[HSF] Heparin Induced Hyperkalemia due to Aldosterone inhibition

[Nasser F. Abou'Seada]

Go on dear friend ... report your case ... 

NFA

> -----Original Message-----
> From: openheart-l-bounces at lists.hsforum.com [mailto:openheart-l-
> bounces at lists.hsforum.com] On Behalf Of prasannasimha
> Sent: Saturday, November 04, 2006 7:01 AM
> To: OpenHeart-L at lists.hsforum.com; ccm
> Subject: [HSF] Heparin Induced Hyperkalemia due to Aldosterone inhibition
> 
> 
> Well, I did a literature search and guess what - the blessed thing is well
documented -
> Heparin induced hyperkalemia due to aldosterone inhibition.
> I did not know that Heparin can also cause priapism !!! Did you know that
????
> Prasanna
> 
> 
> 1: Thromb Haemost. 2005 Nov;94(5):1109-10.
> 
> Effect of unfractionated heparin and long-term treatment with
> low-molecular-weight heparin, bemiparin, on potassium levels.
> 
> Rocha E, Gomez-Outes A, Martinez Gonzalez J, Kakkar VV.
> 
> Publication Types:
>     Letter
> 
> PMID: 16363259 [PubMed - indexed for MEDLINE]
> 
> 2: Kaohsiung J Med Sci. 2005 Mar;21(3):128-33.
> 
> Heparin-induced cardiac tamponade and life-threatening hyperkalema in a
patient
> with chronic hemodialysis.
> 
> Su HM, Voon WC, Chu CS, Lin TH, Lai WT, Sheu SH.
> 
> Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical
> University, Kaohsiung, Taiwan.
> 
> Heparin, a commonly used anticoagulant agent, is frequently used in
patients
> undergoing hemodialysis. As with most medications, heparin has a
significant
> side effect profile. Two of its most important side effects, _/*major
bleeding and
> hyperkalemia, may be devastating without immediate diagnosis and
treatment.*/_
> Major bleeding such as gastrointestinal, genitourinary or intracranial
bleeding
> is occasionally encountered and rarely neglected. However, heparin-induced
> cardiac tamponade is rarely encountered and may be easily overlooked.
Another
> side effect, heparin-induced hyperkalemia, an unusual but well-described
side
> effect, is frequently forgotten until life-threatening arrhythmia has
occurred.
> We report a case involving a 40-year-old male patient with uremia, who had
> received heparin for 10 days for deep vein thrombosis in the left lower
> extremity. Hemopericardium with cardiac tamponade and life-threatening
> hyperkalemia were both noted in this patient.
> 
> Publication Types:
>     Case Reports
> 
> PMID: 15875438 [PubMed - indexed for MEDLINE]
> 
> 3: Pharmacoepidemiol Drug Saf. 2004 May;13(5):299-302.
> 
> Early onset of hyperkalemia in patients treated with low molecular weight
> heparin: a prospective study.
> 
> Koren-Michowitz M, Avni B, Michowitz Y, Moravski G, Efrati S, Golik A.
> 
> Department of Medicine 'A', Assaf-Harofe Medical Center, Zerifin, Israel.
> mayakoren at asaf.health.gov.il
> 
> OBJECTIVE: Data on low molecular weight heparin (LMWH) and induction of
> hyperkalemia is scarce. Therefore, we conducted a prospective study
evaluating
> potassium levels before and after three days of treatment with the LMWH
> Enoxaparin. METHODS: Patients treated with the LMWH Enoxaparin in the
standard
> therapeutic dosages were included. Levels of potassium, sodium, urea,
> creatinine, AST, ALT bicarbonate, pH and platelet counts were examined
before
> and after three days of LMWH treatment. Plasma renin activity (PRA) and
> aldosterone levels were examined in a subgroup of patients. Potassium
levels
> were correlated with disease states and medications known to affect
potassium
> homeostasis. RESULTS: Ninety-seven consecutive patients were enrolled in
the
> study, however, 12 patients were excluded from analysis; therefore 85
patients
> comprised the study group. The most common reason for exclusion (in 9
patients)
> was the absence of a second potassium result. We found an increase in
potassium
> levels from 4.26 +/- 0.04 mmol/L at baseline to 4.43 +/- 0.04 mmol/L on
the
> third day of treatment (mean +/- SE), with potassium levels exceeding 5.0
mmol/L
> in 9% of treated patients. There was no life threatening or symptomatic
> hyperkalemia. PRA and aldosterone levels did not change significantly
during the
> treatment period. There was no correlation between the increase in
potassium
> levels and diabetes mellitus or treatment with angiotensin converting
enzymes
> inhibitors, angiotensin receptor blockers, beta-blockers and non-potassium
> sparing diuretics. CONCLUSIONS: _*Potassium levels increase on the third
day of
> treatment with the LMWH Enoxaparin. This effect may be aldosterone
independent.*_
> Copyright 2003 John Wiley & Sons, Ltd.
> 
> Publication Types:
>     Clinical Trial
> 
> PMID: 15133781 [PubMed - indexed for MEDLINE]
> 
> 4: Ann Pharmacother. 2004 Mar;38(3):404-7. Epub 2004 Jan 12.
> 
> Heparin-induced hyponatremia.
> 
> Norman NE, Sneed AM, Brown C, Ellis CA, Minard G, Brown RO.
> 
> Department of Pharmacy, The Regional Medical Center at Memphis, TN
38103-2807,
> USA. enorman at the-med.org
> 
> OBJECTIVE: To report a case of hyponatremia in a patient receiving
systemic
> unfractionated heparin (UFH) therapy and parenteral nutrition. CASE
SUMMARY: A
> 70-year-old African American woman was started on parenteral nutrition for
> postoperative ileus following an elective surgical procedure. Three days
later,
> she was diagnosed with a pulmonary embolism and intravenous UFH therapy
was
> initiated. During the 7-day course of UFH therapy, the patient's serum
sodium
> concentration steadily declined and urine sodium concentration
progressively
> increased. Physical examination revealed no signs or symptoms of hypo- or
> hypervolemia. The patient's serum potassium concentration increased
modestly,
> although significant hyperkalemia was not observed. After discontinuation
of
> UFH, serum concentrations of both sodium and potassium returned to
baseline
> levels. DISCUSSION: Although heparin-induced hyperkalemia is well
documented,
> cases associated with substantial hyponatremia have been reported less
> frequently. An objective causality assessment revealed that the adverse
drug
> reaction was probable in this case. Hyponatremia and hyperkalemia result
from
> the antagonism of aldosterone by UFH within the zona glomerulosa of the
adrenal
> glands. CONCLUSIONS: _*The use of UFH may result in significant
hyponatremia as
> well as hyperkalemia. Reversal of these electrolyte disturbances occurs
after
> discontinuation of heparin.*_
> 
> Publication Types:
>     Case Reports
> 
> PMID: 14742828 [PubMed - indexed for MEDLINE]
> 
> 5: Eur J Clin Pharmacol. 2003 Sep;59(5-6):373-7. Epub 2003 Jul 8.
> 
> Variations of serum potassium level and risk of hyperkalemia in inpatients
> receiving low-molecular-weight heparin.
> 
> Gheno G, Cinetto L, Savarino C, Vellar S, Carraro M, Randon M.
> 
> Department of Internal Medicine, ASL 3 of the Veneto Region, Bassano del
Grappa,
> Italy. giuseppe.gheno at aslbassano.it
> 
> OBJECTIVES. To observe the variations of serum potassium level in patients
> receiving low-molecular weight heparin, assess the consequent risk of
> hyperkalemia and evaluate the clinical contributory factors. METHODS. A
> prospective study was performed on consecutive inpatients treated with
> low-molecular-weight heparin as indicated by the attending physicians. The
> changes of serum potassium level observed within 5-8 days were tested by
> univariate and multivariate analysis according to demographic and clinical
> variables and concomitant pharmacological therapy. RESULTS. Four hundred
and
> sixteen patients (mean age 73 years; 64% female) were enrolled in the
study over
> 15 months. After receiving nadroparin or enoxaparin (mean daily dosage:
76.3
> anti-factor Xa unit/kg) for a median 6-day period, their mean (+/-SD)
serum
> potassium level increased from 4.2+/-0.5 mmol/l to 4.5+/-0.5 mmol/l (
P<0.0001).
> This change was significantly correlated with baseline potassium, interval
> between potassium samplings, history of hypertension or renal
insufficiency, and
> marginally with aldosterone antagonist treatment. Hyperkalemia, defined as
> potassium exceeding 5.5 mmol/l, developed in ten patients (2.4%) and the
highest
> value observed was 7.6 mmol/l; by multivariate logistic-regression
analysis,
> history of diabetes was the only significant independent predictor (odds
ratio
> 6.5; 95% C.I.=1.7-24.8). CONCLUSION. _*Short-term treatment with
> low-molecular-weight heparin induces a significant increase in serum
potassium
> level but the related incidence of relevant hyperkalemia is low. However,
given
> the high absolute number of patients currently exposed to the risk in many
> clinical settings and the limitation of risk prediction, clinicians should
> prevent this life-threatening complication by a high index of suspicion
and,
> accordingly, a quite routine monitoring of serum potassium.*_
> 
> Publication Types:
>     Clinical Trial
> 
> PMID: 12851802 [PubMed - indexed for MEDLINE]
> 
> 6: Clin Med. 2003 Jan-Feb;3(1):87.
> 
> Serious hyperkalaemia after short use of low molecular weight heparin in a
> diabetic patient.
> 
> Rippin JD, Hado HS, Green N, Elhadd TA.
> 
> Publication Types:
>     Case Reports
>     Letter
> 
> PMID: 12617429 [PubMed - indexed for MEDLINE]
> 
> 7: Ann Thorac Surg. 2002 Nov;74(5):1698-700.
> 
> Heparin-induced hyperkalemia after cardiac surgery.
> 
> Day JR, Chaudhry AN, Hunt I, Taylor KM.
> 
> Department of Cardiothoracic Surgery, Hammersmith Hospital, London, United
> Kingdom. j.day at ic.ac.uk
> 
> Surgeons are increasingly faced with patients suffering from complicated
> pathology in multiple organ systems, to which multiple therapeutic agents
with
> complex adverse effects are often prescribed. We face a daily challenge in
> maintaining an up-to-date knowledge of these complications. Heparin is
widely
> used in surgical practice, yet our awareness of its adverse effects, other
than
> bleeding and thrombocytopenia, remains poor. We will _*present an example
of
> heparin-induced hyperkalemia following administration for cardiopulmonary
bypass
> and intraaortic balloon pump prophylaxis. This is a rare but serious
> complication of heparin therapy, not usually reported in the context of a
> cardiac surgical patient*_. We will also discuss the renal physiology
leading to
> hyperkalemia and the options available for its management.
> 
> Publication Types:
>     Case Reports
> 
> PMID: 12440638 [PubMed - indexed for MEDLINE]
> 
> 8: Pathophysiol Haemost Thromb. 2002 May-Jun;32(3):107-10.
> 
> Effect of low-molecular-weight heparin on potassium homeostasis.
> 
> Abdel-Raheem MM, Potti A, Tadros S, Koka V, Hanekom D, Fraiman G,
Danielson BD.
> 
> Department of Medicine, University of North Dakota School of Medicine,
Fargo, N
> Dak 58102, USA.
> 
> Background: Low-molecular-weight heparins (LMWHs) are being preferred to
> unfractionated heparin (UFH) because of their superior convenience and a
> comparable or slightly better toxicity profile. Whether LMWH has an
inhibitory
> effect on aldosterone that causes hyperkalemia is yet uncertain. Methods:
> Twenty-eight patients (all male; mean age: 70 years, range 52-87 years)
placed
> on LMWH therapy (40 mg subcutaneously every 12 h) for deep venous
thrombosis
> prophylaxis after an operation were included in the study. Transtubular
> potassium concentration gradient (TTKG) was calculated 1 day prior to LMWH
> therapy and again after 4 days of treatment. Of the 28 patients enrolled
in the
> study, we were able to calculate the TTKG in only 19 patients: 9 had a
urinary
> osmolarity (either before or after LMWH therapy) less than the serum
osmolarity,
> making the TTKG calculation unreliable. The Wilcoxon signed-rank test was
used
> to analyze differences in the median serum potassium levels and TTKG
before and
> after LMWH therapy. Results: All patients had adequate renal function
> (creatinine clearance >90 ml/min). _*Mean (+/- SD) serum potassium
concentration
> before LMWH was 4.25 (+/- 0.40) mmol/dl. It increased to 4.35 (+/- 0.41)
mmol/dl
> after initiating LMWH therapy (p = 0.09). Similarly, the mean (+/- SD)
TKKG
> calculated was 5.52 (+/- 2.33) before and 5.97 (+/- 3.06) after 4 days of
LMWH
> (p = 0.54). Conclusions: Unlike UFH, LMWH (**Lovenox in doses used for
> postoperative prophylaxis against deep venous thrombosis does not seem to
have a
> significant effect on potassium homeostasis.*_ Copyright 2002 S. Karger
AG, Basel
> 
> PMID: 12372922 [PubMed - indexed for MEDLINE]
> 
> 9: Ann Ital Med Int. 2002 Jan-Mar;17(1):51-3.
> 
> Heparin-induced life-threatening hyperkalemia.
> 
> Gheno G, Savarino C, Vellar S, Cinetto L.
> 
> Departimento di Medicina Interna, Ospedale Civile di Asiago, ASL 3 Regione
> Veneto di Bassano del Grappa (VI). giuseppe.gheno at tin.it
> 
> Hyperkalemia may occur in many clinical settings and lead to serious
events.
> Heparin-induced hyperkalemia is presumably less well recognized than other
> untoward effects of heparin treatment and more frequent than commonly
perceived.
> To draw attention to this clinically relevant occurrence, we report 2
cases of
> life-threatening bradyarrhythmia associated with heparin prescription.
> _*Heparin-induced hyperkalemia is mediated by an enzymatic block in the
synthesis
> of aldosterone; however, in most cases severe hyperkalemia occurs in the
> presence of additional factors influencing potassium homeostasis.*_
Patients
> treated with heparin should be stratified and adequately monitored
according to
> the outlined risk profile.
> 
> Publication Types:
>     Case Reports
> 
> PMID: 11975115 [PubMed - indexed for MEDLINE]
> 
> 10: Ann Pharmacother. 2000 May;34(5):606-10.
> 
> Fludrocortisone for the treatment of heparin-induced hyperkalemia.
> 
> Sherman DS, Kass CL, Fish DN.
> 
> Department of Pharmacy Practice, School of Pharmacy, University of
Colorado
> Health Sciences Center, Denver, USA.
> 
> OBJECTIVE: To report the use of fludrocortisone for heparin-induced
hyperkalemia
> and to briefly review the available literature relating to heparin-induced
> hyperkalemia. CASE SUMMARY: A 34-year-old African-American man was
admitted to
> the hospital for pneumococcal pneumonia and sepsis. His hospital course
was
> complicated by the development of acute respiratory distress syndrome,
severe
> sepsis, acute renal failure, placement of a tracheostomy, and recurrent
> nasopharyngeal bleeding. The patient also developed a subclavian vein
thrombosis
> with extension to the cephalic and basilic veins secondary to placement of
a
> pulmonary artery catheter; anticoagulation with heparin was required. On
day 9
> of heparin therapy, the patient developed symptomatic hyperkalemia
refractory to
> conventional therapies. Oral fludrocortisone 0.1 mg/d was initiated with
> resolution of the hyperkalemia within 24 hours despite the continued
> administration of heparin. DATA SOURCES: A MEDLINE (1966-October 1999)
search
> was performed to identify case reports and clinical trials discussing
> heparin-induced hyperkalemia or the use of fludrocortisone for
hyperkalemia.
> DISCUSSION: _*Heparin has the potential to induce hyperkalemia by several
> mechanisms, including decreased aldosterone synthesis, reduction in number
and
> affinity of aldosterone II receptors, and atrophy of the renal zona
glomerulosa.
> Fludrocortisone promotes potassium excretion by its direct actions on the
renal
> distal tubules.*_ In this patient, fludrocortisone resulted in a
significant and
> rapid decrease in serum potassium even with continued heparin
administration and
> acute renal failure. CONCLUSIONS: This case suggests that fludrocortisone
is a
> reasonable alternative therapy for patients with hyperkalemia secondary to
> heparin therapy when the continued administration of heparin is necessary.
> 
> Publication Types:
>     Case Reports
> 
> PMID: 10852087 [PubMed - indexed for MEDLINE]
> 
> 11: Clin Appl Thromb Hemost. 1999 Oct;5 Suppl 1:S7-15.
> 
> Clinical aspects of heparin-induced thrombocytopenia and thrombosis and
other
> side effects of heparin therapy.
> 
> Bick RL, Frenkel EP.
> 
> University of Texas Southwestern Medical Center, USA.
> 
> Heparin, first used to prevent the clotting of blood in vitro, has been
> clinically used to treat thrombosis for more than 50 years. Although
several new
> anticoagulant drugs are in development, heparin remains the anticoagulant
of
> choice to treat acute thrombotic episodes. The clinical effects of heparin
are
> meritorious, but side effects do exist. Bleeding is the primary untoward
effect
> of heparin. Major bleeding is of primary concern in patients receiving
heparin
> therapy. However, additional important untoward effects o_*f heparin
therapy
> include heparin-induced thrombocytopenia, heparin-associated osteoporosis,
> eosinophilia, skin reactions, allergic reactions other than
thrombocytopenia,
> alopecia, transaminasemia, hyperkalemia, hypoaldosteronism, and
priapism.*_ These
> side effects are relatively rare in a given individual, but given the
extremely
> widespread use of heparin, some are quite common, particularly HITT and
> osteoporosis. Although reasonable incidences of many of these side effects
can
> be "softly" deduced from current reports dealing with unfractionated
heparin, at
> present the incidences of these side effects with newer low molecular
weight
> heparins appear to be much less common. However, only longer experience
will
> more clearly define the incidence of each side effect with low molecular
weight
> preparations.
> 
> Publication Types:
>     Review
> 
> PMID: 10726030 [PubMed - indexed for MEDLINE]
> 
> 12: Am J Phys Med Rehabil. 2000 Jan-Feb;79(1):93-6.
> 
> Heparin-induced hyperkalemia confirmed by drug rechallenge.
> 
> Orlando MP, Dillon ME, O'Dell MW.
> 
> Department of Internal Medicine, University of Cincinnatti College of
Medicine,
> Ohio, USA.
> 
> Subcutaneous heparin is commonly used as a prophylaxis against deep venous
> thrombosis in a wide variety of hospitalized patients. As with most
medications,
> _*heparin has a significant side effect profile; heparin-induced
hyperkalemia is
> an unusual but well described side effect*_. To increase awareness of
> heparin-induced hyperkalemia and of those patients at greatest risk, we
present
> two cases of documented hyperkalemia induced by heparin and reconfirmed by
drug
> rechallenge.
> 
> PMID: 10678609 [PubMed - indexed for MEDLINE]
> 
> 13: Am J Ther. 1998 Mar;5(2):125-32.
> 
> University of Miami Division of Clinical Pharmacology therapeutic rounds:
> drug-induced hyperkalemia.
> 
> Preston RA, Hirsh MJ MD, Oster MD Jr, Oster HR MD.
> 
> Department of Medicine, University of Miami School, 1500 NW 12th Ave, 15th
Floor
> West, Miami, Florida 33136, USA.
> 
> Drug-induced hyperkalemia is an important but often overlooked problem
> encountered commonly in clinical practice. It may occur in the ambulatory
as
> well as the impatient setting. Every evaluation of a hyperkalemic patient
should
> include a careful review of medications to determine if a drug capable of
> causing or aggravating hyperkalemia is present. Medications generally
produce
> hyperkalemia either by causing redistribution of potassium (beta2
-adrenergic
> blockers, succinylcholine, digitalis overdose, hypertonic mannitol) or by
> impairing renal potassium excretion. Drugs cause impaired renal potassium
> excretion by (1) interfering with the production and/or secretion of
aldosterone
> (nonsterodial anti-inflammatory drugs, angiotensin-converting enzyme
inhibitors,
> angiotensin-II receptor antagonists, heparin, cyclosporine, and FK 506) or
(2)
> blocking the kaliuretic effects of aldosterone (potassium-sparing
diuretics,
> trimethoprim, pentamidine, and nefamostat mesilate). Because severe renal
> insufficeiency is generally required to cause hyperkalemia, an elevated
serum
> potassium concentration in a patient with mild-to-moderate renal failure
should
> not be ascribed to renal failure alone._* A careful search for "hidden"
potassium
> loads and for causes of impaired tubular secretion of potassium (including
> drugs) is necessary. Finally, it is important to recognize that the causes
of
> hyperkalemia may be additive. Patients may have more than one cause of
> hyperkalemia at the same time. Therefore, all potential causes of
hyperkalemia,
> including drugs, should be systematically evaluated in every hyperkalemic
> patient.*_
> 
> Publication Types:
>     Case Reports
> 
> PMID: 10099101 [PubMed - indexed for MEDLINE]
> 
> 14: Artif Organs. 1998 Jul;22(7):614-7.
> 
> Heparin-induced hyperkalemia in chronic hemodialysis patients: comparison
of low
> molecular weight and unfractionated heparin.
> 
> Hottelart C, Achard JM, Moriniere P, Zoghbi F, Dieval J, Fournier A.
> 
> Service de Nephrologie, Medecine Interne, CHU Amiens, France.
> 
> Aldosterone suppression and subsequent hyperkalemia are well described
> reversible side effects of prolonged treatment with heparin. This study
was
> designed to examine whether the discontinuous use of heparin three times a
week
> to prevent thrombosis formation during hemodialysis sessions could also
induce
> hypoaldosteronism and might contribute to increased predialysis kalemia in
> hemodialysis patients. Two different heparinization regimens were
prospectively
> compared in a crossover study of 11 chronic hemodialysis patients. During
2
> consecutive weeks, the patients were dialyzed each week with either their
usual
> doses of unfractionated heparin (UH) (6,160 IU +/- 1,350 IU) or low
molecular
> weight heparin (LMWH) (15 anti-Xa activity [aXa] U/kg + 5 aXa U/kg/h). In
all
> but 2 patients, the predialysis level of plasma K+ was higher with UH than
with
> LMWH, and the mean value was higher (5.66+/-0.83 versus 5.15+/-0.68 mM, p
=
> 0.01) while no differences in the predialysis plasma concentrations of
> creatinine, phosphate, urea, and bicarbonate were observed, excluding the
> potential role of differences in diet and dialysis efficacy in explaining
the
> higher plasma K+ concentration with UH. The mean plasma aldosterone to
plasma
> renin activity (pRA) ratio was higher with LMWH than with UH
(149.54+/-123.1
> versus 111.91+/-86.22 pg/ng/ h, p < 0.05). Individual plasma aldosterone
values
> were found to be correlated to pRAs both during the UH period and the LMWH
> period, and the slope of the positive linear relation between plasma
aldosterone
> and pRA was lower during the UH treatment period (63 versus 105 pg/ng/h).
> Finally, a negative linear correlation was found between the differences
in
> individual predialysis plasma K+ observed during the 2 protocols and the
> differences in the corresponding plasma aldosterone levels, suggesting a
link
> between the higher kalemia and the lower aldosterone responsiveness to
> angiotensin with unfractionated heparin. Although it cannot be concluded
whether
> or not LMWH inhibits aldosterone synthesis, _*should LMWH decrease
aldosterone
> production, this side effect is 33% less marked than that of UH so that
the
> predialysis plasma K+ levels are 10% lower. This property makes LMWH use
> preferable to that of UH in patients with elevated predialysis kalemia.*_
> 
> Publication Types:
>     Clinical Trial
>     Controlled Clinical Trial
> 
> PMID: 9684701 [PubMed - indexed for MEDLINE]
> 
> 15: QJM. 1997 Nov;90(11):725.
> 
> Comment on:
>     QJM. 1997 Jul;90(7):487-92.
> 
> Heparin-induced disturbance of potassium homeostasis.
> 
> Bacon NC.
> 
> Publication Types:
>     Comment
>     Letter
> 
> PMID: 9474355 [PubMed - indexed for MEDLINE]
> 
> 16: Lancet. 1997 Jul 26;350(9073):292-3.
> 
> Comment on:
>     Lancet. 1997 May 17;349(9063):1447-8.
> 
> Effect of low-molecular-weight heparin on serum concentrations of
potassium.
> 
> Wiggam MI, Beringer TR.
> 
> Publication Types:
>     Case Reports
>     Comment
>     Letter
> 
> PMID: 9242823 [PubMed - indexed for MEDLINE]
> 
> 17: Postgrad Med J. 1997 Jul;73(861):433-4.
> 
> Hospital-acquired hyperkalaemia.
> 
> Bacon NC.
> 
> Nuffield Department of Medicine, John Radcliffe Hospital, Oxford, UK.
> 
> Publication Types:
>     Case Reports
> 
> PMID: 9338034 [PubMed - indexed for MEDLINE]
> 
> 18: Miner Electrolyte Metab. 1997;23(1):58-61.
> 
> A case of 'reverse' pseudohyperkalemia.
> 
> Singh PJ, Zawada ET, Santella RN.
> 
> Department of Internal Medicine, University of South Dakota School of
Medicine,
> Sioux Falls 57105-1570, USA.
> 
> Pseudohyperkalemia is diagnosed when the serum potassium level exceeds the
> plasma potassium level by 0.4 mmol/l. This is commonly encountered in
settings
> of high leukocyte or platelet counts, since under these conditions,
potassium,
> an intracellular cation, is released in supranormal amounts during the
process
> of clotting. We report an unusual case wherein the reverse was true, i.e.,
the
> plasma potassium concentrations was higher than that found in the serum.
> Heparin, which is known to cause cell lysis, was used as the
anti-coagulant in
> the plasma tubes. We propose that the underlying mechanism in this
particular
> case is a heightened sensitivity to heparin-induced membrane damage in the
face
> of a hematological malignancy.
> 
> Publication Types:
>     Case Reports
> 
> PMID: 9058371 [PubMed - indexed for MEDLINE]
> 
> 19: JPEN J Parenter Enteral Nutr. 1996 Nov-Dec;20(6):429-32.
> 
> Hyperkalemia secondary to concurrent pharmacotherapy in a patient
receiving home
> parenteral nutrition.
> 
> Brown RO, Hamrick KD, Dickerson RN, Lee N, Parnell DH Jr, Kudsk KA.
> 
> Department of Clinical Pharmacy, University of Tennessee, Memphis 38163,
USA.
> 
> We report a case of probable combined octreotide- and heparin-induced
> hyperkalemia. The patient had been receiving home parenteral nutrition,
> enoxaparin, and octreotide for 10 months. She required very little
potassium in
> her PN solution to maintain serum potassium concentrations in the normal
range.
> The patient reportedly did not receive other medications or have clinical
> conditions that, to our knowledge, cause hyperkalemia. She maintained
normal
> renal function throughout the hospitalization and did not appear to have
any
> significant acid-base disorders. _*Practitioners should be aware of the
potential
> for octreotide and heparin to cause hyperkalemia*_. Regular monitoring of
serum
> potassium concentrations should be done for patients receiving octreotide
and
> heparin to avoid hyperkalemia.
> 
> Publication Types:
>     Case Reports
> 
> PMID: 8950745 [PubMed - indexed for MEDLINE]
> 
> 20: Am J Med. 1995 Jun;98(6):575-86.
> 
> Heparin-induced aldosterone suppression and hyperkalemia.
> 
> Oster JR, Singer I, Fishman LM.
> 
> Medical Service, Department of Veterans Affairs Medical Center, Miami,
Florida
> 33125, USA.
> 
> PURPOSE: To review the effects of heparin and heparinoid compounds on
> aldosterone physiology and associated induction of hyperkalemia. MATERIALS
AND
> METHODS: A comprehensive literature search (of human and animal data) was
> carried out by computer and by using reference citations from primary
sources.
> RESULTS: *_Heparin and its congeners are predictable, potent inhibitors of
> aldosterone production. This inhibitory effect is specific for the zona
> glomerulosa; other corticosteroids are not affected. Aldosterone
suppression
> occurs within a few days of initiation of therapy, is reversible, and is
> independent of either anticoagulant effect or route of administration.
Decreases
> in aldosterone levels may occur with heparin dosages as low as 5,000 U
BID. The
> most important, but probably not the only mechanism of aldosterone
inhibition
> appears to involve reduction in both the number and affinity of the
> angiotensin-II receptors in the zona glomerulosa. Prolonged use of heparin
> causes marked reduction in the width of the adrenal zona glomerulosa.
> CONCLUSIONS: Aldosterone suppression results in natriuresis and less
predictably
> in decreased excretion of potassium. Greater than normal serum potassium
levels
> occur in about 7% of patients, but marked hyperkalemia generally requires
the
> presence of additional factors perturbing potassium balance (in
particular,
> renal insufficiency, diabetes mellitus, or the use of certain
medications).
> Heparin-induced increases in serum potassium need to be better anticipated
by
> clinicians. Serum potassium levels should be monitored periodically in
patients
> being given heparin for 3 or more days, and in patients at relatively high
risk
> for hyperkalemia, the monitoring interval should probably be no greater
than 4
> days._
> *
> Publication Types:
>     Review
> 
> PMID: 7778574 [PubMed - indexed for MEDLINE]
> 
> 1: Am J Med. 1995 Jun;98(6):575-86.
> 
> Heparin-induced aldosterone suppression and hyperkalemia.
> 
> Oster JR, Singer I, Fishman LM.
> 
> Medical Service, Department of Veterans Affairs Medical Center, Miami,
Florida
> 33125, USA.
> 
> PURPOSE: To review the effects of heparin and heparinoid compounds on
> aldosterone physiology and associated induction of hyperkalemia. MATERIALS
AND
> METHODS: A comprehensive literature search (of human and animal data) was
> carried out by computer and by using reference citations from primary
sources.
> RESULTS: Heparin and its congeners are predictable, potent inhibitors of
> aldosterone production. This inhibitory effect is specific for the zona
> glomerulosa; other corticosteroids are not affected. Aldosterone
suppression
> occurs within a few days of initiation of therapy, is reversible, and is
> independent of either anticoagulant effect or route of administration.
Decreases
> in aldosterone levels may occur with heparin dosages as low as 5,000 U
BID. The
> most important, but probably not the only mechanism of aldosterone
inhibition
> appears to involve reduction in both the number and affinity of the
> angiotensin-II receptors in the zona glomerulosa. Prolonged use of heparin
> causes marked reduction in the width of the adrenal zona glomerulosa.
> CONCLUSIONS: Aldosterone suppression results in natriuresis and less
predictably
> in decreased excretion of potassium. _*Greater than normal serum potassium
levels
> occur in about 7% of patients, but marked hyperkalemia generally requires
the
> presence of additional factors perturbing potassium balance (in
particular,
> renal insufficiency, diabetes mellitus, or the use of certain
medications).
> Heparin-induced increases in serum potassium need to be better anticipated
by
> clinicians. Serum potassium levels should be monitored periodically in
patients
> being given heparin for 3 or more days, and in patients at relatively high
risk
> for hyperkalemia, the monitoring interval should probably be no greater
than 4
> days.
> *_
> Publication Types:
>     Review
> 
> PMID: 7778574 [PubMed - indexed for MEDLINE]
> 
> 2: Thromb Res. 1992 Jun 1;66(5):467-73.
> 
> Dose dependent suppression of mineralocorticoid metabolism by different
heparin
> fractions.
> 
> Siebels M, Andrassy K, Vecsei P, Seelig HP, Back T, Nawroth P, Weber E.
> 
> Department Medicine, University Hospital, Heidelberg, Germany.
> 
> One neglected side effect of heparin therapy is the inhibition of adrenal
> aldosterone production leading to occasionally life-threatening
hyperkalaemia.
> This is only reported with (therapeutic) high doses (greater than or equal
to
> 20.000 IU). The complex interplay of mineralocorticoid metabolites was
studied
> in 29 subjects with unfractionated (UFH) and low molecular weight heparin
> (LMWH). Both heparins altered mineralocorticoid metabolism in a dose
dependent
> manner. Whereas no effect was observed with UFH 2 x 5000 IU sc/day or LMWH
2500
> a FXa U sc/day, higher doses significantly suppressed aldosterone and
> 18-hydroxycorticosterone production in plasma and urine. Three out of
seven
> patients receiving UFH 3 x 7500 IU sc/day developed hyperkalaemia. This
study
> shows the _*threshold dosage of UFH leading to suppression of
mineralocorticoid
> metabolism in man and provides information that LMWH as well as UFH can
suppress
> mineralocorticoid production*_. With respect to therapeutic implications
it is
> important that LMWH at 2500 a FXa U sc/d had no effect on
mineralocorticoid
> metabolism in contrast to UFH at a dosage currently used for prevention of
> thromboembolism (3 x 5000 IU sc/d).
> 
> PMID: 1326134 [PubMed - indexed for MEDLINE]
> 
> 3: Eur J Clin Pharmacol. 1992;43(2):185-7.
> 
> A low molecular weight heparin decreases plasma aldosterone in patients
with
> primary hyperaldosteronism.
> 
> Cailleux N, Moore N, Levesque H, Courtois H, Godin M.
> 
> Department of Nephrology, CHU de Rouen, Boisguillaume, France.
> 
> Four patients with primary hyperaldosteronism were treated with nadroparin
4100
> or 6150 antiXa IU daily for 4 days. Plasma and urine sodium and potassium,
and
> plasma aldosterone and renin were monitored before, during and after the
study.
> After four days of treatment, and for the following two days, plasma
aldosterone
> was decreased (by a mean of 49% on Day 6), and urinary Na/K was increased
> (3.7-fold). The direction of the changes was reversed on Day 8. The study
has
> confirmed t_*he effect of low molecular weight heparin on aldosterone, and
makes
> it unlikely that it is related to inhibition of angiotensin II stimulation
in
> these patients, as renin could not be detected in their plasma.*_
> 
> PMID: 1330575 [PubMed - indexed for MEDLINE]
> 
> 4: Ter Arkh. 1985;57(6):78-81.
> 
> [Hypotensive and diuretic effect of heparin in patients with
glomerulonephritis]
> 
> [Article in Russian]
> 
> Kutyrina IM, Nikishova TA, Tareeva IE.
> 
> The hypotensive and diuretic properties of heparin were evaluated in 95
patients
> with different clinical and morphological varieties of chronic
> glomerulonephritis (CGN). The arterial blood pressure dropped in all the
> patients treated with heparin. The maximal effect was attained toward the
end of
> heparin treatment (by the 35th-50th day). In patients with hypertonic and
mixed
> nephritis associated with renal failure, (the glomerular filtration rate
under
> 35 ml/min), the BP lowering induced by heparin was accompanied by the
> deterioration of renal function. The diuretic and natriuretic effects were
> recorded in 81 out of the 95 patients. The maximal values of diuresis and
sodium
> excretion were detected on the 14th-16th day of the treatment during the
use of
> the maximal doses of heparin. It was established that heparin-induced
inhibition
> of aldosterone synthesis plays the key role in the genesis of the
diuretic,
> natriuretic and hypotensive action of the drug. It is concluded that
diuretic
> and hypotensive properties of heparin can be made use of in the treatment
of
> nephrological patients.
> 
> PMID: 4071420 [PubMed - indexed for MEDLINE]
> 
> 5: Acta Med Scand. 1975 Jan-Feb;197(1-2):99-108.
> 
> Inhibition of adrenal function in man by heparin or heparinoid Ro 1-8307.
> 
> Kloppenborg PW, Casparie AF, Benraad TJ, Majoor CL.
> 
> _*Heparin and the heparinoid Ro 1-8307 inhibited the secretory rate of
aldosterone
> in physiological or pathological aldosteronism to the level found in
normal
> subjects on liberal sodium intake. In addition, these compounds inhibited
> corticosterone biosynthesis, although less markedly than that of
aldosterone.
> Indications of interference with cortisol production have not been found.
During
> drug treatment angiotensin, in doses of 5-10 ng/kg b.wt./min, did not
stimulate
> aldosterone secretion. ACTH responsiveness of the adrenals--indicated by
the
> fractional increases of both aldosterone and corticosterone secretory
> rates--remained unchanged. In two studies heparin had no consistent effect
on
> plasma renin activity.*_
> 
> Publication Types:
>     Clinical Trial
>     Controlled Clinical Trial
> 
> PMID: 47702 [PubMed - indexed for MEDLINE]
> 
> 6: Metabolism. 1966 Jun;15(6):542-7.
> 
> Mechanism of heparin inhibition of adrenal steroid A ring reduction.
> 
> Troop RC, Krzanowski PT, Biggs JT Jr.
> 
> PMID: 4379864 [PubMed - indexed for MEDLINE]
> 
> 
> 
> 
> 
> 
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