Why has my hospitalized patient with head and neck cancer developed thrombocytosis few days following surgery?

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.

 

References

  • 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.
Why has my hospitalized patient with head and neck cancer developed thrombocytosis few days following surgery?

What is the significance of Howell-Jolly bodies in the peripheral smear of my patient with a spleen who presents with pneumonia?

Howell-Jolly bodies (HJBs, Figure) 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 (particularly ulcerative colitis), HIV, cirrhosis, primary pulmonary hypertension, splenic irradiation, amyloidosis, sarcoidosis, bone marrow transplantation, and high-dose corticosteroid therapy1-4.

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 vaccines3,5.

HJBs are nuclear remnants in circulating mature red blood cells which are usually pitted by the spleen under normal physiological conditions. 

Final Fun Pearl:  Did you know that  HJBs were named after Henry Howell, an American physiologist who pioneered the use of heparin as an anti-coagulant and Justin Jolly, a French hematologist who was among the first to film mitotic activity in cells?

howelljollymgh

Figure. Howell-Jolly body in an RBC. Photo courtesy of Michael S. Abers, MD

 

References

  1. Di Sabatino, A, Carsetti R, Corazza G. Post-splenectomy and hyposplenic states. Lancet 2011;378:86–97. https://www.ncbi.nlm.nih.gov/pubmed/21474172
  2. Brousse, V, Buffet P, Rees D. The spleen and sickle cell disease: the sick(led) spleen. Br J Haematol 2014;166: 165–176. https://www.ncbi.nlm.nih.gov/pubmed/24862308
  3. 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. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4551333
  4. Ryan FP, Smart RC, Holdsworth CD, et al. Hyposplenism in inflammatory bowel disease 1978;19:50-55. https://www.ncbi.nlm.nih.gov/pubmed/624506
  5. 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.  http://onlinelibrary.wiley.com/doi/10.1111/bjh.13660/full

Contributed by Katarzyna Orlewska, Medical Student, Warszawski Uniwersytet Medyczny, Poland

What is the significance of Howell-Jolly bodies in the peripheral smear of my patient with a spleen who presents with pneumonia?

My patient with metastatic lung cancer has a WBC count >20,000 without an obvious cause. Can it be related to the cancer?

Absolutely! Although tumor necrosis may be associated with mild to moderate leukocytosis, another explanation for a rise in WBC count (particularly when “leukemoid” like) in patients with cancer may be related to granulocyte colony-stimulating factor (G-CSF) production by the neoplasm itself.  

In vivo production of G-CSF by bladder cancer was reported over 25 years ago in a patient with marked leukocytosis (>100,000)1.  Subsequently, numerous G-CSF-producing tumors have been reported, including those associated with the genitourinary  tract (eg, bladder, ureter, prostate), lung, gynecological organs, gallbladder, stomach, esophagus, small intestine, pancreas, mesothelioma, thyroid, and myeloma2.

 In most cases, G-CSF-producing tumors are advanced with very poor prognosis 2.  Although the mechanism underlying a link between G-CSF production and tumor progression is unclear, a direct action on GCSF receptors of tumor cells, formation of more aggressive cancer cells,  and changes in  the function of T-cells and endothelial cells that may enhance tumor growth have been postulated2.

 

References

  1. Ito N, Matsuda T, Kakehi Y, et al. Bladder cancer producing granulocyte colony-stimulating factor. N Engl J Med 1990;323:1709-10. http://www.nejm.org/doi/pdf/10.1056/NEJM199012133232418
  2. Yamano T, Moril E, Ikeda J-I, Aozasa K. Granulocyte colony-stimulating factor production and rapid progression of gastric cancer after histological change in the tumor. Jpn J Clin Oncol 2007;37:793-796. https://academic.oup.com/jjco/article/37/10/793/831502
My patient with metastatic lung cancer has a WBC count >20,000 without an obvious cause. Can it be related to the cancer?

My patient with a recent fall has a low serum 25 (OH) D level. Can vitamin D (VD) deficiency be associated with falls?

Short answer: Yes! Although the essential role of VD in calcium homeostasis and bone health is widely recognized, the extra-skeletal impact of its deficiency is often overlooked, including its effect on muscle function.  In fact, in 30% of patients, VD deficiency may present as proximal muscle weakness before any biochemical signs develop (eg, hypocalcemia, high alkaline phosphatase), likely mediated through VD receptors in muscle tissue 1,2. 

A recent meta-analysis of fall prevention with supplemental vitamin D concluded that at a dose of 700-1000 IU, supplemental vitamin D reduced falls by 19% within 2-3 months of treatment initiation among patients 65 y or older2; this benefit was not affected by type of supplemental VD, gender, age, or level of independence, and may be independent of additional calcium supplementation.  No fall reduction was observed with a daily dose < 700 IU or achieved serum 25 (OH)D levels below 60 nmol. 

References 

  1. Rasheed K, Sethi P, Bixby E. Severe vitamin D deficiency induced myopathy associated with rhabdomyolysis. N Am J Med Sci 2013;5:334-336.
  2. Bischoff-Ferrari HA, Dawson-Hughes B, Orav JE, et al. Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomized controlled trials. BMJ 2009;339:b3692.
My patient with a recent fall has a low serum 25 (OH) D level. Can vitamin D (VD) deficiency be associated with falls?

What’s the connection between hypertension (HTN) and primary hyperparathyroidism (PHPT)?

The prevalence of HTN in patients with PHPT has generally been shown to be higher than the general population irrespective of age. Because elevated PTH levels have also been reported in some patients with essential HTN, the association of high PTH levels with HTN may not always be causal in nature1.

Parathyroid HTN is characterized by increased total peripheral vascular resistance, possibly related to dysregulation of major endocrine pressor factors (eg, sympathetic nervous system and/or the renin-angiotensin-aldosterone  axis), dysfunction of resistance vessels due to altered vasodilatory response and/or enhanced vascular constriction due to to pressor hormones. Abnormal calcium metabolism at the level of vascular smooth muscle cells may be the final common pathway1.

In a longitudinal prospective cohort study of mostly older white women, history of HTN and use of furosemide were associated with a signficantly higher risk of PHPT2.

1. Schiff H, Lang SM. Hypertenson secondary to PHPT: cause or coincidence. Int J Endocrinol 2011;2011, Article ID 974647,6 pages,  http://dx.doi.org/10.1155/2011/974647.
2. Vaidya A, Curhan GC, Paik JM, Kronenberg H, Taylor EN. Hypertension antihypertensive medications, and risk of incident primary hyperparathyroidism. J Clin Endocrinol Metabl 2015;100:2396-2404.  https://www.ncbi.nlm.nih.gov/pubmed/25885946

What’s the connection between hypertension (HTN) and primary hyperparathyroidism (PHPT)?

My patient with atrial fibrillation (AF) with a CHA2DS2-VASc score ≥2 is not a candidate for anticoagulation due to excessive bleeding risk. Does high-dose aspirin provide an effective alternative for stroke prevention in this setting?

 The SPAF (Stroke Prevention in Atrial Fibrillation) trial1 found a 42% reduction in overall risk of stroke with daily aspirin (325 mg). However, critics note that no benefit was observed among patients > 75 y or those with severe stroke.

7 other studies on the topic failed to confirm reduction in the risk of stroke at a range of aspirin doses (25mg bid-1,300mg qd) 2. These studies reported that aspirin is associated with a 19% reduction in stroke incidence (similar to patients with vascular disease), with a 95% CI that crosses zero (-1% to 35%), raising doubts about its actual benefit in AF3. For secondary prevention, aspirin was associated with a 2.5% reduction in the annual risk of stroke. However, these results were influenced by the only trial with a favorable outcome, SPAF-14.

In short, even at higher doses, aspirin may not be the answer for stroke prevention in patients with AF.

 References

  1. Stroke Prevention in Atrial Fibrillation Study. Final results. Circulation 1991;84, 527–39.
  2. January CT, Wann LS, Alpert  JS, et al. 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. Circulation  2014;130, e199–e267.
  3. European Heart Rhythm Association et al. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Europace  2010; 12, 1360–420.
  4. Sabir IN, Matthews GDK,  Huang, CL-H. Antithrombotic therapy in atrial fibrillation: aspirin is rarely the right choice. Postgrad Med J 2013; 89, 346–51.

 

Contributed by Jacqueline Boehme, M.D., Medical Resident, Mass General Hospital

My patient with atrial fibrillation (AF) with a CHA2DS2-VASc score ≥2 is not a candidate for anticoagulation due to excessive bleeding risk. Does high-dose aspirin provide an effective alternative for stroke prevention in this setting?