A simple and rapid approach to hypokalemic paralysis

Hypokalemia with paralysis (HP) is a potentially reversible medical emergency. It is primarily the result of either hypokalemic periodic paralysis (HPP) caused by an enhanced shift of potassium (K(+)) into cells or non-HPP resulting from excessive K(+) loss. Failure to make a distinction between HPP and non-HPP could lead to improper management. The use of spot urine for K(+) excretion rate and evaluation of blood acid-base status could be clinically beneficial in the diagnosis and management. A very low rate of K(+) excretion coupled with the absence of a metabolic acid-base disorder suggests HPP, whereas a high rate of K(+) excretion accompanied by either metabolic alkalosis or metabolic acidosis favors non-HPP. The therapy of HPP requires only small doses of potassium chloride (KCl) to avoid rebound hyperkalemia. In contrast, higher doses of KCl should be administered to replete the large K(+) deficiency in non-HPP.     

Diagnosing thyrotoxic periodic paralysis in the ED

Thyrotoxic periodic paralysis (TPP) and sporadic periodic paralysis (SPP) are the most common causes of hypokalemic periodic paralysis (HPP) in EDs in Asia. Their neuromuscular presentations are almost indistinguishable. We conducted this study to identify clinical clues that can help EPs distinguish between TPP and SPP. Thirty-four patients presenting to the ED with HPP were enrolled during a 3-year period. They did not have known hyperthyroidism before the attack and no family history of paralysis. They all had low K(+) excretion rates. Vital signs and blood biochemistry, including acid-base and electrolytes, were measured. TPP was subsequently established by thyroid function tests. Twenty patients had TPP and 14 patients had SPP. There was no significant difference in age and sex distribution between them. Systolic (SBP) but not diastolic blood pressure (SBP 145 +/- 4 vs 128 +/- 4 mm Hg, P < 0.001) and heart rate (106 +/- 3 vs 73 +/- 3 beats/min, P < 0.001) were significantly higher in those experiencing TPP than SPP. Among the biochemical factors, only plasma phosphate concentration (2.2 +/- 0.2 vs 3.2 +/- 0.2 mg/dL, P < 0.001) was significantly lower in those experiencing TPP than SPP. Systolic hypertension, tachycardia, and hypophosphatemia are clinical clues favoring the diagnosis of TPP.     

Hypokalaemia and paralysis

A patient with a severe degree of hypokalaemia (1.8 mmol/l) and paralysis was brought to the emergency department. Hypokalaemic periodic paralysis was an unlikely diagnosis, because an acid-base disorder (metabolic alkalosis) and a high rate of potassium (K(+)) excretion were present. During an imaginary consultation with Professor McCance, the combination of emphasis on principles of integrative physiology, a deductive analysis, common sense, and clinical skills led to an obvious diagnosis. Nevertheless, a surprise was in store, because renal K(+) wasting persisted for almost 2 weeks after removal of the causative agent. Possible explanations for the continued kaliuresis, as well as therapeutic strategies to avoid potential complications, were considered. This case illustrates the value of applying principles of physiology in a quantitative fashion at the bedside.     

Effects of potassium supplementation on the recovery of thyrotoxic periodic paralysis

Potassium supplements have been recommended to hasten recovery and prevent cardiopulmonary complications in patients with thyrotoxic periodic paralysis (TPP). However, this recommendation has not yet been proven efficacious. Thirty-two patients with acute attacks of TPP over a 3-year-period were divided into 2 groups. Group A (n = 12) was a control group treated with normal saline infusion 125 mL/hr only. Group B (n = 20) received intravenous KCl administration at a rate of 10 mmol/hr in normal saline 125 mL/hr. During the attack and for 6 hours after muscle recovery, hemodynamics were continuously recorded and muscle strength and plasma K(+) concentration were measured hourly. The sex, age, muscle strength, thyroid function, biochemical values including plasma K(+) levels, as well as the time from attack to therapy (3.6 +/- 1.6 v 3.3 +/- 1.0 hr) were not significant between the 2 groups. However, recovery time was significantly shorter in the KCl group than the control (6.3 +/- 3.8 v 13.5 +/- 7.5 hr, P < .01). Rebound hyperkalemia greater than 5.5 mmol/L occurred in 40% patients receiving KCl. The dose of KCl administered and peak K(+) concentration were positively correlated (r = 0.85, P < .001). In conclusion, KCl therapy proves to help the recovery of paralysis in TPP associated with rebound hyperkalemia. KCl supplementation should be given as small as possible (<10 mmol/hr) to avoid rebound hyperkalemia unless there are cardiopulmonary complications.     

Severe hypokalaemia in a Chinese male

A 34-year-old Chinese man developed acute, severe, generalized muscle weakness while mountain climbing. In the Emergency Department that morning, the most striking abnormalities were flaccid paralysis of both upper and lower limbs and a plasma potassium (K+) concentration (P(K)) of 1.7 mmol/l. To explain the basis for this constellation of findings, an imaginary consultation was sought with Professor McCance, the legendary integrative physiologist. Using both a deductive and a quantitative analysis, he illustrated that a simple story of an acute shift of K+ into cells was not sufficient to explain the patient's hypokalaemia. The clue he used to suspect a large total body deficit of K+ was a higher than expected rate of K(+) excretion on the initial spot urine (higher than expected ratio of K+: creatinine in the urine). This interpretation was supported by the fact that the patient needed a large supplement of K(+) to raise his P(K) to just under 3 mmol/l. It was only after more detailed studies based on urine chemistry that an accurate diagnosis and effective treatment could be instituted. The final question was why one of the hallmarks of the diagnosis of hyperaldosteronism (hypertension) was absent, yet hypokalaemia was so severe.     

Fifty cases of primary hyperaldosteronism in Hong Kong Chinese with a high frequency of periodic paralysis. Evaluation of techniques for tumour localisation

Fifty consecutive Chinese patients with primary hyperaldosteronism were studied. All were considered to have an adrenal cortical adenoma, this being proven by surgery in 46 cases. In contrast to other reports, periodic paralysis was a presenting feature in 42 per cent of patients. Other notable symptoms were palpitations (30 per cent) and syncope (12 per cent). Vascular complications were present in 20 per cent of cases. Mean serum potassium level at presentation was 2.1 +/- 0.1 (mean +/- SEM) and sodium 145.0 +/- 0.1 mmol/l. Serum potassium was significantly lower and plasma aldosterone higher in patients with periodic paralysis. Adrenal venography in order to localise the tumour was unreliable and was misleading in two cases. Adrenal venous sampling for steroid analysis was much more helpful, despite the difficulty of obtaining right adrenal venous blood. The side of the adenoma could be predicted in 97 per cent of cases from measurements of left adrenal venous and vena caval aldosterone levels. The use of high resolution CT gave 100 per cent accuracy in all 18 patients who underwent surgery, the smallest detected tumour being 0.8 cm in diameter. Surgery corrected hypokalaemia in all cases, and 37 of the 46 patients required no further antihypertensive treatment.     

Studies on hyperkalemic periodic paralysis. Evidence of changes in plasma Na and Cl and induction of paralysis by adrenal glucocorticoids

In a 19 yr old male with familial hyperkalemic periodic paralysis, paralysis was consistently induced by the administration of potassium chloride, corticotropin-gel, and a variety of glucocorticoids (dexamethasone, 6-methylprednisolone, triamcinolone) but not by mineralocorticoids (D-aldosterone, deoxycorticosterone) or by adrenocorticotropin (ACTH)-gel plus metyrapone. Induced attacks were virtually identical with spontaneous attacks, being associated, after a latent period of a few hours, with a rise in plasma K(+) and HCO(3) (-) and a simultaneous fall in plasma Na(+) and Cl(-) concentrations to an extent implying exchange of 1 K(+) with 2 Na(+) and 2 Cl(-) between extracellular and intracellular fluid. ACTH-induced paralysis was preceded by rising serum inorganic P, and associated with increased plasma glucose, blood lactate, and serum creatine phosphokinase concentrations. In normal subjects ACTH, cortisol, and triamcinolone administration failed to change plasma electrolytes or strength, while ingestion of KCl produced no weakness and smaller changes in plasma K and Na than in the patient.Since the patient and normal subjects showed the same changes in renal excretion of K after the administration of cortisol and KCl, it seems likely that paralysis in the patient resulted from abnormally slow uptake (and/or excessive loss) of K by the muscle cells, possibly caused by an abnormal "ion-exchange pump." Normal adrenocortical function and absence of a peak in plasma 11-hydroxycorticoid (11-OHCS) concentration preceding spontaneous paralysis, indicated that spontaneous paralysis did not result from changes in cortisol secretion. Similar hyperkalemic paralysis was precipitated by ACTH-gel in a brother and first cousin of the propositus. Administration of acetazolamide and fludrocortisone reduced the rise in plasma K concentration and prevented the weakness which otherwise invariably followed KCl administration to the patient. He and two close relatives have been completely protected from severe attacks of paralysis in the past 14 months by treatment with these two medications.     

A simple method for definition of incomplete suppression of aldosterone and its association with hypertension and hypokalaemia in man

By defining a model for control of potassium homoeostasis, patients with unexplained hypokalaemia may then be described as fitting or not fitting the model. Fitting the model implies an abnormality of known control mechanisms (e.g. aldosterone); by contrast, not fitting the model suggests other unknown factors responsible for the hypokalaemia and, possibly, hypertension. In the presence of normal acid-base status, potassium excretion (UK+V) is regulated by plasma potassium (PK+), delivery of sodium to the distal tubule and aldosterone secretion. A linear relationship (correlation coefficient of 0.72) was defined by: UK + V/PK+ = 5.1 X log(UAldoV) X log(UNa+ V) + 1.4 based on a 24 h urine collection and plasma sample, in 16 normal subjects, 50 hypertensive normokalaemic subjects and 11 patients with hyperaldosteronism. The relationship was robust and held true for variations in dietary sodium and potassium intake (5-300 and 20-100 mmol/day respectively) and variations in aldosterone excretion produced by enalapril. Patients with abnormal renal potassium wasting due to known extraneous factors (n = 11) all fell outside the 95% confidence limits. Twelve patients with hypertension and hypokalaemia and renal potassium wasting all fitted within the confidence limits, being no different from 22 controls selected on the basis of age and urinary potassium excretion (30-50 mmol/day). This suggests that in these 12 patients the hypokalaemia (but not necessarily the hypertension) was not due to 'unknown' steroids but rather lack of regulation of the controlling variable, aldosterone.     

An approach to the patient with severe hypokalaemia: the potassium quiz

The objective of this teaching session with Professor McCance is to develop an approach to the management of patients with a very low plasma potassium (K(+)) concentration (P(K)). The session begins with a quiz based on six recent medical consultations for a P(K) < 2 mmol/l. Professor McCance outlined how he would proceed with his diagnosis and therapy, using the synopsis that described each patient. This approach was then applied to a new patient, a 69-year-old woman who had a large volume of dependent oedema and developed a severe degree of weakness and hypokalaemia during more aggressive diuretic therapy that included a K(+)-sparing diuretic. The initial challenge for Professor McCance was to deduce why the K(+)-sparing diuretic was not effective in this patient. He also needed to explain why the P(K) was so low on admission.     

Unusual causes of hypokalaemia and paralysis

We demonstrate how the application of physiological principles may help to identify unusual causes of a very low plasma potassium (K+) concentration (P(K)) and paralysis. In the two patients described, the short time course of the illness suggested that there was an acute shift of K+ into cells. The combination of a low rate of excretion of K+, the absence of a metabolic acid-base disorder, and the fact that the clinical findings occurred very soon after a large intake of carbohydrate supported this impression. Surprisingly, the P(K) remained low for many hours after these stimuli to shift K+ into cells had abated. The missing link in this story was eventually provided by the attending medical team with the help of their mentor, Professor McCance.     

Early diagnosis of thyrotoxic periodic paralysis: spot urine calcium to phosphate ratio

OBJECTIVES: To identify a clinically reliable index of thyrotoxic periodic paralysis (TPP), a life-threatening emergency with unique and effective therapies. DESIGN: Diagnostic study. SETTING: University teaching hospital. PATIENTS: Fifty-three consecutive patients with hypokalemic paralysis during a 3-yr period and 30 thyrotoxic patients without paralysis as the thyrotoxic control group. INTERVENTIONS: For patients with hypokalemic paralysis, blood and second-void spot urine samples were obtained and measured by routine laboratory prior to therapy. For the thyrotoxic control group, blood and spot urine were collected when they visited outpatient clinics. MEASUREMENTS AND MAIN RESULTS: Twenty-nine patients fulfilled the criteria for TPP. Compared with the thyrotoxic control group, the TPP group had significant decreases in plasma potassium (K) and phosphate concentrations associated with very low urine K and phosphate excretion. Compared with the non-TPP group, the TPP group had significantly lower plasma creatinine and phosphate levels, a significantly higher urine calcium to creatinine ratio (0.25 +/- 0.12 vs. 0.08 +/- 0.07 mg/mg, p < .001), and a significantly lower urine phosphate to creatinine ratio (0.08 +/- 0.05 vs. 0.31 +/- 0.23 mg/mg, p < .001). The urine calcium to phosphate ratio had greater discriminatory power between TPP and non-TPP hypokalemic paralysis (4.1 +/- 2.3 vs. 0.5 +/- 0.6 mg/mg, p < .001). Using a urine calcium to phosphate ratio cutoff value of 1.7 mg/mg, sensitivity and specificity for TPP were 100% and 96%, respectively. CONCLUSIONS: Hypercalciuria and hypophosphaturia are characteristic features of TPP.     

The relationship between the plasma potassium concentration and renal potassium excretion in the adrenalectomized rat

The purpose of this study was to evaluate the renal mechanisms which lead to a high urine [K+] in adrenalectomized (ADX) rats devoid of aldosterone. By dividing the urine [K+] by the urine to plasma osmolality ratio the [K+] in the cortical collecting duct luminal fluid can be estimated; dividing this value by the plasma [K+] yields an index of the transtubular [K+] gradient (TTKG) in vivo. The TTKG was close to 7 in aldosterone deficient ADX rats while on a normal K+ diet and fell towards unity when amiloride or a low K+ diet was administered to these rats. With a longer time on a low K+ diet, the TTKG was less than 1 in ADX rats. This suggests that K+ was reabsorbed in the medullary collecting duct under these conditions. Hyperkalaemia appears to have an 'aldosterone-like' action in the cortical collecting duct in vivo in the absence of aldosterone in ADX rats. This action of hyperkalaemia permits normal K+ excretion rates despite the absence of mineralocorticoids.     

Thyrotoxic periodic paralysis in a Chinese population

We retrospectively evaluated the characteristics of adult patients admitted with thyrotoxic hypokalaemic periodic paralysis in Hong Kong. From 1984 to 1993, 45 Chinese adult patients were admitted with acute limb weakness, plasma potassium &les;3.5 mmol/l and thyrotoxicosis confirmed by laboratory investigations. All but one were male. Seventy-five percent of attacks occurred between 9pm and 9am. Half of the attacks occurred between July and October (49.1%), most commonly in August (20%). Mean (+SEM) plasma potassium on admission was 2.17 &plusmn; 0.08 mmol/l (range 1.1-3.5). In 15 episodes (27.3%), plasma potassium on recovery exceeded 5.0 mmol/l, while in three episodes (5.5%), potassium exceeded 6.0 mmol/l. No patient had a positive family history of thyrotoxic periodic paralysis. Only 28.9% had a known history of thyrotoxicosis before their first presentation with periodic paralysis. Twenty-seven (60%) had clinical evidence of thyrotoxicosis. Although all were biochemically thyrotoxic, 11.4% had only a mild degree of thyrotoxicosis (suppressed thyroid-stimulating hormone, high free thyroxine, but normal free triiodothyronine). One quarter of the patients had a normal erythrocyte zinc concentration, indicating either a short history of thyrotoxicosis or transient thyrotoxicosis. The diagnosis of thyrotoxic hypokalaemic paralysis should always be considered in Chinese patients with acute muscle weakness, especially in young males. Absence of clinical thyrotoxicosis does not exclude the diagnosis. Plasma potassium should be monitored carefully during treatment to prevent rebound hyperkalaemia.      

Exogenous factors influencing the human erythrocyte sodium–lithium countertransport system

It has recently been found that the Na+-Li+ countertransport across the human erythrocyte membrane is increased in patients with essential hypertension. We investigated the influence of hypokalaemia, oral contraceptives, diabetes mellitus and essential hypertension on the activity of this transport system. Normal values for the maximal Na+-Li+ transport rate were 0.25 +/- 0.08 mmol l-1 h-1 (males, n = 18) and 0.23 +/- 0.06 (females, n = 14). We found elevated values in women taking oral contraceptives (0.34 +/- 0.07, n = 10, P less than 0.001), in patients with chronic hypokalaemia due to diuretic or laxative abuse (0.41 +/- 0.16, n = 13, P less than 0.005) and in those with essential hypertension (0.32 +/- 0.08, n = 24, P less than 0.001) (all data mean +/- SD). Thus our results with hypertensive patients support the findings of other investigators. However, oral contraceptives and drug-induced hypokalaemia greatly modify this system, indicating a regulation of the Na+-Li+ countertransport by hormones. Thus the transport rate does not seem to be an appropriate test for the diagnosis of essential hypertension.     

Calcium-sensing receptor stimulates luminal K+-dependent H+ excretion in medullary thick ascending limbs of Henle's loop of mouse kidney

The calcium-sensing receptor (CaSR) is known well as a sensor of extracellular calcium for regulating parathyroid hormone secretion. CaSR is located along all nephron segments in the kidney. While hypercalcemia strongly enhances urinary acidification, the relationship between CaSR and acid-base metabolism in the kidney is still uncertain. In the present study, we examined whether CaSR activation caused acid secretion in the medullary thick ascending limb (mTAL), which is one of the major nephron segments involved in both mineral and acid-base regulation. The effects of a potent calcimimetic neomycin (Neo) on intracellular pH (pHi) were analyzed in the in vitro miroperfused mouse mTALs. The mTALs were incubated with 2,7-bis-(2-carboxyethyl)-5(6)-carboxyfluoresceine-acetoxymethylester (BCECF-AM) for microfluorescent pHi measurements. In HCO(3)(-)/CO(2)-buffered solution, the steady-state pHi was 7.17 +/- 0.01 (n = 19). Basolateral Neo at 0.4 mM in basolateral side significantly alkalinized the mTAL cells to 7.28 +/- 0.02 (n = 19), while Neo in the lumen had no effect on pHi. Neo in the basolateral side alkalinized the mTALs in the absence of ambient Na(+) and the presence of H(+)-ATPase inhibitor bafilomycin in the lumen, indicating that the effect of Neo is unrelated to Na(+)-dependent acid-base transporters such as Na(+)-H(+) exchangers and Na(+)-HCO(3)(-) cotransporter, or to luminal H(+)-ATPase. In contrast, the effect of Neo on pHi was inhibited by K(+) removal or treatment with specific H(+)-K(+)-ATPase (HKa) inhibitors, ouabain and Sch-28080, in the lumen. Our results suggest that hypercalcemia induces urinary acidification partly by stimulating luminal K(+)-dependent H(+)-excretion via CaSR in mouse mTALs.     

Persistent hyperkalemia in a patient with diabetes mellitus: a reversible defect in kaliuresis during bicarbonaturia.

The purpose of this report is to apply recent advances in the understanding of the physiology of the excretion of potassium to a patient who had hyperkalemia due to a low rate of excretion of potassium. The defect was first suspected during therapy for diabetic ketoacidosis, when the concentration of potassium in plasma was unusually high (7.3 mmol/l) on admission and the deficit of potassium, as judged from the quantity of potassium infused to maintain normokalemia (40 mmol/24 h), was much less than expected. After recovery from diabetic ketoacidosis, hyperkalemia persisted despite near-normal values for creatinine and glucose in plasma. Excretion of potassium was low, considering the stimulus of hyperkalemia, and did not rise appreciably after the acute or chronic administration of a mineralocorticoid. The transtubular potassium concentration gradient (TTKG) did not exceed 6 after a large dose of fludrocortisone (200 micrograms) was administered. Notwithstanding, the TTKG rose to 14.4 following the intake of acetazolamide. We speculate that the basis for the hyperkalemia was type II hypoaldosteronism.     

Block of human heart hH1 sodium channels by amitriptyline

Amitriptyline is a tricyclic antidepressant used to treat major depression and various neuropathic pain syndromes. This drug also causes cardiac toxicity in patients with overdose. We characterized the tonic and use-dependent amitriptyline block of human cardiac (hH1) Na(+) channels expressed in human embryonic kidney cells under voltage-clamp conditions. Our results show that, near the therapeutic plasma concentration of 1 microM, amitriptyline is an effective use-dependent blocker of hH1 Na(+) channels during repetitive pulses (approximately 55% block at 5 Hz). The tonic block for resting and for inactivated hH1 channels by amitriptyline (0.1-100 microM) yielded IC(50) values (50% inhibitory concentration) of 24.8 +/- 2.0 (n = 9) and 0.58 +/- 0.03 microM (n = 7), respectively. Substitution of phenylalanine with lysine at the hH1-F1760 position, a putative binding site for local anesthetics, eliminates the use-dependent block by amitriptyline at 1 microM. The time constants of recovery from the inactivated-state amitriptyline block in hH1 wild-type and hH1-F1760K mutant channels are 8.0 +/- 0. 5 (n = 6) and 0.45 +/- 0.07 s (n = 6), respectively. A substitution at either hH1-F1760K or hH1-Y1767K significantly increases the IC(50) values for resting and inactivated states of amitriptyline, but the increase is much more pronounced with the hH1-F1760K mutation. Because these two residues were proposed to form a part of the local anesthetic binding site, we conclude that amitriptyline and local anesthetics interact with a common binding site. Furthermore, at therapeutic concentrations, the ability of amitriptyline to act as a potent use-dependent blocker of Na(+) channels may, in part, explain its analgesic actions.     

The effect of glutamine administration on urinary ammonium excretion in normal subjects and patients with renal disease

The effect of acute changes in the delivery rate of glutamine to the kidney on urinary ammonium excretion was studied in man. Healthy subjects and patients with intrinsic renal disease were studied under three different acid-base conditions: unaltered acid-base balance; NH₄Cl-induced acidosis; and NaHCO₃-induced alkalosis. Anhydrous L-glutamine was administered orally in a single dose of 260 mmoles during each of these three acid-base states. We found that endogenous venous plasma glutamine concentration fell during acidosis and rose during alkalosis in both healthy subjects and patients with renal disease. In healthy subjects, orally administered glutamine raised plasma glutamine concentration markedly over a 2-3 hr period. This was accompanied by an increase in urinary ammonium excretion and a rise in urine pH under normal acid-base conditions and during metabolic acidosis. No increase in ammonium excretion occurred when glutamine was administered during metabolic alkalosis in spite of an equivalent rise in plasma glutamine concentration. In patients with renal disease, endogenous venous plasma glutamine concentration was lower than in healthy subjects, perhaps as a result of mild metabolic acidosis. Acute oral glutamine loading failed to increase urinary ammonium excretion significantly during either unaltered acid-base conditions or after NH₄Cl-induced acidosis, even though plasma glutamine rose as high as in healthy subjects. We conclude from these observations that glutamine delivery to the kidney is a rate-limiting factor for ammonium excretion in healthy subjects, both before and after cellular enzyme adaptation induced by metabolic acidosis. In contrast, in patients with renal disease, glutamine delivery is not rate-limiting for ammonium excretion. Presumably other factors, such as surviving renal mass and the activity of intracellular enzymes necessary for ammonia synthesis limit ammonium excretion in these patients.     

重症低钾型周期性瘫痪原因分析及护理干预

目的探讨低钾型周期性瘫痪发生原因，以提高对该病护理的重视，为临床护理奠定基础。方法选择低钾型周期性瘫痪患者64例，总结分析发病原因并提出护理干预措施。结果低钾型周期性瘫痪患者，经积极治疗及护理，低钾症状缓解出院。结论护理上要重视评估，注重原发病的积极治疗，帮助患者寻找原因，积极预防，可以减少其发病率，提高患者工作生活质量。     

Decreased activity of the platelet Na+,K(+)-adenosine triphosphatase enzyme in allergic subjects

A pathogenic role and abnormal function have both been ascribed to the blood platelet in allergy, but the explanation for these observations is unknown. This study compared the cation-stimulated adenosine triphosphatase enzyme (ATPase) activities of platelets from allergic (n = 18), potentially allergic (asymptomatic, positive skin test, n = 5) and normal patients (n = 10), all of whom were without symptoms at the time of the study. Platelets were separated by centrifugation, were sonicated, and were assayed for cation-dependent ATPase activity by spectrophotometry. The mean Na+,K(+)-ATPase activity (in nanomoles per microgram protein per minute) of allergic subjects (0.94 +/- 1.28) was significantly lower than that of normal subjects (3.93 +/- 1.58). No Na+,K(+)-ATPase activity was detectable in platelets from eight of the allergic subjects. The Na+,K(+)-ATPase activity of potentially allergic subjects was intermediate between those of the allergic and normal subjects. A significant negative correlation (p less than 0.01) was observed between serum IgE levels and platelet Na+,K(+)-ATPase values, thus suggesting a relationship between the reduced platelet Na+,K(+)-ATPase and IgE immunoglobulin. No such differences were observed for the Ca+(+)- and Mg+(+)-stimulated ATPases. In vivo dysfunction of the plasma membrane Na+,K(+)-ATPase enzyme in allergic subjects could have profound effects on levels of intracellular cations and thus platelet activation and function.