There are many causes of low serum haptoglobin besides hemolysis, including1-4:
- Cirrhosis of the liver
- Disseminated ovarian carcinomatosis
- Pulmonary sarcoidosis
- Elevated estrogen states
- Repetitive physical exercise
- Blood transfusions
- Drugs (eg, oral contraceptives, chlorpromazine, indomethacin, isoniazid, nitrofurantoin, quinidine, and streptomycin)
- Iron deficiency anemia
- Megaloblastic anemia (by destruction of megaloblastic RBC precursors in the bone marrow)
- Congenital causes
Less well-known is that congenital haptoglobin deficiency (“anhaptoglobinemia”) may not be so rare in the general population at a prevalence of 1% among whites and 4% among African-Americans (>30% in blacks of West African origin)3. Measurement of serum hemopexin, another plasma protein that binds heme, may help distinguish between this condition and acquired hypohaptoglobinemia— in the absence of hemolysis, hemopexin levels should remain unchanged3,5.
Final Fun Fact: Did you know that serum haptoglobin is often low during the first 6 months of life?
- Shih AWY, McFarane A, Verhovsek M. Haptoglobin testing in hemolysis: measurement and interpretation. Am J Hematol 2014;89: 443-47. https://www.ncbi.nlm.nih.gov/pubmed/24809098
- Sritharan V, Bharadwaj VP, Venkatesan K, et al. Dapsone induced hypohaptoglobinemia in lepromatous leprosy patients. Internat J Leprosy 1981;307-310. https://www.ncbi.nlm.nih.gov/pubmed/7198620
- Delanghe J, Langlois M, De Buyzere M, et al. Congenital anhaptoglobinemia versus acquired hypohaptoglobinemia. Blood 1998;9: 3524. http://www.bloodjournal.org/content/bloodjournal/91/9/3524.full.pdf
- Haptoglobin blood test. https://medlineplus.gov/ency/article/003634.htm. Accessed August 6, 2017.
- Smith A, McCulloh RJ. Hemopexin and haptoglobin: allies against heme toxicity from hemoglobin not contenders. Front. Physiol 2015;6:187. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4485156/pdf/fphys-06-00187.pdf
In collaboration with Kris Olson, MD, MPH, Mass General Hospital, Boston, MA
Night sweats (NS) is a common patient complaint, affecting about a third of hospitalized patients on medical wards1. Despite its long list of potential causes, direct relationship between the often- cited conditions and NS is usually unclear2, its cause may remain elusive In about a third to half of cases in the primary care setting, and its prognosis, at least in those >65 y of age, does not appear to be unfavorable 2,3.
Selected commonly and less frequently cited conditions associated with NS are listed (Table)2-9. Although tuberculosis is one of the first conditions we think of when faced with a patient with NS, it should be emphasized that NS is not common in this disease (unless advanced) and is rare among hospitalized patients as a cause of their NS1,9.
In one of the larger study of adult patients seen in primary care setting, 23% reported pure NS and an additional 18% reported night and day sweats5; the prevalence of NS in both men and women was highest in 41-55 y age group. In multivariate analyses, factors associated with pure NS in women were hot flashes and panic attacks; in men, sleep disorders.
Table. Selected causes of night sweats
||Less frequently cited
|Neoplastic/hematologic (eg, lymphoma, leukemia, myelofibrosis)
Infections (eg, HIV, tuberculosis, endocarditis)
Endocrine (eg, ovarian failure, hyperthyroidism, orchiectomy, carcinoid tumor, diabetes mellitus [nocturnal hypoglycemia], pheochromocytoma)
Rheumatologic (eg, giant cell arteritis)
|Gastroesophageal reflux disease
Drugs (eg, anti-depressants, SSRIs, donepezil [Aricept], tacatuzumab)
Sleep disturbances (eg, obstructive sleep apnea)
Panic attacks/anxiety disorder
- Lea MJ, Aber RC, Descriptive epidemiology of night sweats upon admission to a university hospital. South Med J 1985;78:1065-67.
- Mold JW, Holtzclaw BJ, McCarthy L. Night sweats: A systematic review of the literature. J Am Board Fam Med 2012; 25-878-893.
- Mold JW, Lawler F. The prognostic implications of night sweats in two cohorts of older patients. J Am Board Fam Med 2010;23:97-103.
- Mold JW, Holtzclaw BJ. Selective serotonin reuptake inhibitors and night sweats in a primary care population. Drugs-Real World Outcomes 2015;2:29-33.
- Mold JW, Mathew MK, Belgore S, et al. Prevalence of night sweats in primary care patients: An OKPRN and TAFP-Net collaborative study. J Fam Pract 2002; 31:452-56.
- Feher A, Muhsin SA, Maw AM. Night sweats as a prominent symptom of a patient presenting with pulmonary embolism. Case reports in Pulmonology 2015. http://dx.doi.org/10.1155/2015/841272
- Rehman HU. Vitamin B12 deficiency causing night sweats. Scottish Med J 2014;59:e8-11.
- Murday HK, Rusli FD, Blandy C, et al. Night sweats: it may be hemochromatosis. Climacteric 2016;19:406-8.
- Fred HL. Night sweats. Hosp Pract 1993 (Aug 15):88.
Smudge cells (SCs) also known as “basket cells”, are remnants of B lymphocytes ruptured during slide preparation (photo below). Although at low numbers (~0-5% of lymphocytes), SCs may be observed in healthy individuals, when found at higher numbers (>10%)they are associated with chronic lymphocytic leukemia (CLL) and other lymphoproliferative diseases1; the percentage of SCs may not discriminate between these malignancies, however2.
For nearly a century, SCs were thought to be just an artifact of slide preparation resulting from the fragility of CLL cells3. Although the mechanism accounting for the appearance of SCs is still unclear, their formation is inversely correlated with B cell content of vimentin, a cytoskeletal protein essential for rigidity and integrity of lymphocytes 3-5. High vimentin expression is associated with an aggressive variant of CLL and shorter survival times3-5. Therefore, higher number of SCs at the time of CLL diagnosis (>20% or >30%) may actually indicate a better prognosis4-6!
Photo courtesy of U.S. National Library of Medicine
- Petrakis NL, Lieberman E, Fullerton J. The dead leukocyte content of the blood in normal and leukemic patients. Blood. 1957 Apr;12:367-72.
- Matos DM, Perini G, Kruzich C, Rego EM, Falcao RP. Smudge cells in peripheral blood smears did not differentiate chronic lymphocytic leukemia from other B-cell chronic lymphoprolipherative diseases. Rev Bras Hematol Hemoter. 2009;31:333–6.
- Nowakowski GS1, Hoyer JD, Shanafelt TD, et al. Percentage of smudge cells on routine blood smear predicts survival in chronic lymphocytic leukemia. J Clin Oncol. 2009;27:1844-9.
- Nowakowski GS, Hoyer JD, Shanafelt TD, et al. Using smudge cells on routine blood smears to predict clinical outcome in chronic lymphocytic leukemia: a universally available prognostic test. Mayo Clin Proc. 2007;82:449-53.
- Johansson P, Eisele L, Klein-Hitpass L, et al. Percentage of smudge cells determined on routine blood smears is a novel prognostic factor in chronic lymphocytic leukemia. Leuk Res. 2010;34:892-8.
- Gogia A, Raina V, Gupta R, et al. Prognostic and predictive significance of smudge cell percentage on routine blood smear in chronic lymphocytic leukemia. Clin Lymphoma Myeloma Leuk. 2014;14(6):514-7.
Contributed by Khin-Kyemon Aung, medical student, Harvard Medical School, Boston.
An acute rise in platelet count is not uncommon among hospitalized patients and may be related to several factors, including “tissue damage” from a surgical procedure, infection, and acute blood loss1. Postoperative thrombocytosis is thought to be related to increased platelet production as well as redistribution of platelets from the splenic platelet pool to the general circulation1. Increased levels of megakaryocytic growth factors such as thrombopoietin, and pro-or anti-inflammatory cytokines such as interleukin (IL)-1, 3, 6, or 11 may also stimulate megakaryopoeisis in the setting of inflammation2.
Less well known is that enoxaparin (Lovenox), an anticoagulant commonly used for prevention of thromboembolic events in hospitalized patients, may also cause reactive thrombocytosis, usually within the first 2 weeks of therapy and resolving 2 weeks following its discontinuation3.
Although malignancy is also associated with secondary thrombocytosis, given its acute nature in our patient, it is less likely to be playing a role.
- Griesshammer M, Bangerter M, Sauer T, et al. Aetiology and clinical significance of thrombocytosis: analysis of 732 patients with an elevated platelet count. J Intern Med 1999;245:295-300.
- Kulnigg-Dabsch S, Schmid W, Howaldt S, et al. Iron deficiency generates secondary thrombocytosis and platelet activation in IBD: the randomized, controlled thromboVIT trial. Inflamm Bowel Dis 2013;published online, DOI10.1097/MIB.0b013e318281f4db.
- Hummel MC, Morse BC, Hayes LE. Reactive thrombocytosis associated with enoxaparin. Pharmacotherapy 2006;26:1667-1670.
HJBs (Figure) are named after Henry Howell, an American physiologist who pioneered the use of heparin as an anti-coagulant and Justin Jolly, a French hematologist who filmed mitotic activity in cells. HJBs are nuclear remnants in circulating mature red blood cells which are usually pitted by the spleen under normal physiological conditions. They are often indicative of asplenia (either post-splenectomy or congenital absence) or hyposplenism associated with a variety of conditions, including sickle cell disease, autoimmune disorders, celiac disease, inflammatory bowel disease, HIV, cirrhosis, primary pulmonary hypertension, splenic irradiation, amyloidosis, sarcoidosis, bone marrow transplantation, and high-dose corticosteroid therapy1-3.
Patients with pneumonia and HJBs on peripheral smear may be hyposplenic and at risk of potentially serious infections, predominantly caused by encapsulated bacteria eg, Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis3. Such patients should be immunized against these organisms, including sequential receipt of both conjugated and polysaccharide pneumococcal vaccines3,4.
Photo courtesy of Michael S. Abers, MD
- Di Sabatino, A, Carsetti R, Corazza G. Post-splenectomy and hyposplenic states. Lancet 2011;378:86–97.
- Brousse, V, Buffet P, Rees D. The spleen and sickle cell disease: the sick(led) spleen. Br J Haematol 2014;166: 165–176.
- Mathew H, Dittus C, Malek A, Negroiu A. Howell-Jolly bodies on peripheral smear leading to the diagnosis of congenital hyposplenism in a patient with septic shock. Clin Case Rep 2015;3:714-717.
- Kuchar E, Miśkiewicz K , Karlikowska M. A review of guidance on immunization in persons with defective or deficient splenic function. Br J Haematol 2015; 171:683-94. doi: 10.1111/bjh.13660, Epub 2015 Aug 28.
Contributed by Katarzyna Orlewska, Medical Student, Warszawski Uniwersytet Medyczny, Poland