116 Thrombocytopenia Flashcards
One-third of the platelets are stored in the _________, and the remaining two-thirds circulate in _____________ human
Spleen: one-third
Blood vessels: two-thirds
Platelets have a mean lifespan in the circulation of ______ days
7–10 days
Approximately 1 × 10 11 platelets are produced per day
Every day approximately ________% of circulating platelets are removed by the mononuclear phagocyte system, primarily by macrophages in the ____________.
10% to 12%
spleen and liver
The normal platelet count
150–400 × 10 9 /L
Classically thrombocytopenia is defined as platelet count less than __________
less than 150 × 10 9 /L
Throbocytopenia
Severe:
Moderate:
Mild:
Severe (platelet count <20 × 10 9 /L)
Moderate (platelet count 20–70 × 10 9/L)
Mild (>70 × 10 9/L)
The blood-to-anticoagulant ratio should be as recommended. The International Council for Standardization in Hematology recommends the use of ____________ as the anticoagulant.
Ethylenediaminetetraacetic acid (EDTA)
Conditions associated with pseudo thrombocytopenia
- Use of EDTA as an anticoagulant
- Platelet cold agglutinins
- Myeloma
ANTIBODY-INDUCED PLATELET AGGLUTINATION
The antibodies usually are of the Immunoglobulin ________ type.
Immunoglobulin (Ig) G type
IgM and IgA antibodies also have been described
ANTIBODY-INDUCED PLATELET AGGLUTINATION
In most cases, the antibodies are directed against the __________
Integrin αIIbβIII (also termed glycoprotein [GP] IIb/IIIa)
Antibodies directed against integrin αIIbβIII may react simultaneously with the leukocyte Fcγ receptor III (FcγRIII) and attach the platelets to neutrophils and monocytes, inducing a phenomenon known as ______________
Platelet-leukocyte satellitism
The platelets form a rosette around the periphery of leukocytes.
Neutrophils are most frequently involved, but the phenomenon also is occasionally observed with monocytes.
Some antiplatelet antibodies from patients with pseudothrombocytopenia cross-react with negatively charged phospholipids and may exhibit _______________ activity.
Anticardiolipin activity
Thrombocytopenia has been described in patients with acute coronary syndromes treated with the ___________ and other _________________
Abciximab
Integrin αIIbβIII antagonists
Abciximab is associated with both pseudothrombocytopenia and true thrombocytopenia.
The mechanism for platelet clumping with abciximab is unknown; the drug itself likely is not crosslinking the platelets because it is monovalent.
True abciximab-induced thrombocytopenia occurs in approximately 0.3% to 1% of patients treated with the drug.
TRUE OR FALSE
Pseudothrombocytopenia may be accompanied by pseudoleukocytosis
TRUE
Pseudothrombocytopenia may be accompanied by pseudoleukocytosis
Because platelet clumps tend to exceed 20 fl, the clumps may be counted as leukocytes,and even if counted as platelets, several platelets are counted as one.
How can platelet clumping be prevented
- Collecting the sample in EDTA and maintaining its temperature at 37 C.
- Use of sodium citrate, which chelates calcium more weakly than does EDTA but still causes platelet clumping in approximately 10% to 20% of cases with EDTA-induced clumping
- An accurate platelet count can be obtained only by sampling blood directly into ammonium oxalate and manually counting the platelets using a Bruker chamber.
- Flow cytometry may help for determining exact platelet number by immunostaining of the platelets
Even with these measures, however, clumping will still occur in approximately 20% of cases.
Patients with IPD usually present witH
Mucocutaneous bleeding
Spontaneous life-threatening bleeding is rare.
TRUE OR FALSE
Majority of IPDs are inherited as autosomal dominant traits.
FALSE
Majority of IPDs are inherited as autosomal recessive traits.
Laboratory PBS findings of a potential IPD
- MYH9-related diseases (giant platelets and Döhle-like inclusion bodies within leukocytes)
- Bernard-Soulier syndrome (macrothrombocytopenia)
- Gray platelet syndrome (pale platelets)
- Sitosterolemia (giant platelets surrounded by a circle of vacuoles, stomatocytosis).
TRUE OR FALSE
The skin bleeding time is no longer recommended for use in patients with platelet disorders because it is invasive and poorly reproducible.
TRUE
The skin bleeding time is no longer recommended for use in patients with platelet disorders because it is invasive and poorly reproducible.
Platelet function analyzer (PFA-100) occlusion times are usually found to be prolonged.
Gold standard in diagnosing IPDs
Light transmission aggregometry
Uses different concentrations of adenosine diphosphate (ADP), collagen, ristocetin, epinephrine, and arachidonic acid
May be normal in variant forms of IPDs and in some patients with storage pool diseases
Test recommended in patients with platelet granule deficiencies
Platelet nucleotide content and release
Test that can be used in patients with platelet surface glycoprotein deficiencies such as Bernard-Soulier syndrome
Flow cytometric analysis
Test that is able to define characteristic ultrastructural abnormalities; western blotting, enzymelinked immunosorbent assay (ELISA), or radioimmunoassay can be used for qualitative and quantitative analysis of specific platelet proteins.
Electron microscopy
TRUE OR FALSE
Isolated thrombocytopenia is common in patients with nutritional deficiencies.
FALSE
Isolated thrombocytopenia is rare in patients with nutritional deficiencies.
Iron-deficiency anemia (IDA) generally develops after acute or chronic bleeding and is usually accompanied by (thrombocytosis OR thrombocytopenia)
Thrombocytosis
Thrombocytopenia associated with IDA is relatively rare, reported in only 2.3% and 2.4% of pediatric and adult IDA patients, respectively.
TRUE OR FALSE
Thrombocytopenia may be seen in association with vitamin B12 deficiency when the latter results from autoantibodies against parietal cells or intrinsic factor and is associated with ITP.
TRUE
Thrombocytopenia may be seen in association with vitamin B12 deficiency when the latter results from autoantibodies against parietal cells or intrinsic factor and is associated with ITP.
autoimmune
Various other autoimmune disorders can coexist with pernicious anemia, including autoimmune vitiligo and autoimmune thyroiditis.
Mineral deficiency seen in patients who have undergone gastric bypass surgery and may cause anemia, leukopenia, and thrombocytopenia associated with neurologic deficits resembling vitamin B12 deficiency.
Copper deficiency
May be misdiagnosed as having MDS because increased ring sideroblasts and dysplastic precursor cells can be seen in on bone marrow smears
In acute ethanol intoxication, platelet counts in these cases are usually mildly (increased or decreased) severe thrombocytopenia is quite rare.
Platelet counts in these cases are usually mildly decreased (generally >100 109/L)
Usually resolves within 5–21 days with cessation of ethanol ingestion, sometimes with a transient rebound thrombocytosis that may reach up to 1,000,000 109/L.
Suggested mechanism of acute alcohol-related thrombocytopenia
It has been suggested that metabolites of ethanol, especially acetaldehyde, impair the late stages of platelet production and increase platelet destruction
Thus, thrombocytopenia associated with acute alcohol ingestion would be expected to be more frequent in those with poor nutrition (delayed oxidation of acetaldehyde) and those with partial acetaldehyde dehydrogenase defiance.
Mechanisms of thrombocytopenia in chronic ethanol consumption
- Alcoholic liver cirrhosis (both splenomegaly and thrombopoietin deficiency)
- Folic acid deficiency
- Alcohol-induced marrow suppression
Alcoholism (chronic ethanol consumption, which is defined as consumption of >_____ g of ethanol per day
> 80 g of ethanol per day
Thrombocytopenia attributable to pure aplasia or hypoplasia of megakaryocytes
Antibodies against thrombopoietin (TPO) have been described to cause the disorder, as have antibodies against the TPO receptor.
ACQUIRED PURE AMEGAKARYOCYTIC THROMBOCYTOPENIA
Rare
Anticipates the development of full-blown MDS or aplastic anemia and is associated with subtle abnormalities of other lineages, such as macrocytosis and dyserythropoiesis.
Causes of Acquired Pure Megakaryocytric Thrombocytopenia
- Autoimmune suppression of megakaryocyte development, either idiopathic, associated with autoimmune disorders such as systemic lupus erythematosus (SLE) and eosinophilic fasciitis
- Infections such as hepatitis C
May achieve durable remission with therapies designed to blunt the autoimmune response, such as cyclosporine or antithymocyte globulin.
The most common cause of isolated thrombocytopenia in clinical practice
PRIMARY IMMUNE THROMBOCYTOPENIA
Childhood OR Adult ITP
Typically is acute in onset, often developing after a viral infection or vaccination.
Although thrombocytopenia may be severe, it usually resolves spontaneously, within a few weeks up to 6 months.
Chidhood ITP
Childhood OR Adult ITP
A chronic disease of insidious onset and rarely resolves spontaneously.
Adult ITP
TRUE OR FALSE
Most patients with ITP had decreased number of megakaryocytes, and very few of them were producing platelets, so “actual platelet-producing tissue”.
FALSE
Most patients with ITP had an increased number of megakaryocytes, but very few of them were producing platelets, so “actual platelet-producing tissue” might be decreased.
Majority of antiplatelet antibodies in patients with ITP are directed against _________, and the remainder are against the GPIb-IX-V complex and other platelet glycoproteins such as GPIV and integrin αIIβI (GPIa-IIa).
Integrin αIIb–βIII (~80%)
In the late 1980s, two specific assays for the target antigens were described: the immunobead assay100 and the monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay.
Most antiplatelet autoantibodies are IgG; the remainder are IgM and IgA.
TRUE OR FALSE
PAIgG could not be used as a specific laboratory test for ITP in the same way that the direct antiglobulin test is used for the diagnosis of autoimmune hemolytic anemia.
TRUE
PAIgG could NOT be used as a specific laboratory test for ITP in the same way that the direct antiglobulin test is used for the diagnosis of autoimmune hemolytic anemia.
Unfortunately, elevated levels of PAIgG later were found in patients with nonimmune thrombocytopenia
TRUE OR FALSE
There is still no specific laboratory test for ITP, the diagnosis of ITP being based on exclusion of other causes.
TRUE
There is still no specific laboratory test for ITP, the diagnosis of ITP being based on exclusion of other causes.
TRUE OR FALSE
In patients with ITP, both Th1 and Th17 cells have been found to be downregulated, whereas the number and the suppressor functions of the Tregs were found to be increased.
FALSE
In patients with ITP, both Th1 and Th17 cells have been found to be upregulated, whereas the number and the suppressor functions of the Tregs were found to be decreased.
Increased platelet-associated C3, C4, and C9 have been demonstrated on the platelets from patients with ITP.
The main regulator of megakaryopoiesis
Enhances megakaryocyte colony formation and increases the size, number, and ploidy of megakaryocytes, as well as platelet production
Thrombopoietin
TPO binds to the cell-surface receptor c-MPL
TPO levels are markedly elevated in patients with thrombocytopenia associated with megakaryocytic hypoplasia, including disorders such as aplastic anemia or acute leukemia.
TPO is synthesized in greatest quantity in the
LIver
Found in other organs kidney, muscle, and marrow stromal cells.
Hepatic production of TPO is both constitutive (in the steady state) and inducible (by IL-6 during inflammation), and the concentration of TPO to which megakaryocytes are exposed is also determined by the platelet concentration.
This agent,which binds to a region of the TPO receptor that overlaps that bound by authentic TPO
Romiplostim
A small organic thrombopoietin receptor agonist (TRA) that activates TPO receptor signaling by binding to the transmembrane domain of the receptor, a site quite distinct from native and romiplostim binding.
Eltrombopag
Eltrombopag has been approved for use in patients with aplastic anemia
ITP is classified based: on the absence or presence of other diseases :
Primary ITP: absence of any other identified pathology
Secondary ITP
The IWG definition proposed use of the term “immune thrombocytopenia” instead of “idiopathic thrombocytopenic purpura” as the basis for the ITP acronym because the immune nature of ITP is clear, but most patients with ITP do not have purpura.
TRUE OR FALSE
Heparin-induced thrombocytopenia (HIT) and alloimmune thrombocytopenias are not classified as ITP and maintain their standard classifications
TRUE
Heparin-induced thrombocytopenia (HIT) and alloimmune thrombocytopenias are not classified as ITP and maintain their standard classifications
Three phases of ITP:
(a) Newly diagnosed ITP (within 3 months of diagnosis),
(b) Persistent ITP (patients who do not achieve a stable remission between 3–12 months after diagnosis), and
(c) Chronic ITP (continuing for more than 12 months).
ITP was formerly classified as mild, moderate, and severe depending on the platelet counts. However, the degree of thrombocytopenia does not always correlate with bleeding, likely because of the functional effects of the autoantibody on the platelet.
Criteria for response to ITP treatment
- Complete response, CR: platelet count >100 x 109/L and no bleeding symptoms)
- Response, R: platelet count > 30 x 109/L or at least a twofold increase from the baseline count and no bleeding symptoms
- No response, NR: platelet count < 30 x 109/L, < a twofold increase from the baseline count, or presence of bleeding symptoms
The IWG proposed that the term “severe ITP” only be used for
Patients with clinically significant bleeding requiring additional therapy regardless of platelet count.
Duration of response
Time between first measured CR or R to relapse
Corticosteroid dependence
The need for ongoing or repeated glucocorticoid use for at least two months to maintain CR or R.
Refractory ITP
Relapsed after splenectomy (failure to maintain CR or R) and required therapy
On-demand therapy
Therapies used to temporarily increase the platelet count in special situations such as trauma or surgery.
Adjunctive therapies
Treatments that are not designed to increase platelet counts but that may decrease bleeding symptoms by other means, for example, treatment with oral contraceptives or antifibrinolytic drugs.
TRUE OR FALSE
The overall incidence was higher in women than in men
TRUE
The overall incidence was higher in women than in men
ITP can affect males and females of any age
A male predominance was seen in patients younger than 18 years of age and older than 65 years.
Approximately _________ of patients have platelet counts greater than 30 x 109/L at diagnosis and no significant bleeding, unlike patients with a similar platelet level caused by states of reduced production.
One-third
Pattern of bleeding in ITP
Mucocutaneous
Intracerebral hemorrhage is rare and generally occurs in patients with platelet counts less than 10 x 109/L and usually is associated with trauma or vascular lesion
Patients with ITP who present with severe thrombocytopenia (<30 x 109/L) and do not respond to any therapy within 2 years have a _____ fold increased risk of death compared with the general population.
Fourfold
TRUE OR FALSE
The purpuric lesions seen in ITP are palpable, blanch with pressure, and often develop on distal regions of the extremities and on skin areas exposed to pressure (eg, around tight belts and stockings and at tourniquet sites).
FALSE
The purpuric lesions seen in ITP are not palpable, do not blanch with pressure, and often develop on distal regions of the extremities and on skin areas exposed to pressure (eg, around tight belts and stockings and at tourniquet sites).
TRUE OR FALSE
The spleen in ITP usually is enlarged and palpable in some patients, a finding considered to occur with the same incidence as in normal adults.
FALSE
The spleen in ITP usually is not enlarged but may be palpable in some patients, a finding considered to occur with the same incidence as in normal adults.
However, splenomegaly should trigger a search for secondary ITP, such as lymphoma or chronic lymphocytic leukemia
Constitutional symptoms, such as fever, significant weight loss, marked splenomegaly, hepatomegaly, and lymphadenopathy provide evidence that the thrombocytopenia has another cause.
TRUE OR FALSE
Patients with ITP are at an approximately twofold increased risk of venous and arterial thrombosis.
TRUE
Patients with ITP are at an approximately twofold increased risk of venous and arterial thrombosis.
Laboratory Features of ITP
- Isolated thrombocytopenia without erythrocyte or leukocyte abnormalities
- Platelet anisocytosis is a common finding as is large platelet forms
- Platelet distribution width is increased.
The ultrastructure of ITP platelets viewed by electron microscopy is similar to that of normal platelets.
Condition wherein Autoimmune hemolytic anemia with a positive direct antiglobulin (Coombs) test and reticulocytosis with ITP
Evans syndrome
