Leukocytosis: Difference between revisions
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{{SK}} Elevated white blood cell count; Right-shift leukocytosis; Left-shift leukocytosis | {{SK}} Elevated white blood cell count; Right-shift leukocytosis; Left-shift leukocytosis |
Latest revision as of 17:50, 4 April 2019
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Maria Fernanda Villarreal, M.D. [2] Lakshmi Gopalakrishnan, M.B.B.S. [3]; Grammar Reviewer: Natalie Harpenau, B.S.[4]
Synonyms and keywords: Elevated white blood cell count; Right-shift leukocytosis; Left-shift leukocytosis
Overview
Leukocytosis is the elevation of the white blood cell count above the normal range (greater than 11,000 per mm3). Leukocytosis is frequently a sign of an inflammatory response, most commonly the result of infection, but may also occur following certain parasitic infections, bone tumors, strenuous exercise, emotional stress, pregnancy, anesthesia, and epinephrine administration. Leukocytosis may be classified into 5 sub-types: neutrophilia (most common), lymphocytosis, monocytosis, eosinophilia, and basophilia. Other classifications include: Left shift or right shift leukocytosis. The pathogenesis of leukocytosis is characterized by the increase of leukocytes (primarily neutrophils), followed by the proliferation and release of granulocyte and monocyte precursors in the bone marrow, which is then stimulated by several products of inflammation including C3a and G-CSF.[1]
Historical Perspective
- Leukocytosis was first discovered by Paul Kautchakoff in 1846.[1]
Classification
- Leukocytosis may be classified into 5 sub-types:[2]
- Neutrophilia (most common)
- Lymphocytosis
- Monocytosis
- Eosinophilia
- Basophilia.
- Leukocytosis may also be classified into 2 groups:[2]
- Left shift (most common)
- Immature leukocytes increase
- Proliferation and release of granulocyte and monocyte precursors in the bone marrow
- Usually stimulated by several products of inflammation including C3a and G-CSF
- Right shift
- Reduced count or lack of "young neutrophils"
- Associated with the presence of "giant neutrophils"
- Another variant of leukocytosis is the leukemoid reaction.
- The image below demonstrates a graphic figure that illustrates hematopoietic growth factors in leukocytosis.[3]
Pathophysiology
- The pathogenesis of leukocytosis is characterized by:[2]
- An increased release of leukocytes from bone marrow storage pools
- Decreased margination of leukocytes onto vessel walls
- Decreased extravasation of leukocytes from the vessels into tissues
- Increase in number of precursor cells in the bone marrow
Causes
- To see a comprehensive list of all causes of leukocytosis, please click here
Causes of leukocytosis | ||||
---|---|---|---|---|
Neutrophilic leukocytosis (neutrophilia) |
| |||
Eosinophilic leukocytosis (eosinophilia) |
| |||
Basophilic leukocytosis Basophilia |
||||
Monocytosis | ||||
Lymphocytosis |
|
Epidemiology and Demographics
- Leukocytosis is very common.[2]
Age
- Patients of all age groups may develop leukocytosis.
- Normal white blood count differential changes with age.
- Leukocytosis in neonates is more common, in comparison to children and adults.[2]
Gender
- Leukocytosis affects men and women equally.
Race
- There is no racial predilection for leukocytosis.
Risk Factors
- Common risk factors in the development of leukocytosis include:[2]
- Physiological processes (e.g. stress, exercise, pregnancy)
- Drugs (e.g. corticosteroids, lithium, beta agonists)
- Trauma
- Stress
Natural History, Complications and Prognosis
- The majority of patients with leukocytosis are initially symptomatic.[3]
- Early clinical features include:[3]
- Common complications of leukocytosis include:[3]
- Prognosis generally depends on the underlying etiologies.[3]
Diagnosis
Symptoms
- Leukocytosis is usually symptomatic.
- Symptoms of leukocytosis are often unspecific such as:[3]
- Weight loss
- Fevers of unknown origin
- Hyperhidrosis
- Chronic pain
- Fatigue
- Dyspnea
- Malaise
- Obtain history of the following:
- Clinical features
- Duration (e.g. days, weeks, months)
- Remainder of complete blood count
Laboratory Findings
- Laboratory findings that are consistent with the diagnosis of leukocytosis involve the [3] White blood cell count being above the normal range (greater than 11,000 per mm3).
Differentiating Leukocytosis from Other Diseases
Differential diagnosis methods of leukocytosis:
Category | Condition | Etiology | Mechanism | Congenital | Acquried | Clinical manifestations | Para−clinical findings | Gold standard | Associated findings | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Demography | History | Symptoms | Signs | ||||||||||||||||||||||||||
Lab Findings | |||||||||||||||||||||||||||||
Physiologic | Increased bone marrow production | Demargination of peripheral blood neutrophils | Appearance | Fever | Abdominal pain | BP | Asplenia | Hepatosplenomegaly | Lymphadenopathy | Joint involvement | Other | CBC | PBS | Bone marrow exam | ESR/CRP | BUN/Cr | LFT | ||||||||||||
Autonomous | Reactive | WBC | HB | Plt | |||||||||||||||||||||||||
Hematologic | Hereditary neutrophilia[4] | − | + | − | − | + | − | Rare autosomal dominant genetic disorder |
|
Normal | − | − | Nl | − | + | − | − | − | ↑ | Nl | Nl |
|
Nl | Nl | Nl | Nl | Molecular testing |
| |
Myeloproliferative neoplasms[5] |
|
− | + | − | − | + | + | Elderly | Exposure to: | ± | + | Nl | − | + | − | − | ↑/↓ | ↓ | ↑/↓ |
|
|
↑ | Nl | Nl | Bone marrow examination + clinical manifestation |
| |||
Polycythemia vera[6] |
|
− | + | − | − | + | − | Mean age > 60 years old |
|
− | − | ↑ | − | + | + | − |
|
Nl to ↑ | ↑ | ↑ |
|
Nl | Nl | Nl | Bone marrow examination + clinical manifestation | ||||
Microangiopathic hemolytic anemia (MAHA)[7] | − | + | − | − | + | + | Any |
|
+ | + | ↓ | − | + | − | − | ↑ | ↓ | ↑ |
|
NA | ↑ | ↑ | ↑ | Bone marrow examination + clinical manifestation |
| ||||
Leukoerythroblastosis[8] |
|
− | + | − | − | − | + | Any | − | + | Nl | − | + | − | − | ↑ | ↓ | ↓ |
|
|
↑ | Nl | ↑ | Bone marrow biopsy |
| ||||
Immunology/
Rheumatology |
Condition | Etiology | Physiologic | Autonomous increased bone marrow production | Reactive increased bone marrow production | Demargination of peripheral blood neutrophils | Congenital | Acquried | Demography | History | Appearance | Fever | Abdominal pain | BP | Asplenia | Hepatosplenomegaly | Lymphadenopathy | Joint involvement | Other signs | WBC | HB | Plt | PBS | Bone marrow exam | ESR/CRP | BUN/Cr | LFT | Gold standard | Associated findings |
Leukocyte adhesion deficiency[9] |
|
− | + | − | − | + | − | Rare autosomal recessive, LAD II more in Middle East and Brazil |
|
|
+ | − | Nl | − | − | − | − |
|
↑ | ↓ | ↓/↑ |
|
|
Nl | Nl | Nl | Flow cytometry |
| |
Cryopyrin-associated periodic syndromes[10] |
|
− | + | − | − | + | − | Autosomal dominant autoinflammatory syndrome |
|
+ | − | Nl | − | − | − | + | ↑ | ↓ | ↓/↑ |
|
|
↑ | Nl | ↑ | Genetic tests | ||||
Rheumatoid arthritis[11][12] |
|
− | + | − | − | − | + | Any, more in young women, between 30-60 years old |
|
|
+ | − | Nl | − | − | − | + |
|
↑ | ↓ | ↑ |
|
NA | ↑ | Nl | Nl | Clinical manifestation + positive anti-CCP antibodies |
| |
Juvenile onset rheumatoid arthritis[13] |
|
− | + | − | − | − | + | Children under the age of 16 |
|
|
+ | − | Nl | − | − | + | + | ↑ | ↓ | ↑ |
|
NA | ↑ | Nl | Nl | Clinical manifestation + laboratory findings |
| ||
Adult Still's disease[14] |
|
− | + | − | − | − | + | Rare autoimmune disease | NA |
|
+ | − | Nl | − | − | + | + | ↑ | ↓ | ↑ |
|
NA | ↑ | Nl | Nl | Diagnosis of exclusion |
| ||
Kawasaki disease[15] |
|
− | + | − | − | − | + | Autoimmune disease, more in Asian ethnicity boys | NA | + | + | Nl | − | − | + | + |
|
↑ | ↓ | ↑ |
|
NA | ↑ | Nl | Nl | Diagnostic criteria |
| ||
IBD[16] | − | + | − | − | − | + | Autoimmune disease, more in young |
|
+ | + | Nl | − | + | + | + | ↑ | ↓ | ↑ |
|
NA | ↑ | Nl | Nl | Colonoscopy and biopsy | |||||
Sarcoidosis[17] |
|
− | + | − | − | − | + | Autoimmune disease, more in young African American women |
|
+ | + | Nl | − | + | +
Bilateral hilar adenopathy |
+ | ↑ | ↓ | ↑ |
|
NA | ↑ | Nl | Nl | Diagnosis of exclusion |
| |||
Chronic hepatitis[18] | − | + | − | − | − | + | Elderly |
|
+ | + | ↓ | − | + | + | + | ↑ | ↓ | ↑ |
|
NA | ↑ | ↑ | ↑ | Liver biopsy | |||||
Sweet syndrome[19] |
|
− | + | − | − | − | + | Rare | + | + | Nl | − | − | + | + | ↑ | ↓ | ↑ |
|
|
↑ | Nl | Nl | Diagnostic criteria |
| ||||
Acute gout[20] | − | + | − | − | − | + | Older males |
|
+ | − | − | − | − | + | ↑ | ↓ | ↑ |
|
NA | ↑ | ↑ | Nl | Clinical manifestation |
| |||||
Medication | Condition | Etiology | Physiologic | Autonomous increased bone marrow production | Reactive increased bone marrow production | Demargination of peripheral blood neutrophils | Congenital | Acquried | Demography | History | Appearance | Fever | Abdominal pain | BP | Asplenia | Hepatosplenomegaly | Lymphadenopathy | Joint involvement | Other signs | WBC | HB | Plt | PBS | Bone marrow exam | ESR/CRP | BUN/Cr | LFT | Gold standard | Associated findings |
Steroid[21] |
|
− | − | + | + | − | + | Any | − | + | Nl to ↓ | − | − | − | − | ↑ | Nl to ↓ | ↑ |
|
|
↑ | ↑ | Nl | Clinical manifestation + history of drug consumption |
| ||||
Filgrastim (Myeloid growth factor)[22] |
|
− | − | + | + | − | + | Any | + | − | Nl to ↓ | − | − | − | + | ↑ | Nl to ↓ | ↑ | NA | NA | ↑ | Nl | Nl | Clinical manifestation + history of drug consumption |
| ||||
Lithium[23] |
|
− | − | + | + | − | + | Any |
|
− | − | Nl | − | − | − | − |
|
↑ | Nl to ↓ | ↑ | NA | NA | Nl | ↑ | Nl | Clinical manifestation + history of drug consumption | |||
Catecholamines |
|
− | − | + | + | − | + | Any |
|
− | − | Nl to ↓ | − | − | − | − | ↑ | ↑ | ↑ |
|
|
↑ | Nl | Nl | Clinical manifestation + history of drug consumption |
| |||
ATRA[25] |
|
− | − | + | + | − | + | Any | − | − | Nl | − | − | − | − | ↑ | Nl | Nl | NA | NA | ↑ | Nl | ↑ | Clinical manifestation + history of drug consumption | |||||
Other | Condition | Etiology | Physiologic | Autonomous increased bone marrow production | Reactive increased bone marrow production | Demargination of peripheral blood neutrophils | Congenital | Acquried | Demography | History | Appearance | Fever | Abdominal pain | BP | Asplenia | Hepatosplenomegaly | Lymphadenopathy | Joint involvement | Other signs | WBC | HB | Plt | PBS | Bone marrow exam | ESR/CRP | BUN/Cr | LFT | Gold standard | Associated findings |
Infections[26] | − | + | + | + | − | + | Any |
|
|
+ | + | Nl to ↓ | − | ± | ± | ± | ↑ | ↓ | ↑ |
|
|
↑ | Nl | Nl | Clinical manifestation+ culture |
| |||
Allergy[27] |
|
− | + | + | + | − | + | Any |
|
− | − | Nl to ↓ | − | − | − | − | ↑ | ↑ | ↑ |
|
|
↑ | Nl | Nl | Clinical manifestation | − | |||
Post splenectomy[28] |
|
− | − | + | + | − | + | Any |
|
|
± | − | Nl | + | − | − | − | − | ↑ | ↓ | ↑ |
|
|
↑ | Nl | Nl | Clinical manifestation |
| |
Cigarette smoking[29] |
|
− | − | + | + | − | + | Any | − | − | Nl | − | − | − | − | ↑ | ↑ | ↑ | NA | NA | Nl | Nl | Nl | Clinical manifestation | − | ||||
Stress/exercise[30] |
|
+ | − | + | − | − | + | Athlete |
|
− | − | Nl | − | − | − | − | − | ↑ | ↑ | ↑ |
|
|
↑ | Nl | Nl | Clinical manifestation | − | ||
Infancy[31] | Physiologic | + | − | − | − | − | + | Infancy | − |
|
− | − | Nl | − | − | − | − | − | ↑ | ↑ | ↑ | NA | NA | Nl | Nl | Nl | Clinical manifestation | − | |
Pregnancy[32] | Physiologic | + | − | − | − | − | + | Pregnancy | − |
|
− | − | Nl | − | − | − | − | − | ↑ | ↓ | ↑ | NA | NA | Nl | Nl | Nl | Clinical manifestation | − | |
Platelet clumping[33] | Spurious | − | − | − | − | − | + | Any | − |
|
− | − | Nl | − | − | − | − | − | ↑ | Nl | ↑ |
|
Nl | Nl | Nl | Nl | Clinical manifestation | − | |
Mixed cryoglobulinemia[34] | Spurious | − | − | − | − | − | + | Any | − | − | Nl | − | − | − | + | ↑ | Nl to ↓ | ↑ |
|
Nl | Nl | Nl | Nl | Skin biopsy | |||||
Category | Condition | Etiology | Physiologic | Autonomous increased bone marrow production | Reactive increased bone marrow production | Demargination of peripheral blood neutrophils | Congenital | Acquried | Demography | History | Appearance | Fever | Abdominal pain | BP | Asplenia | Hepatosplenomegaly | Lymphadenopathy | Joint involvement | Other signs | WBC | HB | Plt | PBS | Bone marrow exam | ESR/CRP | BUN/Cr | LFT | Gold standard | Associated findings |
References
- ↑ 1.0 1.1 Chabot-Richards DS, George TI (2014). "Leukocytosis". Int J Lab Hematol. 36 (3): 279–88. doi:10.1111/ijlh.12212. PMID 24750674.
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 Abramson N, Melton B (2000). "Leukocytosis: basics of clinical assessment". Am Fam Physician. 62 (9): 2053–60. PMID 11087187.
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 Leukocytosis. Wikipedia. https://en.wikipedia.org/wiki/Leukocytosis Accessed on May 23, 2016
- ↑ Herring, William Benjamin; Smith, Laurin Gresham; Walker, Richard Isley; Herion, John Carroll (1974). "Hereditary neutrophilia". The American Journal of Medicine. 56 (5): 729–734. doi:10.1016/0002-9343(74)90642-1. ISSN 0002-9343.
- ↑ Tefferi A (February 2010). "Leukocytosis as a risk factor for thrombosis in myeloproliferative neoplasms-biologically plausible but clinically uncertain". Am. J. Hematol. 85 (2): 93–4. doi:10.1002/ajh.21614. PMID 20052751.
- ↑ Boiocchi L, Gianelli U, Iurlo A, Fend F, Bonzheim I, Cattaneo D, Knowles DM, Orazi A (November 2015). "Neutrophilic leukocytosis in advanced stage polycythemia vera: hematopathologic features and prognostic implications". Mod. Pathol. 28 (11): 1448–57. doi:10.1038/modpathol.2015.100. PMID 26336886.
- ↑ Morton JM, George JN (June 2016). "Microangiopathic Hemolytic Anemia and Thrombocytopenia in Patients With Cancer". J Oncol Pract. 12 (6): 523–30. doi:10.1200/JOP.2016.012096. PMID 27288467.
- ↑ Canbolat Ayhan A, Timur C, Ayhan Y, Kes G (June 2014). "Leukoerythroblastosis Mimicking Leukemia: A case report". Iran J Pediatr. 24 (3): 332–3. PMC 4276592. PMID 25562031.
- ↑ Levy-Mendelovich S, Rechavi E, Abuzaitoun O, Vernitsky H, Simon AJ, Lev A, Somech R (April 2016). "Highlighting the problematic reliance on CD18 for diagnosing leukocyte adhesion deficiency type 1". Immunol. Res. 64 (2): 476–82. doi:10.1007/s12026-015-8706-5. PMID 26434744.
- ↑ Labrousse M, Kevorkian-Verguet C, Boursier G, Rowczenio D, Maurier F, Lazaro E, Aggarwal M, Lemelle I, Mura T, Belot A, Touitou I, Sarrabay G (September 2018). "Mosaicism in autoinflammatory diseases: Cryopyrin-associated periodic syndromes (CAPS) and beyond. A systematic review". Crit Rev Clin Lab Sci. 55 (6): 432–442. doi:10.1080/10408363.2018.1488805. PMID 30035647.
- ↑ Scott DL, Wolfe F, Huizinga TW (September 2010). "Rheumatoid arthritis". Lancet. 376 (9746): 1094–108. doi:10.1016/S0140-6736(10)60826-4. PMID 20870100.
- ↑ Glant TT, Mikecz K, Rauch TA (February 2014). "Epigenetics in the pathogenesis of rheumatoid arthritis". BMC Med. 12: 35. doi:10.1186/1741-7015-12-35. PMC 3936819. PMID 24568138.
- ↑ Naz S, Mushtaq A, Rehman S, Bari A, Maqsud A, Khan MZ, Ahmad TM (June 2013). "Juvenile rheumatoid arthritis". J Coll Physicians Surg Pak. 23 (6): 409–12. doi:06.2013/JCPSP.409412 Check
|doi=
value (help). PMID 23763801. - ↑ Kadavath S, Efthimiou P (February 2015). "Adult-onset Still's disease-pathogenesis, clinical manifestations, and new treatment options". Ann. Med. 47 (1): 6–14. doi:10.3109/07853890.2014.971052. PMID 25613167.
- ↑ Sundel RP (2015). "Kawasaki disease". Rheum. Dis. Clin. North Am. 41 (1): 63–73, viii. doi:10.1016/j.rdc.2014.09.010. PMID 25399940.
- ↑ Zhang YZ, Li YY (January 2014). "Inflammatory bowel disease: pathogenesis". World J. Gastroenterol. 20 (1): 91–9. doi:10.3748/wjg.v20.i1.91. PMC 3886036. PMID 24415861.
- ↑ Modaresi Esfeh J, Culver D, Plesec T, John B (March 2015). "Clinical presentation and protocol for management of hepatic sarcoidosis". Expert Rev Gastroenterol Hepatol. 9 (3): 349–58. doi:10.1586/17474124.2015.958468. PMID 25473783.
- ↑ Gish RG, Given BD, Lai CL, Locarnini SA, Lau JY, Lewis DL, Schluep T (September 2015). "Chronic hepatitis B: Virology, natural history, current management and a glimpse at future opportunities". Antiviral Res. 121: 47–58. doi:10.1016/j.antiviral.2015.06.008. PMID 26092643.
- ↑ Das A, Burmeister R, Chhaya R, Eisenga B, Kumar A (September 2018). "Sweet Syndrome in a Patient With Systemic Lupus Erythematosus". J Clin Rheumatol. doi:10.1097/RHU.0000000000000904. PMID 30247226.
- ↑ Dalbeth N, Zhong CS, Grainger R, Khanna D, Khanna PP, Singh JA, McQueen FM, Taylor WJ (March 2014). "Outcome measures in acute gout: a systematic literature review". J. Rheumatol. 41 (3): 558–68. doi:10.3899/jrheum.131244. PMC 4217650. PMID 24334652.
- ↑ Shoenfeld Y, Gurewich Y, Gallant LA, Pinkhas J (November 1981). "Prednisone-induced leukocytosis. Influence of dosage, method and duration of administration on the degree of leukocytosis". Am. J. Med. 71 (5): 773–8. PMID 7304648.
- ↑ Crawford J, Armitage J, Balducci L, Becker PS, Blayney DW, Cataland SR, Heaney ML, Hudock S, Kloth DD, Kuter DJ, Lyman GH, McMahon B, Rugo HS, Saad AA, Schwartzberg LS, Shayani S, Steensma DP, Talbott M, Vadhan-Raj S, Westervelt P, Westmoreland M, Dwyer M, Ho M (October 2013). "Myeloid growth factors". J Natl Compr Canc Netw. 11 (10): 1266–90. PMID 24142827.
- ↑ Aiff H, Attman PO, Aurell M, Bendz H, Ramsauer B, Schön S, Svedlund J (May 2015). "Effects of 10 to 30 years of lithium treatment on kidney function". J. Psychopharmacol. (Oxford). 29 (5): 608–14. doi:10.1177/0269881115573808. PMID 25735990.
- ↑ Bedoui S, Lechner S, Gebhardt T, Nave H, Beck-Sickinger AG, Straub RH, Pabst R, von Hörsten S (November 2002). "NPY modulates epinephrine-induced leukocytosis via Y-1 and Y-5 receptor activation in vivo: sympathetic co-transmission during leukocyte mobilization". J. Neuroimmunol. 132 (1–2): 25–33. PMID 12417430.
- ↑ Bi KH, Jiang GS (December 2006). "Relationship between cytokines and leukocytosis in patients with APL induced by all-trans retinoic acid or arsenic trioxide". Cell. Mol. Immunol. 3 (6): 421–7. PMID 17257495.
- ↑ Horasan ES, Dağ A, Ersoz G, Kaya A (October 2013). "Surgical site infections and mortality in elderly patients". Med Mal Infect. 43 (10): 417–22. doi:10.1016/j.medmal.2013.07.009. PMID 24012414.
- ↑ Davis M, van der Hilst J (2018). "Mimickers of Urticaria: Urticarial Vasculitis and Autoinflammatory Diseases". J Allergy Clin Immunol Pract. 6 (4): 1162–1170. doi:10.1016/j.jaip.2018.05.006. PMID 29871797. Vancouver style error: initials (help)
- ↑ Bilello JF, Sharp VL, Dirks RC, Kaups KL, Davis JW (2018). "After the embo: predicting non-hemorrhagic indications for splenectomy after angioembolization in patients with blunt trauma". Trauma Surg Acute Care Open. 3 (1): e000159. doi:10.1136/tsaco-2017-000159. PMC 5887792. PMID 29766137.
- ↑ Lymperaki E, Makedou K, Iliadis S, Vagdatli E (2015). "Effects of acute cigarette smoking on total blood count and markers of oxidative stress in active and passive smokers". Hippokratia. 19 (4): 293–7. PMC 5033137. PMID 27688691.
- ↑ Simpson RJ, Kunz H, Agha N, Graff R (2015). "Exercise and the Regulation of Immune Functions". Prog Mol Biol Transl Sci. 135: 355–80. doi:10.1016/bs.pmbts.2015.08.001. PMID 26477922.
- ↑ Nouatin O, Gbédandé K, Ibitokou S, Vianou B, Houngbegnon P, Ezinmegnon S, Borgella S, Akplogan C, Cottrell G, Varani S, Massougbodji A, Moutairou K, Troye-Blomberg M, Deloron P, Luty AJ, Fievet N (2015). "Infants' Peripheral Blood Lymphocyte Composition Reflects Both Maternal and Post-Natal Infection with Plasmodium falciparum". PLoS ONE. 10 (11): e0139606. doi:10.1371/journal.pone.0139606. PMC 4651557. PMID 26580401.
- ↑ Perseghin P (December 2015). "Erythrocyte exchange and leukapheresis in pregnancy". Transfus. Apher. Sci. 53 (3): 279–82. doi:10.1016/j.transci.2015.11.007. PMID 26621538.
- ↑ Castrillo A, Álvarez I, Tolksdorf F (April 2015). "In vitro evaluation of platelet concentrates suspended in additive solution and treated for pathogen reduction: effects of clumping formation". Blood Transfus. 13 (2): 281–6. doi:10.2450/2014.0162-14. PMC 4385077. PMID 25369589.
- ↑ Cacoub P, Comarmond C, Domont F, Savey L, Saadoun D (September 2015). "Cryoglobulinemia Vasculitis". Am. J. Med. 128 (9): 950–5. doi:10.1016/j.amjmed.2015.02.017. PMID 25837517.