The multiple causes and
myriad presentations of
thrombocytopenia
As heparin exposure increases in hospital patients,
the thrombocytopenia risk rises.
By Patti Radovich, MSN, RN, CNS
MARTIN NABER, age 76, arrives at the
urgent care clinic with severe bruising
of the arms and lower legs. He reports
he has had nosebleeds and generalized fatigue for the last week and had
an upper respiratory infection about a
month ago. When drawing blood
samples, the phlebotomist notes Mr.
Naber is bleeding more than expected,
and applies a pressure dressing to the
venipuncture site. Laboratory values
reveal prolonged clotting time and a
markedly low platelet count. The
physician suspects idiopathic thrombocytopenic purpura (ITP).
Since sustaining a pelvic fracture,
Joan Baumann, age 56, has been
taking prophylactic heparin (5,000
units subcutaneously) every 8 hours.
She has been receiving a heparin
flush through an arterial line. During her second week in the hospital,
the nurse notes her right leg is cooler
than the left and her pulse is thready.
Blood tests show her platelet count
has dropped from a normal level to
90,000 cells/mm3; other studies reveal arterial occlusion. The hematologist diagnoses heparin-induced
thrombocytopenia (HIT). An emergency thrombectomy is performed to
restore blood flow to the leg.
Defined as a platelet count below 150,000 cells/mm3, thrombocytopenia can be innate or acquired.
Though relatively rare, it may be
complex. Bleeding, the major complication, can manifest as petechiae,
purpura on the skin and mucous
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membranes, and epistaxis (nosebleed) of both nostrils. The disorder
isn’t life-threatening unless the
platelet count falls below 20,000
cells/mm3. But its complications or
underlying cause can be fatal.
Various drugs and medical interventions can affect the hematologic system, leaving patients—especially those
requiring critical care—at risk for thrombocytopenia. This article explores the
types and causes of thrombocytopenia,
clinical features, and treatment.
Acute vs. chronic ITP
Acute ITP (also called primary immune thrombocytopenia) is an acquired immune-mediated disorder
marked by a platelet count below
100,000 cells/mm3 without obvious
initiating factors or underlying causes. It accounts for approximately
89% of thrombocytopenia cases and
is more common in children. As in
Mr. Naber’s case, ITP may follow an
infection. It usually lasts 1 to 2
months and resolves spontaneously
without long-term consequences.
Chronic ITP has an insidious onset.
It usually arises between ages 20 and
50, affects more women than men,
and commonly occurs in persons with
other immune-associated disorders,
such as systemic lupus erythematosus.
Causes of thrombocytopenia
Thrombocytopenia may stem from
hemorrhage; bone marrow abnormalities, such as aplastic anemia;
bone cancer; infections; certain
medications; and disorders in which
platelets are destroyed. Four general
conditions can affect platelet counts
and cause thrombocytopenia—
decreased platelet production, increased platelet destruction, greater
platelet utilization, and impaired
platelet distribution. (See Platelets:
Putting the brakes on bleeding.)
Decreased platelet production
Platelet production may decrease
from any condition that injures or depresses the bone marrow, such as
cancer, certain drugs and chemicals,
and radiation exposure. In druginduced thrombocytopenia, an antigenantibody reaction leads to immune
complexes that destroy platelets
through complement-mediated lysis.
Many drugs can affect the platelet
count and function, underscoring
the importance of taking a patient’s
complete drug history.
Increased platelet destruction
Shortened platelet survival due to
platelet destruction can result from immune reactions. Snake venom and
such drugs as quinidine, morphine,
and heroin can destroy platelets
through complement activation or a
drug antibody-platelet antigen response. Other antigen-antibody responses, such as those seen in sepsis
and malaria, can destroy platelets
through drug antibody-platelet antigen
reactions or complement activation.
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Hemolytic-uremic syndrome
stems from infectious colitis and release of bacterial toxins that lead to
hemolytic anemia and acute renal
failure, as well as thrombocytopenia. T-cell mediated platelet destruction and impaired platelet production occur in ITP.
Increased platelet utilization
This condition occurs in ITP; proteins on the platelet-cell membrane
stimulate production of autoantibodies (usually immunoglobulin G),
which adhere to the platelet membrane. Although platelets function
normally, the spleen reacts as if
they’re foreign and destroys them
after just 1 to 3 days of circulation.
Impaired platelet distribution
This phenomenon occurs with
splenomegaly. The enlarged spleen
can hold a large number of platelets,
making them unavailable to the circulating blood volume. Patients with
cirrhosis, lymphoma, or leukemia
may develop this condition.
Another condition that impairs
platelet distribution is disseminated
intravascular coagulation (DIC),
which arises as a complication of an
acute condition. In DIC, platelets are
consumed when release of tissue
factor activates internal coagulation
pathways, as with infection or vascular endothelial injury. The underlying condition triggers a response
that causes thrombin generation and
secondary fibrinolysis. Thrombin
generation activates platelets and increases intravascular fibrin, resulting
in thrombocytopenia and formation
of thrombi (microclots). Thrombi
obstruct capillaries in organs and
tissues, leading to tissue necrosis.
Ultimately, coagulation factors are
depleted; thrombocytopenia and
thrombus formation present a clinical picture of bleeding and thrombosis. DIC may occur acutely in patients with acute respiratory distress
syndrome or sepsis. It also can be
chronic, as in some cases of cancer
and aortic aneurysm.
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Platelets: Putting the brakes on bleeding
Platelets (also called thrombocytes) are small cell fragments produced when large
bone-marrow cells called megakaryocytes disintegrate and are released into the
circulation in large numbers. Thrombopoietin, a glycoprotein hormone, regulates
platelet production by the marrow.
Capable of changing shape, platelets circulate in the bloodstream for about 10
days. A reserve of platelets is sequestered in the spleen and released into the
bloodstream when needed.
The main function of platelets is to maintain hemostasis by adhering to damaged blood-vessel walls and aggregating to form a barrier to blood flow. Platelet
function, adhesion, and aggregation are maintained by alpha granules, von Willebrand factor, fibrinogen, thromboxane A2, platelet factor 4, and thromboglobulin.
When heparin is the cause
Repeated heparin exposure can
cause HIT, an immune-mediated
drug reaction. Approximately 3% of
patients receiving I.V. heparin develop a transient form of mild to
moderate thrombocytopenia. An estimated 600,000 new cases of HIT
occur each year. In half that number, thrombotic complications arise.
Typically, HIT arises 5 to 14 days
after the patient starts heparin but
may present within 24 hours in patients with previous heparin exposure. The platelet count is below
100,000 cells/mm3 or 50% lower
than the patient’s baseline value.
HIT is rarely associated with severe
thrombocytopenia (platelet count
below 10,000 cells/mm3).
Assessment
As Mr. Naber’s and Ms. Baumann’s
cases show, thrombocytopenia has
diverse presentations. In some patients, signs and symptoms reflect
blood loss; in others, increased coagulation and clot formation. General signs and symptoms include:
• petechiae on the anterior chest,
arms, neck, or oral mucous
membranes
• spontaneous bleeding from the
gums or both nostrils
• oozing of blood from incisions
and intravascular catheter sites
• excessive vaginal bleeding
• occult blood in the stool
• hematuria
• ecchymosis
• abdominal pain
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• absent bowel sounds
• neurologic changes, such as confusion, headache, blurred vision,
and coma.
ITP most often presents as petechiae, purpura, bleeding gums,
epistaxis, and menorrhagia. Rarely,
patients with acute ITP develop GI
bleeding and hematuria. On assessment, they may have a spleen of
normal size, no other identifiable
causes of thrombocytopenia, and
normal bone marrow with a low
platelet count. Usually, the diagnosis
is made when all other thrombocytopenia causes have been ruled out.
Treatment
Treatment varies with the underlying cause. To determine if the patient requires treatment, practitioners consider the extent of bleeding;
comorbidities that may increase the
bleeding risk, complications of various therapies; tolerance of side effects; whether potential interventions could cause bleeding; other
medications being administered;
and the patient’s concerns, expectations, activity level, and lifestyle.
Treatment guidelines have been
established for ITP and HIT. Typically, ITP is managed with oral prednisone or other glucocorticoids,
which suppress the autoimmune response. Some patients who respond
to these drugs relapse when the drug
is withdrawn; they may then receive
alternative immunosuppressants, such
as azathioprine, cyclophosphamide,
or cyclosporine. If thrombocytopenia
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persists despite immunosuppressant
therapy or if the disorder causes active bleeding or necessitates a rapid
rise in the platelet count, I.V. immunoglobulin may be given. Patients
unresponsive to medical management may require a splenectomy.
In HIT, all heparin is withdrawn
and the patient is evaluated for less
obvious heparin exposure, such as
heparin-coated catheters and heparin
flushes. Both symptomatic and
asymptomatic patients are at risk for
thrombolic events because the drug
reaction can continue for some time
after heparin withdrawal. Once all heparin is halted, an alternative anticoagulant (such as argatroban, lepirudin,
or bivalirudin) must be initiated.
In thrombocytopenia caused by
decreased platelet production, the
patient’s medications must be reviewed for those that could cause
thrombocytopenia; these must be
withdrawn or their dosage reduced.
(See Drugs that can cause thrombocytopenia.) Drug withdrawal or a
dosage reduction may resolve the
problem, but some patients may
need anti-inflammatory agents for
immunosuppression. If decreased
platelet production stems from snake
venom, antivenin administration may
either improve or complicate the
clinical picture. Antivenin stems coagulopathy resulting from envenomation but may not reverse all processes triggered by the snakebite.
Coagulopathy may recur and the antivenin’s effect on coagulation may
mask initial signs of recurrence. The
patient’s laboratory studies should be
monitored continuously to assess for
stabilization of coagulation or recurrence of coagulation abnormalities.
In thrombocytopenia brought on
by altered platelet distribution, the
underlying cause must be treated.
In many cases, spleen size decreases with treatment and the level of
circulating platelets rises.
Nursing interventions
Nursing interventions include prevention, early identification, and manage12
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Drugs that can cause thrombocytopenia
The drugs below have been linked to thrombocytopenia development.
• Penicillins
• Digoxin
• Aspirin
• Phenytoin
• Furosemide
• Cephalosporins
• Quinine
• Gentamycin
• Chemotherapeutic
• Ribavirin
• Heparin
agents
• Rifampin
• Ibuprofen
• Chlorothiazide
• Sulfonamides
• Indomethacin
• Cimetidine
• Tamoxifen
• Morphine
• Clarithromycin
• Thiazide diuretics
• Naproxen
• Cocaine
ment of thrombocytopenia and its
complications. Take steps to minimize
the patient’s risk of injury, as by preventing falls, reducing the bleeding
risk, and preventing infection. Be
aware that thrombocytopenia increases the risk of infection in patients receiving corticosteroids. Steroid-related
skin changes, bruising, and bleeding
under the skin increase the risk of
skin breakdown. Microemboli and altered coagulation raise the risk of ischemia of the extremities and altered
organ function. To minimize these
problems, ensure continuity of care
and evaluate skin and organ function.
When assessing the patient for
potential complications and response to treatment, closely monitor
laboratory values, especially:
• platelet count, which may indicate the patient’s response to
treatment
• white blood cell count, with an
elevation indicating infection
• hemoglobin, hematocrit, and coagulation tests, which may suggest ongoing bleeding or a positive response to treatment
• renal function tests, such as urinalysis, serum creatinine, and
creatinine clearance.
Monitor the patient’s fluid intake
and output to evaluate hydration
status and check stools for occult
blood. Remember that in thrombocytopenia, increased bleeding may
lead to hypovolemia, which can affect sensory perception and set the
stage for falls and renal dysfunction.
If the patient requires isolation due
to immunosuppressants or infection,
perform a psychosocial assessment
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to evaluate psychosocial needs.
To minimize the bleeding risk,
restrict the use of venipuncture, razors, toothbrushes, dental floss, tampons, and intramuscular and subcutaneous injections. Know that
placement of nasogastric tubes, rectal tubes, and suctioning equipment
may be restricted. As ordered, withhold drugs that can alter coagulation. In some patients, occupational
or physical therapy may be restricted due to the increased risk of
bleeding and falls. Good oral care
(using oral swabs, a normal saline
rinse, or other mouthwash as appropriate) helps to keep mucous membranes moist and minimize bleeding.
Teach the patient and family how
to avoid injury. Determine the types
of assistance the patient may need
with activities of daily living. Point
out that some activity restrictions
may be needed to minimize the injury risk. Teach patients and family
members how to recognize signs
and symptoms of infection and ischemia. Make sure they know when
to contact the physician or seek immediate medical help.
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Selected references
Donovan JL, Tran MT, Kanaan AO. An
overview of heparin-induced thrombocytopenia. J Pharm Pract. 2010;23(3):226-234.
http://jpp.sagepub.com/content/23/3/226.
abstract. Accessed November 30, 2010.
Munro N. Hematologic complications of critical
illness. AACN Adv Crit Care. 2009;20(2):145-154.
Visit www.AmericanNurseToday.com/
Archives.aspx for a list of references.
Patti Radovich is a clinical nurse specialist and
manager of nursing research at Loma Linda University
Medical Center in Loma Linda, California.
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