severe sickle cell pain episodes

The purpose of this report is to characterize the acute multiorgan failure syndrome that complicates some episodes of sickle pain. A retrospective chart review was used to identify episodes of sickle pain complicated by the acute failure of at least two of three organs: lung, liver, or kidney. The defining criteria of organ failure were established, and the clinical characteristics, laboratory values, treatment methods, and outcomes were noted in episodes that met the criteria. Seventeen episodes of acute multiorgan failure were identified in 14 patients, 10 with sickle cell anemia and 4 with hemoglobin SC disease. Most episodes occurred during a pain event that was unusually severe for the patient. The onset of organ failure was associated with fever, rapid fall in hemoglobin level and platelet count, nonfocal encephalopathy, and rhabdomyolysis. Bacterial cultures were negative in all but four episodes. Aggressive transfusion therapy was associated with survival and with rapid recovery of organ function in all but one episode. The syndrome developed in patients who had previously exhibited relatively mild disease with little evidence of chronic organ damage and relatively high hemoglobin values in steady state. Acute multiorgan failure syndrome is a severe, life-threatening complication of pain episodes in patients with otherwise mild sickle cell disease. The syndrome appears to be reversed with prompt, aggressive transfusion therapy. High baseline hemoglobin levels may represent a predisposing factor.

Thrombo-embolic disease after splenectomy for hereditary stomatocytosis.

Nine cases of hereditary stomatocytosis (HSt) are presented which show documented thrombotic complications after splenectomy. In three cases, patients became severely ill with pulmonary hypertension and a fourth developed portal hypertension. One unsplenectomized affected adult relative had suspected but unconfirmed thrombotic pathology; the six other affected unsplenectomized adults did not. Since splenectomy is of only limited therapeutic benefit in stomatocytosis, it should be not be performed without careful consideration. A tendency to iron overload, even without hypertransfusion and irrespective of splenectomy, is evident in many of these patients.

Universal versus targeted screening of infants for sickle cell disease: A cost-effectiveness analysis

OBJECTIVEnTo compare the health outcomes, costs, and incremental cost-effectiveness of universal neonatal screening for sickle cell disease (SCD) with screening targeted to African Americans.nnnSTUDY DESIGNnA cost-effectiveness analysis was done by using a Markov simulation model that considered the costs and outcomes associated with the prevention and treatment of sepsis in those with sickle cell anemia and sickle beta(0)-thalassemia. Three strategies were compared: (1) no screening, (2) targeted screening of African Americans, and (3) universal screening for SCD.nnnRESULTSnIn the base case analysis, targeted screening of African Americans compared with no screening cost

Vitamin K deficiency in the newborn infant: Prevalence and perinatal risk factors

6709 per additional year of life saved, and universal screening compared with targeted screening cost

Practical guide to the diagnosis of thalassemia

30,760 per additional year of life saved. In a sensitivity analysis, the cost per additional year of life saved with universal screening compared with targeted screening was positively correlated with the delivery rate of targeted screening and was inversely related to the proportion of African Americans in the population.nnnCONCLUSIONSnTargeted screening of African American newborns for SCD compared with no screening is always cost-effective. Universal screening compared with targeted screening always identifies more infants with disease, prevents more deaths, and is cost-effective given certain delivery rates for targeted screening and proportions of African Americans in the population.

941 PREVALENCE OF VITAMIN K DEFICIENCY IN NEWBORN INFANTS: INFLUENCE OF PERINATAL RISK FACTORS

The prevalence of vitamin K deficiency in newborn infants and the influence of perinatal risk factors were studied prospectively in 934 infants. A noncarboxylated prothrombin assay to detect proteins induced in vitamin K absence (PIVKA-II) was used to determine the presence of vitamin K deficiency; of 934 cord blood samples assayed, 2.9% were positive for PIVKA-II (0.015 to 0.15 U/ml). All infants found to have detectable PIVKA-II were born at term. The number of infants positive for PIVKA-II was greater in the group small for gestational age (7.4%) than in those appropriate (2.7%) or large (3.1%) for gestational age. Nine categories of perinatal risk groups were defined: however, the majority of infants who were PIVKA-II positive (63%) were normal. All infants received prophylactic vitamin K, and no infant with PIVKA-II in the cord sample subsequently had clinical bleeding. In two patients the rate of 50% disappearance of PIVKA-II after vitamin K administration approximated 70 hours. Two PIVKA-II positive patients with active bleeding or disseminated intravascular coagulation had an accelerated disappearance of 20 to 40 hours. The long disappearance time of PIVKA-II in a steady state may allow detection of vitamin K deficiency despite administration of vitamin K. The majority of cases of neonatal vitamin K deficiency occurred in normal newborn infants. Therefore, all infants should receive prophylactic vitamin K at birth.

Functional asplenia in hemoglobin SC disease

Thalassemias occur in individuals of all ethnic backgrounds and are among the most common genetic diseases worldwide. The diagnosis of thalassemia can easily be part of primary medical practice. Here we outline a practical approach to the detection of thalassemias in three common clinical settings. The first involves any patient with a low mean corpuscular volume (MCV) with or without anemia. The second is a neonatal screening result indicating possible presence of thalassemia. Finally, evaluation for thalassemia should be considered in the context of family planning or pregnancy in patients whose ethnicity indicates origin from high risk geographic areas. We also review the various types of the thalassemia syndromes and provide an overview of general therapeutic considerations.

Newborn Screening for Hemoglobinopathies in Colorado: The First 10 Years

Measurement of noncarboxylated prothrombin (PIVKA-II assay) was used to study 559 infants for vitamin K (vit K) deficiency. This test, performed by immunoelectrophoresis of plasma before and after BaCO3 precipitation, is sensitive to 0.03 u/ml PIVKA-II, has an intra- and inter-test coefficient of variation of 3-5%, and is negative in liver disease. Catagories of infants studied and results are as follows. As part of an ongoing study of 1,000 cord bloods, 534 cords were assayed and 2.6% were PIVKA-II positive (0.03-0.15 u/ml). The PT of the PIVKA-II positive samples ranged from 11.5-23 seconds and correlated inversely with prothrombin activities of 10-55%. SGA infants were at increased risk for K deficiency (14%); however, other groups were not (preterm, post-term, infants with fetal distress, and infants of mothers with hypertension or third trimester infection), Interestingly, of 16 infants born to mothers on chronic anticonvulsant therapy, only one showed PIVKA-II. Eight breast-fed infants who were given neonatal vit K did not develop a deficiency by two months of age. A K deficient infant given 1 mg vit K and then fed entirely by parenteral nutrition without supplemental vit K showed absence of PIVKA-II for five weeks.In summary, 2.6% of all newborns may be vit K deficient at birth. While most K deficient infants were born of normal pregnancies and deliveries, SGA infants were more likely to be PIVKA positive. Vit K is stored in newborns to an appreciable degree.