Thrombocytopenia medical therapy: Difference between revisions

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{{Thrombocytopenia}}
{{Thrombocytopenia}}
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==Overview==
==Overview==
The treatment of thrombocytopenia depends on the underlying cause.
==Treatment==
==Treatment==
Treatment is guided by etiology and disease severity.  The main concept in treating thrombocytopenia is to eliminate the underlying problem, whether that means discontinuing suspected drugs that cause thrombocytopenia, or treating underlying sepsis.  Diagnosis and treatment of serious thrombocytopenia is usually directed by a [[hematologist]].
===Supportive measures===
*Platelet transfusion


Specific treatment plans often depend on the underlying [[etiology]] of the thrombocytopenia.
===Treatment of the underlying cause===
*'''Viral'''
**Anti-viral medications
**Hydration and supportive measures


===Thrombotic thrombocytopenic purpura (TTP)===
*'''Drug-induced'''
Treatment of [[thrombotic thrombocytopenic purpura]] is a medical emergency, since the [[hemolytic anemia]] and platelet activation can lead to [[renal failure]] and changes in the level of consciousness.  Treatment of [[thrombotic thrombocytopenic purpura|TTP]] was revolutionized in the 1980s with the application of [[plasmapheresis]].  According to the Furlan-Tsai hypothesis
**Discontinuation of the offending agent
<ref>{{cite journal |author=Furlan M, Lämmle B |title=Aetiology and pathogenesis of thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome: the role of von Willebrand factor-cleaving protease |journal=Best Pract Res Clin Haematol |volume=14 |issue=2 |pages=437-54 |year=2001 |pmid=11686108}}</ref>
**Antidote for the offendating agents
<ref>{{cite journal |author=Tsai H |title=Advances in the pathogenesis, diagnosis, and treatment of thrombotic thrombocytopenic purpura |journal=J Am Soc Nephrol |volume=14 |issue=4 |pages=1072-81 |year=2003 |pmid=12660343}}</ref>
, this treatment theoretically works by removing [[antibodies]] directed against the [[von Willebrand factor]] cleaving [[protease]], [[ADAMTS13|ADAMTS-13]].  The [[plasmapheresis]] procedure also adds active [[ADAMTS13|ADAMTS-13]] [[protease]] [[proteins]] to the patient, restoring a more physiological state of [[von Willebrand factor]] multimers.  Patients with persistent antibodies against [[ADAMTS-13]] do not always manifest [[thrombotic thrombocytopenic purpura|TTP]], and these antibodies alone are not sufficient to explain the how [[plasmapheresis]] treats [[thrombotic thrombocytopenic purpura|TTP]].


===ITP===
*'''Thrombotic microangiopathy'''<ref name="pmid27149490">{{cite journal| author=Li QY, Yu F, Zhou FD, Zhao MH| title=Plasmapheresis Is Associated With Better Renal Outcomes in Lupus Nephritis Patients With Thrombotic Microangiopathy: A Case Series Study. | journal=Medicine (Baltimore) | year= 2016 | volume= 95 | issue= 18 | pages= e3595 | pmid=27149490 | doi=10.1097/MD.0000000000003595 | pmc=4863807 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27149490 }} </ref>
In many cases, ITP is self-limited, and does not require treatment. Platelet counts less than ten thousand per mm3 usually require treatment (less than fifty thousand requires treatment, less than ten thousand is a potentially dangerous situation) and patients with significant bleeding and thrombocytopenia due to ITP are also usually treated. The threshold for treating ITP has decreased since the 1990s, and hematologists recognize that patients rarely bleed with platelet counts greater than ten thousand, though there are documented exceptions to this observation.  Treatments for ITP include:
**Plasma exchange
*[[Prednisone]] and other [[corticosteroids]]
**Fresh frozen plasma
*[[Intravenous gamma globulin]]
*[[Splenectomy]]
*[[Danazol]]
*[[Rituximab]]


Thrombopoetin analogues have been tested extensively for the treatment of ITP.  These agents had previously shown promise but had been found to stimulate antibodies against endogenous [[thrombopoeitin]] or lead to [[thrombosis]].
*'''Sepsis'''
**Antibacterial agents
**Antiviral agents
**Antifungal agents


A medication known as AMG 531 was found to be safe and effective for the treatment of ITP in refractory patients.
*'''Pseudothrombocytopenia'''
<ref>{{cite journal |author=Bussel J, Kuter D, George J, McMillan R, Aledort L, Conklin G, Lichtin A, Lyons R, Nieva J, Wasser J, Wiznitzer I, Kelly R, Chen C, Nichol J |title=AMG 531, a thrombopoiesis-stimulating protein, for chronic ITP |journal=N Engl J Med |volume=355 |issue=16 |pages=1672-81 |year=2006 |pmid=17050891}}</ref>
**Use of calcium citrate instead of EDTA during blood collection
AMG 531 is a [[peptide]] that bears no [[sequence homology]] with endogenous [[human]] [[thrombopoeitin]], so it is not as likely to lead to neutralizing antibodies as previous peptide [[thrombopoeitin]] analogues.
<ref>{{cite journal |author=Broudy V, Lin N |title=AMG531 stimulates megakaryopoiesis in vitro by binding to Mpl |journal=Cytokine |volume=25 |issue=2 |pages=52-60 |year=2004 |pmid=14693160}}</ref>


===Heparin-induced thrombocytopenia and thrombosis (HITT)===
*'''Immune thrombocytopenia purpura (ITP)'''
Discontinuation of heparin is critical in a case of HITT. Beyond that, however, care must be taken to avoid a thrombosis, and patients started directly on [[warfarin]] after a diagnosis of HITT are at excess risk of venous limb gangrene. For this reason, patients are usually treated with a type of [[blood thinner]] called a [[direct thrombin inhibitor]] such as the [[FDA]]-approved [[lepirudin]] or [[argatroban]]. Other [[blood thinners]] sometimes used in this setting that are not [[FDA]]-approved for treatment of HITT include [[bivalirudin]] and [[fondaparinux]]. [[Platelet transfusions]] are not a routine component of the treatment of [[HITT]], since thrombosis, not bleeding, is the usual associated problem in this illness.
**Corticosteroids: These medications can take up to 48 hours to take effect. Steroids are first-line therapy for ITP. Adverse effects include infection, muscle loss, adipose deposition, cataracts, glaucoma, and Cushing's syndrome.
**Intravenous immunoglobulin: This medication has an immediate effect, typically within hours. IV immunoglobulin is first-line therapy for ITP.
** Rituximab: This is a monoclonal antibody that targets CD20 on B cells and eliminates antibody-producing B cells. It is used as second-line therapy. Adverse effects include infections, hepatitis B reactivation, and progressive multifocal leukoencephalopathy.
**Fostamatinib: This is a spleen tyrosine kinase (SYK) inhibitor that functions by blocking signaling through the Fc receptor in B cells.<ref name="pmid23190017">{{cite journal| author=Baluom M, Grossbard EB, Mant T, Lau DT| title=Pharmacokinetics of fostamatinib, a spleen tyrosine kinase (SYK) inhibitor, in healthy human subjects following single and multiple oral dosing in three phase I studies. | journal=Br J Clin Pharmacol | year= 2013 | volume= 76 | issue= 1 | pages= 78-88 | pmid=23190017 | doi=10.1111/bcp.12048 | pmc=3703230 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23190017  }} </ref> Adverse effects include hypertension, hepatotoxicity, diarrhea, and neutropenia.
**Eltrombopag: This is a TPO receptor agonist and is third-line therapy. Liver tests must be monitored while taking eltrombopag. It can cause thrombosis.
**Romiplostim: This is a TPO receptor agonist and is third-line therapy. It can cause thrombosis.


===Contraindicated medications===
==References==
{{MedCondContrAbs
{{reflist|2}}


|MedCond = Thrombocytopenia|Abciximab|Ticlopidine|Enoxaparin|Fondaparinux}}
[[Category:Hematology]]


{{MedCondContrAbs
{{WS}}
 
{{WH}}
|MedCond = History of thrombocytopenia following prior exposure to|Tirofiban}}
 
==References==
{{Reflist|2}}
[[Category:Needs content]]

Latest revision as of 01:25, 20 December 2018

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Shyam Patel [2]

Overview

The treatment of thrombocytopenia depends on the underlying cause.

Treatment

Supportive measures

  • Platelet transfusion

Treatment of the underlying cause

  • Viral
    • Anti-viral medications
    • Hydration and supportive measures
  • Drug-induced
    • Discontinuation of the offending agent
    • Antidote for the offendating agents
  • Thrombotic microangiopathy[1]
    • Plasma exchange
    • Fresh frozen plasma
  • Sepsis
    • Antibacterial agents
    • Antiviral agents
    • Antifungal agents
  • Pseudothrombocytopenia
    • Use of calcium citrate instead of EDTA during blood collection
  • Immune thrombocytopenia purpura (ITP)
    • Corticosteroids: These medications can take up to 48 hours to take effect. Steroids are first-line therapy for ITP. Adverse effects include infection, muscle loss, adipose deposition, cataracts, glaucoma, and Cushing's syndrome.
    • Intravenous immunoglobulin: This medication has an immediate effect, typically within hours. IV immunoglobulin is first-line therapy for ITP.
    • Rituximab: This is a monoclonal antibody that targets CD20 on B cells and eliminates antibody-producing B cells. It is used as second-line therapy. Adverse effects include infections, hepatitis B reactivation, and progressive multifocal leukoencephalopathy.
    • Fostamatinib: This is a spleen tyrosine kinase (SYK) inhibitor that functions by blocking signaling through the Fc receptor in B cells.[2] Adverse effects include hypertension, hepatotoxicity, diarrhea, and neutropenia.
    • Eltrombopag: This is a TPO receptor agonist and is third-line therapy. Liver tests must be monitored while taking eltrombopag. It can cause thrombosis.
    • Romiplostim: This is a TPO receptor agonist and is third-line therapy. It can cause thrombosis.

References

  1. ↑ Li QY, Yu F, Zhou FD, Zhao MH (2016). "Plasmapheresis Is Associated With Better Renal Outcomes in Lupus Nephritis Patients With Thrombotic Microangiopathy: A Case Series Study". Medicine (Baltimore). 95 (18): e3595. doi:10.1097/MD.0000000000003595. PMC 4863807. PMID 27149490.
  2. ↑ Baluom M, Grossbard EB, Mant T, Lau DT (2013). "Pharmacokinetics of fostamatinib, a spleen tyrosine kinase (SYK) inhibitor, in healthy human subjects following single and multiple oral dosing in three phase I studies". Br J Clin Pharmacol. 76 (1): 78–88. doi:10.1111/bcp.12048. PMC 3703230. PMID 23190017.

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