[Show abstract][Hide abstract] ABSTRACT: To determine the prevalence of iron deficiency (ID) and iron deficiency anemia (IDA) in a sample of children with Down syndrome (DS) and to evaluate the effect of macrocytosis on the diagnosis of ID/IDA in these children.
Children with DS ≥ 12 months of age who were followed at the Duke University Medical Center Comprehensive DS Clinic from December 2004 to March 2007 were screened for ID/IDA with a complete blood count, reticulocyte count, iron panel, and erythrocytic protoporphyrins.
A total of 114 children were enrolled, with a median age of 4.7 years. ID was identified in 12 subjects (10%), and IDA was identified in 3 subjects (3%). ID/IDA would not have been accurately diagnosed in 13 of 15 subjects (86%) if red blood cell (RBC) indices alone had been used for screening. Abnormal RBC indices with low transferrin saturation were 100% sensitive for ID/ IDA screening.
Prevalence of ID/IDA in children with DS was comparable with that in the general pediatric population. Macrocytosis had implications for screening of ID/IDA with only RBC indices. We suggest ID/IDA screening in DS children be done with a laboratory panel at least including complete blood count, reticulocyte count, transferrin saturation, and serum ferritin.
The Journal of pediatrics 12/2010; 157(6):967-971.e1. DOI:10.1016/j.jpeds.2010.06.011 · 3.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hydroxyurea improves laboratory parameters and prevents acute clinical complications of sickle cell anemia (SCA) in children and adults, but its effects on organ function remain incompletely defined.
To assess the safety and efficacy of hydroxyurea in young children with SCA and to prospectively assess kidney and brain function, 14 young children (mean age 35 months) received hydroxyurea at a mean maximum tolerated dose (MTD) of 28 mg/kg/day.
After a mean of 25 months, expected laboratory effects included significant increases in hemoglobin, MCV and %HbF along with significant decreases in reticulocytes, absolute neutrophil count, and bilirubin. There was no significant increase in glomerular filtration rate by DTPA clearance or Schwartz estimate. Mean transcranial Doppler (TCD) velocity changes were -25.6 cm/sec (P < 0.01) and -26.8 cm/sec (P < 0.05) in the right and left MCA vessels, respectively. At study exit, no child had conditional or abnormal TCD values, and none developed brain ischemic lesions or vasculopathy progression by MRI/MRA. Growth and neurocognitive scores were preserved and Impact-on-Family scores improved.
These pilot data indicate hydroxyurea at MTD is well-tolerated by both children and families, and may prevent chronic organ damage in young children with SCA.
[Show abstract][Hide abstract] ABSTRACT: Partial splenectomy is an alternative to total splenectomy for the treatment of congenital hemolytic anemias (CHAs) in children, although the feasibility of this technique in the setting of massive splenomegaly is unknown. This study was designed to evaluate the safety and efficacy of partial splenectomy in children with CHAs and massive splenomegaly. This retrospective study examined 29 children with CHAs who underwent partial splenectomy. Children were divided into 2 groups based on splenic size: 8 children had splenic volumes greater than 500 mL, whereas 21 children had splenic volumes less than 500 mL. Outcome variables included perioperative complications, transfusion requirements, hematocrits, reticulocyte counts, bilirubin levels, splenic sequestration, and splenic regrowth. All 29 children underwent successful partial splenectomy with 0.02 to 10 years of follow-up. After partial splenectomy, children overall had decreased transfusion requirements, increased hematocrits, decreased bilirubin levels, decreased reticulocyte counts, and elimination of splenic sequestration. Children with massive splenomegaly had similar outcomes compared with children without massive splenomegaly. Long-term complications included 3 mild infections, 4 cases of gallstones requiring cholecystectomy, and 1 child who required completion splenectomy. Partial splenectomy is a safe, effective, and technically feasible option for children with various CHAs, even in the setting of massive splenomegaly.
Journal of Pediatric Surgery 04/2008; 43(3):466-72. DOI:10.1016/j.jpedsurg.2007.10.025 · 1.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hydroxyurea has hematologic and clinical efficacy in sickle cell anemia (SCA), but its effects on transcranial Doppler (TCD) flow velocities remain undefined. Fifty-nine children initiating hydroxyurea therapy for clinical severity had pretreatment baseline TCD measurements; 37 with increased flow velocities (> or = 140 cm/s) were then enrolled in an institutional review board (IRB)-approved prospective phase 2 trial with TCD velocities measured at maximum tolerated dose (MTD) and one year later. At hydroxyurea MTD (mean +/- 1 SD = 27.9 +/- 2.7 mg/kg per day), significant decreases were observed in the right middle cerebral artery (MCA) (166 +/- 27 cm/s to 135 +/- 27 cm/s, P < .001) and left (MCA) (168 +/- 26 cm/s to 142 +/- 27 cm/s, P < .001) velocities. The magnitude of TCD velocity decline was significantly correlated with the maximal baseline TCD value. At hydroxyurea MTD, 14 of 15 children with conditional baseline TCD values improved, while 5 of 6 with abnormal TCD velocities whose families refused transfusions became less than 200 cm/s. TCD changes were sustained at follow-up. These prospective data indicate that hydroxyurea can significantly decrease elevated TCD flow velocities, often into the normal range. A multicenter trial is warranted to determine the efficacy of hydroxyurea for the management of increased TCD values, and ultimately for primary stroke prevention in children with SCA.
[Show abstract][Hide abstract] ABSTRACT: We present a case of intracranial haemorrhage detected by ultrasound at 36 weeks gestation in a foetus who was ultimately diagnosed with severe factor V deficiency. An abnormality of the foetal heart rate, auscultated at a routine antenatal visit, prompted an investigation that led to an ultrasound examination and detection of an intracranial haemorrhage and low amniotic fluid volume. An intrauterine foetal demise was averted. The clinical scenario in this case raises the issue of how often a stillbirth with intracranial haemorrhage may result from unrecognized factor deficiency.
[Show abstract][Hide abstract] ABSTRACT: Secondary erythrocytosis in cyanotic congenital heart disease (CCHD) causes substantial morbidity because of complications of hyperviscosity, including stroke and chronic end organ damage. Phlebotomy provides temporary improvement but leads to iron deficiency and can actually increase blood viscosity. We describe the successful use of hydroxyurea (hydroxycarbamide) in four patients with uncorrected CCHD and symptomatic secondary erythrocytosis. In all patients, hydroxyurea improved symptoms of hyperviscosity. Substantial decreases in the red blood cell (RBC) count were observed, along with increases in the mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH), leading to only modest declines in the circulating hemoglobin concentration. Two patients experienced transient mild myelosuppression, which promptly resolved with dose reduction of hydroxyurea. Hydroyxurea provides a novel and useful therapeutic approach to reduce hyperviscosity from secondary erythrocytosis in patients with CCHD, while preserving oxygen carrying capacity and avoiding iron depletion by phlebotomy.
American Journal of Hematology 08/2007; 82(8):740-3. DOI:10.1002/ajh.20925 · 3.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Venous thromboembolism (VTE) is a common disorder associated with significant morbidity and mortality. Despite important advances in understanding the etiology of VTE, delivery of care to patients with thrombosis and thrombophilia is frequently incomplete and highly variable. A comprehensive model of health care has been used successfully to treat and prevent complications for people with hemophilia and other chronic disorders. The effectiveness of an integrated healthcare model for patients with all coagulation disorders has yet to be evaluated. The Division of Hereditary Blood Disorders of the Centers for Disease Control and Prevention (CDC) is collaborating with eight Thrombosis and Hemostasis Centers (pilot sites) to provide health-related services and conduct research directed toward the reduction or prevention of complications of thrombosis and thrombophilia. The initial objectives of the collaboration are to (1) determine the efficacy of integrated multidisciplinary care and prevention services for people with hemostatic disorders, (2) assess unmet needs for service delivery and identify outreach strategies to improve access to care, (3) develop effective messages aimed at disease management and prevention, and (4) foster the development of training programs to enhance provider skills for the delivery of patient care. To address these objectives, the investigators and CDC have developed and implemented a web-based patient registry to follow prospectively service allocation and patient outcomes. Funding for the program began in October 2001. All eight funded centers are affiliated with U.S. medical schools. Principal investigators at the centers are hematologists (five adult, two pediatric) or cardiologists. Faculty in obstetrics-gynecology, surgery, and multiple other specialties are integral to the model of care at the centers. Other critical components at the centers are clinical laboratory services, training programs, research networks, and education and outreach programs. From August 2003 to March 2006, over 2,600 patients were enrolled in the registry, accounting for a total of more than 5,000 visits to the centers. Immediate goals of the data collection at the centers are to characterize patients receiving care at centers and document the state of health services provided. Long-term goals are to evaluate prospectively clinical outcomes for patients receiving multidisciplinary care and prevention services at centers. The network of data collection across centers will facilitate future collaborative clinical and epidemiologic investigations and enhance collective expertise in hemostasis and coagulation disorders.
Journal of Thrombosis and Thrombolysis 03/2007; 23(1):1-7. DOI:10.1007/s11239-006-9002-y · 2.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although functional asplenia in sickle cell disease (SCD) begins early in life and has important clinical consequences, quantitative measurement of splenic function is not readily available. A novel high-throughput flow cytometric method for quantitating Howell-Jolly bodies (HJB) has been developed which isolates HJB-containing CD71(+) and CD71(-) erythrocytes. Analysis of these cell populations allows quantitative measurement of splenic filtrative function and possible chromosomal damage.
Blood specimens from 147 children with SCD were analyzed using a high-throughput flow cytometric method. Enumeration of the following populations was accomplished: 1) CD71(+) reticulocytes among total erythrocytes, identifying the youngest erythroid cell population; 2) HJB-containing CD71(+) reticulocytes, which isolate young erythrocytes containing micronuclei as an index of cytogenetic damage; and 3) HJB-containing CD71(-) erythrocytes, identifying older erythrocytes containing micronuclei, indirectly measuring splenic function.
Children with HbSC (n = 24) had slightly elevated HJB frequencies, while children with HbSS (n = 125) had highly elevated frequencies within CD71(+) cells (0.44% +/- 0.40%, normal 0.12% +/- 0.06%, p < 0.001) and CD71(-) cells (2493 +/- 2303 per million RBC, normal 20 +/- 11, p < 0.001). Using a multiple regression model, the frequency of HbSS CD71(+) reticulocytes containing HJB was significantly influenced by hydroxyurea use (p < 0.0001), age (p = 0.0288), and splenectomy (p = 0.0498). Similarly, mature CD71(-) erythrocytes containing HJB were positively correlated with hydroxyurea (p = 0.0001), age (p < 0.0001), and splenectomy (p = 0.0104).
HJB quantitation by flow cytometry is a novel assay for measuring splenic function and may be valuable for investigating the efficacy and safety of therapeutic options for children with SCD.
[Show abstract][Hide abstract] ABSTRACT: Hematologic abnormalities are common in individuals with Down syndrome (DS). Increased erythrocyte mean corpuscular volume (MCV) is frequently found among DS infants and remains elevated throughout life in two-thirds of patients, making interpretation of red cell indices for diagnosis of nutritional anemias or bone marrow failure disorders more challenging. Transient myeloproliferative disorder (TMD) associated with pancytopenia, hepatosplenomegaly, and circulating immature WBCs, is found almost exclusively in DS infants with an incidence of approximately 10%. In most cases, TMD regresses spontaneously within the first 3 months of life, but in some children, it can be life threatening or even fatal. Despite the high rate of spontaneous regression, TMD can be a preleukemic disorder in 20-30% of children with DS. The types of malignancy, response to therapy, and clinical outcome in children with DS are also unique. There is an increased risk of leukemia with an equal incidence of lymphoid and myeloid leukemia. Acute megakaryocytic leukemia (AMKL) subtype is the most common form of acute myeloid leukemia (AML) in this setting, and is uncommon in children without DS. Somatic mutations of the gene encoding the hematopoetic growth factor GATA1 have been shown to be specific for TMD and AMKL in children with DS. Myelodysplastic syndrome can precede AML. Children with DS and leukemia are more sensitive to some chemotherapeutic agents such as methotrexate than other children which requires careful monitoring for toxicity. Although the risk for leukemia is higher in individuals with DS, these patients have a lower risk of developing solid tumors, with the exception of germ cell tumors, and perhaps retinoblastoma and lymphoma.
American Journal of Medical Genetics Part C Seminars in Medical Genetics 08/2006; 142C(3):149-57. DOI:10.1002/ajmg.c.30096 · 3.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Congenital Pelger-Huët anomaly (PHA) is an autosomal dominant disorder characterized by hypolobulated neutrophils with coarse clumping of the nuclear chromatin. PHA has been recently linked to the gene encoding the lamin B receptor, located at chromosome 1q41-43. The authors report a case of PHA in a child with interstitial deletion of the 1q subtelomeric region (1q42.3-44), providing supportive evidence to this linkage. All neutrophils in the peripheral blood smear had the characteristic unsegmented or bilobed appearance. Additional features in this child included failure to thrive, developmental delay, cleft palate, seizure disorder, and dysmorphic facial features.
[Show abstract][Hide abstract] ABSTRACT: Transfusions prevent secondary stroke in children with sickle cell anemia (SCA) but also cause iron overload. Alternatives for stroke prophylaxis with effective therapy to reduce iron burden are needed.
For 35 children with SCA and stroke, transfusions were prospectively discontinued. Hydroxyurea was prescribed for stroke prophylaxis, and phlebotomy removed excess iron. Initial patients discontinued transfusions before hydroxyurea therapy, but later patients overlapped transfusions with hydroxyurea until tolerating full-dose therapy.
Children received hydroxyurea for 42 +/- 30 months (range, 3-104 months). Hydroxyurea (26.7 +/- 4.8 mg/kg per day) led to mild neutropenia (3.9 +/- 2.3 x 10(9)/L) with significant increases in hemoglobin concentration, mean corpuscular volume, and fetal hemoglobin. Stroke recurrence rate was 5.7 events per 100 patient-years, but children receiving overlapping hydroxyurea therapy had only 3.6 events per 100 patient-years. For 26 children with >6 months of phlebotomy, 14,311 +/- 12,459 mL blood (315 +/- 214 mL/kg) was removed, with serum ferritin decreasing from a median of 2722 to 298 ng/mL. Among patients completing phlebotomy, liver biopsy documented normal histology and no excess iron deposition.
For children with SCA and stroke, hydroxyurea effectively prevents secondary stroke and serial phlebotomy leads to complete resolution of transfusional iron overload.
Journal of Pediatrics 10/2004; 145(3):346-52. DOI:10.1016/j.jpeds.2004.04.058 · 3.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hydroxyurea improves hematologic parameters for children with sickle cell disease (SCD), but its long-term efficacy at maximum tolerated dose (MTD) has not been determined. Between 1995 and 2002, hydroxyurea therapy was initiated for 122 pediatric patients with SCD including 106 with homozygous sickle cell anemia (HbSS), 7 with sickle hemoglobin C (HbSC), 7 with sickle/beta-thalassemia (HbS/ beta-thalassemia [6 HbS/beta0, 1 HbS/beta+]), and 2 with sickle hemoglobin OArab (HbS/OArab). Median age at initiation of therapy was 11.1 years. Hydroxyurea was escalated to MTD, with an average dose of 25.4 +/- 5.4 mg/kg per day; the average duration of hydroxyurea therapy has been 45 +/- 24 months (range, 6-101 months). Hydroxyurea was discontinued for 15 (12%) children with poor compliance. Mild transient neutropenia occurred, but no hepatic or renal toxicity was noted. Hydroxyurea therapy led to significant increases in hemoglobin level, mean corpuscular volume, and fetal hemoglobin (HbF) level, whereas significant decreases occurred in reticulocyte, white blood cell, and platelet counts and serum bilirubin levels. Children with variant SCD genotypes also had hematologic responses to hydroxyurea. HbF induction has been sustained for up to 8 years without adverse effects on growth or increased numbers of acquired DNA mutations. Long-term hydroxyurea therapy at MTD is well tolerated by pediatric patients with SCD and has sustained hematologic efficacy with apparent long-term safety.
[Show abstract][Hide abstract] ABSTRACT: Infection with human parvovirus B19 is known to cause transient erythroid aplasia in children with hemolytic anemia but has also been associated with bone marrow necrosis and morphologic changes suggesting myelodysplasia. The authors describe a previously healthy child who presented with severe hypoplastic anemia. Initial bone marrow aspiration revealed erythroid hyperplasia, dyserythropoiesis, and multinucleated erythroid cells with nuclear budding and bridging, consistent with the diagnosis of congenital dyserythropoietic anemia. Serologic testing documented acute parvovirus infection, and on recovery the correct diagnosis of unsuspected congenital spherocytosis was established. This case expands the spectrum of hematologic disease associated with acute parvovirus infection.
[Show abstract][Hide abstract] ABSTRACT: Immune thrombocytopenic purpura and autoimmune hemolytic anemia are typically idiopathic processes without underlying systemic illness. Four children with autoimmune cytopenia had low immunoglobulin levels that led to the diagnosis of common variable immunodeficiency. Routine screening of immunoglobulins is suggested for children with chronic or recurrent immune thrombocytopenic purpura and autoimmune hemolytic anemia.
Journal of Pediatrics 12/2003; 143(5):662-5. DOI:10.1067/S0022-3476(03)00445-1 · 3.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the prevalence and clinical consequences of previous parvovirus B19 exposure in a large cohort of pediatric patients with sickle cell anemia (SCA).
Prospective serologic testing for previous parvovirus B19 exposure was performed in steady-state pediatric patients with SCA, either prior to starting hydroxyurea therapy or in preparation for transition to the adult service. A retrospective chart review was performed to ascertain whether patients had a documented history of a transient aplastic crisis.
The prevalence of serologic evidence of previous parvovirus infection increased with age. The overall prevalence in 102 children with SCA was 53%, ranging from 44% between 5 and 9 years of age to 71% between 17 and 21 years of age. Only 27% of patients had a previous clinically recognized transient aplastic crisis.
By the teenage years, most pediatric patients with SCA have serologic evidence of previous parvovirus B19 exposure. However, subclinical parvovirus infection appears to be common in children with SCA, since most patients have no documented previous transient aplastic crisis.
[Show abstract][Hide abstract] ABSTRACT: Hydroxyurea therapy reduces hemolysis and decreases serum bilirubin levels in children and adults with sickle cell anemia (SCA) and may therefore help prevent the development of cholelithiasis in this patient population. We recently reported that a promoter polymorphism in the uridine diphosphoglucuronate glucuronosyltransferase 1A (UGT1A) gene affects steady-state bilirubin levels and the incidence of gallstones in children with SCA. We have now analyzed the influence of the UGT1A genotype on the therapeutic response to hydroxyurea. A large cohort of children with SCA taking hydroxyurea therapy at the maximum tolerated dose demonstrated significant reductions in hemolysis independent of UGT1A promoter polymorphism genotype, but the hydroxyurea-related decreases in serum bilirubin levels were significantly different. Children with the wild-type 6/6 UGT1A genotype demonstrated normalized bilirubin levels with hydroxyurea therapy, but children with the heterozygous 6/7 or abnormal 7/7 genotypes did not. Children with the abnormal 7/7 genotype, which confers the phenotype of Gilbert syndrome, had bilirubin levels greater than 3 mg/dL despite full-dose hydroxyurea therapy. These data indicate the UGT1A promoter polymorphism is a powerful nonglobin genetic modifier in SCA that influences serum bilirubin both at baseline and on hydroxyurea therapy. UGT1A promoter polymorphisms may therefore influence the ability of hydroxyurea to prevent gallstone formation in patients with SCA.
Journal of Laboratory and Clinical Medicine 05/2003; 141(4):279-82. DOI:10.1067/mlc.2003.28 · 2.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Genetic mutations in the uridine diphosphate (UDP)-glucuronosyltransferase 1A (UGT1A) enzyme promoter have been associated with unconjugated hyperbilirubinemia and Gilbert syndrome. The effects of UGT1A promoter polymorphisms on serum bilirubin levels and symptomatic gallstone formation were studied in a cohort of children with sickle cell anemia (SCA).
The UGT1A promoter genotype was deterrmined for 115 consecutive children with SCA. Steady-state laboratory parameters and previous cholecystectomy for symptomatic gallstones were recorded retrospectively, then analyzed according to UGT1A genotype.
Children with SCA had a lower frequency of the normal (TA)6 UGT1A promoter allele (0.413) than the abnormal (TA)7 allele (0.461). A previously described shorter (TA)5 allele (frequency 0.074) and longer (TA)8 allele (frequency 0.052) were also observed. Children with the 7/7 UGT1A genotype had a significantly higher mean bilirubin level (5.8 +/- 3.1 mg/dL) than those with the 6/6 (2.4 +/- 0.8 mg/dL) or 6/7 genotype (3.0 +/- 1.1 mg/dL; P < 0.001 by analysis of variance). Patients with the 7/7 genotype were more likely to have previous cholecystectomy (87.5%) than those with the 6/6 (35.7%) or the 6/7 genotype (36.1%; P = 0.002 by chi2).
Genetic variation in the UGT1A promoter significantly influences serum bilirubin levels and the development of symptomatic cholelithiasis in children with SCA. The UGT1A promoter polymorphisms represent an important nonglobin genetic modifier of clinical disease expression in SCA.
[Show abstract][Hide abstract] ABSTRACT: In the last half century the molecular biology, pathophysiology and natural history of sickle cell disease have been well defined. Sickle cell disease causes microvascular occlusion, which is manifested in most organ systems. The genitourinary tract is most commonly affected by hematuria, urinary tract infection and priapism but other more serious sequelae have been identified.
We performed a computerized MEDLINE search from 1965 to the present and a bibliographic review of cross references. These references were analyzed for meaningful findings and case reports.
The diagnosis and management of sickle cell disease have advanced rapidly with a significant increase in the life expectancy of affected patients and recognition of a greater number of genitourinary complications. Renal function may be mildly altered or lost completely. Patients with sickle cell disease are at increased risk for urinary tract infection. Priapism is a painful complication of sickle cell disease that is poorly understood and challenging to treat and prevent. Testicular infarction has also been noted. Furthermore, renal medullary carcinoma, a highly lethal tumor, develops almost exclusively in young patients with sickle cell trait.
Heightened awareness of the genitourinary complications of sickle cell disease may prevent end stage disease, including renal failure and impotence. New forms of therapy for sickle cell disease, such as hydroxyurea, may prevent these complications in the future.
The Journal of Urology 10/2001; 166(3):803-11. DOI:10.1097/00005392-200109000-00003 · 4.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hydroxyurea (HU) has laboratory and clinical efficacy in hemoglobin SS (HbSS) disease, but its benefits in hemoglobin SC (HbSC) disease are unknown. A recent adult HbSC disease pilot trial with HU therapy documented a modest laboratory benefit. Our goal was to evaluate the laboratory and clinical responses of selected pediatric patients with severe HbSC disease to HU therapy.
As part of a retrospective case series, patients were selected from the Duke Pediatric Sickle Cell Program based on the frequency and severity of their vasoocclusive events or an episode of acute chest syndrome. Oral HU therapy was started as a single daily dose and increased to the maximally tolerated dose based on myelosuppression. Laboratory evaluation was performed at baseline and monthly thereafter. Once the maximum tolerated dose was reached, laboratory data were monitored bimonthly.
We treated six severely affected pediatric HbSC patients with HU for a median of 27 months. Mean corpuscular volume increased significantly (+26 fL) without change in hemoglobin concentration (-0.1 g/dL); neutrophils decreased significantly. Percentage of fetal hemoglobin (+8.5%) and percentage of F cells (+35.7%) increased significantly. Two experienced only mild and reversible toxicity.
The laboratory responses in our pediatric patients with HbSC disease were striking, with increases in percentage of fetal hemoglobin and percentage of F-cells approaching responses observed in adult and pediatric patients with HbSS disease. All patients improved clinically. Our findings demonstrate that HU therapy benefits pediatric patients with severe HbSC disease, although larger clinical trials of HU therapy in HbSC disease are warranted.
[Show abstract][Hide abstract] ABSTRACT: Thrombophilia can result from either inherited or acquired conditions. We describe a teenager who developed extensive thrombosis requiring aggressive and prolonged anticoagulation. Laboratory evaluation revealed an acquired lupus anticoagulant, consistent with the antiphospholipid antibody syndrome (APS). DNA analysis revealed inherited thrombophilic mutations in the factor V and methylene tetrahydrofolate reductase genes. We believe that the combination of inherited and acquired hypercoagulable conditions affected her therapeutic response to anticoagulant therapy. Inherited thrombophilic DNA mutations may contribute to the hypercoagulability observed in patients with acquired thrombophilic conditions such as APS and systemic lupus erythematosus.
The Journal of Rheumatology 03/2001; 28(2):370-2. · 3.19 Impact Factor