compression stockings, and surgery.3 In 10 RCTs
involving 2,174 patients, LMWH given for 8 to
12 days significantly lowered the incidence of SVT
extension and/or recurrence compared with placebo
when using either prophylactic (OR 0.32; 95% CI,
0.16–0.65) or treatment doses (OR 0.33; 95% CI,
0.16–0.18). Although the incidence of VTE was lower
initially in both the prophylactic (OR 0.25; 95% CI,
0.03–2.25) and therapeutic (OR 0.26; 95% CI, 0.03–
2.34) treatment groups, the difference did not reach
statistical significance.
Two RCTs (n=267) showed NSAIDs were more
effective than placebo in reducing pain, inflammation,
and recurrence/extension of SVT (OR 0.33; 95% CI,
0.16–0.68). There was no difference in the incidence
of VTE. Two RCTs (n=274) evaluated NSAIDs versus
LMWH. LMWH showed a statistically insignificant
reduction of VTE (OR 0.93; 95% CI, 0.23–3.83) and
SVT extension (OR 1.18; 95% CI, 0.53–2.60) relative
to NSAIDs. These studies suffered from small sample
sizes, making comparisons difficult.3
Compression stockings plus LMWH appeared to
be more effective at preventing VTE (OR 0.07; 95%
CI, 0.00–1.32) or SVT extension/recurrence (OR 0.07;
95% CI, 0.01–0.52) when compared with compression
stockings alone. However, the authors noted that the
difference between compression stockings alone versus
compression stockings plus LMWH for preventing
VTE was not statistically significant.3
The Cochrane review noted a comparison
between LMWH and saphenofemoral disconnection
in 1 unblinded RCT (n=60). This procedure did not
significantly lower the risk of extension/recurrence
compared with LMWH; however, the confidence
interval was wide (OR 0.31; 95% CI, 0.03–3.17).3
Venous ligation in 592 patients showed a
nonsignificant reduction in VTE (OR 0.32; 95% CI,
0.06–1.62) and SVT recurrence/extension (OR 0.42;
95% CI, 0.15–1.16). However, venous stripping with
elastic stockings showed a significant decrease in SVT
extension and recurrence (OR 0.07; 95% CI, 0.01–
0.57) compared with elastic stockings alone.3
The American College of Chest Physicians
Guidelines advocates medical treatment over surgical
intervention for SVT. Prophylactic-dose LMWH or
intermediate doses of unfractionated heparin for at
least 4 weeks are recommended. Alternatively, warfarin
with a target INR of 2 to 3 (bridged for at least 5 days
with LMWH) can be used. NSAIDs are recommended
in patients with short-segment SVT or SVT that is
distant from the saphenofemoral junction.4
Michael M. Braun, DO
Madigan Army Medical Center
Joint Base Lewis-McChord, WA
Megan Belprez, MD
Womack FMR Clinic
Fort Bragg, NC
The opinions and assertions contained herein are the private views
of the authors and are not to be construed as official or as reflecting the views
of the US Army Medical Department of the US Army at large.
1. Wichers IM, et al. Neth J Med. 2008; 66(10):423–427. [LOE 2b]
2. Decousus H, et al. Ann Intern Med. 2010; 152(4):218–224. [LOE 2b]
3. Di Nisio M, et al. Cochrane Database Syst Rev. 2007; (2):CD004982. [LOE 1a]
4. Kearon C, et al. Chest. 2008; 133(6 suppl):454S–545S. [LOE 1a]
What is the differential diagnosis
for an elevated monocyte count
in a patient with an acute febrile illness?
Evidence-Based Answer
Monocytosis can have many causes in a febrile patient
with an acute illness. Etiologies can be broadly grouped
into hematologic disorders, infections, inflammatory
causes, and miscellaneous causes. The history and
physical examination should guide the clinician in
developing a differential diagnosis and planning further
work-up. (SOR: C, based on expert opinion.)
Currently available information regarding the causes of
monocytosis in a febrile patient is limited to narrative
reviews and expert opinions from textbooks. Authors
report that opinions are based on case reports and case
series, many of which are decades old.
According to an authoritative text,1 the differential
for an acute febrile illness with monocytosis can be
broadly broken down into hematologic disorders and
malignancies, infections, inflammatory causes, and
miscellaneous causes. Experts state that the differential
diagnosis is broad but can usually be narrowed through
careful history and examination.2
According to a narrative review2 and general
medical and authoritative texts,1,3–5 hematologic
disorders causing monocytosis include various forms of
leukemia, Hodgkin and non-Hodgkin lymphoma, and
chronic or congenital neutropenia. Myelodysplastic
disorders can exhibit monocytosis in up to 25%
Evidence-Based Practice / Vol. 15, No. 2
11
of cases.1 Profound monocytosis is more likely to
represent a hematologic disorder or malignancy than
other causes. Nonhematologic malignancies can also
cause monocytosis.1,5 The relative immunosuppression
present with some malignancies can lead to infections,
and hence a presentation with acute fever.
Although most general medical textbooks list
infection as a cause of monocytosis, according to
1 authoritative text,1 infections do not typically cause
isolated monocytosis. Both general medical and
authoritative textbooks list various bacterial, viral,
and protozoan causes of monocytosis.1,3–5 Bacterial
infections that could cause monocytosis and fever
include tuberculosis, syphilis, subacute bacterial
endocarditis,
ehrlichiosis/anaplasmosis,
Rocky
Mountain spotted fever, and brucellosis. The resolution
of an acute bacterial infection such as pneumonia can
also result in monocytosis.1 Viral causes of monocytosis
and acute fever include dengue hemorrhagic fever,
cytomegalovirus
infection,
and
varicella-zoster
infection. Malaria and leishmaniasis are protozoan
illnesses that can also result in monocytosis.
Inflammatory and rheumatologic causes of
monocytosis and fever include subacute lupus
erythematosus, rheumatoid arthritis, temporal arteritis,
sarcoidosis, and inflammatory bowel disease.1,3–5 A
narrative review2 also supports these associations.
Williams Hematology1 is the only text to include celiac
disease as a possible cause of monocytosis.
Miscellaneous causes of fever and monocytosis
include Kawasaki disease,1 postsplenectomy state,1,3,5
and drug reactions.3
Bridget DeLong, MD
Stuart Hannah, MD
Melissa Stiles, MD
U of WI Department of Family Medicine
Madison, WI
1.Lichtman MA. Monocytosis and monocytopenia. In: Lichtman MA, Kipps TJ, Seligsohn
Uri, Kaushansky K, Prchal JT, eds. Williams Hematology. 8th ed. New York, NY: McGrawHill Professional; 2010. [LOE 5]
2.Cunha BA. Infect Dis Clin North Am. 2007; 21(4):1137–1187. [LOE 5]
3.Boxer LA. Leukocytosis. In: Kliegman RM, Behrman RE, Jenson HB, Stanton B, eds.
Nelson Textbook of Pediatrics. 18th ed. Philadelphia, PA: Saunders Elsevier; 2007.
[LOE 5]
4.Holland SM, Gallin JI. Disorders of granulocytes and monocytes. In: Fauci AS, Braunwald
E, Kasper DL, et al, eds. Harrison’s Principles of Internal Medicine. 17th ed. New York,
NY: McGraw Hill Professional; 2008. [LOE 5]
5.Dinauer MC, Coates TD. Disorders of phagocyte function and number. In: Hoffman R,
Furie B, Benz EJ Jr, McGlave P, Silberstein LE, Shattil SJ, eds. Hematology: Basic Principles. 5th ed. Philadelphia, PA: Churchill Livingston Elsevier; 2008. [LOE 5]
12
Evidence-Based Practice / February 2012
Can medication prevent a transfusion reaction
in someone with a history of febrile transfusion
reactions?
Evidence-Based Answer
No. Medication administration prior to transfusions
does not reduce the incidence of febrile, nonhemolytic
transfusion reactions (FNHTR), even in patients with
a history of FNHTR. (SOR: B, based on a systematic
review of low quality studies.)
A Cochrane review assessed the clinical effects
and safety of pharmacologic interventions for the
prevention of allergic and FNHTR in patients with and
without a history of transfusion reactions.1 Criteria for
considering studies for review included both published
and unpublished RCTs with patients requiring a blood
transfusion including cancer, hematologic malignancy,
and chronic transfusions.
Of the 3 double-blind RCTs evaluated in the
Cochrane review, 1 included patients with a history of
either allergic or FNHTR, 1 excluded patients with a
history of FNHTR, and 1 included only patients with a
history of FNHTR. Due to heterogeneous study designs,
a meta-analysis could not be performed.1
The study that included patients with either allergic
or FNHTR was a double-blind prospective RCT
evaluating the efficacy of acetaminophen 650 mg p.o.
plus diphenhydramine 25 mg IV versus placebo during
leukocyte-reduced platelet transfusions.2 Information
on timing of the premedication was not provided.
Of the 15 patients reporting a history of FNHTR,
4 reactions were reported in 14 transfusions in patients
receiving premedications compared with 3 reactions
reported in 13 transfusions in patients receiving placebo.2
The other applicable study in the Cochrane
review was a double-blind crossover RCT evaluating
73 patients with history of FNHTR.1 Participants
on hematology or gastrointestinal wards were
serially randomized to hydrocortisone 50 mg IV,
diphenhydramine 50 mg IV, both, or placebo.
Each medication was infused 30 minutes prior to
transfusions. Blood products used were not described.
The Cochrane review mentioned “prevention of
FNHTR” in 47 patients receiving both treatments,
16 patients receiving hydrocortisone alone, 6 receiving
diphenhydramine alone (odds ratio favoring
hydrocortisone of 2.38; 95% CI, 1.07–5.27), and