Download Isolated Acute Thrombocytopenia in a 21-Year

Case Studies
Isolated Acute Thrombocytopenia in a 21-Year-Old
Caucasian Male
Charles Beavers, MD,1 William Kern, MD,2 Kenneth Blick, PhD, ACS, ABCC, NACB 2
( 1University of Oklahoma, Pathology, 2University of Oklahoma Health Sciences Center, Pathology, Oklahoma City, OK)
DOI: 10.1309/LMGIB39R5HHCRASO
Clinical History
Patient: 21-year-old Caucasian male.
Chief Complaint: Bleeding gums.
History of Present Illness: The patient is
a basic training recruit who presented to an
outside hospital after 3 days of bleeding gums
and 1 episode of hematuria. Upon waking,
he first noticed gum bleeding in the morning
after spitting out a mouthful of blood. For 2
more days, the patient awoke with blood in his
mouth and also noted frank blood in his urine
on day 3. He then presented to an outside
hospital for treatment. The patient received
3 units of platelets on admission; however,
his platelet count did not increase. He denied
hematochezia and melena. One week previous,
the patient recounted having a sore throat with
cough and fever.
Medical History: The patient reported no
chronic illnesses. He denied any history of
blood disorders in his family. He recounted he
had not drank alcohol or smoked in the last 5
weeks of basic training. He reported 20 total
sexual partners in his lifetime. The patient
tested negative for HIV and ANA prior to the
current encounter.
Current Medications: Tessalon (antitussive),
Tylenol. No thrombocytopenia-associated
agents were found in the patient’s previous
medical history.
Questions
1. What are this patient’s most striking clinical and laboratory
findings?
2. How do you explain these findings?
3. Could this patient be experiencing heat stroke?
4. What is this patient’s diagnosis?
5. What is the etiology of this patient’s condition?
6. What is the standard therapy for this patient’s disorder?
7. What is the diagnostic approach of ruling in this disease and
excluding other similar disorders?
Possible Answers
1. The patient has a significant history for bleeding gums,
hematuria, petechiae and purpura, bruising, and recent history
of an upper respiratory infection. In addition, the patient’s
complete blood count (Table 1) reveals that he is extremely
thrombocytopenic, but significantly is neither neutropenic or
anemic. Coagulation studies (Table 2) point out that the patient has no apparent factor deficiency. Furthermore, fibrinogen and fibrin split products essentially rule out disseminated
intravascular coagulation (DIC). The peripheral blood smear
(Image 1) confirms that there are very few platelets in circulation, and no platelet clumping is apparent; the red and white
blood cell morphologies appear normal, with no immature
precursors observed. Also, no schistocytes are present on the
smear, making thrombotic thrombocytopenic purpura (TTP)
unlikely. The history of recent platelet transfusion also becomes important by showing that no increase occurred after
transfusion suggesting a consumptive process.
2. The patient’s bleeding symptoms are most likely
related to his platelet deficiency. A lack of platelets attaching to von Willebrand factor (vWF) at an area of exposed
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Physical Examination: Temperature, 36.3°C;
blood pressure, 130/75; pulse, 65. He was
alert and oriented and in no apparent distress.
Petechie and purpura of the lips and gums
were present. Small hemorrhagic lesions
were also present on the hard palate. There
was a petechial rash below the knees and
on the patient’s feet bilaterally and bruising
on the right antecubital surface of the arm.
Hepatosplenomegaly and lymphadenopathy
were not present.
Principal Laboratory Findings
Table 1, Table 2, and Image 1.
endothelium would prevent the formation of an initial platelet
plug. Since primary hemostasis via the platelet plug would be
insufficient in this condition, secondary hemostasis occurring
from fibrin cross-linkage would also be inhibited.1 An absence
of other contributing factors, such as a positive ANA, positive
HIV test, medication history, schistocytes, or multi-lineage
abnormalities in the blood smear, also supports our diagnosis
of platelet deficiency due to consumption.
3. The patient’s history of intense exercise makes it necessary to rule out heat stroke. Heat stroke has been documented
to cause liver failure, petechial hemorrhage, fibrinolysis,
thrombocytopenia, and even DIC.2 It is unlikely that the
patient is experiencing heat stroke because his bleeding symptoms and thrombocytopenia did not resolve with rest. The
patient was also euvolemic with laboratory results that did not
suggest excessive coagulation or a lack of coagulation factors.
4. Most likely diagnosis: Acute immune thrombocytopenic
purpura (ITP) due to anti-platelet antibodies. Although most
individuals with acute ITP are children less than age 8, our patient’s signs and symptoms fit more closely with the childhood
presentation of the disorder. Chronic ITP would be much
more common in a middle-aged female, possibly with other
autoimmune stigmata and a history of multiple remissions and
relapses. Mortality due to ITP most often occurs from intracranial hemorrhage in these individuals with a 1% lifetime risk.3
5. Immune thrombocytopenic purpura is an autoimmune
disease typically thought of as a consumptive process although
recent evidence indicates that production deficits occur due to
megakaryocyte injury as well.4 Surprisingly, only about 70%
of ITP patients present with detectable anti-platelet antibodies. Because other disorders may be associated with these same
antibodies, testing for them is neither diagnostically sensitive
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Case Studies
Table 1_Hematology Laboratory Results
Test
Patient’s Result
Reference Interval
White blood cells
Red blood cells
Hemoglobin
Hematocrit
Platelets
8.40
4.53
13.5
39.7
<6.0
4.0–11.0 K/mm3
4.50–5.90 M/mm3
13.0–18.0 g/dL
39.0–52.0%
140–440 K/mm3
Table 2_Coagulation Laboratory Results
Test
Patient’s Result
Reference Interval
Prothrombin time
International normalized ratio
Partial thromboplastin time
Fibrinogen
Fibrin split products
10.3
1.0
23.0
338
<10
9.5–11.0 seconds
0.9–1.2 ratio
25.0–32.0 seconds
150–450 mg/dL
<10 mcg/mL
Image 1_Our patient’s blood smear revealing a paucity of platelets.
nor specific enough for ITP. Autoantibodies are first produced
when CD4+ T-helper type 2 (Th2) cells are sensitized, sometimes by viral illness in children, but is typically idiopathic in
adults. The Th2 cells then activate a B cell to clonally differentiate into plasma cells, which then begin producing the offending antibody towards platelets. The most common antigenic
sites on platelets are GP IIb/IIIa (fibrinogen receptor) and GP
Ib-IX (vWF receptor). After platelets have been opsonized, they
are then phagocytized by macrophages that attach to platelet
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LABMEDICINE j Volume 40 Number 6 j June 2009
antibodies via the Fc fragment receptor. Macrophages break
down the platelet into epitopes and then present them on its
surface to other Th2 cells which stimulate other B cells to begin
producing more antibodies against the platelets, resulting in a
vicious cycle.5 Megakaryocytes in the bone marrow may also
be damaged by these autoantibodes and/or CD8+ killer T cells,
but much is still unknown about this process. Of particular
note and inexplicably, endogenous thrombopoetin levels do not
increase in ITP, unlike other thrombocytopenic diseases.6
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Case Studies
6. American and British treatment guidelines have recommended that patients receive treatment for thrombocytopenia if
they have 1) significant bleeding risk; 2) <20 K/mm3 platelets
and moderate bleeding (mucosal); or 3) <10 K/mm3 platelets
with no bleeding symptoms. Standard first-line therapy for
ITP includes high-dose corticosteroids, platelet transfusion,
IVIg, and/or IV anti-D.7 Plasmapheresis has not yet shown to
be of benefit unless the patient presents with IgM antibodies.8
Refractory thrombocytopenia has also been historically treated
with splenectomy and even low-dose chemotherapy, but this is
becoming more rare. Novel treatments include 1) anti-plasma
cell therapy with Rituximab; 2) stimulating the megakaryocytes
to increase production via thrombopoeitin analogues; or 3)
preventing antibodies from binding to the Fc receptor on the
macrophage.9
In order to diagnose ITP, no single laboratory test establishes the diagnosis, but rather 3 criteria must be satisfied. The
patient must have 1) an isolated thrombocytopenia with an
otherwise normal peripheral complete blood count and smear;
2) an absence of lymphadenopathy and hepatosplenomegaly;
and 3) an increase in platelets in response to traditional therapy (steroids, IVIg, or IV anti-D).10
Patient Followup
The patient was admitted for 4 days, his platelet level responded significantly to 116 k/mm3, and bleeding symptoms
were completely resolved. On followup, the patient has had
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no recurrence of disease, and again corresponds more with the
profile of an acute childhood ITP presentation.11 LM
Keywords: ITP, immune thrombocytopenic purpura, autoimmune
disease, thrombocytopenia, platelet destruction.
1. Cotran, Kumar, and Collins. Robbins Pathologic Basis of Disease. 6th ed. (1999)
117–121.
2. Beard ME, Hickton CM. Haemostasis in heat stroke. Br J Haematol.
1982;52:269–274.
3. Godeau B, Provan D, Bussel J. Immune thrombocytopenic purpura in adults.
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Diagnosis and management. Pediatr Clin N Am. 2008;55:393–420.
6. Aledort LM, Hayward C, Chen M-G, et al. Prospective screening of 205 patients
with ITP, including diagnosis, serological markers, and the relationship between
platelet counts, endogenous thrombopoietin, and circulating antithrombopoietin
antibodies. Am J Hematol. 2004;76:205–213.
7. George JN, Woolf SH, Raskob GE, et al. Idiopathic thrombocytopenic purpura:
A practice guideline developed by explicit methods for the American Society of
Hematology. Blood. 1996;88:3–40.
8. Patel TC, Moore SB, Pineda AA, et al. Role of plasmapheresis in
thrombocytopenic purpura associated with Waldenström’s macroglobulinemia.
Mayo Clin Proc. 1996;71:597–600.
10. Bromberg ME. Immune thrombocytopenic purpura—The changing therapeutic
landscape. N Engl J Med. 2006;355:1643–1645.
11. Kuwana M, Kurata Y, Fujimura K, et al. Preliminary laboratory based diagnostic
criteria for immune thrombocytopenic purpura: Evaluation by multi-center
prospective study. J Thromb Haemostas. 2006;4:1936–1943.
12. Tarantino MD, Bolton-Maggs PH. Update on the management of immune
thrombocytopenic purpura in children. Curr Opin Hematol. 2007;14:526–534.
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