More on: is laboratory monitoring of low-molecular-weight heparin necessary?
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Publications and source records attributed to A M Shojania.
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The sensitivity of the reagents for activated partial thromboplastin time (APTT) test varies greatly. Consequently the physicians who prescribe heparin based on certain APTT ratios may order different doses of heparin and produce different levels of anticoagulation in their patients, depending on the sensitivity of APTT reagent used by the laboratory. The authors have been recommending that physicians in their hospital use a therapeutic range for heparinization based on the sensitivity of the APTT reagent and keep the APTT of patients within the range of APTT of pooled normal plasma containing 0.2-0.4 units of heparin per milliliter. Because the patient's response to heparin in vivo may be different from that of pooled normal plasma, the authors planned to compare the effect of these two methods of heparin monitoring on heparin usage and complications of heparin therapy. In a retrospective study, the authors reviewed the hospital records of patients treated with continuous intravenous heparin for the management of thromboembolic disorders during two periods: one period in which the laboratory used an APTT reagent with low in vitro sensitivity to heparin (LSH) and another period in which the authors used an APTT reagent with high sensitivity to heparin (HSH). The authors found that there were no significant differences between the incidence of bleeding or thrombotic complication in the two periods. Furthermore, they found that in both periods, the patients had received similar total doses of heparin during the first 72 hours of therapy. However, as was expected from in vitro sensitivity, the APTT of patients during the LSH period was significantly lower than those during the HSH period. More heparin would have been used during the LSH period compared to the HSH period of physicians were to use the APTT ratio method for monitoring the therapy. The authors conclude that using the therapeutic range for monitoring heparin therapy based on the heparin response of pooled normal plasma will result in a more comparable level of heparinization from year to year and from center to center than by using the APTT ratio method.
Hereditary high phosphatidylcholine hemolytic anemia (HHPCHA) is a hematological disorder characterized by chronic hemolytic anemia with a dominant pattern of inheritance. The affected members show increased numbers of target cells and/or stomatocytes in peripheral blood smears, have reduced erythrocyte osmotic fragility, increased autohemolysis as well as markedly increased erythrocyte membrane Na+, K(+)-ATPase activity. Erythrocyte membrane phosphatidylcholine is increased but plasma levels of this phospholipid are normal. Only 10 families affected with this disorder have been described in the literature. We are reporting a new family with HHPCHA in which there are two affected and four presumed affected members. In addition to anomalies commonly reported in HHPCHA, we found alterations in erythrocyte membrane acetylcholinesterase kinetics (low Vmax), reduced erythrocyte superoxide dismutase activity and increased susceptibility of erythrocytes to glutathione depletion on in vitro exposure to hydrogen peroxide. The pathogenesis and clinical features of previously reported cases of HHPCHA are also discussed.
The variations between different lots of activated partial thromboplastin time (APTT) produced by three major North American suppliers were evaluated over the past eight years. The authors found significant variations between the heparin sensitivity of the APTT reagents produced under the same name by the same supplier. The variations were so much that, using the recommended APTT ratio or prolongation of APTT for monitoring heparin therapy, one would have achieved significantly different intensity of heparinization from year to year.
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A 41-year-old man with posthepatic liver cirrhosis and bleeding tendency was found to have a circulating anticoagulant with potent antithrombin activity. The thrombin time of the patient's purified fibrinogen was normal. This anticoagulant was residing in the patient's IgG fraction, and his IgG fraction could prolong the thrombin time of purified fibrinogen, suggesting that this circulating anticoagulant was an antibody. No heparin was detected in the patient's plasma. However, the antithrombin activity of this anticoagulant could be neutralized by toluidine blue or methylene blue ex vivo.
The hematological aspects of the original case of Rhmod are reported. The subject, as in other reported cases, had a chronic hemolytic anemia characterized by stomatocytosis, reduced osmotic fragility, and abnormal autohemolysis correctable with the addition of glucose. The 51Cr red cell survival studies showed the spleen to be the preferential site of red cell destruction and splenectomy produced a dramatic improvement in red cell survival. The topic of Rh deficiency syndrome (Rhnull and Rhmod) is briefly reviewed with regard to the number of cases reported, to genetic aspects, to the hematological findings, and to the results of splenectomy.
The in vitro effect of heparin on platelet aggregation was studied in three groups: in 26 subjects recently treated with heparin, in 18 subjects on maintenance hemodialysis, and in 20 normal controls. With the aid of Technicon H6000, platelet counts and platelet aggregations were compared in whole blood samples collected in ethylenediaminetetraacetic acid (EDTA) and in heparinized tubes. Although there was no significant difference between platelet count of heparinized and EDTA blood in the control group, the dialysis group and the group recently treated with heparin showed significantly lower platelet counts and more platelet aggregation in heparinized tubes than in EDTA tubes. We speculate that the majority of subjects exposed to heparin develop an antibody or a proaggregator which can aggregate or agglutinate platelets in the presence of heparin and causes destruction of platelets; but only in a small percentage of subjects receiving heparin is this reaction severe enough to cause thrombocytopenia.
Our observation that the effect of a patient's autoantibody with a potent antithrombin activity could be inhibited by toluidine blue and methylene blue led us to investigate the effect of these dyes in several immunochemical reactions in vitro. Both dyes reduced the titer or prevented the detection of IgG-specific single- and double-stranded DNA-binding antibodies and rheumatoid factors but did not reduce the titer of antinuclear factor and had no effect on detection of microsomal and thyroglobulin antibodies. These dyes did not aggregate or precipitate the immunoglobulins and their inhibitory effect in serum could be removed by dialysis of serum. The possible mechanism of action of these dyes in immunochemical reactions is discussed.
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A 48-year-old man with systemic lupus erythematosus (SLE) developed disseminated intravascular coagulation (DIC) with clinical bleeding. Since no other cause for DIC could be demonstrated, he was treated with prednisone, which rapidly corrected his DIC. This case demonstrates the need for a complete hematological investigation of patients with SLE who present with hemostatic abnormalities.
Granulocytic sarcoma (GS) is an extramedullary tumor composed of granulocytic precursor cells. The tumor usually develops during the course of myelogenous leukemia or myeloproliferative disorders and may represent the initial manifestation of leukemia. Rarely, GS is recognized as an isolated tumor without any evidence of leukemia. However, in such cases, leukemia generally develops within 1 to 2 years of the diagnosis of GS. We are reporting a case of a 45-year-old woman who was diagnosed as having an isolated GS of the right breast in August 1980. She was treated with a partial mastectomy followed by 1 year of combination chemotherapy as used in the cases of acute myeloblastic leukemia and has remained free of disease to the present time. That is, she has not developed leukemia or recurrence of GS for 64 months. Based on this experience and on the review of the literature, we recommend that all cases of GS be treated with combination chemotherapy as in cases of acute myeloblastic leukemias.
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The fetus, the neonate, and the pregnant woman have a greater requirement for folic acid and vitamin B12 and are more likely to suffer from a deficiency of these vitamins. This article reviews the source, requirement, absorption, and metabolism of these vitamins and discusses the problems attributed to their deficiency in pregnancy and in the neonatal period.
A couple who were first cousins had three children: an older son with Bloom syndrome (BLS) and homozygous lecithin-cholesterol acyltransferase (LCAT) deficiency; the second child (a son) and the parents are LCAT deficiency and the youngest child (a daughter), is homozygous for LCAT deficiency. The use of genetic markers gave no evidence of linkage of BLS and LCAT loci.