'Thrombocytopenia' (or '-paenia', or 'thrombopenia' in short) is the presence of relatively few
platelets in
blood.
Generally speaking a normal platelet count ranges from 150,000 and 450,000 per mm
3. These limits, however, are determined by the 2.5th lower and upper
percentile, and a deviation does not necessarily imply any form of disease. The number of platelets in a blood sample also decreases rather quickly with time and a low platelet count may be caused by a delay between sampling and analysis.
Signs and symptoms
Often, low platelet levels do not lead to clinical problems; rather, they are picked up on a routine
full blood count. Occasionally, there may be
bruising, particularly purpura in the forearms,
nosebleeds and/or bleeding
gums.
It is vital that a full medical history is elicited, to ensure the low platelet count is not due to a secondary process. It is also important to ensure that the other blood cell types
red blood cells, and
white blood cells, are not also suppressed.
Diagnosis
Laboratory tests might include:
full blood count,
liver enzymes,
renal function,
vitamin B12 levels,
folic acid levels,
erythrocyte sedimentation rate, and peripheral blood smear.
If the cause for the low platelet count remains unclear,
bone marrow biopsy is often undertaken, to differentiate whether the low platelet count is due to ''decreased production'' or ''peripheral destruction''.
Causes
Decreased platelet counts can be due to a number of disease processes:
Decreased production
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vitamin B12 or
folic acid deficiency
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leukemia or
myelodysplastic syndrome
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★ Decreased production of
thrombopoietin by the
liver in
liver failure.
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Sepsis, systemic
viral or
bacterial infection
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Dengue fever can cause thrombocytopenia by direct infection of
bone marrow megakaryocytes as well as immunological shortened
platelet survival
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★ Hereditary syndromes
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Congenital Amegakaryocytic Thromboytopenia (CAMT)
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Thrombocytopenia absent radius syndrome
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Fanconi anemia
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Bernard-Soulier syndrome, associated with large platelets
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May-Hegglin anomaly, the combination of thrombocytopenia, pale-blue leuckocyte inclusions, and giant platelets
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Grey platelet syndrome
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Alport syndrome
Increased destruction
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idiopathic thrombocytopenic purpura (ITP)
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thrombotic thrombocytopenic purpura (TTP)
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hemolytic-uremic syndrome (HUS)
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disseminated intravascular coagulation (DIC)
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paroxysmal nocturnal hemoglobinuria (PNH)
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antiphospholipid syndrome
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systemic lupus erythematosus (SLE)
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post transfusion purpura
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neonatal alloimmune thrombocytopenia (NAITP)
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★ Splenic sequestration of platelets due to
hypersplenism
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Dengue fever has been shown to cause shortened platelet survival and immunological platelet destruction
Medication-induced
The most comprehensive list of thrombocytopenia-inducing medications is maintained by Dr. James George at Ohio State University
at this website, though last updated in 2004. A small subset of drug-induced thrombocytopenia culprits:
★ Direct myelosuppression
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★ Valproic acid
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★ Methotrexate
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★ Carboplatin
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★ Interferon
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★ Other chemotherapy drugs
★ Immunological platelet destruction
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★ Drug binds
Fab portion of an
antibody. The classic example of this mechanism is the
quinidine group of drugs. The Fc portion of the antibody molecule is not involved in the binding process.
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★ Drug binds to Fc, and drug-antibody complex binds and activates platelets.
Heparin induced thrombocytopenia (HIT) is the classic example of this phenomenon. In HIT, the heparin-antibody-platelet factor 4 (PF4) complex binds to Fc receptors on the surface of the platelet. Since Fc portion of the antibody is bound to the platelets, they are not available to the Fc receptors of the reticulo-endothelial cells, so therefore this system cannot destroy platelets as usual. This may explain why severe thrombocytopenia is not a common feature of HIT.
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Heparin-induced thrombocytopenia (HIT or ''white clot syndrome''): this is a rare but serious condition that may occur in a hospitalized population. The most common clinical setting for HIT is in postoperative coronary artery bypass graft recipients, who may receive large quantities of heparin during surgery. HIT typically occurs about a week after exposure to heparin. The heparin-PF4 antibody complex will activate the platelets, and this can often lead to
thrombosis. The term HITT, where the last T stands for thrombosis, denotes the concept that heparin-induced thrombocytopenia often is associated with
thrombosis.
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.
Specific treatment plans often depend on the underlying
etiology of the thrombocytopenia.
Thrombotic thrombocytopenic purpura (TTP)
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
TTP was revolutionized in the 1980s with the application of
plasmapheresis. According to the
Furlan-Tsai hypothesis
[3]
[4]
, this treatment theoretically works by removing
antibodies directed against the
von Willebrand factor cleaving
protease,
ADAMTS-13. The
plasmapheresis procedure also adds active
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
TTP, and these antibodies alone are not sufficient to explain the how
plasmapheresis treats
TTP.
ITP
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 requres treatment, less than ten thousand is a potentioally 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:
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Prednisone and other
corticosteroids
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Intravenous gamma globulin
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Splenectomy
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Danazol
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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.
A medication known as
AMG 531 was found to be safe and effective for the treatment of ITP in refractory patients.
[5]
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.
[6]
Heparin-induced thrombocytopenia and thrombosis (HITT)
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.
Congenital amegakaryocytic thrombocytopenia (CAMT)
Bone Marrow/Stem Cell Transplant is the only thing that ultimately cures this genetic disease. Frequent platelet transfusions are required to keep the patient from bleeding to death until transplant is done.
References
1. Vancomycin-induced thrombocytopenia: a challenge and rechallenge, Howard C, Adams L, Admire J, Chu M, Alred G, , , Ann Pharmacother, 1997
2. NEJM 2007 356:904, PMID available on 3/2/07 "Vancomycin Induced Immune Thrombocytopenia
3. Aetiology and pathogenesis of thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome: the role of von Willebrand factor-cleaving protease, Furlan M, Lämmle B, , , Best Pract Res Clin Haematol, 2001
4. Advances in the pathogenesis, diagnosis, and treatment of thrombotic thrombocytopenic purpura, Tsai H, , , J Am Soc Nephrol, 2003
5. AMG 531, a thrombopoiesis-stimulating protein, for chronic ITP, 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, , , N Engl J Med, 2006
6. AMG531 stimulates megakaryopoiesis in vitro by binding to Mpl, Broudy V, Lin N, , , Cytokine, 2004
External links
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