A 22-year-old white man with no prior medical problems presented to the
emergency department with profuse nose bleeding. He also noticed unusual mild
headaches and bruises on his thighs and arms. The nose bleeding started about
half an hour ago and was not responding to local pressure. He was not on any
medications and denied use of illicit drugs. Physical examination revealed
bleeding from the left nostril and multiple bruises on his legs, abdomen and
arms. There was no evidence of pallor, lymphadenopathy or organomegaly.
nose was packed immediately in the emergency department and stat blood
specimens for complete blood count, cross and match, and chemistry were drawn.
A CT scan of the head was normal. The blood tests revealed a white count of 5.0
K/uL, hemoglobin 13.0 gm/dL and platelets of 7 K/uL. His blood group was
A-negative and blood chemistry was normal including creatinine, lactate
dehydrogenase (LDH) and liver function tests. He was also tested negative for
HIV and hepatitis. Peripheral smear showed no schistocytes, normal red blood
cell morphology and many large platelets.
A diagnosis of immune thrombocytopenic purpura was made in this otherwise
healthy young man and he was started on intravenous immunoglobulin G (IVIG) at
a dose of 2 gm/kg. He responded well to the treatment and his platelets
increased to 45 K/uL within 24 hours. Eventually, he was discharged home at a
platelet count of 80 K/uL with an appointment for follow-up in a week.
days later he came to the emergency department again with complaints of mild
headaches and frequent nose bleeds. Blood count showed stable hemoglobin, but
platelet count was 10 K/uL. The treatment with IVIG was started and steroids
were added, but this time also the response was short lived. He was immunized
appropriately and was referred for splenectomy. He had an excellent response
and his platelet count normalized within a couple of days. Unfortunately, his
disease relapsed within a month and his platelet count dropped to 15 K/uL once
Peripheral blood smear of a patient with ITP showing decreased number of
platelets and a large platelet in the middle.
Source: W Razaq
A) Post-splenectomy trial of steroids.
B) Vincristine infusion.
Rituximab weekly x 4.
D) Platelet transfusions.
Wajeeha Razaq, MD, is an Assistant Professor of Clinical Medicine in the
Department of Internal Medicine, Section of Hematology/Oncology at the
University of Nebraska and is a member of the HemOnc Today
ITP is a clinical syndrome in which a decreased number of platelets manifest
as bleeding diathesis, easy bruising and capillary blood leakage into the mucus
membranes and skin.
In this disease, the platelets are coated with autoantibodies to platelet
membrane antigens resulting in phagocytosis by the reticuloendothelial system
(figure 2). Increased destruction of platelets combined with inadequate
compensation by the bone marrow results in thrombocytopenia. ITP is a diagnosis
of exclusion and other cause of thrombocytopenia eg, leukemia, thrombotic
thrombocytopenic purpura, drug reactions and myelodysplastic syndrome should be
ruled out. Most cases of ITP especially in children are mild and self-limited
and do not require any medical intervention. Some of the ITP patients have
moderate to severe thrombocytopenia with clinical findings that require medical
The goal of the treatment is to increase the number of platelets to a safe
level permitting the patients to live normal lives while awaiting spontaneous
remissions. ITP is an incurable disease and relapses are common.
Asymptomatic patients with a platelet count greater than 20 K/uL should not
require routine hospitalization. Although there is no specific platelet count
that defines an indication of initial treatment, it has been seen in many
studies that patients with platelet count between 20 K/uL to 50 K/uL rarely
develop bleeding complications. For many years, glucocorticoids or IVIG
remained the initial therapies of choice for these patients. Anti Rh° (D),
later became available for Rh positive patients with response comparable to
steroids or IVIG.
Refractory ITP is defined as persistence of ITP for more than three months,
no response to splenectomy and platelet count less than 30 K/uL. There is no
standard algorithm for treatment of these patients but chemotherapy agents such
as azathioprine, cyclophosphamide and rituximab (Rituxan, Genentech) have been
used with good response. The simplest way to treat chronic refractory ITP is to
start steroids and try to achieve a safe platelet level at the lowest possible
dose. Because of the adverse effects related to chronic steroid use, it
can’t be given for a long time, so immunosuppressive agents have been
tried with variable success rates. Rituximab, an anti-CD20 antibody, is an
efficacious treatment for non Hodgkin’s Lymphoma. There has been a great
interest in its use in autoimmune diseases like ITP. The mechanism of action of
rituximab in ITP is assumed to be the selective depletion of CD20 B cells that
affects autoantibody production. Cooper et al treated 18 chronic ITP patients
with rituximab and 16 of them achieved a complete response that was maintained
for 72 weeks (Br J Haematol. 2004;125:232-239). A systematic
review of several uncontrolled studies demonstrated that the use of this
monoclonal antibody produces response in 62% of chronic ITP patients.
(Ann Intern Med. 2007;146:25–33) These studies show that
rituximab has limited but valuable activity in refractory ITP patients.
We treated our patient with rituximab (375 mg/m2 weekly for four
weeks) and his platelet count went up from 15 K/uL to 175K/uL within a month.
He is been in remission for 18 months.
Perhaps a careful history of upper gastrointestinal distress would lead to
endoscopy, Helicobacter pylori infection and amelioration of ITP by antibiotic
treatment. Perhaps not, but worth consideration.
– Harry S. Jacob, MD
Chief Medical Editor