PubMed Health⌕ Search

Biomedical subjects

W E Hathaway

Publications and source records attributed to W E Hathaway.

At least 19 recordsLinked to original sources
PubMed1990

The coagulopathy of childhood leukemia. Thrombin activation or primary fibrinolysis?

Little information is available on the prevalence and etiology of the coagulopathy present in some children with acute leukemia at disease presentation. We studied 102 children with newly diagnosed acute leukemia (50 retrospective: Group A; and 52 prospective: Group B) with prothrombin time (PT), partial thromboplastin time (PTT), thrombin time (TT), fibrinogen (FIB), and fibrin degradation products (FDP). All patients in Group B also had assessment of thrombin activation by measurement of the crosslinked fibrin fragment, D-dimer, and of primary fibrinolysis with the B beta 1-42 peptide. Additionally, ten patients from Group B had Factors II, V, VII, and X measured, and eight of these patients had measurement of tissue factor from sonicated bone marrow cells. Thirty-two percent of Group A and 40% of Group B had totally normal coagulation studies, whereas 20% of Group A and 10% of Group B had a severe coagulopathy on disease presentation. A high percentage of both groups had elevated PT (Group A, 52%; Group B, 27%) and increased FDP (Group A, 39%; Group B, 25%). In Group B, 38% of the patients had a positive D-dimer, whereas only 4% of this prospective group had an elevated B beta 1-42 peptide (P less than 0.00001). Nine of ten patients with a positive D-dimer had low levels of one or more of the extrinsic pathway factors. Three of four patients with the highest tissue factor levels were of monocytoid leukemia cell type. These data indicate that the coagulopathy associated with acute leukemia of childhood is usually mediated by thrombin activation.

Adolescent↗
PubMed1990

Evaluation of the safety, recovery, half-life, and clinical efficacy of antithrombin III (human) in patients with hereditary antithrombin III deficiency. Cooperative Study Group.

Antithrombin III (Human) (AT III) was administered to 18 patients with documented hereditary AT III deficiency. In eight patients with no ongoing clinical symptoms of thrombosis, the percent increase per unit AT III infused per kilogram of body weight ranged from 1.56% to 2.74%, and the half-life from 43.3 to 77.0 hours. No significant difference was noted between patients receiving and those not receiving coumarin therapy. In clinically ill patients, the in vivo recovery was significantly lower and ranged from 0.64% to 1.90% increase per unit AT III infused/kg. Efficacy of AT III was evaluated in 13 patients for the prevention or treatment of thrombosis. AT III was efficacious as assessed by the absence of thrombotic complications after surgery and/or parturition, and the nonextension and nonrecurrence of thrombosis in patients exhibiting an acute thrombotic episode. No side effects were noted. Follow-up studies indicated no hepatitis B seroconversion and no alanine aminotransferase elevations in patients who were not transfused with other blood products.

Adult↗
PubMed1990

Use of DDAVP in inherited and acquired platelet dysfunction.

Twenty-one patients with prolonged bleeding times secondary to inherited disorders of platelet function and eight patients with prolonged bleeding times secondary to acquired platelet dysfunction were given 0.3 micrograms per kilogram of DDAVP, 1-deamino-8-D-arginine vasopressin, intravenously. Sixteen of twenty-two DDAVP trials in patients with inherited platelet dysfunction (73%) and seven of the nine DDAVP trials in patients with acquired platelet dysfunction (78%) resulted in normalization or shortening of the prolonged bleeding times by at least 4 min. The bleeding time response did not correlate with changes in the levels of von Willebrand factor (vWf) antigen or ristocetin cofactor activity, nor was it associated with changes in vWf multimeric analysis or in vitro platelet aggregations following the administration of DDAVP. Shortening of the bleeding time with DDAVP was seen in patients with a failure to release/storage pool type defect, thromboxane synthesis type defect, Bernard-Soulier syndrome, Glanzmann's thrombasthenia, the May-Hegglin anomaly, liver disease, nonuremic renal disease, myelofibrosis, and Tangier's disease.

Adolescent↗
PubMed1989

Heparin cofactor II in adults and infants with thrombosis and DIC.

Heparin cofactor II (HC II) was measured by a chromogenic activity assay in normal preterm infants (gestational age, 28-36 weeks; n = 17; 29% +/- 11.5 [mean +/- 1 SD], range 11-51), normal full-term infants (n = 18; 49% +/- 6.6 [mean +/- 1 SD], range 36-58), and normal adults (n = 38; 101% +/- 14 [mean +/- 1 SD], range 73-130). Normal children attained adult levels at approximately 5 to 7 months of age. The lower values in preterm and term infants most likely reflect immature liver function. Neither adults and children with a history of thrombosis with prior negative evaluation (n = 74), patients with documented protein C and protein S deficiency (n = 4), nor sick infants without evidence of consumptive coagulopathy (n = 15) had significantly lower levels of HC II activity. Infants with disseminated intravascular coagulation (n = 2) had strikingly lower levels of HC II activity.

Disseminated Intravascular Coagulation↗
PubMed1989

Hyponatremia and seizures in young children given DDAVP.

Desmopressin (DDAVP), a synthetic vasopressin, temporarily corrects bleeding abnormalities associated with mild hemophilia A, von Willebrand disease, and disorders of platelet function. The side effects of DDAVP are considered benign although most of its use has been in adults and older children. We report four children under the age of 2 years who became hyponatremic after intravenous DDAVP administration (0.3 microgram/kg). Three of them developed grand mal seizures. A review of the literature and these cases indicate that associated risk factors for hyponatremia after DDAVP administration include stress, surgery, anesthesia and narcotics (endogenous release of antidiuretic hormone), vomiting (loss of Na+), liver disease (hindered metabolism of DDAVP), renal tubular acidosis (chronically low serum Na+), multiple doses of DDAVP, and overhydration with hyponatremic fluids. DDAVP is not a benign drug in this age group and shows a serious potential for hyponatremia and seizures. Fluid restriction, avoidance of hyponatremic solutions, and close monitoring of serum electrolytes and urine output for at least 15-20 hr after the administration of DDAVP, when used in children under the age of 2 years, is warranted.

Deamino Arginine Vasopressin↗
PubMed1989

Effect of intravenous immune globulin on the coagulopathy of Kawasaki syndrome.

We studied the effects of immune globulin and aspirin versus aspirin alone on platelet count, platelet activation, and factor-mediated coagulation in patients with Kawasaki syndrome. Coagulation tests were performed on the day of admission to the study and 4 to 6 days later. Twenty-three patients were enrolled; 12 received immune globulin intravenously plus aspirin, and 11 received aspirin alone. At initiation of the study the groups were comparable with regard to age, sex, race, and time from onset of illness to study entry. Coagulation values were similar at entry with the exception that the aspirin group had a geometric mean platelet count that was higher than the platelet count in the aspirin-immune globulin group (p = 0.02). Four days after entry there were no significant differences between the two groups in any coagulation studies. Although the immune globulin preparation used has been effective in reducing the prevalence of coronary artery aneurysms, it appears to have no early effect on reduction of platelet activation or other measures of coagulopathy. The mechanism of action of immune globulin in patients with Kawasaki syndrome remains to be elucidated.

Adolescent↗
PubMed1988

Bleeding diathesis in Noonan syndrome: a common association.

The Noonan syndrome (NS) is a multiple congenital anomalies (MCA) syndrome with well-known manifestations. Excessive bleeding has been described occasionally. We report on 19 patients with NS and a bleeding diathesis. Several different defects are identified in the coagulation and platelet systems occurring singly or in combination. Clinical expression is variable. It is concluded that bleeding diatheses occur in NS at a much higher frequency than previously suspected. Consideration is given to possible relationship to underlying metabolic defects which could explain the diverse nature of the bleeding diatheses and also play a role in the pathogenesis of NS. The variety of bleeding diatheses may also reflect heterogeneity within NS. NS patients frequently undergo surgery with increased risk of bleeding. Appropriate evaluation and management is discussed. Evaluation of all NS patients and their families for bleeding disorders should provide important information about the frequency and type of bleeding diatheses which occur and perhaps help to clarify the etiology and pathogenesis of NS.

Adolescent↗
PubMed1987

Collagen-binding of von Willebrand's factor antigen in the classification of von Willebrand's disease.

Analysis of the multimeric structure of von Willebrand's factor (vWf) was compared with vWf-binding to collagen in subjects' plasma. The percentage binding of vWf to collagen was determined by both an enzyme-linked immunosorbent assay (ELISA) method and quantitative immunoelectrophoresis. Normal subjects, type I von Willebrand's disease (vWd), and type II vWd were studied. The authors have found by correlating collagen-binding results with multimeric analysis that normal controls exhibit 85.4 +/- 5.1% collagen absorption of their vWf, patients with type I vWd 80.8 +/- 5.3%, whereas patients exhibiting a deficiency of high molecular weight vWf have 32.3 +/- 16.6% collagen absorption of vWf. The results suggest that this functional assay of vWf can be used in the classification of vWd and in the detection of new dysfunctional forms of vWf.

Antigens↗
PubMed1987

New insights on vitamin K.

Vitamin K catalyzes the post-translational carboxylation of coagulation proteins C, S, and factors II, VII, XI, and X. Detection of the noncarboxylated forms allows an indirect and specific measure of the vitamin K deficiency found in early, classic, and late hemorrhagic disease of the newborn (HDN), malabsorption syndromes, and drug related (warfarin, anticonvulsants, and antibiotics) states. Idiopathic late HDN (CNS bleeding) occurs in exclusively breast-fed infants and is prevented by appropriate parenteral and oral vitamin K prophylaxis given at birth. All newborn infants and older infants with malabsorption syndromes should receive prophylactic vitamin K.

Child↗
PubMed1986

Vitamin K deficiency in the newborn infant: prevalence and 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.

Biomarkers↗
PubMed1986

Abnormal antithrombin III with defective serine protease binding (antithrombin III "Denver").

A hereditary (three family members) deficiency of antithrombin III (AT-III) in which AT-III antigen (AT-III ag) is normal in spite of low heparin cofactor and antithrombin activity is described. Plasma levels were: AT-III ag, 0.92-0.96 U/ml; AT-III heparin cofactor activity, 0.54-0.62 U/ml; progressive antithrombin activity index, 0.13-0.18; anti-Xa activity, 0.50-0.56 U/ml. Plasma crossed immunoelectrophoresis (CIE) patterns performed with and without added heparin were normal, but serum CIE revealed a decreased complex peak. Purification of the patient's plasma AT-III by heparin-sepharose affinity chromatography showed a normal protein recovery and elution profile, but the purified AT-III fraction showed only 50% of the normal progressive thrombin neutralization and anti-Xa activity. When thrombin-antithrombin (TAT) complexes were formed by incubating with excess thrombin, SDS-polyacrylamide gel electrophoresis (PAGE) analysis revealed that half the patient AT-III formed TAT complexes while the remainder migrated as free AT-III. All the control AT-III formed TAT complexes. The patient's nonreacting AT-III (AT-III "Denver"), isolated by affinity chromatography, showed CIE and SDS-PAGE migration patterns characteristic of normal AT-III but failed to bind thrombin or Xa. Calculations from turnover studies in one patient and normal subjects with autologous 131I-AT-III suggested that AT-III "Denver" is removed from the plasma slightly more rapidly than normal. These studies indicate that the patients' variant AT-III molecule was characterized by normal heparin interaction but defective binding and inhibition of thrombin and Xa. These characteristics allow isolation of the nonreactive variant molecule by heparin-sepharose affinity chromatography.

Antithrombin III↗