Peter McPhedran

Enalapril treatment of posttransplant erythrocytosis: efficacy independent of circulating erythropoietin levels

To determine the mechanism of action by which angiotensin-converting enzyme (ACE) inhibitors lower hematocrit in patients with posttransplant erythrocytosis, indices of red blood cell production and red blood cell destruction were obtained serially for 6 months from 10 renal transplant patients receiving treatment with enalapril for this problem. Before treatment, five patients had an elevated red blood cell mass, four had plasma volume contraction, and one had both. The mean hemoglobin concentration decreased by 2 g/dL (range, 0.5 to 3.3 g/dL), from 17 +/- 1 g/dL to 15 +/- 1 g/dL (P = 0.001) following 6 months of enalapril therapy. Similarly, the mean hematocrit decreased by 8% (range, 3% to 12%), from 52% +/- 2% to 44% +/- 3% (P = 0.001) during the same period. The mean reticulocyte count tended to decrease, although the change was not significant. The red blood cell mass decreased dramatically by 15% to 50%, from 32 +/- 9 mL/kl to 23 +/- 4 mL/kg (P = 0.008). Although serial erythropoietin levels declined steadily in two patients, there was no consistent change in the other patients. Mean levels decreased modestly, from 20 +/- 11 mU/mL at baseline to 12 +/- 5 mU/mL at 6 months, a change that was not statistically significant. Mean levels at each time point were not statistically different from the mean pretreatment value. Furthermore, during enalapril therapy, there was no correlation between mean circulating erythropoietin level and mean hematocrit (r = 0.43, P = 0.20) or hemoglobin concentration (r = 0.36, P = 0.30) or between changes in these parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Ayurvedic herbal medicine and lead poisoning

Although the majority of published cases of lead poisoning come from occupational exposures, some traditional remedies may also contain toxic amounts of lead. Ayurveda is a system of traditional medicine that is native to India and is used in many parts of world as an alternative to standard treatment regimens. Here, we report the case of a 58-year-old woman who presented with abdominal pain, anemia, liver function abnormalities, and an elevated blood lead level. The patient was found to have been taking the Ayurvedic medicine Jambrulin prior to presentation. Chemical analysis of the medication showed high levels of lead. Following treatment with an oral chelating agent, the patients symptoms resolved and laboratory abnormalities normalized. This case highlights the need for increased awareness that some Ayurvedic medicines may contain potentially harmful levels of heavy metals and people who use them are at risk of developing associated toxicities.

Bleeding disorder due to platelet prostaglandin H synthase-1 (PGHS-1) deficiency

Defective platelet prostaglandin H synthase (PGHS) activity has been recognized as a cause of bleeding disorders, but the defect has not been characterized. We evaluated three female patients aged 37, 48 and 55 who presented with a mild bleeding disorder due to platelet dysfunction. None of the patients had underlying diseases or reported use of aspirin or other nonsteroidal anti‐inflammatory drugs. Coagulation screening tests and platelet count were normal in each patient. Platelet aggregation in response to adenosine diphosphate (ADP), collagen and epinephrine were subnormal, characterized by an abnormal second‐wave aggregation and propensity for disaggregation. Arachidonate‐induced platelet aggregation was defective, whereas PGH2‐induced aggregation was normal. Platelet thromboxane A2 (TXA2) production in response to arachidonic acid was reduced in all three patients, i.e. 11.7, 4.6 and 4.4 ng TXB2/3  108 plt respectively (normal range was 49–81 ng/3 10 8 plt), whereas they were normal in response to exogenous PGH2, i.e. 71.4, 56.6 and 48.9 ng/3  108 plts, respectively (normal range 49–85 ng/3  108 plt). These results are consistent with a deficiency of platelet PGHS activity. The level of the constitutive platelet PGHS‐1 and TXA2 synthase (TXAS) proteins were determined on platelet microsomal fractions by Western blot analysis using affinity‐purified polyclonal antibodies highly specific for human PGHS‐1 and TXAS, respectively. In two patients the 70 kD PGHS‐1 protein was undetectable, whereas it was normal in the third patient. The 60 kD TXAS band was normal in all three patients. These findings indicate that human platelet PGHS‐1 deficiency is due to two types of enzyme defects: type 1 defect is manifested by an undetectable PGHS‐1 protein in platelets whereas the type 2 defect is manifested by a normal quantity of PGHS‐1 protein which has an impaired catalytic activity.

Hypocalcemia in a Dialysis Patient Treated With Deferasirox for Iron Overload

Deferasirox is a new iron chelator approved recently for chelation therapy in iron-overloaded patients. It is considered safe and efficacious in most patients, but has not been tested formally in patients with end-stage renal disease. We report a case of a patient with end-stage renal disease secondary to sickle cell nephropathy who developed recurrent symptomatic hypocalcemia while on therapy and later reexposure with this medication for iron overload from long-term blood transfusions. This is the first case report of this complication with deferasirox therapy in a patient with end-stage renal disease.

Isoniazid-Induced Pure Red Cell Aplasia

The clinical courses of four individuals with pure red cell aplasia associated with isoniazid use are described. Erythroblastopenia in these individuals resolved following cessation of this antituberculous therapy. A clonal assay system that quantitates erythroid precursor cells was used to investigate the pathogenesis of the red cell aplasia in three of the patients. Using this technique, however, we were unsuccessful in demonstrating an inhibitory effect of acute phase serum, isoniazid or a combination of the two on erythroid colony formation. We conclude that isoniazid usage alone appears to be associated with a readily reversible form of acquired pure red cell aplasia. In addition, the results of our in vitro studies emphasize the limitations of bone marrow culture systems when used to implicate offending drugs in the production of drug related cytopenias.

Successful childbirth by a patient with congenital factor XI deficiency and an acquired inhibitor

Summary. Acquired inhibitors in factor XI deficiency (FXI) are rare. The presence of an inhibitor during pregnancy poses a potential haemorrhagic risk to the fetus. We report an uncomplicated pregnancy and successful childbirth by a woman with congenital FXI deficiency and an acquired inhibitor, and discuss the persistence of residual FXI activity in the presence of an inhibitor.

COMPREHENSIVE TESTING FOR THALASSEMIA TRAIT

The thalassemias are a group of hereditary blood conditions that occur with considerable frequency in ethnic groups tracing their origins to countries that border the Mediterranean Sea, the Middle East, and Southeast Asia.l The conditions result from genetic defects causing deficient synthesis of hemoglobin polypeptide chains, and are manifested by microcytic, hypochromic anemias of varying degrees of severity. In the homozygous state, thalassemia genes cause severe and often lethal diseases for which there is no cure.2 The heterozygous state, thalassemia trait, is usually benign, but has clinical and genetic implications. Diagnosis of thalassemia trait is suggested by a familial microcytosis and is usually confirmed by demonstration of characteristic changes in the proportions of Hgb A? and F or unbalanced polypeptide chain synthe~is .~-~ These latter diagnostic tests are somewhat complicated and expensive, and this has inhibited the screening of populations at risk for these defects. Techniques for rapid, accurate electronic measurement of red cell size have recently become available. A preliminary study at this institution by one of us (P.M.) indicated that about 25% of hospital patients with microcytosis determined with an electronic cell counter (Coulter Model S) had thalassemia trait.6 This suggested that measurement of mean corpuscular volume (MCV) might be used as a screening test for thalassemia trait but did not indicate its reliability. The present report describes a comprehensive testing program for thalassemia trait in high-risk populations. This program included education, voluntary testing with evaluation of several screening methods, and individual genetic counseling. The program was designed to conform with the recommendations of the Institute of Society, Ethics and Life Sciences regarding the initiation and operation of genetic screening programs.’

Acute Adrenal Insufficiency as a Complication of Urological Surgery

Acute adrenal insufficiency postoperatively is an uncommon problem and, if unrecognized, it may cause serious morbidity and can be fatal. It can occur as the result of acute bilateral adrenal hemorrhage associated with anticoagulation, inadvertent injury to or removal of a solitary adrenal gland, or postoperative stress in an individual with incipient adrenal insufficiency. Its manifestations, such as fever, tachycardia, hypotension, lethargy, abdominal pain and gastrointestinal dysfunction, mimic the other more common postoperative complications and compound the difficulty in establishing the correct diagnosis. Once the diagnosis is made the condition is readily managed successfully. We report 3 cases of acute adrenal insufficiency occurring after salvage cystectomy, ileal replacement of the ureter and retropubic prostatectomy, which illustrate the salient clinical features, problems in diagnosis and predisposing risk factors. All 3 patients survived once the diagnosis of adrenal insufficiency was made. These cases emphasize the need to be aware of the possibility of this complication to make the correct diagnosis and to institute proper treatment.