Drug Induced
Kidney
Disease
Introduction
• Numerous diagnostic and therapeutic agents have
been associated with the development of druginduced kidney disease (DIKD) or nephrotoxicity.
• It is a relatively common complication with variable
presentations depending on the drug and clinical
setting, inpatient or outpatient.
Introduction
• Manifestations of DIKD include
•
•
•
•
•
acid–base abnormalities,
electrolyte imbalances
urine sediment abnormalities
proteinuria
pyuria and/or hematuria
Diagnosis
• The initial diagnosis of DIKD typically involves detection of elevated
serum creatinine and blood urea nitrogen, for which there is a
temporal relationship between the toxicity and use of a potentially
nephrotoxic drug.
Clinical Presentation
• decline in GFR leading to a rise in Scr and BUN.
• Alterations in renal tubular function without loss of
glomerular filtration may be evident.
Symptoms
• Patients may complain of malaise, anorexia, vomiting, shortness of breath, or
edema, volume overload and HTN, particularly in the outpatient setting.
Signs
• Decreased urine output may be an early sign of toxicity, particularly with
radiographic contrast media, NSAIDs, and ACEIs, with progression to volume
overload and hypertension.
• Proximal tubular injury: Metabolic acidosis with bicarbonaturia; glycosuria in
the absence of hyperglycemia; and reductions in serum phosphate, uric acid,
potassium, and magnesium due to increased urinary losses.
• Distal tubular injury: Polyuria from failure to maximally concentrate urine,
metabolic acidosis from impaired urinary acidification, and hyperkalemia
from impaired potassium excretion.
Laboratory Tests
• An abrupt (within 48 hours) reduction in kidney function defined as
an absolute increase in Scr of 0.3 mg/dL (27 mol/L),
• Percentage increase in Scr of 50% (1.5-fold from baseline),
• Reduction in urine output (documented oliguria of less than 0.5 ml/kg
per hour for more than 6 hours)]
• routine laboratory monitoring is essential for recognizing DIKD.
• Scr or BUN concentrations and urine collection for creatinine
clearance may subsequently be measured to quantify the degree of
decline in GFR.
The primary principle for
prevention of DIKD
1.
Avoid the use of nephrotoxic agents for patients at increased risk for
toxicity.
2.
Awareness of potentially nephrotoxic drugs and knowledge of risk
factors that increase renal vulnerability
3.
Adjustment of medication dosage regimens based on accurate estimates
of renal function, and careful and adequate hydration to establish high
urine flow rates
4.
Other preventative strategies are still theoretical and/or investigational
and relate directly to the specific nephrotoxic mechanisms of a given
drug.
Acute Tubular Necrosis (ATN)
1. Aminoglycoside Nephrotoxicity
Clinical presentation:
• Gradual progressive rise in Scr and BUN and decrease in creatinine
clearance.
• Patients usually present with nonoliguria, i.e., they maintain urine volumes
greater than 500 mL/day and sometimes have microscopic hematuria and
proteinuria.
• Hypomagnesemia
Aminoglycoside Nephrotoxicity
• Full recovery of renal function is common if aminoglycoside therapy
is discontinued immediately upon discovering signs of toxicity.
• severe AKI may develop occasionally, and for these individuals renal
replacement therapy may be required
• The diagnosis of aminoglycoside-associated nephrotoxicity is often
difficult, particularly in critically ill patients with multiple
comorbidities and is confounded by other factors that are
independently associated with the development of AKI
• For instance, concurrent dehydration, sepsis, hypotension, ischemia,
and use of other nephrotoxic drugs frequently contribute to AKI in
patients who are receiving aminoglycosides.
Aminoglycoside Nephrotoxicity
Risk factors
Aminoglycoside Nephrotoxicity
Management
• Aminoglycoside use should be discontinued or the dosage regimen revised
if AKI is evident
• [i.e., Scr increase of 0.5 mg/dL (44 mol/L) or more that is not
attributable to another cause]
• Other nephrotoxic drugs should be discontinued if possible
• The patient should be maintained adequately hydrated and
hemodynamically stable.
• Short-term renal replacement therapy may be necessary, but ESRD has
rarely been reported to be solely the result of aminoglycoside toxicity.
2. Radiographic Contrast Media Nephrotoxicity
• CIN is usually transient in nature
• presenting most commonly as non-oliguria with kidney injury
apparent within the first 24 to 48 hours after the
administration of contrast.
• The Scr concentration usually peaks between 3 and 5 days after
exposure, with recovery after 7 to 10 days.
• The urine sodium concentration and fractional excretion of
sodium are frequently low, with the latter typically <1%
(<0.01).
Radiographic Contrast Media Nephrotoxicity
Risk Factors
• Decreased renal blood flow
• Preexisting kidney disease, GFR <60 mL/min/1.73 m2
• patients' specific risk factors
• Congestive heart failure, dehydration/volume depletion, and hypotension.
• Atherosclerosis and reduced effective circulating arterial blood volume
• Diabetes (diabetic nephropathy).
• Larger volumes or doses of contrast and use of low- and high-osmolar contrast
agents
•
• Intraarterial administration of contrast confers greater risk than intravenous
administration.
• concurrent use of nephrotoxins and drugs that alter renal hemodynamics such as
NSAIDs and ACEIs also increases risk.
Radiographic Contrast Media Nephrotoxicity
Management
• Currently there is no specific therapy
• Supportive care
• Monitor Renal function (e.g., Scr, urine output),
electrolytes (e.g., sodium, potassium), and volume
status closely
• renal replacement therapy should be used as
indicated and needed
3. Amphotericin B Nephrotoxicity
• Dose-dependent nephrotoxicity is often evident after administration of
cumulative doses of 2 to 3 g as nonoliguria, renal tubular potassium, sodium, and
magnesium wasting, impaired urinary concentrating ability, and distal renal
tubular acidosis.
• Time to onset of kidney injury varies, ranging from a few days to weeks.
• Tubular dysfunction usually manifests 1 to 2 weeks after treatment is begun
• Potassium and magnesium replacement may be necessary
• Renal function should be closely monitored
Amphotericin B Nephrotoxicity
Risk Factors
1.
2.
3.
4.
5.
6.
7.
preexisting kidney disease,
large individual and cumulative doses
short infusion times
volume depletion
hypokalemia,
increased age,
concomitant administration of diuretics and other
nephrotoxins (cyclosporine in particular)
Amphotericin B Nephrotoxicity
Management
1.
discontinuation of therapy and substitution of alternative antifungal
therapy, if possible.
2.
Renal tubular dysfunction and glomerular filtration will improve
gradually to some degree in most patients, but damage may be
irreversible.
3.
Renal function indices should be closely followed, with Scr and BUN
concentrations checked daily, and serum magnesium, potassium, and
calcium concentrations should be monitored daily and corrected as
needed.
Hemodynamically Mediated Kidney Injury
1. ACEIs and ARBs
• Therapy with ACEIs and ARBs will acutely reduce GFR; so a
moderate rise in Scr after initiation of therapy should be
anticipated.
• An increase in Scr of up to 30% is commonly observed within 3
to 5 days of initiating therapy and is an indication that the drug
has begun to exert its desired pharmacologic effect.
• The increase in Scr typically stabilizes within 1 to 2 weeks and is
usually reversible upon stopping the drug.
ACEIs and ARBs
Pathogenesis
ACEI- or ARB-mediated kidney injury is the result of a decrease in glomerular
capillary hydrostatic pressure sufficient to reduce glomerular ultrafiltration.
• Normally, the kidney attempts to maintain GFR by dilating the afferent
arteriole and constricting the efferent arteriole in response to a decrease in
renal blood flow.
• During states of reduced blood flow, the juxtaglomerular apparatus
increases renin secretion. Plasma renin converts angiotensinogen to
angiotensin I, and ultimately angiotensin II by angiotensin-converting
enzyme. Angiotensin II constricts the afferent and efferent arterioles, but
has a greater effect on the efferent arterioles, resulting in a net increase in
intraglomerular pressure.
• Additionally, renal prostaglandins, prostaglandin E2 in particular, are
released and induce a net dilation of the afferent arteriole, thereby
improving blood flow into the glomerulus.
• Together these processes maintain GFR and urine output
ACEIs and ARBs
ACEIs and ARBs
• When ACEI therapy (e.g., enalapril or ramipril) is initiated, the synthesis of
angiotensin II is decreased, thereby preferentially dilating the efferent arteriole.
• This reduces outflow resistance from the glomerulus and decreases hydrostatic
pressure in the glomerular capillaries, which alters Starling forces across the
glomerular capillaries to decrease intraglomerular pressure and GFR and then
often leads to nephrotoxicity.
ACEIs and ARBs
ACEIs and ARBs
Risk Factors
• Patients with bilateral renal artery stenosis or stenosis in a single kidney
(i.e., renal transplant)
• Patients with decreased effective arterial blood volume (i.e., prerenal
states), especially those with congestive heart failure, volume depletion
from excess diuresis or gastrointestinal fluid loss, hepatic cirrhosis with
ascites, and nephrotic syndrome
• Patients with preexisting kidney disease
• Patients receiving concurrent nephrotoxic drugs
ACEIs and ARBs
Prevention
1.
Recognizing the presence of preexisting kidney disease and other diseases.
2.
Initiate therapy with very low doses of a short-acting ACEI (e.g., captopril 6.25 mg to 12.5 mg), then
gradually titrate the dose upward and convert to a longer-acting agent after patient tolerance has been
demonstrated.
3.
Outpatients may be started on low doses of long-acting ACEIs (e.g., enalapril 2.5 mg) with gradual dose
titration every 2 to 4 weeks until the maximum dose or desired response is achieved.
4.
Renal function indices and serum potassium concentrations must be monitored carefully, daily for
hospitalized patients and every 2 to 3 days for outpatients.
5.
Use of concurrent hypotensive agents and other drugs that affect renal hemodynamics (e.g., NSAIDs,
diuretics) should be discouraged and dehydration avoided.
ACEIs and ARBs
Management
• Acute decreases in renal function and the development of hyperkalemia
usually resolve over several days after ACEI or ARB therapy is discontinued.
• Occasionally patients will require management of severe hyperkalemia.
• ACEI or ARB therapy may frequently be reinitiated, particularly for patients
with congestive heart failure, after intravascular volume depletion has been
corrected or diuretic doses reduced.
• Slight reductions in renal function [maintenance of a Scr concentration of 2
to 3 mg/dL (177 to 265 mol/L)] may be an acceptable trade-off for
hemodynamic improvement in certain patients with severe congestive
heart failure or renovascular disease not amenable to revascularization.77
2. NSAIDs and Selective COX-2 Inhibitors
• AKI can occur within days of initiating therapy, particularly with a
short-acting agent such as ibuprofen, or within days of some other
precipitating event (e.g., intravascular volume depletion).
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•
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Diminished urine output,
weight gain, and/or edema.
Urine sodium concentrations [<20 mEq/L (<20 mmol/L)]
fractional excretion of sodium [<1% (0.01)] are usually low
Elevated BUN, Scr, potassium, and blood pressure
NSAIDs and Selective COX-2 Inhibitors
Risk Factors
• age >60 years,
• preexisting kidney disease
• hepatic disease with ascites
• congestive heart failure
• intravascular volume depletion/dehydration,
• concurrent diuretic therapy
• or systemic lupus erythematosus.
 Combined use of NSAIDs or COX-2 inhibitors and concurrent nephrotoxic
drugs, particularly other drugs that affect intraglomerular autoregulation
should be avoided in high-risk patients.11
NSAIDs and Selective COX-2 Inhibitors
Management
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•
•
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Discontinuation of therapy
Supportive care.
Kidney injury is rarely severe, and recovery is usually rapid.
Occasionally, the hemodynamic insult is sufficiently severe to
cause atn, which can prolong injury.24
Drug Induced
Liver
Disease
Introduction
• The number of drugs associated with adverse reactions involving the liver is
extensive
• Alcohol-induced liver disease is the most common type of drug-induced liver
disease.
• All other drugs together account for less than 10% of patients hospitalized for
elevated liver enzymes.
• Drug-induced liver disease accounts for as much as 20% of acute liver failure in
pediatric populations and at least that many of adults with acute liver failure.
• In approximately 75% of these cases, liver transplantation is ultimately required
for patient survival.
• Of patients who required liver transplantation according to the United Network
for Organ Sharing, acetaminophen, isoniazid, antiepileptics, and antibiotics
collectively account for just over 60% of cases.
Risk Factors of DILI
• adults are at higher risk than children (with the notable exception
of DILI from valproic acid, which is more common in children).
• Women may be more susceptible than men, which may in part be
due to their generally smaller size
• Alcohol abuse
• malnutrition in some cases, as is seen with acetaminophen toxicity
The National Institutes of Health (NIH) maintains a searchable
database of drugs, herbal medications, and dietary supplements
that have been associated with DILI
CLASSIFICATION
Drug-induced liver injury (DILI) can be classified in several ways, including:
• Clinical presentation:
• Hepatocellular (cytotoxic) injury
• Cholestatic injury
• Mixed injury
• Mechanism of hepatotoxicity:
• Predictable
• Idiosyncratic
• Histologic findings, such as:
• Hepatitis
• Cholestasis
• Steatosis
• Typically, DILI is initially categorized based on its clinical presentation. If a liver
biopsy is required to make the diagnosis or assess the degree of damage, DILI can
then be further categorized based on its histologic findings
Clinical presentation
• DILI is often characterized by the type of hepatic injury. The type of injury is reflected by the pattern of liver
test abnormalities
Hepatocellular injury (hepatitis):
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•
•
Disproportionate elevation in the serum aminotransferases compared with the alkaline phosphatase
Serum bilirubin may be elevated
Tests of synthetic function may be abnormal
Cholestatic injury (cholestasis):
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•
•
Disproportionate elevation in the alkaline phosphatase compared with the serum aminotransferases
Serum bilirubin may be elevated
Tests of synthetic function may be abnormal
• DILI is considered acute if the liver tests have been abnormal for less than three months and chronic if they
have been abnormal for more than three months
CLINICAL MANIFESTATIONS
Acute presentations of drug-induced liver injury (DILI) include
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•
•
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mild asymptomatic liver test abnormalities
cholestasis with pruritus
an acute illness with jaundice that resembles viral hepatitis
acute liver failure
Chronic liver injury can resemble other causes of chronic liver disease, such as
•
•
•
•
autoimmune hepatitis
primary biliary cirrhosis
sclerosing cholangitis
alcoholic liver disease.
• In some patients, chronic injury secondary to DILI progresses to
cirrhosis.
• The presence of jaundice (serum bilirubin >2 times the ULN) in
association with an elevation in serum aminotransferases (>3
times the ULN) is associated with a worse prognosis
Symptoms and examination findings
• Many are asymptomatic and only detected because of laboratory
testing.
• Acute DILI may develop
• Malaise, low-grade fever, anorexia, nausea, vomiting,
• Right upper quadrant pain, jaundice, acholic stools, or dark urine.
• Hepatomegaly may be present on physical examination.
• In severe cases, coagulopathy and hepatic encephalopathy, indicating
acute liver failure
•
Chronic DILI may develop
• Significant fibrosis or cirrhosis
• Signs and symptoms of decompensation (eg, jaundice, palmar
erythema, and ascites
• Hypersensitivity reactions
• other organs toxicity (eg, bone marrow, kidney, lung, skin, and blood
vessels)
Management
• The primary treatment is withdrawal of the offending drug.
• Early recognition of drug toxicity and monitoring for acute liver
failure.
• Few specific therapies have been shown to be beneficial in
clinical trials.
• Two exceptions are
• N- acetylcysteine for acetaminophen toxicity.
• L-carnitine for cases of valproic acid overdose
• Glucocorticoids are of unproven benefit for most forms of drug
hepatotoxicity, although they may have a role for treating
patients with hypersensitivity reactions
• Give glucocorticoids to patients with
• hypersensitivity reactions who have progressive cholestasis
despite drug withdrawal or who have biopsy features that
resemble those seen in autoimmune hepatitis.
• Extrahepatic manifestations of a hypersensitivity reaction
that warrant glucocorticoid treatment (eg, severe
pulmonary involvement in patients with DRESS [drug
reaction with eosinophilia and systemic symptoms])
PROGNOSIS
•Acute liver injury
• The majority of patients will experience complete recovery once the offending
medication is stopped.
• In the setting of cholestatic injury, jaundice can take weeks to months to resolve.
• Factors associated with a poorer prognosis in patients with hepatocellular
injury include:
• The development of jaundice (bilirubin >2 times ULN) in the setting of ALT >3 times
ULN)
• Acute liver failure due to antiepileptics in children
• Acute liver failure due to acetaminophen requiring hemodialysis
• An elevated serum creatinine
• Chronic liver injury
• generally resolves upon discontinuation of the offending
drug, but this pattern of liver injury may progress to
cirrhosis and liver failure.
• Cholestasis can be prolonged, requiring several months (>3
months) to resolve
• A progression to chronic disease is reported to occur in
approximately 5 to 10 percent of adverse drug reactions
and is more common among the cholestatic/mixed types of
injury
Drug Induced
Hematologic
Disease
Introduction
 Can be :
 Predictable hematologic disease (e.g., antineoplastics), or
 Idiosyncratic reactions which is not directly related to the drugs’
pharmacology.
 Drug-induced hematologic disorders are generally rare adverse
effects associated with drug therapy.
 Reporting during postmarketing surveillance of a drug is usually the
method by which the incidence of rare adverse drug reactions is
established.
 Because drug-induced blood disorders are potentially dangerous,
rechallenging a patient with a suspected agent in an attempt to
confirm a diagnosis may not be ethical.
Drugs may produce hematologic toxicity by
one of three general mechanisms:
1) Direct drug (or a metabolite) toxicity
2) Toxicity due to a drug effect on a genetic
abnormality in the bone marrow
3) Toxicity involving immune mechanisms.
The most common drug-induced hematologic
disorders include
1) Agranulocytosis or leukopenia (loss of the white blood
cells)
2) Aplastic anemia (loss of all the formed elements of the
blood)
3) Thrombocytopenia (loss of the platelets)
4) Hemolytic anemia (loss of the red blood cells).
 The incidence of these adverse hematologic drug reactions,
the relative importance of various etiologic chemicals, and
their resultant morbidity and mortality vary.
Drugs Induced Agranulocytosis (Leukopenia)
 Defined as a reduction in the number of granulocytes to
≤500 cells/mm3.
 Drug-induced agranulocytosis is classified as Type 1 (due to
an immune mechanism) and Type II (drug effect on bone
marrow DNA synthesis).
 In Type I reactions, blood immunoglobins are directed
against drug-related antigens located on circulating
leukocytes.
Table: Drugs Associated with Agranulocytosis
• Occurs most commonly in females and the elderly
(i.e. >60 years of age),
• Has an estimated annual incidence of 1.1 to 12
cases per million population.
• overall mortality rate of agranulocytosis is estimated
to be 3.5% to 16%.
• Mortality rate is highest among the elderly and
patients with renal failure, bacteremia, or shock at
the time of diagnosis.
Clinical Presentation
• Sore throat, fever, malaise, weakness, chills, and other signs
and symptoms of infection.
• Onset: can appear rapidly, within days to weeks after the
initiation of the offending drug.
• But the time to onset is >1 month for most of these agents
• Median duration of exposure prior to the development of
agranulocytosis ranges from 19 to 60 days for most drugs.
Management
• Removal of the offending drug.
• Most cases of neutropenia resolve over time.
• Symptomatic treatment (e.g., antimicrobials for
infections) and appropriate vigilant hygiene practices
are necessary.
• Sargramostim (GM-CSF 300 mcg/day sc) and
filgrastim (G-CSF) can be used.
DRUG-INDUCED APLASTIC ANEMIA
• First described by Ehrlich in 1888.
• It is a rare, serious disease of unclear etiology.
• An incidence of two to seven cases per million
inhabitants reported.
• This incidence is different in different regions.
• The young and elderly are at increased risk.
• It is characterized by pancytopenia.
• It is considered the most serious drug-induced blood
dyscrasia.
Drugs Suspected of Inducing Aplastic Anemia
• Severe aplastic anemia is seen with a bone marrow of less
than 25% of normal cellularity or a bone marrow of less than
50% of normal cellularity with less than 30% of the
hematopoietic cells and at least two of the following
peripheral blood values:
• 1) granulocytes fewer than 500/mm3
• 2) platelets fewer than 20,000/mm3
• 3) anemia with reticulocytes fewer than 1%.
• About 65% of people with aplastic anemia die within 4
months of diagnosis; few die after this 4-month period
Drugs Associated with Aplastic Anemias
Management
• Remove the suspected offending agent.
• Then provide adequate supportive care;
• Appropriate antimicrobial therapy for the treatment
of infection
• Transfusion support with erythrocytes and
platelets.
• Do not include chemoprophylaxis, except in patients
undergoing allogeneic hematopoietic stem cell
• transplantation (HSCT).
• Fever of unknown origin should be initially managed with
broad-spectrum antibiotics.
If treatment is required;
 The two major treatment options are
 Allogeneic HSCT – Rx of choice for young pts.
 Immunosuppressive therapy- Tends to be first-line therapy
for older patients and those who are not candidates for
HSCT.
Combination therapy with antithymocyte
globulin (ATG) and cyclosporine.
Cyclosporine monotherapy
Corticosteroids are sometimes added to ATGbased immunosuppression.
Drug Induced Thrombocytopenia
• Drug-induced immune thrombocytopenia is characterized by
acute purpura, confluent petechiae or ecchy-mosesparticularly after mild trauma-and gastrointestinal, central
nervous system, or urinary tract bleeding,all associated with a
mild or severe lack of blood platelets.
• Drugs may induce marrow hypoplasia, destroy platelets
directly, or be responsible for an immune reaction.
Thrombocytopenia may be associated with several disease
states (acute leukemia, Gaucher's disease, systemic lupus
erythematosus, sarcoidosis); drug-induced thrombocytopenia
usually remits 1 to 2 weeks after drug discontinuance.
• is usually defined as a platelet count below 100,000
cells/mm3 or >50% reduction from baseline values.
• The annual incidence of drug-induced
thrombocytopenia is approximately 10 cases per
1,000,000 population.
Drugs Associated with Thrombocytopenia
Mechanisms
• Direct toxicity reactions,
Result in suppressed thrombopoiesis and produce
a decrease in the number of megakaryocytes in
the bone marrow.
Mostly by cancer chemotherapy agents,
 often by organic solvents, pesticides, drugs that
influence folic acid metabolism, and inamrinone.
• Hapten type immune reactions – eg. heparin induced
reaction.
Mechanisms cont….
• Platelet-reactive auto antibodies
• Gold compounds and procainamide
• The causative drug does not have to be present for
the reaction to occur.
• Drug dependent antibodies
• Requires the presence of the drug to allow
antibody binding.
DRUG-INDUCED HEMOLYTIC ANEMIA
• Causes: defective RBCs or abnormal changes in the
intravascular environment.
• Mechanisms: immune or metabolic.
• The onset of drug-induced hemolytic anemia is
variable and depends on the drug and mechanism of
the hemolysis.
Drugs Associated with Hemolytic Anemia
DRUG-INDUCEDIMMUNE HEMOLYTIC ANEMIA
• Best diagnosed by Coombs test:
• Direct (or direct antiglobulin test [DAT])- involves
combining the patient’s RBCs with the antiglobulin serum.
• Indirect - combining the patient’s serum with normal RBCs,
then subjecting them to the direct Coombs test.
• Mechanisms: hapten mediated, innocent bystanders,
autoimmune.
• Eg. Streptomycin, sulfonamides, semi synthetic penicillines.
• Rx: withdrawal,
immunoglobulin.
supportive,
steroids,
rituximab,
DRUG-INDUCED OXIDATIVE HEMOLYTIC ANEMIA
 Most often accompanies a glucose-6-phosphate dehydrogenase
(G6PD) enzyme deficiency.
NADPH in RBCs keeps glutathione in a reduced state.
Reduced glutathione is a substrate for glutathione peroxidase
 An enzyme that removes peroxide from RBCs, thus
protecting them from oxidative stress.
 Without reduced glutathione, oxidative drugs can oxidize the
sulfhydryl groups of hemoglobin, removing them prematurely
from the circulation (i.e., causing hemolysis).
 Rx: removal and avoidance of offending agents.
DRUG-INDUCED MEGALOBLASTIC ANEMIA
• In this case the development of RBC precursors called
megaloblasts in the bone marrow is abnormal.
• May be due to the direct or indirect effects of the
drug on DNA synthesis.
• Antimetabolite class of chemotherapeutic agents is
most frequently associated with it.
• Other drugs are cotrimoxazole, phenytoin, or the
barbiturates.
Management
• The anemia becomes an accepted side effect of
therapy if it is due to chemotherapy
• Folinic acid 5 to 10mg qid if it is due to SMX-TMP.
• Folic acid supplementation of 1 mg every day if it is
due to antiepileptic agents (phenytoin, phenobarb).
Drugs Associated with Oxidative Hemolytic Anemia
Drugs Associated with Megaloblastic
Anemia
Heparin –induced thrombocytopenia
• At least two types:
• HIT Type I- most common, occurs in approximately
10% to 20% of patients treated with heparin.
• It is a mild, reversible, nonimmunemediated
reaction that usually occurs within the first 2
days of therapy.
• Is usually an asymptomatic condition and is
thought to be related to platelet
aggregation.
HIT cont….
 HIT type II- is less common but more severe and can
be associated with more complications.
 Approximately 1 to 5% of patients receiving
unfractionated heparin and up to 0.8% of patients
receiving lowmolecular- weight heparin (LMWH) can
develop HIT.
 The platelet count generally begins to decline 5 to 10
days after the start of heparin therapy.
 patients who have had recent, major surgery are one of
the highest risk groups
Causes of HIT
• HIT is caused by the development of antibodies against platelet
factor-4 (PF-4) and heparin complexes.
• LMWHs bind less well to PF-4 than unfractionated heparin, and
therefore antibody formation is less common.
• Thrombosis is one of the major complications of
HIT…..anticoagulants needed.
• Less common complications are heparin-induced skin necrosis
and venous gangrene of the limbs.
• RX: Remove heparin, symptomatic rx, steroids???
Thank You!