Y6S2 - Internal Medicine (Hypertension + Hemolytic Anemia)
Hypertension & Hemolytic Anemia Quiz
Test your knowledge on hypertension and hemolytic anemia with our comprehensive quiz designed for veterinary professionals! This quiz covers essential topics such as secondary hypertension, target organ damage, and immune-mediated hemolytic anemia in both dogs and cats.
Prepare to challenge yourself with an array of questions, including:
- Causes of hypertension
- Management strategies in dogs and cats
- Infectious causes of hemolytic anemia
What are the categories of hypertension?
Type I Hypertension
Type II Hypertension
Situational Hypertension
Terminal Hypertension
Regenerative Hypertention
Secondary Hypertension
Pre-Hypertension
Idiopathic Hypertension
Iatrogenic Hypertension
Stage 1 to 4 Hypertension
Situational hypertension = increases in BP that occur as a consequence of the in-clinic measurement process in an otherwise normotensive animal.
- Caused by autonomic nervous system alterations that arise from the effects of excitement or anxiety on higher centers of the central nervous system
- Resolves under conditions that decrease or eliminate the physiologic stimulus (altering measurement conditions to decrease the animal's anxiety and measuring BP in the animal's home environment)
Secondary hypertension = persistent, pathologically increased BP concurrent with a disease or condition known to cause hypertension, or hypertension associated with the administration of a drug or ingestion of a toxic substance.
- May persist despite effective treatment of the primary condition and BP may increase after treatment is initiated
- Presence of a condition known to cause secondary hypertension, even if effectively resolved by therapeutic intervention, should prompt serial follow-up evaluation
Idiopathic hypertension = persistent pathological hypertension in the absence of any identifiable underlying cause and represents a complex multifactorial disorder involving genetic, lifestyle, and environmental factors.
Situational hypertension = increases in BP that occur as a consequence of the in-clinic measurement process in an otherwise normotensive animal.
- Caused by autonomic nervous system alterations that arise from the effects of excitement or anxiety on higher centers of the central nervous system
- Resolves under conditions that decrease or eliminate the physiologic stimulus (altering measurement conditions to decrease the animal's anxiety and measuring BP in the animal's home environment)
Secondary hypertension = persistent, pathologically increased BP concurrent with a disease or condition known to cause hypertension, or hypertension associated with the administration of a drug or ingestion of a toxic substance.
- May persist despite effective treatment of the primary condition and BP may increase after treatment is initiated
- Presence of a condition known to cause secondary hypertension, even if effectively resolved by therapeutic intervention, should prompt serial follow-up evaluation
Idiopathic hypertension = persistent pathological hypertension in the absence of any identifiable underlying cause and represents a complex multifactorial disorder involving genetic, lifestyle, and environmental factors.
Possible causes for a Secondary hypertention:
Hyperthyroidism in dogs
Diabetes mellitus
Obesity
Glucocorticoids
Cocaine
Diazepam
DOGS:
- Chronic kidney disease (9-93%)
- Acute kidney disease (15-87%)
- Hyperadrenocorticism (naturally occurring or iatrogenic) (20-80%)
- Diabetes mellitus (24-67%)
- Obesity
- Primary hyperaldosteronism
- Pheochromocytoma (43-86%)
- Hypothyroidism
- Brachycephalic
CATS:
- Chronic kidney disease (19-65%)
- Diabetes mellitus (0-15%)
- Hypothyroidism (5-87%)
- Obesity
- Primary hyperaldosteronism (50-100%)
- Pheochromocytoma
- Hyperadrenocorticism
DOGS:
- Chronic kidney disease (9-93%)
- Acute kidney disease (15-87%)
- Hyperadrenocorticism (naturally occurring or iatrogenic) (20-80%)
- Diabetes mellitus (24-67%)
- Obesity
- Primary hyperaldosteronism
- Pheochromocytoma (43-86%)
- Hypothyroidism
- Brachycephalic
CATS:
- Chronic kidney disease (19-65%)
- Diabetes mellitus (0-15%)
- Hypothyroidism (5-87%)
- Obesity
- Primary hyperaldosteronism (50-100%)
- Pheochromocytoma
- Hyperadrenocorticism
What are the tissues affected by Target Organ Damage?
Liver
Kidneys
Lungs
Heart
Blood vessels
Nerves
Eyes
Spleen
Brain
Spinal cord
Skin
Esophagus
Management of Hypertension in DOGS can be made with:
Monotherapy of CCB
Alpha- and beta-adrenergic blockers for hypertension associated with pheochromocytoma
Diuretics in CKD affected dogs
RAAS inhibitors and calcium channel blockers
Tylenol
Telmisartan
Azithromycin
Enalapril
Vicodin
Aldosterone antagonists
Management of hypertension in dogs:
Antihypertensive treatment should be individualized to the patient, based on animal's concurrent conditions, with a therapeutic goal of decreasing likelihood of future TOD (decreasing SBP by at least 1 SBP substage).
In most dogs, hypertension = not an emergency and SBP decreased gradually over several weeks.
Certain disease conditions may be best addressed using specific classes of agents:
- alpha- + beta-adrenergic blockers for HT associated with pheochromocytoma
- aldosterone receptor blockers for HT because of adrenal tumors associated with hyperaldosteronism
Otherwise, RAAS inhibitors and calcium channel blockers (CCB) = most widely recommended antihypertensive agents for use in dogs
- Because of antiproteinuric effect + high prevalence of CKD in hypertensive dogs, RAAS inhibitors = often 1st-line antihypertensive agents in dogs
- In dogs with CKD, clinically relevant decrease in proteinuria (UPC ratio decreased by ≥50%, preferably to <0.5) = 2ary goal of antihypertensive TT
- Available RAAS inhibitors = ACEi, ARB, and aldosterone antagonists, but most clinical experience = with ACEi
- ACEi (0.5-2.0 mg enalapril or benazepril/ kg PO q12h) = usually recommended as initial drug of choice in a hypertensive dog.
- ARB (1.0 mg telmisartan/kg PO q24h) = alternative method for RAAS inhibition
- Exception to use of a RAAS inhibitor as initial, sole agent, TT = severely hypertensive dogs (SBP > 200 mm Hg) => initial coadministration of a RAAS inhibitor + CCB (0.1-0.5 mg/kg amlodipine PO q24h) is appropriate
- Use of CCB as monotherapy in dogs should be avoided because CCB preferentially dilate renal afferent arteriole potentially exposing glomerulus to damaging increases in glomerular capillary hydrostatic pressure
- Because ACEi and ARBs preferentially dilate the renal efferent arteriole, coadministration of a RAAS inhibitor + CCB = have a limited effect on glomerular capillary hydrostatic pressures
If an antihypertensive regimen is ineffective = increase the dosage of currently used agents or add an alternative agent.
Diuretics = not first-choice, particularly given the prevalence of CKD in hypertensive dogs and adverse consequences of diuretic-induced dehydration and volume depletion in this setting.
- Diuretics can be considered in small subset of hypertensive animals in which volume expansion is clinically apparent (eg, those with edema).
Antihypertensive agents in general, and RAAS inhibitors in particular, should be used with caution in dehydrated dogs in which GFR may decrease precipitously with their use.
Unless severe hypertension with rapidly progressive TOD is present, these patients should be carefully rehydrated and then re-evaluated before instituting antihypertensive treatment.
Management of hypertension in dogs:
Antihypertensive treatment should be individualized to the patient, based on animal's concurrent conditions, with a therapeutic goal of decreasing likelihood of future TOD (decreasing SBP by at least 1 SBP substage).
In most dogs, hypertension = not an emergency and SBP decreased gradually over several weeks.
Certain disease conditions may be best addressed using specific classes of agents:
- alpha- + beta-adrenergic blockers for HT associated with pheochromocytoma
- aldosterone receptor blockers for HT because of adrenal tumors associated with hyperaldosteronism
Otherwise, RAAS inhibitors and calcium channel blockers (CCB) = most widely recommended antihypertensive agents for use in dogs
- Because of antiproteinuric effect + high prevalence of CKD in hypertensive dogs, RAAS inhibitors = often 1st-line antihypertensive agents in dogs
- In dogs with CKD, clinically relevant decrease in proteinuria (UPC ratio decreased by ≥50%, preferably to <0.5) = 2ary goal of antihypertensive TT
- Available RAAS inhibitors = ACEi, ARB, and aldosterone antagonists, but most clinical experience = with ACEi
- ACEi (0.5-2.0 mg enalapril or benazepril/ kg PO q12h) = usually recommended as initial drug of choice in a hypertensive dog.
- ARB (1.0 mg telmisartan/kg PO q24h) = alternative method for RAAS inhibition
- Exception to use of a RAAS inhibitor as initial, sole agent, TT = severely hypertensive dogs (SBP > 200 mm Hg) => initial coadministration of a RAAS inhibitor + CCB (0.1-0.5 mg/kg amlodipine PO q24h) is appropriate
- Use of CCB as monotherapy in dogs should be avoided because CCB preferentially dilate renal afferent arteriole potentially exposing glomerulus to damaging increases in glomerular capillary hydrostatic pressure
- Because ACEi and ARBs preferentially dilate the renal efferent arteriole, coadministration of a RAAS inhibitor + CCB = have a limited effect on glomerular capillary hydrostatic pressures
If an antihypertensive regimen is ineffective = increase the dosage of currently used agents or add an alternative agent.
Diuretics = not first-choice, particularly given the prevalence of CKD in hypertensive dogs and adverse consequences of diuretic-induced dehydration and volume depletion in this setting.
- Diuretics can be considered in small subset of hypertensive animals in which volume expansion is clinically apparent (eg, those with edema).
Antihypertensive agents in general, and RAAS inhibitors in particular, should be used with caution in dehydrated dogs in which GFR may decrease precipitously with their use.
Unless severe hypertension with rapidly progressive TOD is present, these patients should be carefully rehydrated and then re-evaluated before instituting antihypertensive treatment.
Management of Hypertension in CATS can be made with:
ACEi as first-line agent
CCB
Angiotensin converting enzyme inhibitors + ARB in dehydrated cats
Management of hypertension in CATS:
CCB (amlodipine besylate) = first choice for antihypertensive treatment because of established efficacy in cats with idiopathic hypertension or in those with CKD.
- Transdermal application = efficacy of this route of administration has not been established, PO administration = preferred route of administration.
- Adverse effects of amlodipine: peripheral edema + gingival hyperplasia = uncommon in cats
- Despite dramatic efficacy, amlodipine besylate = no increased survival time in hypertensive cats
- For cats with systemic hypertension and hyperthyroidism, amlodipine besylate = 1st-line antihypertensive agent, combined with management of hyperthyroidism
Key predictive factor in survival of hypertensive cats = proteinuria
- Significant decrease in proteinuria = identified in cats either borderline proteinuric or proteinuric when treated with CCB
- However, combined use of amlodipine + ACEi or amlodipine + ARB = reportedly well tolerated
- Nevertheless, based on potential for proteinuria to contribute to progression of renal disease in cats and its association with survival of cats with CKD = antiproteinuric treatment should be considered in this situation
Telmisartan = ARB for TT of feline proteinuria due to CKD.
- Efficacy of telmisartan in severely hypertensive cats and with overt ocular and CNS hypertensive TOD = not demonstrated
- Combination of amlodipine besylate + telmisartan = well tolerated in cats
ACEi in cats as a 1st-line antihypertensive agent = not recommended.
- Benazepril = used in cats that require a 2nd antihypertensive agent and, clinically, combination of ACEi + amlodipine besylate = well tolerated
Angiotensin converting enzyme inhibitors + ARB = dilate renal efferent arteriole thereby decreasing intraglomerular pressure and magnitude of proteinuria.
- 2ary consequence of efferent arteriolar dilatation = theoretical tendency for GFR to decrease
- Potential for acute exacerbation of azotemia with concurrent ACEi and ARB => careful monitoring = recommended
- Not started in dehydrated cats in which GFR may decrease precipitously => carefully rehydrated and then re-evaluated before instituting ACEi or ARB TT
Diuretics = not routinely used as antihypertensive agents in cats
Beta-blockers (atenolol) = useful to control heart rate in some tachycardic hypertensive cats (with hyperthyroidism), but negligible antihypertensive effect => NOT used as a sole agent for the management of hypertension
Vasodilator drugs (hydralazine) = rarely required for management of hypertension in cats, but they have historically been useful in emergency situations
In cats with primary hyperaldosteronism, management with aldosterone antagonists (spironolactone), potassium supplementation, and adrenalectomy (if feasible) = necessary
- However, antihypertensive TT with amlodipine besylate = often required for adequate BP control and should be started concurrently
- Medical combination TT can be utilized in long term for management of patients with primary hyperaldosteronism and hypertension when no surgery
- Facial dermatitis and excoriation = rare adverse effect of spironolactone in cats
- Limited information is available about the effect of adrenalectomy on ongoing requirements for antihypertensive TT in cats with primary hyperaldosteronism
- Some individual affected cats have not required TT with amlodipine besylate postoperatively
- If another, nonadrenal, concurrent disease (such as CKD) was present and contributing to the pathogenesis of hypertension in an individual cat, adrenalectomy alone would not be expected to resolve systemic hypertension.
- In such case, ongoing antihypertensive management with amlodipine besylate would be required
- Careful monitoring of BP therefore is recommended in the peri- and post-operative period in cats with primary aldosteronism treated with adrenalectomy
Pheochromocytoma = rarely reported in the cat.
- Combination TT with phenoxybenzamine, α1- and α2- adrenergic blocker, and amlodipine besylate, may be required to adequately control BP
- For cats with tachyarrhythmias, beta-adrenergic blocker (atenolol) treatment = only added after α-adrenergic blockade
- For cats undergoing adrenalectomy, careful BP monitoring is required in postop period, as persistent hypertension or hypotension may occur
Management of hypertension in CATS:
CCB (amlodipine besylate) = first choice for antihypertensive treatment because of established efficacy in cats with idiopathic hypertension or in those with CKD.
- Transdermal application = efficacy of this route of administration has not been established, PO administration = preferred route of administration.
- Adverse effects of amlodipine: peripheral edema + gingival hyperplasia = uncommon in cats
- Despite dramatic efficacy, amlodipine besylate = no increased survival time in hypertensive cats
- For cats with systemic hypertension and hyperthyroidism, amlodipine besylate = 1st-line antihypertensive agent, combined with management of hyperthyroidism
Key predictive factor in survival of hypertensive cats = proteinuria
- Significant decrease in proteinuria = identified in cats either borderline proteinuric or proteinuric when treated with CCB
- However, combined use of amlodipine + ACEi or amlodipine + ARB = reportedly well tolerated
- Nevertheless, based on potential for proteinuria to contribute to progression of renal disease in cats and its association with survival of cats with CKD = antiproteinuric treatment should be considered in this situation
Telmisartan = ARB for TT of feline proteinuria due to CKD.
- Efficacy of telmisartan in severely hypertensive cats and with overt ocular and CNS hypertensive TOD = not demonstrated
- Combination of amlodipine besylate + telmisartan = well tolerated in cats
ACEi in cats as a 1st-line antihypertensive agent = not recommended.
- Benazepril = used in cats that require a 2nd antihypertensive agent and, clinically, combination of ACEi + amlodipine besylate = well tolerated
Angiotensin converting enzyme inhibitors + ARB = dilate renal efferent arteriole thereby decreasing intraglomerular pressure and magnitude of proteinuria.
- 2ary consequence of efferent arteriolar dilatation = theoretical tendency for GFR to decrease
- Potential for acute exacerbation of azotemia with concurrent ACEi and ARB => careful monitoring = recommended
- Not started in dehydrated cats in which GFR may decrease precipitously => carefully rehydrated and then re-evaluated before instituting ACEi or ARB TT
Diuretics = not routinely used as antihypertensive agents in cats
Beta-blockers (atenolol) = useful to control heart rate in some tachycardic hypertensive cats (with hyperthyroidism), but negligible antihypertensive effect => NOT used as a sole agent for the management of hypertension
Vasodilator drugs (hydralazine) = rarely required for management of hypertension in cats, but they have historically been useful in emergency situations
In cats with primary hyperaldosteronism, management with aldosterone antagonists (spironolactone), potassium supplementation, and adrenalectomy (if feasible) = necessary
- However, antihypertensive TT with amlodipine besylate = often required for adequate BP control and should be started concurrently
- Medical combination TT can be utilized in long term for management of patients with primary hyperaldosteronism and hypertension when no surgery
- Facial dermatitis and excoriation = rare adverse effect of spironolactone in cats
- Limited information is available about the effect of adrenalectomy on ongoing requirements for antihypertensive TT in cats with primary hyperaldosteronism
- Some individual affected cats have not required TT with amlodipine besylate postoperatively
- If another, nonadrenal, concurrent disease (such as CKD) was present and contributing to the pathogenesis of hypertension in an individual cat, adrenalectomy alone would not be expected to resolve systemic hypertension.
- In such case, ongoing antihypertensive management with amlodipine besylate would be required
- Careful monitoring of BP therefore is recommended in the peri- and post-operative period in cats with primary aldosteronism treated with adrenalectomy
Pheochromocytoma = rarely reported in the cat.
- Combination TT with phenoxybenzamine, α1- and α2- adrenergic blocker, and amlodipine besylate, may be required to adequately control BP
- For cats with tachyarrhythmias, beta-adrenergic blocker (atenolol) treatment = only added after α-adrenergic blockade
- For cats undergoing adrenalectomy, careful BP monitoring is required in postop period, as persistent hypertension or hypotension may occur
Hypentension: In which conditions immediate emergency treatment is needed?
SBP 160-179 mmHg
SBP 160-179 mmHg + signs of intracranial TOD
SBP >180 mmHh
SBP >180 mmHh + signs of intracranial TOD
Regardless of knowledge of predisposing disease conditions, diagnosis of SBP ≥ 180 mm Hg (high TOD risk category) in a patient with signs of intracranial TOD (eg, focal facial seizures) necessitates immediate emergency treatment.
The need for aggressive treatment in such cases typically requires 24-hour care capability, and referral to such a facility is warranted when 24-hour care is not available.
Regardless of knowledge of predisposing disease conditions, diagnosis of SBP ≥ 180 mm Hg (high TOD risk category) in a patient with signs of intracranial TOD (eg, focal facial seizures) necessitates immediate emergency treatment.
The need for aggressive treatment in such cases typically requires 24-hour care capability, and referral to such a facility is warranted when 24-hour care is not available.
What are the infectious causes of IMHA in DOGS?
Piroplasms
Adenovirus
Coronavirus
Babesia spp.
Anaplasma spp.
Bordetella spp.
Infectious causes of IMHA in DOGS:
- Piroplasms (Babesia spp.) => Intermediate to High evidence
- B. gibsoni
- B. canis
- Anaplasma spp. => Low evidence
- A. phagocytophilum
- A. platys
- Other vector-borne agents => Negligable to Low evidence
- Dirophilaria immitis
- Ehrlichia spp.
- Borrelia spp.
- Mycoplasma spp.
- Bartonella spp.
- Leishmania infantum
Infectious causes of IMHA in DOGS:
- Piroplasms (Babesia spp.) => Intermediate to High evidence
- B. gibsoni
- B. canis
- Anaplasma spp. => Low evidence
- A. phagocytophilum
- A. platys
- Other vector-borne agents => Negligable to Low evidence
- Dirophilaria immitis
- Ehrlichia spp.
- Borrelia spp.
- Mycoplasma spp.
- Bartonella spp.
- Leishmania infantum
What are the infectious causes of IMHA in CATS?
Calicivirus
Babesia felis
Herpesvirus
Feline Leukemia Virus
Hemotropic Mycoplasma spp.
Infectious causes of IMHA in CATS:
- Babesia felis => Intermediate evidence
- Hemotropic Mycoplasma spp. => High evidence
- M. heamofelis
- Viral infections => Low evidence
- Feline leukemia virus
Infectious causes of IMHA in CATS:
- Babesia felis => Intermediate evidence
- Hemotropic Mycoplasma spp. => High evidence
- M. heamofelis
- Viral infections => Low evidence
- Feline leukemia virus
Vaccine can be a cause for IMHA:
False
True all the time
True, but only in the 1st month
True, but only after the 1st month
The most effective vaccines elicit robust immune responses only against the pathogen of interest.
However, vaccines also may elicit unfavorable immune responses resulting from mechanisms such as molecular mimicry, bystander cell activation, or downregulation of self-tolerance, which contribute to autoimmunity.
For dogs, 32 papers mentioned that vaccines could be a trigger for IMHA, of which only 12 papers describe 79 clinical cases with documented temporal associations of ≤30 days between vaccine administration and IMHA.
The most effective vaccines elicit robust immune responses only against the pathogen of interest.
However, vaccines also may elicit unfavorable immune responses resulting from mechanisms such as molecular mimicry, bystander cell activation, or downregulation of self-tolerance, which contribute to autoimmunity.
For dogs, 32 papers mentioned that vaccines could be a trigger for IMHA, of which only 12 papers describe 79 clinical cases with documented temporal associations of ≤30 days between vaccine administration and IMHA.
Which statements about drugs-induced IMHA are true? And which drug(s) can cause IMHA?
Prevalence drugs-induced IMHA in dogs and cats is high or overreported
Prevalence drugs-induced IMHA in dogs and cats is rare or underreported
Amlodipine
Sulfadiazine
Propylthiouracil
Prednisolone
The prevalence of drug-induced IMHA in dogs and cats is either rare or underreported. However, a lack of evidence does not preclude the possibility of a drug or toxin triggering IMHA.
In the first study of 105 cats, 7 cats with hyperthyroidism treated with propylthiouracil developed immune-mediated drug reactions.
This finding was followed by a prospective, un-blinded, non-randomized trial in which 17 healthy cats were given the same drug, causing 9 to develop Coombs' test-positive anemia.
One additional case report describes warfarin exposure in a cat with IMHA, with an IME value of 1.70.
The prevalence of drug-induced IMHA in dogs and cats is either rare or underreported. However, a lack of evidence does not preclude the possibility of a drug or toxin triggering IMHA.
In the first study of 105 cats, 7 cats with hyperthyroidism treated with propylthiouracil developed immune-mediated drug reactions.
This finding was followed by a prospective, un-blinded, non-randomized trial in which 17 healthy cats were given the same drug, causing 9 to develop Coombs' test-positive anemia.
One additional case report describes warfarin exposure in a cat with IMHA, with an IME value of 1.70.
Administration of fresh frozen plasma routinely in dogs with IMHA is recommended:
True
False
Recommendation 6:
We do not recommend administering fresh frozen plasma routinely to dogs with IMHA.
Strength of recommendation: Strong
Recommendation 6:
We do not recommend administering fresh frozen plasma routinely to dogs with IMHA.
Strength of recommendation: Strong
Administration of cyclophosphamide in dogs with IMHA is recommended:
True
False
Recommendation 11:
We recommend that cyclophosphamide not be administered to dogs with IMHA.
Strength of recommendation: Strong
Recommendation 11:
We recommend that cyclophosphamide not be administered to dogs with IMHA.
Strength of recommendation: Strong
Use of more than 3 immonosuppressive drugs in dogs with IMHA at the same time is recommended:
True
False
Recommendation 13:
We suggest that the use of ≥3 immunosuppressive drugs at the same time should be avoided.
Strength of recommendation: Weak
Recommendation 13:
We suggest that the use of ≥3 immunosuppressive drugs at the same time should be avoided.
Strength of recommendation: Weak
In case of drug-associated myelosuppression, discontinuation of the causative agent is recommended:
True
False
Recommendation 23:
As soon as myelosuppression is documented, we recommend that the causative drug be discontinued.
Strength of recommendation: Strong
Recommendation 23:
As soon as myelosuppression is documented, we recommend that the causative drug be discontinued.
Strength of recommendation: Strong
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