Autoimmune hemolytic anemia medical therapy: Difference between revisions

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Latest revision as of 11:23, 20 September 2018

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Assosciate Editor(s)-In-Chief: Prashanth Saddala M.B.B.S; Shyam Patel [2], Irfan Dotani [3]

Overview

The mainstay of therapy for autoimmune hemolytic anemia is immunosuppression, since the pathophysiology of autoimmune hemolytic anemia involves immunological activation which leads to the destruction of red blood cells. Suppression of the immunological activation via medications has been the cornerstone of therapy for many decades. Medications include corticosteroids, azathioprine, rituximab, mycophenolate mofetil, cyclosporine A, and cyclophosphamide.

Medical Therapy

Medical treatment of autoimmune hemolytic anemia is summarized below:


Medication	Mechanism of action	Response rate	Dosing and Administration	Adverse effects	Metabolism	Notable features

Corticosteroids	Inhibition of IL-2 Inhibition of arachidonic acid production Inhibition of NF-kappaB signaling	70-85% Response usually occurs within 2 weeks^[1]	Prednisone 1 to 1.5mg/kg PO daily for 1-3 weeks until hemoglobin improves to 10g/dl; rapid taper down to 20mg PO daily; slow taper over months from 20mg to 0mg Treat for 3-4 months with low-dose prednisone^[1]	Immunosuppression Opportunisitic infection Bone density loss Loss of muscle mass Increased adipose deposition hypertension cataracts Glaucoma	Extensive hepatic metabolism	First-line therapy is co-administer calcium supplementation with vitamin D (for bone protection) Co-administer H2 receptor antagonist for GI protection if high risk for gastrointestinal bleeding
Azathioprine^[2]	Purine synthesis inhibitor Converts to 6-mercaptopurine Antibody-dependent cell-mediated cytotoxicity	40-60%	1-3 mg/m2 IV weekly for 4 weeks	Hepatitis B reactivation Progressive multifocal leukoencephalopathy	Hepatic metabolism to 6-mercaptopurine and 6-thiouric acid	Higher cost of therapy than corticosteroids
Rituximab^[3]	CD20 monoclonal antibody Antibody-dependent cell-mediated cytotoxicity Depletion of B cells	83-87% overall response rate 54-60% complete response rate	375 mg/m2 IV weekly for 4 weeks 100 mg IV weekly for 4 weeks	Hepatitis B reactivation Progressive multifocal leukoencephalopathy Infusion reaction	Unknown	Higher cost of therapy than corticosteroids
Mycophenolate mofetil	Noncompetitive, selective, reversible inhibitor of inosine monophosphate (IMP) dehydrogenase Inhibits T cell proliferation by inhibiting purine synthesis	Variable	1-1.5 g PO every 12 hours	Hyperglycemia Hyperlipidemia Leukopenia Infections	Enterohepatic recirculation to MPA, the active form of mycophenolate mofetil	Higher cost of therapy than corticosteroids
Cyclosporine A	Inhibits calcineurin-mediated NFAT dephosphorylation and activation (calcineurin inhibitor) Inhibits T cell proliferation	Variable	1 mg/kg PO every 12 hours	Tremor Nephrotoxicity Hypertension Infection Headache Gingival hyperplasia	VIa hepatic CYP3A4 to metabolites AM1, AM9, and AM4N	Nephrotoxicity limits its use in patients with renal dysfunction
Cyclophosphamide^[2]	DNA alkylating agent Inhibits T cell proliferation	Variable	50 mg/kg daily for 4 days	Bone marrow suppression Nausea and vomiting Hemorrhagic cystitis Bladder cancer	Hepatically metabolized to 4-hydroperoxycyclophosphamide and 4-aldophosphamide	Chemotherapeutic agent

References

↑ ^1.0 ^1.1 Zanella A, Barcellini W (2014). "Treatment of autoimmune hemolytic anemias". Haematologica. 99 (10): 1547–54. doi:10.3324/haematol.2014.114561. PMC 4181250. PMID 25271314.
↑ ^2.0 ^2.1 Salama A (2015). "Treatment Options for Primary Autoimmune Hemolytic Anemia: A Short Comprehensive Review". Transfus Med Hemother. 42 (5): 294–301. doi:10.1159/000438731. PMC 4678315. PMID 26696797.
↑ Fozza C, Longinotti M (2011). "Use of rituximab in autoimmune hemolytic anemia associated with non-hodgkin lymphomas". Adv Hematol. 2011: 960137. doi:10.1155/2011/960137. PMC 3087411. PMID 21547266.

Template:WikiDoc Sources

[pmid25271314-1] 1.0 ^1.1 Zanella A, Barcellini W (2014). "Treatment of autoimmune hemolytic anemias". Haematologica. 99 (10): 1547–54. doi:10.3324/haematol.2014.114561. PMC 4181250. PMID 25271314.

[pmid26696797-2] 2.0 ^2.1 Salama A (2015). "Treatment Options for Primary Autoimmune Hemolytic Anemia: A Short Comprehensive Review". Transfus Med Hemother. 42 (5): 294–301. doi:10.1159/000438731. PMC 4678315. PMID 26696797.

[pmid21547266-3] Fozza C, Longinotti M (2011). "Use of rituximab in autoimmune hemolytic anemia associated with non-hodgkin lymphomas". Adv Hematol. 2011: 960137. doi:10.1155/2011/960137. PMC 3087411. PMID 21547266.

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[3]

@@ Line 2: / Line 2: @@
 {{Autoimmune hemolytic anemia}}
-{{CMG}} '''Assosciate Editor(s)-In-Chief:''' [[User: Prashanthsaddala|Prashanth Saddala M.B.B.S]]; {{shyam}}
+{{CMG}} '''Assosciate Editor(s)-In-Chief:''' [[User: Prashanthsaddala|Prashanth Saddala M.B.B.S]]; {{shyam}}, [[User:Irfan Dotani|Irfan Dotani]] [3]
-Please help WikiDoc by adding more content here.  It's easy!  Click  [[Help:How_to_Edit_a_Page|here]]  to learn about editing.
 ==Overview==
+The mainstay of therapy for autoimmune hemolytic anemia is [[immunosuppression]], since the pathophysiology of autoimmune hemolytic anemia involves [[immunological]] activation which leads to the destruction of [[red blood cells]]. Suppression of the [[immunological]] activation via medications has been the cornerstone of therapy for many decades. Medications include [[corticosteroids]], [[azathioprine]], [[rituximab]], [[mycophenolate]] mofetil, [[cyclosporine]] A, and [[cyclophosphamide]].
 ==Medical Therapy==
 Medical treatment of autoimmune hemolytic anemia is summarized below:
-{| style="border: 0px; font-size: 90%; margin: 3px; width: 600px" align=center
+{| style="border: 0px; font-size: 90%; margin: 3px; width: 600px" align="center"
-|valign=top|
+| valign="top" |
 |+
 ! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Medication}}
@@ Line 24: / Line 22: @@
 |-
 | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
-Corticosteroids
+[[Corticosteroids]]
 | style="padding: 5px 5px; background: #F5F5F5;" |
-Inhibition of IL-2 Inhibition of arachidonic acid production
+* Inhibition of [[IL-2]] Inhibition of [[arachidonic acid]] production
-Inhibition of NF-kappaB signaling
+* Inhibition of NF-kappaB signaling
 | style="padding: 5px 5px; background: #F5F5F5;" |
--85%
+* 70-85%
-Response usually occurs within 2 weeks<ref name="pmid25271314">{{cite journal| author=Zanella A, Barcellini W| title=Treatment of autoimmune hemolytic anemias. | journal=Haematologica | year= 2014 | volume= 99 | issue= 10 | pages= 1547-54 | pmid=25271314 | doi=10.3324/haematol.2014.114561 | pmc=4181250 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25271314  }} </ref>
+* Response usually occurs within 2 weeks<ref name="pmid25271314">{{cite journal| author=Zanella A, Barcellini W| title=Treatment of autoimmune hemolytic anemias. | journal=Haematologica | year= 2014 | volume= 99 | issue= 10 | pages= 1547-54 | pmid=25271314 | doi=10.3324/haematol.2014.114561 | pmc=4181250 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25271314  }} </ref>
 | style="padding: 5px 5px; background: #F5F5F5;" |
-Prednisone 1 to 1.5mg/kg PO daily for 1-3 weeks until hemoglobin improves to 10g/dl; rapid taper down to 20mg PO daily; slow taper over months from 20mg to 0mg
+* [[Prednisone]] 1 to 1.5mg/kg PO daily for 1-3 weeks until hemoglobin improves to 10g/dl; rapid taper down to 20mg PO daily; slow taper over months from 20mg to 0mg
-Treat for 3-4 months with low-dose prednisone<ref name="pmid25271314">{{cite journal| author=Zanella A, Barcellini W| title=Treatment of autoimmune hemolytic anemias. | journal=Haematologica | year= 2014 | volume= 99 | issue= 10 | pages= 1547-54 | pmid=25271314 | doi=10.3324/haematol.2014.114561 | pmc=4181250 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25271314  }} </ref>
+* Treat for 3-4 months with low-dose [[prednisone]]<ref name="pmid25271314">{{cite journal| author=Zanella A, Barcellini W| title=Treatment of autoimmune hemolytic anemias. | journal=Haematologica | year= 2014 | volume= 99 | issue= 10 | pages= 1547-54 | pmid=25271314 | doi=10.3324/haematol.2014.114561 | pmc=4181250 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25271314  }} </ref>
 | style="padding: 5px 5px; background: #F5F5F5;" |
-Immunosuppression, opportunisitic infection, bone density loss, loss of muscle mass, increased adipose deposition, hypertension, cataracts, glaucoma
+* [[Immunosuppression]]
+* [[Opportunistic infection|Opportunisitic infection]]
+* [[Bone density loss]]
+* Loss of muscle mass
+* Increased adipose deposition
+* [[hypertension]]
+* [[cataracts]]
+* [[Glaucoma]]
 | style="padding: 5px 5px; background: #F5F5F5;" |
-Extensive hepatic metabolism
+* Extensive hepatic metabolism
 | style="padding: 5px 5px; background: #F5F5F5;" |
-First-line therapy
+* First-line therapy is co-administer calcium supplementation with vitamin D (for bone protection)
-Co-administer calcium supplementation with vitamin D (for bone protection)
+* Co-administer H2 receptor antagonist for GI protection if high risk for gastrointestinal bleeding
-Co-administer H2 receptor antagonist for GI protection if high risk for gastrointestinal bleeding
 |-
 | style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
-Azathioprine
+[[Azathioprine]]<ref name="pmid26696797">{{cite journal| author=Salama A| title=Treatment Options for Primary Autoimmune Hemolytic Anemia: A Short Comprehensive Review. | journal=Transfus Med Hemother | year= 2015 | volume= 42 | issue= 5 | pages= 294-301 | pmid=26696797 | doi=10.1159/000438731 | pmc=4678315 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26696797  }} </ref>
+| style="padding: 5px 5px; background: #F5F5F5;" |
+* Purine synthesis inhibitor
+* Converts to [[6-mercaptopurine]]
+* [[Antibody-dependent cell-mediated cytotoxicity]]
 | style="padding: 5px 5px; background: #F5F5F5;" |
-Purine synthesis inhibitor
+* 40-60%
-Converts to 6-mercaptopurine
-Antibody-dependent cell-mediated cytotoxicity
 | style="padding: 5px 5px; background: #F5F5F5;" |
--60%
+* 1-3  mg/m2 IV weekly for 4 weeks
 | style="padding: 5px 5px; background: #F5F5F5;" |
--3  mg/m2 IV weekly for 4 weeks
+* [[Hepatitis B]] reactivation
+* Progressive [[Leukoencephalopathy|multifocal leukoencephalopathy]]
 | style="padding: 5px 5px; background: #F5F5F5;" |
-Hepatitis B reactivation, progressive multifocal leukoencephalopathy
+* Hepatic metabolism to [[6-mercaptopurine]] and 6-thiouric acid
 | style="padding: 5px 5px; background: #F5F5F5;" |
-Higher cost of therapy than corticosteroids
+* Higher cost of therapy than [[corticosteroids]]
 |-
 | style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
-Rituximab
+[[Rituximab]]<ref name="pmid21547266">{{cite journal| author=Fozza C, Longinotti M| title=Use of rituximab in autoimmune hemolytic anemia associated with non-hodgkin lymphomas. | journal=Adv Hematol | year= 2011 | volume= 2011 | issue=  | pages= 960137 | pmid=21547266 | doi=10.1155/2011/960137 | pmc=3087411 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21547266  }} </ref>
+| style="padding: 5px 5px; background: #F5F5F5;" |
+* [[CD20]] monoclonal antibody
+* [[Antibody-dependent cell-mediated cytotoxicity]]
+* Depletion of [[B cell|B cells]]
 | style="padding: 5px 5px; background: #F5F5F5;" |
-CD20 monoclonal antibody
+* 83-87% overall response rate
-Antibody-dependent cell-mediated cytotoxicity
+* 54-60% complete response rate
-Depletion of B cells
 | style="padding: 5px 5px; background: #F5F5F5;" |
--87% overall response rate
+* 375 mg/m2 IV weekly for 4 weeks
--60% complete response rate
+* 100 mg IV weekly for 4 weeks
 | style="padding: 5px 5px; background: #F5F5F5;" |
-mg/m2 IV weekly for 4 weeks
+* [[Hepatitis B]] reactivation
-mg IV weekly for 4 weeks
+* [[Progressive multifocal leukoencephalopathy]]
+* Infusion reaction
 | style="padding: 5px 5px; background: #F5F5F5;" |
-Hepatitis B reactivation, progressive multifocal leukoencephalopathy, infusion reaction
+* Unknown
 | style="padding: 5px 5px; background: #F5F5F5;" |
-Higher cost of therapy than corticosteroids
+* Higher cost of therapy than [[Corticosteroid|corticosteroids]]
 |-
 | style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
-Mycophenolate mofetil
+[[Mycophenolate]] mofetil
+| style="padding: 5px 5px; background: #F5F5F5;" |
+* Noncompetitive, selective, reversible inhibitor of [[Inosine monophosphate|inosine monophosphate (IMP)]] dehydrogenase
+* Inhibits [[T cell proliferation]] by inhibiting purine synthesis
 | style="padding: 5px 5px; background: #F5F5F5;" |
-Inosine monophosphate dehydrogenase inhibitor
+* Variable
-Inhibits T cell proliferation
 | style="padding: 5px 5px; background: #F5F5F5;" |
-Variable
+* 1-1.5 g PO every 12 hours
 | style="padding: 5px 5px; background: #F5F5F5;" |
--1.5 g PO every 12 hours
+* [[Hyperglycemia]]
+* [[Hyperlipidemia]]
+* [[Leukopenia]]
+* [[Infections]]
 | style="padding: 5px 5px; background: #F5F5F5;" |
-Hyperglycemia, hyperlipidemia, leukopenia, infections
+* Enterohepatic recirculation to MPA, the active form of [[Mycophenolic acid|mycophenolate mofetil]]
 | style="padding: 5px 5px; background: #F5F5F5;" |
-Higher cost of therapy than corticosteroids
+* Higher cost of therapy than [[Corticosteroid|corticosteroids]]
 |-
 | style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
-Cyclosporine A
+[[Cyclosporine]] A
+| style="padding: 5px 5px; background: #F5F5F5;" |
+* Inhibits calcineurin-mediated [[NFAT|NFAT dephosphorylation]] and activation (calcineurin inhibitor)
+* Inhibits [[T cell proliferation]]
 | style="padding: 5px 5px; background: #F5F5F5;" |
-Calcineurin inhibitor
+* Variable
-Inhibits T cell proliferation
 | style="padding: 5px 5px; background: #F5F5F5;" |
-Variable
+* 1 mg/kg PO every 12 hours
 | style="padding: 5px 5px; background: #F5F5F5;" |
-mg/kg PO every 12 hours
+* [[Tremor]]
+* [[Nephrotoxicity]]
+* [[Hypertension]]
+* [[Infection]]
+* [[Headache]]
+* [[Gingival hyperplasia]]
 | style="padding: 5px 5px; background: #F5F5F5;" |
-Tremor, nephrotoxicity, hypertension, infection, headache, gingival hyperplasia
+* VIa hepatic CYP3A4 to metabolites AM1, AM9, and AM4N
 | style="padding: 5px 5px; background: #F5F5F5;" |
-Nephrotoxicity limits its use in patients with renal dysfunction
+* [[Nephrotoxicity]] limits its use in patients with renal dysfunction
 |-
 | style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
-Cyclophosphamide
+[[Cyclophosphamide]]<ref name="pmid26696797">{{cite journal| author=Salama A| title=Treatment Options for Primary Autoimmune Hemolytic Anemia: A Short Comprehensive Review. | journal=Transfus Med Hemother | year= 2015 | volume= 42 | issue= 5 | pages= 294-301 | pmid=26696797 | doi=10.1159/000438731 | pmc=4678315 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26696797  }} </ref>
+| style="padding: 5px 5px; background: #F5F5F5;" |
+* [[Alkylating agent|DNA alkylating agent]]
+* Inhibits [[T cell proliferation]]
 | style="padding: 5px 5px; background: #F5F5F5;" |
-DNA alkylating agent
+* Variable
-Inhibits T cell proliferation
 | style="padding: 5px 5px; background: #F5F5F5;" |
-Variable
+* 50 mg/kg daily for 4 days
 | style="padding: 5px 5px; background: #F5F5F5;" |
-mg/kg daily for 4 days
+* [[Bone marrow suppression]]
+* [[Nausea and vomiting]]
+* [[Hemorrhagic cystitis]]
+* [[Bladder cancer]]
 | style="padding: 5px 5px; background: #F5F5F5;" |
-Bone marrow suppression, nausea, vomiting, hemorrhagic cystitis, bladder cancer
+* Hepatically metabolized to 4-hydroperoxycyclophosphamide and 4-aldophosphamide
 | style="padding: 5px 5px; background: #F5F5F5;" |
-Chemotherapeutic agent
+* [[Chemotherapeutic agent]]
 |}
-The maintain of therapy for autoimmune hemolytic anemia is immunosuppression, since the pathophysiology of autoimmune hemolytic anemia involves immunological activation which leads to destruction of [[red blood cells]]. Suppression of the immunological activation via medications has been the cornerstone of therapy for many decades.
-*'''[[Corticosteroids]]''': Corticosteroids is the major class of medications used for treatment. Corticosteroids are the first-line therapy. Efficacy of corticosteroids is approximately 70-85%.<ref name="pmid25271314">{{cite journal| author=Zanella A, Barcellini W| title=Treatment of autoimmune hemolytic anemias. | journal=Haematologica | year= 2014 | volume= 99 | issue= 10 | pages= 1547-54 | pmid=25271314 | doi=10.3324/haematol.2014.114561 | pmc=4181250 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25271314  }} </ref> The initial dose of prednisone is 1 to 1.5mg/kg orally once daily. After a response is seen, steroids should be tapered over 6-12 months. Rapid taper of steroids can result in adrenal insufficiency, which can manifest as hypotension and fatigue and can be fatal.<ref name="pmid25271314">{{cite journal| author=Zanella A, Barcellini W| title=Treatment of autoimmune hemolytic anemias. | journal=Haematologica | year= 2014 | volume= 99 | issue= 10 | pages= 1547-54 | pmid=25271314 | doi=10.3324/haematol.2014.114561 | pmc=4181250 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25271314  }} </ref> Of note, steroids are effective only for warm-antibody type autoimmune hemolytic anemia. Steroids are not effective for cold-antibody type autoimmune hemolytic anemia. Given the multiple adverse effects of steroids, it is not ideal for a patient to remain on steroids for long-term management. If long-term immunosuppression is required for control of autoimmune hemolytic anemia, and alternative immunosuppression should be attempted.
-**''Adverse effects'': The adverse effects of corticocsteroids include immunosuppression, opportunisitic infection, bone density loss, loss of muscle mass, increased adipose deposition, hypertension, cataracts, glaucoma.
 ==References==
 {{Reflist|2}}
-{{Hematology}}
-[[Category:Hematology]]
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Autoimmune hemolytic anemia medical therapy: Difference between revisions

Latest revision as of 11:23, 20 September 2018

Overview

Medical Therapy

References

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