What could be causing low serum haptoglobin in my patient with no evidence of hemolysis?

 

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
  • Hemodilution
  • 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?

References

  1. 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
  2. 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
  3. 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
  4. Haptoglobin blood test. https://medlineplus.gov/ency/article/003634.htm. Accessed August 6, 2017.
  5. 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

What could be causing low serum haptoglobin in my patient with no evidence of hemolysis?

Why does my patient with alcoholic liver disease have spider angiomas?

 

Spider angiomas (SAs), collections of small blood vessels radiating from a central, dilated arteriole that form near the surface of the skin, are  found in 10-15% of healthy adults and young children, as well as in a variety of conditions, including pregnancy, women taking oral contraceptive pills (OCPs),  thyrotoxicosis, and chronic liver disease1.  

Although the exact mechanism of the formation SAs has not been fully elucidated, several hypotheses have been offered:

  • Arteriolar vasodilation caused by estrogen excess due to impaired hepatic metabolism in cirrhosis; 2this is supported by the association of SAs also with other high-estrogen states, such as in pregnancy and OCPs.
  • Vasodilatory effects of substance P, a neuropeptide partially inactivated by the liver and elevated in patients with liver disease. 3 
  • Neovascularization promoted by vascular endothelial growth factor and basic fibroblast growth factor released by damaged hepatocytes. 4
  • Alcohol itself may contribute, as SAs are more commonly seen in individuals with alcoholic cirrhosis than in those with non-alcoholic causes of liver disease. 2

For unknown reasons, in adults spider angiomas most commonly occur in areas drained by the superior vena cava, namely the face, arms, neck, and chest.

 

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References

  1. Khasnis A, Gokula RM. Spider nevus. J Postgrad Med 2002;48:307.         
  2. Li CP, Lee FY, Hwang SJ, et al., Spider angiomas in patients with liver cirrhosis: role of alcoholism and impaired liver function. Scand J Gastroenterol 1999;  34: 520-3.https://www.ncbi.nlm.nih.gov/pubmed/10423070
  3. Li CP, Lee FY, Hwang SJ, et al., Role of substance P in the pathogenesis of spider angiomas in patients with nonalcoholic liver cirrhosis. Am J Gastroenterol 1999; 94: 502-7.https://www.ncbi.nlm.nih.gov/pubmed/10022654
  4. Li CP, Lee FY, Hwang SJ,  et al., Spider angiomas in patients with liver cirrhosis: role of vascular endothelial growth factor and basic fibroblast growth factor. World J Gastroenterol 2003; 9: 2832-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4612064/ 

Contributed by Camille Mathey-Andrews, Medical Student, Harvard Medical School

 

Why does my patient with alcoholic liver disease have spider angiomas?