PubMed Health⌕ Search

Biomedical subjects

C A Holtkamp

Publications and source records attributed to C A Holtkamp.

At least 19 recordsLinked to original sources
PubMed1990

Reduced serum haptoglobin values in hemophiliacs receiving monoclonally purified factor VIII concentrates.

Hemophiliacs often have mild anemia, and hemolysis has been suggested as the likely mechanism on the basis of the reduced serum haptoglobin values frequently observed in these patients. It has been suggested that hypohaptoglobinemia results from isohemagglutinins or other contaminating proteins in the infused factor concentrates. The advent and increased utilization of Factor VIII concentrates that are highly purified by use of monoclonal antibodies have provided the opportunity to study whether proteins other than Factor VIII contained in the concentrate induce hemolysis. Of 49 consecutively studied Factor VIII-deficient hemophiliacs, 19 (39%) had a reduced serum haptoglobin level (less than 27 mg/dl). In particular, 16 of 35 (46%) of patients receiving only monoclonally purified Factor VIII products (Monoclate or Hemofil-M) had a reduced serum haptoglobin value. Haptoglobin measurements were variable on repeat measurement in 8 patients. Haptoglobin levels did not correlate with type or severity of hemophilia, hemoglobin value, or alterations in liver function. Low serum haptoglobin values were also observed in children with leukemia, without apparent hemolysis, who had extensive cutaneous hemorrhage associated with thrombocytopenia. We propose that reduced serum haptoglobin values in hemophiliacs do not result from immune-mediated hemolysis due to contaminating proteins in the concentrate. Moreover, hypohaptoglobinemia may not be due to hemolysis at all but may instead result from dissolution of hematomas and other foci of internal hemorrhage.

Adolescent↗
PubMed1990

The bleeding time may be longer in children than in adults.

The bleeding time, the most frequently performed test reflecting in vivo platelet function, is the duration of blood flow from a standardized incision on the volar surface of the forearm. Normal values have been determined in adult subjects, but with the exception of neonates, data on the range of bleeding time values in pediatric patients are unavailable. Standard hematology textbooks imply that bleeding time values in children are similar to those of adults. We have reviewed our 9 years of experience with 137 children (mean age 6.5 years) who were referred for diagnostic evaluation of a bleeding disorder but whose history and physical examination were felt by us to be inconsistent with an abnormality of hemostasis. Bleeding time values in these individuals (mean 6.0 min, 95th percentile 9.0 min) were compared with those of 85 normal adult volunteers (mean 4.4 min, 95th percentile 6.5 min). The Simplate-I disposable device and vertical (perpendicular to elbow crease) incision direction were used in both groups. This difference between the pediatric and adult bleeding time values is statistically significant (p less than 0.0001). Neither age nor sex had a significant effect on the pediatric bleeding time measurements. We conclude that the bleeding time, when performed as described, is longer in children than in adults and that pediatric standards for bleeding time should be used in order to avoid a spurious diagnosis of a primary hemostatic disorder in some normal children.

Adolescent↗
PubMed1989

Splenic phagocytic function in children with sickle cell anemia receiving long-term hypertransfusion therapy.

To determine the effects of blood transfusions on splenic function in older patients with sickle cell anemia, we investigated splenic function in 12 patients who had had cerebrovascular accidents and who were being treated at two collaborating centers using different transfusion protocols. Splenic function was assessed by radionuclide scan and pocked erythrocyte count. Patients were 6 to 18 years of age and had been receiving transfusions for 7 months to 10 years (median 4.2 years). Of the 12 children, five had normal or increased splenic size and function (normal scan and normal or minimally elevated pocked erythrocyte count). All were receiving intensive transfusion therapy, with the aim of maintaining the hemoglobin S level at less than 20%. The other seven patients had abnormal splenic function (absent radionuclide uptake and elevated pocked erythrocyte count); each was receiving less intensive transfusion therapy, with the pretransfusion hemoglobin S level usually at 30% to 40%. No patient developed bacterial septicemia while receiving hypertransfusion therapy. We conclude that splenic function during a long-term transfusion program is variable, depending in part on the "intensity" of transfusion therapy. Apparent splenic involution and fibrosis may be a reversible event in some patients.

Adolescent↗
PubMed1989

A comparative study of variables affecting the bleeding time using two disposable devices.

A number of variables affect the result of the bleeding time, the most frequently used test assessing primary hemostasis. Although the test is now usually performed with one of several commercially available disposable devices, most previous studies of the bleeding time have evaluated only the original template device described nearly 20 years ago. Therefore, we compared two commonly used bleeding time devices (Surgicutt and Simplate) with regard to multiple variables affecting the test in 40 hematologically normal young adults. Bleeding time was performed by the modified Ivy method according to the manufacturers' instructions in both horizontal (transverse) and vertical directions, before and two hours after a test dose of 650 mg of aspirin was administered. With both horizontal and vertical incisions, Simplate bleeding time values were greater than with the Surgicutt device (P = 0.0025). Bleeding time in the horizontal direction was greater than vertical with both devices (P = 0.0001). Values in males and females were not significantly different. Aspirin sensitivity, the difference between preaspirin and postaspirin values, was greatest with the use of the Surgicutt device in the horizontal position (mean postaspirin value 8.0 minutes). Both devices produced a reproducible uniform incision, caused minimal discomfort, and resulted in little or no scarring. The authors conclude that the results with Surgicutt and Simplate devices were comparable in many respects but that a horizontal Surgicutt bleeding time might be most sensitive in detecting disorders of primary hemostasis. Comparative studies of different bleeding time devices in normal subjects are necessary in order to accurately assess their clinical utility.

Adult↗
PubMed1988

Reduced hemoglobin values in children and young adults with hemophilia.

Mild leukopenia and thrombocytopenia are common in multitransfused hemophiliacs. Because little attention has previously been directed to measurements of erythropoiesis in these patients, we prospectively examined hemoglobin concentration and RBC indices in 94 children and young adults with hemophilia during comprehensive clinic visits. Additional studies performed in many included serum transferrin saturation, ferritin, haptoglobin, and free erythrocyte protoporphyrin measurements. Hemoglobin concentrations were recorded as age-related percentile values. Hemophiliacs of all ages and degrees of severity often had lower than average values for hemoglobin; 31% had values less than the third percentile, 46% less than the tenth percentile, and 83% less than the mean value. Reduced hemoglobin percentile values were unrelated to age, severity of disease, or human immunodeficiency virus antibody status. Only five patients had an obvious cause for anemia. Serum ferritin, transferrin saturation, and erythrocyte protoporphyrin values were usually normal, indicating that iron deficiency and anemia of chronic disease were uncommon. Although serum haptoglobin was reduced in 44% of the patients, reticulocyte count was infrequently increased. We conclude that hemoglobin values are frequently less than the mean normal values for age in hemophiliacs. Although frank anemia is common, it is usually mild and without obvious cause. Hemophiliac individuals with slightly reduced hemoglobin values probably do not routinely require detailed investigation for occult blood loss, iron deficiency, or inflammation.

Adolescent↗
PubMed1987

Formation and disappearance of pocked erythrocytes: studies in human subjects and laboratory animals.

The pocked or "pitted" RBC count is being increasingly utilized as a test of splenic function. Since little is known about patterns of formation and removal of the characteristic organelles in the pocked RBC, we performed serial pocked RBC counts following splenectomy in six patients and in three animal species (dogs, rats, and rabbits). In the patients, pocked RBC counts began to rise within 1 week following splenectomy and reached a plateau (40-60%) by 60-100 days. Similar results were obtained following splenectomy of dogs, except that the plateau value was less. Pocked RBCs in splenectomized rats rose initially, but after the sixth week there was a progressive decline in their numbers; splenosis or accessory spleens were not visualized at autopsy. Rabbits had only a slight and inconsistent rise in pocked RBCs after splenectomy. When the rate of removal of pocked RBCs from the circulation was determined by transfusion of blood from splenectomized dogs in eusplenic animals, the pocked RBC count rapidly decreased within 3 to 6 hours. Pocked RBCs did not disappear when crosstransfused into a splenectomized recipient animal. Prior treatment of the recipient dog with either corticosteroids or vincristine did not affect the pattern of removal of pocked RBCs. We conclude that pocked RBCs rise slowly following splenectomy, disappear rapidly from the circulation in the presence of a normal spleen, and vary in pattern of rise and peak levels following splenectomy of different laboratory animals.

Animals↗
PubMed1987

Pocked erythrocyte counts in patients with hereditary spherocytosis before and after splenectomy.

The pocked (pitted or vacuolated) erythrocyte count has become increasingly utilized as a simple inexpensive test of splenic reticuloendothelial function. Values are less than 2.0% in normal subjects and 20 to 70% following splenectomy. Because scant and conflicting data are available about pocked erythrocyte measurements in hemolytic anemias other than the hemoglobinopathies, we performed pocked erythrocyte counts in 27 patients with hereditary spherocytosis. Prior to splenectomy patients often had elevated values (mean 4.9%). This unexpected observation suggests that hemolytic anemia may result in congestion of the red pulp and/or induced mild splenic reticuloendothelial blockade. As expected, but contrary to a previous report, pocked erythrocyte values following splenectomy were markedly increased (mean 54.9%).

Adolescent↗
PubMed1985

Plasma levels of platelet and vascular prostaglandin derivatives in children with sickle cell anaemia.

Platelet and vascular endothelial prostaglandin derivatives were measured by radioimmunoassay in the plasma of 39 children with homozygous sickle cell anaemia and 27 control subjects. The levels of both thromboxane B2 and 6-keto-PGF1alpha, the stable end-products of platelet and vascular prostaglandin metabolism, were significantly (p less than 0.001) greater in sickle cell anaemia plasma than in the plasma of the controls. There were no differences in levels of either 6-keto-PGF1alpha or thromboxane B2 between steady state and vaso-occlusive crisis in the sickle cell patients. Injury to the endothelial lining of blood vessels may occur in sickle cell anaemia as a consequence of contact with the abnormal erythrocytes.

Adolescent↗
PubMed1985

Splenic reticuloendothelial function in children with cancer.

We studied splenic function in children with cancer by quantitation of pitted, or pocked, erythrocytes (pocked RBC count), that is, the percentage of erythrocytes containing one or more membrane-bound vesicles, as determined by phase interference microscopy. The mean pocked RBC count in 93 normal children and adults was 0.49% (range 0% to 2.0%), with only 2.4% of normal subjects having values greater than 1.5%. Mean pocked RBC count in 28 children after splenectomy was 37% (range 3.2% to 81%). Among 181 children with cancer (525 specimens), the mean pocked RBC count was 1.06% (range 0% to 12.6%). Fifty-nine (32%) patients had one or more values greater than 1.5%, and 25 (13.8%) children had measurements greater than 3.0%, a level previously suggested to have clinical significance. Elevated pocked RBC counts (greater than 1.5%) occurred in more than one third of children with Wilms tumor and acute lymphoblastic leukemia, and in both patients with juvenile chronic myelogenous leukemia. Elevations in pocked RBC counts were not related to specific chemotherapy regimens or to disease activity. Mild splenic reticuloendothelial hypofunction occurs in many children with cancer and may contribute to the risk of infection in these patients.

Acute Disease↗
PubMed1984

Prednisone therapy for children with newly diagnosed idiopathic thrombocytopenic purpura. A randomized clinical trial.

The efficacy of corticosteroids in childhood acute idiopathic thrombocytopenic purpura (ITP) is controversial and has infrequently been evaluated in a controlled randomized fashion. We administered prednisone (2 mg/kg/day for 14 days with subsequent tapering and discontinuation by day 21) or placebo to 27 children, aged 10 years or less, with newly diagnosed ITP. Platelet count, bleeding time (a test of the integrity of the platelet-microvasculature interaction), and clinical bleeding score (based on a 0-4 scale) were determined before (day 0) and six times following initiation of drug therapy (days 1-2, 3-5, 7, 14, 21, and 28). There were no statistically significant (p less than 0.05) differences between the two treatment groups in any of the three study parameters except on day 7 of therapy when children receiving prednisone had higher platelet counts and lower bleeding scores and bleeding times than those taking placebo. Bleeding time correlated inversely with the platelet count in both treatment groups. Prednisone did not appear to influence bleeding time independent of its effect on platelet count. This treatment regimen of prednisone did not clearly improve hemostasis in childhood acute ITP except transiently at the end of 1 week of treatment.

Bleeding Time↗
PubMed1983

Evidence against enhanced platelet activity in sickle cell anaemia.

Although numerous studies have provided indirect evidence for enhanced platelet activity in sickle cell anaemia, little attention has been directed to examination of platelet alpha and dense granule release in the sickling disorders. We simultaneously measured by radioimmunoassay plasma levels of the alpha granule constituents beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) in 43 children with sickle cell anaemia in steady state and 24 patients during severe vaso-occlusive crisis. beta-TG levels during steady state (50 +/- 3.6 ng/ml, mean +/- SEM) were greater (P less than 0.001) than in normal controls (36 +/- 1.6), but there was no additional significant rise during crisis (55 +/- 5.9). PF4 levels were similar (P = 0.12) in both steady state (10 +/- 1.2 ng/ml) and crisis (9.3 +/- 2.3) to those of normal controls (6.0 +/- 0.8). The similarity of beta-TG/PF4 ratios in normal and sickle cell anaemia patients as well as the positive correlation (P less than 0.05) between platelet count and beta-TG and PF4 suggested that an artefactual in vitro platelet activation was responsible for some of the observed increased beta-TG and PF4 levels. Further evidence against enhanced platelet activity in these sickle cell patients included normal intraplatelet content of the dense granule constituent 5-HT and a normal ATP/ADP ratio. From this data we conclude that platelet activation in children with sickle cell anaemia appears minimal.

Adolescent↗
PubMed1983

Bacterial infection and splenic reticuloendothelial function in children with hemoglobin SC disease.

Although the epidemiology and pathophysiology of serious bacterial infection in homozygous sickle cell anemia (SS disease) have become increasingly well understood, information about infection risk and splenic reticuloendothelial function in hemoglobin SC disease is quite limited. Therefore, the type and frequency of invasive bacterial disease were examined in 51 children with SC disease followed for 370 person-years and splenic function was assessed in 31 patients by quantitation of pitted erythrocytes. Seven serious bacterial infections occurred in four of the patients, five due to Streptococcus pneumoniae and two to Haemophilus influenzae. A primary focus of infection was present in all episodes, none of which proved fatal. Although 30 episodes of pneumonia or chest syndrome occurred in 20 of the patients, a bacterial etiology was proven in only three instances. Splenic function was usually impaired, with a mean pit count of 7.1% +/- 8.2% (range 0% to 22.9%). This is significantly greater than normal, but less than pit counts in patients with SS disease or asplenic subjects. Children with SC disease may have a greater risk of bacterial infection than normal children, but their infection rate is not nearly as high as that in patients with SS disease.

Adolescent↗
PubMed1981

Platelet aggregation, malondialdehyde generation and production time in children with sickle cell anaemia.

In view of prior reports of platelet activation in the sickling disorders, platelet aggregation, malondialdehyde (MDA) production following stimulation with N-ethylmaleimide, and/or production time (survival) measurements were examined in 44 children with homozygous sickle cell disease. Aggregation in response to epinephrine, collagen, and adenosine diphosphate was similar to or only slightly less than in normal black controls, rendering highly unlikely the circulation of a sizable population of refractory or "exhausted" platelets. The platelets from the normal blacks aggregated less in response to epinephrine than those from white control subjects. MDA generation in sickle cell platelets was not increased, and platelet production time was not shortened in 6 patients studied during crisis. These observations do not support the occurrence of a marked degree of platelet activation and consumption in sickle cell anaemia.

Adenosine Diphosphate↗
PubMed1981

Racial differences in ristocetin-induced platelet aggregation.

Several investigators have reported defective ristocetin-induced platelet aggregation (RIPA) in individuals whose red blood cells contain sickle haemoglobin, but the race of control subjects in these studies was not stated. Therefore, maximal amplitude of RIPA was examined in 75 normal whites and blacks, of 16 of whom had sickle trait defined by haemoglobin electrophoresis and sickle prep. Final ristocetin concentrations in platelet rich plasma were 1.1, 1.2 and 1.5 mg/ml. Mean aggregation at 1.1 mg/ml was significantly less in blacks (mean 31%) than in whites (mean 72%) (P less than 0.001). 60% of blacks but only 11% of whites had less than 50% RIPA at 1.1 mg/ml. RIPA was entirely absent in 19% of blacks. Differences in RIPA between black and white subjects were also present at ristocetin concentrations of 1.2 and 1.5 mg/ml but were less striking. RIPA in 25 children with homozygous sickle cell anaemia was similar to that in the normal AA and AS blacks. Differences in RIPA could not be explained by age, sex, presence of sickle haemoglobin, or medications. Addition of normal plasma or platelets did not correct reduced RIPA in seven blacks, and their plasma inhibited normal RIPA responses. Reduced platelet aggregation to low concentrations of ristocetin is a normal finding in many blacks, is not related to the presence of sickle haemoglobin, and appears to be due to a plasma inhibitor against RIPA.

Adolescent↗
PubMed1981

Platelet number and function in Diamond-Blackfan anemia.

Congenital red cell aplasia (Diamond-Blackfan anemia) is occasionally associated with hematologic defects other than a deficiency of red blood cell progenitors, but such alterations have not been well studied. The frequency and magnitude of abnormalities in platelet count and platelet function were therefore examined in 38 patients. Thrombocytosis was seen in 21 patients, and 12 had mild thrombocytopenia on at least one occasion. Elevated platelet counts were demonstrated repeatedly in nine children. The three patients with the lowest platelet counts also had leukopenia. Platelet aggregation was normal in all 16 patients in whom it was studied, and bleeding times were within the normal range in 14 of them. Bleeding signs and symptoms were not observed. It is concluded that thrombocytosis or thrombocytopenia often occurs but that platelet function is normal in patients with Diamond-Blackfan anemia.

Adolescent↗
PubMed1980

Reduced antithrombin III levels during L-asparaginase therapy.

Antithrombin III levels were measured in serum before, during, and after therapy with three different dosage regimens of L-asparaginase in 11 children with acute lymphoblastic leukemia. Levels determined by both functional and immunologic methods were transiently reduced during alternate-day or daily L-asparaginase treatment but not affected when the drug was administered only every 10 days. The probable mechanism of this effect is impaired hepatic synthesis of antithrombin III, resembling the acute and transient deficiency of other asparagine-rich proteins during L-asparaginase administration.

Adolescent↗